The Truth About Anti-Aging Supplements: Expectations vs. Reality

Many anti-aging supplements will go so far as to claim they can make people look and feel 10, 15, or even 20 years younger by reversing the aging process. If that was the case, we could theoretically become immortal by taking those supplements. 

Let's be clear: Aging is an intrinsic part of all life. Unfortunately, no data, let alone in humans, suggests that we can completely flip the aging process on its head in healthy cells — at least not through nutritional interventions. 

Understandably, many gerontologists and respected aging researchers have tried to distance themselves from the pseudoscience of the "anti-aging" movement [1]. From a biological standpoint, jargon like "anti-aging" is more accurately describing "pro-longevity." 

The good news is there are undoubtedly certain micronutrients and lifestyle choices that reduce the rate at which healthy cells age. Arguably the three most popular "anti-aging" supplements at this point are nicotinamide mononucleotide (NMN), nicotinamide riboside (NR), and nicotinamide adenine dinucleotide (NAD+/NADH). 

What Are NAD+, NR, and NMN?

NAD+ is a coenzyme and oxidizing agent involved in myriad metabolic reactions. As electrons are transferred between molecules, NAD+ is reduced to NADH, which is then oxidized back to NAD+ in a cyclical fashion as oxidation-reduction reactions proceed.

In vitro and in vivo studies have shown that the ratio of NAD+/NADH in cells plays a vital role in preserving DNA integrity and reducing the risk of many diseases, notably cardiovascular disease and neurodegenerative diseases, by increasing sirtuin and telomerase activity [2]. A diminution of the NAD+ to NADH ratio in cells is a hallmark of aging since these molecules are critical coenzymes for oxidation-reduction reactions throughout the body.

Perturbed NAD+ homeostasis is also associated with greater risks of age-related diseases such as Parkinson's disease and Alzheimer's disease [3]. Thus, NAD+ precursors are a growing area of interest for mitigating aging pathologies and extending lifespan. 

Since NMN and NR are orally bioavailable precursors of NAD+, they are promising candidates for slowing the aging process and promoting longevity [4]. Human data confirms the NAD+-boosting properties of NMN and NR supplements [5]. Still, it remains unclear whether this has beneficial effects in otherwise healthy, active adults with proper NAD+ homeostasis. 

Ironically, calorie restriction and exercise are the most practical ways to increase the NAD+/NADH ratio and fight cellular aging [6]. If you're already doing both of those (hopefully you are), don't expect to see a huge difference from taking NAD+ precursors like NMN and NR. While NR and NMN supplements are certainly intriguing, their therapeutic potential is far from conclusive when weighing the current body of human evidence [7]. 

Does Telomerase Reverse Aging?

With the recent onslaught of anti-aging proponents in the alternative healthcare space, telomerase has gained praise as holding the key to "immortality." The problem with that notion is that it leads people to believe that "more telomerase activity is better," which isn't necessarily the case.

So, does taking supplements that increase telomerase activity reverse aging? 

It's doubtful.

Despite many NAD+, NR, and NMN supplements being marketed as elixirs that turn your life clock back tens of years by protecting telomeres, that's a wild extrapolation of what the research shows and our understanding of biological aging [8]. 

For one, the telomerase enzyme naturally lacks activity in somatic (body) cells that comprise the vast majority of human tissues. This is an intrinsic mechanism that reduces the risk of cancer development since telomerase fuels cancer cell growth and replication. On the contrary, cancer cells become immortal by avoiding replicative senescence altogether, a ramification of persistent telomerase activity [9].  

As such, any drug or nutrient that indiscriminately activates telomerase can also increase cancer risk. In fact, the immortalization of cells is what leads to cancer. Indeed, preliminary evidence shows a negative effect of increasing NAD+ levels via supplementation by increasing tumorigenesis in mice [9].

The lifespan of normal cells is extendable by increasing telomerase activity, but once they divide a finite number of times and lose their capacity to carry out basic life-sustaining processes, that's it; they become senescent, and there's no going backward. Recent research suggests that the accumulation of senescent cells is a key modulator of NAD+ homeostasis, which complicates the use and safety of NAD+ precursors for aging purposes [10]. 

A more practical approach down the road would be consuming "senolytics," agents that destroy senescent cells. According to recent studies, curcumin, quercetin, and fisetin are three promising senolytic micronutrients [11].

For longevity benefits, we want to increase telomerase activity in human stem cells and systemic senolysis. The current alternative is receiving stem cell injections to regenerate aging tissue since NAD+ precursors don't appear to be discriminate activators of telomerase. A likely future approach for safe anti-aging will be genetic modification and the use of effective senolytic supplements [12]. 

Are NAD+ Precursors like NR and NMN Supplements Worth It?

Now, should you be fearful that taking NAD+ precursor supplements will give you cancer? Based on preliminary human studies, probably not. In general, research on these supplements shows either no benefit or modest improvements in biomarkers of disease and aging [13]. 

That might make you think it's prudent to take NR and NMN supplements because you have nothing to lose and everything to gain, right? Well, not quite. The cost of NAD+ precursor supplements are, for all intents and purposes, absurd — often upwards of $5 per serving. While they can promptly boost NAD+ levels, we simply don't know if taking these supplements for a few weeks or months leads to meaningful long-term health outcomes [14]. 

Again, a short-term increase in telomerase activity is not going to add years to your life or make you feel like your 20 years younger. Odds are, NAD+ precursors will need to be taken indefinitely to have the desired "anti-aging" effect that most consumers want.

But remember, we cannot completely halt the aging process by taking these supplements, nor can we antagonize it in the sense that the term "anti-aging" implies.The molecular mechanisms governing aging are immensely complex, and NAD+ homeostasis is just one of possibly many potential targets. 

To reiterate from earlier, if you already lead a reasonably healthy lifestyle and eat a proper diet, you're doing the two best evidence-based things you can do to support longevity [15]. Spending tons of money on anti-aging NAD+ supplements in hopes of living until your 150 years old is probably not the most sensible decision until we have more data to support the overly ambitious claims.