NAD’s central role in the future of medicine

An interview with Dr. Fenton Le Bon

Fenton Le Bon, MD, MBA, is a licensed psychiatrist, medical practice developer, and the co-founder and CEO of Molecular World Health, a new company created to offer medical therapeutics based on key foundational molecules already present in the body to optimize wellness, healthy aging, and the treatment and prevention of disease.

Dr. Le Bon has spent most of his career in traditional psychiatric practice and building alternative medical clinics in the US and Argentina. In Miami, he founded a private psychiatric and corporate consulting practice, focusing on new treatment modalities for eating disorders and addiction medicine. In Georgia, he founded Eastman Mental Health, an integrated multidisciplinary outpatient practice, treating adults, adolescents and children for general psychiatric disorders, as well as developing programs such as state-based in-patient long-stay wilderness programs for the treatment of substance use. In Argentina, he founded Las Sierras Healing and Empowerment, a clinic treating substance use disorders. Now returned to the States, he is working to advance nonprescription NAD treatment delivery options to support as many people as possible in managing or eliminating chronic pain, restoring cognitive functioning, maintaining sobriety, and optimizing wellness.

Dr. Le Bon earned his BA in philosophy from the University of Southern California, his MD from the Medical College of Pennsylvania, and completed his internship and residency in psychiatry at the University of Florida School of Medicine. He received his MBA from the Warrington School of Business at the University of Florida.

During his residency, he trained under Mark Gold, MD, considered one of the primary founders of addiction medicine and an early proponent of dopamine’s central role in addiction. Dr. Le Bon is honored to advance the work of Dr. Gold, and of Dr. Richard Mestayer and Paula Norris Mestayer, M.Ed., LPC, FAPA, who are pioneers in NAD addiction treatment in the US. With them, he is working toward the shared understanding that “addiction is a brain disease. When the brain is treated, it can heal.”

NAD Research: Please tell us about your background in addiction and how you discovered intravenous NAD as an effective treatment for it.

Dr. Le Bon: About 30 years ago now, I had the honor of working under Dr. Mark Gold in my residency program at Shands Hospital, University of Florida. Dr. Gold is considered the father of biological addiction because he basically discovered every important primary aspect of it—from dopamine as the centerpiece to treatments addressing dopamine deficiency. When I finished my psychiatric residency, I started private practice in general psychiatry and addiction medicine. Next, I went to Georgia and worked in addiction wilderness programs with recovering patients, with the goal of addressing, not just the addictive substance, but the cues and clues that lead individuals to abuse the substance.

Then I moved to Argentina and started a wilderness program for substance use disorders there. Dr. Gold knew that I was interested in innovative treatments for addiction, and one day he reached out to tell me about an innovative doctor named Richard Mestayer, who was involved in NAD research, was getting amazing results with intravenous NAD, and was going to present at a conference sponsored by the Positive Sobriety Institute in Chicago. So I called Dr. Mestayer and we struck up a friendship, and recently I arrived here in Springfield, Louisiana, to see how we might collaborate.

Before arriving, I’d read the literature Dr. Mestayer and his associates had published; however, until you’ve seen the results, that understanding is only conceptual. When I came to Springfield Wellness Center and saw their tremendous success with withdrawal symptoms, cravings, and even with Parkinson’s symptoms, I went from being a believer to an experiencer. That’s why I’m so enthusiastic about what we’re doing.

NAD Research: What do you think explains intravenous NAD’s effectiveness at treating addiction?

Dr. Le Bon: Well, we don’t know specifically, but we believe that the NAD molecule has the ability to cause “heterodimerization” of the dopamine receptor. [MedGen describes “heterodimerization” as “a biophysical interaction between two dissimilar biological molecules or subunits, such as between two proteins.”]

With the understanding that dopamine is the centerpiece of the brain’s reward system, as well as the centerpiece of withdrawal cravings and other addiction symptomatology, combined with the clinical evidence that intravenous NAD inhibits cravings and withdrawal symptoms, we strongly believe that NAD is affecting the brain’s dopamine response. It’s allowing the brain to “reset,” which is why they’ve called their treatment “brain restoration.” This is all theoretical, but that’s our best guess.

There are also other neurotransmitter pathways that we believe NAD affects. But we know that it has a profound influence on dopamine receptors and the pathways subsequent to that.

Certainly, we need much more research in this, and we need money to fund it. But there’s no question that 20 years’ worth of success leads us to strongly believe that is why it works.

NAD Research: One question that has been of interest to me since Michael Payne referenced the existence of “circulating NAD,” is whether intravenous NAD might be working on the brain through circulating NAD as the IV sends NAD into the bloodstream.

Dr. Le Bon: We don’t know exactly how the NAD is achieving its results. Dr. Mestayer and Dr. Ross Grant, as you know, were the first people to do the NAD pharmacokinetics study, and hypothesize that it has direct brain benefits. We also hypothesize that NAD is reduced to another molecule, possibly extracellularly. And we also believe that NAD precursors can enter the cell. Exactly how NAD gets into the cell or gets across the blood-brain barrier hasn’t been demonstrated. But with every new piece of research that Dr. Mestayer and Dr. Grant are doing, we’re getting closer to understanding why NAD is such a miracle molecule.

NAD Research: Do you think that intravenous NAD and NAD delivered by other means—the SphenoCath, sublingually, topically, or by injection—work in the same way, via the same mechanisms?

Dr. Le Bon: Probably not. Intravenous NAD is special. We get different responses—not just more profound responses, but different responses—from intravenous NAD. Oral NAD is probably not as effective, given that it’s likely to be broken down in the stomach or consumed by the liver. (Each human liver cell has 2,000 mitochondria, and we know that NAD is absolutely integral with mitochondrial function, so ingested NAD might never make it past the liver.)

Topical NAD, the NAD cream, has been shown anecdotally to dramatically increase wound healing and also to work very well for pain, whether chronic pain, muscle pain, osteoarthritis pain, or peripheral vascular-ischemia-induced claudication pain. We have some ideas about why it works, but the most important thing is that it does work.

The specific mechanisms by which NAD works by each of the different delivery methods are not yet understood, but it is clear that intravenous NAD is the quintessential treatment. Studies have shown it to work for cognitive decline, Parkinson’s, and migraines, as well as for addiction withdrawal and cravings. We’ve even seen that it works, anecdotally, for traumatic brain injury.

We also have studies that show that NAD delivered by SphenoCath (intranasally) works for Parkinson’s and migraines, but how and why we still don’t know. By the way, that’s actually quite in keeping with most medications throughout history. We have an idea of why and how they work, but we don’t completely know the pathway for most medicines that are in use.

NAD Research: At a previous talk this year you gave a pretty comprehensive overview of the different roles that NAD plays in the body. A number of people told me afterward that the talk was very helpful. Do you have the ability to summarize some of it right now?

Dr. Le Bon: Certainly. In the old days, way back when I went to medical school, we believed that NAD simply was the foundational molecule for the production of ATP, which is the basic energy fuel that all cells use. NAD picks up hydrogens from the Krebs cycle and puts them into the electron transport chain in the mitochondria, which produces ATP for energy. Later on we also discovered, through the work of Dr. Ross Grant and others, especially his team in Australia, that NAD is also the foundational molecule for anti-inflammation through the sirtuin system—SIRTS 1 through 6.  

For example, the sirtuin system is intimately involved with the production of superoxide dismutase, which is a primary enzyme associated with reducing reactive oxygen species and free radicals, which are very destructive to cell components and organelles. It turns out that NAD is the primary anti-inflammatory molecule in the sirtuin pathways. NAD is also involved in DNA repair through its involvement with PARP (Poly ADP-ribose polymerase). The main role of PARP is to detect and initiate an immediate cellular response to metabolic, chemical, or radiation-induced DNA damage. NAD is required as the substrate for generating ADP-ribose monomers, which combine to form PARP. DNA repair is the body’s very first step in preventing cancer.

We also know that NAD is essential for eliminating pathogens in the body, through three different receptors on natural killer T cells (CD8, CD38, and CD57). These natural killer cells have to do with the identification of foreign bodies, which would include viruses, bacteria, parasites, cancer cells, and also transplanted tissues (which might possibly be the one contraindication for NAD).

So NAD is essential for cellular energy production, anti-inflammation, combatting oxidative stress, and disease protection. Focusing just on cancer, we have anecdotal evidence that NAD cream can reduce, if not eliminate, squamous cell carcinomas. Which is not surprising when you think about it, because inflammation-triggered mutations are at the root of many cancers. So there are really three different pathways for NAD to be involved with cancer protection and removal: anti-inflammation, DNA repair, and natural killer T cell enhancement.

All of this is very exciting, and we still are just scratching the surface. Take coronary artery disease, for example, which is the most common cause of death in the United States. Coronary artery disease is caused by cholesterol plus inflammation. It’s not just cholesterol. We all know people with high levels of cholesterol and whistle-clean coronary arteries. We’ve known for many years that coronary artery plaques are created by narrowing in the coronary arteries, and that narrowing is caused by what’s called a foam cell. A foam cell is a macrophage that sort of eats cholesterol, like a PacMan if you will, and dies, and gets incorporated into the cells of the endothelium of the smooth muscle of the coronary arteries, triggering an inflammatory response. So, hyper-inflammation plus cholesterol makes a foam cell, which causes coronary plaques, which causes coronary artery disease, which is the number one killer of people in the United States. This also goes for stroke and vascular disease. However, if you have adequate NAD levels you’ll see a decrease in these inflammatory cycles.

Inflammation is also the linchpin of cancer, peripheral vascular disease, cerebral vascular disease, and diabetes. Along with coronary artery disease, these are all of our top killers, and NAD is likely to be beneficial in preventing or treating all of them.

NAD Research: Excellent. Thank you. Has the study about topical NAD removing squamous cell carcinoma been published?

Dr. Le Bon No, it’s totally anecdotal. We saw it in a friend of ours and were amazed. As we know, an inflammatory cancer is often more aggressive, all other things being equal. The path from normal skin to actinic keratosis to squamous cell carcinoma is really a pathway for metaplasia and neoplasia. And at the heart of that is a path of increasing loss of differentiation, which is associated, theoretically, with inflammation, which brings cytokines to the tissue, which causes mutation, which causes more cancer, which can cause necrosis, which can cause more inflammatory stimuli, and the circle goes round and round. So what we see with NAD is really amazing and, though we don’t yet know the mechanism, it really makes sense when we understand NAD’s role in fighting inflammation and repairing DNA. So we’re very excited to do a larger study to confirm our anecdotal results because what we’ve seen with our own eyes was really quite astounding.

NAD Research: Please tell us about your experience utilizing photobiomodulation treatment in conjunction with NAD for addiction detox.

Dr. Le Bon: Photobiomodulation (PBM) is synergistic with NAD, and I’ll explain how. When infrared and near-infrared light strikes the mitochondrial cytochrome called C oxidase, it induces that chromophore to enhance the production of ATP. Now, as we know, NAD is one of the key ingredients the mitochondria need to make fuel. So, when you combine NAD and infrared or near-infrared light, you get doubly enhanced ATP production. I like the analogy that adding light to the chromophore in the mitochondria is like turning on an oven where the cookie dough (in the form of NAD) is ready to bake. If I want to make more cookies, I need to add more dough, in this case, NAD, and enhance the oven functionality, which is the mitochondria.

NAD Research: What are the clinical results?

Dr. Le Bon: In some patients, adding PBM to the IV NAD treatment decreases the flushing that is an occasional side effect if the drip rate is too high. So that is one benefit. But the larger benefit is enhanced ATP production. This has been shown in numerous studies, including those by Dr. Michael Hamblin, who is really the father of photobiomodulation. He’s done some fantastic groundbreaking research in this field.

We’ve already discussed that NAD is essential for ATP production, and so the two treatments—NAD and PBM—combined are very synergistic. This is very helpful for people undergoing addiction detox, as their NAD levels are believed to be depleted by the oxidative stress of substance use—as well as whatever stress drove them to substance use in the first place.

We also see that PBM enhances topical NAD’s ability to inhibit pain. We put the cream on a wound or a pain site and shine infrared or near-infrared light on the area, which speeds pain reduction and wound recovery. Our evidence is anecdotal at this point because we just started integrating NAD and photobiomodulation at the beginning of this year (2023). We’re also interested in using IV NAD for traumatic brain injury, chronic traumatic encephalopathy, and Parkinson’s, all of which have been shown in the literature to be improved with photobiomodulation.

NAD Research: Does it matter how/where you apply the light for enhancing intravenous NAD treatment for addiction detox?

Dr. Le Bon: We like to shine it on the inner wrist, as research suggests that there are free-flowing oxidating mitochondria in the blood. By shining the light here, we can get high vascular exposure location to the light.

NAD Research: What future do you see for NAD in addiction?

Dr. Le Bon: Our goal is to make intravenous NAD the absolute standard protocol for addiction detox programs. Twenty years of success and published studies would lead one to conclude that IV NAD should really be used in detox protocols and emergency rooms and other detox facilities.

We also see these benefits continue with boosters, which means that IV NAD is not only beneficial for detox, but also for rehabilitation and recovery. It’s important to distinguish between the two—detox and rehab. Springfield Wellness Center is working on both. Some patients appear to get a complete reset of their dopamine receptors and never need a booster. Others come back periodically for boosters to maintain their sobriety. This is what we call rehabilitation. It takes a while for their addicted brain to completely recover. Either way, it’s our belief that intravenous NAD should not only be the standard of care for detox, but also for rehabilitation. I personally believe this is true not just for substance addictions, but also for process addictions, whether it’s gambling, or sex, or pornography, or food, or even sugar. We know all of their common pathways lead to dopamine, so it’s not surprising that intravenous NAD, which is associated with a change in dopamine receptors, would work for all kinds of addictions across the board.

NAD Research: One thing I am increasingly frustrated by is the bias towards so-called “medically assisted” detox treatment, which isn’t detox at all, but just replaces one narcotic with another. The FDA’s own report, which it commissioned about whether to include NAD in its 503B Bulks list, said as much: that methadone is just a replacement narcotic. Would you be willing to speculate as to when the FDA might, as a result, approve NAD for addiction detox, or other, conditions?

Dr. Le Bon: I think the best way to suggest that traditional medicine change the treatments they’re using is not so much to disprove their current approach but to simply show an alternative with a better benefit. That’s our strategy: not to criticize the existing treatments but to simply demonstrate something (intravenous NAD) that is so clearly better that other treatments will fall by the wayside. That’s what I think our task is. But of course, we’re talking about huge sums of money to take a drug to the FDA for acceptance. On average it takes about half-a-billion to 1-billion dollars and about 10 years to take a medication through all the clinical trials up to FDA approval.

When you really think about it, that’s almost absurd. If you went to a computer store and asked for the most up-to-date technology and the salesman told you, “I have the newest thing. It was developed 10 years ago,” you’d probably be somewhat disappointed. The same if you went to a car dealership and asked to buy the newest model of car and they told you, “Here it is. It was developed 10 years ago.” But, that’s exactly what is happening with new drugs because, on average, it takes 10 years. So we’re hoping that these things will change in the future and that we won’t have to wait 10 years for these new technologies to benefit our patients.

NAD Research: But is “medically assisted detox” fair to patients—who are prescribed a lifetime of narcotic addiction as “care”?

Dr. Le Bon: I think as NAD treatment gains more recognition for its success in addiction, the entire perspective on addiction treatment will change—starting with the patients who have benefited. The rest of the addiction treatment community will then have to re-evaluate their notions through necessity.

NAD Research: Thank you. And how you would like to summarize the future for NAD and overall health?

Dr. Le Bon: We believe that the future of NAD treatments will be as broad as NAD’s roles are in the body. NAD is the foundational molecule for energy, inflammation and, we believe, cancer protection due to its role in DNA repair. These roles affect every single cell in the body.

If NAD is the linchpin in every single cell, then it will affect every branch of medicine.

Now, sometimes people come to me and ask, “How do we know that NAD is such an important molecule? What about all these other molecules that exist in the body and are necessary for health.”

My answer comes down to the principle of energy conservation. A biological system, an organism, is very, very energy efficient. So to appreciate how important a molecule is, you have to ask how much energy the body commits to creating and maintaining this molecule. And you also have to ask, how many different pathways does the body dedicate to producing it?

It turns out that the body commits significant energy to creating and maintaining NAD levels, through several different mechanisms and pathways—the Preiss-Handler pathway (PHP), generating NAD from nicotinic acid; the de novo synthesis pathway (DNP), generating NAD from tryptophan; and the salvage pathway (SP). The body has also chosen NAD as the single most important molecule to be feeding into ATP, which is the only molecule that all the cells of the body use for energy production. So NAD is very important, and we believe that it will be equally important all across the board of medicine. Cardiologists will use it because cardiac cells depend on it; nephrologists will use it because renal cells depend on it; neurologists will use it because brain cells depend on it; dermatologists will use it because skin cells depend on it; surgeons will use it for post-operative care.

Surgical use is a special case in itself. We could imagine NAD being used either pre- or post-operatively to inhibit postoperative cognitive decline, which is more prevalent nowadays because the operations are longer and many are taking place in older populations, who are already subject to cognitive decline.

We can also see NAD used for diabetic wound care and diabetes is rampant, due to our elderly population and to the obesity epidemic. So NAD can play a role in almost any disease system, whether it’s administered intravenously, topically, or sublingually.

Unfortunately, when we tell people that NAD can be used for all of these various symptoms and diseases, they often become skeptical because we’ve been brainwashed by big pharma to believe that every single symptom and every single disease needs its own separate medication to treat it. But that’s because we’re not used to looking at foundational molecules that already exist in our body. If you look at the mechanisms of a cell and discover a molecule used in all the mechanisms, it’s not surprising that the loss of that molecule will lead to one or many disease states, nor that the replacement or restoration of that molecule will enhance each type of cell’s function and address many diseases.

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