Glycine to Increase Longevity and Decrease Depression
Research suggests that glycine may provide multiple health benefits when intake is increased.
STORY AT-A-GLANCE
Glycine has been shown to extend lifespan in animal studies and mitigate chronic disease and disability, thereby increasing healthspan
Glycine has anticancer effects, reduces insulin and alleviates neuroinflammation; it may also protect against depression and is essential for collagen synthesis
To gain all of glycine’s healing potential, doses of 10 to 20 grams a day may be optimal
You need at least 12 grams of glycine daily for optimal collagen turnover, plus another 3 grams per day to form glutathione
Excess methionine from eating animal products without the connective tissues decreases longevity, but adding glycine will reduce the methionine/glycine ratio to counter the negative side effects of excess methionine
Glycine has neurotransmitter qualities, improves depression and is also useful for improving sleep quality by helping relaxation at night by being very similar to the neurotransmitter GABA
Glycine, a nonessential amino acid, meaning your body can make it, but most of us as we age are simply unable to make enough of it, especially if our dietary intake is low because we are not eating enough connective tissue and collagen in our diet.
New research is emerging showing glycine is a powerful longevity enhancer, one that's not only inexpensive but also has a pleasant, slightly sweet flavor. In fact, glycine is sometimes used as a sugar substitute, and I personally take 1 teaspoon with each of my two meals and before bedtime for its health-enhancing qualities.
Research shows glycine extends lifespan in worms, mice and rats while improving health in models of age-related disease.1 If there were any doubt about its importance, consider that collagen — the most abundant protein in your body2 — is made mostly of glycine. It's also a precursor to glutathione, a powerful antioxidant that declines with age.
As noted by Siim Land, author of "Metabolic Autophagy," in the video above,3 however, there are two glycine benefits that appear key to its actions as a veritable fountain of youth — inducing autophagy and mimicking the longevity benefits of methionine restriction.4
How Glycine May Influence Aging
Glycine is a receptor for the enzyme glycine N-methyltransferase (GNMT), which plays a role in methionine clearance, according to a review published in Ageing Research Reviews.5 Glycine is the acceptor for GNMT, an enzyme responsible for methionine clearance. GNMT converts glycine to sarcosine, "an autophagy-inducing metabolite."6
Further, in mice deficient in GNMT, levels of free methionine may be seven-fold higher, while S-adenosyl-L-methionine may increase by 35-fold.7 This matters, as methionine is involved in cancer cell growth and metabolism, while methionine restriction inhibits cancer cell growth.8
Methionine restriction has been shown to improve longevity, extending lifespan in mice while lowering levels of insulin, glucose and insulin-like growth factor 1. Limiting methionine also yields a host of additional antiaging benefits in ice, like reducing liver damage after exposure to dangerous amounts of acetaminophen and reducing overall frailty.9
"Since a low level of methionine signifies a low nutrient state, methionine restriction is thought to act as a caloric restriction mimetic," the Ageing Research Reviews report explains.10 Glycine, in turn, the researchers noted, "may prolong life by serving as a methionine restriction mimetic."11 It does this because it lowers the methionine/glycine ratio which may be more important than the absolute level of methionine consumption.
You Need Glycine for Collagen Synthesis
Indeed, in a study on mice using data from the National Institute on Aging's Interventions Testing Program, a team of scientists revealed that feeding a diet with 8% glycine increased lifespan significantly, by 4% to 6%, in males and females, while offering additional benefits like reduced risk of dying from lung cancer.12
Some animal studies have shown up to a 28.4% median increase in lifespan when eating a diet containing 8% or 12% glycine.13 There are also direct antiaging effects via collagen synthesis. Land explains:14
"Glycine also has a very important role in antiaging directly by helping to reduce wrinkles, and collagen synthesis. Glycine makes up every third amino acid in collagen, which is why there is such a large requirement of glycine for optimal collagen turnover.
The less collagen or glycine you consume, the slower your collagen turnover is. Slow collagen turnover increases the damage that occurs to your collagen, such as glycation and oxidation, and reduces collagen deposition into tissues.
Collagen is the most abundant protein in the human body, making up approximately 30% of all your protein by mass. It makes up your hair, teeth, skin, nails, organs, arteries, cartilage, bones, tendons and ligaments. Collagen is literally the glue that holds you together. So making sure that you preserve your collagen is very important for slowing down aging, especially when it comes to wrinkles.
Starting at the age of 20 you lose just under 10% of your skin's collagen content every decade. So, by the time you're 75 years old you would have lost 50% of your skin's collagen content … up until very recently it was thought that the collagen turnover was very slow and it only happened over the course of many years — over the entire lifespan.
However, recently it was shown that college turnover happens every day and is part of your daily protein turnover."
Glycine Protects Against Age-Related Disease
Also significant is glycine's potential to mitigate chronic disease and disability, thereby increasing healthspan throughout your body. Glycine receptors exist in the central nervous system, for instance, which means glycine acts as a neurotransmitter.15 The Ageing Research Reviews study compiled multiple examples of glycine's ability to fight age-related disease in animals, including:16
Suppressed tumor growth in mice with melanoma17
Decreased fasting glucose, insulin, triglyceride and insulin-like growth factor 1 in male rats18
Preserved muscle mass and reduced inflammatory markers in mice with cancer cachexia19
Improved endothelial function in older rats20
Even intermittently restricting methionine leads to benefits like improved glucose homeostasis, reduced obesity and protection against fatty liver
Reduced weight gain and improved bone mineral density in a mouse model designed to mimic postmenopausal bone loss21
Protected against cardiac hypertrophy22
Alleviated neuroinflammation and protected against cognitive deficits in mice with neurodegeneration23
Human trials confirm what the animal models suggest — that glycine is protective against a range of chronic diseases. In a study of 60 people with metabolic syndrome, 15 grams of glycine a day for three months had reduced oxidative stress and improved systolic blood pressure.24
In older adults, limited availability of glycine and cysteine may lead to decreased synthesis of glutathione — composed of the three amino acids cysteine, glycine and glutamic acid — such that glutathione deficiency is widespread in this population.25 The lack of glutathione, perhaps driven by limited glycine, in older adults may be a key element driving the oxidative stress and mitochondrial dysfunction that lead to age-related degeneration. Land notes:26
"The benefits of glycine generally have to do with improving the blood sugar levels, fasting insulin levels, triglycerides, even lowering the demand for sleep, improving brain function and health, helping with just overall aspects of vitality.
… a lot of the longevity benefits come from the methane restriction and the autophagy stimulation that pretty much helps to clean out the cells from the dysfunctional components as well as boosting glutathione levels, which just enables the body to function with less inflammation and oxidative stress, which is very crucial for aging and it also pretty much buffers against the methionine toxicity."
Glycine With NAC Supports Mitochondrial Health
Researchers at Baylor College of Medicine also looked into supplementation with a combination of glycine and N-acetylcysteine (NAC), two glutathione precursors known as GlyNAC when taken together.
They had previously shown that young mice deficient in glutathione had mitochondrial dysfunction, and supplementing with GlyNAC in older mice not only improved glutathione deficiency but also mitochondrial impairment, oxidative stress and insulin resistance.27
Additional previous research they conducted in HIV patients28 found GlyNAC supplementation improved "deficits associated with premature aging" in this population.29 This included improvements to oxidative stress, mitochondrial dysfunction, inflammation, endothelial dysfunction, insulin resistance, genotoxicity, strength and cognition.30
A subsequent pilot trial in older humans found similar results, with GlyNAC supplementation for 24 weeks correcting glutathione deficiency and improving multiple measures of health, including:31
Mitochondrial dysfunction
Oxidative stress
Inflammation
Endothelial dysfunction
Insulin resistance
Genomic damage
Cognition
Strength
Gait speed
Exercise capacity
Body fat levels
Waist circumference
Further, GlyNAC supplementation improved four of nine hallmarks of aging associated with most age-related disorders — mitochondrial dysfunction, inflammation, insulin resistance and genomic damage.32 Glycine, the team noted, is an important methyl-group donor. "Methyl groups are abundant in DNA and are important components of multiple cellular reactions. Glycine is also important for normal brain function."33
In addition to supporting brain function,34 supplemental glycine may be useful for the "prevention and control of atherosclerosis, heart failure, angiogenesis associated with cancer or retinal disorders and a range of inflammation-driven syndromes, including metabolic syndrome."35
Glycine's Link to Depression
As a major neurotransmitter,36 glycine's role in brain health is receiving increasing attention. The results of a 15-year study conducted by University of Florida researchers also suggest it may be involved in depression. The finding relates to a receptor called GPR158. When suppressed in mice, stress-induced depression is less likely.
When they determined the structure of GPR158, they realized it's an amino acid receptor — for glycine. "We were barking up the completely wrong tree before we saw the structure," study author Kirill Martemyanov told Medical News Today. "We said, 'Wow, that's an amino acid receptor. There are only 20, so we screened them right away and only one fit perfectly … it was glycine."37
After learning that GPR158 binds to glycine and acts as a metabotropic glycine receptor, they named it mGlyR.38 The team explained in the journal Science:39
"Glycine signals through mGlyR to inhibit production of the second messenger adenosine 3′,5′-monophosphate. We further show that glycine, but not taurine, acts through mGlyR to regulate neuronal excitability in cortical neurons. These results identify a major neuromodulatory system involved in mediating metabotropic effects of glycine, with implications for understanding cognition and affective states."
Glycine is also useful for improving sleep quality.40 "It can help to relax at night by being very similar to GABA," Land says. "… It's beneficial for … reducing the time it takes to fall asleep. People who ingested 3 grams of glycine within one hour before bedtime saw an improvement in subjective sleep quality, fell asleep faster and were less sleepy during the day."41
How Much Glycine Is Enough?
To gain all of glycine's healing potential, doses of 10, 15, or 20 grams a day may be necessary. Land suggests you need at least 12 grams of glycine daily for optimal collagen turnover, plus another 3 grams per day to form glutathione and other compounds:42
"Your body only makes 3 grams of glycine per day, and if you only consume around 2 to 3 grams of glycine from foods then it means that almost all of us are in a 10-gram glycine deficit every day," he says.
"… I think most people would benefit for at least 5 to 10 grams of glycine a day, which is, uh kind of a moderate amount … if you are eating a lot of muscle meat … or you're just interested in getting more of the benefits of glycine then you can take even up to 20 grams a day."
In addition to supplements, collagen is an outstanding source of glycine. My personal preference is to use a less denatured (unhydrolyzed) organic collagen supplement, as it has a more balanced amino acid profile or, better yet, simply boost your collagen intake by making homemade bone broth using bones and connective tissue from grass fed, organically raised animals.
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As Dr. Mercola establishes in this relevant article, the methionine/glycine ratio is essential. Inflammation is a common factor in cancer, cardiovascular disease, and diabetes, as well as arthritis and other inflammatory diseases.
Studies establish an inverse association of plasma glycine levels between patients with insulin resistance and diabetes, cardiovascular disease, and cancer. This suggests that low blood glycine levels can lead to a hyperinflammatory state, predisposing the body to a spectrum of chronic diseases including cancer.
Plasma glycine levels in human populations, while may be adequate for the biochemical functions of glycine, including protein synthesis, may not be sufficient for the cellular physiological role of glycine in membrane voltage stabilization, cell activation. in macrophages and other cells.
Glycine comprises one-third of the mole fraction of collagen, and it is postulated that such chronic diseases have been on the rise because the consumption of glycine-rich bone and connective tissues has declined in recent decades.
Amino acid metabolism suggests a more complex relationship between glycine and methionine, the latter of which is abundant in muscle meats. Specifically, glycine is the only substrate for glycine-N-methyltransferase, which comprises the only major pathway of methionine clearance. Triggered by the absorption of a methionine-rich meal, elimination of excess methionine requires two to three molar equivalents of glycine per mole of methionine. Therefore, it could be hypothesized that high consumption of methionine-rich, glycine-poor muscle meats without the connective tissues as staple foods causes a net reduction in plasma glycine levels.
This hypothesis among the participants of the EPIC study in the United Kingdom. Carnivores consuming high methionine and low glycine intake had the lowest plasma glycine levels than other diets.
Observational studies, a clinical trial in Mexico City a decade ago reported the reversal of type 2 diabetes with the consumption of 15 g/day of supplemental glycine for 90 days. Glycine decreases proinflammatory cytokines and increases interferon-γ in patients with type 2 diabetes.
Observationally, the inverse association of type 2 diabetes and prediabetes with plasma glycine has been abundantly documented, as evidenced by the recent SRMA of 46 studies.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4839172/ (2016)-----
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4859380/ (2016).-----
https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/abs/10.1002/bmc.3893 (2017).-----
https://www.jbc.org/article/S0021-9258(17)30753-6/fulltext (2009).---
https://www.nature.com/articles/ejcn2015144 (2015).---
https://link.springer.com/article/10.1007/BF03346417 (2008).----
https://www.bmj.com/content/360/bmj.k134/rr-1 (2018).---
Glycine administration modulates dietary amino acid levels especially methionine, which may increase healthy lifespan in mice and provide a basis for further investigation of the effects of diet on aging and old-age diseases.
https://onlinelibrary.wiley.com/doi/full/10.1111/acel.12953 (2019)
GLYNAC (GLYCINE AND N-ACETYLCYSTEINE) SUPPLEMENTATION IMPROVES IMPAIRED MITOCHONDRIAL FUEL OXIDATION AND LOWERS INSULIN RESISTANCE IN PATIENTS WITH TYPE 2 DIABETES.
https://www.mdpi.com/2076-3921/11/1/154 (2022)
Glycine supplementation improves various components of the metabolic syndrome, such as diabetes, obesity, hyperlipidemia, and hypertension. In the future, the use of glycine may have a significant clinical impact in the treatment of patients with metabolic syndrome.
https://link.springer.com/article/10.1007/s40618-021-01720-3 (2022)
Glycine and N-acetylcysteine (GlyNAC) supplementation in older adults improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, endothelial dysfunction, genotoxicity, muscle strength, and cognition
https://onlinelibrary.wiley.com/doi/full/10.1002/ctm2.372 (2021)
INDUCTION OF GLUTATHIONE BIOSYNTHESIS BY GLYCINE-BASED TREATMENT MITIGATES ATHEROSCLEROSIS
https://www.sciencedirect.com/science/article/pii/S2213231722000854 (2022)
EXTRACELLULAR SERINE AND GLYCINE ARE REQUIRED FOR MOUSE AND HUMAN SKELETAL MUSCLE STEM AND PROGENITOR CELL FUNCTION
https://www.sciencedirect.com/science/article/pii/S2212877820301800 (2021)
Higher levels of glycine, glutamine, betaine, indolepropionate, and (phosphatidylcholines) were associated with a lower risk of type 2 diabetes.
https://diabetesjournals.org/care/article/45/4/1013/144892/Metabolomics-and-Type-2-Diabetes-Risk-An-Updated (2022)
Glycine is synthesized from serine, threonine, choline, and hydroxyproline through interorgan metabolism primarily involving the liver and kidneys. The main pathway is glycine synthesis is a serine cleavage reaction that yields two different products: a glycine molecule plus a C1 unit carried by tetrahydrofolate for other metabolic processes. Metabolism requires much more glycine than C1 units. The amount of glycine available from synthesis, around 3 g/day, together with that from the diet, may be below the amount needed for all metabolic uses, including collagen synthesis by 10 g per day. day for a person of 70 kg. This result supports that glycine is a semi-essential amino acid.
http://www.ncbi.nlm.nih.gov/pubmed/20093739 .---
http://www.ncbi.nlm.nih.gov/pubmed/19179765 .---
http://www.ncbi.nlm.nih.gov/pubmed/23615880.---
Glycine also plays a role in the transmission of nerve signals and the removal of toxins from the body. Glycine stimulates the production of serotonin, the "feel good" hormone that helps elevate mood, improve sleep, and improve memory. Glycine is anti-inflammatory and antioxidant, both of which are properties that reduce the risk of heart disease. Therefore, some researchers have looked at the connection between glycine and heart disease.
TOP 9 BENEFITS AND USES OF GLYCINE
https://www.healthline.com/nutrition/glycine .-----
Glyphosate in particular is working synergistically with most other factors to increase toxic effects. Glyphosate causes insidious damage through its action as an amino acid analogue of glycine, and that this interferes with natural protective mechanisms against other exposures.
https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC6695815/ (2019)
Glycine also plays an important role in fighting inflammation, as explained by Dr. Mercola in the article "Glycine Suppresses Oxidative Damage by Inhibiting Superoxide NOX Production and Raising NADPH Levels," and is used in the detoxification process. As a result of glyphosate toxicity, many people do not have sufficient glycine levels for efficient detoxification.
NADPH is used as a reducing reservoir of electrons that serves to recharge antioxidants once they are oxidized. NADPH is also needed to produce steroid hormones and fats.
To prevent many chronic diseases, we need to find a way to inhibit or modulate NOX. Such strategies include avoiding fructose, practicing nutritional ketosis, and taking spirulina, niacin, glycine, and collagen supplements.
Glycine might be beneficial in preventing or treating metabolic syndrome, diabetic complications, and cardiac hypertrophy, as well as fatty liver disorders.
https://articulos.mercola.com/sitios/articulos/archivo/2022/04/01/que-son-la-nadph-y-la-nox.aspx (2022)
FOODS BY GLYCINE CONTENT
https://www.nutritionvalue.org/foods_by_Glycine_content.html .----
https://wholefoodcatalog.info/nutrient/glycine/foods/ .----
There were 92 comments on this article on the day it was posted, a few days ago, now there are 8 including my comment now. There were a lot of good information and good questions.