Glycine

 

• Improves anti-oxidant status — goes very well with NAC. Does this in a way different from vitamins (doesn’t force cells to pick up or make antioxidants; rather antioxidants are made on-demand as much as a cell need) 

• Reduces glucose AUC & HA1C when given with a high carb meal.

• Improved mice lifespan by 4.7% in ITP, by 28% in an earlier study. 

• Glycine supplementation attenuates NAFLD in mice by stimulating hepatic fatty acid oxidation and glutathione synthesis.

• Reduced platelet aggregation and increased bleeding time.

• Improves sleep quality. 

• Increases HGH when taken at high doses.

Glycine supplementation extends lifespan of male and female mice, 2019

Diets low in methionine extend lifespan of rodents, though through unknown mechanisms. Glycine can mitigate methionine toxicity, and a small prior study has suggested that supplemental glycine could extend lifespan of Fischer 344 rats. We therefore evaluated the effects of an 8% glycine diet on lifespan and pathology of genetically heterogeneous mice in the context of the Interventions Testing Program. Elevated glycine led to a small (4%–6%) but statistically significant lifespan increase, as well as an increase in maximum lifespan, in both males (p = 0.002) and females (p < 0.001). 

Dietary glycine supplementation mimics lifespan extension by dietary methionine restriction in Fisher 344 rats, 2011

Dietary methionine (Met) restriction (MR) extends lifespan in rodents by 30–40% and inhibits growth. Since glycine is the vehicle for hepatic clearance of excess Met via glycine N-methyltransferase (GNMT), we hypothesized that dietary glycine supplementation (GS) might produce biochemical and endocrine changes similar to MR and also extend lifespan. Seven-week-old male Fisher 344 rats were fed diets containing 0.43% Met/2.3% glycine (control fed; CF) or 0.43% Met/4%, 8% or 12% glycine until natural death. In 8% or 12% GS rats, median lifespan increased from 88 weeks (w) to 113 w (28%). We propose that more efficient Met clearance via GNMT with GS could be reducing chronic Met toxicity due to rogue methylations from chronic excess methylation capacity or oxidative stress from generation of toxic by-products such as formaldehyde. This project received no outside funding.

Glycine treatment decreases proinflammatory cytokines and increases interferon-gamma in patients with type 2 diabetes, 2002

Materials/subjects and methods: Seventy-four patients, with Type 2 diabetes were enrolled in the study. The mean age was 58.5 yr, average age of diagnosis was 5 yr. 5 g/d glycine or 5 g/d placebo, po tid, for 3 months.

HbA1c scores were reduced by -1.4 in the treatment group (before treatment: 8.3±1.9 VS. after glycine treatment: 6.9±1.3). The proinflammatory biomarker TNF-R1 (a marker of TNF-α) was significantly lower in the glycine treatment group as compared to the control group.

IFN-γ levels increased in the glycine treatment group by +38% and decreased in the control group by -43%. In the type 2 diabetic state, certain parts of the immune system can become depressed, which is associated with lower production of IFN-γ.

Taken together, this study implies that glycine treatment improves immune function, reduces inflammation and improves basal glucose levels.

Glycine reduces platelet aggregation, 2013

The researchers found that compared to the control, the glycine fed rats had increased bleeding time (about double) which corresponded to reduced platelet aggregation. In the human platelet arm of the trial (in vitro), added glycine also inhibited platelet aggregation.

Effects on cancer

• Dietary glycine decreases both tumor volume and vascularization in a combined colorectal cancer liver metastasis and chemotherapy model, 2019

• Dietary Melatonin and Glycine Decrease Tumor Growth through Antiangiogenic Activity in Experimental Colorectal Cancer Liver Metastasis, 2021

• Dietary glycine inhibits the growth of B16 melanoma tumors in mice, 1999

• Dietary glycine prevents the development of liver tumors caused by the peroxisome proliferator WY-14,643, 1999

Glycine fuels cancer cells, Nature (link)

Cancer cells use different metabolic pathways to their normal counterparts; this metabolic switch is necessary to support their rapid proliferation in oxygen- and nutrient-poor conditions. Mootha and colleagues perform metabolic profiling of the NCI-60 cancer cell line collection and report a key role for glycine in supporting rapid cellular proliferation.

The authors created metabolic consumption and release (CORE) profiles of the individual cancer cell lines to identify metabolites that are taken up or released. Correlating the CORE profiles with known cell proliferation rates revealed that glycine was generally consumed by highly proliferative cancer cells and released by slowly proliferating cells. Tracing radiolabelled glycine in a rapidly proliferating cell line revealed that it was used in de novo purine nucleotide synthesis.

Intriguingly, non-transformed, yet highly proliferative, cells also consumed glycine, suggesting that this amino acid supports rapid proliferation. Indeed, depleting extracellular glycine or knocking down the glycine-synthesizing enzyme SHMT2 blocked rapid proliferation by prolonging the G1 phase of the cell cycle. Glycine depletion did not affect slowly proliferating cells. Expression analyses of genes encoding mitochondrial glycine synthesis enzymes revealed that upregulation of these genes correlated with greater mortality and worse prognosis in breast cancer. Thus, the glycine synthesis pathway represents an attractive target for the development of anti-cancer therapeutics.

The metabolic response to ingested glycine, 2002

Design: Nine healthy subjects were tested on 4 separate occasions. Plasma glucose, insulin, glucagon, and glycine concentrations were measured at various times during a 2-h period after the ingestion of 1 mmol glycine/kg lean body mass, 25 g glucose, 1 mmol glycine/kg lean body mass + 25 g glucose, or water only, given in random order.

Results: Plasma concentrations of glycine and glucagon were elevated after the ingestion of glycine, as expected. The serum insulin concentration also was slightly elevated after the ingestion of glycine alone. When glycine was ingested with glucose, the plasma glucose area response was attenuated by > 50% compared with the response after the ingestion of glucose alone. The dynamics of the insulin response after the ingestion of glycine plus glucose were modestly different from those after the ingestion of glucose alone, but the area response was not significantly different.

Conclusion: The data are compatible with the hypothesis that oral glycine stimulates the secretion of a gut hormone that potentiates the effect of insulin on glucose removal from the circulation.

[MIXED] Oral supplementation with glycine reduces oxidative stress in patients with metabolic syndrome, improving their systolic blood pressure, 2013

“Glycine lowered systolic blood pressure in 60 patients with metabolic syndrome”

Reactive oxygen species derived from abdominal fat and uncontrolled glucose metabolism are contributing factors to both oxidative stress and the development of metabolic syndrome (MetS). This study was designed to evaluate the effects of daily administration of an oral glycine supplement on antioxidant enzymes and lipid peroxidation in MetS patients. The study included 60 volunteers: 30 individuals that were supplemented with glycine (15 g/day) and 30 that were given a placebo for 3 months. We analysed thiobarbituric acid reactive substances (TBARS) and S-nitrosohemoglobin (SNO-Hb) in plasma; the enzymatic activities of glucose-6-phosphate dehydrogenase (G6PD), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) in erythrocytes; and the expression of CAT, GPX, and SOD2 in leukocytes. Individuals treated with glycine showed a 25% decrease in TBARS compared with the placebo-treated group. Furthermore, there was a 20% reduction in SOD-specific activity in the glycine-treated group, which correlated with SOD2 expression. G6PD activity and SNO-Hb levels increased in the glycine-treated male group. Systolic blood pressure (SBP) also showed a significant decrease in the glycine-treated men (p = 0.043). Glycine plays an important role in balancing the redox reactions in the human body, thus protecting against oxidative damage in MetS patients.

Mixed: Glucose went up 13%, HA1C dropped, Insulin unchanged. 

Glycine Metabolism and Its Alterations in Obesity and Metabolic Diseases. 2019

Subjective effects of glycine ingestion before bedtime on sleep quality, 2006

The effects of glycine on sleep quality were examined in a randomized double-blinded cross-over trial. The volunteers, with complaints about the quality of their sleep, ingested either glycine (3 g) or placebo before bedtime, and their subjective feeling in the following morning was evaluated with the St. Mary's Hospital Sleep Questionnaire and Space-Aeromedicine Fatigue Checklist. The glycine ingestion significantly improved the following elements: “fatigue”, “liveliness and peppiness”, and “clear-headedness”. These results suggest that glycine produced a good subjective feeling after awakening from sleep.

Sleep (Amazon)

• consistently improved my sleep for 3 years

3 grams per night has caused a consistent and significant improvement in my sleep quality. This effect has been consistent and has not decreased at all even after several years of use. This is the only supplement I never go without, not even a single day. I stick with Life Extension because their supplements are high-quality and consistent but I've used other glycine supplements and they have worked equally well.

Glycine stimulated growth hormone release in man

The influence of glycine, the simplest amino acid, on pituitary function has been investigated in the present study. Different doses (4, 8, or 12 g) of glycine were intravenously infused over 15 or 30 min in normal subjects. Serum levels of GH (growth hormone) and Prl (prolactin) were measured before and after the infusion, and also blood sugar levels were determined. The dose of 4 or 8 g glycine induced a significant increase in serum GH (P less than 0.05 or P less than 0.001, respectively); however, a more pronounced and significant increase in serum GH levels was observed after infusion at a dose of 12 g glycine (P less than 0.001). It was clearly observed that the dose-dependent GH release to intravenous glycine occurred in normal subjects. On the contrary, serum Prl level was not changed significantly, and blood sugar level was transiently, but significantly (P less than 0.05), increased after the infusion of 12 g glycine. The present data suggest that glycine might play an important role in the control of hypothalamic-pituitary function.

Stimulatory effect of glycine on human growth hormone secretion

Glycine (250 ml 0.3 M glycine) was administered orally to 19 nonobese normal subjects and 12 subjects with partial gastrectomy. In the normal subjects, a clear and significant increase of serum human growth hormone (hGH) level was observed (p less than 0.001), whereas serum immunoreactive insulin (IRI), prolactin (PRL) and blood sugar (BS) levels were not affected after the drug administration. A more pronounced and significant increase of hGH value in serum was found in the subjects with gastrectomy than in the normal controls (p less than 0.001). Thus we administered the drug intraduodenally in normal subjects. The similar rise of hGH to that of the gastrectomied group was obtained in normals by this administration. The facts demonstrated that glycine is one of the stimulatory agents inducing the pituitary gland to secrete hGH. In addition, in nonobese diabetics, no significant increase of serum hGH level, even after the intraduodenal administration of glycine, was observed in the present study.