Lizzo Giulia, Migliavacca Eugenia, Lamers Daniela, Frézal Adrien, Corthesy John, Vinyes-Parès Gerard, Bosco Nabil, Karagounis Leonidas G, Hövelmann Ulrike, Heise Tim, von Eynatten Maximilian, Gut Philipp
Nestlé Institute of Health Sciences, Lausanne, Switzerland.
Profil, Neuss, Germany.
Front Aging. 2022 Mar 7;3:852569. doi: 10.3389/fragi.2022.852569. eCollection 2022.
Glycine and cysteine are non-essential amino acids that are required to generate glutathione, an intracellular tripeptide that neutralizes reactive oxygen species and prevents tissue damage. During aging glutathione demand is thought to increase, but whether additional dietary intake of glycine and cysteine contributes towards the generation of glutathione in healthy older adults is not well understood. We investigated supplementation with glycine and n-acetylcysteine (GlyNAC) at three different daily doses for 2 weeks (low dose: 2.4 g, medium dose: 4.8 g, or high dose: 7.2 g/day, 1:1 ratio) in a randomized, controlled clinical trial in 114 healthy volunteers. Despite representing a cohort of healthy older adults (age mean = 65 years), we found significantly higher baseline levels of markers of oxidative stress, including that of malondialdehyde (MDA, 0.158 0.136 µmol/L, < 0.0001), total cysteine (Cysteine-T, 314.8 276 µM, < 0.0001), oxidized glutathione (GSSG, 174.5 132.3 µmol/L, < 0.0001), and a lower ratio of reduced to oxidized glutathione (GSH-F:GSSG) (11.78 15.26, = 0.0018) compared to a young reference group (age mean = 31.7 years, = 20). GlyNAC supplementation was safe and well tolerated by the subjects, but did not increase levels of GSH-F:GSSG (end of study, placebo = 12.49 7.2 g = 12.65, -value = 0.739) or that of total glutathione (GSH-T) (end of study, placebo = 903.5 7.2 g = 959.6 mg/L, -value = 0.278), the primary endpoint of the study. Post-hoc analyses revealed that a subset of subjects characterized by high oxidative stress (above the median for MDA) and low baseline GSH-T status (below the median), who received the medium and high doses of GlyNAC, presented increased glutathione generation (end of study, placebo = 819.7 4.8g/7.2 g = 905.4 mg/L, -value = 0.016). In summary GlyNAC supplementation is safe, well tolerated, and may increase glutathione levels in older adults with high glutathione demand. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT05041179, NCT05041179.
甘氨酸和半胱氨酸是生成谷胱甘肽所需的非必需氨基酸，谷胱甘肽是一种细胞内三肽，可中和活性氧并防止组织损伤。随着年龄增长，谷胱甘肽的需求量被认为会增加，但在健康老年人中，额外的膳食摄入甘氨酸和半胱氨酸是否有助于谷胱甘肽的生成，目前还不太清楚。我们在114名健康志愿者中进行了一项随机对照临床试验，研究了三种不同日剂量（低剂量：2.4克，中剂量：4.8克，或高剂量：7.2克/天，比例为1:1）的甘氨酸和N-乙酰半胱氨酸（GlyNAC）补充剂，为期2周。尽管该队列是健康老年人（平均年龄 = 65岁），但我们发现与年轻对照组（平均年龄 = 31.7岁，n = 20）相比，氧化应激标志物的基线水平显著更高，包括丙二醛（MDA，0.158±0.136 μmol/L，P < 0.0001）、总半胱氨酸（Cysteine-T，314.8±276 μM，P < 0.0001）、氧化型谷胱甘肽（GSSG，174.5±132.3 μmol/L，P < 0.0001），以及还原型谷胱甘肽与氧化型谷胱甘肽的比例（GSH-F:GSSG）更低（11.78±15.26，P = 0.0018）。GlyNAC补充剂对受试者来说是安全且耐受性良好的，但并未提高GSH-F:GSSG水平（研究结束时，安慰剂组 = 12.49，4.8克组 = 12.65，P值 = 0.739）或总谷胱甘肽（GSH-T）水平（研究结束时，安慰剂组 = 903.5，7.2克组 = 959.6 mg/L，P值 = 0.278），而这是该研究的主要终点。事后分析显示，一部分以高氧化应激（高于MDA中位数）和低基线GSH-T状态（低于中位数）为特征的受试者，在接受中剂量和高剂量的GlyNAC后，谷胱甘肽生成增加（研究结束时，安慰剂组 = 819.7，4.8克/7.2克组 = 905.4 mg/L，P值 = 0.016）。总之，GlyNAC补充剂是安全的，耐受性良好，并且可能会提高谷胱甘肽需求量高的老年人的谷胱甘肽水平。临床试验注册：https://clinicaltrials.gov/ct2/show/NCT05041179，NCT05041179。
