Collagen is the most abundant protein in the body and a major component of connective tissue such as bone, skin, muscles, tendons and cartilage¹. Collagen is part of the connective tissue that lies directly beneath the innermost cell layer of the gut wall (the intestinal epithelium). If the gut barrier is damaged (“leaky gut”), toxins that come from gut bacteria can enter the bloodstream².
Collagen and the intestinal barrier
Collagen and the seals between gut cells
Research has examined collagen hydrolysate in relation to the tightness of the intestinal wall, recorded via the expression of tight cell contacts. In lab tests on gut cells, one of the things measured was how much of two linking proteins (ZO-1 and occludin) was present – proteins that seal the gaps between the cells.
Increase in ZO-1 and occludin
The formation and distribution of the tight junction proteins ZO-1 and occludin are central to the integrity of the epithelium. In the lab, gut cells were first treated with collagen peptides from pollock skin and then exposed to an inflammatory messenger (TNF-α). Afterwards, two proteins that seal the gaps between the cells (ZO-1 and occludin) were broken down less than without the peptides³. When these proteins break down, the cell layer becomes leakier; whether the same happens in the human gut is something a cell experiment cannot show.
Inhibition of MLCK activation
Myosin light chain kinase (MLCK) is an enzyme involved in how tightly the junctions between intestinal cells are held together. In these lab experiments, the cells also produced less of an enzyme that can loosen the connections between gut cells (MLCK) after the collagen peptides were added. The enzyme was also less active³. This, too, was measured in cells in the lab, not in the body.
Gut-wall cells in animal studies
The same measurements were also looked at in mice with artificially induced bowel inflammation (colitis). Inflammation markers, which indicate how strong an inflammation is, were measured as well.
In vivo models for barrier regeneration
In one study, mice with an artificially induced bowel inflammation (colitis) were given collagen peptides from the innards of abalone, a sea snail, by mouth. They lost less weight, and their colon shortened less⁴. Both are standard measures of how severe this kind of inflammation is in mice: sick animals lose weight, and the inflamed colon shrinks.
Reduction of pro-inflammatory markers
In this animal study, three inflammatory messengers were lower in the blood (TNF-α, IL-1β and IL-6)⁴. The body uses these signalling substances to drive inflammation, and lower levels are read as a sign of weaker inflammation. This was measured in mice – the study does not show whether the same holds for people.
Collagen and the microbiome
The complex ecosystem in your gut, the microbiome, is also being studied in connection with collagen peptides.
Collagen peptides and gut bacteria
Gut bacteria make short-chain fatty acids such as butyric, propionic and acetic acid – mainly from fibre, but partly also from protein fragments (peptides). This is general knowledge about gut bacteria, not yet a finding about collagen; what has been measured for collagen follows below.
Nitrogen supply for SCFA producers
Two gut bacteria, Faecalibacterium prausnitzii and Akkermansia muciniphila, produce a lot of short-chain fatty acids.
Increase in SCFA concentration
In mice with bowel inflammation (colitis), the amount of acetic, propionic and butyric acid in the gut rose after they were given collagen hydrolysate from tilapia skin⁵. Gut bacteria make these short-chain fatty acids from food residues. The cells of the gut lining use them as a source of energy, so higher levels are usually read as a favourable sign. The mouse study does not show whether the same is true in people. Butyrate is a short-chain fatty acid that serves as an energy source for the epithelial cells of the intestinal wall.
Shift in the composition of the microbiota
The composition of the microbiome has also been examined under collagen supplementation. Mice with artificially induced bowel inflammation (colitis) were given collagen peptides from cod skin. In these mice, bacteria that are often more common during bowel inflammation were rarer (Proteobacteria, including Pseudomonas). A group from a family with many butyric-acid producers was more common (Lachnospiraceae NK4A136)⁶. What such shifts mean for health is not yet settled even in people – and this was a mouse study.
Reduction of dysbiosis
These are animal data.
Data in humans
Digestive wellbeing under collagen hydrolysate has also been examined in people – more on that below.
The animal collagen products from the Kollagen Institut contain hydrolysed collagen peptides. The ingredient list shows exactly what each product contains.
Inflammatory markers and tissue repair: what has been studied
Beyond the intestinal barrier, collagen peptides have also been examined in relation to inflammatory markers and the intestinal mucosa. The available data come mainly from cell cultures and animal models. Below you will find a detailed breakdown of the mechanisms.
Reduction of pro-inflammatory messenger substances
Inhibition of TNF-α, IL-1β and IL-6
TNF-α, IL-1β and IL-6 are signalling proteins that cell-culture work uses as readouts. In the lab, immune cells were provoked with a component of bacteria, much as in an infection. When peptides from beef bone gelatin were added, the cells released fewer inflammatory messengers (IL-6 and TNF-α)⁷. The body uses these signalling substances to set off inflammation. Less of them is read as a sign of a weaker inflammatory response – here, though, only in cells in a lab dish, not in the body.
Reduction of NO production
Nitric oxide (NO) is formed by the enzyme iNOS. In these experiments the cells also produced less nitric oxide (NO)⁷. Immune cells release more of this gas during inflammation; less of it fits a weaker inflammatory response – again measured only in cells in the lab.
Effect of porcine bone collagen peptides
In LPS-stimulated cell cultures, a lower secretion of IL-6 and TNF-α was recorded for porcine bone collagen peptides. These are laboratory readouts in isolated cells.
The gut lining in animal models
Rapid epithelial renewal in colitis models
Mice with artificially induced bowel inflammation were given the peptides through a stomach tube. They lost less weight, had less blood in their stool and had lower blood levels of the inflammatory messengers TNF-α and IL-6⁸. These are standard signs that the inflammation was milder in the animals; the mouse study does not show whether people respond in a similar way.
Role of native collagen matrix
In the body, collagen in its native, fibrillar form is part of the tissue matrix that is rebuilt during wound healing. This describes the structural protein already present in tissue, not an effect of an orally taken supplement.
Collagen-integrin interaction
Integrins α1β1 are receptors on epithelial cells to which collagen binds. This binding is one of the mechanisms researchers examine in animal models of the intestinal mucosa.
Limits and possible counter-effects
Aggravation of colitis symptoms
In mice with artificially induced bowel inflammation, collagen peptides from marine animals made the inflammation worse. In the lab, they pushed immune cells (macrophages) towards a pro-inflammatory form (M1)⁸. These were experiments in mice and cells; they do not show whether the same happens in people.
Different effects depending on the source
Not all collagen types are studied in the same way: type VI collagen, for example, is being researched in mice in connection with lymph vessels and inflammatory cells in the colon.
The Multi Collagen capsules contain five types of collagen. Handy if you want several collagen types in one product.
Bioavailability and absorption
Hydrolyse zu bioverfügbaren Peptiden
A lab model recreated digestion in the stomach and small intestine; collagen hydrolysates broke down into an even wider range of peptides. In the researchers' assessment, some of these are not absorbed into the blood at all but reach the colon, where bacteria ferment them⁹. What this means for you: probably not all of the collagen you take ends up in the blood. How large that share is, and what it does in the colon, the lab model does not show.
Influence of gastric pH and enzymes
The body can't absorb collagen whole; it first has to be broken down into peptides, which then pass from the gut into the blood¹⁰.
Clinical effects on digestive symptoms
Reduction of flatulence and bloating
In a study without a comparison group, in which everyone knew what they were taking, healthy women took 20 g of collagen peptides daily for 8 weeks. Of the 14 women who completed the study, 13 reported fewer digestive symptoms, including bloating¹¹. Because there was no comparison group, it is impossible to say whether this was due to the peptides; most of the 40 participants also did not complete the study.
Nutrient absorption and the gut wall
Vitamins and minerals are absorbed through the innermost cell layer of the gut wall; collagen is a building block of the connective tissue beneath it.
Application in practice
If you want to take collagen, the amount and how you take it matter as well as which product you choose. Below you will find detailed recommendations, divided into easy-to-follow steps, with references to studies and optimal times.
Recommended dosage
The amounts used in gut-barrier studies are sometimes well above a usual daily serving. The Kollagen Institut daily serving is 2.5–5 g; stick to that amount.
Lowest amount used in studies
A review of several skin studies reports that they used 2.5 to 10 g of collagen hydrolysate a day¹². These studies looked at the skin, not the gut.
For vegans, an alternative to animal collagen is the Vegan Amino Acid Complex. It contains no collagen, but a mixture of plant-based amino acids.
Highest amount used in studies
The study in healthy women mentioned above used 20 g of collagen peptides a day.
Duration of use
Intake in these studies lasted between 8 and 24 weeks¹².
Recommended intake
Timing and what you take collagen with can affect how well the peptides are absorbed.
On an empty stomach
There is no set time for taking it; you can, for example, take your powder in the morning before breakfast.
What to mix it with
You can stir your collagen powder into water, juice or a smoothie, for example.
Evening intake time
Alternatively, you can take collagen in the evening.
Selection and combination
Hydrolyzed collagen with low molecular weight
When buying, look for information such as “hydrolyzed collagen” or “molecular weight < 5 kDa” if small peptide size matters to you.
Supplementary nutrients
Some people combine collagen with zinc, copper or pro- and prebiotics.