Take any collagen molecule from the human body—skin, tendon, cartilage, bone—and read its sequence: every three amino acids, one glycine. Without exception, across more than a thousand positions. This isn't a biochemist's curiosity: it's a geometric constraint, and it has a consequence that researchers spent fifteen years exploring.
This guide follows this idea in the order of the studies: why glycine is imposed every three residues, the model that calculates the body doesn't produce enough of it, the laboratory experiment showing collagen synthesis rising when more is added, then the two human trials, conducted with gelatin and hydrolyzed collagen enriched with vitamin C. At each step, what the study shows and what it doesn't.
One-third glycine, by geometry. The collagen triple helix leaves room, every three residues, only for the smallest amino acid. A calculated deficit. A metabolic model published in the Journal of Biosciences compares all known flows: approximately 3 g per day produced, 1.5 to 3 g from diet, and a shortfall of approximately 10 g per day to cover all uses including collagen. A mechanism demonstrated in the laboratory. Chondrocytes cultured with more glycine produce 60 to 75 % more type II collagen.
Two human trials, conducted with gelatin or hydrolyzed collagen enriched with vitamin C: 15 g one hour before exercise doubles a blood marker of collagen synthesis in eight men; 20 g per day for three weeks returns explosive strength to baseline levels in 50 athletes. Small trials, on markers or athletes. Vitamin C is the indispensable cofactor for the entire chain.
Why one amino acid in three
Collagen is a triple helix : three chains wound around each other, so tightly that with each turn, one of the three passes through the center of the whole. At this spot, there is room for no side chain. Only one amino acid has none: glycine, whose radical is a simple hydrogen atom. The collagen sequence is therefore a strict repetition, glycine, X, Y, where X and Y are most often proline and hydroxyproline, which stiffen the chain. Over more than a thousand positions, not a single exception: the slightest substitution of glycine distorts the helix, and this is precisely what happens in genetic collagen diseases.
A third of the most abundant protein in the body, approximately 30% of all our proteins, is therefore made of a single amino acid. This observation prompted the following question: where does all this glycine come from, and do we have enough?
The model that calculates a deficit
The capacity to synthesize glycine from serine is constrained by the stoichiometry of the glycine hydroxymethyltransferase reaction, which limits the amount of glycine produced to not exceed that of one-carbon units produced. This constraint predicts a lack of available glycine in the absence of adequate compensatory processes. We tested this prediction by comparing all reported flows of glycine production and consumption in an adult human. Detailed evaluation of all possible sources shows that synthesis from serine represents more than 85 percent of the total, and that the amount available through synthesis, approximately 3 g per day, added to that from diet, on the order of 1.5 to 3 g per day, may be significantly lower than the amount needed for all metabolic uses, including collagen synthesis, of approximately 10 g per day for a 70 kg human. This result supports earlier suggestions that glycine is a semi-essential amino acid.
Meléndez-Hevia E, De Paz-Lugo P, Cornish-Bowden A, Cárdenas ML. J Biosci 2009;34(6):853-872. DOI: 10.1007/s12038-009-0100-9
This work must be read for what it is: a rigorous flow calculation, which adds up all known sources and uses of glycine and finds the account doesn't balance. It is not a clinical trial, and its authors do not claim it is. But it poses a precise and testable hypothesis, that glycine is the limiting factor for collagen synthesis, and it is this hypothesis that the same team went on to test in the laboratory nine years later.
Laboratory experiment
Bovine articular chondrocytes were cultured under a wide range of concentrations of glycine, proline, and lysine, and type II collagen was measured every 48 hours for 15 days. Increasing concentrations of proline and lysine stimulate type II collagen synthesis at low concentration, but these effects decline before 1.0 millimole per liter. Increasing glycine from 1.0 millimole per liter exceeds these effects and continues more persistently, from 60 to 75 percent. With the effects of proline and lysine falling within the physiological range while that of glycine corresponds to a much higher range, these results demonstrate a severe glycine deficit for collagen synthesis. Increasing dietary glycine could be a strategy to help cartilage regeneration.
de Paz-Lugo P, Lupiáñez JA, Meléndez-Hevia E. Amino Acids 2018;50(10):1357-1365. DOI: 10.1007/s00726-018-2611-x
It shows a mechanism : cells that produce cartilage produce significantly more when given more glycine, and no more when given more proline or lysine beyond a threshold. This is consistent with the 2009 model, and it's what we expect if glycine is the limiting factor. It does not show that ingesting glycine regenerates human cartilage: these are bovine cells, in a dish, at chosen concentrations. Moving to humans requires trials, and there are some, but not with glycine alone.
Human trials
Eight healthy men consumed 5 or 15 g of gelatin enriched with vitamin C, or a placebo. After the first drink, blood was drawn every 30 minutes to measure amino acids. One hour after the supplement, subjects performed six minutes of rope jumping to stimulate collagen synthesis, three times daily for three days. Gelatin increased circulating glycine, proline, hydroxyproline, and hydroxylysine, with a peak one hour after intake. Ligaments reconstituted and treated for six days with serum collected one hour after 5 or 15 g of gelatin showed increased collagen content and improved mechanics. Subjects who took 15 g of gelatin one hour before exercise showed a doubling of type I collagen amino-terminal propeptide in the blood, indicating increased synthesis. These data suggest that adding gelatin to an intermittent exercise program improves collagen synthesis and may play a role in injury prevention and tissue repair.
Shaw G, Lee-Barthel A, Ross ML, Wang B, Baar K. Am J Clin Nutr 2017;105(1):136-143. DOI: 10.3945/ajcn.116.138594
This is the trial that brought gelatin and collagen into sports nutrition, and it is instructive both in its design and its results. Keith Baar's team, at the Australian Institute of Sport and University of California, Davis, measured three things: collagen amino acids rise in the blood and peak one hour after intake; this blood causes more collagen to be produced in cultured ligaments; and in the participants themselves, 15 g taken one hour before a brief exercise double a blood marker of synthesis. Eight people, three days, one marker: it's small, and this is what led to the next trial.
Fifty male athletes aged 18 to 25 were randomly assigned to either 20 g of hydrolyzed collagen with 50 mg of vitamin C or a placebo of 20 g of maltodextrin, ingested daily 60 minutes before training, for three weeks of the same strength training program. Over the three weeks, the maximum rate of force development in the collagen group returned to its baseline level, while that in the placebo group remained reduced. Both groups had declined at the second test; only the treated group had recovered by the third. Power and rate of force development in the eccentric phase of jumping were improved. No difference was observed in maximum strength.
Lis DM, Jordan M, Lipuma T, Smith T, Schaal K, Baar K. Int J Sport Nutr Exerc Metab 2022;32(2):65-73. DOI: 10.1123/ijsnem.2020-0313
The second trial moves from marker to function: rate of force development, which depends on tendon stiffness, is preserved under collagen and vitamin C during an intensive program, and not under placebo. No gain in maximum strength, which depends on muscle and not tendon. The result is consistent with the hypothesis of better-supported connective tissue, and it remains a three-week trial in young athletes.
Both trials include vitamin C, and this is not a detail. Collagen synthesis proceeds through thehydroxylation of proline and lysine, the step that stabilizes the triple helix, and this step requires vitamin C. Without it, chains form but don't hold: this is the mechanism of scurvy. Providing glycine or collagen without vitamin C is like delivering bricks without mortar. Our two collagens contain it, 80 and 120 mg per dose.
Glycine alone or collagen
| Question | What the studies show | Nature of the evidence |
|---|---|---|
| Is glycine the limiting factor for collagen? | Calculated deficit of approximately 10 g per day; type II collagen synthesis increased by 60 to 75% in vitro | Metabolic model and cellular study |
| Does increased intake increase synthesis in humans? | Marker doubled with 15 g gelatin and vitamin C before exercise; explosive force preserved with 20 g collagen and vitamin C | Two randomized trials, 8 and 50 participants, with collagen and not glycine alone |
| Are there trials with glycine alone? | Yes, on sleep, at 3 g before bedtime | Randomized trials, detailed in our glycine guide |
| How much glycine in a dose of collagen? | Approximately one third of the weight: around 3 g per 10 g, 1.5 g per 5 g | Collagen composition, order of magnitude |
The reasoning of the model says that glycine is lacking; the trials say that providing hydrolyzed collagen, that is glycine with the proline and hydroxyproline that accompany it in the sequence, and vitamin C, increases a synthesis marker and preserves a function. The two do not contradict each other: they answer different questions. For collagen synthesis, it is collagen and vitamin C that have the trial data; for sleep, it is glycine alone. Our glycine guide and our marine collagen guide detail each their own area.
10 g of type 1 marine collagen per dose, that is around 3 g of glycine with the proline and hydroxyproline of the sequence, and 80 mg of vitamin C, the cofactor of hydroxylation. In powder form, in a beverage, one hour before exercise if you follow the trial protocol. Thirty days per jar.
See Marine Collagen PowderThe cited trials focus on synthesis markers and explosive strength in athletes, not on joint disease. Our Novagen, 5 g of tripeptides and 120 mg of vitamin C, is the other format.
Frequently asked questions
Why does collagen contain so much glycine?
By geometry. Collagen is a triple helix of three chains wound very tightly, and every three amino acids, the chain passes through the center of the helix where there is room only for the smallest amino acid that exists: glycine, whose side chain is a simple hydrogen atom. The collagen sequence is therefore a repetition of glycine, X, Y, where X and Y are often proline and hydroxyproline. One amino acid in three is glycine, approximately one third of the protein, by structural necessity and not by chance.
Does the body make enough glycine?
A metabolic model published in the Journal of Biosciences answers no. Its authors compared all known flows of production and consumption of glycine in a 70 kg adult: synthesis from serine, which accounts for more than 85% of production, provides approximately 3 g per day, diet provides 1.5 to 3 g, and all metabolic uses, including collagen synthesis, would require approximately 10 g more. They conclude that glycine is a semi-essential amino acid. This is a theoretical flux calculation, solid in its method, but not a clinical trial; it poses a hypothesis that other studies subsequently tested.
Does glycine increase collagen synthesis?
In the laboratory, yes, and markedly. The same team cultured bovine articular chondrocytes, the cells that produce cartilage, with increasing concentrations of glycine, proline and lysine, and measured the type II collagen produced over fifteen days. Proline and lysine increase synthesis at low concentration then plateau; glycine, from 1 millimole per liter, increases it by 60 to 75%, persistently. The authors see this as proof of severe glycine deficiency for collagen synthesis. This is an in vitro study on animal cells: it shows a mechanism, not an effect in humans.
Are there trials in humans?
Yes, with gelatin or hydrolyzed collagen, which provide glycine with proline and hydroxyproline. The reference trial is that of the Australian Institute of Sport and the University of California at Davis, published in theAmerican Journal of Clinical Nutrition : eight men, in a crossover double-blind design, took 5 or 15 g of gelatin enriched with vitamin C or a placebo one hour before six minutes of jump rope, three times a day for three days. Blood glycine, proline, hydroxyproline and hydroxylysine increased, with a peak at one hour; reconstituted ligaments treated with participants' serum produced more collagen; and 15 g doubled type I collagen propeptide, a blood marker of synthesis. A second trial, in 50 athletes over three weeks, showed that 20 g of hydrolyzed collagen and 50 mg of vitamin C before training brought the rate of strength development back to its baseline level, whereas the placebo group remained below it.
Why is vitamin C associated in these trials?
Because collagen synthesis goes through a step that vitamin C makes possible: the hydroxylation of proline and lysine, which stabilizes the triple helix. Without vitamin C, the chains form but do not hold, which is the mechanism of scurvy. Trials on collagen synthesis therefore systematically combine vitamin C with gelatin or hydrolyzed collagen, and our two collagens contain it, 80 and 120 mg per dose.
Glycine alone or collagen: which to choose?
Human trials on collagen synthesis were conducted with gelatin or hydrolyzed collagen, not with glycine alone: it is therefore collagen, with vitamin C, that has the data for this specific question. Glycine alone has its own data, particularly on sleep, detailed in our guide. The reasoning of the metabolic model says that the limiting factor is glycine; the trials say that providing it in the form of hydrolyzed collagen, with proline and hydroxyproline, increases a synthesis marker. The two do not contradict each other; they answer different questions.
How much glycine in a dose of collagen?
Approximately one third of the weight. A dose of 10 g of marine collagen provides around 3 g of glycine, a dose of 5 g approximately 1.5 g, with the proline and hydroxyproline that accompany it in the collagen sequence. These are orders of magnitude based on collagen composition, not values measured on our products.
What to know about glycine and collagen?
That collagen is one third glycine by geometric necessity. That a metabolic model calculates a deficit of approximately 10 g of glycine per day to synthesize it, and that an in vitro study shows increased synthesis of 60 to 75% at high concentration. That human trials, conducted with gelatin or hydrolyzed collagen enriched with vitamin C before exercise, show a doubled synthesis marker and recovery of explosive strength. That these trials are small and focus on markers or athletes. And that vitamin C is the essential cofactor for the entire chain.
Sources
The studies cited below were identified via PubMed.
- Meléndez-Hevia E, De Paz-Lugo P, Cornish-Bowden A, Cárdenas ML. A weak link in metabolism: the biosynthetic capacity for glycine does not meet the requirement for collagen synthesis. Journal of Biosciences, 2009;34(6):853-872. DOI
- de Paz-Lugo P, Lupiáñez JA, Meléndez-Hevia E. High glycine concentration increases collagen synthesis by articular chondrocytes in vitro. Amino Acids, 2018;50(10):1357-1365. DOI
- Shaw G, Lee-Barthel A, Ross ML, Wang B, Baar K. Gelatin supplementation enriched with vitamin C before intermittent activity increases collagen synthesis. American Journal of Clinical Nutrition, 2017;105(1):136-143. DOI
- Lis DM, Jordan M, Lipuma T, Smith T, Schaal K, Baar K. Collagen and vitamin C supplementation increases the rate of lower limb force development. International Journal of Sport Nutrition and Exercise Metabolism, 2022;32(2):65-73. DOI
