My wife recently texted me about a new study out of the Baylor College of Medicine on a combination supplement, “GlyNAC,” with strongly positive data about its use in elderly patients. It claimed an outright plethora of age reversing benefits. I assumed the study would be an embarrassment of flaws. However, when I actually read it, I was surprised: this actually seems promising! Why had I not heard of it?
I had to dig around to find any reporting on it at all, outside of Baylor, which clearly needs to bolster their PR department. Well, at least the Bluff City area heard about this study, even if the bulletin got the medical college wrong:
The short-ish story on the trial, which was published in the peer-reviewed Journals of Gerontology, Series A, is that it was small (11 overweight adults, average age 71, in the GlyNAC group, and 12 in the placebo group), looked at a bushel of lab and clinical endpoints, and came out of the group, headed by Dr. Rajagopal V Sekhar, MD, which had published almost all the existing research on this combination of glycine and N-acetyl cysteine. Not encouraging, I know. But at least there were no conflicts of interest, right?
Good. Well, actually… not so good. The Baylor press release ‘fessed up to this little gem:
So, we have research conducted at an institution with a vested interest in its success, all sitting in the back pocket of one of the most reviled mega-corporations in the universe! Not an ideal combination. The data, though, is rather bewitching.
It’s a double-blinded, randomized, placebo-controlled trial, for starters, unlike the group’s prior (also encouraging but even smaller) study, which was open label, meaning researchers and participants knew what they were taking. Despite a scattershot endpoint approach which puts my inner skeptic on highest alert — including 5 measures of physical function, 5 of body composition, 25 “Hallmarks of Aging” laboratory biomarkers, a slate of metabolic labs, systolic and diastolic blood pressure, and a Quality of Life survey — the results are hard to dismiss. As I discussed in my tepid review of another mitochondrial-targeted supplement, Urolithin A, if you pick enough endpoints, a few are likely to pop up positively enough, even if only by chance, to generate some headlines and selling points for your product. In the case of GlyNAC, though, almost all their endpoints were positive.
Weight loss? Almost 5 pounds in 4 months. Blood pressure? From a mean of 132/79 to 124/76. Blood sugar barely budged, but insulin levels dropped a remarkable — practically unbelievable — two-thirds. Gait speed and chair-rise testing improved almost to the level of the young adult (25 year old average) comparator group. Grip strength improved to beyond the young adult levels! This was no placebo effect - there was virtually no improvement in any category for the placebo participants. As to the lab tests, nearly every single one of the biochemical markers for aging, inflammation, mitochondrial function, etc. showed a statistically significant improvement, often many times that of the placebo.
So, the next question has to be: does this make any sense? There is some biological plausibility here. NAC, as any ER doctor will tell you, plays an extremely effective role with both IV and oral forms in preventing liver failure after Tylenol overdoses. The mechanism of action is thought to be via supporting the activity of the critically-important intracellular and mitochondrial antioxidant, glutathione. Glycine is also known as a glutathione precursor, and has been found to have all sorts of possible benefits, from its function as a calming neurotransmitter to improving metabolic health.
The authors assert that by combining glycine and NAC, and thereby also increasing available glutathione, all three compounds work independently and together in a manner they term, the “power of three.” Yes, they actually wrote, “power of three,” with italics, in a peer-reviewed scientific journal. It almost sounds like… a marketing theme is born?
That really sums up this supplement for me. It sounds great, it looks great, but it smells a little fishy.
Maybe the authors have hit on two straight — really three, since they also published a 2013 study with mouse and human participants featuring similarly positive results — remarkably lucky trials that benefited from the potential random effects of a tiny sample size. Or maybe there is something rotten in the state of Denmark.
I have absolutely no reason to suspect Dr. Sekhar of foul play, but hypotheticals of misreported data, coached participants, or outright fabrication have to be considered whenever a study reports results that seem almost too good to be true. Ivermectin’s “100% effective” prophylaxis in an Argentina study that probably never happened comes to mind; as does that 2012 study on how to promote honesty which was — you guessed it — fabricated; and, recently, the disturbing allegations that seminal work on a branch of the amyloid hypothesis of Alzheimer’s disease was fraudulent. This stuff happens in science. There’s a lot of pressure to create winning research.
All that said, I am inclined to take this work at face value. I hope some of my patients will volunteer themselves as guinea pigs, though keeping in mind that this trial did not find benefit for young healthy folks, and the study group was composed of overweight seniors in relatively good health; results might not apply to a lean and chipper 70-year-old, or an 80-year-old diabetic with advanced kidney disease. I do like the ease of testing facilitated by the study design: run baseline labs including fasting glucose and insulin, perhaps a cholesterol panel and an inflammatory marker like high-sensitivity CRP; perform a cognitive test like the Montreal Cognitive Assessment (“MoCA”), since the prior study showed a marked improvement in MoCA scores; have patients perform a 30 second chair stand test; and ask them to see how far they can walk at a rapid pace in 6 minutes at the local track. Take the GlyNAC for 3-4 months. Rinse, lather, and repeat testing.
For those inclined to do the same (after consultation with their doctors, of course), I will point out that our dear friends at Nestlé sell their proprietary GlyNAC product as “Celltrient Cellular Protect.” However, the doses used in the trials were rather huge: 100 mg per kg per day, or about 7000mg each of NAC and glycine for an average weight adult. For reference, this is about double the maximum of what I ever recommend for NAC (I sometimes suggest it for hard-to-treat lung ailments given some encouraging data), and about twice the typical “full” glycine dose. The Celltrient product only contains 1200mg of each, and sells on their website for about $70 per 28 day supply. A 185-pound person would need about 7 of those packets every day at around $500 a month to match the study protocol!
While I won’t name any names, the more reputable supplement brands charge about $5/day for that amount of NAC, while the less expensive brands are about a third the price. Glycine is relatively cheap; it can be bought by the kilogram for $25. I do worry about quality controls from really inexpensive supplement makers, especially when consuming massive amounts of their products.
I might be talking myself out of trialing this cocktail with my patients. That’s a roughly $1000 experiment to run for four months, plus two sets of labs. (And, yes, the benefit appeared to evaporate once the supplement was stopped.) Lower doses might fare as well, I suppose, but another trial run by different investigators — many of them on Nestlé’s payroll — found only marginal benefit in biomarkers with higher dose ranges, and none in the 1200mg cysteine/1200mg NAC dosing found in the Celltrient product.
That leaves the wealthy and/or desperate to give this regimen a try. I’ll update this post if I get any takers. In a perfect world, the NIH will find and support a different research team to attempt to replicate these findings. Long term safety of these huge doses would need to be tracked; a reader pointed out to me that NAC mega-dosing is not without health concerns. To be clear, though, if these findings were replicated, it would be a huge deal. Reversing cognitive, physical, and metabolic age-related decline with a well-tolerated supplement would fall in the “Discovery of the Decade” category. It would be a complicated mess, financially, but someone other than Nestlé would need to patent a formulation of this and produce it, and insurance would have to pay for it.
In our imperfect world? Nestlé with its growing supplement empire will continue to be the sole force behind research on GlyNAC, and we physicians will never be sufficiently convinced to recommend it; and those lacking the resources to trial incredibly expensive supplements will never know if GlyNAC was “the one that got away.”
