Magnesium Glycinate & Glycine

This white paper was prepared for Natural Calm by Dr. Alison Smith to evaluate the benefits of magnesium glycinate and glycine as an amino acid. There are many marketing claims around glycine, however, we wanted to know the facts about how glycine works in the body.

Natural Calm products are primarily magnesium citrate. We do incorporate magnesium glycinate together with magnesium citrate in some of the speciality products, including new Calmful Sleep.

Learn more about the amino acid, glycine, and how it works in magnesium glycinate.

Magnesium Glycinate and the Amino Acid, Glycine: Absorbability and Bioavailability

By Alison Smith Ph.D., Neuroscience

Which magnesium salt is most effective, in terms of absorbability and bioavailability? 

Research indicates that organic magnesium salts are more absorbable and bioavailable than inorganic salts ^1,2. 

Organic magnesium salts are created in a laboratory by combining an inorganic magnesium salt, derived from earth or rock sources, with either an acid or an amino acid. 

Magnesium salts combined with amino acids are referred to as amino acid chelates.

Magnesium glycinate (also known as magnesium bisglycinate or magnesium diglycinate) is one such organic magnesium salt, or amino acid chelate, that is created by combining inorganic magnesium with an amino acid called glycine.

This white paper contains two parts. Part one explores the importance of glycine for human health, and part two investigates the absorbability and bioavailability of magnesium glycinate supplements.

Part I: What is Glycine?

Amino acids are the basic building blocks of proteins, and they are essential not only for a healthy body but for life itself. We simply could not exist without them––they ensure our survival and play an integral role in all cellular processes. 

Scientists have discovered over 500 different amino acids in nature; however, the human body only requires twenty of them for human cellular function ³. These twenty amino acids are referred to as the standard amino acids ⁴.

The human body can naturally produce half of the standard amino acids––the other half, called the essential amino acids, must be acquired through the diet. 

Glycine is classified as a non-essential amino acid since the body naturally produces it; however, research shows that the amount of glycine produced by the body is not sufficient enough to keep up with metabolic demands ⁵; therefore, oral supplementation or eating foods rich in glycine might be warranted.

Glycine is the smallest amino acid, so small that it can squeeze through the tiniest spaces ⁴. It plays a major role in collagen and elastin formation ⁶, as well as bile acid function. 

Interestingly, it also acts as a neurotransmitter in the central nervous system ⁷.  A chronic glycine deficiency can result in impairment of growth, immune and nervous system function, and nutrient metabolism ⁸.

Glycine: Implications for Health and Nutrition

Of the total amino acid content in the human body, 11.5% of it is glycine. 

This amino acid plays a pivotal role in nutrition and metabolism, and for that reason, we require approximately 2 grams of glycine produced by the body or acquired through the diet each day. 

80% of the total glycine in the body is used for protein synthesis, and without it, cellular function would suffer ⁹. 

The following is a list of health conditions in which glycine plays a critical role:

Obesity and Type II Diabetes: 

There is evidence that plasma concentration of glycine is reduced in obese and type II diabetic patients ¹⁰. 

Oral glycine supplementation may be an effective treatment since it can reduce free fatty acids and triglycerides in the blood and fat cell size within intra-abdominal fat of obese subjects ¹¹.

Inflammation: 

Glycine is anti-inflammatory and immunomodulatory ¹². It reduces inflammatory reactions by encouraging an influx of chloride into the cell membrane thus hyperpolarizing the cell, decreasing calcium entry, thus making the cell less active overall. 

Glycine also reduces the production of proinflammatory cytokines and the expression of adhesion molecules in blood vessels ¹³, and enhances the activity of macrophages and leukocytes––immune cells that help to clean up injured or infected tissue ¹⁴. 

All of these effects have the potential to reduce atherosclerosis in cardiac patients ¹⁵.

Sleep: 

Two separate double-blind studies showed that the administration of 3 grams of glycine, before bedtime, improved quality of sleep, the feeling of fatigue the next day, sleep satisfaction, and time to sleep onset ^16,17. 

No adverse side effects were observed even when subjects ingested up to 9 to 31 grams of glycine per day ^18,19.

Nervous System Function: 

Glycine and GABA (gamma-Aminobutyric acid) are the main inhibitory neurotransmitters of the central nervous system. They both activate receptors in the brain and spinal cord that allow an influx of chloride into central nervous system cells––chloride inhibits the cell thus reducing cellular activation ²⁰.  

Inhibition is an imperative process in the central nervous system; without it, normal behavioural and motor function would be impossible because inhibition allows precise movements, thoughts, and attention, and the ability to stop or change a neurological response. 

Defects in inhibition result in psychiatric disorders like ADHD, obsessive-compulsive disorder (OCD), and Tourette’s syndrome ²¹. There is evidence that glycine supplementation may reduce OCD ²². 

Glycine has also been shown to improve auditory nerve function in diabetic patients by reducing nerve damage imposed by excessive sugar in the bloodstream ²³.

Oxidative Stress: 

Through aerobic metabolism or some pathological processes, the body naturally produces oxidants: harmful substances like free radicals, hydrogen peroxide, and hydroxyl radicals that damage healthy tissues, protein, and DNA––a destructive process referred to as oxidative stress ²⁴. 

A cell’s ability to defend itself against oxidative stress depends on several antioxidant defence mechanisms including the production of glutathione: a tripeptide synthesized from the amino acids glycine, glutamate, and cysteine; it counteracts the activity of oxidants and reduces oxidative stress ^25,26. 

Two studies by Sekhar et al. ^25,27 report that both diabetic and elderly patients have glutathione deficiency and supplementation with glycine and cysteine restores glutathione levels, which in turn reduces oxidative stress, diabetic symptoms, and aging. 

Glycine supplementation also reduces oxidative stress and blood pressure in patients with metabolic syndrome and might benefit patients with vascular disease or atherosclerosis ^15,28.

Stroke: 

Following an ischemic stroke, it is incredibly important to receive treatment as soon as possible––the administration of medication to break down the blood clot in the brain before 4.5 hours post-stroke is ideal ²⁹. 

There is also preliminary evidence that 1-2 grams of sublingual glycine started within 6-hours post-stroke, and given for 5-days, has neuroprotective effects in ischemic stroke patients: it reduces mortality, the time period of neurological deficits, and the imbalance between excitatory and inhibitory neurotransmitters within the brain ³⁰.

Muscle: 

Research shows that supplemental glycine helps to protect muscle from certain wasting conditions such as cancer cachexia––muscle and fat wasting due to cancer ^31,32, sepsis, or reduced caloric intake ³³.

Cancer: 

Glycine supplementation has anticancer properties. Evidence shows glycine to inhibit hepatic (liver) and B16 melanoma (skin) cancer cell proliferation and angiogenesis. 

In the liver, a type of macrophage called Kupffer cells protect the liver against pathogens and toxins; however, in doing so, they produce oxidants––harmful substances that damage liver cells and cause cancer. Glycine supplementation is reported to block oxidant production by Kupffer cells, which in turn reduces liver cancer cell production ⁹. 

Glycine also blocks blood vessel formation (angiogenesis) in B16 skin cancer (melanoma) tumours, reducing their size by upwards of 65% ^9,34.

Connective Tissue Integrity: 

Glycine is a precursor of collagen production: collagen is an important connective tissue component of skin, tendon, and cartilage; it provides function and structure to the body. 

Being the smallest amino acid, glycine fits between the tight junctions between larger amino acids that help to form collagen proteins. Glycine is also a flexible amino acid, and it gives collagen its pliability and elasticity ⁹.

Liver Toxicity: 

Glycine plays a protective role against alcohol-induced liver toxicity by shielding liver cell membrane structure from the damaging effects of oxidative stress produced by alcohol in the liver ³⁵. 

By slowing stomach emptying of alcohol and reducing the by-products of alcohol like acetaldehyde (a type of oxidant), glycine can reduce blood alcohol level and the damaging effects of alcohol ⁹.

Part II: The Effectiveness of Magnesium Glycinate Supplements

With the vast array of magnesium salts available in capsule, liquid, or powder form, consumers can be left feeling confused by all the choices. Which magnesium supplement should they choose? Which is the most effective?

Magnesium glycinate is a popular organic magnesium salt available as a supplement; however, there is very little research on its effectiveness in the human body in terms of absorbability and bioavailability.

Here is what the current research can tell us:

Magnesium Glycinate: Absorption and Bioavailability

Organic magnesium salts, like magnesium glycinate, are created in a laboratory by combining an inorganic magnesium salt with either an acid or an amino acid (a protein). 

For example, magnesium citrate is created by combining an inorganic magnesium with citric acid, and magnesium glycinate is created by combining an
inorganic magnesium with the amino acid, glycine.

Overall, organic magnesium salts are demonstrably more soluble, absorbable, and bioavailable than inorganic magnesium salts.

Magnesium glycinate is a type of organic magnesium salt; therefore, it is considered as a highly absorbable and bioavailable form of magnesium ^1,2. 

In a review article by Coudray et al. ², magnesium glycinate is listed as a ‘good’ source of magnesium since it is soluble, absorbable, and bioavailable. Schuette et al. ³⁶ report magnesium diglycinate as an absorbable form of magnesium for some patients with intestinal resection.

Magnesium Glycinate in the Treatment of Health Conditions

More research is required to understand how magnesium glycinate helps in the treatment of various health conditions. 

The current research demonstrates that 300 mg of magnesium bisglycinate, given daily, significantly reduces the frequency and intensity of pregnancy-induced leg cramps ³⁷. 

The administration of 125-300 mg of magnesium glycinate or taurinate is reported to help in rapid recovery from major depression ³⁸.

Intestinal Absorption of Amino Acid Chelates

How the intestine absorbs magnesium glycinate is not entirely understood. The predominant absorption mechanism described in the literature involves a magnesium salt breaking apart in the gastric juices of the stomach; this process releases ionic magnesium, ready for absorption through the intestine. 

The ionic magnesium then travels to the distal intestine where it is absorbed through passive diffusion or via facilitated diffusion through ion channels ^39,40.

There is a theory that amino acid chelates, including magnesium glycinate, are absorbed by a different mechanism; however, it has not been confirmed. 

The theory states that amino acid chelates remain intact despite exposure to gastric juices in the stomach. The complex, instead, enters the intestine whole and is absorbed by peptide channels in the intestinal wall, opposed to passive diffusion or facilitated diffusion through ion channels ⁴¹. 

Again, this theory has not been proven and more research is required.

For more information on the science behind magnesium absorption and how magnesium citrate compares to magnesium glycinate, see the results of a 2017 clinical trial currently under peer review for publication. 

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