NAD (nicotinamide adenine dinucleotide) is a molecule that supports basic cellular function and metabolism in a number of important ways, including protecting our DNA (Sambeat et al, 2019), converting food into usable energy and regulating our sleep-wake cycles. NAD decreases as we age, and low levels of NAD are associated with increased risk of heart disease, Type 2 diabetes, Alzheimer’s disease, and accelerated aging. Decreased NAD levels in our bodies can result from 1. the body making less NAD as we age, 2. more NAD being used in the body as we age because of aged related stress and damage, including oxidative damage, and 3. poor diet, including increased alcohol consumption as we age. Some excellent work has found that SIRT, a molecule dependent on NAD to be synthesized in our bodies, is involved in preventing stem cell aging that even prevents a pro-inflammatory state of the macrophages in our innate immune system (Luo et al, 2019), and also prevents aging-associated inflammation and insulin resistance (He et al, 2020).
There are two forms of vitamin B3, nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), receiving attention for their ability to increase NAD levels. In mice studies, NR and NMN increase NAD levels, while some newer, small studies suggest the same is found in humans. Sounds great, right? NAD is important to a number of normal cellular functions and keeps some of our cell types young, so taking “NAD supplements” must be healthy and will slow the aging process. Where can I buy this stuff?
If you’ve read my book, “Thinking And Eating For Two: The Science of Using Systems 1 and 2 Thinking to Nourish Self and Symbionts,” you’ll know to ask a few important questions before running off to the store to buy this supplement. And, after having asked those few questions, you’ll know the NAD supplement offered at your local store or online is a waste of money and potentially dangerous.
First, assuming that what you buy is actually the NAD supplement, and that is a big “if” given the supplement industry is rife with fraud, the increase in the concentration of NAD in blood cells shows that NR works to raise the concentration of NAD, but it is not evidence that having more NAD will increase life span or health span in humans, or even improve cellular function of any particular group of cells. We also don’t know how much NAD was getting into and affecting muscles or other organs, and that is difficult to measure. One study, sponsored by one of the NAD supplement companies, found no correlation between the age of subjects and the level of NAD in their muscle and brain tissue (Elhassan et al, 2019). Therefore blood may not be an indicator for NAD throughout the body; not serving as a biomarker for the therapeutic effects in other tissues. The same study by Elhassen et al found that the supplement didn’t help improve the subject’s grip strength, muscle blood flow and metabolism, but concerningly increased a protein thought to be increased in type 2 diabetes and insulin resistance.
We also need to understand what levels of NAD are healthy. Is too much NDA dangerous? Some studies found that it is. Deterioration of metabolic health, and dysfunction in fat cells along with an induction of glucose intolerance were found in those mice fed a large quantity of NAD supplements (Shi et al, 2019). Other studies in mice report similar results (Kourtzidis et al, 2018). Pools of increased NAD may also be a risk factor for cancer (Hong et al, 2019). And all NAD supplements are not the same in their actions, and supplements don’t act the same way as do the natural, endogenous precursors to NAD (Sambeat et al, 2019).
Again, if you’ve read my book, you know to ask the question, “compared to what?” If you go to Clinicaltrials.gov to see the basic study design of the trials testing NAD supplements, you’ll discover a level of stupidity in trial design that boggles the imagination. What is the NAD supplement being compared to? In none of the studies is diet being controlled for. And we know diet is very important for the levels of NAD in the body. For example, vegetables such as broccoli and cabbage contain 0.25–1.12 and 0.0–0.90 mg NMN/100 gm, fruits like avocado, tomato contain 0.36–1.60 and 0.26–0.30 mg NMN/100 gm, whereas raw beef has 0.06–0.42 mg NMN/100 gm. So if people are eating a poor diet, like most Americans, their natural supplementation of NMN will be low and easily raised by a NAD supplement. Further, without controlling diet in the NAD supplement group versus placebo group, especially in trials with small numbers of subjects, diet can easily confound the data. Moreover, in at least some of the studies, the placebo group was taking a sugar pill. Sugar has numerous deleterious effects within our different organs and microbiome, all of which can impact the clinical trials. The important clinical trial would be to compare the NAD supplement group with a group eating a whole food plant based diet. But given you can’t patent a whole food plant based diet, the monetary incentives are not in place to perform such a study. The mentality of all such gimmicks is to find that one “magic pill” to make me healthy and young, a reductionist strategy appealing to the lazy consumer, and to companies and providers who make a lot of money selling quackery. I have more to say about NAD and other supplements in my book. Hope springs eternal, but so do stupidity and greed.
References
Elhassan YS et al (2019) Nicotinamide riboside augments the human skeletal muscle NAD+ metabolome and induces transcriptomic and anti-inflammatory signatures in aged subjects: a placebo-controlled, randomized trial. BioRxiv, doi: https://doi.org/10.1101/680462
He M et al (2020) An Acetylation Switch of the NLRP3 Inflammasome Regulates Aging-Associated Chronic Inflammation and Insulin Resistance. Cell Metabolism, DOI:https://doi.org/10.1016/j.cmet.2020.01.009.
Hong SM et al (2019) Increased nicotinamide adenine dinucleotide pool promotes colon cancer progression by suppressing reactive oxygen species level. Cancer Sci. 2019 Feb; 110(2): 629–638
Kourtzidis I.A., Dolopikou C.F., Tsiftsis A.N., Margaritelis N.V., Theodorou A.A., Zervos I.A., Tsantarliotou M.P., Veskoukis A.S., Vrabas I.S., Paschalis V., et al. (2018) Nicotinamide riboside supplementation dysregulates redox and energy metabolism in rats: Implications for exercise performance. Exp. Physiol. 103:1357–1366. doi: 10.1113/EP086964.
Luo H et al (2019) Mitochondrial Stress-Initiated Aberrant Activation of the NLRP3 Inflammasome Regulates the Functional Deterioration of Hematopoietic Stem Cell Aging. Cell Rep. 26(4):945-954.e4.
Sambeat A et al (2019) Endogenous nicotinamide riboside metabolism protects against diet-induced liver damage. Nature Communications volume 10, Article number: 4291
Shi W et al (2019) High Dose of Dietary Nicotinamide Riboside Induces Glucose Intolerance and White Adipose Tissue Dysfunction in Mice Fed a Mildly Obesogenic Diet. Nutrients. 11(10).
Stem Cells, Health, Technology 