IV NAD Therapies | NAD Therapies 703-844-0184 | NAD for alcohol and opioid addiction | IV Drip | Fairfax, Va 22304

IV Medical Center | NOVA Health Recovery | IV NAD Treatment Program for Alcoholism, Opioid addiction, aging | 703-844-0184

 

                                 IV NAD+

Turn Back Time and Experience More Energy and Improved Mood…

About This IV

NAD+ IV

What if there was a compound that could turn back time, restore energy, improve athletic performance, bring back clarity of thought, reverse depression and help cure cravings for alcohol and drugs even in the most addicted individuals?

There is such a substance. It is called NAD+, and it occurs naturally in every cell in your body.

Compelling research has shown that supplementing with NAD+ may help you withdraw from addictive substances safely, overcome anxiety and depression, handle acute and chronic stress more effectively, and cope better with PTSD.

In fact, clinics across the US are starting to use IV infusions of NAD+ to help people withdraw from drug and alcohol addiction with minimal symptoms in as little as 7-14 days of treatment. These individuals report feeling calm and content and say they lost their “cravings” after a full course of treatment.

And NAD+ may actually prolong life, protect DNA, slow down aging and help restore function in neurodegenerative illness due to its effects on the genes that govern aging.

Unfortunately, drugs, alcohol, stress, medications, chronic illness and age all contribute to a decrease in our NAD+ stores. As NAD+ goes down, so does our energy. Cells age and deteriorate. Your health falls apart at the very root.

This IV aims to undo that process by replenishing NAD+. Using IV infusion therapy we administer this anti-aging compound directly into your blood circulation so your cells have access to as much as they need.

Between 3-14 consecutive days of NAD+ therapy combined with amino acid infusions, minerals, and B-Vitamins are typically recommended for full effect. Treatment is tailored to your individual needs after a detailed consultation.

Added to this therapy is oral Niagen.

and Slow Release Niacin

What is NAD ?

NAD+

NAD stands for “Nicotinamide Adenine Dinucleotide”. It is closely related to the B vitamin Niacin and can also be synthesized from the amino acid l-tryptophan. It plays crucial roles in energy production (as ATP) inside mitochondria as part of the “electron transport chain”. NAD is also necessary for the production of a group of proteins called “Sirtuins” which play a key role in aging, cell death, stress resistance, inflammation, energy efficiency, and mitochondrial biogenesis.

Science

The nicotinamide adenosine dinucleotide (NAD) molecule alternates between two forms. Which one is present depends on how it is being utilized. NAD+ is the reduced (active) form of the molecule. NADH is the oxidized (inactive) form of the same molecule.

Energy production in your mitochondria—the little energy factories that pump out ATP—ABSOLUTELY depends on NADH (the inactive form) being recycled back to active NAD+. If this recycling stops and NADH accumulates the cell runs out of energy and it may die. This was clearly shown in a recent study on brain and kidney cells.1

It goes without saying, then, that depleted levels of NAD+ and accumulation of NADH, or a low ratio of NAD+/NADH, can create problems for your mitochondria and your cells. Indeed, it results in low levels of cellular energy and may be one of the primary contributing factors to “mitochondrial dysfunction”. a condition we now know is implicated in a wide variety of chronic illnesses including autoimmune disorders, diabetes, and others.

Restoring NAD+ levels reverses this process and allows cells to return to full energy status, offering a possible way to undo mitochondrial damage and the resulting chronic illness.

NAD+ as an Anti-Aging Molecule

Medical researchers have long known that a group of enzymes called sirutins play a crucial role in how the body ages—especially SIRT1 and SIRT3. We don’t yet understand precisely how they work, but what we do know is exciting. SIRT enzymes appear to switch off genes that promote aging such as those that cause inflammation, fat synthesis and storage, and blood sugar management issues.

Up until now the only way we knew to positively impact these SIRT enzymes was to go on a very low-calorie diet. As uncomfortable as it may be, caloric restriction is one of the few ways that has repeatedly been shown to lead to a longer life.

However, the tide appears to be turning. You see, recent research indicates that NAD+ plays a key role in the creation and activation of the sirutins.

Doctors out of the Department of Developmental Biology at the Washington University School of Medicine were the first to show this link in 2014.2 The authors note:

NAD(+) levels decline during the aging process and may be an Achilles’ heel, causing defects in nuclear and mitochondrial functions and resulting in many age-associated pathologies. Restoring NAD(+) by supplementing NAD(+) intermediates can dramatically ameliorate these age-associated functional defects, counteracting many diseases of aging, including neurodegenerative diseases.”

These findings were corroborated in 2016 when the scientific journal Rejuvenation published an article where the authors discussed how low NAD+ levels are DIRECTLY associated with cellular aging, and they emphasized that this process can be prevented by increasing the levels of NAD+ within cells.

So is NAD+ a fountain of youth? It could be. More research needs to be done. But one thing seems clear: It certainly has an impact on your body at the cellular level, and it may just turn back the hands of time.

NAD+’s Role in Exercise and Endurance

It is well known that ATP levels get depleted in muscles while exercising. This simply stands to reason. However, until recently we didn’t know how NAD+ was implicated in this process.

A study done in 2010 using both trained and untrained healthy volunteers helped tease out the relationship. The researchers showed that intense exercise decreases NAD+. When the study participants took an antioxidant supplement containing pycgnogenol (which stimulates NAD+ production and protects it from turning into the inactive, oxidized form of the molecule), NAD+ levels increased and exercise performance and “time to fatigue” also improved.3

Using a direct IV infusion of NAD+ is certainly a more efficient way of raising NAD+ levels than taking an indirect, oral supplement that acts as a stimulator for NAD+. So we know that this IV can improve athletic performance, and it likely has a more pronounced effect than the study cited above.

NAD+’s Role in Reversing Chronic Illness and Neurodegenerative Disease

At the end of the day, health and energy production are intimately related. If your mitochondria aren’t functioning or they are producing too little energy, you are going to experience symptoms. When the problem becomes too severe it turns into illness.

The link between NAD+, energy production, and chronic illness really couldn’t be clearer. Low NAD+ results in low ATP levels. Low ATP levels quickly depletes your cell’s energy reserves. Left unchecked, and this can lead to cell death.

How all of this shows up in your body depends on which cells are being affected. If nerve cells are affected, the lack of energy may manifest itself as depression, anxiety, fatigue and lack of focus. In severe cases where the nerve cells are dramatically impacted or even die, neurodegenerative illness like Parkinson’s disease and Multiple Sclerosis may manifest themselves. In the worst cases—like mass cellular death—this may lead not only transient symptoms such as tremors, spasms, tingling, numbness and blurred vision, but to permanent, irreversible disability.

If your heart cells are affected, it can lead to cardiovascular disease. If your lung cells are affected pulmonary disorders may present themselves. Basically, when the cells in your organs and tissues don’t have enough energy, illness results.

IV NAD+ combined with IV amino acids can be beneficial in restoring energy production—especially in the nerve tissue—and may even prevent permanent damage.

One 2014 study showed that rat nerve cells pre-treated with high concentrations of NAD+ before being deprived of oxygen survived the challenge and recovered much faster than cells not bathed in the extra protective NAD+.4 Nicotinamide pre-treatment ameliorates NAD(H) hyperoxidation and improves neuronal function after severe hypoxia

A more recent review article published in 2015 builds on this. After scientists examined all of the available scientific evidence they recommended NAD+ supplementation and restoration as a new therapeutic opportunity for a wide variety of neurodegenerative diseases.5

Some of the conditions which may benefit from NAD+ infusion therapy include:

  • Multiple Sclerosis
  • Parkinson’s disease
  • Alzheimer’s disease
  • Chronic Fatigue
  • Fibromyalgia
  • Mitochondrial Dysfunction

NAD+’s Role in Addiction:

Perhaps the most exciting and controversial use medicine has found for NAD+ so far is in the treatment of drug and alcohol dependency. Despite the controversy, the basic science is sound, and the early results are extraordinary. Patients are reporting total recovery from addiction within 7-14 days with no subsequent craving for their substance of choice and few withdrawal symptoms.

To understand NAD+’s relationship to drug and alcohol abuse, let’s look at its role in the metabolism of alcohol

After you drink, your body tries to process and eliminate every molecule of alcohol. This is done in the liver where ethyl alcohol is converted to acetaldehyde. NAD+ is critical to this process. Alcohol donates one hydrogen molecule IRREVERSIBLY to NAD+ converting it to NADH. That NAD+ molecule is now gone and the NADH in your system begins to build. As this happens repeatedly, the NAD+/NADH balance swings out of favor, and serious problems can occur.

In a 2012 review article, the authors conclude that it is this NAD+ depletion and NADH accumulation that disables the mitochondria in your liver cells from being able to make energy ATP.6This leads to liver cell death. Your body is then even less capable of processing the alcohol out of your system, which may set the stage for chemical dependency.

Building on this principle, several addiction clinics in the United States have been using IV NAD+ combined with IV amino acid therapy with great success. Dr. Ken Starr of the Wellness Group in San Louis Obispo and Dr. Metsayer of the Springfield Wellness Clinic in Louisana have been using a combination of daily IV infusions of NAD+ and amino acids for treatments lasting 10-14 consecutive days to drastically alleviate the symptoms of withdrawal from opiates, benzodiazepines and alcohol.

Their therapy, termed “Brain Restoration” (BR+) is many times combined with traditional FDA approved medications such as suboxone and naltrexone to achieve a much smoother transition to sobriety with drastically fewer unpleasant symptoms. Remarkably, many of their patients report the subjective loss of “craving” for the drug previously abused after the NAD+ and amino acid combination therapy.

Link to Magazine Article on NAD

References

1 Chance, Britton, et al. “Intracellular Oxidation-Reduction States in Vivo The microfluorometry of pyridine nucleotide gives a continuous measurement of the oxidation state.” Science 137.3529 (1962): 499-508.

2 Imai, Shin-ichiro, and Leonard Guarente. “NAD+ and sirtuins in aging and disease.” Trends in cell biology 24.8 (2014): 464-471.

3 Mach, John, et al. “The Effect of Antioxidant Supplementation on Fatigue during Exercise: Potential Role for NAD+ (H).” Nutrients 2.3 (2010): 319-329.

4 Shetty, Pavan K., Francesca Galeffi, and Dennis A. Turner. “Nicotinamide pre-treatment ameliorates NAD (H) hyperoxidation and improves neuronal function after severe hypoxia.” Neurobiology of disease 62 (2014): 469-478.

5 Verdin, Eric. “NAD+ in aging, metabolism, and neurodegeneration.” Science 350.6265 (2015): 1208-1213.

6 Cederbaum, Arthur I. “Alcohol metabolism.” Clinics in liver disease 16.4 (2012): 667-685.  Alcohol metabolism

Intermittent Fasting = NAD regeneration

Archway Apothecary NAD compounding

Addiction-Treatment Daniel Thoomas

BLOG Regarding NAD

ADDICTION RECOVERY
Introduction
Addiction is America’s most-neglected disease. According to a study conducted at Columbia
University, “40 million Americans age 12 and over meet the clinical criteria for addiction involving
nicotine, alcohol, or other drugs.” That is greater than the number of Americans with heart
disease, diabetes, or cancer! An estimated additional 80 million people in this country are “risky
substance users.” This means that, while not technically addicted, they use tobacco, alcohol, and
drugs in ways that threaten public health and safety. The cost to government related to addiction
is nearly $500 billion annually.
Nearly 50,000 people died of drug overdoses in the United States in 2015. This is greater than
the number of deaths attributed to motor-vehicle accidents, homicides, and suicides combined!
Overdose deaths from opiates (narcotic painkillers like OxyContin, Percodan, and methadone, as
well as heroin) have become the fastest-growing drug problem in the United States.
Anyone can become an addict if he or she uses mood-altering substances. There are many
reasons people become addicted, but nobody begins by believing they will become a slave to the
substance and that it will consume and control their life. Some people begin experimenting with
drugs or alcohol to feel high. Others begin because of a legitimate health problem requiring
prescription pain medication. And some are genetically-prone to addiction. In any case, we can
help!
Imagine living life to the fullest without the use of drugs or alcohol. Imagine drugs or alcohol no
longer monopolizing your life. Living life sober is the way to genuine health, happiness, and
satisfaction! For those looking to overcome their addiction to drugs or alcohol, our program
offers a genuine solution and the first step to successful recovery and returning to a normal life.
Our outpatient program provides a powerful jump-start to sobriety by restoring mental clarity
and eliminating or profoundly reducing the cravings that drive relapse. We combat addiction at
the very source: Your brain. The good news is, with our help, the brain can be healed! And what
used to take months or years can now be accomplished in just 10-14 days.
Our holistic and natural approach helps restore normal brain physiology, and helps put the brain
back to a healthy state. By combining clinical neuroscience with metabolic and nutritional
medicine, our cutting-edge treatment balances and improves brain function by restoring optimal
nutrient levels, hormones, and essential brain chemicals to help people overcome addiction. This
alleviates the overwhelming craving for drugs and alcohol, and virtually eliminates the need to
ever use addictive substances to feel normal.
Drugs and alcohol are potent neurotoxins (brain poisons). As such, they fundamentally alter the
very structure and function of the brain. The resultant damage causes the brain to atrophy
(shrink), neural pathways to shift, neurotransmitters to diminish, and cellular receptors to lose
their sensitivity. These alterations can adversely affect a person’s intellect, emotions, personality,
and the ability to make good decisions. Additionally, they can put a person at risk for developing
early-onset Alzheimer’s disease.Addiction is magnified by an unhealthy brain because the person is using drugs or alcohol to feel
better. If you stop the use of drugs or alcohol without addressing the underlying brain
dysfunction, therapy will be incomplete and relapse is likely. However, once the brain is
functioning better, the person will have more energy, improved mental clarity, and greater
emotional resolve to understand and stop their compulsive behavior. This results in a new ability
to make choices that are helpful and self-supportive instead of harmful and self-destructive, and
enable the person to actively engage in the overall recovery process.
The Struggle to Overcome Addiction
The harsh reality is, overcoming addiction can be extremely difficult, and majority of people
who try to give up an addiction will ultimately fail. This is called “relapse” and it occurs because
drugs and alcohol cause profound and long-lasting changes in brain chemistry. Addictions are
exacerbated by an unhealthy brain because the person is using substances to feel better. Although
many substances reward a user with feelings of intoxication or euphoria, this gratification comes
at a severe cost. As such, the highs are followed by lows that can be devastating.
When a chemically-dependent person is denied access to a substance to which he or she is
addicted, the brain goes into a turmoil that manifests itself in the physical symptoms of
withdrawal. These symptoms may include irritability, anxiety, depression, agitation, insomnia,
hot and cold sweats, muscle aches and pains, abdominal cramping, nausea, vomiting, diarrhea,
tremors, and hallucinations.
Conventional addiction treatment that relies solely or mostly on psychotherapy or behavioral
counseling too often yields disappointing results. The “revolving door” of relapse is one of the
most persistent hindrances to successful outcomes. In addition, it is idealistic and naïve to think
one can rise above addiction on their own, or in a treatment program that is not properly
structured.
Most drug rehab programs are ultimately ineffective because they fail to treat the underlying
factors that create and/or sustain destructive addictive behavior. Therefore, addicts will continue
to use chemical substances to “self-medicate” to achieve a sense of normality. Cellular receptors
have lost their sensitivity, and this leads to an increased use of substances to feel pleasure or
simply to feel normal. People will continue to use drugs, or will relapse, until their brain function
is first improved. All the psychotherapy and behavioral counseling in the world cannot overcome
this! The fact is, you simply cannot “talk” a person out of a biochemical craving that has gained
dominance in their lives.
Psychological issues associated with addiction do need to be addressed. However, addressing
these issues is easier and more effective when the person has greater mental clarity and freedom
from unrelenting cravings. Only then is genuine and lasting addiction recovery truly possible.
Using such an approach, we can help people who have failed with other programs to reach a new
level of comfort and control.

A Better Solution
When a person stops taking drugs, their brain can eventually heal on its own (provided they
don’t relapse). This period of drug-free adjustment can be a lengthy and painful process that can
take months to years. This can be physically difficult and emotionally devastating for the addict
and their family. There is a better way! Our process reverses the imbalances that can disrupt
brain chemistry, and restores and accelerates the natural healing ability of the brain. By using a
drug-free and non-addictive combination of neuroactive hormones, amino acids, vitamins,
minerals, and co-enzymes, we can:
 Promote rapid detox without the agony of intense withdrawal symptoms.
 Eliminate by 70-100% the ceaseless and overwhelming cravings that are the primary
cause of relapse.
 Begin to reverse the damage that drug or alcohol abuse has done to the brain.
 Address the neurochemical imbalances that are at the root of addiction.
 Begin to reverse brain atrophy by stimulating the growth of new brain cells.
 Reset the brain and re-establish old (original) neural pathways.
 Replenish neurotransmitters (chemical messengers in the brain).
 Restore sensitivity of cellular receptors.
 Reduce fatigue, apathy, and despair.
 Reduce anxiety, depression, and compulsive behavior.
 Replenish and rebalance the brain to restore normal cognitive function.
 Restore mental clarity, emotional balance, and a true sense of well-being.
 Improve pain tolerance.
 Provide optimism and motivation about returning to an addiction-free life.
Our treatment program utilizes oral and intravenous (IV) compounds that are administered over a
10-14-day period by a registered nurse under a doctor’s supervision. Ten days are needed for
addiction to painkillers, such as Dilaudid, Fentanyl, Lortab, OxyContin, oxycodone, Percocet,
and Vicodin; alcohol; heroin; marijuana; sedatives, such as Ambien and Lunesta; and tobacco
(nicotine). Fourteen days are needed for those coming off methadone; Suboxone; cocaine;
stimulants, such as Adderall, methamphetamine, and Ritalin; and benzodiazepines, such as
Klonopin, Valium, and Xanax. (Note: The response of people addicted to benzodiazepines is less
predictable, but overall, treatment is effective. Those with multiple addictions may need 14-16
days of treatment.)
On Days 1-4, treatment typically lasts 8 hours. On Days 5-10, treatment time can decline to 6
hours. On Days 11-14, treatment may last 4 hours. The symptoms of withdrawal vanish quickly,
and the cravings begin to subside soon after. Between the 4th and 8th day, patients typically
report feeling energized and having a profound sense of mental clarity and ability to focus.
By the end of the 10-14 days, patients report little or no craving or desire to use drugs or alcohol.
At that point, with armed with improved cognition and absence of unrelenting cravings, patients
can begin to function normally, work, be present for their families, and enjoy the lives they had
nearly destroyed.Each day of the treatment, the nurse inserts an IV catheter into a vein. The patient relaxes in a
comfortable recliner while the IV solution is slowly infused through the vein. Most people relax
or sleep, watch TV, listen to music, read, or check their email. Snacks and meals are provided.
The IV ingredients are made by US-licensed compounding pharmacies. While other programs
utilize addictive medications such as methadone or Suboxone, we use only non-addictive
medications and all-natural substances, so you do not have to worry about substituting one
addiction for another.
Treatment is very safe. Infusions are well tolerated and any side effects are negligible and
subside at the end of the infusion. The most commonly reported side effect is feeling slightly flulike
which passes rapidly. Patients don’t need cardiac or respiratory monitoring. At the end of
each day, they return home or to their hotel room.
Patients must complete the entire series of treatments to receive the full benefits. To ensure the
results are not eroded over time, patients are given a booster IV infusion every three months for
the first year, as well as recommended use of oral supplements. If a person does relapse, a oneor
two-day IV treatment is usually sufficient to get back on track to an addiction-free life. The
goal is to strengthen and stabilize sobriety, especially for 5+ years. At that point, studies have
shown that the chances of relapse drop dramatically.
The cost for treatment is $850 per day for the 10-14-day treatment. Treatment includes in-office
medications, supplements, and physician fees. Other offices charge $1,200-$1500 per day for
similar treatment. At-home medication (if needed) and supplements are extra, as is drug
counseling.
The Power of IV Therapy
IV therapy is a method of administering concentrated solutions of vitamins, minerals, and other
therapeutic substances directly into the bloodstream, bypassing the digestive tract where many
nutrients may be partially lost due to poor absorption. It is a safe and highly effective method for
quickly restoring key substances needed for energy production and optimal cellular function. It
can be a very powerful tool in the prevention and treatment of a wide variety of chronic diseases,
and it is especially useful in the treatment of addiction.
By temporarily creating higher-than-normal blood levels of important nutrients, IV
therapy drives these nutrients straight into the cells within seconds by delivering them directly
into the body’s circulation. This provides better bioavailability compared to oral nutrients, and
avoids side effects like nausea, heartburn, and diarrhea that can accompany high oral doses. The
resultant cellular repair and revitalization can be rapid and dramatic.
The Importance of Optimizing ATP Production
From the electric-powered devices we use in our homes to the gasoline-powered cars we drive;
everything needs a source of energy (power) to function. The human body is no different. Instead
of electricity or gasoline, the body is powered by an energy source called adenosine triphosphate
(ATP) which is made from the food we eat by the tiny capsule-shaped cellular structures callemitochondria. Mitochondria are often referred to as the “powerhouses” of the cells. They
generate energy in the form of ATP that our cells need to do their jobs.
It is ATP that powers the highly energy-intensive cellular mechanisms needed to maintain our
health and fight disease, such as tissue regeneration; preventing cell injury and death; DNA and
cellular repair; killing of bacteria, viruses, and cancer cells; and removal of toxins, just to name a
few. Without sufficient energy in the form ATP, our body’s ability to carry out its normal
functions is undermined.
Recent discoveries in cellular biology have found that the root cause of disease (and even aging
itself) may all boil down to decaying energy production. When mitochondria become
dysfunctional (decrease in the number and/or function of mitochondria) and the supply of ATP
drops, our cells face an energy crisis, and the body is unable to function normally to maintain our
health and fight disease. We now understand that mitochondrial health translates to overall
health, and we now know that drugs and alcohol are toxic to mitochondria. More and more
medical researchers are finding that mitochondrial dysfunction and the resultant ATP deficiency
may be an unrecognized healthcare crisis.
While mitochondria dysfunction affects various parts of the body in different ways, the brain is
particularly susceptible to it. Brain function is especially dependent on energy. Your brain
requires an enormous amount of energy to function normally. A single brain cell consumes nearly
5 billion molecules of ATP per second—at rest!
Having an effective way to stimulate mitochondrial activity and produce more ATP represents a
breakthrough approach in the fight against drug and alcohol addiction. By using a combination
of IV and oral nicotinamide adenine dinucleotide (NAD), coenzyme Q10 (CoQ10), and
magnesium, we can dramatically increase mitochondrial output of ATP.
NAD is a derivative of vitamin B3 (niacin), and is a naturally occurring co-enzyme that plays a
key role in metabolism and energy production in each of our 100 trillion cells of the body. NAD
is a central component of glycolysis, the citric acid cycle, and the electron transport chain, which
are all involved in cellular respiration and the production of ATP for energy.
NAD fluctuates between NAD+ and NADH. NAD+ is the oxidized or active form. NADH is the
reduced or inactive form. Having a high NAD+-to-NADH ratio is crucial for good health. Low
ratios are associated with drug and alcohol addiction, as well as a long list of other medical
conditions, including neurodegenerative diseases, obesity, metabolic syndrome, and diabetes.
NAD is almost like “rocket fuel” for the brain. Optimizing NAD+ levels allow brain cells to
operate at full-energy status, and provide the brain with the vital energy needed to support and
hasten its inherent and natural healing abilities. Besides drug and alcohol addiction, research and
clinical experience has shown the following mental-health and neurological conditions may
improve by administering NAD:
 ADHD
 Alzheimer’s disease
 Amyotrophic Lateral Sclerosis (ALS) Anxiety
 Chronic fatigue
 Depression
 Fibromyalgia
 Insomnia
 Ischemic stroke
 Migraine headaches
 Multiple sclerosis
 Parkinson’s disease
 Post-traumatic Stress Disorder (PTSD)
 Traumatic Brain Injury
CoQ10 plays a central role in the production of ATP due to its activation of the electron transport
chain in the mitochondria. In addition, ATP requires magnesium (Mg) to be biologically active.
What is called ATP is actually Mg-ATP. Our treatment literally floods the brain with nourishing
and highly-therapeutic NAD, CoQ10, and magnesium, as well as important vitamins, minerals,
and amino acids.

                                                    Intermittent Fasting and NAD

______________________________________________________

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There is hardly a person on this planet who does not cherish the moment their taste buds make contact with good food or a refreshing beverage. We are creatures of comfort, and this sometimes leads to indulgence. Unfortunately these indulgences can come with hidden dangers. Today there are many people who fast to manage their body weight, but it is nothing new; it has been practiced since ancient times for physical and spiritual purification.

Fasting is just the restriction of specific foods for set periods of time. When some people hear the word they dismiss it, wrongly assuming only monks and yogis fast. Research into longevity genes and the ways different schemes of caloric restriction affect their expression is changing this view. Fasting is and has been the norm in many societies throughout history. If fasting is something you would like to try, you must first decide on which approach is best for you.

Occasional Short Fasts is where I recommend people start. These can last 6, 12, or 24 hours. This means you could fast for 6 hours straight at any time of the day, although mornings are generally preferred. As one can imagine, this approach offers a great deal of flexibility. Once you decide what you are abstaining from, you can plan accordingly. For example, if you are abstaining from milk products, make sure there are no dairy temptations around you.

Intermittent Fasts – With this type of fasting, you cycle between periods of eating and fasting. It’s not about what food you should eat but when you should eat. Intermittent fasting involves daily 16 hour fasts or fasting for 24 hours twice a week. Some people use the 16/8 Method. This involves skipping breakfast and restricting the window of consumption to 8 hours. This is followed by a 16 hour fast  More than another fitness fade, it is also a means of organizing and simplifying your life.

Water Fasting is close to my heart. After the cells use up the glucose from your last meal your body has to find another source of energy, which means glycogen (a polysaccharide stored in the liver and muscle tissue) must be broken down to supply it. After the glycogen is used up, the cells begin burning fatty acids for energy.

Extended Fasts is a sure but hard path. It is probably the second most extreme form of fasting, since you are expected to go 2-3 days without eating. The most extreme fasting would be dry fasting during which you don’t consume anything, including water. During a long fast, your body stays in ketosis for an extended period. It suppresses hunger and lets you  get your mind off food.

I have fasted for three days at a time. I usually water fast (consuming only water throughout the fasting sessions)  The absence of calories for three days sets the body on edge, but also maximizes immunity against diseases and encourages various cellular repair processes. Still don’t believe me? Let’s look at some facts and figures gleaned from the cutting edge of longevity science.

How Fasting Changes Our Bodies

Fasting remains a part of every major religion in the world. Jesus Christ, the yogis of India, Buddha and the prophet Muhammad all shared a common belief in the healing power of fasting. In spiritual terms, it is considered cleansing or purificatory, but practically, it amounts to the same thing. Dietary alterations can go a long way to counteracting the ravages of time.

The body undergoes many positive changes during fasting. While fasting, our body generates its own energy by burning stored resources made from excess fats, carbs, and sugars to produce energy. The liver then converts fats into chemicals called ketone bodies, which are then used as an energy source. Chemicals and toxins are absorbed from the food are then stored as fat reserves and released during fasting.

Medical studies show that during a fast abnormal tissues growths, like tumors, become more susceptible to remission. One of the first major studies took place in 1945 and showed that intermittent fasting not only prolonged life but reduced the prevalence of breast cancer tumors in rats. A more recent study in 2009 proved the practice can even reduce the severity of side effects of high-dose chemotherapy.  Valter Longo, associate professor of gerontology and biology at USC, was part of the 2009 study. His study results were explained this way:

“In essence, these cells are waiting out the lean period, much like hibernating animals. But cancerous tumors respond differently to starvation; they do not stop growing, nor do they hibernate because their genetic pathways are stuck in an ‘on’ mode. Longo realized the starvation response might differentiate healthy cells from cancer cells by their increased stress resistance and that healthy cells might withstand much more chemotherapy than cancer cells.”

A few years later, Longo reported that fasting alone was enough to treat many types of cancer in mice. Because the body’s healthy cells were in this hibernation mode, the cancer cells tried to find other ways to divide and spread, without  much success.

Other processes that sustain the foundational infrastructure of the body are fostered by fasting, which means the production anti-aging growth hormones is increased. Now we are getting somewhere! Has your interest piqued yet? Our bodies are resilient and quite capable of healing themselves.

Unfortunately, we may internally mutilate our bodies with unhealthy food. This interferes with our bodies innate potential to rebuild cells and lengthen our lifespans. By encouraging regeneration, fasting results in healthier cells, tissues, and organs. There’s a tentative hypothesis circulating among  doctors and nutritionists that fasting allows the body to concentrate its resources on ridding itself of diseases and poisons rather than using them to digest food.

Scientists and Doctors who Support CR and Fasting

Clive Maine McCay – An American biochemist, gerontologist, nutritionist and professor, discovered CR increases the lifespans of rats in 1934. Fifty years later his work was recognized as a viable research model for aging.

Valter Longo – An Italian biogerontologist and a cell biologist who serves as the director of USC Longevity Institute. He has published several articles on calorie restrictions and its longevity benefits.

Dr Kris Verburgh – a medical doctor, researcher and author. By the age of 25 he had written three books. His writes, “ageing is a very complex process. The rate of ageing is influenced by our genes, our environment, and more specifically, by how and what we eat. Powerful interventions that slow down the ageing process will come to see the light in the coming decades. For now, the most potent tool at our disposal to impact the rate of ageing, is our diet.”

Calorie Restriction

“Have breakfast like a king, lunch like prince, and dinner like a beggar.” Not having to cook large meals in the evening not only saves time but also paves a path for better eating habits.

If fasting seems or sounds tough, a more trendy approach to healthy eating and cellular repair is Calorie Restriction (CR). According to Dr Kris Verburgh, an author, medical doctor, and gerontological researcher, Calorie Restriction is the practice of limiting dietary energy intake. In CR energy intake is minimized, but sufficient quantities of various micronutrients must still be consumed. For example, males between 19-30 need about 2600 calories a day. During CR they would eat 2000 calories daily. The average lifespan in developed nations is approximately  80 years and the maximum lifespan is approximately 120 years.

CR works at the molecular level by regulating transcription factors. While the average lifespan is determined by genetic factors and lifestyle choices, there are few interventions known to science that can increase maximum lifespan in model organisms. CRand rapamycin (a compound that has successfully extended maximum mouse lifespans – even brief rapamycin treatment in middle-aged mice lived up to 60 percent longer than the control group) if you practice CR, your body will generally think it must prepare itself to deal with scarcity. CR inhibits growth and promotes maintenance. This may not sound like an entirely good thing, but if growth (constant production and replacement of cells and proteins and DNA, etc), is inhibited via CR, then we age less rapidly.

If we eat like we normally do, with an overabundance of food, then the body will no longer go into a “power-saving mode.” Therefore, plenty of proteins are created, mitochondria (the energy power plants of our cells) run at full speed creating free radicals. These cellular activities cause the body to age faster. CR is very beneficial to our overall health. There are extensive benefits to CR which will be discussed later in this article. However, when commencing calorie restriction, people must take caution not to become deficient in essential nutrients. CR is most certainly not suitable for everyone especially for pregnant women, children, and people with certain illnesses.

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The crystallographic structure of yeast sir2.

Sirtuins

Many scientists believe  CR activates a longevity factor belonging to a class of genes called Sirtuins (SIRT1). The following information comes from primarily from a paper somewhat dramatically titled Unlocking the Secrets of Longevity Genes. A few years ago scientists believed aging is not just deterioration, but an active continuation of an organism’s preprogrammed developmental cycle. These two ideas turned out to be complimentary.

By optimizing the body’s functions for survival, these genes maximize an animal’s chances of enduring a famine. If they are activated over prolonged periods, they can dramatically extend the organism’s lifespan. Scientists believe CR is a biological stressor, and like natural food scarcity it induces a defensive response. In mammals its reported effects include changes in repair, energy production, and the activation of programmed cell death, also called apoptosis. The survival mechanisms turned on by CR stalls the progressive damage suffered at the cellular level on a daily basis.  This is seen as a breakthrough when it comes to anti-aging, as the longer we keep our cells and organs functioning, the longer we are able to healthfully and happily live.

Another critical process influenced by Sirtuins is inflammation. Inflammation has been connected to cancer, arthritis, heart disease, diabetes, and assorted neurodegenerative disorders. SIRT1 is activated by NAD+, an important substrate in energy and oxidation reactions, so SIRT1 acts as an energy and redox sensor. Nicotinamide adenine dinucleotide (NAD+) is a classical coenzyme; it plays an important role in the regulation of NAD+-consuming enzymes, including sirtuins, poly-ADP-ribose polymerases (PARPs), and CD38/157 ectoenzymes.

NAD+ biosynthesis, mediated by nicotinamide phosphoribosyltransferase (NAMPT), and SIRT1, function together to regulate metabolism and circadian rhythm. NAD+ levels decline over time and may be an Achilles’ heel, causing defects in nuclear and mitochondrial functions, and thus contributing to age-associated pathologies, including neurodegenerative disorders.Restoring NAD+ by supplementing with NAD+ intermediates can dramatically ameliorate these age-associated defects. Thus, the combination of sirtuin activation and NAD+ intermediate supplementation may be an effective anti-aging intervention. We have already touched heavily on CR but here’s a brief overview of Calorie Restriction mimetics and enhancers.

Resveratrol activates sirtuins, a powerful family of “information regulator” proteins that inhibit NF-kB, thereby reducing inflammation throughout the body. Resveratrol also prevents inflammatory mast cells from releasing the histamines that trigger asthma and allergic reactions. Resveratrol decreases production of the adhesion molecules that attract inflammatory cells to vascular walls, one of the principal culprits behind atherosclerosis. Adhesion molecules also permit cancer cells to invade tissue and metastasize. Resveratrol’s influence on NF-kB, a critical protein complex that governs response to proinflammatory cytokines, and in turn plays a significant role in free radicals, cholesterol levels, immune function and cancer prevention.
Pterostilbene – found in blueberries, pterostilbene is a polyphenol closely related to resveratrol. It limits NF-kB activity through multiple complementary mechanisms. In vitro, pterostilbene suppresses invasive tumor activity and enhances therapeutic destruction of cancer cells.
Quercetin can protect against chronic inflammatory conditions such as asthma, inflammatory bowel disease, and arthritis is due in part to its capacity for NF-kB inhibition.
Grape seed extract also disrupts cellular inflammation signaling by blocking NF-kB. Its effect on proinflammatory cytokine production in fat cells may even help combat obesity and type 2 diabetes.

These nutraceuticals have been shown to generate many of the same effects in the body as CR without significant dietary modification. They “mimic” CR’s favourable impact on genes associated with the aging process.

Benefits of Fasting, Intermittent Fasting(IF) and Calorie Restriction(CR)

Several labs have conducted tests on rodents and other mammals in regards to examine the effects of CR and IF. In 2006 Christiaan Leeuvenburgh of the University of Florida’s Institute on Ageing showed eating 8 percent less and exercising a little more over a lifespan can reduce or even reverse age-related cell and organ damage in rats. Let’s look at a few more examples.

Changes to the function of cells, genes and hormones –

  • during fasting your body initiates important cellular repair processes and charges to hormone levels.
  • Inducement of cellular repair, such as the removal of waste materials from cells, also known as autophagy. Increased autophagy may protect against several diseases including cancer and Alzheimer’s Disease.
  • Gene expression – beneficial changes to longevity and protection against diseases.

Helps Lose Weight and Belly Fat –

  • Forces you to eat fewer meals, lowers your insulin levels, raises growth hormone levels, and increases your metabolic rate by between 3.6 – 14%, helping you burn more calories.
  • Lowers the risk of type 2 diabetes – one study in diabetic rats showed IF protects against kidney damage, one of the severe and common complications of the disease.
  • Reduces oxidative stress and inflammation. Oxidative stress is one of the key players in aging and chronic diseases.

Prevents Heart Diseases –

  • Heart diseases is the world’s number one killer. Good news is fasting can improve risk factors for heart diseases such as blood pressure, total and LDL cholesterol, triglycerides, inflammatory markers and blood sugar levels. However, more studies need to be done in humans before recommendations can be made.

Fasting Can Help Prevent Cancer –

  • There’s beneficial effects on metabolism that may lead to reduced risk of cancer. Although human studies are needed, promising evidence from animals studies indicates fasting may help prevent cancer.

Fasting is Good for the Brain –

  • Fasting increases a hormone called brain-derived neurotrophic factor. BDNF helps protect the brain.

Fasting Helps with Life Extension – the faintest prospect anything extending lifespans is  exciting. Studies in rats have shown fasting extends lifespan just as well as continuous caloric restriction. In one study, rats that fasted every other day lived 83% longer than the control. Although it has not been proven to be as helpful to humans, fasting has become a popular trend amongst the anti-ageing crowd. Given the known benefits to metabolism and a sundry of biomarkers, as well as the numerous similarities between humans and other mammals, it may be safe to conclude fasting will be a viable option for health-conscious longevity enthusiasts.

As mentioned earlier, fasting can deliver excellent results to people who are looking to lose weight  or improve their overall health, but it is not a walk in the park. You need to be strong enough to fight the pangs of hunger. With few exceptions humans love shortcuts, so I have compiled a few natural appetite suppressants that might come in handy when you need to curb the urge.

Almonds are a rich source of antioxidants, vitamin E and magnesium, almonds increases the feeling of fullness and helps with weight management.

Ginger works as stimulant that energizes the body and improves digestion, thereby making you less hungry.

Cayenne Pepper – just half a teaspoon of this fiery goodness can boost your metabolism.

Apples are filled with soluble fiber and pectin, which helps you feel full. It also regulates your glucose and boost your energy level.

Green Tea in moderation suppresses appetite. The major appetite suppressant factor lies behind its effects on norepinephrine(stress hormone)and dopamine (neurotransmitter key to regulating the brain’s rewards and pleasure centres).

Green Leafy Vegetables serve as low calorie appetizers before your meal. Plus, you get a lot of good vitamins and minerals, but always watch what dressings you put on your salads!

High Fibre Fruits and Vegetables are the best for filling you up. These delay the emptying of your stomach and makes you feel full, which helps you control your weight. These fibre foods include oatmeal, lentils, apples, oranges, pears, oat bran, strawberries, nuts, flaxseeds, beans, blueberries, cucumbers and celery.

Exercise helps burn calories, tones muscles, and improves cardiovascular health. Even though it’s a temporary appetite suppressant, some people find exercising makes them find healthier food choices.

Time – Time is an appetite suppressant?. When you eat too fast you end up eating those few extra calories that are not needed. Try waiting before reaching for a second helping. Sit back and enjoy your meals slowly.

Mint is a handy suppressant. Try drinking mint tea if you are trying to cut back on snacking.

Although these are all well-known appetite suppressants, before you consume anything you haven’t before, please consult your doctor.

Keep in mind that when applying any this information to yourself, please be mindful that you still need vitamins and minerals. Fasting is not about starving yourself. For some people, it’s a way of life. Never go to the extremes when you haven’t fasted before. If you suffer from heart disease, autoimmune disorders, cancer or any other ailment linked with inflammation, please, once again, consult your doctor and speak to a nutritionist to put together a healthful regime. Food is still a necessity. Fasting is not something to do everyday!

As promising as it all seems, more human trials are still needed. Fasting isn’t a cure-all, but it appears to assist in cellular repair, weight loss, and in the prevention of . For now, cultivate healthy eating habits, exercise regularly, stay informed on the latest information, and try to lead a stress-free life.

 Works Cited:

Alarcon De La Lastra, Catalina, and Isabel Villegas. “Resveratrol as an anti‐inflammatory and anti‐aging agent: Mechanisms and clinical implications.” Molecular nutrition & food research 49.5 (2005): 405-430.

Bitto, Alessandro, et al. “Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice.” eLife 5 (2016): e16351.

Carlson, Anton J., and Frederick Hoelzel. “Apparent prolongation of the life span of rats by intermittent fasting.” J Nutr 31 (1946): 363-375.

Folsom, Aaron R., et al. “Prospective study of coronary heart disease incidence in relation to fasting total homocysteine, related genetic polymorphisms, and B vitamins The Atherosclerosis Risk in Communities (ARIC) Study.” Circulation 98.3 (1998): 204-210.

Fresco, P., et al. “New insights on the anticancer properties of dietary polyphenols.” Medicinal research reviews 26.6 (2006): 747-766.

Gallí, Mara, Frédéric Van Gool, and Oberdan Leo. “Sirtuins and inflammation: Friends or foes?.” Biochemical pharmacology 81.5 (2011): 569-576.

Ho KY, Veldhuis JD, Johnson ML, et al. Fasting enhances growth hormone secretion and amplifies the complex rhythms of growth hormone secretion in man. Journal of Clinical Investigation. 1988;81(4):968-975.

Kim, Hyon Jeen, et al. “Modulation of redox-sensitive transcription factors by calorie restriction during aging.” Mechanisms of ageing and development 123.12 (2002): 1589-1595.

Marziali, Carl. “Fasting Weakens Cancer in Mice.” USC News. University of Southern California, 8 Feb. 2012. Web. 10 Sept. 2016.

Safdie, Fernando M., et al. “Fasting and cancer treatment in humans: A case series report.” Aging (Albany NY) 1.12 (2009): 988-1007.

Sinclair, David A., and Lenny Guarente. “Unlocking the secrets of longevity genes.” Scientific American 294.3 (2006): 48-57.

Sohal, Rajindar S., and Richard Weindruch. “Oxidative stress, caloric restriction, and aging.” Science (New York, NY) 273.5271 (1996): 59.

Verdin, Eric. “NAD+ in aging, metabolism, and neurodegeneration.” Science 350.6265 (2015): 1208-1213.

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What is NAD?

NAD+ stands for Nicotinamide (nick-o-tin-a-mide) Adenine (ad-a-nine) Dinucleotide (di-nuke-lee-a-tide). It is an essential molecule found in every cell of your body; a coenzyme of Vitamin B3 (niacin), which means it’s a small helper molecule that binds to a protein molecule in order to activate an enzyme. Enzymes are responsible for over 5,000 different biochemical reactions throughout the body and NAD+ participates in more reactions than any other vitamin-derived molecule. NAD+ is basically the building block of a healthy body that the brain, our internal organs and neurological systems need to function at optimal efficiency.

Why is NAD important?

As we age, our NAD+ levels decline. Addiction, depression, stress and illness also deplete our NAD+ levels. A significant increase in NAD+ levels helps to restore brain functionality. As a result, patients have experienced increased clarity of mind, better problem-solving ability, improved focus and concentration, increased energy, improvement in mood, decreased anxiety levels, and reduced cravings. This revolutionary alternative treatment heals brain-destroying diseases such as alcoholism, addiction, chronic stress, depression and anxiety.

What does NAD do?

NAD+ is needed for metabolic functions to take place in all the cells in your body, including your brain. Scientists have shown that NAD+ significantly decreases as we age, so it’s beneficial to replenish NAD+ levels so your body can function at optimal levels. NAD+ is involved in these roles throughout the body:

1. Energy production (ATP): NAD+ helps your cells convert food into energy by acting as an electron transporter during cell metabolism.

2. DNA repair: A constant supply of NAD+ is needed for the activation of PARPs, which detect and repair damaged DNA.

3. Gene expression: Your body has a class of proteins called sirtuins that help regulate certain metabolic pathways and genetic expressions. Sirtuins are NAD-dependent and the more sirtuin activity, the better for health and longevity. Increased sirtuin activity can help increase metabolism, decrease inflammation, extend cell life, and prevent neurodegeneration.

4. Cell signaling: NAD+ is also released from the intercellular space to the extracellular space for communication. Research is revealing that NAD and ATP may alert the immune response when the cell is under stress or when there is inflammation.

5. Neurotransmitter: Although more research still needs to be conducted, in some instances, NAD+ meets the pre- and postsynaptic criteria for a neurotransmitter. NAD+ is released from smooth muscle, neurosecretory cells, and brain synaptosomes for cell-to-cell communication.

6. Enzyme activity: NAD+ and NADH are used in processes such as metabolizing alcohol and converting lactate to pyruvate in the body.

 

What is NAD Therapy?

NAD+ Therapy involves a high dose intravenous infusion of NAD+ that goes straight into the bloodstream. IV therapy allows NAD+ to bypass the digestive system for better absorption. NAD+ works rapidly to repair cells throughout the body and neurons in the brain. When your NAD+ levels are increased, your cells produce more energy, your good genes are “turned on”, DNA is repaired, and many other functions are optimized. Since NAD+ is such a powerful and prolific molecule in the body, high dose IV therapy can be helpful for many different conditions including:

  • Substance abuse
  • Addiction
  • Alcoholism
  • Anxiety
  • Stress
  • Depression
  • PTSD
  • Chronic Fatigue
  • Chronic Pain
  • Neurodegenerative disorders

Research of NAD+ also shows promise for therapy of sleep disorders and behavioral disorders such as autism.

At the end of treatment with NAD+ therapy, clients have generally reported the following benefits:

  • Increased energy
  • Improved mood
  • Increased mental clarity
  • Increased focus and concentration
  • Improved memory
  • Decreased pain
  • Improved eyesight and hearing
  • Enhanced sense of purpose
  • Reduced cravings of substances
  • Minimal to no withdrawal symptoms during treatment
  • Disclaimer – NAD+ qualifies as a supplement under FDA guidelines. These statements have not been evaluated by the Food and Drug Administration. Intravenous NAD+ therapy is not intended to diagnose, treat, cure, or prevent any disease.
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Brain Restoration: ‘Too Good To Be True’ for Addiction and Disease?

By Royce Amy Morales03/20/14

Could megadoses of energy-giving NAD—which allegedly relieves withdrawal symptoms, flushes out stored drugs in the body and replenishes balance in the brain—really be the cure-all for addiction as well as many other diseases and mental health disorders?

brain repair.jpg

 

When Paul decided again it was time to do something about his drug addiction, he knew the usual routes wouldn’t work. While using a variety of substances for at least two-thirds of his life – injecting heroin in the last 20 years of it – he also became a veteran of just about every traditional rehab/detox program in the book. Twelve to be exact; with no permanent results or positive outcomes to speak of.

Hearing the remarkable claims from a Brain Restoration Therapy outpatient clinic immediately sent him into skeptic mode: This is too good to be true. How can I kick drugs with just an infusion of some concoction?  What about withdrawal?  Side effects?  And, if it really works, will it last? Sounded far too simple for this jaded, somewhat cynical, pushing-60 drug addict.

Figuring he had nothing to lose, he called and arranged a free consultation. After listening to details of their success rate and impressed with assertions of little or no withdrawal symptoms, he signed up for the treatment – albeit with some reluctance. His wife’s divorce threat had something to do with enrolling, but it was more about life hitting bottom one more time.

Groggily arriving at the crack of 9 am the next day, a warmly friendly nurse in navy blue scrubs hooked him up to an IV. Told that all he needed to do was relax, he settled into the oversize leather lounge chair. If nothing else he’d be able to listen to music, watch a few videos, and read a bit, he thought. Observing the slow drip of clear liquid entering his veins, he listlessly wondered what he would do next if this latest treatment failed.

At the end of the first eight-hour treatment, Paul says he already felt different. He couldn’t quite explain it, he recalls, but his mind was clearer. He felt energized. More alive. And definitely more present.

Returning daily for nine more treatments, he noticed a growing list of undeniable and rather dramatic changes. His outlook was more positive and he was optimistically able to imagine a future for himself, one he’d stopped envisioning years ago. His mind was as sharp as it had been prior to years of drug use.

The best part, he says, true to the claims, there were few or no withdrawal symptoms, therefore no need for a replacement drug to get him through yet another grueling detox. He also realized he had no cravings, the primary cause of his continued bouts of relapse. His disbelief completely gone, he recalls, he concluded he was drug free.

But would it last?

Ann Rodgers, the Director of Brain Restoration Therapy, meets me at the door of the Center for Health and Wellbeing in San Diego, CA., where the clinic operates under medical supervision. It’s difficult to not get caught up in her animated explanation of the benefits of this program. “The treatment utilizes a megadose of NAD [Nicotinamide Adenine Dinucleotide is a co-enzyme of niacin that is the key fuel for energy production in every cell of the body] in an IV form, and it’s clinically proven with a 90% no-craving statistic,” she excitedly offers.

Listening quietly as she rapidly fires glowing statistics in my direction, my skeptical mind revs into full gear. “With literally no reported side-effects,” she says, “the protocol reduces withdrawal symptoms by 70-80% without using replacement drugs, and restores the patient’s clarity and well-being to pre-use levels. Six to ten days of treatment is like a seven or eight month jump-start to recovery.” All this expounded with the tone of a bragging parent.

Rodgers tells me that although relatively new to America, NAD treatment has been successfully used in South Africa since 1961, with centers there reporting more than 22,000 people treated. [Rodgers could not provide any research report from South Africa to confirm this, only a report from individual clinicians who treated patients with NAD. Separately, I could not confirm the 22,000 figure.]

The first NAD clinic to open in the States was in Springfield, Louisiana, founded by psychotherapist Paula Mestayer, M.Ed, LPC, FAPA, along with her psychiatrist husband Richard. The couple discovered the treatment when their 16-year-old adopted daughter became addicted to alcohol and found her way into NAD treatment. Thrilled to see her positive results, they conducted their own research and in 2001, putting aside their cumulative years of treating addicts with therapy, they opened the Springfield Wellness Center on a private 500-acre estate. They claim to have treated more than 1,000 patients since then with NAD.

Springfield Wellness Center’s ten day addiction detox, Mestayer asserts when I contact her, has been used successfully on people hooked on prescription drugs, alcohol, opiates, benzos, stimulants, cocaine, marijuana, suboxone, and methadone.

Mestayer noted in our interview that “like a thumb print, all brains are unique, so this protocol is more like an art than a science.” Each patient, she pointed out, responds differently to NAD, with one factor being their type of addiction. She therefore adjusts the dosage and prescribes booster NAD treatments when necessary, especially when a patient feels vulnerable or if any cravings return. “I always emphasize that there may be a period of time where they need maintenance, either by an occasional booster or other means of support. Some patients have gone nine years without needing a booster, but many do.” Mestayer generally prescribes oral NAD as a supplement to the IVs, on the grounds that the more NAD that builds up in an addict’s system, the less prone he or she is to succumbing to cravings.

Mestayer emphasizes that the treatment is “not a cure, but rather maintenance,” and notes that it remains a mystery as to why NAD works more successfully on some addictions than others. “The highest success rate is on alcohol and opiate users,” she says. “The only failures are people who were using during the treatment or not committed to their maintenance.” Even so, she like Rodgers encourages all patients to seek therapy and support groups to address underlying psychological issues.

In California, I asked Rodgers if the treatment is just a substitute “high.” Rodgers countered with “it’s a state of well-being that allows the client to feel content with their life, so many don’t even consider going back to being an addict, no desire for that miserable life anymore. It’s as if they become themselves again, back to their natural state, seeing themselves as a different person, separate from being an addicted person. It’s not just a detox; it’s a total state of sobriety.”

With only a handful of other U.S. clinics in existence, the technology has yet to become familiar to most of the recovery community. Even so, Ann Rodgers says she is certain that once knowledge of NAD spreads, it will be seen as a revolution in addiction treatment. “[Members of] the AA community have been resistant to it at first, but once they read the evidence and witness the results, they embrace it,” she claims.

Her San Diego clinic is modern, serenely comfortable and well-appointed. Located on the first floor of the larger health center, it’s been open for over three years and has treated nearly 40 patients. Rodgers recently opened another facility in Los Angeles, CA, at the Center for Optimum Health.

HOW THE TREATMENT WORKS

Dr. Janette Gray, a California licensed internist and a pioneer in combining allopathic and holistic medical approaches, is the center’s medical director. Board certified in Holistic Integrative Medicine, she worked for years in the prison system helping inmates get off drugs and has extensive experience with the agonies of drug withdrawal. “Seizures, nausea and vomiting, intense sweating and physical pain are standard, but that is greatly minimized with this program,” she tells me. “The most common withdrawal symptom is feeling a little bit flu-ish…[which] passes quickly.”

Gray rattles off to me a scientific explanation behind the BR treatment. The protocol, she says, employs a proprietary NAD formula administered by IV. NAD is an element that reacts with oxygen in the cell’s mitochondria in order to create energy for movement, breathing, heartbeat, blood pumping, digesting food, brain functions, and generally living life. It is available in low doses over the counter.

Studies have found that those with extremely low NAD levels (which can be present even at birth) are far more vulnerable to addiction as well as other diseases and to chronic physical conditions. There is a preponderance of low levels of NAD present in Western society as it is mostly lost in cooking and food processing. What little remains is broken down by stomach acid, degraded before it’s absorbed from the digestive tract.

When the clinic’s all-natural NAD is received directly through an IV, the nutrients bypass the stomach and go directly to the receptors in the brain, Gray tells me. According to Gray, this immediately produces palpable positive results as the nutrients bathe the brain in a continuous pool of natural and highly therapeutic co-enzymes.

Since NAD is a detoxifier, it takes days (rather than weeks or months), to flush out stored drugs from the body and its organs, replenish balance in the brain, and reverse damage. Results can be mental clarity, cognitive function increase, focus and concentration returns, more energy, better mood, positive outlook. And this happens cold turkey.

“We find that one of the big reasons this treatment works is because it’s so rapid,” Gray says. The majority of drug addicted individuals, she claims, need about ten days of infusions, sometimes less. “It keeps people inspired when they see fast results,” she adds, “especially when they feel better than they did before, or perhaps ever in their life.”

Based on each individual, Gray like Mestayer sometimes recommends a periodic “booster” which can be one or two days of IV to support the results achieved in the initial treatment. She also prescribes a co-enzyme that, she says, helps maintain higher levels of NAD in the body. If a client relapses, she claims, one or two treatments can quickly get them sober and craving-free again.

The clinic also offers a four day “Tune Up” treatment for those suffering from stress, anxiety, irritability, low energy, PTSD and depression. The clinics also address other non-substance related addictions such as gambling.

NAD was first discovered in 1936, but World War II stopped the research. It was patented for treatment of drug addiction and schizophrenia in 1961 based on an 11,000 patient study. Sloughed aside with the discovery of methadone – a far more lucrative choice at the time for drug companies – NAD went “underground.”

Research has shown that NAD increases the synthesis of certain neurotransmitters in the brain known to be effective in correcting specific chemical imbalances. Some of these chemical imbalances underpin addiction, mental illness, anxiety, aggression, depression, despair and hopelessness. Fatigue is often the first signal of NAD deprivation; other clues may include depression and anxiety in children. Almost any chronic disease, including Parkinson’s, can also be indicative of deficiency.

There is some research and other reports indicating that NAD might be effective treatment for a host of other ailments including schizophrenia, PTSD, chronic fatigue, weak immune system, memory disturbance, sleep problems, concentration defects, blood pressure, poor cholesterol levels, sugar metabolism and diabetes, muscle pain and weakness, joint pain and stiffness, headaches, fevers, sore throats and swollen lymph glands. Clinical research has shown it is a potent biological antioxidant which can aid in preventing cell damage and a variety of diseases, cancer included.

There is also some evidence that NAD therapy can help with aging. Dr. David Sinclair, professor of genetics at Harvard Medical School, in a paper published in the journal Cell, describes a compound naturally made by young cells that is able to revive older cells, allowing them to be energetic and youthful again. With adequate amounts of NAD, aging can theoretically be reversed, he asserts. “When we give the molecule, the cells think oxygen levels are normal and everything revs back up again,” Sinclair wrote.

Pondering these claims raises the un-researched theory of whether NAD deficiency might be an unrecognized epidemic disease of our time.

THE BIOCHEMICAL PATH TO PERSONAL DEFICIENCY

Before I interviewed patients of the two clinics to determine whether they validated the positive assertions of Rodgers, Gray and Mestayer (they do, as you will read below), I decided to research more carefully the biology of the NAD process to determine whether there is a basis in science for their claims even in the absence of double-blind long-term studies. What I learned is relevant to the health, mental vitality and even possibly, as Sinclair asserts, to the aging of each of us, not only to addicts.

I learned that a range of vitamins, minerals, carbohydrates, proteins and fats from our diet provide the building blocks to create what medicine refers to as the “Citric Acid Cycle,” which names the energy it takes to produce NAD and link it with hydrogen (NADH). NADH enters the electron transport chain in the mitochondria and is sparked with oxygen – and the outcome is energy. This in turn fuels the 86,000 daily beats of the heart, enabling muscles to contract, and provides the cellular energy requirements of the 100 trillion cells of the body. The brain consumes about one-third of all the energy produced, so if the NADH is low, brain functions suffer. If any of the nutritional factors that produce NAD are low, energy production is weakened.

Often NAD deficiency is first evident in brain-related symptoms of poor concentration, difficulty focusing, and attention deficit disorders. If the energy shortage lasts long enough, brain neurons cannot synthesize neurotransmitters. When this occurs, the molecules of consciousness (such as serotonin, dopamine, and noradrenaline) are affected. Anxiety, depression, sleep disturbance and other mood changes can then arise.

Also important to know is that the crucial enzymes that catalyze the Citric Acid Cycle are inhibited or destroyed by chemical toxins that create oxidative, or free radical damage. Sources of the damage include cigarette smoke, drugs, chronic stress, sedentary living, as well as the accumulation of the myriad toxins found in daily life such as in pesticides.

Along with acquired NAD deficiency, there may also be a genetic disorder that is present at birth. Symptoms can appear in young children as difficulty sleeping, behavioral problems, hyperactivity, impaired concentration, academic stress and underachievement.

Moreover, NAD deficiency that induces fatigue and depression increases a propensity to use drugs and alcohol in order to improve energy and mood – simply to feel better. The self-medicating cycle is a common story reported by many addicts, and leads to even lower NAD. A vicious cycle ensues.

There is some history to using megavitamins as potential cures for addiction, including dating back to Bill Wilson’s (aka “Bill W.” the revered co-founder of Alcoholics Anonymous) ideas and experience. In 1960 Wilson underwent a major shift in his beliefs about the value of nutrition in achieving sobriety when he met Dr. Humphry Osmond, who introduced him to the concept of megavitamin therapy. Curious, Wilson became a guinea pig, taking 3,000 mg of niacin daily. Within a few weeks, fatigue and depression (symptoms of low NAD) which had plagued him for years, were gone.

Seeking to share this exciting discovery, Wilson gave the same doses to 30 of his close friends in AA, hoping it could be replicated. Of the 30, 20 he later reported became free of anxiety, tension and depression in one or two months. This dramatically reduced their alcohol consumption.

Wilson wrote a detailed report called “The Vitamin B 3 Therapy” and distributed thousands of copies as a pamphlet. Because the information was controversial, way ahead of its time and ran counter to the precepts of the 12-Step Program, Wilson became unpopular with the board of directors of AA International and the information was squelched

THE PATIENTS HAVE THEIR SAY

Unfortunately, newer in-depth scientific studies in the U.S. on the long-term benefit of NAD treatment on addiction and alcoholism have never been financed. That leaves largely the claims of clinic operators and their patients to bear out the assumption that, by virtue of its catalytic role in the body, NAD might in fact be an effective agent in addiction and alcohol treatment.

Rodger’s California centers are too new to have meaningful data on the long-term effects of NAD treatment based on follow-up interviews with patients, though Rodgers says she intends to set up a formal study of her patients in the near future. Mestayer’s Louisiana clinic did collect data for some years which was lost when their clinic was hit hard during hurricane Katrina. She has been collecting more recent statistics on the long-term effects of the NAD formula her clinic uses which, she claims, show an even higher success rate than the earlier formula.

In fact, the statistics if true are astounding, with some earlier participants in the Louisiana clinic achieving, according to Mestayer, nine years of sobriety.

“Statistically,” Rodgers claims, “70% of patients are craving-free by day five; 90% by day ten.” She adds that some reported having no physical memory of how drugs even felt, clearing their desire for them.

As testimonials, Rodgers provided me several video-taped former patients, each boasting tremendous success. One was from a man who claimed he had been taking 30 Oxycontins a day for 12 years. Another was from a woman who had been suicidal, shot speed for 20 years. Another woman reported a personal trauma that threw her into deep depression. Each claimed to have maintained a drug free life since their treatment.

I inquire about Paul who went through treatment three years ago: Is he still clean and sober?  

“Not only is he clean and sober, he paid for two of his friends to do the treatment,” Rodgers tells me, with tears in her eyes. “He no longer defines himself as an addict since his thought patterns have shifted and he sees life so differently.”

Separately, I interviewed four people who have gone through treatment at either the San Diego or Springfield, Louisiana centers. Their stories:

 • Doug, a health-conscious personal fitness trainer who experienced CTS (Chronic Traumatic Encylopathy) from several football injuries, would drink copious amounts of vodka at night to allow his amped-up body and mind to relax and shut down. He tried exercise and nutrition to get past anxiety-based insomnia; nothing worked. He knew that a 12-step program or therapy that dealt with past history wouldn’t work for him given that his issue was clearly a chemical imbalance. After just 20 minutes with his first NAD IV, he experienced a state of well-being he hadn’t felt in his entire adult life. His angst was gone, and the neuro-transmitters that lay dormant in his brain felt alive again.  After the first day of treatment he was able to sleep soundly, and he told me he’d been craving-free for more than four months. He takes an NAD supplement and goes back monthly for a booster.

 • After several tours of duty in Iraq, Patrick, a Marine, became a heavy heroin user after trying many other ways to self-medicate his PTSD and resulting insomnia. He admitted himself to two traditional inpatient treatments, one lasting 57 days. The first day out of each, he relapsed. After day four of the NAD treatment, during which he experienced no withdrawal symptoms, he felt completely clear and now sleeps without nightmares. He gets boosters once a month and has been drug free for several years.

 • Steve, also an Iraq veteran, had nine neck surgeries in five years. He used pain pills and opiate drugs to deal with constant physical pain as well as intense PTSD. He entered the NAD program out of a desperate desire to be free of his addictions in that he has children and perceived a good life ahead of him. Starting the NAD program with a pain scale of eight, within ten days the pain eased down to a one. On bad days, he says, it now goes up to a two, but is easily managed with a couple of Aleve. With only slight withdrawal symptoms, he told me he is now 100% craving free and his PTSD is also gone. He continues to take the oral NAD supplement but has not needed any booster treatments. He did the program in November, 2013.

 • Sandy is a young woman whose addiction to pain killers and amphetamines spiraled from recreational use to a full-on necessity. For three years she was not able to get out of bed without drugs, the lowest point of her life. She researched various other programs and told me she was baffled by the concept of replacing one drug addiction with another as a “cure.” After eight days of NAD treatment, she no longer thinks about using at all. Her mood is good, her energy is up, and she’s happy, she reported. Clean for a year and a half, she believes it was the combination of the in-home IV treatment she received and the warm caring from the clinic staff that made the difference. She has had two boosters and believes she won’t need any more to remain addiction free.

I ask Ann Rodgers if the treatment works for everyone and if not, is there a typical profile of the person for whom it doesn’t work?  “No, it doesn’t work 100% of the time,” she replies. “Interestingly, sometimes it doesn’t work for young heroin addicts. It could be because they aren’t emotionally mature enough to deal with their issues, or perhaps they don’t have a good support system in place yet.”

One young man, Rodgers notes, went through the program a year ago and did extremely well until he entered an intimate relationship. “That triggered emotional issues,” Rodgers says, and he returned to the arms of heroin. The Center then refused to treat him again as he refused to enter rehab, an essential aftercare resource in which clinic patients are encouraged to participate.

“Patients often feel like a fish-out-of-water when out of the drug culture they are accustomed to, and they need to find a structure to help them live drug free,” Rodgers explained. Accordingly, patients are informed of the importance of addressing any long-standing psychological issues and of re-learning how to live life as a non-addicted person, and they are encouraged to enter after-care programs that provide such support. “Rehab programs work so much better after doing NAD therapy since the person is so clear, more willing to make it work in their lives,” Rodgers says. “Their confidence allows them to make significant shifts in other areas of life so they are far less likely to relapse when they re-enter society.

“We really see ourselves reversing the customary order of mind/body to body/mind… by addressing the bio-chemical issues first it makes it so much easier to shift other areas of an addict’s life.”

The staff advocates other follow-up support groups that can include 12-step programs and/or conjunctive therapies such as outside psychological and spiritual counseling. As part of one of the largest integrative medicine centers in California, the Center for Health and Wellbeing, its own related therapeutic center offers intensive psychotherapy along with a recovery coach. Patient options include an IOP, sober living, or simply going home. The center also offers a full menu of complementary programs including massage therapy, cranial sacral therapy, naturopathic, nutritional counseling, acupuncture, marriage and family therapy and chiropractic, all of which Dr. Gray prescribes on an individual basis.

Separate from after-care, could NAD itself turn out to be something of a miracle cure or at least pre-cure for addicts? As more people go through the programs, there will be more statistics on permanency of results but no fully authenticated research until some serious independent and double-blind studies are undertaken by scientists, medical professionals or companies who can attract the funds to finance research. Meanwhile, NAD figures to remain something of a blip on the treatment scene attracting people like Paul who said simply: “There is just nothing to lose.”

–_____________________________________________________________________________________________

NIACIN THERAPY USED BY ABRAM HOFFER

Do It Yourself Healing

Vitamin B-3: Niacin and Its Amide
by A. Hoffer, M.D., Ph.D.

The first water soluble vitamins were numbered in sequence according to priority of discovery. But after their chemical structure was determined they were given scientific names. The third one to be discovered was the anti-pellagra vitamin before it was shown to be niacin. But the use of the number B-3 did not stay in the literature very long. It was replaced by nicotinic acid and its amide (also known medically as niacin and its amide). The name was changed to remove the similarity to nicotine, a poison. 

The term vitamin B-3 was reintroduced by my friend Bill W., co-founder of Alcoholics Anonymous, (Bill Wilson). We met in New York in 1960. Humphry Osmond and I introduced him to the concept of mega vitamin therapy. We described the results we had seen with our schizophrenic patients, some of whom were also alcoholic. We also told him about its many other properties. It was therapeutic for arthritis, for some cases of senility and it lowered cholesterol levels. 

Bill was very curious about it and began to take niacin, 3 g daily. Within a few weeks fatigue and depression which had plagued him for years were gone. He gave it to 30 of his close friends in AA and persuaded them to try it. Within 6 months he was convinced that it would be very helpful to alcoholics. Of the thirty, 10 were free of anxiety, tension and depression in one month. Another 10 were well in two months. He decided that the chemical or medical terms for this vitamin were not appropriate. He wanted to persuade members of AA, especially the doctors in AA, that this would be a useful addition to treatment and he needed a term that could be more readily popularized. He asked me the names that had been used. I told him it was originally known as vitamin B-3. This was the term Bill wanted. In his first report to physicians in AA he called it “The Vitamin B-3 Therapy.” Thousands of copies of this extraordinary pamphlet were distributed. Eventually the name came back and today even the most conservative medical journals are using the term vitamin B-3. 

Bill became unpopular with the members of the board of AA International. The medical members who had been appointed by Bill, felt that he had no business messing about with treatment using vitamins. They also “knew” vitamin B-3 could not be therapeutic as Bill had found it to be. For this reason Bill provided information to the medical members of AA outside of the National Board, distributing three of his amazing pamphlets. They are now not readily available.

Vitamin B-3 exists as the amide in nature, in nicotinamide adenine dinucleotide (NAD). Pure nicotinamide and niacin are synthetics. Niacin was known as a chemical for about 100 years before it was recognized to be vitamin B-3. It is made from nicotine, a poison produced in the tobacco plant to protect itself against its predators, but in the wonderful economy of nature which does not waste any structures, when the nicotine is simplified by cracking open one of the rings, it becomes the immensely valuable vitamin B-3. 

Vitamin B-3 is made in the body from the amino acid tryptophan. On the average 1 mg of vitamin B-3 is made from 60 mg of tryptophan, about 1.5% Since it is made in the body it does not meet the definition of a vitamin; these are defined as substances that can not be made. It should have been classified with the amino acids, but long usage of the term vitamin has given it permanent status as a vitamin. The 1.5% conversion rate is a compromise based upon the conversion of tryptophan to N-methyl nicotinamide and its metabolites in human subjects. I suspect that one day in the far distant future none of the tryptophan will be converted into vitamin B-3 and it then will truly be a vitamin. According to Horwitt [1], the amount converted is not inflexible but varies with patients and conditions. For example, women pregnant in their last three months convert tryptophan to niacin metabolites three times as efficiently as in non-pregnant females. Also there is evidence that contraceptive steroids, estrogens, stimulate tryptophan oxygenase, the enzyme that converts the tryptophan into niacin.

This observation raises some interesting speculations. Women, on average, live longer then men. It has been shown for men that giving them niacin increases their longevity. [2] Is the increased longevity in women the result of greater conversion of tryptophan into niacin under the stimulus of their increase in estrogen production? Does the same phenomenon explain the decrease in the incidence of coronary disease in women? 

The best-known vitamin deficiency disease is pellagra. More accurately it is a tryptophan deficiency disease since tryptophan alone can cure the early stages. Pellagra was endemic in the southern U.S.A. until the beginning of the last world war. It can be described by the four D’s: dermatitis, diarrhea, dementia and death. The dementia is a late stage phenomenon. In the early stages it resembles much more the schizophrenias, and can only with difficulty be distinguished from it. The only certain method used by early pellagrologists was to give their patients in the mental hospitals small amounts of nicotinic acid. If they recovered they diagnosed them pellagra, if they did not they diagnosed them schizophrenia. This was good for some of their patients but was not good for psychiatry since it prevented any continuing interest in working with the vitamin for their patients who did not recover fast, but who might have done so had they given them a lot more for a much longer period of time, the way we started doing this in Saskatchewan. I consider it one of the schizophrenic syndromes.

Indications
I have been involved in establishing two of the major uses for vitamin B-3, apart from its role in preventing and treating pellagra. These are its action in lowering high cholesterol levels [3] and in elevating high density lipoprotein cholesterol levels (HDL), and its therapeutic role in the schizophrenias and other psychiatric conditions. It has been found helpful for many other diseases or conditions. These are psychiatric disorders including children with learning and behavioral disorders, the addictions including alcoholism and drug addiction, the schizophrenias, some of the senile states. Its efficacy for a large number of both mental and physical conditions is an advantage to patients and to their doctors who use the vitamin, but is difficult to accept by the medical profession raised on the belief that there must be one drug for each disease, and that when any substance appears to be too effective for many conditions, it must be due entirely to its placebo effect, something like the old snake oils.

I have thought about this for a long time and have within the past year become convinced that this vitamin is so versatile because it moderates or relieves the body of the pernicious effect of chronic stress. It therefore frees the body to carry on its routine function of repairing itself more efficiently. The current excitement in medicine is the recognition that hyperoxidation, the formation of free radicals, is one of the basic damaging processes in the body. These hyperexcited molecules destroy molecules and damage tissues at the cellular level and at the tissue level. 

All living tissue which depends on oxygen for respiration has to protect itself against these free radicals. Plants use one type of antioxidants and animals use another type. Fortunately there is a wide overlap and the same antioxidants such as vitamin C are used by both plants and animals. There is growing recognition that the system adrenaline -> adrenochrome plays a major role in the reactions to stress. I have elaborated this in a further report for this journal. [4]

The catecholamines, of which adrenalin is the best known example, and the aminochromes, of which adrenochrome is the best known example, are intimately involved in stress reactions. Therefore to moderate the influence of stress or to negate it, one must use compounds which prevent these substances from damaging the body. Vitamin B-3 is a specific antidote to adrenalin, and the antioxidants such as vitamin C, Vitamin E, beta carotene, selenium and others protect the body against the effect of the free radicals by removing them more rapidly from the body. Any disease or condition which is stress related ought therefore to respond to the combined use of vitamin B-3 and these antioxidants provided they are all given in optimum doses, whether small or large as in orthomolecular therapy. I will therefore list briefly the many indications for the use of vitamin B-3.

For each condition I will describe one case to illustrate the therapeutic response. For each condition I can refer to hundreds and thousands of case histories and have already in the literature described many of them in detail. [5]

Psychiatric
1) The Schizophrenias. I have reviewed this for this journal. [6]

2) Children with Learning and/or Behavioral Disorders.

In 1960 seven year-old Bruce came to see me with his father. Bruce had been diagnosed as mentally retarded. He could not read, could not concentrate, and was developing serious behavioral problems such as cutting school without his parents’ knowledge. He was being prepared for special classes for the retarded. He excreted large amounts of kryptopyrrole, the first child to be tested. I started him on nicotinamide, one gram tid. Within four months he was well. He graduated from high school, is now married, has been fully employed and has been paying income tax. He is one case out of about 1500 I have seen since 1960. 

Current treatment is more complicated as described in this Journal. [7]

3) Organic Confusional States, non-Alzheimers forms of dementia, electroconvulsive therapy-induced memory disturbances. 

In 1954 I observed how nicotinic acid relieved a severe case of post ECT amnesia in one month. Since then I have routinely given it in conjunction with ECT to markedly decrease the memory disturbance that may occur during and after this treatment. I would never give any patient ECT without the concomitant use of nicotinic acid. It is very helpful, especially in cardiovascular-induced forms of dementia as it reverses sludging of the red blood cell and permits proper oxygenation of the cells of the body. For further information see Niacin Therapy in Psychiatry. [8]

In September 1992, Mr. C., 76 years-old, requested help with his memory. He was terribly absentminded. If he decided to do something, by the time he arrived where he wanted to do it he had forgotten what it was he wanted to do. His short-term memory was very poor and his long-term memory was beginning to be affected. I started him on a comprehensive vitamin program including niacinamide 1.5 G daily. Within a month he began to improve. I added niacin to his program. By February 1993 he was normal. April 26, 1993, he told me he had been so well he had concluded he no longer needed any niacin and decreased the dose from 3.0 G to 1.5 G daily. He remained on the rest of the program. Soon he noted that his short term memory was failing him again. I advised him to stay on the full dose the rest of his life. 

4) An antidote against d-LSD,9,10 and against adrenochrome. [5]

5) Alcoholism.

Bill W. conducted the first clinical trial of the use of nicotinic for treating members of Alcoholics Anonymous. [11] He found that 20 out of thirty subjects were relieved of their anxiety, tension and fatigue in two months of taking this vitamin, 1 G tid. I found it very useful in treating patients who were both alcoholic and schizophrenic. The first large trial was conducted by David Hawkins who reported a better than 90% recovery rate on about 
90 patients. Since then it has been used by many physicians who treat alcoholics. Dr. Russell Smith in Detroit has reported the largest series of patients. [12]

Physical
1. Cardiovascular
Of the two major findings made by my research group in Saskatchewan, the  nicotinic acid-cholesterol connection is well known and nicotinic acid is used worldwide as an economical, effective and safe compound for lowering cholesterol and elevating high density cholesterol. As a result of my interest in nicotinic acid, Altschul, Hoffer and Stephen [3] discovered that this vitamin, given in gram doses per day, lowered cholesterol levels. Since then it was found it also elevates high density lipoprotein cholesterol thus bringing the ratio of total over HDL to below 5. 

In the National Coronary Study, Canner [2] showed that nicotinic acid decreased mortality and prolonged life. Between 1966 and 1975, five drugs used to lower cholesterol levels were compared to placebo in 8341 men, ages 30 to 64, who had suffered a myocardial infarction at least three months before entering the study. About 6000 were alive at the end of the study. Nine years later, only niacin had decreased the death rate significantly from all causes. Mortality decreased 11% and longevity increased by two years. The death rate from cancer was also decreased.

This was a very fortunate finding because it led to the approval by the FDA of this vitamin in mega doses for cholesterol problems and opened up the use of this vitamin in large doses for other conditions as well. This occurred at a time when the FDA was doing its best not to recognize the value of megavitamin therapy. Its position has not altered over the past four decades. 

Our finding opened up the second major wave of interest in vitamins. The first wave started around 1900 when it was shown that these compounds were very effective in small doses in curing vitamin deficiency diseases and in preventing their occurrence. This was the preventive phase of vitamin use. The second wave recognized that they have therapeutic properties not directly related to vitamin deficiency diseases but may have to be used in large doses. This was the second or present wave wherein vitamins are used in therapy for more than deficiency diseases. Our discovery that nicotinic acid was an hypocholesterolemic compound is credited as the first paper to initiate the second wave and paved the way for orthomolecular medicine which came along several years later.

2. Arthritis
I first observed the beneficial effects of vitamin B-3 in 1953 and 1954. I was then exploring the potential benefits and side effects from this vitamin. Several of the patients who were given this vitamin would report after several months that their arthritis was better. At first this was a surprise since in the psychiatric history I had taken I had not asked about joint pain. This report of improvement happened so often I could not ignore it. A few years later I discovered that Prof. W. Kaufman had studied the use of this vitamin for the arthritides before 1950 and had published two books describing his remarkable results. [13] Since that time this vitamin has been a very important component of the orthomolecular regimen for treating arthritis. 

The following case illustrates both the response which can occur and the complexity of the orthomolecular regimen. Patients who are early into their arthritis respond much more effectively and are not left with residual disability. 

K.V. came to my office April 15, 1982. She was in a wheelchair pushed by her husband. He was exhausted, depressed, and she was one of the sickest patients I have ever seen. She weighed under 90 pounds. She sat in the chair on her ankles which were crossed beneath her body because she was not able to straighten them out. Her arms were held in front of her, close to her body, and her fingers were permanently deformed and claw-like. She told me she had been deeply depressed for many years because of the severe pain and her major impairment. As she was being wheeled into my office I saw how ill she was and immediately concluded there was nothing I could do for her, and had to decide how I could let her know without sending her even deeper into despair. However I changed my mind when she suddenly said, “Dr. Hoffer, I know no one can ever cure me but if you could only help me with my pain. The pain in my back is unbearable. I just want to get rid of the pain in my back.” I realized then she had a lot of determination and inner strength and that it was worthwhile to try and help her.

She began to suffer from severe pain in her joints in 1952. In 1957 it was diagnosed as arthritis. Until 1962 her condition fluctuated and then she had to go into a wheelchair some part of the day. She was still able to walk although not for long until 1967. In 1969 she depended on the wheelchair most of the time, and by 1973 she was there permanently. For awhile she was able to propel herself with her feet. After that she was permanently dependent on help. For the three years before she saw me she had gotten some home care but most of the care was provided by her husband. He had retired from his job when I first saw them. He provided the nursing care equivalent to four nurses on 8 hour shifts including holiday time. He had to carry her to the bathroom, bathe her, cook and feed her. He was as exhausted as she was but he was able to carry on.

She was severely deformed, especially her hands, suffered continuous pain, worse in her arms, and hips and her back. Her ankles were badly swollen and she had to wear pressure bandages. Her muscles also were very painful most of the day. She was able to feed herself and to crochet with her few useful fingers, but it must have been extremely difficult. She was not able to write nor type which she used to do with a pencil. A few months earlier she had been suicidal. On top of this severe pain and discomfort she had no appetite, was not hungry and a full meal would nauseate her. Her skin was dry, she had patches of eczema, and she had white areas in her nails. 

I advised her to eliminate sugar, potatoes, tomatoes and peppers, (about 10% of arthritics have allergic reactions to the solanine family of plants). She was to add niacinamide 500 mg four times daily (following the work of W. Kaufman), ascorbic acid 500 mg four times daily (as an anti-stress nutrient and for subclinical scurvy), pyridoxine 250 mg per day (found to have anti-arthritic properties by Dr. J. Ellis), zinc sulfate 220 mg per day (the white areas in her nails indicated she was deficient in zinc), flaxseed oil 2 tablespoons and cod liver oil 1 tablespoon per day (her skin condition indicated she had a deficiency of omega 3 essential fatty acids). The detailed treatment of arthritis and the references are described in my book. [14]

One month later a new couple came into my room. Her husband was smiling, relaxed and cheerful as he pushed his wife in in her chair. She was sitting with her legs dangling down, smiling as well. I immediately knew that she was a lot better. I began to ask her about her various symptoms she had had previously. After a few minutes she impatiently broke in to say, “Dr. Hoffer, the pain in my back is all gone.” She no longer bled from her bowel, she no longer bruised all over her body, she was more comfortable, the pain in her back was easily controlled with aspirin and was gone from her hips, (it had not helped before). She was cheerful and laughed in my office. Her heart was regular at last. I added inositol niacinate 500 mg four times daily to her program. 

She came back June 17, 1982, and had improved even more. She was able to pull herself up from the prone position on her bed for the first time in 15 years, and she was free of depression. I increased her ascorbic acid to 1 gram four times daily and added vitamin E 800 IU. Because she had shown such dramatic improvement I advised her she need no longer come to see me.

September 1, 1982, she called me on the telephone. I asked her how she was getting along. She said she was making even more progress. I then asked her how had she been able to get to the phone. She replied she was able to get around alone in her chair. Then she added she had not called for herself but for her husband. He had been suffering from a cold for a few days, she was nursing him, and she wanted some advice for him.

After another visit October 28, 1983, I wrote to her doctor “Today Mrs. K.V. reported she had stayed on the whole vitamin program very rigorously for 18 months, but since that time had slacked off somewhat. She is regaining a lot of her muscle strength, can now sit in her wheelchair without difficulty, can also wheel herself around in her wheelchair but, of course, can not do anything useful with her hands because her fingers are so awful. She would like to become more independent and perhaps could do so if something could be done about her fingers and also about her hip. I am delighted she has arranged to see a plastic surgeon to see if something can be done to get her hand mobilized once more. I have asked her to continue with the vitamins but because she had difficulty taking so many pills she will take a preparation called Multijet which is available from Portland and contains all the vitamins and minerals and can be dissolved in juice. She will also take inositol niacinate 3 grams daily.”

I saw her again March 24, 1988. About 4 of her vertebra had collapsed and she was suffering more pain which was alleviated by Darvon. It had not been possible to treat her hands surgically. She had been able to eat by herself until six months before this last visit. She had been taking small amounts of vitamins. She was able to use a motorized chair. She had been depressed. I wrote to her doctor, “She had gone off the total vitamin program about two or three years ago. It is very difficult for her to swallow and I can understand her reluctance to carry on with this. I have therefore suggested that she take a minimal program which would include inositol niacinate 3 grams daily, ascorbic acid 1 gram three times, linseed oil 2 capsules and cod liver oil 2 capsules. Her spirits are good and I think she is coming along considering the severe deterioration of her body as a result of the arthritis over the past few decades.” She was last seen by her doctor in the fall of 1989.

Her husband was referred. I saw him May 18, 1982. He complained of headaches and a sense of pressure about his head present for three years. This followed a series of light strokes. I advised him to take niacin 3 grams daily plus other vitamins including vitamin C. By September 1983 he was well and when seen last March 24, 1988 was still normal.

3. Juvenile Diabetes
Dr. Robert Elliot, Professor of Child Health Research at University of Auckland Medical School is testing 40,000 five-year old children for the presence of specific antibodies that indicate diabetes will develop. Those who have the antibodies will be given nicotinamide. This will prevent the development of diabetes in most the children who are vulnerable. According to the Rotarian for March 1993 this project began 8 years ago and has 3200 relatives in the study. Of these, 182 had antibodies and 76 were given nicotinamide. Only 5 have become diabetic compared to 37 that would have been expected. Since 1988 over 20,100 school children have been tested. None have become diabetic compared to 47 from the untested comparable group. A similar study is underway in London, Ontario. 

4. Cancer
Recent findings have shown that vitamin B-3 does have anti-cancer properties. This was discussed at a meeting in Texas in 1987, Jacobson and Jacobson. [15] The topic of this international conference was “Niacin, Nutrition, ADP-Ribosylation and Cancer,” and was the 8th conference of this series.

Niacin, niacinamide and nicotinamide adenine dinucleotide (NAD) are interconvertable via a pyridine nucleotide cycle. NAD, the coenzyme, is hydrolyzed or split into niacinamide and adenosine dinucleotide phosphate (ADP-ribose). Niacinamide is converted into niacin, which in turn is once more built into NAD. The enzyme which splits ADP is known as poly (ADP-ribose) polymerase, or poly (ADP) synthetase, or poly (ADP-ribose) transferase. Poly (ADP-ribose) polymerase is activated when strands of deoxyribonucleic acid (DNA) are broken. The enzyme transfers NAD to the ADP-ribose polymer, binding it onto a number of proteins. The poly (ADP-ribose) activated by DNA breaks helps repair the breaks by unwinding the nucleosomal structure of damaged chromatids. It also may increase the activity of DNA ligase. This enzyme cuts damaged ends off strands of DNA and increases the cell’s capacity to repair itself. Damage caused by any carcinogenic factor, radiation, chemicals, is thus to a degree neutralized or counteracted.

Jacobson and Jacobson, conference organizers, hypothesized that niacin prevents cancer. They treated two groups of human cells with carcinogens. The group given adequate niacin developed tumors at a rate only 10% of the rate in the group deficient in niacin. Dr. M. Jacobson is quoted as saying, “We know that diet is a major risk factor, that diet has both beneficial and detrimental components. What we cannot assess at this point is the optimal amount of niacin in the diet… The fact that we don’t have pellagra does not mean we are getting enough niacin to confer resistance to cancer.” About 20 mg per day of niacin will prevent pellagra in people who are not chronic pellagrins. The latter may require 25 times as much niacin to remain free of pellagra.

Vitamin B-3 may increase the therapeutic efficacy of anti-cancer treatment. In mice, niacinamide increased the toxicity of irradiation against tumors. The combination of normobaric carbogen with nicotinamide could be an effective method of enhancing tumor radiosensitivity in clinical radiotherapy where hypoxia limits the outcome of treatment. Chaplin, Horsman and Aoki16 found that nicotinamide was the best drug for increasing radiosensitivity compared to a series of analogues. The vitamin worked because it enhanced blood flow to the tumor. Nicotinamide also enhanced the effect of chemotherapy. They suggested that niacin may offer some cardioprotection during long-term adriamycin chemotherapy. 

Further evidence that vitamin B-3 is involved in cancer is the report by Nakagawa, Miyazaki, Okui, Kato, Moriyama and Fujimura [17] that in animals there is a direct relationship between the activity of nicotinamide methyl transferase and the presence of cancer. Measuring the amount of N-methyl nicotinamide was used to measure the activity of the enzyme. In other words, in animals with cancer there is increased destruction of nicotinamide, thus making less available for the pyridine nucleotide cycle. This finding applied to all tumors except the solid tumors, Lewis lung carcinoma and melanoma B-16.

Gerson [18] treated a series of cancer patients with special diets and with some nutrients including niacin 50 mg 8 to 10 times per day, dicalcium phosphate with vitamin D, vitamins A and D, and liver injections. He found that all the cancer cases were benefited in that they became healthier and in many cases the tumors regressed. In a subsequent report Gerson elaborated on his diet. He now emphasized a high potassium over sodium diet, ascorbic acid, niacin, brewers yeast and lugols iodine. Right after the war there was no ready supply of vitamins as there is today. I would consider the use of these nutrients in combination very original and enterprising. Dr. Gerson was the first physician to emphasize the use of multivitamins and some multiminerals. More details are 
in Hoffer. [19]

Additional evidence that vitamin B-3 is therapeutic for cancer arises from the National Coronary Study, Canner. [2]

5. Concentration Camp Survivors
In 1960 I planned to study the effect of nicotinic acid on a large number of aging people living in a sheltered home. A new one had been built. I approached the director of this home, Mr. George Porteous. I arranged to meet him and told him what I would like to do and why. I gave him an outline of its properties, its side effects and why I thought it might be helpful. Mr. Porteous agreed and we started this investigation. A short while after my first contact Mr. Porteous came to my office at University Hospital. He wanted to take nicotinic acid himself, he told me, so that he could discuss the reaction more intelligently with people living in his institution. He wanted to know if it would be safe to do so. 

That fall he came again to talk to me and this time he said he wanted to tell me what had happened to him. Then I discovered he had been with the Canadian troops who had sailed to Hong Kong in 1940, had been promptly captured by the Japanese and had survived 44 months in one of their notorious prisoner of war camps. 

Twenty-five percent of the Canadian soldiers died in these camps. They suffered from severe malnutrition from starvation and nutrient deficiency. They suffered from beri beri, pellagra, scurvy, infectious diseases, and brutality from the guards. 

Porteous, a physical education instructor, had been fit weighing about 190 pounds when he got there. When he returned home he weighed only 2/3rds of that. On the way home in a hospital ship the soldiers were fed and given extra vitamins in the form of rice polishings. There were few vitamins available then in tablets or capsules. He seemingly recovered but had remained very ill. He suffered from both psychological and physical symptoms. He was anxious, fearful and slightly paranoid. Thus, he could never be comfortable sitting in a room unless he sat facing the door. This must have arisen from the fear of the guards. Physically he had severe arthritis. He could not raise his arms above his shoulders. He suffered from heat and cold sensitivity. In the morning he needed his wife’s help in getting out of bed and to get started for the day. He had severe insomina. For this he was given barbiturates in the evening and to help awaken him in the morning, he was given amphetamines. 

Later I read the growing literature on the Hong Kong veterans and there is no doubt they were severely and permanently damaged. They suffered from a high death rate due to heart disease, crippling arthritis, blindness and a host of other conditions. 

Having outlined his background he then told me that two weeks after he started to take nicotinic acid, 1 gram after each meal, he was normal. He was able to raise his arms to their full extension, and he was free of all the symptoms which had plagued him for so long. When I began to prepare my report [20] I obtained his Veterans Administration Chart. It came to me in two cardboard boxes and weighed over ten pounds, but over 95% of it was accumulated before he started on the vitamin. For the ten years after he started on the vitamin there was very little additional material. One could judge the efficacy of the vitamin by weighing the chart paper before and after he started on it. Porteous remained well as long as he stayed on the vitamin until his death when he was Lieutenant Governor of Saskatchewan. In 1962, after having been well for two years, he went on a holiday to the mountains with his son and he forgot to take his nicotinic acid with him. By the time he returned home almost the entire symptomatology had returned. 

Porteous was enthusiastic about nicotinic acid and began to tell all his friends about it. He told his doctor. His doctor cautioned him that he might damage his liver. Porteous replied that if it meant he could stay as well as he was until he died from a liver ailment he would still not go off it. His doctor became an enthusiast as well and within a few years had started over 300 of his patients on the vitamin. He never saw any examples of liver disease from nicotinic acid. 

I have treated over 20 prisoners from Japanese camps and from European concentration camps since then with equally good results. I estimated that one year in these camps was equivalent to 4 years of aging, i.e. four years in camp would age a prisoner the equivalent of 16 years of normal living. 

George Porteous wanted every prisoner of war from the eastern camps treated as he had been. He was not successful in persuading the Government of Canada that nicotinic acid would be very helpful so he turned to fellow prisoners, both in Canada (Hong Kong Veterans) and to American Ex-Prisoners of War. These American veterans suffered just as much as had the Canadian soldiers since they were treated in exactly the same abysmal way. The ones who started on the vitamin showed the same response. Recently one of these soldiers, a retired officer, wrote to me after being on nicotinic acid 20 years that he felt great, owed it to the vitamin and that when his arteries were examined during a simple operation they were completely normal. He wrote, “About two years ago, I was hit, was bleeding down the neck. The MDs took the opportunity to repair me. They said the arteries under the ears look like they had never been used.” 

There is an important lesson from the experiences of these veterans and their response to megadoses of nicotinic acid. This is that every human exposed to severe stress and malnutrition for a long enough period of time will develop a permanent need for large amounts of this vitamin and perhaps for several others. 

This is happening on a large scale in Africa where the combination of starvation, malnutrition and brutality is reproducing the conditions suffered by the veterans. Those who survive will be permanently damaged biochemically, and will remain a burden to themselves and to the community where they live. Will society have the good sense to help them recover by making this vitamin available to them in optimum doses?

Doses
The optimum dose range is not as wide as it is for ascorbic acid, but it is wide enough to require different recommendations for different classes of diseases. As is always the case with nutrients, each individual must determine their own optimum level. With nicotinic acid this is done by increasing the dose until the flush (vasodilation) is gone, or is so slight it is not a problem. 

One can start with as low a dose as 100 mg taken three times each day after meals and gradually increase it. I usually start with 500 mg each dose and often will start with 1 gram per dose especially for cases of arthritis, for schizophrenics, for alcoholics and for a few elderly patients. However, with elderly patients it is better to start small and work it up slowly.

No person should be given nicotinic acid without explaining to them that they will have a flush which will vary in intensity from none to very severe. If this is explained carefully, and if they are told that in time the flush will not be a problem, they will not mind. The flush may remain too intense for a few patients and the nicotinic acid may have to be replaced by a slow release preparation or by some of the esters, for example, inositol niacinate. The latter is a very good preparation with very little flush and most find it very acceptable even when they were not able to accept the nicotinic acid itself. It is rather expensive but with quantity production the price might come down.

The flush starts in the forehead with a warning tingle. Then it intensifies. The rate of the development of the flush depends upon so many factors it is impossible to predict what course it will follow. 

The following factors decrease the intensity of the flush: a cold meal, taking it after a meal, taking aspirin before, using an antihistamine in advance. 

The following factors make the flush more intense: a hot meal, a hot drink, an empty stomach, chewing the tablets and the rate at which the tablets break down in liquid. 

From the forehead and face the flush travels down the rest of the body, usually stopping somewhere in the chest but may extend to the toes. With continued use the flush gradually recedes and eventually may be only a tingling sensation in the forehead. If the person stops taking the vitamin for a day or more the sequence of flushing will be re-experienced. Some people never do flush and a few only begin to flush after several years of taking the vitamin. With nicotinamide there should be no flushing but I have found that about 2% will flush. This may be due to rapid conversion of the nicotinamide to nicotinic acid in the body.

When the dose is too high for both forms of the vitamin the patients will suffer from nausea at first, and then if the dose is not reduced it will lead to vomiting. These side effects may be used to determine what is the optimum dose. When they do occur the dose is reduced until it is just below the nausea level. With children the first indication may be loss of appetite. If this does occur the vitamin must be stopped for a few days and then may be resumed at a lower level. Very few can take more than 6 grams per day of the nicotinamide. With nicotinic acid it is possible to go much higher. Many schizophrenics have taken up to 30 grams per day with no difficulty. The dose will alter over time and if on a dose where there were no problems, they may develop in time. Usually this indicates that the patient is getting better and does not need as much. I have divided all patients who might benefit from vitamin B-3 into the following categories.

Category 1. These are people who are well or nearly well, and have no obvious disease. They are interested in maintaining their good health or in improving it. They may be under increased stress. The optimum dose range varies between 0.5 to 3 grams daily. The same doses apply to nicotinamide.

Category 2. Everyone under physiological stress, such as pregnancy and lactation, suffering from acute illness such as the common cold or flu, or other diseases that do not threaten death. All the psychiatric syndromes are included in this group including the schizophrenias and the senile states. It also includes the very large group of people with high blood cholesterol levels or low HDL when it is desired to restore these blood values to normal. The dose range is 1 gram to 10 grams daily. For nicotinamide the range is 1 1/2 g to 6 g. 

Nicotinamide does not affect cholesterol levels.

Side Effects
Here are Dr. John Marks’ conclusions. [21]

“A tingling or flushing sensation in the skin after relatively large doses (in excess of 75 mg) of nicotinic acid is a rather common phenomenon. It is the result of dilation of the blood vessels that is one of the natural actions of nicotinic acid and one for which it is used therapeutically. Whether this should therefore be regarded as a true adverse reaction is a moot point. The reaction clears regularly after about 20 minutes and is not harmful to the individual. It is very rare for this reaction to occur at less than three times the RDA, even in very sensitive individuals. In most people much larger quantities are required. The related substance nicotinamide only very rarely produces this reaction and in consequence this is the form generally used for vitamin supplementation.

“Doses of 200 mg to 10 g daily of the acid have been used therapeutically to lower blood cholesterol levels under medical control for periods of up to 10 years or more and though some reactions have occurred at these very high dosages, they have rapidly responded to cessation of therapy, and have often cleared even when therapy has been continued.

“In isolated cases, transient liver disorders, rashes, dry skin and excessive pigmentation have been seen. The tolerance to glucose has been reduced in diabetics and patients with peptic ulcers have experienced increased pain. No serious reaction have been reported however even in these high doses. The available evidence suggests that 10 times the RDA is safe (about 100 mg).”

Dr. Marks is cautious about recommending that doses of 100 mg are safe. In my opinion, based upon 40 years of experience with this vitamin the dose ranges I have recommended above are safe. However with the higher doses medical supervision is necessary.

Jaundice is very rare. Fewer that ten cases have been reported in the medical literature. I have seen none in ten years. When jaundice dose occur it is usually an obstructive type and clears when the vitamin is discontinued. I have been able to get schizophrenic patients back on nicotinic acid after the jaundice cleared and it did not recur.

Four serious cases have been reported, all involving a sustained release preparation. Mullin, Greenson & Mitchell (1989) [22] reported that a 44 year-old man was treated with crystalline nicotinic acid, 6 grams daily, and after 16 months was normal. He then began to take a sustained-release preparation, same dose. Within three days he developed nausea, vomiting, abdominal pain, dark urine. He had severe hepatic failure and required a liver transplant. Henkin, Johnson & Segrest found three patients who developed hepatitis with sustained release nicotinic acid. When this was replaced with crystalline nicotinic acid there was no recurrent liver damage. [23]

Since jaundice in people who have not been taking nicotinic acid is fairly common it is possible there is a random association. The liver function tests may indicate there is a problem when in fact there is not. Nicotinic acid should be stopped for five days before the liver function tests are given. One patient who had no problem with nicotinic acid for lowering cholesterol switched to the slow release preparations and became ill. When he resumed the original nicotinic acid he was well again with no further evidence of liver dysfunction. I have not seen any cases reported anywhere else. I have described much more fully the side effects of this vitamin elsewhere. [24]

Inositol hexaniacinate is an ester of inositol and nicotinic acid. Each inositol molecule contains six nicotinic acid molecules. This ester is broken down slowly in the body. It is as effective as nicotinic acid and is almost free of side effects. There is very little flushing, gastrointestinal distress and other uncommon side effects. Inositol, considered one of the lesser important B vitamins, does have a function in the body as a messenger molecule and may add something to the therapeutic properties of the nicotinic acid.

Conclusion
Vitamin B-3 is a very effective nutrient in treating a large number of psychiatric and medical diseases but its beneficial effect is enhanced when the rest of the orthomolecular program is included. The combination of vitamin B-3 and the antioxidant nutrients is a great anti-stress program.

Reprinted with the permission of the author:
Abram Hoffer, M.D., Ph.D.

References
1. Horwitt MK: Modern Nutrition in Health and Disease. Fifth Ed. RS Goodhart and ME Shils. Lea & Febiger, Phil. 1974.

2. Canner PL, Berge KG, Wenger NK, Stamler J, Friedman L, Prineas RJ & Freidewald W: Fifteen year mortality Coronary Drug Project; patients long term benefit with niacin. American Coll Cardiology 8:1245-1255, 1986.

3. Altschul R, Hoffer A & Stephen JD: Influence of Nicotinic Acid on Serum Cholesterol in Man. Arch Biochem Biophys 54:558-559, 1955.

4. Hoffer A: The Schizophrenia, Stress and Adrenochrome Hypothesis. In Press, 1995.

5. Hoffer A: Orthomolecular Medicine for Physicians. Keats Pub, New Canaan, CT, 1989.

6. Hoffer A: The treatment of schizophrenia. In Press 1995.

7. Hoffer A: The Development of Orthomolecular Medicine. In Press, 1995.

8. Hoffer A: Niacin Therapy in Psychiatry. C. C. Thomas, Springfield, IL, 1962.

Hoffer A & Osmond H: New Hope For Alcoholics, University Books, New York, 1966. Written by Fannie Kahan.

Hoffer A & Walker M: Nutrients to Age Without Senility. Keats Pub Inc, New Canaan, CT, 1980.

Hoffer A & Walker M: Smart Nutrients. A Guide to Nutrients That Can Prevent and Reverse Senility. Avery Publishing Group, Garden City Park, New York, 1994.

9. Agnew N & Hoffer A: Nicotinic Acid Modified Lysergic Acid Diethylamide Psychosis. J Ment Science 101:12-27, 1955. 

10. Ivanova RA, Milstein GT, Smirnova LS & Fantchenko ND: The Influence of Nicotinic Acid on an Experimental Psychosis Produced by LSD 25. Journal of Neuropathology and Psychiatry of CC Korsakoff 64:1172-1176, 1964. In Russian. Translated by Dr. T.E. Weckowicz.

11. Wilson B: The Vitamin B-3 Therapy: The First Communication to A.A.’s Physicians and A Second Communication to A.A.’s Physicians, 1967 and 1968.

12. Smith RF: A five year field trial of massive nicotinic acid therapy of alcoholics in Michigan. Journal of Orthomolecular Psychiatry 3:327-331, 1974.

Smith RF: Status report concerning the use of megadose nicotinic acid in alcoholics. Journal of Orthomolecular Psychiatry 7:52-55, 1978.

13. Kaufman W: Common Forms of Niacinamide Deficiency Disease: Aniacin Amidosis. Yale University Press, New Haven, CT, 1943.

Kaufman W: The Common Form of Joint Dysfunction: Its Incidence and Treatment. E.L. Hildreth and Co., Brattelboro, VT, 1949.

14. Hoffer A: Orthomolecular Medicine For Physicians, Keats Pub, New Canaan, CT, 1989.

15. Jacobson M & Jacobson E: Niacin, nutrition, ADP-ribosylation and cancer. The 8th International Symposium on ADP- Ribosylation, Texas College of Osteopathic Medicine, Fort Worth, TX, 1987.

Titus K: Scientists link niacin and cancer prevention. The D.O. 28:93-97, 1987.

Hostetler D: Jacobsons put broad strokes in the niacin/cancer picture. The D.O. 28:103-104, 1987.

16. Chaplin DJ, Horsman MP & Aoki DS: Nicotinamide, Fluosol DA and Carbogen: a strategy to reoxygenate acutely and chronically hypoxic cells in vivo. British Journal of Cancer 63:109-113, 1990.

17. Nakagawa K, Miyazaka M, Okui K, Kato N, Moriyama Y & Fujimura S: N1-methylnicotinamide level in the blood after nicotinamide loading as further evidence for malignant tumor burden. Jap. J. Cancer Research 82:277-1283, 1991.

18. Gerson M: Dietary considerations in malignant neoplastic disease. A prelimary report. The Review of Gastroenterology 12:419-425, 1945.

Gerson M: Effects of a combined dietary regime on patients with malignant tumors. Experimental Medicine and Surgery 7:299-317, 1949. 

19. Hoffer A: Orthomolecular Oncology. In, Adjuvant Nutrition in Cancer Treatment, Ed. P. Quillin & R. M. Williams. 1992 Symposium Proceedings, Sponsored by Cancer Treatment Research Foundation and American College of Nutrition. Cancer Treatment Research Foundation, 3455 Salt Creek Lane, Suite 200, Arlington Heights, IL 60005-1090, 331-362, 1994.

20. Hoffer A: Hong Kong Veterans Study. J Orthomolecular Psychiatry 3:34-36, 1974.

21. Marks J: Vitamin Safety. Vitamin Information Status Paper, F. Hoffman La Roche & Co., Basle, 1989.

22. Mullin GE, Greenson JK & Mitchell MC: Fulminant hepatic failure after ingestion of sustained-release nicotinic acid. Ann Internal Medicine 111:253-255, 1989.

23. Henkin Y, Johnson KC & Segrest JP: Rechallenge with crystalline niacin after drug-induced hepatitis from sustained-release niacin. J. American Medical Assn. 264:241-243, 1990.

24. Hoffer A: Niacin Therapy in Psychiatry. C. C. Thomas, Springfield, IL, 1962.

Hoffer A: Safety, Side Effects and Relative Lack of Toxicity of Nicotinic acid and Nicotinamide. Schizophrenia 1:78-87, 1969.

Hoffer A: Vitamin B-3 (Niacin) Update. New Roles For a Key Nutrient in Diabetes, Cancer, Heart Disease and Other Major Health Problems. Keats Pub, Inc., New Canaan, CT, 1990.

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Longevity Facts Article on NAD for Aging

Dr. David Sinclair discusses how NMN boosts NAD reverses aging in blood vessels

NMN and NAD Reverse Aging of Blood Vessels in New Study

Reading Time: 5 minutes. >>Harvard professor Dr. David Sinclair reports that the NAD boosting NMN compound reverses aging in blood vessels and restores muscle strength in a new study published March 22nd. [This article first appeared on LongevityFacts. Author: Brady Hartman. ]

Using the NAD boosting molecule NMN, Dr. David Sinclair’s team reversed blood vessel and muscle aging in mice, while boosting their exercise endurance.  As Dr. Sinclair says

“We’ve discovered a way to reverse vascular aging by boosting the presence of naturally occurring molecules in the body that augment the physiological response to exercise” adding “The approach stimulates blood vessel growth and boosts stamina and endurance in mice and sets the stage for therapies in humans to address the spectrum of diseases that arise from vascular aging.”

The team says the achievement paves the way for similar therapies for humans and published the results of their study on March 22 in the journal Cell.

David A. Sinclair, Ph.D. is best known for his research on the NAD molecule and its role in increasing health in aging bodies. Dr. Sinclair is a professor in the Department of Genetics and a Co-Director of the Paul F. Glenn Laboratories for the Biological Mechanisms of Aging at Harvard Medical School (HMS) as well as a Professor at the University of New South Wales, Sydney.

In a video accompanying the new study, published by Harvard News, Dr. David Sinclair describes the compound NMN boosts levels of NAD in the bodies of aging mice, and how that restores muscle function.

Vascular aging leads to a deterioration in many organs and tissues throughout the human body, as Dr. David Sinclair says:

“As we age, the tiniest blood vessels in our bodies wither and die, reducing the blood flow to organs and tissues. Vascular aging causes many diseases — cardiovascular, neurological, muscle wasting, frailty, and even aging. Here at Harvard Medical School, we’ve reversed the process in mice, setting the stage for radical new therapies to help people. The new study has unraveled the cascade of interactions between blood vessels and muscles. “

NMN Boosts NAD in aging endothelial cells.
NMN Boosts NAD in aging endothelial cells. Source: Harvard Medical School (HMS) (video).

Dr. David Sinclair also describes the how aging of the cells lining our blood vessels leads to a decline in our vascular systems and muscles, saying:

“Endothelial cells, which line the walls of blood vessels, are essential for the health and growth of the vessels. And as endothelial cells age, blood vessels begin to atrophy and die. Blood flow to many parts of the body diminishes, organs and tissues begin to function less well. Blood vessel demise hits muscles especially hard because muscles rely on a robust blood supply for their function. This process can be slowed down with regular exercise, but only up to a point. Over time, even exercise fails to stave off blood vessel demise and muscle loss. “

Decline in NAD causes aging blood vessels and loss of muscle tissue says Dr. David Sinclair.
The decline in NAD causes aging blood vessels and loss of muscle tissue says Dr. David Sinclair. Credit: Lewis Lipsitz via HMS.

The new study suggests that this loss of blood flow is a key driver behind age-related muscle loss and frailty. Even if we exercise, our muscles shrink as we get older, as Dr. David Sinclair says

“The new findings have cracked the mystery behind this process. As our blood vessels age, they become deaf to the signals from exercise muscles. This actually leads to the muscles shrinking as we get older, and therefore we’re less able to exercise and grow new blood vessels. A vicious cycle indeed. “

NMN boosts NAD in aging blood vessels according to Dr. David Sinclair.
NMN boosts NAD in aging blood vessels according to Dr. David Sinclair. Source: HMS (video).

The declining levels of NAD in our bodies cause this aging process. However,  using NMN to boost levels of NAD stimulates a sirtuin protein called SIRT1, as Dr. David Sinclair describes

“The two key players in the crosstalk between blood vessels and muscles are a molecule called NAD and a protein called SIRT1. NAD boosts SIRT 1, which in turn enables the conversation between muscles and blood vessels. But both NAD and SIRT1 decline as we age. They can no longer perform their role as the interface between muscles and blood vessels.”

Finally, the researcher describes how giving the compound NMN to mice boosted their levels of NAD, producing remarkable results, as Dr. David Sinclair says,

“In our new study, we gave mice NMN, a chemical compound commonly found in the body and previously shown to boost NAD levels, which in turn boosts SIRT1. These mice had better endothelial function, blood vessel growth and improved blood supply to their muscles. “

Mice treated with NAD booster NMN outperform untreated ones according to Dr. David Sinclair
Mice treated with NAD booster NMN outperform untreated ones. Source: Dr.  Sinclair / HMS.

The most striking effect of was a significant boost in the mice’s ability to exercise. The aging mice treated with NMN gained between 56 and 80 percent greater exercise capacity, compared with untreated ones by being able to run much farther on a treadmill.  According to Dr. Sinclair, the mice treated with NMN had improved exercise capacity due to improvements in vascular function, saying

“And what was most striking? These animals’ capacity for exercise improved dramatically. In fact, the old mice treated with NMN had up to 80 percent greater exercise capacity, compared with the untreated old mice.”

Dr. David Sinclair suggests that NMN and NAD may reverse aging in blood vessels and restore the muscle tissue of Seniors one day.
Dr. David Sinclair suggests that NMN and NAD may reverse aging in blood vessels and restore the muscle tissue of Seniors one day. Credit: Dr. David Sinclair / Harvard Medical School.

Sinclair believes that the results achieved in mice can eventually be translated to humans, helping to counter age-related diseases with a vascular component, such as frailty, heart attack, stroke or even forms of dementia such as Alzheimer’s disease. As Dr. David Sinclair says in his parting words,

“These results, I believe, can help millions of people who have lost their mobility, or simply can no longer exercise, either through frailty, disability or old age. This sets the stage for new medicines that will be able to restore blood flow in organs that have lost it, either through a heart attack, a stroke or even in patients with dementia.

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Ben Greenfield Podcast on NAD for aging

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[8:21] Dr. Ross Grant and Dr. Philip Milgram

[10:40] How Thomas Got Into NAD Research

[20:04] Dr. Milgram’s Story and Thomas

[21:15] Dr. Milgram’s on NAD

[21:51] What is Hyperalgesia?

[22:14] How NAD Breaks Addiction

[23:27] What exactly is NAD

[27:07] NAD and Anti-Aging

[33:55] NAD Supporting Supplements

[39:19] Nicotinamide Supplementation and dosage

[42:26] The use of Resveratrol supplement

[44:54] Delivery Mechanisms of NAD

[48:23] Other Things Combined With NAD

[50:30] NAD and Exercise Performance

[53:33] Ways To Naturally Increase NAD

[58:09] Going back to Anti-Aging

[1:01:15] Is there a blood test for NAD levels?

[1:03:11] NAD and Lyme disease

[1:05:35] Exciting thing in the realm of NAD

[1:12:15] Dr. Milgram’s website nadtreatmentcenter.com

[1:14:29] End of Podcast

Ben:  Hey, it’s Ben Greenfield.  I actually found today’s podcast episode so fascinating that I had to bring it to you right away in lieu of our normal weekly Q & A, which will be back next week. I think you’re really going to find today’s episode quite fascinating.  It’s about anti-aging.  So, before we jump into today’s podcast about how you can reverse Benjamin Button yourself, I wanna tell you about today’s sponsor which is Kimera Koffee.

Now, if you go to k-i-m-e-r-a-k-o-f-f-e-e dot com, you can get 10% off Kimera Koffee, and they’re actually available now in, drumroll please, Australia through this distributor called Optimoz. Now I know I have lots of listeners down under, and they have a URL that you can use.  Here it is: optimoz.  That’s o-p-t-i-m-o-z dot com dot AU, and the good folks over at Kimera, where they infuse their coffee with nootropics to really get your brain spinning, they wanted me to tell you about this.  So optimoz.com.au.  I suppose if you live in the US, or Canada, you could probably go there and order from Australia, although I would recommend you instead go to kimerakoffee.com and just use code Ben to get 10% off.

This podcast is also brought to you by something that I highly encourage people to get more of: greens.  And my wife recently did her own iridology test, where she had her iris examined for things that might be needing attention in her body, and one of the things that they noticed was that she could perhaps use a little bit of a metal clean-up.  It may sound like woo-woo, but this iridology stuff is really fascinating.  I’ve got a podcast coming up on it.  And one of the ways that you can clean up metals in your body is via the use of something called chlorella, and many greens actually act quite similarly to chlorella with this effect.

And there’s one form of greens powder that she’s using now everyday, it’s called Organifi.  Now, you can get 20% off this same stuff that tastes really good, you can add it to a smoothie, if I have a smoothie and just has, say, lettuce in it, I’ll add this greens powder to make it more dense and green, so I feel very good about myself.  You can get it at bengreenfieldfitness.com/fitlife, and if you use discount code Ben, you will get 20% off.  That’s bengreenfieldfitness.com/fitlife with code Ben to get 20% off.

And then finally, there is a mattress company that you may or may not have heard of, and it’s a sleep brand that created one mattress.  But they take this one mattress to rule them all, just like the ring in Lord of The Rings, in case you missed that association, they sell it directly to consumers.  They limit commission driven, inflated prices, I think Freakonomics actually did a fascinating episode on mattresses and how they’re actually, they’re skipping the middleman, and delivering the mattresses straight to you.

This particular mattress is made by a company called Casper, which has an award-winning sleep service developed in-house with a sleek design, and it’s delivered in this tiny, little, how-did-they-fit-that-all-in-there sized box.  They also have things like an adaptive pillow and soft, breathable sheets.  Free shipping, free returns to US and Canada.  You can try for a hundred nights, risk free, just sleeping on it with all your body odors, and chemicals, and everything, and if you don’t like it, they’ll pick it up, and they’ll refund you everything.  So, that’s pretty cool.  You can get $50 off this mattress when you go to casper.com/ben and you use promo code Ben.  Casper.com/ben and promo code Ben, and terms and conditions apply, I’m supposed to tell you that.

So, that being said, don’t you love that way that I segue into the episode?  That being said, let’s go ahead and listen to this fascinating episode with three, count ’em, not one, not two, but three guests, on NAD.

In this episode of The Ben Greenfield Fitness Show:

“We checked around various pathways, and it looked like NAD levels were increased with this supplement.  Now we thought that that was probably functioning as a preservation of NAD, so it makes sense because of NADs role in being handled efficiently or make the mitochondria in where you’re producing the energy.”  “The NAD business, you know, it’s been around actually for many, many years.  But because of human greed, it’s sort of been kept underground.”  “Music sounds beautiful.  I can really have an emotional response to music.  I can really hear all the nuances to it.  He responded well, it’s because your nerves are revived.”

He’s an expert in human performance and nutrition, voted America’s top personal trainer and one of the globe’s most influential people in health and fitness.  His show provides you with everything you need to optimize physical and mental performance.  He is Ben Greenfield.  “Power, speed, mobility, balance – whatever it is for you that’s the natural movement, get out there! When you’re look at all the studies done… studies that have shown the greatest efficacy…”  All the information you need in one place, right here, right now, on the Ben Greenfield Fitness podcast.

Ben:  Hey folks, it’s Ben Greenfield, and I wanna tell you about an article I recently read in Scientific American.  This article was called “Beyond Resveratrol: The Anti-Aging Nad Fad”, and NAD referring to NAD.  And what this article includes, among many other things, is, for example, quote, “Recent research suggests it may be possible to reverse mitochondrial decay with dietary supplements that increase cellular levels of a molecule called NAD.”  And there’s another part of the article that says, quote, “The mitochondria in muscles of elderly mice were restored to a youthful state after just a week of injections with NMN, a molecule that naturally occurs in cells and boosts levels of NAD.”  Well, since that article was published a few months ago, I have received an onslaught of questions about this mysterious molecule called NAD.

And it just so happens that a friend of mine, named Thomas Ingoglia, he knows one of the best NAD scientists on the face of the planet.  He’s in contact with one of the best NAD clinicians on the planet, both with decades of experience, second to none when it comes to NAD, and I actually consider Thomas himself to be one of the most knowledgeable and frequent users of NAD who I’ve ever met.  He’s one of the few guys that’s been playing around with it in combination with things like cryotherapy, and blueberry extract, and hyperbaric oxygen, and all these other biohacks that have allowed him to turn completely around from being bedridden sick and losing half his family in a car crash, to being in the best health of his life, including crushing his first Spartan race with me last year, prior to which he actually took high doses of NAD.

And the problem is a lot of NAD clinical researchers seem to mostly be underground at the moment.  The FDA doesn’t look kindly at NAD supplement companies and integrative doctors who use NAD.  They’re skeptical of naturopathy, and the first impulse is to turn these type of compounds into patentable drugs because that’s a language that the FDA speaks, and NAD can be dangerous.  I’ve spoken with Thomas and he knows a guy personally who has poisoned himself while using NAD incorrectly and hospitalized himself with the same substances we’re gonna be talking about in this podcast episode.

So, yeah.  You need to proceed with caution and with the type of formal clinical information that Thomas has opened my eyes to, and Thomas is actually on the call with me today, but I don’t just have Thomas here with me today.  Along with Thomas, first of all, we have Dr. Ross Grant, PhD., and Dr. Grant is one of the most prolific authors in the field of NAD, and he specializes in the effect of NAD on the brain.  He’s been researching it since 1994, back when nobody was doing NAD research.  He’s the clinical associate professor at the University of Sydney Medical School, and the CEO of the Australasian Research Institute, and a biochemical pharmacologist himself.  So he’s a smart cookie, and he specifically researches NAD and its role in oxidative stress, and the human cellular response to oxidative stress and how NAD affects that.  And in addition to Dr. Grant, we’re also, as if that weren’t enough, joined by Dr. Philip Milgram, who is an M.D., and Philip Milgram is based out of the NAD Treatment Center in San Diego, California, and he specifically helps people in recovery from addiction using NAD protocols.

So, between Dr. Grant, Dr. Milgram, and Thomas, we have quite a few folks who specialize in NAD.  So if you’re curious about this stuff, you are in the right place.  Now before I jump in, and I’m gonna jump in starting, with Thomas, and Thomas telling us his story and how he first kinda discovered NAD, I wanna tell you that all the show notes for everything that we’re gonna talk about, including a link to that article that first kinda sparked my own interest in this, you can find at bengreenfieldfitness.com/nad.  That’s bengreenfieldfitness.com/nad.  So, with that being said, let’s just go through here real quick so everybody can know everybody else’s voices.

Dr. Grant, welcome to the show and thank you for coming on at 4 A.M., Australian time.

Ross:  You’re most welcome, Ben.

Ben:  And Thomas, welcome.

Thomas:  Thank you, Ben.

Ben:  And finally, Dr. Milgram, welcome to the show.

Philip:  My privilege, Ben.

Ben:  Alright.  Well, fantastic.  Well, Thomas, like I mentioned, you’re the guy who kinda first became my outlet into the wide world of NAD.  So tell me a little bit about how you first discovered NAD, and how you got to the point where you were kind of dug deep into a health hole, so to speak when it came to needing some serious healing.

Thomas:  Well, I’d like to start by saying that this all really began when I lost half my family in a car crash a few weeks after I lost them, old friends to drugs and alcohol, I had a friend who knocked on my door the day that he killed himself, and he had abused drugs, and he had severe psychological problems because of it.  But I had lost my dad, and my brother, and my nephew instantly in a head-on collision, and it was very hard for me because I was chronically ill for about seven years.  I was suffering from what doctors called Fibromyalgia and Chronic Fatigue Syndrome, and I took opiate drugs at that time.

My illness was brutal.  I spent a lot of time in bed.  I had trouble standing for periods of, let’s say, over 45 minutes.  I was very sick.  I would get headaches, there were so many different symptoms that I had, and I was very fatigued all the time.  And going to the funerals, because we had a funeral in Costa Rica, and I had to go see my mom in Hawaii where the accident took place, the car crash, it was just, it was very hard on me, and I was very angry.  And I made a point that at the funeral, to myself, that I would do anything and everything to cure myself.

Ben:  So, do you know what exactly it was that was causing you to be in a position where like you couldn’t stand up for 45 minutes, or for more than 45 minutes?  Or what exactly the infection was?

Thomas:  Well, it’s crazy because when people ask me, I’m forced to tell them that, you know, I don’t know.  I mean, the Mayo Clinic couldn’t figure out what was going on.  I do know that there were some tests for Lyme that showed positive results.  I do believe I had a lot of the symptoms for antibiotic adverse reaction, and I put some of the claim on that.  And then also, there’s a concept called opiate-induced hyperalgesia which is this idea that longer term use of opiates will cause pain throughout your body.  So, you know, I think it was probably sort of a mixture of those things, and we can go down a rabbit hole on this great deal and I’d rather, maybe save that for another time, but needless to say that it was a nightmare, and I was looking for something that would be beneficial for me, no matter what I had.

Ben:  So you were more or less addicted to opiates and extremely sick?

Thomas:  Yeah, and tired.

Ben:  Okay, and so what did you do from there?

Thomas:  Well, I was up late at night in one of my support groups, and someone would mention NAD, and I was like, “Okay.  I’ll give it a shot.”  And I called Springfield Wellness Clinic, which was the longest running NAD clinic in the country for 15 years.  They may have treated over a thousand patients, and they told me, “You know what?  We have a place in San Diego where it’s being done.”  And so, I was like, “Great!  I live in San Diego.”  So, I started the treatment and it’s intravenous NAD+, and that’s very important that you get the right molecule.  It’s not NADH, which is completely different.

Ben:  Okay.  So, when you say intravenous, you’re actually getting this stuff injected?

Thomas:  Yeah, it’s into your vein.  It’s a lengthy treatment.  I ended up going for 12 days.  It might be like seven hours a day, and then I was a noisy patient, I was not easy to be around.  They asked me to give up opiates and I was scared and, you know, just kind of grumpy.  But after that, about the day seven, the day nine, things began to change.  I remember Anne Rogers saying, “Your eyes are shining.  You’re changing.  I can see it,” and I was a little bit surprised that she could see that I was changing physically, and that happens to quite a lot of chronically ill patients.  Their face and cheeks just start to get color, it doesn’t happen with everyone, and then a day later, they get more color and gloss in their eyes.  Their eyes no longer look, like dull.  So…

Ben:  I mean, I’ve done IV injections before, like Myer’s cocktails where you get high dose glutathione, and vitamin C, and a host of different vitamins, but with this NAD, is it just NAD that you’re injecting when you do something like this intravenously?  Or are you including other things like vitamin complex, or things along those lines?

Thomas:  You know, the NAD doctors that are involved with the Mestayer model, where Mestayer is the doctor in Springfield.  They worked to customize the protocol, her patient, and so, other things that you might see in Myer’s cocktails might be added at some point, just so you know that the supplements aren’t mixed in the same bag.

Ben:  Okay.  Gotcha.

Philip:  Let me jump in real quick.  There are definite protocols that Dr. Mestayer from Louisiana has worked on, and we’re also working on on improving and yes, it is similar to getting Myer’s cocktail.  It’s an intravenous slow drip at the rate that the person can tolerate it, and then we add other minerals, and we individualize the treatment according to testing and what the patient’s personal needs are to enhance the NAD experience.  The NAD is the most active ingredient but we use these other compounds, because there’s an art to this, it’s not just starting an IV and running NAD in.

Ben:  Okay.  Gotcha.  Now, I do wanna definitely ask you about some of the protocols that you do there Dr. Milgram, but back to you Thomas, in terms of starting into this, you’re literally saying within days of beginning NAD injections that your health completely turned around?

Thomas:  Yeah, I mean, I remember being in the ocean, swimming in the ocean about a week afterwards, and I just remember looking around and everything I sensed was just richer and full of more color, and my pain went down by 50% in the first 10 days of treatment, and then I started to go down further over the next six months and a year, and it said it might be beneficial to keep coming in every so often to get a booster, and I was diligent in doing that.  And I felt healthier, and less pain, and more energy, you know, every time I came in.  So…

Ben:  Interesting.

Thomas:  At that point, I went back to old doctors and just sort of talk to them, and some of these doctors were like, they said, you have no idea what you just stumbled upon.  We just came to a conference, we were just at a conference, I was just talking about this, and you should pursue this and then they gave the whole “you-should-go-to-medical-school” thing, but it was really motivational, and they encouraged me go to medical conferences which I did, and I got the same responses that these integrative medical conferences that I went.  And I also remember meeting with a scientist who was working in the NAD field for coffee, and he asked me about my story.  I remember telling him, I was like, “You know there’s one thing that I gotta tell you about, and that’s the music sounds beautiful.  Like, I can really have an emotional response to music.  I can really hear all the nuances in it.”  And he responded, “Well, it’s because your nerves are revived.”

Ben:  Wow.

Thomas:  I dissected mice on NAD and we noticed a difference in their nerve connections to their ears, and I don’t know, I was sort of, at that point, that was incredible.  But it was six months after I did the NAD that I saw the article by David Sinclair.  Well, I saw it in Time magazine, the journal article he did and so, at that point I was like, “What did I stumble upon?”  They’re using a precursor, and we’re using, you know…

Philip:  The actual NAD.

Thomas:  The actual NAD.  Yeah.

Ben:  Okay.  Gotcha.  So there is a difference, I know, and I wanna delve into that here in a moment, but Dr. Milgram, in terms of you and your story, are you the person who Thomas actually hooked up with, in terms of his first experience with NAD?

Philip:  Yes.  He hooked up with this lady that I worked with together with Dr. Mestayer in Louisiana, and her name was Anne Rogers, she was looking to bring it to San Diego, and she found me as an addiction medicine doctor, and also somebody interested integrative medicine and nutrition, and individualized medical care with metabolic nutrition, and just serendipity, she found me.  I’ve been doing addiction medicine for 25 years.  I’ve been in treatment myself for opiates, in recovery since March 23rd, 1988.  Then I studied intervention with Vernon Johnson, the guy that invented intervention back in 1991, and I’ve dedicated my life to this because this really changes people’s lives.  I’ve been involved in Tom’s therapy, I was trained by Dr. Mestayer in Louisiana, and who’s been doing it since 2001, and then I’ve been involved with administering NAD to Tom, yes.

Ben:  Okay.  Gotcha.  And you yourself, if I’m not mistaken, didn’t you used to have some kind of like addiction issues that you overcame with NAD as well?

Philip:  I didn’t overcome them with NAD.  I’ve been medical director of several detox places but originally, I was just exposed to the old, white knuckle type of detox where they prescribe high levels of drugs to counteract withdrawal symptoms like valium, benzodiazepines, and other heavy duty drugs, and I’ve been doing that for 25 years.  When we came to NAD, it’s a game changer.  There’s virtually no withdrawal symptoms, the hyperalgesia is decreased, and…

Ben:  What’s hyperalgesia?

Philip:  What Tom referred to that opiates, in a way makes it a cycle that makes you use more opiates.  It actually increases your sensation of pain, then you require more opiates.

Ben:  Okay.  Gotcha.

Philip:  It’s a vicious cycle.

Ben:  Gotcha.  How is NAD actually breaking addiction?  Like how does this work?

Philip:  Well, I can’t give you the answer in 25 words or less, but it actually works at the epigenetic level to decrease withdrawal symptoms.  Okay?  It also works at the mu-opioid receptor level to decrease this exaggerated response of pain through the sodium and calcium-gated channels.  And it also decreases anxiety by having an effect on the bundled up chromatin that comes from lack of NAD.

Ben:  Okay.  So someone who’s like anxious, who’s having withdrawal symptoms, and who has like a chemical addiction to opiates.  It’s working on all three of those different platforms to decrease the addiction to opiates, and let me know if I’m correct about that, but also decrease addiction to other substances as well?

Philip:  Yes.  And in fact, it has the greatest effect on alcohol addiction.  It’s amazing.  It actually acts at the metabolism and genetic expression of alcohol predisposition.  Again, I can go as deep into this as you’d like.

Ben:  Well, what I’m curious, I guess the first thing and I’m sure a lot of our listeners are wondering this too, and perhaps this is a question for you, Dr. Milgram, or for Dr. Grant, but what exactly is NAD?  Like, what is it and what does it do?

Philip:  Well, it’s like we’re on a phone call talking about relativity, and we have Einstein on the phone with us.  Why don’t we have Dr. Grant, who’s one of the world’s experts on this, how he answers this question.

Ross:  Yeah.  Look, I’m happy to make a few comments and I’ll try and make them fairly brief, but NAD probably, is what could be considered one of the master regulators of cell metabolism and often when people talk about different molecules having this amazing impact, they’re often sort of talking at a level which is on molecules functioning at a fairly high level in a cell.  But here, we actually do have a molecule which is fundamental to the way the cell functions, and its levels as it goes up and down has an influence on multiple different areas.  So NAD itself, I mean apart from the clinical benefit as Dr. Milgram has talked about, and obviously Tom has experience, but at its fundamental level it’s actually involved in a number of different things.

It’s a co-factor, which we’ve known for many decades now.  So, you know, alcohol dehydrogenase as you need NAD, in fact it’s the NAD that runs out when people are trying to metabolize alcohol, and so they’re ending up with high levels of alcohol as a result, but it’s needed as a co-factor.  Another one is to lactate dehydrogenase, et cetera, which is also involved with that buildup of lactate, when you’re using your muscles.  It’s an electron transporter.  Now what that means is that you need to, when you’re turning the food you eat into the energy that the body needs to the muscles, et cetera, you need to be able to transfer the electrons from that food that you took down, what we call a respiratory chain in the mitochondrion, and that’s how we generate the energy, ATP.

Ben:  Okay.

Ross:  NAD is critical for that.  You know, it’s also needed for DNA repair, so, our DNA is getting damaged all the time, and I guess we’ll talk about aging a little bit later on, but it’s a really important molecule.  Well for now call a substrate, so it’s actually used up by the enzymes, or one of the key group of enzymes, there are a number of them, but basically it repairs particularly, and it’s actually used by those enzymes in order to help prepare the DNA.

Ben:  So, your body makes NAD on its own?

Ross:  It makes NAD on its own, and it makes it from a few different precursors.  So I know that was mentioned before, about nicotinamide mononucleotide or NMN, but there’s a number of precursors that it can actually make it from.  It can make it actually, originally also, from the molecule tryptophan, which is an amino acid people would have linked up in their minds to things like serotonin, which is one of these neurotransmitters, but happy to get into that a little bit later on, the epigenetic signaling its involved with as we know, the switching on and switching off genes by changing acetylation patterns, and these are sorta linked to people might have heard in a sort of aging medicine, or aging sort of like chemistry with the sirtuins, and NAD is a precursor to that, so sirtuins might be important.

And I guess a lot of the enthusiasm about resveratrol is the fact that it was theoretically driving sirtuin activity.  What’s interesting is that sirtuins are like a factory, like any enzyme, they won’t function unless they have, if you like, the raw material for that factory to work on, and NAD is that raw material.

Ben:  Okay.  Gotcha.  Now, I took physiology in college, like physiology and biochemistry, and what we were basically told was that NAD, or this nicotinamide adenine dinucleotide was basically, all it does is it carries electrons, right.  Like it’s involved in redox reactions in the cell, and you basically have it, this NAD+ gets an electron from other molecules, it gets reduced, and that makes this stuff called NADH, which then can donate electrons, and it’s just essentially one of the ways that the human body kinda keeps working as a giant battery.  We never learned about any of this stuff regarding like anti-aging, or addiction, or it acting on these sirtuin pathways you’re talking about, and so, I guess that’s my first question, especially after hearing you and reading this Scientific American article about how this could be the new anti-aging drug of the future.  How exactly is it working when it comes to NAD?  I know that you just mentioned this sirtuin pathway, and I know that’s intimately involved with aging, so can you go into, not only what this sirtuin pathway is, but what’s the proposed mechanism between, or as to how NAD would actually help someone when it comes to anti-aging?

Ross:  Yeah.  I mean, it’s a very good question and all of the answers aren’t known in here.  What we do know is that when it comes to aging, so if you think of what’s actually happening when somebody is aging, they’re actually getting an accumulation of damage within the cell, and that accumulation of damage particularly around the DNA, is affecting the way those cells function and therefore the way the organ functions.  And a couple of the key things that characterize aging is that part from the cumulative damage is also this decrease in energy, and just a decrease in what we might call the viability of the cell.

So very simply, where does NAD set in?  NAD, we know, can improve energy efficiency because one of the key things that’s needed in order for the mitochondrion to work well, in order for the energy to be produced, is that we need to have an efficient supply of these NAD molecules, as you said, to be able to transfer those electrons so that we end up having a mitochondrion being able to convert literally the energy we take in, mix it with the oxygen that we also breathe, and finally produce ATP at the end.  If you don’t have NAD, the mitochondrion doesn’t work.  Therefore, you don’t generate the energy.

Now, at the epigenetic level, then we have again NAD as a master regulator at that point.  If NAD levels drop, then the epigenetic switches, and people would be aware that now we know we have methylation patterns, and acetylation patterns, and what these are is just molecules that set on and off, both the DNA as well as the chromatin that sits around with the proteins, to allow the genes to either be switched on or switched off.  If you’ve got lots of NAD around, it is able to switch on, so sirtuins act, they deacetylate things, and they’re able to switch on pathways that are linked to improving cell viability, and in other words improving the health of the cell.  Now, remember this is at a global level, so it’s not just happening in one organ, it’s actually happening across the body, including the brain, as well as the muscles, as well as other tissue.  And so this increases things like a radio oxidant production, and basically keep cells working in what we would consider to be a younger state of metabolism.

Ben:  Okay.  Gotcha.  So essentially all we’re doing is we’re allowing our mitochondria to function more efficiently when we have adequate NAD, and we’re also fighting a lot of the oxidation that could cause aging, but by giving our body extra NAD via something like the intravenous injections that Thomas and Dr. Milgram were talking about, we’re not just able to, for example, fight off some of the bad things that can happen when we’re addicted to a substance, but we can literally activate these anti-aging pathways.

Ross:  Correct, and I guess the other important thing is that it looks like we were able to increase the repair of DNA that might get damaged in the course of normal metabolism.

Philip:  Ben, can I chime in here?

Ben:  Yeah.  For sure.

Philip:  I’ve got a list, you know, I want you to get out of thinking that it’s just NAD to NAD+ in the Krebs cycle. That’s what we learned, making ATP.  That’s what we learned back in Biology 101, but this is much greater than this.  It’s an epigenetic co-factor in blocking over-reactive genes that are not being expressed properly.

Ben:  So what do you mean by that?

Philip:  In histone acetylation, methylation, phosphorylation, and DNA methylation, and micro RNA, it has an effect to allow the histones to get tightened up in the chromatin, and of course, very greatly simplifying this, and the NAD actually helps unbundle this.  Though it actually works to remodel your chromatin by its effect on these sirts and the PARPS, it actually affects DNA repair.  It affects the CD38 gene for increasing immune function.  It causes the mitochondrial biogenesis.  It increases the production, and effectiveness of each individual mitochondria.  It actually offers a neuroprotective device qualities protecting the nerves from demyelination and other things.  It being explored at Harvard for use in ALS, multiple sclerosis, Parkinson’s disease, Alzheimer’s disease.  It also again, it’s very important that the sensation of pain by the gated calcium and sodium channels, the voltage-gated chain, the NAD helps that function properly so you don’t have this hyperalgesia.  It may act itself as a neurotransmitter, and it has an effect on autophagy.

Ben:  Really?  So it can also act as an actual neurotransmitter?

Philip:  That’s still being studied.  That’s sort of nebulous, probably beyond the scope of this discussion.

Ben:  Okay, but basically it could potentially be involved in like cell-to-cell communication?

Philip:  Yes.

Ben:  Okay.  Interesting.

Ross:  Yeah.  And I can jump in there and yeah, it certainly support that, it looks like NAD probably does serve as a neurotransmitter by systemically as well as in the central nervous system.

Ben:  Interesting.  Okay.  So, this Scientific American article it, obviously, based on some of the cool things about NAD that you guys have just talked about, it goes into how there’s a lot of different NAD sources being created right now.  Like there’s this stuff called Niagen.  There’s something called Basis by I think a pharmaceutical company Elysium.  They talked in this article about things that can assist with your body’s own production of NAD, like resveratrol, that we’d find in red wine or in supplement form, or something called pterostilbene.  Can you help us cut through all this clutter, Dr. Grant, as far as what the best way is to actually get NAD into our bodies, and what exactly the status is as far as the development of pharmaceuticals or the development of supplements?

Ross:  Yeah, sure.  Look, to get it into the body, and this is one of the reasons why clinics like Dr. Milgram’s and Dr. Mestayer will use IV NAD, if you want to get NAD into the body efficiently, what we call a 100% bioavailability, you know, when it’s all getting in, then the best way is to take an IV.  The unfortunate thing is, and even though there’s a lot of work that needs to be done still in this area, it looks like if you take NAD orally, and I’ve seen supplemental tablets for NAD out there, but taking it orally, unfortunately, you’re pretty much not going to absorb it across the gastrointestinal tracks.  So from the stomach and the gut, you’re not gonna absorb NAD very efficiently.  So, to what to get NAD up efficiently, it’s intravenous.

Now, there are a few other ways in which the body can actually make NAD, so that what we call precursors, and you mentioned one of them, niagen.  Niagen’s a fairly new one, and that was identified actually originally from milk in around about 2007, but that is called nicotinamide riboside.  And nicotinamide, yeah, nicotinamide riboside actually gets converted into NMN, which is one of the other precursors that are also available, the one you talked about in one of the other article.  So you can get those two, and those two will be absorbed across the gap.  So you can get effectively NAD increased from taking those orally.

The other two ways of getting them is by the classic vitamin B3’s that you’ll get from over-the-counter at the drugstore, and that would be nicotinic acid which is the acid form of vitamin B3, and this is the one that the…

Ben:  You said B like boy?

Ross:  Yeah, B like boy.

Ben:  Okay.

Ross:  So, vitamin B3.  So the nicotinic acid form is the one that’s been used for actually quite a few decades now to reduce cholesterol.  It’s the one unfortunately that has a side effect that gives you flushing.  We can talk about why that happens.  But then the other molecule that you’ll also get, again across the counter and in many supplements, is the amide form called nicotinamide.  Now, you’ll notice that NAD is nicotinamide adenine dinucleotide.  So that is the nicotinamide version.  Now nicotinamide can also be, what we call, recycled.  It’s in what we call the salvage pathway.  It can be recycled through to NAD.  The negative thing with having too much nicotinamide, as opposed to the other types of NAD precursor that I’ve mentioned, is that nicotinamide is a byproduct.  Now, you’ve heard we’ve talked about CD38, we’ve talked about sirtuins, and talked about the PARPS.  So CD38, the immune modulators, the Sirts, the epigenetic modulators, and PARPS, the DNA repair enzymes.  Now all of those three, when they use NAD, they will actually generate nicotinamide as a byproduct.

Ben:  Okay.

Ross:  And the important thing about that is that that nicotinamide, as the levels start to go up in the cell, the nicotinamide starts to inhibit those enzymes, the CD38s, the sirtuins, the PARPs.  And so too much nicotinamide, unfortunately, can stop the very reactions that you want to have acting.

Ben:  Interesting.  Okay.

Ross:  So, we would probably suggest that getting it from some of the other sources, the nicotinamide riboside, NMN, or nicotinic acid would be better.

Ben:  Okay.  And the NMN, is that something that one can, for example, purchase in like a supplement form, or this nicotinamide riboside?

Ross:  Both NMN and nicotinamide riboside can be purchased.

Ben:  Okay.  And the absorption of those in the gut is sufficient to actually increase NAD levels inside the human body?

Ross:  Yes, they do.  And there has been some studies in animals particularly, in fact we’re in the middle of preparing to conduct what we call a head-to-head on these so that we can see which one is actually the better one.  And most of them there is evidence that both of them will significantly increase NAD.  We’re probably favoring the riboside at the moment as opposed to the NMN, but both of them seem to be able to do it.

Ben:  Okay.  So…

Philip:  And again, Ben, it’s dose related.  You know, think of the breakdown of nicotinamide adenine dinucleotide into nicotinamide and adenine, okay?  That reaction of breaking the NAD down to nicotinamide is where the Sirt and the CD38, and the PARPs are generated and activated.  So if you have too much of the nicotinamide, it can actually force that to not happen.  So I would say like people that are taking too much nicotinamide is probably not a good idea.

Ben:  And how much would be too much? ‘Cause if you look on like Amazon, right, like if you go to Amazon, you do a search for like nicotinamide supplements, you’ll find like NOW Foods, and Life Extension, and all these other companies selling like 500mg capsules of nicotinamide, like that’s about the dose you’ll see in a lot of these.  When you say, “If you take too much, you’re gonna shut down those positive pathways that you’re trying to activate,” how much would be too much if someone were just gonna like try to get a nicotinamide supplement from one of these companies?

Philip:  Well, usually they come as 250 or 300mg, and they suggest two a day, and I think that’s the proper dose.  But people will think, “Oh, wow.  If a little bit is good, a lot is better,” and they’re taking more than that, I think they may actually be doing themselves disfavor.

Ben:  Okay.  So once you’re exceeding, like close to about 600mg, you’re saying that that could be Bad News Bears?

Philip:  Correct.  Just like too much vitamin D.

Ben:  Okay.  So, nicotinamide, we can buy nicotinamide, also known as NMN supplements on a website, like Amazon for example, from a good company, and we could take anywhere from 300 to 600mg of that to activate some of these anti-aging, or antioxidant pathways, or new mitochondrial-building pathways.  Now this nicotinamide riboside, which is not the NMN form, is that also something that you can find in supplemental form?

Ross:  Yes, you can find nicotinamide riboside as a supplement, and nicotinamide riboside, like NMN, will be converted through to NAD.  In fact, nicotinamide riboside is converted first to NMN, and then through to NAD, and for reasons that we still don’t understand, it seems to be [0:41:35] ______ way of getting there, and you can take, unlike the nicotinamide, which is actually having to be recycled through the pathway, and it recycles through NMN as well, but nicotinamide riboside, you probably can take up to, I would think, easily 500 to even possibly 1,000mg a day without too much concern ’cause you’re not gonna be generating nicotinamide directly.  If you’re supplementing with nicotinamide on its own, so that’s the vitamin B3 that’s often out there, if you supplement that on its own, you’re already increasing the body’s nicotinamide, and that’s doing the inhibition.  But taking the other two, the NR, the nicotinamide riboside, or the NMN, neither of those will produce nicotinamide until it goes through NAD.

Ben:  Okay.  Gotcha.  Now this article for example, the one in Scientific American talked a lot about resveratrol, which you find in wine, and the fact that resveratrol can kinda like rev up the sirtuin pathways.  And when we rev up the sirtuin pathways, we can do things like form new mitochondria, or keep mitochondria running smoothly.  Now, when it comes to resveratrol, is that something that you would take in conjunction with something like NAD injections, or one of these nicotinamide supplements, or is that something that one would use on its own?  What are your thoughts on the use of something like a resveratrol supplement?

Ross:  Yeah, I’m happy to make a comment.  I think that there is some positives with certainly the antioxidant effects that come from the stilbenes, which resveratrol is one, and…

Ben:  What’d you call, the stil, the pterostilbene?

Ross:  Yeah.  The pterostilbenes.  They’re a class of molecules that are what we call in the phytonutrient class.  So, there’s mention of them coming from things like the skin of red grapes, and from blueberries, and in fact, you even get them from things like peanuts, et cetera.

Ben:  Is that why Thomas that you told me that you were using like a blueberry extract in conjunction with your NAD injections?

Thomas:  That was just something that I had originally gotten from a brain conference that I went to, but as soon as I found that out, yeah, I’m very pretty religious on taking my blueberry extract.

Ben:  Okay.  And that’s because this pterostilbene that Dr. Grant was talking about, you’re gonna find that in addition to resveratrol in things like blueberries, and grapes, and dark purple, and blue type of fruits, or berries?

Ross:  Mhmm.

Thomas:  Yeah.

Ben:  Okay.  Gotcha.

Philip:  And we’ve found that NAD really is the most important thing to increase your Sirt 1 through 7 activity, but resveratrol specifically, you need that for Sirt 2.

Ben:  Okay.  Gotcha.  So there’s different sirtuin pathways that are activated by different forms of supplements and you would, for example, take resveratrol in conjunction with NAD to get the best of both worlds.

Philip:  Correct.

Ross:  Yeah.  Though theoretically, there seems to be a fairly good benefit.  I mean all the sirtuins need NAD, some of them get switched on a little more efficiently than others in different parts of the cell.

Ben:  Now, in terms of the best delivery mechanism, it sounds like intravenously that you can really get very, very high levels of NAD compared to some of these supplements that we’re talking about, but how much of a difference is it?  I mean, are we talking about like a night and day difference between intravenous injections versus someone using a supplement, like a resveratrol mixed with an NAD supplement?  Are we talking about a slight difference?  I mean, in terms of comparison between intravenous delivery versus oral delivery, how do these different delivery mechanisms vary?

Thomas:  In my personal experience, I just think that intravenous NAD is, you know, I haven’t seen anything that’s like it in comparison.

Philip:  Let me respond on a clinical level.  You know, we suffer from lack of NAD because we’re using it up and not replenished in proper levels, and it’s the cause of underlying aging, and other disease processes.  So I think that you have to sort of flood the body with NAD to start off with, but then you can supplement, and that’s why we use intravenous.  Then you can supplement NAD with a pure source of NAD that we give intranasally that I think is a very good method of continuing to substitute to boost your NAD levels.

But, you know, the NAD business has been around actually for many, many years.  But because of human greed, it’s sort of been kept underground.  People wanted to make money on it, so they called it different things.  They called it Coenzyme 1, they called it amino acid therapy when Dr. Hitt was doing it down in Mexico.  But then it was analyzed by Dr. Mestayer and his friends in Louisiana, and found that the active ingredient was actually pure NAD.  And they now have the pure source of, you wanted NAD that doesn’t have a contamination in it, you want it so that it has a high level, it’s not very stable at room temperature for a prolonged period of time, so it has to be gotten fresh, and be made up fresh and used quickly, and that’s why we have these protocols, and then we also use it with other nutrients to individualize therapy for people’s individual needs.

Ben:  Okay.  Gotcha.  So, in terms of other things, are you talking about things aside from like blueberry extract and resveratrol that play well with something like NAD when it comes to the anti-aging or the addiction mitigating effect?

Philip:  Correct.  Not only that we need to add things to enhance the NAD experience, and we know what those are, certain minerals and, but also, it seems like a lot of the things that we’ve been doing for detox for years actually go and work against these…

Ben:  Like what?

Philip:  Like benzodiazepines.  We do not give benzodiazepines when we do NAD therapy.

Ben:  You mean like valium, and stuff like that?

Philip:  It’s like anti-NAD.

Ben:  Would that be, for example, like a valium?

Philip:  Valium, Xanax.

Ben:  Okay.  So basically, a lot of these will actually have an effect that inhibits mitochondrial function?

Philip:  Correct.

Ben:  Okay.  Gotcha.  And what are some of the   things  that  combine  well  with  NAD?    You mentioned minerals as one.

Philip:  Well, magnesium, calcium, potassium, but we also handling the side effects, there’s drugs that we use and drugs that we don’t use that we’ve found to not inhibit NAD, but decrease some of the withdrawal symptoms, and enhance the NAD thing. I mean, we’ve developed this over the years.  Dr. Mestayer has been working on it, and we’ve develop these and increased these even more.

Ben:  It’s really interesting because I did a podcast with a guy named Dr. David Minkoff a few weeks ago where we talked about cancer and mitochondria, and anti-aging, and it seems that a lot of this kinda overlaps in terms of, you know, we spoke of hyperbaric oxygen therapy to enhance oxygen availability for enhancing mitochondrial function.  I mean, I know that’s something that Thomas, you told me that you had experimented a little bit with.  I’ve talked about cold therapy, and cold thermogenesis for enhancing mitochondrial function and the amount of nitric oxide that you have in your body.

You know, you guys are now bringing up other ways to enhance mitochondrial function such as mixing NAD with resveratrol, with minerals.  It seems to me that when we’re talking about like anti-aging, that there are all these different things that seem to kind of be going after the same effect, which is, more or less, improving mitochondrial health, while also improving the ability of DNA to repair, in the case of NAD.  But I know that, and I have a question for Dr. Grant actually about this, I know that the effect of this stuff can go beyond anti-aging and, for example, could kinda reach into the realm of fitness, which I think a lot of our listeners might be interested in.  As far as the research on NAD and anything such as VO2 Max, or lactate tolerance, or time to exhaustion, or anything like that, Dr. Grant, have there been studies on NAD, and how it affects the actual fitness or exercise performance?

Ross:  There’s been very few and I suspect that that’s going to rapidly change.  We’re involved in a study a little while ago now where we were looking at the influence of a particular supplement that was being provided to athletes, and seeing what the effect was, that will be getting a 15% improvement in what they called ‘Time to Fatigue’, as you’ve mentioned, so they could exercise about 15% minutes longer, and it was the exercise physiologists who brought the problem to our lab, and asked us to have a look, and see what we thought could be the issue.

So we checked around various pathways and it looked like NAD levels were actually increased with this supplement.  Now we thought that that was probably functioning as a preservation of NAD.  So it makes sense because of NAD’s role in being able to efficiently or make the mitochondrion where you’re producing the energy, where you’re making that happen efficiently.  And, as I mentioned, with lactate dehydrogenase being able to convert that more efficiently through the pyruvate.  So increasing NAD, it makes sense that you would have the potential for increase in fitness.

Ben:  Okay.  Gotcha.  So, what they’re saying is it may improve time to exhaustion by somehow working on the ability to turn over lactic acid more quickly, but it’s not actually something that’s been fleshed out in actual human research?

Ross:  In great detail.

Ben:  Okay.  Gotcha.

Thomas:  But then also, by acting through specifically the Sirt1, we found some of the things that you and your experience have shown to increase, improve the human condition.  Things like fasting, mechanically stretching muscles, exercise, low glucose diets, proper circadian rhythm sleep cycles, actually act to let the Sirt1 and the NAD work properly.  And that’s why they work, it works through the NAD and Sirt pathway for these things that you can do to be a healthy person, that’s why they work.  A lot of the better diets, the ketogenic diet, Atkin’s diet, Paleo diets, that’s how they work, they also work to increase Sirt1.

Ben:  Right.

Ross:  And that’s true, and the good thing with an activation of things like Sirt1 is it looks like we’ll end up getting an increase generation of mitochondrions.  You actually increase the number of mitochondrion as well as the efficiency of energy productions.  So, it [0:53:01] ______.

Philip:  And especially in the brain.

Ross:  Mhmm.  In the brain and in the muscles as well.  But, yes, certainly both.

Ben:  We’re talking now about, like, you know, some different lifestyle strategies that could, for example, enhance these Sirt1 pathways, you know, in a similar way as NAD, such as some of the things you were talking about, like ketosis, we mentioned calorie restriction, we mentioned cryotherapy, hyperbaric oxygen chambers.  What are some of the best ways to actually raise NAD levels naturally with other food strategies, or other lifestyle strategies, or other biohacks, for example?

Ross:  Yeah.  Look, I’m happy to jump in there with some of the lifestyle elements, which I think are particularly important.  If you want to turn over your NAD fast, in other words, if you want to drop your NAD, which is not what we’re gonna do and I’m just using that, then you’re gonna have any condition which has an increase in inflammation and what we call oxidative stress, or free radical damage.  Both of those, not only does it signal through to increase the CD38 activity, but it also increases PARP activity, which is the DNA repair.  So inflammation, free radical damage, both of those are gonna decrease your NAD, which is what you don’t want.

So, very simply, any of the lifestyle behaviors that are going to improve that is going to increase your NAD naturally.  And this includes taking in less calories, we know that using whole foods and some of the work in the brain that we’ve done which is interesting, showing that the caroteniods particularly, so these are the molecules that are coming from the red, yellow, and green leafy sort of veggies, these are particularly high in caroteniods and these can actually help preserve, particularly in the brain, NAD levels.  Exercising, eating whole grains, I mean these are gonna be able to provide things like your nicotinic acid and vitamin B3, et cetera, on their own.  But all of these, essentially doing those things that you’d be [0:54:52] ______ , most people would recognize were healthy for them is going to help to increase their NAD and maintain high NAD levels, and therefore high sirtuin activity, et cetera.

Ben:  Okay.  Gotcha.  What about light therapy?  You hear a lot about like infrared light and your infrared intranasal light, things along those lines, how about light?  Does it play a role here?

Ross:  Look, I don’t know, nobody’s done any work on that directly, as far as I’m aware, not specifically with NAD, but there is work that’s been done on light therapy of different wavelengths, even through the blue wavelengths decreasing inflammation within certain parts of the body, particularly in people with pain.  So, where there’s benefit that’s there, and I guess there’s still a lot of work still going on there, that photomodulation, that if it’s going to decrease pain, which is associated with cytokine signaling and increase in inflammatory cytokines drive or increase your pain, then there is going to be benefits with NAD.  And that probably works both ways, so the higher NAD is able to shut down some of those pathways.

Ben:  Okay.  Gotcha.  What about you, Thomas?  I know you’ve experimented with some things when it comes to enhancing your response to NAD therapy and supplementation.  What are some ways that you’re using food or lifestyle strategies to increase your own levels of NAD?

Thomas:  Personally, I had a very substantial decrease in pain and a very strong uptake in energy in that 12 days I initially did NAD therapy, but I wasn’t a 100% back to recovery and so, I was still desperately trying to make some changes and I think, sort of accidentally, I was really cutting down on my caloric intake, I was eating more vegetables, and my carbohydrate intake had come down, and I think that that may have contributed to sort of the positive impact that sort of accentuated the high levels of NAD that I had.  And when that happened to me in over the course of, let’s say, a year, I had lost about 40 pounds in fat ’cause I did a body comp.  And then it was a lot, I think it was actually a year and a half, and then at that point, I met up with you at the Spartan race in Las Vegas and it was my first Spartan, and I ended up placing at the top one and a half percent.

Ben:  Prior to that race, you actually took some NAD.  I remember we were in the condo, and you were taking something, but you didn’t do an IV, right?  You just basically were using like one of these nicotinamide type of supplements we were talking about?

Thomas:  No, actually I did IV NAD a few days before I arrived, and I wanted to see what kind of impact that had.  I don’t, I’m not sure, I mean this is just anecdotal, I definitely, I mean it’s obvious, I already said that, yeah, I mean, I had no energy before, and now I’m doing all these things.  But as far as me personally, having this immediate effect, I don’t know where but that’s something that needs to be looked at a little bit more.

Ben:  Okay.  Gotcha.  Now, I wanna get into anti-aging here real quick.  Dr. Grant, I know that you mentioned that NAD levels will drop when we age, which is perhaps why NAD is being proposed as an anti-aging supplement, but how much?  Like is this a significant drop?  Has this been studied in terms of the actual decrease?

Ross:  Yeah, absolutely.  I mean, we did some early studies back in 2011, we were just looking at animals, and across the age range you can see, while you know, accumulation of damage within the body, and things like PARPs go up the enzyme that’s actually trying to repair the DNA go up, NAD drops.  And then we said, “Alright, what we saw in animals, we thought we’d better have look at that in humans”.  So we looked at it in, with the pelvic, non-sun exposed skin, all the eight way from, sort of eight day old circumcisions up to 79 year old hip replacement, and you could see again the damage sort of accumulating with time, and particularly after the age of 60.  But then you could see the NAD drop fairly consistently with inflammation and oxidative damage, and in 2014 we published some work showing the same sort of decline within the brain, and this can be anywhere up to 40%.  So there is a significant drop that can happen…

Ben:  Forty percent is how much it could decrease as you age.

Ross:  Yeah.

Ben:  Is that just due to everything from oxidation to DNA damage, to living in an industrialized area where you’ve got lots of inflammation, free radicals, and things like that?

Ross:  Yeah, it’s predominantly what causes that inflammation and oxidative damage.  So as were saying lock-in formation of cell will drive oxidative damage inflammation which then damage the DNA, so you’ve got an increase in [0:59:51] ______ that drive the CD38.  Now, CD38 is definitely involved in the immune function as Dr. Milgram is saying earlier, but CD38 probably has some other function.  We have some other what we called NAD like a hydrolases that function in ways that were not really quite sure in a cell but these seem to go up to certain CD38 when we have inflammation going on and that seems to be also a primary driver of decreasing NAD as we get older.

So, there is a significant drop in NAD and it depends where you’ll look for I mean, whether or not it’s enough in the plasma or whether it’s in the tissue itself.  So it can vary depending on the different tissues, but certainly in the plasma they can give quite some significant shift.  And also in the fluid that drains the brain called the cerebral spinal fluid which is a good indicator of what actually happening clinically within the tissues.

Ben:  Okay.

Philip:  I remember reading some studies that they tested people under 45 and over 45 for their NAD levels and they found that 300% increase in the average between the pre- 45 and post-45.  Also, another study shows that it seems to exponentially increase after age 60 the loss of NAD.

Ross:  The loss of NAD that’s certainly what we found after the age of 60.  So, there seems to be an acceleration of damage and therefore an acceleration of the rapid loss of NAD as a result.

Ben:  Can you actually test your own NAD levels, like is there a blood test for that?

Ross:  Yeah look, we have actually offered that to one or two of our clinics here in Australia or any because we know that they can actually get sample to us in a particular way which preserve NAD.  The trouble with doing it and sending it through a normal pathology lab is a) they won’t do the test, and b) the samples itself once it collected needs to be preserved extremely quickly otherwise NAD will change very rapidly, and so you’ll get abnormal results.  So it is possible to do it but it’s a bit tricky to do it sort of in a regular basis in a normal lab at this stage.

Philip:  We are gonna be dealing clinical trials in our facility and in conjunction with Dr. Mathai in Louisiana to do this the right way, and actually test people with the special testing that Dr. Grant is talking about.  We had to purchase this special centrifuge and we have to handle the samples in a certain way, and we are gonna be deforming clinical studies on this.

Ben:  Well, vitamin B3 is also known as nicotinic acid or niacin or nicotinamide, couldn’t you just measure your vitamin B3 levels?

Ross:  Vitamin B3 is an important precursor to NAD and as we mentioned nicotinamide, if you take nicotinic acid, yes you’ll be able to generate NAD through that pathway.  If you take nicotinamide, nicotinamide is that sort of complicated situation where it’s both can be made back into NAD but it’s actually a byproduct of NAD.  So nicotinamide is going up doesn’t necessarily mean that NAD is going up.  Nicotinamide going up could actually mean that you’re turning over NAD quite a lot.  So, difficulty there.

Ben:  Okay, gotcha.  And I’ve got a few other questions: the first is I know that a lot of people listening in and Thomas kinda briefly mentioned that he thought that some of his symptoms may have been indicative of something like Lyme disease, and I’ve heard a few snippets here and they’re about the use of NAD for the use of something like Lyme which I know is a frustrating issue for a lot of people who have chronic fatigue is this Lyme infection.  What’s the link between NAD and the treatment of Lyme disease?

Ross:  Well, I’m not sure if Dr. Milgram wants to make comment there.  I can sort of begin that one off.  Lyme disease is originally as a Borrelia infection which is a spirochetal bacteria.  And people think to end up with chronic fatigue, reduced energy, and there are some central nervous system dysfunction that can happen with people at a chronic stage, and one of the things that NAD will do as we’ve talked about in essentially from the beginning of our discussion is that it has a significant improvement in being able to increase the efficiency of energy production.  So it’s probably working on at that level, I don’t know of anybody who’s done any specific studies to look at mechanism and I guess that’s where we probably still lacking a bit of information but improving energy production, improving the way the immune system probably functions which is the primary driver often behind and this is sub-clinical so it’s hard to test a little bit.  It seems almost certain that you’ve got disregulated immune function.  Again, maybe through CD38, some of these [1:04:50] ______ maybe out of half ways but we probably able to modulate more efficiently the immune function as well as increasing mitochondrial function.

Ben:  Okay, got you.

Philip:  It’s a controversial subject, Ben, about treating Lyme disease, and I know doctors, well intentioned, wonderful doctors that have lost their medical license by treating Lyme disease.  But I can say that for sure the NAD in many cases can help decrease some of the symptoms of Lyme disease.  We’re not treating the cause of Lyme disease which is antibiotics treating a bacteria but some of the symptoms can be lessened with NAD.

Ben: Now Dr. Milgram and Dr. Grant, as we’re coming up towards the end here, is there anything else that you want to throw in as far as things that you find exciting in the realm of NAD research or the use of NAD as an anti-aging drug or for the use in other conditions?

Philip:  Well, even the MTHFR gene has improved with NAD.  The…

Ben:  When you say the MTHFR gene has improved with NAD, what do you mean?

Philip:  Well, again, this unspooling of the DNA, it may make the expression of the MTHFR gene change through a snip called C677T.

Ben:  And for people who are listening, can you explain this MTHFR gene?

Philip:  I’d rather like to talk about, more about some other things that I’m really excited about NAD.

Ben:  Okay.

Philip:  I have been doing addiction treatment for 25 years, and I’ve treated hundreds of patients, the good old-fashioned way of white knuckling it, and seeing them go through terrible withdrawal symptoms, through cravings, and the NAD virtually stops that.  It’s just absolutely amazing.  They have like a brain, people say they feel like they’ve never used before, or drank.  Their cravings are decreased.  It’s just amazing, and I’m really excited about, not only the anti-aging things that they’ve talked about, and there’s people like Dr. Watson, and if you have a chance to hear Dr. Watson talk from UCLA, he is extremely excited about the effects of NAD for an anti-aging.  And also, these different disease processes that we’ve before had no way to treat them.  Things like fibromyalgia, or chronic fatigue syndrome, Alzheimer’s disease, Parkinson’s disease, ALS.  They’re finding that NAD can make a difference in the therapy of these patients.  I think, in my opinion, and this is just an opinion, NAD will turn out to be one of the greatest advances in medical science since Fleming invented penicillin.

Ben:  Wow.  That’s quite the claim.  And in terms of people using NAD, you’re thinking that it’s gonna be just like these type of injections that you’re doing, that are gonna get the most efficacy?  Or are you just talking about NAD in general use as a supplement?

Philip:  I think you need to flood the body with NAD to start off with, and then we’re looking that this place that found out where, what is actually was in Dr. Hitt’s amino acid therapy from Mexico, it was pure NAD.  They are manufacturing a pure source of NAD that we are now using as supplementation.  And then you can also use the nicotinamide riboside, and other dietary things to enhance this.  And also it’s important that you do all of the things that, you’re expert in Ben, with the fasting, the mechanical stretch, the exercise, the low glucose, proper circadian rhythms, and sleep, all these things will enhance the effectiveness of your own NAD to work.

Ben:  Yeah, and I think that’s the key here whenever we talk about like a new anti-aging drug, or we talk about like this Scientific American article is they’ll talk about the use of things like resveratrol, or NAD, or nicotinamide, or many of these other compounds, and they’ll say that in terms of like mice and mitochondria, that the effects of NAD simulate the effect of calorie restriction, for example.  And the way I like to think about things is that you first do the lifestyle strategies, right.  Like consume more dark berries, blueberries, or grapes, or resveratrol containing compounds, engage in calorie restriction, expose your body to good amounts of oxygen, pay attention to things like air, and light, and water, and electricity, and all those other things that can affect mitochondrial variables.

I’m not saying you cover up a bad lifestyle with something like NAD injections, or the use of some of these NAD supplements that we’ve talked about, but it sounds like, especially as you age, and especially based off of what Dr. Grant said as you get past 60, if you want to engage in some type of anti-aging protocol, it sounds like this might be a smart one to throw into the mix based on actual research that’s been done on what this can do to everything from DNA to cellular damage.

Thomas:  Correct.

Ross:  Yeah.  Absolutely.

Philip:  And also, when Dr. Grant is the world’s expert on oxidative stress and NAD, and he brought up a point as we were talking about preparing for this conference.  He talked about, you know, if you have a lot of rust around, you have a lot of oxidation going around, the NAD’s not gonna be as effective.  So you have to have a healthy lifestyle which will enhance your NAD expression.

Ben:  Yeah.  Yeah.  Exactly.  As with a lot of these things we talked about here, you can’t cover up a bad lifestyle with a pill.  Well guys, first of all, Dr. Grant, I wanna thank you so much for coming on the show, as I know it’s extremely early over in Australia.

Ross:  You’re most welcome.

Ben:  And Dr. Milgram also.  Thank you for coming on and devoting your time.  And Thomas, thank you for your introduction to Dr. Milgram and Dr. Grant, and for kinda opening my eyes to NAD.

I have a couple more quick questions.  As far as any further resources Thomas, for folks, you had mentioned to me a book written by a guy named Dr. Nady Braidy, called “NAD+ Metabolism In Neurodegeneration and Ageing,” which I know is available on Amazon.  Is that what you would consider to be the best resource for people to delve more into NAD, or are there other places you would point people to?

Thomas:  I think that’s a great resource.  It’s heavy reading.  That was written by Dr. Grant’s student, and now colleague of Dr. Grant, and I think that would that’s a great place to start if you wanna go heavy into the science.  Dr. Milgram also has a blog at his website, nadtreatmentcenter.com, and the blog gets updated with new science as it unfolds.

Ben:  Okay.

Thomas:  So that’s nadtreatmentcenter.com.

Ben:  Cool.  I’ll link to that, and I’ll also link to everything else that we talked about including this Scientific American article, some of the resveratrol supplements that we discussed, the book by Nady Braidy, et cetera if you just go to bengreenfieldfitness.com/nad.  And if you go to bengreenfieldfitness.com/nad, that is also where you can leave any questions, any comments, any feedback that you have about today’s episode, or anything else that you wanna pipe in on in terms of your own personal experience with NAD, or other anti-aging protocols that we discussed in today’s show.  So gentlemen, thank you all for joining on the show today.

Philip:  Thank you.

Ross:  You’re welcome.

Thomas:  My privilege.

Ben:  Alright, folks.  So, this Ben Greenfield, along with Dr. Grant, Dr. Milgram, and Thomas Ingoglia signing out from bengreenfieldfitness.com.  Once again, you could check out the show notes at bengreenfieldfitness.com/nad.  Thanks for listening and have a healthy week.

You’ve been listening to the Ben Greenfield fitness podcast.  Go to bengreenfieldfitness.com for even more cutting-edge fitness and performance advice.

 

 

Scientific American recently published the article “Beyond Resveratrol: The Anti-Aging NAD Fad“, an article that proposes that…

…”recent research suggests it may be possible to reverse mitochondrial decay with dietary supplements that increase cellular levels of a molecule called NAD (nicotinamide adenine dinucleotide)”…

…and also that…

…”the mitochondria in muscles of elderly mice were restored to a youthful state after just a week of injections with NMN (nicotinamide mononucleotide), a molecule that naturally occurs in cells and, like NR, boosts levels of NAD”…

Since that article was published I’ve received an onslaught of questions about this mysterious molecule called NAD.

It just so happens that a friend of mine, Thomas Ingoglia, known as one of the best NAD scientists on the planet and is also in contact with the best NAD clinicians on the planet – both with decades of experience second to none. I consider Thomas himself to be one of the most knowledgeable and frequent users of NAD I’ve ever met, and one of the few that has been playing around with NAD in combination with cryotherapy, blueberry extract, hyperbaric oxygen and other “biohacks” to completely turn him around from being bed-ridden sick and losing half his family in a car crash to being in the best health of his life, including crushing his first Spartan race with me last year (prior to which took high doses of NAD).

Problem is, most NAD clinical researchers are all underground at the moment. The FDA doesn’t look kindly at NAD supplement companies and integrative doctors, they are quite skeptical of naturopathy, and their first impulse is to turn these things and others into patentable drugs because that’s the language the FDA speaks. Plus, NAD can be dangerous. Thomas even knows a guy personally (ironically, a Phd in toxicology that poisoned himself due to his own error) who hospitalized himself experimenting with the substances we’re going to be talking about in this podcast episode. So you need to proceed with caution and with the formal clinical information Thomas has opened my eyes to.

Along with Thomas, today’s podcast features Dr. Ross Grant, Phd. Dr. Grant is perhaps the most prolific authors in the field of NAD, and he specializes on NAD in the brain. He started researching NAD research back in 1994 while being laughed at, when no one was doing NAD research.

Dr. Ross Grant is Clinical Associate Professor at the University of Sydney Medical School and CEO of the Australasian Research Institute, Sydney Adventist Hospital. A biochemical pharmacologist with a Ph.D. in Neurochemistry/Neuropharmacology, Dr. Grant’s research is focused on NAD – specifically the role of oxidative stress – e.g. emotional stress, diet, and exercise – and NAD metabolism on brain cell death and cellular degeneration. A secondary interest is in the effect of exposure to novel nutritional components, such as polyphenols, on human cellular response to oxidative stress, with a goal of detecting and correcting early degenerative biochemical changes associated with aging-related degenerative disease.

Dr. Grant is a member of the Australian Society for Medical Research (ASMR), Australian Neuroscience society (ANS), Australian Society of Clinical & Experimental Pharmacology and Toxicology, Nutrition Society of Australia (NSA). With forty-eight articles published in peer-reviewed scientific journals, Dr. Grant is perhaps the most prolific author in the field of NAD research.

In addition to Dr. Grant, we are joined by Dr. Philip Milgram, MD, from the NAD Treatment Center in San Diego, California. Dr. Milgram recovered from his own challenges with addiction and now helps other people in recovery from addiction, specifically by using NAD protocols. He trained in 1991 with Vernon Johnson, the man who coined the term “Intervention”. He was certified as a Prevention Specialist by the Certifying Board of Alcohol and Drug Counselors (CCBADC) in 2001, and has three degrees in counseling from UCSD; in Counseling and Interpersonal Communication, Alcohol and Drug Counselor and Advanced Intervention.

In addition to NAD Treatment Center, Dr. Milgram served as the original Medical Director of Confidential Recovery and the Pemarro Detox Center. He has also served as the Medical Consultant for The Soledad House Recovery Home for Women and ABC Recovery since they opened. He is a member of the attending staff at Scripps Memorial Hospital in La Jolla and Board Certified in Obstetrics and Gynecology. Dr. Milgram is a member of The American Society of Addiction Medicine, the California Association of Addiction Medicine, International Doctors in AA, Like-Minded Docs Addiction Medicine, The American College of Preventive Medicine, the American Society of Anti-Aging Medicine, and the American Nutraceutical Association.

During our discussion, you’ll discover:

-An easy explanation of what exactly NAD is and what it does inside your body…

-The protocol Thomas used to go from being addicted to opiates and chronically fatigued to completely healed…

-How NAD can break addictions to alcohol, food, opiates and more…

-The relationship between anti-aging and NAD…

-The important difference between Nicotinamide Riboside vs. Nicotinamide (NMN) vs. NAD+…

-The best way to “flood your body” with NAD, and why grapes and blueberries are so important when it comes to your NAD levels…

-What kind of compounds, foods and lifestyle strategies enhance the effect of NAD…

-How NAD can increase your time to exhaustion during exercise by over 15%…

-How Thomas used NAD to enhance his performance in a Spartan race…

-The best way to test your own NAD levels…

-How NAD can be used in the treatment of Lyme Disease…

-The best resource for people to delve more into NAD research…

-And much more!

Resources from this episode:

Book by Nady Braidy: NAD+ metabolism in neurodegeneration and ageing

NAD Treatment Center in San Diego, California

Nicotinamide supplements (be careful with dosage on this, as we discuss in podcast!)

Nicotinamide Riboside supplements (dosage also discussed in podcast)

Resveratrol supplements

Wild blueberry concentrate supplements

Thorne Resveracel (resveratol + NAD)

Pau D’ Arco Bark tea that can be brewed and blended with fats such as coconut oil or krill oil to create NAD-based phosopholipids

Disclaimer:

NADinfusions are an experimental treatment, and do not have FDA approval and haven’t been fully evaluated. To the best of our knowledge there are no lasting problems. This IV therapy has been around for decades but it has mostly been underground. Over ten thousand patients have had NADintravenous treatment  but this is not a panacea and not everyone is going to have positive results.

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Scientific American Article on NAD for aging

 

Beyond Resveratrol: The Anti-Aging NAD Fad

Whenever I see my 10-year-old daughter brimming over with so much energy that she jumps up in the middle of supper to run around the table, I think to myself, “those

ADVERTISE young mitochondria.” Mitochondria are our cells’ energy dynamos.

The views expressed are those of the author(s) and are not necessarily those of Scientific American.

Whenever I see my 10-year-old daughter brimming over with so much energy that she jumps up in the middle of supper to run around the table, I think to myself, “those young mitochondria.”

Mitochondria are our cells’ energy dynamos. Descended from bacteria that colonized other cells about 2 billion years, they get flaky as we age. A prominent theory of aging holds that decaying of mitochondria is a key driver of aging. While it’s not clear why our mitochondria fade as we age, evidence suggests that it leads to everything from heart failure to neurodegeneration, as well as the complete absence of zipping around the supper table.

Recent research suggests it may be possible to reverse mitochondrial decay with dietary supplements that increase cellular levels of a molecule called NAD (nicotinamide adenine dinucleotide). But caution is due: While there’s promising test-tube data and animal research regarding NAD boosters, no human clinical results on them have been published.

 

Structure of nicotinamide adenine dinucleotide, oxidized (NAD+). (Image: NEUROtiker/Wikimedia)

 

NAD is a linchpin of energy metabolism, among other roles, and its diminishing level with age has been implicated in mitochondrial deterioration. Supplements containing nicotinamide riboside, or NR, a precursor to NAD that’s found in trace amounts in milk, might be able to boost NAD levels. In support of that idea, half a dozen Nobel laureates and other prominent scientists are working with two small companies offering NR supplements.

The NAD story took off toward the end of 2013 with a high-profile paperby Harvard’s David Sinclair and colleagues. Sinclair, recall, achieved fame in the mid-2000s for research on yeast and mice that suggested the red wine ingredient resveratrol mimics anti-aging effects of calorie restriction. This time his lab made headlines by reporting that the mitochondria in muscles of elderly mice were restored to a youthful state after just a week of injections with NMN (nicotinamide mononucleotide), a molecule that naturally occurs in cells and, like NR, boosts levels of NAD.

It should be noted, however, that muscle strength was not improved in the NMN-treated mice—the researchers speculated that one week of treatment wasn’t enough to do that despite signs that their age-related mitochondrial deterioration was reversed.

NMN isn’t available as a consumer product. But Sinclair’s report sparked excitement about NR, which was already on the market as a supplement called Niagen. Niagen’s maker, ChromaDex, a publicly traded Irvine, Calif., company, sells it to various retailers, which market it under their own brand names. In the wake of Sinclair’s paper, Niagen was hailed in the media as a potential blockbuster.

In early February, Elysium Health, a startup cofounded by Sinclair’s former mentor, MIT biologist Lenny Guarente, jumped into the NAD game by unveiling another supplement with NR. Dubbed Basis, it’s only offered online by the company. Elysium is taking no chances when it comes to scientific credibility. Its website lists a dream team of advising scientists, including five Nobel laureates and other big names such as the Mayo Clinic’s Jim Kirkland, a leader in geroscience, and biotech pioneer Lee Hood. I can’t remember a startup with more stars in its firmament.

A few days later, ChromaDex reasserted its first-comer status in the NAD game by announcing that it had conducted a clinical trial demonstrating that “a single dose of NR resulted in statistically significant increases” in NAD in humans—the first evidence that supplements could really boost NAD levels in people. Details of the study won’t be out until it’s reported in a peer-reviewed journal, the company said. (ChromaDex also brandishes Nobel credentials: Roger Kornberg, a Stanford professor who won the Chemistry prize in 2006, chairs its scientific advisory board. He’s the son of Nobel laureate Arthur Kornberg, who, ChromaDex proudly notes, was among the first scientists to study NR some 60 years ago.)

 

Sirt1 protein, red, circles the cell’s chromosomes, blue. (Image: Ana Gomes/Sinclair Lab)

 

The NAD findings tie into the ongoing story about enzymes called sirtuins, which Guarente, Sinclair and other researchers have implicated as key players in conferring the longevity and health benefits of calorie restriction. Resveratrol, the wine ingredient, is thought to rev up one of the sirtuins, SIRT1, which appears to help protect mice on high doses of resveratrol from the ill effects of high-fat diets. A slew of other health benefits have been attributed to SIRT1 activation in hundreds of studies, including several small human trials.

Here’s the NAD connection: In 2000, Guarente’s lab reported that NAD fuels the activity of sirtuins, including SIRT1—the more NAD there is in cells, the more SIRT1 does beneficial things. One of those things is to induce formation of new mitochondria. NAD can also activate another sirtuin, SIRT3, which is thought to keep mitochondria running smoothly.

The Sinclair group’s NAD paper drew attention partly because it showed a novel way that NAD and sirtuins work together. The researchers discovered that cells’ nuclei send signals to mitochondria that are needed to maintain their normal operation. SIRT1 helps insure the signals get through. When NAD levels drop, as they do with aging, SIRT1 activity falls off, which in turn makes the crucial signals fade, leading to mitochondrial dysfunction and all the ill effects that go with it.

NAD boosters might work synergistically with supplements like resveratrol to help reinvigorate mitochondria and ward off diseases of aging. Elysium is banking on this potential synergy—its NR-containing supplement includes a resveratrol-like substance called pterostilbene (pronounced tero-STILL-bean), which is found in blueberries and grapes.

Why pterostilbene instead of resveratrol?

While resveratrol has hogged the anti-aging spotlight over the past decade, unsung researchers in places like Oxford, Miss., have quietly shown that pterostilbene is a kind of extra-potent version of resveratrol. The pterostilbene molecule is nearly identical to resveratrol’s except for a couple of differences that make it more “bioavailable” (animal studies indicate that about four times as much ingested pterostilbene gets into the bloodstream as resveratrol). Test-tube and rodent studies also suggest that pterostilbene is more potent than resveratrol when it comes to improving brain function, warding off various kinds of cancer and preventing heart disease.

Elysium isn’t the only pterostilbene vendor. In fact, ChromaDex also offers pterostilbene for supplements separately from Niagen.

How excited should we be about all this? If I were a middle-aged mouse, I’d be ready to spend some of the nickels and dimes I’d dragged off the sidewalk to try NR supplements. Even before Sinclair’s paper, researchers had shown in 2012 that when given doses of NR, mice on high-fat diets gained 60 percent less weight than they did on the same diets without NR. Further, none of the mice on NR showed signs of diabetes, and their energy levels improved. The scientists reportedly characterized NR’s effects on metabolism as “nothing short of astonishing.”  The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity.

 

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