The Evidence for GlyNAC: A Randomized Double-Blind Human Clincal Trial

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by Nils Osmar. Updated October 25, 2022. Medical Disclaimer

According to a recent randomized, double blind human clinical trial conducted by researchers at Baylor College of Medicine, elderly men and women given a compound called GlyNAC (composed of equal parts glycine and NAC) experienced an increase in their glutathione levels. The study was published in the The Journals of Gerontology in 2022. No improvements were seen in patients receiving a placebo.

Study participants also saw improvements in their:

  • Mitophagy (removal of damaged mitochondria from the body)
  • Inflammation
  • Insulin resistance
  • Endothelial dysfunction
  • Mitochondrial dysfunction
  • Genomic damage
  • Stem cell fatigue
  • Cellular senescence
  • Muscle strength
  • Gait speed
  • Exercise capacity
  • Waist circumference
  • Blood pressure.
  • Oxidative stress

Note again that this was a human study, which gives it higher ranking than the animal studies often cited in support of other anti-aging compounds. To read the study itself, go to: Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial. (See summary: “GlyNAC supplementation reverses aging hallmarks in aging humans“.)

Could GlyNAC also increase lifespan?

Reversing the signs and symptoms of aging is a striking accomplishment. But can GlyNAC also increase lifespan?

The honest answer is, we don’t yet know. Life extension can’t be proven in human beings because it would take longer than a typical human lifespan to know whether taking a particular compound had made a difference. But recent animal studies have shown that the compounds found in GlyNAC (glycine and NAC), when taken together in equal amounts, do increases lifespan in animals.

In an article entitled, Supplementing GlyNAC Extends Mouse Life Span the authors wrote:

A researcher at Baylor College of Medicine, Dr. Rajagopal Sekhar, associate professor of medicine… Sekhar’s team reports the results of a study in mice, which provides proof-of-concept that supplementing GlyNAC – a combination of glycine and N-acetylcysteine as precursors of the natural antioxidant glutathione – can increase lifespan and improve multiple key age-associated defects.

…For over two decades, Sekhar has studied natural aging in older humans and aged mice. His work contributes to providing a better understanding of how glutathione deficiency, increased oxidative stress, mitochondrial dysfunction and multiple additional hallmark defects of aging contribute to the aging process and how they can be reversed with GlyNAC supplementation.

“…When we discovered that GlyNAC supplementation can correct mitochondrial defects in aging, we asked an important question: Could GlyNAC supplementation from a younger age extend length of life?” said Sekhar…. The researchers housed the mice under stable environmental conditions. When mice reach an age of 65-weeks, they typically begin to show a drop in glutathione levels and develop mitochondrial dysfunction and oxidative stress. At this age, Sekhar’s team switched the diets of half of the mice to receive GlyNAC, and the other half continued their diet without the supplement… Then, the researchers let the mice continue aging undisturbed and recorded how long they lived.

“We were excited to find that the mice that received GlyNAC lived 24% longer than those that did not receive GlyNAC,” Sekhar said….

My thoughts:

  • People aren’t mice. We may not know for decades whether taking GlyNAC leads to a similar increase in lifespan in humans.
  • But the Journals of Gerontology study suggests that the same mechanisms that increase lifespan in animals are occurring in humans,

What I’m doing:

To me, restoring glutathione to young adult levels is a key part of my personal anti-aging strategy. I don’t know if it will increase my lifespan but there are clear anti-aging benefits, according to the Baylor study. I would rank it up there with activating the sirtuin 6 gene, restoring NAD+ levels to those of young adults, and restoring AKG levels, as essential anti-aging interventions.

To activate the SIRT6 gene, I’m taking a form of fucoidan (DoNotAge’s SIRT6 Activator.) which has been shown in lab studies to switch sirtuin 6 on, along with a black elderberry extract from Gaia Herbs which is rich in cyanidin, which some studies have shown also activates SIRT6. I take both supplements along with NMN (nicotinamide mononucleotide) because NMN has been found to increase NAD+ levels which the sirtuin genes use as fuel. I also take a potent AMPK activator, Jarrow glucosamine, along with my NAD+ boosters.

To replenish AKG levels, I’m taking a Ca-AKG from DoNotAge and an AAKG supplement from Nutracost.

To restore glutathione, I’m taking a whey supplement after my workouts, and taking NAC and Glycine together in the evenings. (My current brands are NOW Foods and LifeExtension. Pure Encapsulations sells a GlyNAC powder which I’m also thinking of trying soon.)

One other bonus (for GlyNAC) is that a find that taking NAC with glycine in the evening supports better sleep as long as I don’t overdo it. When I take a high dose (such as 3 grams of each), it can interfere with my sleep. Low doses (around 1 gram of each) work much better for me as sleep aids. (With that said, I know many people who maintain that high doses work well for them. What’s safe and effective for one person may not necessarily be for another.) The main point being that sleep is so important that anything that helps it scores some bonus points, in my estimation.

Other interventions

I do like GlyNAC (a lot), but in addition to supplementing with it, I’m also still :

  • Doing resistance training (I agree with Peter Attia that there’s no sense in arguing about which diet or supplements work best, unless we also have our exercise house in order).
  • Taking supplements which help the body naturally produced more testosterone and growth hormone. (I am aware of the studies showing a correlation between raising hGH levels and higher rates of cancer; but the studies done on people taking recombinant hGH by way of injection, not naturally raising their levels to approximate those of young adults by eating a good diet, exercising, and taking supportive supplements. And even the injections may be fine if we’re doing things to offset the bad effects.)
  • In the TRIIM trial, people were given hGH injections, metformin, zinc, vitamin D and DHEA; the result was a 2.5 year reversal of epigenetic aging, which suggests that the study participants are likely to live 2.5 years longer, not shorter, lives after injecting hGH.)
  • But again, to be clear, I’m not injecting hGH, I’m doing things like fasting and exercising and taking herbal supplements which have been found to increase hGH naturally.
  • Re: testosterone, some studies similarly suggest that injecting testosterone increases our risk of cancer. But raising testosterone also correlates with an increase in life expectancy and a much higher quality of life, particularly for males. If it comes down to a choice, I’d rather die at the age of 90 with cancer than die ten years earlier without it. But even this isn’t a concern on my radar, because there’s zero proof that I’m aware of that raising T levels naturally with supplements such as tongkat ali and HMB and resistance training has a pro-cancer or life-shortening effect.
  • Eating (some) high nutrient meals rich in protein, including leucine. It’s very true that leucine activates mTOR, which is pro-growth, not pro-life-extension. That’s why I’m also…
  • I’m also doing a lot of fasting to activate the sirtuins and autophagy, activate AMPK, and suppress mTOR periodically. (I do intermittent fasting, either in the form of full water fasting or drinking a fasting-mimicking smoothie in the morning, while skipping breakfast and eating my first meal with protein around noon or 1 p.m.)
  • See my full protocol on this page.

Rating GlyNAC

I regard GlyNAC as vitally important, but not necessarily more important than the other interventions I’ve listed above. In my opinion, to live optimal healthy lives, we also need NAD+ ; we need AKG; we need healthy (young adult) levels of the hormones I mentioned above.

Not medical advice

This article is not intended as, and should not be taken as, medical advice. I’m not advising that people eat any particular diet or take any particular supplements, just reporting on what I’m doing. All supplements can have side effects; I would encourage people to research both possible benefits and side effects before starting on any supplementation regimen.  See full Medical Disclaimer

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Related article: more about glutathione:

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