Summary

• Glycine is arguably a conditionally essential amino acid present in many foods. Collagen-rich animal foods are especially rich sources.
• Supplementing the diets of mice with glycine extends lifespan in both females and males.
• Glycine seems to positively affect several hallmarks of aging, suggesting it directly affects the aging process.
• Glycine can positively affect the function of many body systems. For example, it can affect the central nervous system in ways that improve sleep and cognition and the endocrine system in ways that improve blood sugar control.
• Blood levels of glycine are inversely associated with various disease states, such as type-2 diabetes.
• Glycine is in the morning step of Coastline at a dose used at meals in several studies reporting positive effects of glycine on metabolic control and inflammation.
• Glycine has an excellent safety profile, even at doses well above the levels that typify the diets of most people.

What is glycine?

Glycine is an amino acid that some people consider to be conditionally essential, for it cannot always be made by your body in sufficient amounts from other amino acids, such as serine, choline, or hydroxyproline. Glycine is present in most protein-rich foods, and connective tissue-rich animal foods are the most abundant sources of glycine, for collagen is about 30% glycine by weight. 

Glycine has an array of pro-longevity actions and, while almost all of us consume some glycine each day, typical intakes might not be sufficient to meet metabolic needs for glycine, such as to support collagen synthesis. This is significant, for collagen is the main protein in connective tissues and the most abundant protein in your body. Some scientists have suggested supplemental doses of about 10 g glycine each day might be needed to close this gap, although to us this seems slightly inflated. 

Effects of glycine on lifespan and healthspan 

Glycine has been found to extend the lifespan of several model organisms, including in roundworms by up to 33% and in rats by about 20%. Perhaps the most convincing demonstration of this comes from the Interventions Testing Program (ITP), widely considered the gold standard of this type of experiment. Specifically, the ITP study found that, started at age 9 months (equivalent to about age 30 in humans), an 8% glycine diet increased average (median) lifespan by 3.7% in female mice and 6.2% in male mice. It also increased maximum lifespan in males — that is to say, the longest-lived males fed glycine lived statistically longer than the longest-lived males in the control group. 

Graph taken from the paper linked above — would need to adapt or get permission to include

Interestingly, the glycine‐supplemented females were lighter than controls, but there was no effect on bodyweight in males. When the scientists examined the mice’s bodies at the end of their lives, the glycine‐treated mice were less likely than controls to die of a lung cancer (pulmonary adenocarcinoma), and glycine did not increase the incidence of any the 40 types of pathology they considered, suggesting that glycine positively affected healthspan too.

Exactly how glycine prolongs life is not clear, but studies of other animals leave clues. Initially it was thought that glycine might mimic methionine restriction, which has repeatedly been found to prolong lifespan by reducing aberrant methylation and perhaps thereby affecting some of the same hallmarks of aging through which Calorie restriction acts, including deregulated nutrient sensing (reducing growth-promoting pathways such as mTOR, insulin, and IGF-1) and chronic inflammation resulting from excessive oxidative stress. This was based on the fact that glycine is the sole acceptor for methyl groups, acting via glycine‐N‐methyl transferase, a key enzyme in the only pathway used to clear methionine in mammals. Whether glycine extends lifespan by mimicking methionine restriction is questionable, however, for glycine doesn’t necessarily reduce blood methionine concentrations. 

Some of glycine’s positive effects are likely mediated through other actions. Regarding the hallmarks of aging, glycine appears to help maintain proteostasis in some cells. For example, by stimulating the expression of an enzyme (glyoxalase 1), glycine might help reduce levels of advanced glycation end products (AGEs — great name, right? Couldn’t make it up) in the cells that line blood vessel walls. AGEs are proteins disfigured and made dysfunctional by glucose sticking to them, which in turn act on their receptors (RAGEs — even better name) and increase oxidative stress, contributing to chronic inflammation, another hallmark.

While there’s been relatively research on this in humans, people have speculated that reduced oxidative stress is especially important to many of glycine’s pro-longevity properties. Glycine counters oxidative stress and exerts anti-inflammatory effects in several ways. There are glycine receptors on some immune cells, including macrophages. Macrophages are cells of the innate immune system often likened to Pac Man due to the way they gobble up invaders. Macrophages can be “polarized” in different ways, affecting whether they serve inflammatory or anti-inflammatory functions. By binding to its receptors on immune cells, glycine influences macrophage polarization in ways that counter inflammation. Glycine is also a precursor for glutathione, often dubbed the “master” antioxidant made by your body. (Glutathione can probably be further increased by combining glycine with N-acetylcysteine in a combination known as “glyNAC”, and in the last few years several clinical trials have shown that glyNAC can produce impressive health benefits in older adults — we’ll have more to say about this in the future.)

Regarding glycine’s other actions on health-promoting mechanisms, glycine is a key building block for other important structures and molecules, including collagen, haem, creatine, nucleic acids, and uric acid. Glycine can improve reactions involving the transfer of single carbon units (“one-carbon metabolism”) and mitochondrial function. Glycine is an important neurotransmitter too, both by acting as a co-agonist at some glutamate (NMDA) receptors and by activating its own receptors throughout the central nervous system. Interestingly, whereas you might hear some people say glycine is an inhibitory neurotransmitter, we now know that glycine has both inhibitory and excitatory actions in the nervous system, for scientists have recently identified excitatory glycine receptors. 

 

Positive effects of glycine on human health

Observational studies have documented lower blood glycine levels in people suffering from diabetes and other metabolic disorders. We can’t infer that low glycine levels cause disease in these instances though, so the effects of glycine per se are best unveiled through clinical trials of glycine supplementation. Here are some examples of what these experiments have shown.

Glycine can improve symptoms of several psychiatric conditions

The effects of glycine on the central nervous system have been better studied than glycine’s actions on other bodily systems. Many of these experiments have tested whether high doses of glycine benefits patients with various psychiatric conditions, testing outcomes including symptoms of obsessive compulsive disorder, schizophrenia, alcohol hallucinosis (which is when alcohol abuse leads to hearing things that don’t happen and experiencing delusional beliefs), broadly finding positive effects on central nervous system function. Interestingly, people with schizophrenia tend to have shorter lives than the rest of us, and both schizophrenia and brain aging in general might be due in part to low-functioning NMDA receptors. Some of the documented positive effects of glycine use in these studies are probably due in part to glycine binding these receptors. 

Glycine can improve sleep quality and cognition

The effects of glycine on central nervous system functions of healthy adults have been less intensively explored than its effects on psychiatric conditions. Regarding healthy people, high doses of glycine (0.8 g glycine per kg bodyweight per day — that’s 60 g per day for a 75-kg person!) can transiently negatively affect something called “pre-pulse inhibition”, which basically reflects how well the central nervous system responds to a strong stimulus when it’s forewarned by a weaker stimulus. The effects of lower doses of glycine on brain function have been found to be beneficial, however. Specifically, studies have found that taking 3 g glycine shortly before bedtime improves sleep quality, also reducing daytime sleepiness and improving daytime alertness and memory. Interestingly, a study of patients with overactive bladder found taking 3 g glycine twice a day made them fall asleep faster, reduced urination at night and the need to pee at this time, and decreased nighttime blood pressure, implying that glycine can positively affect cardiovascular health too. This is consistent with a study of metabolic syndrome patients that reported that 5 g glycine 3 times a day for 3 months reduced systolic blood pressure. 

How glycine improves sleep probably again relates to glycine’s action at NMDA receptors, in particular on the suprachiasmatic nucleus. This brain region is the conductor of the orchestra of biological clocks in your body, setting the daily timing of when your body is optimised for different processes, including sleep. By acting at these receptors, glycine might promote the relaxation of peripheral blood vessels and subsequent lowering of core temperature, which helps initiate sleep. Whether this sleep-enhancing only occurs when glycine is taken before bed has not yet been studied. 

Glycine supplementation can improve blood sugar control and reduce inflammation

Regarding metabolic health, healthy adults who took 5 g glycine 30 minutes before a bolus of glucose, a simple sugar, had a greater subsequent insulin response, reducing the blood sugar swing after the glucose. This effect on insulin might be mediated by increased glucagon-like peptide-1, a hormone that potentiates glucose-stimulated insulin production. Similarly, another study found that taking 75 mg of glycine per kg fat-free mass (3.6 to 5.4 g, for these people) with 25 g glucose reduced peak blood sugar levels by 15% and the total glucose response over 2 h by 50% compared to glucose alone, although this research didn’t find glycine affected total insulin production. 

Repeated over time, such improvements in blood sugar control might lead to significant health benefits. For example, in type-2 diabetes, a placebo-controlled study found that supplementing 5 g glycine per meal (15 g per day) for 3 months reduced HbA1c, a measure of average glucose levels over the previous 115 days or so. Glycine did not quite significantly reduce fasting glucose (-23% vs -10%) or a marker of resistance to the glucose-disposing hormone insulin, but it did decrease several markers of chronic inflammation, namely interleukin-6, interferon-gamma interferon-γ, TNF-receptor 1, resistin, and interleukin-1β.

Glycine might positively affect other bodily systems in certain conditions

The effects of glycine on several bodily systems haven’t been well studied yet, but it might have some positive effects. For example, glycine offset muscle wasting during haemodialysis, even compared with branched-chain amino acids, one of which triggers muscle protein synthesis. Based on existing research and the mechanisms by which glycine seems to act, we expect we’ll see various other positive effects. For example, despite the abundance of collagen in the skin (part of the integumentary system) and the fact that glycine is a key component of collagen, the effects of glycine supplementation per se on people’s skin health have not been studied, to our knowledge.

Our use of glycine

Regarding dose, the morning step of Coastline contains 5 g glycine, the same dose shown to insulin responses and a dose used at individual meals in several studies reporting positive effects on blood sugar control and inflammation. 

Regarding timing, glycine is in the morning step in part to help minimise blood sugar swings to your first meal. The other reason is that we’re pragmatic: We wanted to use a meaningful dose of glycine, and you’d have to take loads of pills if you wanted to use it at night.

Regarding form, clinical trials and lifespan experiments use regular glycine powder, a white, water-soluble, sweet-tasting substance. (The name glycine is derived from a Greek word meaning “sweet tasting”, and glycine is sweet enough that some experimenters use glucose as its placebo!) We use conventional glycine too. 

Glycine typical dietary intakes and safety

Glycine is in most protein-rich foods, including meat, eggs, dairy, soybeans, and lentils, and many of us consume about 2 to 3 g glycine each day, some more, some less. Since glycine makes up about a third of the amino acids in collagen, collagen-rich animal foods are especially good glycine sources. Familiar examples of glycine-rich foods include the skins of chicken, turkey, and fish, the ligaments around the bones of chicken and turkey legs, and stocks made from leftover bones and meat. 

A part of the normal human diet, glycine is perfectly safe at reasonable doses. Even massive amounts of glycine are surprisingly safe — one study had people with obsessive compulsive disorder gradually increase their dose to 60 g glycine a day in a 12-week-long study, with few adverse events (at such heroic doses, we’d expect some people to experience digestive discomfort though).