My Cinderella Anti-Aging Molecule — (Possibly) The Most Underestimated Pill For Healthy Aging

Growing old is a damaging business.

No matter how much exercise you do or how well you watch your weight or diet, you will experience some decline in most of your physiological functions.

One of the major reasons for this state of affairs is oxidative stress.

It is the kind of stress that occurs when metabolic reactions produce waste molecules that are very similar to water or oxygen, but with a major difference:

Instead of playing nice with their surroundings (water and oxygen don’t do harm), they react violently with any other molecule they meet (hence the name — reactive oxygen species, ROS).

The consequence for the “other molecule” is irreparable damage and the inability to fulfill its intended biological function.

These things happen every second in every single cell of our organism.

Fortunately, cells have defense mechanisms in place. They are called antioxidants, and they solely target ROS.

In the defense of ROS: They are not all bad. ROS fulfill important signaling functions. Which is why cells need to maintain a delicate balance between ROS and antioxidants.

When that balance gets out of whack, it is almost always in the direction of too much ROS activity.

That’s when oxidative stress sets in. And that’s what happens during the aging process.

Fortunately, we are blessed with selfless manufacturers who preach the antioxidant virtues of their vitamin C or E pills, and many other natural antioxidant compounds [1].

The funny thing about their anti-oxidant line-up:

• First, a really powerful antioxidant doesn’t even show up in there. It’s melatonin, and you know it from the first part of this two-part blog miniseries.
• Second, another antioxidant molecule has made it into the manufacturers’ portfolio, but it doesn’t do what it’s supposed to. Its name is glutathione (GSH).

Why and how I target this glutathione system is part of the next section.

Glutathione, the most under-appreciated antioxidant

Glutathione’s role has been likened to that of motor oil in your car’s combustion engine [2].

Here is why:

Most of a cell’s ROS production and damage happen in the mitochondria. Mitochondria are the organelles that produce a cell’s energy currency, the ATP molecules.

The most powerful defenses against ROS play out here, too. One is melatonin.

The other one is the GSH system. Without its protective effect, the lifespan of a cell can be very short. Like the lifespan of your car’s engine can be very short if you don’t pay attention to lubricating it properly. Hence the analogy.

Once the GSH defense is down, the doors to Alzheimer’s disease, Parkinson’s disease, liver disease, cancer, heart attack, stroke, and diabetes are open [3].

All are diseases that we commonly associate with aging.

So, to boost glutathione defense, I take it as a supplement, right?

Wrong.

How to supplement GSH

Oral GSH administration would do squat to its availability in cells. Going the oral route, GSH pretty much falls through the cracks of digestion [4].

But there is another way to boost it. By taking its precursor molecule, N-Acetylcysteine (NAC).

The name might ring a bell if you ever took an expectorant (a medicine that helps you clear mucus from the airways by coughing it up easier) when you had a cold. Or if you ever had paracetamol poisoning and needed your liver to be ?cleansed” of it.

Those are the on-label uses for NAC (sometimes sold under the abbreviation ACC).

Obviously, I am not interested in those.

I am interested in…

NAC’s off-label use as a precursor of GSH

As such, it has proven its efficacy in several studies.

For example, NAC prevented premature aging of endothelial cells (the inner lining of the arteries, which determines arterial function) [5].

In older adults (here I am), NAC supplementation together with glycine (an aminoacid) improved [6]:

• endothelial and mitochondrial function
• immune function
• cognitive function

Contrary to the study, I omit the glycine. My heavily meat-based diet delivers enough of this amino acid, so there is no need to supplement it.

The safety record for NAC supplementation

It is exceptionally safe to take. In low (<600 mg/day) and higher doses [7].

I take it every evening. Half a fizzy tablet of 600 mg. It tastes really nice, slightly acidic, and very much like effervescent powder. I have noticed no side effects since I started taking it three years ago.

Does NAC keep me biologically younger?

Possibly. I do everything in my power to prevent my personal horror scenarios of aging: stroke, heart attack, and dementia.

Taking NAC and melatonin is the easy part. More challenging are the daily exercise routines, watching my diet, and keeping my weight. Without those, aging would probably have left deeper skid marks on my physiology.

I see the NAC-Melatonin strategy as an additional firewall against the creeping functional decay that comes with aging.

So far, I can’t complain. I don’t have any of the chronic conditions that plague two-thirds of my same-age baby-boomer peers. I don’t take any medication (other than those supplements), and my vascular age is 10 years below my calendar age.

Maybe the Cinderella molecule really deserves its nickname. Being the one that does all the dirty work of cleansing lungs and livers, its anti-aging beauty may just have been overlooked.

PS:

In case this post stimulates you to follow my example, here is my…

CAVEAT

Do not take this post as medical advice. Nor as a recommendation to take NAC or anything else as a supplement. My only purpose of writing this post is to share what I do in order to make this “aging-business” as little damaging as possible.

References

[1] Bielli A, Scioli MG, Mazzaglia D, Doldo E, Orlandi A. Antioxidants and vascular health. Life Sci 2015;143:209–16. doi:10.1016/j.lfs.2015.11.012.

[2] Hristov BD. The Role of Glutathione Metabolism in Chronic Illness Development and Its Potential Use as a Novel Therapeutic Target. Cureus 2022;14. doi:10.7759/cureus.29696.

[3] Wu G, Fang YZ, Yang S, Lupton JR, Turner ND. Glutathione Metabolism and Its Implications for Health. J Nutr 2004;134:489–92. doi:10.1093/jn/134.3.489.

[4] Allen J, Bradley RD. Effects of oral glutathione supplementation on systemic oxidative stress biomarkers in human volunteers. J Altern Complement Med 2011;17:827–33. doi:10.1089/acm.2010.0716.

[5] Khan SY, Awad EM, Oszwald A, Mayr M, Yin X, Waltenberger B, et al. Premature senescence of endothelial cells upon chronic exposure to TNFα can be prevented by N-acetyl cysteine and plumericin. Sci Rep 2017;7:39501. doi:10.1038/srep39501.

[6] Kumar P, Liu C, Hsu JW, Chacko S, Minard C, Jahoor F, et al. Glycine and N-acetylcysteine (GlyNAC) supplementation in older adults improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, endothelial dysfunction, genotoxicity, muscle strength, and cognition: Re. Clin Transl Med 2021;11:e372. doi:10.1002/ctm2.372.

[7] Tenório MCDS, Graciliano NG, Moura FA, de Oliveira ACM, Goulart MOF. N-Acetylcysteine (NAC): Impacts on Human Health. Antioxidants 2021;10.