Amino Acids & Precursors — References

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Parent Topic: Amino Acids & Precursors | References Hub: 02 - Compounds & Molecules References MOC

Landmark Peer-Reviewed Studies

Citation: Kumar, P., Liu, C., Suliburk, J., Hsu, J. W., Muthupillai, R., Jahoor, F., Minard, C. G., Taffet, G. E., & Sekhar, R. V. (2023). 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(1), 75–89.
Identifiers: PMID: 36696205 (PubMed · Europe PMC) | DOI: 10.1093/gerona/glac135 (DOI · SciDB · Scholar)
Study Design & Sample Size: 16-week randomized, double-blind, placebo-controlled clinical trial in older adults aged 61–80 years ( $n = 24$ , randomized to GlyNAC vs. isocaloric alanine placebo) compared against a young adult reference cohort ( $n = 12$ , aged 21–40 years).
Key Quantitative Outcomes: Supplementation with GlyNAC ( $100 mg/kg/day$ glycine + $100 mg/kg/day$ N-acetylcysteine) increased erythrocyte total glutathione (RBC-GSH) by $+ 164%$ ( $p < 0.001$ ), reduced oxidative stress (plasma TBARS by $- 72%$ and 8-iso-PGF2 $α$ by $- 65%, p < 0.001$ ), improved mitochondrial fatty acid oxidation by $+ 78%$ , reduced HOMA-IR insulin resistance by $- 64%$ , lowered IL-6 by $- 78%$ and TNF- $α$ by $- 54%$ , reduced systolic blood pressure by $- 7.6 mmHg$ , and restored gait speed and grip strength to levels indistinguishable from young controls.

Citation: Singh, P., Gollapalli, K., Mangiola, S., Schranner, D., Yusuf, M. A., Chamoli, M., Shi, S. L., Lopes Bastos, B., Kurade, M., Viana, R. N., … & Yadav, V. K. (2023). Taurine deficiency as a driver of aging. Science, 380(6649), eabn9257.
Identifiers: PMID: 37289866 (PubMed · Europe PMC) | DOI: 10.1126/science.abn9257 (DOI · SciDB · Scholar)
Study Design & Sample Size: Multi-species translational investigation across mice ( $N > 250$ ), C. elegans, middle-aged rhesus macaques (Macaca mulatta), and human epidemiological/exercise cohorts ( $N = 11, 966$ in EPIC-Norfolk).
Key Quantitative Outcomes: Serum taurine concentrations in 60-year-old humans were $> 80%$ lower than in 5-year-old individuals. Oral taurine supplementation ( $1, 000 mg/kg/day$ in mice; human equivalent $\sim 3 - 6 g/day$ ) increased median lifespan by $+ 10 - 12%$ and life expectancy at 28 months by $+ 18 - 25%$ ( $p < 0.001$ ). In middle-aged rhesus monkeys, 6 months of taurine ( $250 mg/kg/day$ ) increased lumbar spine BMD, reduced fasting glucose by $- 19%$ , lowered hepatic AST/ALT by $- 36%$ , and reduced lipid peroxides.

Citation: Schwedhelm, E., Maas, R., Freese, R., Jung, D., Lukacs, Z., Jambrecina, A., Spickler, W., Schulze, F., & Böger, R. H. (2008). Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. British Journal of Clinical Pharmacology, 65(1), 51–59.
Identifiers: PMID: 17662090 (PubMed · Europe PMC) | DOI: 10.1111/j.1365-2125.2007.02990.x (DOI · SciDB · Scholar)
Study Design & Sample Size: Double-blind, randomized, placebo-controlled crossover trial in healthy adults ( $N = 20$ ) comparing 6 regimes of oral L-citrulline ( $0.75 - 3.0 g$ twice daily) vs. immediate-release and sustained-release L-arginine.
Key Quantitative Outcomes: $3.0 g$ twice daily L-citrulline increased the minimum plasma L-arginine concentration ( $C_{m i n}$ ) and the L-arginine/ADMA ratio significantly more than $3.2 g$ L-arginine ( $p < 0.01$ ), and increased urinary nitrate and cyclic GMP (cGMP) excretion by $+ 28%$ ( $p = 0.01$ ).

Citation: Yamadera, W., Inagawa, K., Chiba, S., Bannai, M., Takahashi, M., & Nakayama, K. (2007). Glycine ingestion improves subjective sleep quality in human volunteers, correlating with polysomnographic changes. Sleep and Biological Rhythms, 5(2), 126–131.
Identifiers: DOI: 10.1111/j.1479-8425.2007.00262.x (DOI · SciDB · Scholar) | Google Scholar ID: Yamadera2007GlycineSleep
Study Design & Sample Size: Randomized, single-blind, placebo-controlled crossover polysomnography (PSG) trial in human volunteers with dissatisfaction in sleep quality ( $N = 11$ ).
Key Quantitative Outcomes: Ingestion of $3.0 g$ glycine before bedtime significantly shortened latency to sleep onset ( $p = 0.019$ ) and latency to slow-wave sleep (SWS, $p = 0.043$ ) without altering REM architecture, while significantly improving next-day psychomotor vigilance and reducing daytime sleepiness ( $p = 0.008$ ).