A Combination of NAC and Glycine Promotes Healthy Aging in Older Adults

by | Apr 10, 2024 | 2023, Aging, NAC (N-Acetyl Cysteine), Recent Articles

Written by Taylor Woosley, Science Writer. 16-week supplementation with 100 mg of glycine and 100 mg of NAC significantly improved glutathione concentrations by 164% and resulted in a significant reduction in IL-6 by 78%, TNF-α by 54%, and hsCRP by 41% in older adults.

Aging womanAging is a complex process that affects humans at the molecular, cellular, tissue, and systemic levels1. An important aspect of aging is the presence of inflammageing, a low-grade chronic inflammation that progressively increases with age, contributing to age-related diseases and frailty2. Furthermore, cellular senescence, associated with the pro-inflammatory senescence-associated secretory phenotype, interlinks with inflammation and acts as an important driver for organismal aging3.

Glycine is a simple non-essential amino acid which acts as a vital building block for glutathione (GSH), a robust antioxidant that becomes less abundant as we age4. Additionally, N-acetylcysteine (NAC) is a synthetic derivative of the endogenous amino acid L-cysteine which is a precursor of GSH that plays a role in modulating oxidative stress5. Previous research on supplementation with a combination of glycine and NAC (GlyNAC) shows a significant improvement in correcting GSH deficiency, oxidative stress, mitochondrial dysfunction, inflammation, and endothelial dysfunction6.

Kumar et al. conducted a double-blind, placebo-controlled randomized controlled trial to examine the effect of a GlyNAC supplementation on GSH concentrations, oxidative stress (OxS), mitochondrial fatty-acid oxidation (MFO), insulin resistance (IR), inflammation, endothelial function, physical function, and body composition. Subject inclusion consisted of young adults (aged 21-40 years) and older adults (aged 61-80 years), with body mass index (BMI) >27, who had stopped all nonvitamin nutritional supplements for 4-weeks prior to the trial beginning. Fasted blood samples were obtained to measure plasma lipids, liver profile, BUN, creatinine, thyroid stimulating hormone (TSH), free T4, glucose, HbA1c, and complete blood counts. Furthermore, all subjects completed baseline studies of glucose tolerance test, physical function tests (gait speed, upper and lower extremity strength, and rapid 6-minute walk test), DEXA and liver scans, calorimetry, tracer studies, and muscle biopsy.

23 participants were randomized to receive either GlyNAC (n=11) or placebo (alanine) (n=12) for a 16-week intervention. Those in the GlyNAC group consumed 100 mg/kg/d each of glycine and NAC daily. The placebo group consumed 200 mg/kg/d of alanine daily. Studies were repeated 2 weeks after beginning supplementation and young adult subjects were released at the end of 2 weeks. The older adults returned at the end of weeks 4, 8, and 12 to measure liver transaminases and creatinine and then underwent a final study at the end of the 16-weeks of supplementation. OxS and oxidative damage were measured using ELISA assays as plasma concentrations thiobarbituric acid reducing substances (TBARS) and 8-Iso-Prostaglandin-F2a. Biomarkers of inflammation and endothelial function assessed included interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) interleukin-10 (IL-10), human soluble intercellular adhesion molecule 1 (sICAM1), soluble vascular cell adhesion molecule 1 (sVCAM1), and high-sensitivity human C-reactive protein.

Physical function measures, body composition, blood pressure, and lipids were compared between 3 cohorts at baseline, change in response at 16-weeks versus baseline among older adults receiving placebo (OAP) and older adults receiving GlyNAC (OAG), 16-week OAP/OAG versus young adults at baseline, and OAP versus OAG at 16-weeks.

Young adult subjects (7 men, 5 women) were 25.6 years ± 2.5 years of age, OAG (8 men, 4 women) were 71.4 ± 4.2 years, and OAP (4 men, 8 women) were 70.8 ± 3.9 years. Significant findings of the study are as follows:

  • At 0 weeks, both the OAG and OAP group had 66% lower muscle GSH concentrations compared to the YA group. Only the OAG group experienced significantly improved GSH concentrations by 121% after 2-weeks and by 164% after 16-weeks.
  • Only the OAG group had a significant improvement in total RBC-GSH (tGSH) (by 173% after 2-weeks and 225% after 16-weeks) and in reduced RBC-GSH (rGSH) (by 195% after 2-weeks and 225% after 16-weeks).
  • Changes in oxidative stress measured by plasma TBARS concentrations and F2-I concentrations show that only the OAG group had significantly lower markers after 2-weeks (TBARS 42% lower; F2-I 44% lower) and 16-weeks (TBARS 72% lower; F2-I 72% lower) to levels not different from the YA group at baseline.

Results of the 16-week double-blind, placebo-controlled randomized controlled trial show that Gly-NAC supplementation significantly improved glutathione concentrations and reduced oxidative stress and inflammatory markers in older adult subjects. Findings suggest a combination of glycine and NAC may be beneficial to improve markers of aging. Study limitations include the use of only healthy older adult subjects.

Source: Kumar, Premranjan, Chun Liu, James Suliburk, Jean W. Hsu, Raja Muthupillai, Farook Jahoor, Charles G. Minard, George E. Taffet, and Rajagopal V. Sekhar. “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.” The Journals of Gerontology: Series A 78, no. 1 (2023): 75-89.

© The Author(s) 2022. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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Posted April 10, 2024.

Taylor Woosley studied biology at Purdue University before becoming a 2016 graduate of Columbia College Chicago with a major in Writing. She currently resides in Glen Ellyn, IL.

References:

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