GlyNAC: Your Anti-Aging Weapon? Science Says... Carl Germano, CN

In addition to my paper on the role of quercetin + nicotinamide co-crystal (NADPro?) to address declining NAD levels during aging, continued published studies support the complementary role that n-acetylcysteine + glycine co-crystal (GlyNACPro?) has on other aspects of aging.? ???

Aging has also been characterized by a progressive decline in physiological function, often accompanied by elevated oxidative stress, mitochondrial dysfunction, and various hallmarks of biological aging. Addressing these challenges in older adults has proven difficult, calling for novel interventions.

Glutathione (GSH) deficiency, a key antioxidant molecule, has been implicated in the pathogenesis of these age-related changes. GSH acts as a potent antioxidant and detoxifier and plays a starring role in defending our cells against the ravages of time. It directly counters free radicals, detoxifies toxins, and protects our cellular powerhouses, mitochondria, ensuring efficient energy production and shielding them from oxidative stress. Unfortunately, GSH levels naturally decline with age. Reduced synthesis and increased use leave our cells vulnerable to free radical attacks, toxin buildup, and mitochondrial dysfunction – all hallmarks of cellular aging. However, the story does not end there. Research suggests we can be our own GSH champions. By fueling our bodies with precursor-rich foods or with specific supplements, we can support optimal GSH levels and empower our cells to face the challenges of aging with greater resilience. Therefore, strategies aimed at elevating GSH levels have emerged as potential avenues for promoting healthy aging.

While glutathione supplements exist on the market, oral glutathione supplementation presents several challenges for directly elevating intracellular levels, hindering its application in clinical practice. Being a tripeptide, oral glutathione has limited bioavailability, with pure glutathione degrading significantly in the digestive tract or via first pass metabolism in the liver before reaching target tissues. One of the more promising supplements to help maintain healthy levels of GSH in the body is called GlyNAC, a combination of glycine and N-acetylcysteine (NAC).? GlyNAC has demonstrated its ability to increase GSH levels in preclinical studies. Notably, GlyNAC supplementation in aged mice improved GSH deficiency, oxidative stress, mitochondrial fatty-acid oxidation, and insulin resistance. These findings prompted further investigation into the potential benefits of GlyNAC supplementation in humans.

In addition to previously published studies supporting the use of GlyNAC in aging, yet another well-designed clinical trial investigated the potential of GlyNAC supplementation to combat age-associated abnormalities in older adults. This randomized, double-blind, placebo-controlled study enrolled both older and younger individuals, tracking their health markers over 16 weeks. Compared to younger participants, older adults exhibited diminished glutathione levels, heightened oxidative stress, mitochondrial dysfunction, increased inflammation, impaired endothelial function, insulin resistance, and various hallmarks of aging, alongside slower gait speed, reduced muscle strength, increased waist circumference, and elevated systolic blood pressure. Interestingly, only supplementation with GlyNAC in older adults, not placebo, demonstrated significant improvements: glutathione levels rose, oxidative stress markers dipped, mitochondrial function enhanced, inflammation markers subsided, and physical function flourished in terms of gait speed, muscle strength, and walking performance. While endothelial function and insulin resistance showed modest improvements, body composition and blood pressure remained largely unchanged. Importantly, GlyNAC supplementation proved safe and well-tolerated throughout the study. These findings suggest GlyNAC's potential as a safe and effective nutritional intervention to address age-associated abnormalities and promote healthier aging in older adults.

While NAC has been recommended as a potential candidate to raise glutathione in the body, supplementing NAC-alone does not provide glycine, and?only GlyNAC provides both the glycine and NAC needed for GSH synthesis.? In addition, orally delivered NAC undergoes extensive first-pass metabolism resulting in about 90% loss by enzymatic deacetylation to form cysteine in the small intestine. As we have seen, this mainly gets converted to cystine and is of little use in healthy individuals or those suffering from a chronic undersupply of glutathione (GSH) due to aging or disease.?While immensely helpful in cases of severe GSH depletion, NAC by itself does not address the problem of supplementing GSH in cases of gradual depletion such as chronic illness or just simply getting older.? To address this issue, the scientists at Verdant Nature have employed their BioSNEDS? (self emulsifying dietary delivery system) technology to the combination of NAC+glycine called GlyNACPro?.?GlyNACPro? is a unique co-crystal molecule consisting of both NAC+glycine that was developed under the IP owned by Verdant Nature to increase the stability, solubility, permeation, and bypass liver degradation. GlyNACPro? is available in both emulsion or powder forms and is fully water dispersible, neutral tasting, and odorless which makes it applicable in a variety of dosage formats including gummies, beverages, lozenges, tablets, capsules, softgels, etc.

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References

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. Kumar P, Liu C, Suliburk J, Hsu JW, Muthupillai R, Jahoor F, Minard CG, Taffet GE, Sekhar RV., J Gerontol A Biol Sci Med Sci. 2023 Jan 26;78(1):75-89.

GlyNAC (Glycine and N-Acetylcysteine) Supplementation in Old Mice Improves Brain Glutathione Deficiency, Oxidative Stress, Glucose Uptake, Mitochondrial Dysfunction, Genomic Damage, Inflammation and Neurotrophic Factors to Reverse Age-Associated Cognitive Decline: Implications for Improving Brain Health in Aging.?Kumar, P.; Osahon, O.W.; Sekhar, R.V., Antioxidants?2023,?12, 1042.

A Randomized Controlled Clinical Trial in Healthy Older Adults to Determine Efficacy of Glycine and N-Acetylcysteine Supplementation on Glutathione Redox Status and Oxidative Damage. Lizzo G, Migliavacca E, Lamers D, Frézal A, Corthesy J, Vinyes-Parès G, Bosco N, Karagounis LG, H?velmann U, Heise T, von Eynatten M, Gut P. Front Aging. 2022 Mar 7;3:852569.

GlyNAC Supplementation Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Aging Hallmarks, Metabolic Defects, Muscle Strength, Cognitive Decline, and Body Composition: Implications for Healthy Aging, Rajagopal V Sekhar, Journal of Nutrition, 2021, Volume 151, Issue 12, 3606-3616,

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: Results of a pilot clinical trial. Kumar P, Liu C, Hsu JW, Chacko S, Minard C, Jahoor F, Sekhar RV. Clin Transl Med. 2021 Mar;11(3):e372.

Pharmacokinetics and bioavailability of reduced and oxidized N-acetylcysteine. Olsson, B., et al., European Journal of Clinical Pharmacology, 1988. 34(1): p. 77-82.