Could supplementing with glycine and N-acetylcysteine improve “hallmarks of aging”? Original paper

In this randomized controlled study, supplemental glycine and N-acetylcysteine improved a wide range of outcomes related to cardiometabolic health and physical function in older adult participants. However, despite including a placebo group, there was no direct comparison to determine whether these outcomes were statistically significant compared to a placebo.

The effect of supplementing with glycine and N-acetylcysteine (GlyNAC) on several “hallmarks of aging” (a term used by the study authors).

The study outcomes included glutathione levels, oxidative stress, mitochondrial fat oxidation, insulin resistance, inflammation, physical function, health-related quality of life, blood pressure, and body composition.

24 older adults between the ages of 61 and 80 (12 men, 12 women) and 12 younger adults between the ages of 21 and 40 (7 men, 5 women). All participants had a BMI greater than 27.

In this randomized controlled study, the participants received GlyNAC (200 milligrams per kilogram of bodyweight per day, or mg/kg/day, i.e., 100 mg/kg/day of Gly + 100 mg/kg/day of NAC) or a placebo (alanine; 200 mg/kg/day) for 16 weeks (older adults) or 2 weeks (younger adults).

Physical function was assessed via gait speed, a chair-rise test, grip strength, and a rapid 6-minute walk test. Insulin resistance was assessed using HOMA-IR. Inflammation and oxidative stress markers included interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10) sICAM1, sVCAM1, C-reactive protein (CRP), TBARS, and F-2 isoprostane levels. Body composition measures, including total body fat and lean mass, were assessed using dual X-ray absorptiometry (DXA).

The following improvements were observed in the GlyNAC-supplemented older adults after 16 weeks but did not change in the placebo-supplemented or young adult groups:

• Muscle, total red blood cell, and reduced red blood cell glutathione levels increased by 165%, 225%, and 259%, respectively.
• Oxidative stress levels decreased — TBARS and F-2 isoprostanes were 72% lower.
• Gait speed, upper-extremity (grip strength), and lower-extremity (chair-stand test) physical function improved.
• Mitochondrial fat oxidation increased by 78%.
• HOMA-IR decreased (improved) by 64%.
• IL-6, TNF-alpha, sICAM1, sVCAM1, and CRP decreased (improved), and IL-10 increased (improved).
• Waist circumference and systolic blood pressure decreased.

However, there was no comparison to determine whether the above changes were statistically significant compared to the placebo group.

Because the statistical significance of the outcomes reported were based on comparisons to the start of the trial, rather than comparing the supplement group to the placebo group, the results should be considered weaker than they would be in a traditional randomized controlled trial.^[1]

In addition to the primary outcomes, several other outcomes were found to improve over time in the GlyNAC-supplemented older adults, including a marker of mitochondrial function (i.e., low fat oxidation and high glucose oxidation), intracellular communication (i.e., high inflammatory cytokines and low anti-inflammatory cytokines), nutrient sensing (e.g., [HOMA-IR), genomic stability (i.e., markers of DNA damage), proteostasis (PINK1 and LC3AB expression), stem-cells (PAX7 expression), and cellular senescence (muscle p16^INK4α expression). However, these changes were also not compared to the placebo group to determine if they were statistically significant.

Remarkably, after supplementation, many of the outcomes — glutathione levels, oxidative stress, gait speed, mitochondrial fat oxidation, HOMA-IR, and inflammation — improved in older adults to levels that were similar to those of the younger adults.