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    HomeHealthThe painfully weak evidence on taking collagen to treat arthritis

    The painfully weak evidence on taking collagen to treat arthritis


    One Thursday in September, I awoke with achy knees. That was nothing new. I’ve had knee ache on and off for a number of years. Earlier than the pandemic, I had visited an orthopedist, who instructed me that I’d misplaced some cartilage in my knee joint — an early signal of osteoarthritis.

    “Come on, I’m simply over 50,” I instructed her. “That’s a lot too younger for arthritis.”

    “Yeah,” she laughed, “I hear that lots.”


    My knees aren’t practically dangerous sufficient for surgical procedure, however I’ve tried most every little thing else. A steroid injection supplied reduction, however just for per week. Injections of rooster comb (it’s for real) didn’t assist me, and positively didn’t assist the roosters. Bodily remedy labored once I did the workout routines religiously, however I’d lapsed in current months.

    So I believed I would strive collagen dietary supplements.


    Collagen is a protein that makes up two-thirds of the dry weight of cartilage in knees and different joints. It’s additionally a significant part of tendons, ligaments, and pores and skin. With age, the physique makes much less collagen, and that helps clarify numerous what occurs to pores and skin and joints — together with knees. In 2019, shoppers worldwide purchased $1.8 billion in collagen dietary supplements, hoping to interchange a few of what they’d misplaced.

    There’s a sure frequent sense to the concept, but it surely’s not clear how the collagen in oral dietary supplements is meant to get from the mouth to the knees. Whether or not collagen is ingested from dietary supplements or from meals akin to eggs, bone broth, or rooster wings, digestion breaks collagen down into its part amino acids and peptides. To make new collagen, the physique has to place these parts again collectively once more — and that’s precisely what the physique will get worse at with age. It’s a bit like bringing additional mortar to a development website after the bricklayers have gone house for the day.

    A 2012 Science journal article on cartilage described it as “intrinsically unable to heal.” Regardless of many years of analysis, involving applied sciences rather more refined than taking collagen dietary supplements, the objective of “cartilage regeneration stays elusive.”

    But in case you search standard well being websites for collagen and arthritis, you’ll find absolutely anything you wish to hear. Penn Medicine, quoting a employees doctor, claims that collagen “could assist battle the signs of osteoarthritis within the knee with few unintended effects.” VeryWellHealth claims the analysis is “combined however exhibits promise.” A WebMD page on collagen says that “due to a small however rising physique of proof suggesting it might enhance pores and skin, ease arthritis signs, promote wound therapeutic, and fend off muscle losing, former skeptics within the medical subject are…starting to return round.” But on one other WebMD web page, a distinguished professor of rheumatology dismisses the concept that collagen can “assist you develop cartilage. … It doesn’t,” she says.

    Perusing these websites, I acquired a bit confused. However my confusion was solely starting.

    Since even essentially the most skeptical WebMD web page mentioned that collagen dietary supplements “received’t harm if you wish to strive them,” I figured I would as effectively order some. I began purchasing on the web and inside minutes I used to be overwhelmed. Collagen dietary supplements are available in many manufacturers and types — powders, liquids, capsules, tablets, gummies, “tremendous” collagen, vegan collagen, hydrolyzed collagen, “magnificence collagen,” collagen for hair loss, and extra. I had no thought what variety I ought to take. And no matter I selected, I had no thought how a lot I ought to take, how usually I ought to take it, or how quickly I ought to count on reduction.

    I turned to the scholarly literature, and shortly discovered a meta-analysis, revealed within the journal Worldwide Orthopaedics, claiming to summarize essentially the most rigorous analysis on oral collagen dietary supplements and osteoarthritis. The authors discovered 114 revealed articles and winnowed them down to only 5 that had assigned sufferers at random to take collagen or a placebo. After calculating a weighted common of the trial outcomes, the authors concluded that “collagen is efficient in bettering [osteoarthritis] signs.”

    Midway by the article, although, I used to be beginning to have doubts. I’m a statistician who’s revealed analysis on meta-analysis. This one, as I identified in a letter to the journal that had revealed it, was filled with crimson flags.

    The primary crimson flag was that the outcomes had been in all places. One article reported massive advantages of collagen dietary supplements, two reported a lot smaller advantages, and two discovered no profit in any respect. Trials can yield completely different outcomes for varied causes, however not one of the apparent explanations match the outcomes on collagen. For instance, trials with bigger doses or longer therapy durations didn’t report bigger results. On the contrary, trials that lasted simply 10 to 13 weeks claimed higher advantages than trials that lasted 24 to 48 weeks. And trials through which sufferers took simply 2 to 10 grams a day claimed bigger results than trials through which sufferers took 10 to 40 grams a day.

    The outcomes didn’t make sense. I had the identical questions as once I began: If I ordered a collagen complement, how massive a dose ought to I take? How quickly I ought to count on reduction? I nonetheless had no thought, and I used to be beginning to suppose that nobody else knew, both.

    If dose and period didn’t clarify the disparity in outcomes, what did? The one factor that appeared to matter was the variety of sufferers within the research. An article reporting two very small trials, every of which had simply 18 to 19 sufferers taking collagen, appeared to point out dramatic advantages. However the largest trials, with 54 to 111 sufferers taking collagen, discovered that the dietary supplements improved signs by lower than 5 factors on a scale that ran from zero to 100 — a distinction so small that sufferers usually say they really feel “much the same.”

    That’s essential, as a result of research with extra sufferers have a tendency to provide extra exact estimates. The bigger research had been most likely nearer to right in suggesting that collagen didn’t make sufferers really feel noticeably higher. So why did the smaller research counsel bigger advantages?

    To verify, I examined the article that claimed the biggest results and instantly noticed an enormous crimson flag, proper on the title web page. 4 of the 5 authors had been employed by Nitta Gelatin, “a trusted producer of gelatin and collagen components for the meals, dietary complement, and pharmaceutical markets.”

    That turned out to be not the exception, however the rule. As I realized with a bit digging, all 5 articles within the meta-analysis had been both funded by a collagen firm or included some authors who had been being paid by a collagen firm, both as staff or consultants.

    Business-sponsored analysis isn’t essentially biased however, for a wide range of causes, it’s extra more likely to counsel that the sponsor’s products are beneficial. Among the many causes is what’s known as “reporting bias.” As a substitute of conducting one massive research, an organization can sponsor a bunch of small research and solely publish those that seem to point out advantages. As a result of the revealed research aren’t typical of what most research discovered, they have an inclination to magnify the profit that customers can usually count on.

    Lately, the U.S. and another international locations have taken steps to scale back reporting bias in scientific trials. Some of the essential steps is known as preregistration. Authors planning a scientific trial should state publicly and prematurely how the trial is designed and what outcomes they plan to report. Preregistration is required by a wide range of organizations, together with the Meals and Drug Administration, the Nationwide Institutes of Well being, the World Well being Group, the European Union, and the Worldwide Committee of Medical Journal Editors.

    However collagen, as a minimally regulated complement, slips by the cracks of many preregistration necessities that apply to medicine. And two of the collagen trials had been carried out in Mexico and Ecuador, where no registry exists through which researchers can preregister trials.

    Just one of the 5 collagen articles was preregistered. It concluded that collagen might need advantages, however the outcomes confirmed patterns that I discovered onerous to know. True, the group taking collagen confirmed dramatic enhancements over the course of the six-month trial — however so did the management group, which took placebo drugs that weren’t supposed to assist. In actual fact, the enhancements within the placebo and collagen teams differed by a virtually unnoticeable quantity — once more simply over 5 factors on a scale that ran from 0 to 100. Fewer sufferers within the therapy group reported taking acetaminophen (Tylenol), however that was true even within the first week of the research, when the therapy and management teams had been reporting virtually similar ranges of ache. Though another collagen trial additionally discovered dramatic enhancements in each the therapy and management group, I discovered the concept of huge enhancements within the management group onerous to swallow. Osteoarthritis shouldn’t be a situation that normally will get higher by itself.

    Whatever the outcomes, a trial through which solely 54 members took collagen wouldn’t be practically sufficient to get collagen authorized if it had been categorized as a drug slightly than a complement. A trial that small could be a Phase 2a trial, also called a pilot or proof-of-concept trial. Nonetheless to return could be the Section 2b trial to estimate the optimum dose, after which Section 3 trial to check the drug in a bigger group of sufferers. Section 3 trials usually enroll tons of or 1000’s of members — extra if the impact is small, because the impact of collagen on arthritis probably is. If there’s an impact in any respect.

    All this brings me to a query that has bothered me since I began making an attempt to type out the proof. Why is the analysis on collagen seemingly caught at a preliminary stage? If executives of collagen firms actually consider that they’re promoting a product that relieves signs of knee osteoarthritis — a situation that afflicts greater than 600 million adults worldwide — why haven’t they sponsored an impartial, preregistered trial with tons of or 1000’s of members, the type of trial whose outcomes may very well be revealed in a prime medical journal?

    If these executives thought there was a good probability of constructive outcomes, sponsoring a trial could be a a lot better use of cash than something they could spend on promoting or advertising and marketing. With a big and rigorous scientific trial to help using collagen for osteoarthritis, the marketplace for collagen would increase dramatically. Docs would normally advocate it. Sufferers would expertise reduction. Firms making these dietary supplements would revenue handsomely, and the executives who sponsored the trial might write their very own tickets.

    The truth that there hasn’t been such a trial means that collagen executives aren’t in any respect assured about how it could come out. They’re not really positive that their product works. And if the individuals who promote collagen dietary supplements don’t actually consider in them, why ought to anybody with achy knees purchase them?

    Paul T. von Hippel is a statistician and professor with the Heart for Well being and Social Coverage on the LBJ Faculty of Public Coverage, College of Texas, Austin.

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