Collagen or Glycine?
August 20, 2021
Skin rejuvenation, recovery from injuries in athletes, reduction of pain and prevention
of diseases that affect the joints, tendons, ligaments and bones - especially with aging, etc...
Collagen consumption has been extended as a dietary supplement for several years [2,3,4,5]
There are mainly two types of collagen depending on the source:
- of mammals: it is the most common and cheapest. It is extracted from cows and pigs, mainly from the skin, but also of bones and cartilage.
- of fish: less common - more expensive. Mainly from the skin, but also from the bones and cartilage.
And there are mainly three types according to the commercial form:
- gelatin: in leaves or powder. It must be hydrated, added to a hot liquid (without boiling) and left to rest for a few hours before consuming
- soluble powder: soluble in hot or cold liquids
- capsules: taken as a normal pill
The beneficial effects of collagen are known and it is also known that the body
synthesizes collagen but does not synthesize enough of it:
"(...) the amount of glycine available from synthesis, about 3 g/day, together with that
available from the diet, in the range 1.5-3.0 g/day, may fall significantly short of the amount
needed for all metabolic uses, including collagen synthesis by about 10 g per day for a 70 kg human.
This result supports earlier suggestions in the literature that glycine is a semi-essential amino
acid and that it should be taken as a nutritional supplement to guarantee a healthy metabolism"
" Results of the recent studies indicate that endogenous synthesis of glycine, proline, and Hyp is inadequate for maximal growth, collagen production, or feed efficiency in pigs, chickens, and fish" .
It has also been shown that the intake of collagen accompanied by vitamin C significantly increases the collagen synthesis . So, comercial collagen usually includes vitamin C.
Glycine and Collagen
It has recently been discovered that the synthesis of collagen in the human body is limited by the
availability of a non-essential amino acid, glycine. The body synthesizes glycine, and also absorbs it
from food, but the fact that there is not enough available glycine limits the synthesis of collagen.
"(...) proline and lysine produce a great effect at low concentration, but this effect decreases from 0.6 mM and 0.85 mM, respectively, while the effect of glycine, although lesser at low concentration, exceeds the previous ones from ≈ 1.0 mM and, unlike the previous ones, this increase continues more persistently even up to higher concentrations. The greater effects produced by proline and lysine are within their physiological concentration in plasma, while the effect of glycine corresponds to a much higher range, demonstrating a severe generalized glycine deficiency for synthesizing collagen. The normal plasma concentration of glycine is 0.25-0.5 mM (Felig and Wahrent 1971; Javitt et al. 2001), which corresponds to a normal intake of 1.50-3.00 g/day (Gibson et al. 2002). According to the results reported by Javitt et al. (2001), an increase in the diet of 10 g/day could increase the plasmatic concentration between 3 and 4 times up to 1–2 mM, which means an increase about 200% in collagen synthesis (Fig. 5b)."
According to this study , increasing glycine in the diet may well be a strategy for helping cartilage regeneration by enhancing collagen synthesis, which could contribute to the treatment and prevention of osteoarthritis.
Typically, commercial preparations of collagen warn not to overpass the recomended doses; Recomended doses are about 10 g and usually include 25 to 80 mg of vitamin C and other special nutrients. Collagen or gelatin comercial products that are in powder format carry their 10 g dispenser. When we buy collagen pills, usually we are indicated the daily number of pills. Pills are usually 1 or 1.5 g tablets, so to reach 10 g of collagen you need to take 6 to 10 a day, depending on the product.
However, taking a supplement of 10 g of collagen a day means taking a supplement of 2 g of glycine a day, as well as intaking the rest of the collagen proteins, as well as added vitamin C and other nutrients, such as hyaluronic acid or Magnesium, depending of the producte formula.
Why it is recomended not to overpass the 10 g usual doses?
Is it about preventing excessive intake of glycine? No
No RDA, UL or CDRR has been defined for glycine, as it is currently considered sufficient in the average diet of the apparently healthy population and at the same time is not considered a risk factor for toxicity or chronic disease.
However, in addition to the RDAs-type recommendations, which define the minimum recommended intake
of some nutrients, there are also recommendations on the proportion of protein in the diet, in relation
to carbohydrates and lipids, measured in terms of energy:
For each 10 g of collagen we intake, protein % increases more than 1%
Also, UL limits are defined for vitamin C (2000mg) and Mg (350 mg, if Mg as supplement)
So, warning to not overpass the recomended doses is not due to glycine.
It is clear, then, that consuming a significant amount of protein daily in the form of collagen just because it accompanies the amino acid that really interests us, glycine, may not be necessary - at least for those people who already have a balanced intake of protein in their diet.
On the other hand, consuming this supplement daily, from a certain age, and probably teaming up with your partner, is expensive.
It is much cheaper and more efficient to consume 10 g of pure glycine directly, than 10 g of collagen (2 g of glycine plus 8 g of the other amino acids that we may not need) which is not enough to reach the target of a 10 g supplement of glycine.
Glycine is the simplest amino acid that exists. It can be artificially synthesized and can also be extracted by isolation from silk fiber, gelatin and sugar cane  as well as soy
"Glycine protects against shock caused by hemorrhage, endotoxin and sepsis, prevents ischemia/reperfusion and cold storage/reperfusion injury to a variety of tissues and organs including liver, kidney, heart, intestine and skeletal muscle, and diminishes liver and renal injury caused by hepatic and renal toxicants and drugs. Glycine also protects against peptidoglycan polysaccharide-induced arthritis and inhibits gastric secretion and protects the gastric mucosa a gainst chemically and stress-induced ulcers. Glycine appears to exert several protective effects, including antiinflammatory, immunomodulatory and direct cytoprotective actions. Glycine acts on inflammatory cells such as macrophages to suppress activation of transcription factors and the formation of free radicals and inflammatory cytokines. In the plasma membrane, glycine appears to activate a chloride channel that stabilizes or hyperpolarizes the plasma membrane potential. As a consequence, agonist-induced opening of L-type voltage-dependent calcium channels and the resulting increases in intracellular calcium ions are suppressed, which may account for the immunomodulatory and antiinflammatory effects of glycine. Lastly, glycine blocks the opening of relatively non-specific pores in the plasma membrane that occurs as the penultimate event leading to necrotic cell death."
 ^ 2016: Vitamin C-enriched gelatin supplementation before intermittent activity augments collagen synthesis https://pubmed.ncbi.nlm.nih.gov/ 27852613/
 ^ Jhawar, Nikita et al. “Oral collagen supplementation for skin aging: A fad or the future?.” Journal of cosmetic dermatology vol. 19,4 (2020): 910-912. doi:10.1111/jocd.13096
Barati, Meisam et al. “Collagen supplementation for skin health: A mechanistic systematic review.” Journal of cosmetic dermatology vol. 19,11 (2020): 2820-2829. doi:10.1111/jocd.13435
"The evidences obtained from these systematic reviews indicated that oral administration of intact or hydrolyzed collagen improves clinical manifestation of skin health. Almost all of the included studies reported the beneficial effects of collagen supplementation, and no inconsistencies have been seen in this regard between studies. "
García-Coronado, Juan Mario et al. “Effect of collagen supplementation on osteoarthritis symptoms:
a meta-analysis of randomized placebo-controlled trials.” International orthopaedics vol. 43,3 (2019):
"The results of this meta-analysis showed that collagen is effective in improving OA symptoms by the decrease of both total WOMAC index and VAS score. "
 ^ Kirmse, Marius et al. “Prolonged Collagen Peptide Supplementation and Resistance Exercise Training Affects Body Composition in Recreationally Active Men.” Nutrients vol. 11,5 1154. 23 May. 2019, doi:10.3390/nu11051154
 ^ National Center for Biotechnology Information (2021). PubChem Compound Summary for CID 750, Glycine. Retrieved August 18, 2021 from https://pubchem.ncbi.nlm.nih.gov/ compound/Glycine.
2018: High glycine concentration increases collagen synthesis by articular chondrocytes in vitro:
acute glycine deficiency could be an important cause of osteoarthritis
https://www.ncbi.nlm.nih.gov/ pmc/articles/ PMC6153947/
"(...) increasing glycine in the diet may well be a strategy for helping cartilage regeneration by enhancing collagen synthesis, which could contribute to the treatment and prevention of osteoarthritis."
Razak, Meerza Abdul et al. “Multifarious Beneficial Effect of Nonessential Amino Acid, Glycine: A Review.” Oxidative medicine and cellular longevity vol. 2017 (2017): 1716701. doi:10.1155/2017/1716701
"Glycine is very effective in improving the health and supports the growth and well-being of humans and animals. There are overwhelming reports supporting the role of supplementary glycine in prevention of many diseases and disorders including cancer. Dietary supplementation of proper dose of glycine is effectual in treating metabolic disorders in patients with cardiovascular diseases, several inflammatory diseases, obesity, cancers, and diabetes. Glycine also has the property to enhance the quality of sleep and neurological functions"
 ^ Pérez-Torres, Israel et al. “Beneficial Effects of the Amino Acid Glycine.” Mini reviews in medicinal chemistry vol. 17,1 (2017): 15-32. doi:10.2174/1389557516666160609081602
 ^ Zhong, Zhi et al. “L-Glycine: a novel antiinflammatory, immunomodulatory, and cytoprotective agent.” Current opinion in clinical nutrition and metabolic care vol. 6,2 (2003): 229-40. doi:10.1097/00075197-200303000-00013
 ^ Matilla, B et al. “La glicina: un nutriente antioxidante protector celular” [Glycine: a cell-protecting anti-oxidant nutrient]. Nutricion hospitalaria vol. 17,1 (2002): 2-9.
 ^ Meléndez-Hevia, Enrique et al. “A weak link in metabolism: the metabolic capacity for glycine biosynthesis does not satisfy the need for collagen synthesis.” Journal of biosciences vol. 34,6 (2009): 853-72. doi:10.1007/s12038-009-0100-9
Li, Peng, and Guoyao Wu. “Roles of dietary glycine, proline, and hydroxyproline in collagen synthesis
and animal growth.” Amino acids vol. 50,1 (2018): 29-38. doi:10.1007/s00726-017-2490-6
"Glycine, proline, and hydroxyproline (Hyp) contribute to 57% of total amino acids (AAs) in collagen, which accounts for one-third of proteins in animals. As the most abundant protein in the body, collagen is essential to maintain the normal structure and strength of connective tissue, such as bones, skin, cartilage, and blood vessels. Mammals, birds, and fish can synthesize (glycine)"