Vitamin and NADH Infusion
While acceptance of the COVID-19 vaccine has generally been high, hesitancy and even refusal remain issues for some. I’ve wondered if vaccines might be better received (by some of the refusers) if, instead of an intramuscular injection, they were offered via intravenous infusions in beautiful “wellness clinics”, perhaps with a few vitamins and electrolytes added for good measure. For some, all those preferences for “natural” methods are ignored when it comes to intravenous infusions. How else to explain the perennial popularity of intravenous infusions of vitamins among naturopaths? These treatments are very popular with celebrities and influencers, too. Even Dr. Oz called them “cutting edge” way back in 2013 (that video is sadly no longer available). Not only do advocates claim vitamin injections offer medical benefits for an array of medical conditions (from cancer to macular degeneration to fibromyalgia and more), they are touted as helpful for preventing illness, too. Despite the continued hype, there is no evidence that vitamin infusions are necessary if you have a functioning gastrointestinal tract and are able to eat food.

Nicotinamide adenine dinucleotide (NAD) and its hydrate (NADH) therapy are dietary supplements touted to support brain illnesses (Alzheimer’s disease, Parkinson’s disease, dementia, depression) as well as high blood pressure and high cholesterol. It’s also promoted conditions like jet lag and even improve athletic performance. Given intravenously it’s also promoted as a treatment for drug addiction. Addiction is a topic that deserves more treatment here at SBM owing to the sheer amount of misinformation and bad science and policy that exists. When a reader recently pointed me to an NPR program on the inappropriate promotion of NAD for addiction, I thought it was worth taking a closer look at this product.

What is NAD/NADH/NAD+?

Nicotinamide adenine dinucleotide is a molecule present in every cell. NAD exists in an oxidized form (NAD+) and a reduced form (NADH). A coenzyme, its activity was first observed in 1906 when biochemists observed that a yeast extract could accelerate alcohol fermentation. It was isolated in the 1930s and synthesized in the 1950s. The primary and most important function of NAD+ is in cellular metabolism – it is present in every cell in the body. NAD is formed in the mitochondria from reactions with niacin, nicotinamide, and tryptophan. Many cellular functions utilized NAD and NAD phosphate (NADP) including the metabolism of tissues, lipids, and carbohydrates. Because it is involved in so many cellular functions and because there is some evidence that NAD levels may decrease with aging and with certain diseases, there is interest in whether supplementation with NAD could provide medicinal and even anti-aging effects. Given the importance of NAD to cellular function, the body can synthesize it through a number of different biochemical pathways. For the same reason, NAD and its synthesis pathway are the target of research in the treatment of diseases. For example, isoniazid, an antibiotic used to treat tuberculosis, is activated by an enzyme in Mycobacterium tuberculosis that then binds to NADH to create a molecule that inhibits cell wall production.

Does NAD therapy have medicinal potential?

Given the crucial function of NAD to cellular activity, and the systems the body has in place to synthesize it, it would be surprising if cellular function was sensitive to dietary or other forms of administration. There seem to be very few clinical trials that give us any meaningful information.

Parkinson’s disease: what appears to be the sole randomized, double-blind, placebo controlled trial was conducted in the 1990s to follow-up on anecdotal reports of benefits. A small trial (9 patients) found no benefit of intravenous or intramuscular supplementation.

Chronic fatigue: Natural Medicines Database rates this as “possibly effective” noting some trials suggested NADH might reduce symptoms of CFS when used alone or in combination with coenzyme q10. In one trial, benefits waned, in another, measures of fatigue improved. A third small trial was felt to be promising with results warranting a larger trial (which hasn’t appeared, 20+ years later).

Dementia: NADH supplements appear to be ineffective. After 12 weeks of oral treatment, dementia patients had no improvement in memory, cognition, or behavior.

I should also point to a 2020 systematic review that found only 18 clinical trials of NAD or NAD precursors like nicotinamide. Only two of these trials were considered adequately powered: A trial evaluating the supplementation of nicotinamide on the progression to Type 1 diabetes, which was negative, and an open label trial in Parkinson’s disease, which was positive.

NAD for addiction treatment

There is considerable interest in making NAD available for the treatment of addiction, but there is a lack of published evidence showing that this therapy is effective.

One provider claims:

It has been determined that the excessive use of drugs and alcohol will deplete the body’s natural stores of NAD. Because of this, the brain cannot receive the same energy it usually would from breaking down food. NAD Therapy floods the brain with the co-enzyme to replenish its stores, providing 4 key effects.

  • It flushes out all of the drugs that are still in the user’s system.
  • It reduces withdrawal effects, which can be extremely difficult and uncomfortable to tolerate.
  • It curbs the cravings for alcohol and Opioids and lessens the pain of withdrawal, making recovery easier physically and mentally.
  • It allows the body to produce energy more naturally, without a crash or jitters like Caffeine and sugar or the negative effects that come with other substances.

From an investigation into NAD marketing conducted by NPR in 2019:

Cheryl had taken Jason to the clinic out of desperation. Jason, now in his late 30s, has struggled with addiction since he was a teenager. Cheryl saw his drug use escalate after he was prescribed a benzodiazepine for his anxiety, and he eventually began using heroin and meth. Over the years, Jason would try to get into recovery, but treatment programs didn’t help him for very long.

“I thought he was going to die,” Cheryl says. (Side Effects and NPR are using only first names because Jason worried he would lose his job if his employer found out about his addiction history.)

In late 2016, she saw a local TV news segment about a clinic called Emerald Neuro-Recover. The staff there treats addiction with something called NAD therapy, an IV infusion that can contain amino acids and other nutritional supplements, including nicotinamide adenine dinucleotide, a compound found in living cells.

The infusion, which is delivered over 10 to 15 days, cost $15,000, and it wasn’t covered by insurance. But the TV report said Emerald’s treatment was “proven to wipe drug cravings away.” Cheryl was intrigued.

There is no published evidence to show that NAD therapy has any benefit in the treatment of addiction. But that hasn’t stopped an industry from flourishing:

“I don’t know where those claims could come from, but it doesn’t seem realistic to me,” says Emily Zarse, an addiction psychiatrist in Indianapolis. She says there’s insufficient evidence to support using NAD therapy over other standard treatments: “There’s no actual data on any of these things.”

For an additional $400 fee, Emerald patients can have their brain scanned at a nearby clinic to document their progress with NAD therapy. An Emerald brochure shows a series of scans from a woman whose “brain is suffering from alcoholism.” Areas that glow red, orange and yellow — “HYPERACTIVE and OVERACTIVE” — totally disappear from the scans after 12 days of NAD therapy, according to the company.

“This is totally bogus,” says Leslie Hulvershorn, an addiction psychiatrist at the Indiana University School of Medicine with expertise in brain imaging, who reviewed the images via email. “We do not have research in our field that allows us to use EEG or any other brain imaging technique to document treatment response.”

After decades of research, still no benefits shown

Despite decades of pre-clinical research and a number of clinical trials that are small and lacked rigorous controls, there is no persuasive or convincing evidence that supplementation with NAD or its precursors has any medicinal or health benefits for the treatment of addiction or any other medical condition. Regrettably there is no shortage of providers that are willing to sell access to this therapy at exorbitant cost. Evidence and ethics are no barrier to provision, it seems.

Author

  • Scott Gavura, BScPhm, MBA, RPh is committed to improving the way medications are used, and examining the profession of pharmacy through the lens of science-based medicine. He has a professional interest is improving the cost-effective use of drugs at the population level. Scott holds a Bachelor of Science in Pharmacy degree, and a Master of Business Administration degree from the University of Toronto, and has completed a Accredited Canadian Hospital Pharmacy Residency Program. His professional background includes pharmacy work in both community and hospital settings. He is a registered pharmacist in Ontario, Canada. Scott has no conflicts of interest to disclose. Disclaimer: All views expressed by Scott are his personal views alone, and do not represent the opinions of any current or former employers, or any organizations that he may be affiliated with. All information is provided for discussion purposes only, and should not be used as a replacement for consultation with a licensed and accredited health professional.

Posted by Scott Gavura

Scott Gavura, BScPhm, MBA, RPh is committed to improving the way medications are used, and examining the profession of pharmacy through the lens of science-based medicine. He has a professional interest is improving the cost-effective use of drugs at the population level. Scott holds a Bachelor of Science in Pharmacy degree, and a Master of Business Administration degree from the University of Toronto, and has completed a Accredited Canadian Hospital Pharmacy Residency Program. His professional background includes pharmacy work in both community and hospital settings. He is a registered pharmacist in Ontario, Canada. Scott has no conflicts of interest to disclose. Disclaimer: All views expressed by Scott are his personal views alone, and do not represent the opinions of any current or former employers, or any organizations that he may be affiliated with. All information is provided for discussion purposes only, and should not be used as a replacement for consultation with a licensed and accredited health professional.