Do Collagen Supplements Work?

Today, we explore the effect of collagen on the body, and we start with a story about collagen supplements.

Collagen supplements have become quite the trendy treatment for aging skin, available in an array of pills, powders, and products, from bars and gummies to collagen coffee and beer. Social media is said to be “inundated with paid ads marketing unsubstantiated claims.” What claims, if any, can be substantiated?

The word collagen comes from the Greek kola, meaning “gum,” and gen, meaning “producing.” Its gelling nature is exemplified by Jell-O gelatin (which is basically just cooked collagen).

It is our most abundant protein and the main structural component of most of the tissues in our body. For example, up to three quarters of our skin by weight may be pure collagen. There are actually dozens of different types, but they all share a characteristic triple helix configuration of coiled subunits. What happens when we eat it?

If someone would have asked for my educated guess about taking collagen before I took a deep dive for my book How Not to Age, I would have dismissed it as witch-doctory woo-woo. Eating skin for your face would seem to make as much sense as eating brains to make yourself smarter, or eyeballs to improve your vision. After all, when you eat proteins, they are broken down into their constituent amino acids, which are then rebuilt into any protein your body needs. And, of all proteins to eat, collagen is the only protein in our food supply that’s truly incomplete. That is, it’s missing an essential amino acid.

Other dietary proteins, including all plant proteins, contain all of the essential amino acids—in fact, that’s why they’re called essential, since animals like us can’t make them. Collagen, though, is missing the amino acid tryptophan. So, the only protein source that you couldn’t live on is Jell-O, since it effectively has a protein quality score of zero. But obviously that’s not all people eat; so, significant amounts of collagen could be incorporated into the diet without keeling over. But tryptophan is special. Randomizing people to even a single meal of a gelatin-based protein drink can lead to memory impairments within hours, due to “acute tryptophan depletion” (presumably due to a drop in the brain of serotonin, which is made from tryptophan, and doesn’t just regulate mood, but learning and memory as well). So, the idea of collagen supplements never made sense to me. But the proof is in the pudding (or rather, perhaps, the Jell-O). What, does the science say?

My assumption that collagen proteins would get completely broken down in the digestive tract was wrong. Feed people gelatin from pig skin or chicken feet, and little pieces of collagen particles can be found floating in their bloodstream within hours. Though no further tracking has been done in humans, in rodents, collagen fragments from gelatin consumption can end up in cartilage and skin. Now, biologically, there is no mechanism by which these fragments could be directly incorporated into new collagen, but there may be an indirect way collagen bits could boost collagen deposition––as appears to happen in rat skin. What about in people?

Some of the collagen studies lack control groups. I’m reminded of that vintage Star Trek episode Mudd’s Women, where Kirk successfully swaps out a youth-giving supplement for a placebo without the aliens noticing. Randomized controlled trials are scarce, but a systematic review and meta-analysis of the available data showed that, although outcomes were mixed, on average, there were beneficial effects for skin hydration, elasticity, and roughness. Despite some favorable results, much of the dermatology community has remained skeptical, suggesting the collagen supplement industry may just be flooding the zone with poor quality, biased studies.

The studies are often funded by collagen supplement manufacturers, and the overall quality of evidence is considered to be “limited, contradictory,” “not particularly robust… .” A 2022 review entitled “Myths and media in oral collagen supplementation for the skin, nails, and hair” in the Journal of Cosmetic Dermatology concluded that “Dermatologists should be aware of the unsubstantiated proclamations of collagen made by companies [which] surpass any evidence currently supported by the literature.” And, given the insufficient evidence, “collagen cannot be routinely recommended at this time.” Moreover, the evidence is considered to be “particularly unconvincing” when compared to methods more definitely shown to have a positive effect on skin collagen, such as sunscreen use, smoking cessation, and a healthy diet.

In our next story, we see if collagen can beat out a placebo for knee osteoarthritis.

Nearly a millennium ago, a medieval nun suggested eating gelatin to reduce joint pain. Unfortunately, when it was put to the test in a multicenter, randomized double-blind placebo-controlled trial, it didn’t work. A dozen years later, looking at knee and hip osteoarthritis, there was still no overall evidence for collagen supplements working better than placebo. However, the latest compilation of studies purported to show a benefit for improving osteoarthritis symptoms. In one symptom index, it appeared to help with stiffness, but not pain or disability. But an overall improvement in symptoms and a different index of pain were statistically significant.

If, however, you exclude the smallest study, whose authors were employees of a collagen company, all of the results lost clinical importance––meaning the overall effects were unnoticeably small. In fact, every single one was funded by collagen companies, or directly run by company employees.

Another thing you’ll notice about these data is that with this one exception, the smaller the study, the larger the effect. This pattern is a common sign of publication bias—the tendency to do a whole bunch of small trials, but publish only the ones that work to your advantage, and secretly shelve the rest. Coupled with all of the conflicts of interest, concerns have been raised that additional small studies may have been conducted but conveniently disappeared. And then, other fishy findings are that smaller doses appeared to have larger effects, as did using it for a shorter amount of time. Okay, but the last study was published in 2016. What’s happened since then?

A comprehensive systematic review published in 2022 was surprised to note that the last study done on collagen supplements for rheumatoid arthritis was published more than a decade ago, and the last osteoarthritis study was still that 2016 one. Why? Well, one possible reason is the high incidence of adverse side effects reported in those taking collagen supplements. Or another reason may be that they simply don’t work very well.

I mean, if collagen company executives truly believed they were selling something that worked, why don’t they do more studies? If they thought collagen had a decent chance of working, they could make out like bandits. The fact that they haven’t sponsored such a trial suggests they’re not so confident it would actually show benefit.

One study has been published since 2016––the biggest yet, with more than 150 people. Funded by a collagen company, researchers found a significant drop in knee pain and a significant improvement in knee function among those randomized to collagen supplements. But, they also found a significant drop in knee pain and improvement in knee function in those randomized to the placebo, with no real difference between them. So, the fact that effectively a sugar pill worked as well as the collagen supplements suggests that collagen doesn’t work.

But that does raise another point. If you look at what was used for controls in the collagen studies, it was basically just sugar or sawdust. So, even if collagen was found to be helpful in some way, there is no proof that collagen has any effects beyond just being a source of amino acids, like any other protein. So, if any purported collagen effect is just a matter of increased amino acid availability, then why not just like have some extra hummus or something?

Finally today, we reveal which foods may be able to increase collagen deposition and prevent wrinkles.

As we age, the synthesis of collagen decreases by about 1 percent a year, which may contribute to the development of wrinkles. Though we don’t have evidence that collagen is superior than any other proteins for aging skin, those who do want to try it are advised to contact the manufacturers to clarify its source. Most collagen supplements don’t disclose this information, and for good reason. Terrestrial sources can include a witch’s brew of kangaroo and rat tails, duck feet, horse tendons, alligator bones, and frog skin. Aquatic sources are mainly from fish skins, bones, heads, scales, fins, and entrails.

Recommended questions for manufacturers include: “What measures were used to protect against contamination or adulteration? If sourced from fish, were low-mercury fish used? If sourced from cows, what steps were taken to ensure that no brain or nervous system matter was included, in order to prevent prion disease?” In the United States, collagen is exempt from FDA prohibitions against using risky tissues like brains—prohibitions in place to protect consumers against bovine spongiform encephalopathy, also known as mad cow disease.

So, for food safety, religious, ethical, or allergy-related reasons, there have been calls for non-animal alternatives. For example, 2 to 4 percent of the population is allergic to bovine collagen. To solve the mad cow conundrum, there have been calls to genetically engineer cattle without prions to “offer a safe source of collagen-based materials.” But why not just get plants to make it? A technique has been perfected to produce collagen from plants, but it has not yet reached commercial viability.

It’s hard to beat the cost of feet.

But, what about all of the vegan collagen products on the market? If you look closely, you’ll see the small print: vegan collagen builder or vegan collagen booster. It’s not actually collagen, since collagen is made by animals, but you’re an animal—you make collagen. So, they’re suggesting their supplements can boost production, but since it appears none of them have ever been put to the test, I assume it’s all a load of bunk. But, there are some foods and nutrients that have been investigated.

Researchers burned the butts of 20 women with a UV lamp before and after half of them ate three tablespoons of tomato paste each day for three months. And, there was a significant reduction in MMP-1 levels in the derrières of those who had been randomized to the tomatoes. (That’s a major collagen-eating enzyme that plays a key role in skin aging caused by the sun.) Butt biopsies also show that the amount of beta-carotene found in about one and a third cup of sweet potato can boost collagen production as much as four-fold within three months.

To test the effects of greens, Korean researchers randomized older women to the amount of chlorophyll found in a few tablespoons of cooked spinach a day. After three months, skin biopsies showed a significant increase in collagen production, accompanied by an increase in skin elasticity and a decrease of facial wrinkles. Unfortunately, this was just a before-and-after comparison to baseline study, with no control group. But there have been placebo-controlled randomized trials, and of kale no less.

Compared to placebo, there was a significant improvement in a noninvasive measure of skin collagen status after 10 months of being randomized to an extract of curly kale. The researchers concluded that “a healthy lifestyle including a diet rich in carotenoids is the best prevention strategy against premature skin aging.” That led to dermatology journal commentaries with titles like “Eat plenty of green leafy vegetables for protection from the pro-aging rays of the sun.”

But might it actually be more than that? Sulforaphane, the cruciferous compound in kale and broccoli, may be able to mobilize cellular defenses that protect skin against damage by UV radiation, as well as mitigate the premature skin aging induced by air pollution particulate matter––though this was on skin cells in a petri dish.

Soybean compounds can increase collagen deposition and prevent wrinkles in mice. But what about in people? Given improvements of skin aging seen with menopausal hormone therapy, but concerned about the side effects, researchers in Brazil tried giving phytohormones––plant hormones in the form of soy phytoestrogens. Twenty-nine postmenopausal women were given the amount in four servings a day of soy foods for six months. Unfortunately, there was no control group, but they did take skin biopsies before and after, and found a significant improvement in skin thickness, along with increased collagen content and elastic fibers. The biopsies of 25 out of 29 women showed an increase in collagen.

You could also throw in some vitamin C-rich foods, as vitamin C appears to stimulate collagen production from human skin cells. Defective wound healing has long been known as a major manifestation of scurvy, the vitamin C-deficiency disease. A remarkable series of grisly experiments performed on British conscientious objectors during World War II involved being subjected to cuts and stab wounds after being randomized to different levels of vitamin C. The researchers found that the average daily vitamin C intake to prevent weak scar formation was about 95 mg, which is actually higher than the current recommendations––but nothing you can’t get from half a bell pepper.

Vitamin B12 also appears to be necessary for maximal collagen synthesis, which may explain why collagen synthesis rates appear to be about 10 percent lower in vegetarians, because the prevalence of B12 deficiency among those eating plant-based diets is so high. That is one of the reasons why it’s critically important that everyone consuming a plant-based diet ensure a regular, reliable source of vitamin B12.