SaveYourself.ca •Sensible advice for aches, pains & injuries
 

Arthritis is not caused by a lack of glucosamine or chondroitin. And it isn’t treated by them either. If you think they’re helping you, that’s the placebo talking.

Can Supplements Help Arthritis and Other Aches and Pains?

Debunkery and analysis of supplements and food-like medicines (nutraceuticals), especially glucosamine, chondroitin, and creatine, mostly as they relate to pain

5,500 words, updated Dec 12th, 2013
by Paul Ingraham, Vancouver, Canadabio
I am a science writer, the Assistant Editor of ScienceBasedMedicine.org, and a former Registered Massage Therapist with a decade of experience treating tough pain cases. I’ve written hundreds of articles and several books, and I’m known for sassy, skeptical, referenced analysis and a huge bibliography. I am a runner and ultimate player, and live in beautiful downtown Vancouver, Canada. • full bioabout SaveYourself.ca

Includes information on the following nutraceuticals and ergogenic aids: creatine, chondroitin sulfate, glucosamine, whey protein, glutamine, turmeric/curcumin, bromelain, caffeine, and Protandim.

There are several popular nutritional supplements that people take because they are supposed to be “good for” your muscles and joints. They aren’t considered pain-killers, but people take them for pain. They aren’t anti-inflammatories, per se, but people believe they will reduce inflammation. They aren’t performance-enhancing “drugs”, but athletes and bodybuilders take them like almost like drugs to enhance their performance.

What they all have in common is that they are “food-like” — not a food, not a vitamin, but edible and supposedly good for your body one way or another. As nutritional supplementation has been studied and tested more carefully over the years, the results of have been discouraging, particularly for the average person with no particular problem to solve. New science is showing that even supplement staples like calcium may have more risks1 and fewer benefits2 than anyone suspected.

Unicorn horn velvet!

“So anabolic it’s illegal in 9 countries.” This is from a very good parody by NutraPlanet.com of the hyperbolic claims that are all-too common in the nutraceutical industry.

Unicorn horn velvet!

“So anabolic it’s illegal in 9 countries.” This is from a very good parody by NutraPlanet.com of the hyperbolic claims that are all-too common in the nutraceutical industry.

In this climate of discouraging science, it certainly pays to be skepticfal about pretty much anything that sounds too good to be true, even simple vitamin and mineral supplementation. Nutraceuticals are on the fringes of supplementation, and are much more suspect. Here is a summary of the most popular:

supplement & summary effectiveness safety more information
Glucosamine. Like chondroitin sulfate, known as being “good for cartilage.” An abundant monosaccharide (amino sugar) and a building block of proteins and fats, especially in cell walls. Made commercially by extracting it from crustacean exoskeletons as a supplement used to treat osteoarthritis (especially hips and knees) via alleged anti-inflammatory and other happy effects on cartilage. low plausibility, no good research news in general,34 and it notably bombed two particularly good new tests in 2010,56 benefits for osteoarthritis possibly real but barely clinically significant, like “taking a car from 40mpg to 42mpg” (Examine.com editor Sol Orwell) probably safe at recommended doses, possible pancreatic damage with more7Examine.com, Wikipedia, QuackWatch and the book Snake Oil Science (Bausell)
Creatine. Marketed as “nature’s muscle builder” and an energy-boosting performance enhancer. A form of stored energy for muscles, primarily used by athletes and bodybuilders. The most legitimate sports supplement. heavily studied, and the only major nutraceutical that probably works as advertised no serious safety concernsExamine.com has an extremely detailed & heavily referenced creatine page
Chondroitin sulfate. Known as being “good for cartilage” because it is major component of cartilage, and it has much in common with glucosamine (they are often sold together). Chondroitin sulfate is chemically complex, and it’s almost impossible to know what you’re really getting. heavily studied, but no clear good news,8 and a huge slam from the NEJM in 20069 “well tolerated for up to three years,” but many known rare and minor side effectsWikipedia
Whey protein. Mixture of globular proteins isolated from whey, the liquid material created as a by-product of cheese production. Prized by athletes as a protein source to aid in building muscle. Wild speculation that it also has anti-inflammatory properties. no controversy regarding bodybuilding benefits, but almost no data at all about anti-inflammatory effectsnumerous side effects and safety concerns
Glutamine & Arginine. Abundant but non-essential amino acids (protein building blocks), mainly stored in muscle. Depleted in the critically ill, glutamine is used medically to aid tissue repair. Athletes and bodybuilders imagine running low on these substances after harsh workouts and hope “topping them up” will help repair/build muscle. See detailed section below for much more. Both of these amino acids have a mess of barely understood properties which might be relevant to exercise performance and recovery,10 such as anti-inflammatory effect,11 stimulation of growth hormone production,12 or dilating blood vessels.13 nearly unstudied in the context of athletic performance and recovery, some promising scraps of basic science only; conflicting evidence even for medical use with critically ill patients both are generally well tolerated, but have long lists of possible side effects and numerous safety concerns for chronic supplementation: “neurological effects were the most frequently observed” problems with glutamine14, and arginine is “associated with death in certain groups of heart patients”15no good sources known16
Collagen. Extremely abundant proteinacious building block of connective tissue, currently popular as an arthritis treatment in the form of products like Genacol. Usually used for skin and nails. However, assuming extra collagen is helpful in any way, it is probably impossible to get it by eating it in the form of a supplement.17 extremely limited and poor quality evidence probably safe — it’s just protein, and already a major component of other foods — but unstudied Scott Gavura’s collagen review for ScienceBasedMedicine.org
Turmeric/curcumin. Curcumin is the biologically active part of turmeric. Many health benefits claimed, including anti-inflammatory effects. evidence too limited to be even suggestive possibly safe, minor digestive side effects most likelyWikipedia
Bromelain. A pineapple enzyme, better known as a meat tenderizer, that may also have anti-inflammatory properties. limited but somewhat promising possibly safe, minor digestive side effects most likelyeCAM
Protandim. Patented “blend of phytonutrients” from a multi-level marketing company, with slick marketing emphasizing anti-aging effects … which should set off every caveat emptor alarm you’ve got. The product allegedly treats pain and inflammation via antioxidant effects and “activating” the Nrf2 protein. a handful of test-tube and animal studies, no human studies related to pain at all, only two (irrelevant and negative) human studies mostly unstudied, unknown a good overview on ScienceBasedMedicine.org,1819 Wikipedia

Examine.com emerged in 2012 as a great new source of information about supplements & nutraceuticals, with a much more ambitious scope than this page. Check ‘em out. They are still growing strong in late 2013.

Examine.com emerged in 2012 as a great new source of information about supplements & nutraceuticals, with a much more ambitious scope than this page. Check ‘em out. They are still growing strong in late 2013.

Do nutraceuticals show promise in general?

No, they do not. Many of the supplements above make little or no sense even in principle: regardless of whether or not we need a substance, it is often impossible to get more simply by eating it.20 And nearly all of them have been failing a basic credibility test for years: a lack of good evidence of efficacy, and not for lack of trying in the case of the popular ones. Only one of them (creatine) is a clear winner. Not one other is definitely helpful.

If any of the others truly had significant therapeutic effects, it shouldn’t be hard to prove it, should it? There should be studies that don’t just “kinda” show some benefit … maybe …. There should be studies that leave no doubt there is something there.

There’s a lot of seemingly conflicting evidence about nutraceuticals. However, there’s a pattern of much ado about nothing. Even the most generous interpretations of the most positive-seeming results are still kind of underwhelming. Only one of them (creatine) is a clear winner. Not one other is definitely helpful.Generally speaking, nutraceuticals fail the “impress me” test.

And that squares nicely with the anecdotal evidence, which is hardly impressive either, despite great commercial success and lots of enthusiasm.21

Instead mostly we just have a mess of weak, confusing evidence, and it probably won’t get any better. It’s rare for anything particularly good to finally emerge from that kind of mess. The history of medicine shows us clearly that most popular remedies lacking good scientific support usually turn out to be popular because they are popular (and aggressively marketed) — not because they ever actually worked.

I am not optimistic about nutraceuticals in general.

What about the most famous — glucosamine?

Glucosamine — leading by example?

Glucosamine is the best-selling of all nutraceuticals, and so you’d hope it was also the best — if any of them work, it should be this one. But glucosamine has never been particularly plausible as a medicine,22 and it’s been slammed by the research evidence so far. The bad news really piled up in 2010 with two F-grades on large, fair tests — one for low back pain and another for knee pain (referenced above in the chart) — and another flunk from a huge 2010 meta-analysis of 3800 patients.23 If glucosamine were a student, its parents would get called in for a conference about little glucosamine’s poor performance. Perhaps there’s something going on at home? Here’s the conclusion on the report card for knee pain for both glucosamine and chondroitin sulphate:24

Over 2 years, no treatment achieved a clinically important difference in pain or function as compared with placebo.

The pile of glucosamine failures is now getting rather tall. In July 2010, Dr. Harriet Hall reviewed the evidence of absence of any glucosamine benefits at ScienceBasedMedicine.org and concluded that glucosamine proponents

… can always complain that maybe it works for knees but not for hips, or that a different dosage might have worked better, or that it works for some small sub-set of patients. There will always be “one more study” to do. … This new study confirms my opinion that we shouldn’t spend any more research dollars doing “one more study” on glucosamine.

Not that this evidence will actually stop people from “believing” in glucosamine and buying it in bulk! Glucosamine bottlers will really appreciate everyone’s continued gullibility.

Ergo-what? The overlap between ergogenic aids and nutraceuticals and energy drinks

Ergogenic aids are quite literally anything — any external influence on the body — that can improve physical or mental performance, or recovery from fatigue and injury. These include devices, drugs, nutrition and even morale boosters. It’s a broad category!

The most familiar of the ergogenic aids are the energy drinks, like Red Bull, Full Throttle, or Rockstar. Virtually every imaginable ergogenic aid has been put into drink form for you. Pharmacist and writer Scott Gavura cuts energy drinks down to size in a recent analysis:

Despite the impressive lists of ingredients and slick marketing, these products are essentially caffeine delivery vehicles, most of which come loaded with sugar.

I believe many people use ergogenic aids because they believe that anything that enhances performance is also a kind of medicine. Perhaps a body that feels stiff, painful and weak needs “performance enhancement” as much as an athlete? Or more? Adaptation to exercise and healing from injury may just be two ends of the same spectrum — different extremes of the same fundamental process. To recover from exercise is like minor healing. Maybe.

While that might work in some cases, it doesn’t necessarily follow. It’s equally clear that enhanced performance can come at a cost. Performance-enhancing steroids are obviously an ergogenic aid, but also have such serious side effects that no one thinks of those as “medicine.” Or consider caffeine, discussed more below: it is widely used as an ergogenic aid, and yet it also makes sense that it could actually increase vulnerability to pain, even if only by interfering with sleep.

I think it’s a crucial (and interesting) part of the psychology of this kind of supplementation. Whether it makes sense or not, the perfomance-enhancer = medicine idea may actually be the reason why a lot of people are taking something like creatine for pain problems … even though it’s known primarily as an ergogenic aid, and not a pain medication. Let’s get into that a little deeper…

Creatine and pain: is there a connection?

First, let’s just establish that creatine probably actually works as advertised: maybe the only major one that does. Once upon a time, I was too hard on creatine. It was a victim of my cynicism about the industry. I didn’t take it seriously, didn’t look at it closely enough, and tarred it with the same brush as other much less useful products. I’m pleased that the lads at Examine.com eventually turned me around on this topic. (Well, it was really the evidence.)

So, creatine, I’m sorry I misjudged you. You seem like a stand-up nutraceutical!

I’ve looked for negative and skeptical evidence and opinions on creatine. The negative opinions aren’t hard to find, but they are all of the same species that mine was: entirely reasonable general cynicism about supplements. And yet the cynicism doesn’t seem to be justified in this particular case, because actual negative evidence is awfully scarce, and there is plenty of pretty clearly positive evidence. For instance, if you read QuackWatch’s creatine page, it’s remarkably nice. Although “not recommended for the average athlete,” that’s based mostly on a lack of safety evidence (which has emerged since).

Creatine is straightforward: claims made for it are not extraordinary, it seems to work, and there is now plenty of evidence showing that it’s very likely to be safe as well. Examine.com’s mighty creatine page is, as far as I can tell, pretty much spot on. I think it’s well done, extremely thorough, and balanced. If you want the creatine science, go there (“453 unique references”).

I honestly see no reason why somebody shouldn't supplement creatine, nor do I see any logical basis for the seeming 'fear' of this compound in society. Its safe, it healthy, its cheap, and for most people it just works. Get some Creatine Monohydrate, take 5g a day, and you're good to go.

If humans didn't make any in the body, this thing would be a vitamin. There do exist deficiency symptoms that result in mental retardation.[2] They're rare, but they pretty much establish the importance of this molecule as a vitamin-like compound.

Kurtis Frank, The “Editors' Thoughts on Creatine” on examine.com

(The only fly in the creatine ointment that I know of is that it gives some people trouble with sleep, and that happened to me. See my insomnia article for the story. But I think this probably isn’t a major issue for many people.)

The pain connection

Writing about nutraceuticals isn’t exactly on my bucket list. I’m keen on them to the extent they might help with pain. The connection is obvious with glucosamine (supposedly an arthritis fighter), but there is no clear connection between creatine supplementation and pain. So what am I going on about it for?

The following is pure speculation and may be ridiculous. Truth not guaranteed. Chance of wishful thinking: 60–70%.

So creatine’s main benefit is muscle fatigue resistance. Muscle cells take longer to tire out when they have extra creatine in their little cellular pantries. I don’t know about you, but I often have a hard time telling the difference between pain and fatigue.It’s an energy intermediate that helps replenish the fuel molecule, adenosine triphosphate (ATP is one of greatest hits of organic chemistry). Bobybuilders take creatine so they can lift longer. It’s firmly in the category of an athletic performance enhancer, and not a “treatment” for anything … except fatigue at the end of a set. Could this be relevant to certain kinds of pain? Perhaps.

I don’t know about you, but I often have a hard time telling the difference between pain and fatigue. That’s not entirely a coincidence of course.

Exercise recovery, performance enhancement, and treatments are different aspects of the same thing. People “recover” from both exercise and injury. An increase in function is called an effective “treatment” if you start out in a bad place, but it’s a “performance enhancer” if you were healthy to begin with. There are so many overlapping factors in what constitutes function and dysfunction that it is generally plausible that anything that is known to increase performance in healthy athletes may also “increase performance” — treat — unhealthy people in pain. It all depends on the specifics, of course. In this case, muscle pain and fatigue might be related.

Muscle is a likely factor in many common body pains. The exact mechanism of this is unknown, but muscle fatigue seems to be a risk factor for episodes of muscle pain — and not just the soreness that always follows an ordinary workout. “Fatigue” is a complex state, a spectrum of biological circumstances, not just energy depletion in muscles during exercise. That biology probably overlaps to some degree with body pain. Most people with acute muscle pain also report feelings of weakness and fatigue. By no means do those sensations necessarily mean that more fuel in muscle cells would help … but it’s not out of the question.

And it’s not expensive.

And it’s at least as safe as eating Twinkies. Quite likely safer.

And it will, if nothing else, probably increased your resistance to fatigue at the gym.

And maybe it will help with some chronic body pains. I think it’s a rational thing to try, at least, because the biology of muscle fatigue might have enough in common with the biology of aching.

Bromelain, a lesser known anti-inflammatory nutraceutical that might be more evidence-based

Bromelain is worthy of a closer look. It is one of two pineapple enzymes, plus a few other compounds. It’s best known as a meat tenderizer, but may have anti-inflammatory properties as well. Somewhat less of a “nutra” and more of a “ceutical”, bromelain could possibly have the potential to be used in place of anti-inflammatory drugs.

What jumps out at me about bromelain is that the evidence looks a little better than for some of the other popular nutraceuticals. Some half-decent research has been done on it, although nowhere near enough to actually come to anything like a conclusion.

In 2004, Brien et al reviewed one dozen studies of bromelain research in Evidence-based Complementary & Alternative Medicine.25 Despite a blatant conflict of interest — Brien works for a bromelain manufacturer — the review seems balanced, and the authors do not fail to point out weaknesses in the evidence or concerns about adverse effects. Their conclusion is cautiously positive, and it does seem to be justified by the evidence reviewed: in this study bromelain certainly seemed to do something to help people with painful osteoarthritis.

“The currently available data do indicate the potential of bromelain in treating osteoarthritis.”

However — and this is really important perspective — we already have medications that “do something” to help people with painful osteoarthritis. To really qualify as a replacement for existing medications, bromelain (or any other nutraceutical) would not only have to work just as well, but also have fewer side effects. “Effective but safer alternative treatments would be of benefit to osteoarthritis sufferers,” write Brien et al.

This has not even remotely been established yet. Until it is, bromelain is nothing more than a possibly effective nutraceutical that might or might not have fewer side effects. Remember that side effects can be rare and widely variable, so even if many people have no problems, lots of others might — you can’t say that bromelain has no side effects just because you got away with taking it!

Caffeine improves physical and cognitive performance during exhaustive exercise, but also carries a risk of actually increasing pain

Caffeine is widely believed to be an ergogenic aid … and it probably is.

I’ve played a lot of ultimate with players who are younger, fitter, and more talented. I’m just happy that I can play on the same field and not embarrass myself … much. Without a doubt, the most limiting factor is exhaustion: I often make tactical mistakes or throw “swill” (ultimate slang for a lousy throw) not because I don’t know how to play the game, but because I’m just too whipped to play it well. The older I get, the more it happens.

Caffeine to the rescue!

According to Medicine & Science in Sports & Exercise, caffeine really will “significantly improve” not only endurance performance, but “complex cognitive ability during and after exercise.”26 Sign me up! I’ve already pretty much embraced caffeine as one of those rare pleasures in life that has minimal downside — this is just gravy!

The researchers studied 24 well-trained cyclists, giving them either 100mg of caffeine or a placebo and then testing their endurance and their mental function during and after workouts. The signal was loud and clear: caffeine consumption boosted their performance. I can hardly wait to eat some caffeine before my next game!

But there are also problems: caffeine makes us hyper, and is probably somewhat exhausting. We pump more adrenalin, exhaust ourselves, lose sleep: risk factors for pain. Chronic, excessive caffeine usage is likely to be an aggravating factor in cases of chronic pain. So here we have a substance that is, on the one hand, almost certainly an effective ergogenic aid, but probably also an aggravator of pain, especially when used to excess.

If you’re going to drink it (and you probably are) what’s the best source of caffeine? Scott Gavura reports that “coffee has more caffeine than many energy drinks. A 16 oz ‘grande’ coffee at Starbucks has 320mg of caffeine … in comparison, a Red Bull has 151mg/16 oz.”

So go ahead and enjoy your Red Bull. But when that liquid candy stops appealing to you, I’ve got some shade-grown, bird-friendly, passive-organic, fair-trade, home-roasted coffee for you to try.

(It also doesn’t dehydrate you. That’s a silly myth.27)

Glutamine and arginine for exercise recovery and soreness? Faith-based supplementation based on the extreme (and controversial) example of critically ill patients

I have always really paid for my workouts. I get DOMS (delayed onset muscle soreness) something awful, and always have — some unsolved mystery about my biochemistry. It starts soon after a run or a game of ultimate, and last 2-3 days. The only thing that helps is being as fit as possible at all times: if I take a break, it will be nasty when I get back to it. After griping to my (excellent) doctor about this recently, he recommended that I try arginine supplementation. Why?

Amino acids and healing

Both glutamine and arginine are abundant non-essential amino acids (protein building blocks). Both are needed for tissue repair, which is the basic reason for thinking they might help with exercise recovery. There is not much reason to emphasize arginine over glutamine, since the rationale for using both is pretty similar — and similarly weak, as their clinical effects are generally complicated and under-studied.

Glutamine is the most abundant non-essential amino acid in the body, much of it stored in muscle. Both glutamine and arginine can become depleted in people recovering from major injury and illness, in which case they are regarded as “conditionally essential” — that is, essential during emergencies, when there’s a great deal of tissue rebuilding going on. For this reason, glutamine especially is used medically to treat the critically ill, but the value of this is still scientifically controversial. Arginine is used less, mostly because of safety concerns.

Extrapolating from that extreme (and sort-of medically endorsed) usage, athletes and bodybuilders take a lot of the stuff because they believe that their exertions may be so harsh that they run low on amino acids in the aftermath, and they hope that topping them up will help them repair and build muscle. However, it is unlikely and generally implausible that healthy athletes are ever glutamine depleted in the first place,28 and therefore it is also a bit unlikely that they can benefit from supplementation for this reason.

There are other possible reasons. Guessing about how this stuff works out in the real world is basically gambling with your biochemistry.Both of these amino acids, and a few others, generally have a mess of barely understood properties which might be relevant to exercise performance and recovery, such as stimulation of growth hormone production, or dilating blood vessels. Guessing about how this stuff works out in the real world is basically gambling with your biochemistry, though.

The state of the research for arginine and glutamine supplementation is, predictably, rather poor. Their use appear to be faith-based, not evidence-based.

I spent about a half hour poking around for glutamine/arginine science on the web and PubMed, and determined only that they are nearly unstudied in the context of athletic performance. 99% of search results are places to buy the stuff, with another .9% being blog posts enthusiastically recommending it because “research has shown” that it works (almost always not mentioning what research). I was unable to find any thorough critical analysis of either (although MayoClinic.com has dry but thorough evidence summaries for both). I found one good-news study, but it’s weak sauce.29

There’s some encouraging scraps of basic science about both amino acids, but even their medical usage — glutamine for critically ill patients — remains controversial because the evidence is incomplete and conflicting. So there’s really no hope that we will know any time soon what, if anything, either of these substancs do for something as trivial as a little bit of exercises muscle soreness after exercise.

Meanwhile, there are numerous safety concerns for chronic supplementation of either. For glutamine “neurological effects were the most frequently observed,” and arginine is “associated with death in certain groups of heart patients.”

But it worked for me!

Good! But please curb your enthusiasm: even if something really did “work for you,” that doesn’t mean it’s working for anyone else. To be considered safe and effective, a medicine or treatment has to have a solid cost-benefit profile for most people, most of the time. There are lots of treatments that are good for a handful of people, once in a blue moon. If you are one of those lucky ones, please don’t assume it means that the product is the best thing since sliced bread.

It’s more likely that you healed all by yourself, however.

It’s pretty unlikely that any nutraceuticals should get the credit for healing. It was probably all you: lucky natural healing, and maybe some of your mind powers! Placebo, in other words. Placebo is a powerful, extensively studied, and very real and interesting phenomenon. See The Strange Powers of the Placebo Effect 2:57 for a terrific 3-minute video tour of the “the many strange effects of placebos.”

These products aren’t proven. Placebo is.

Sometimes you can get a nice synergy between natural healing and placebo which really makes an impression. That is: if your tissues are already just starting to recover naturally (perhaps too little to have even noticed, or not enough to get excited about), and then you add a good placebo effect, recovery can be striking and rapid. Since desperate patients are nearly always using some treatment or another at the time that this happens, it usually gets the credit — but obviously it shouldn't. This kind of confusion about the real cause of recovery is the norm, not the exception.

Nowhere in health care do testimonials and anecdotes seem to play a bigger role than they do here: with things you put in your mouth. Unfortunately, they are pretty much worthless.

The Multi-Level Marketing Connection

Many nutraceuticals and supplements are sold using “multi-level marketing” (MLM), in which products are mostly sold internally to recruited distributors, and the real money is made by getting kickbacks from all your recruits and their recruits. I have direct personal experience with MLMs, having been sucked in by one of them for almost a year in the early 1990s — a very embarrassing chapter of my life, but full of valuable lessons. I know from that experience all too well that MLMS success depends on becoming an intense proselytizer: you have to not only sell the product, but sell the idea of that the product is so great that your customer should become a distributor.

The whole thing is powered by hype and dreams of getting rich quick.

That’s all kind of gag inducing, but MLMs are actually fundamentally fraudulent. Many people are under the false impression that some MLM schemes are “not really a pyramid” or otherwise okay, but even the best of them are still dubious, distasteful, and harder to make money with than it seems at first. MLMs are technically legal, but they shouldn’t be. As with supplements themselves, legality is a poor guideline — many scams are legal!They are technically legal, but they shouldn’t be. As with supplements themselves, legality is a poor guideline — many scams are legal!

It says something about supplements that they are so routinely sold by such scammy methods. Probably every imaginable product has been sold via MLMs, but supplements and snake oils are that industry’s favourite product category by far.

Alternative medicine practitioners are juicy targets for MLM recruiters. Because of their, er, “accepting nature,” they are easily recruited, and simultaneously become victims to a scam themselves … and then start passing it on to their patients. For instance, it’s extremely common for chiropractors and naturopaths to sell nutraceuticals and supplements in their offices, and they are often distributing for an MLM as well as retailing. In my career in massage therapy I encountered many colleagues who attempted to recruit me into an MLM, usually to sell supplements.

MLMs practically constitute a subculture of alternative medicine. Make of that what you will.

Information is Beautiful

Here’s a great way to conclude this tour of nutraceuticals: in 2009 InformationIsBeautiful.net published a brilliant, beautiful and interactive visualization of the popularity and effectiveness of popular dietary supplements. It’s a very good graph, but notice that it neglects a crucial factor: risk. No biological benefit of anything you put into your body can ever be meaningful without contrasting it with the possible dangers of doing so, and unfortunately that consideration is routinely overshadowed by discussion — and lovely diagramming — of the possible benefits. Nevertheless, pretty interesting (and pretty) diagram:

Rather a lot of products are below the “worth it” line! There are also many above the "worth it" line, but please notice that very few of those have anything to do with body pain — only one in fact, devil's claw.

About Paul Ingraham

I am a science writer, former massage therapist, and assistant editor of Science-Based Medicine. I have had my share of injuries and pain challenges as a runner and ultimate player. My wife and I live in downtown Vancouver, Canada. See my full bio and qualifications, or my blog, Writerly. You might run into me on Facebook and Google, but mostly Twitter.

What’s New In this Article?

A simple version of this article was initially published in January 2010. It was updated semi-regularly for a year, and finally reached a critical mass of worthiness first thing in January 2011. Regular updates have continued ever since.

Friday, December 7, 2012 — Turned around on creatine. That stuff seems to work as advertised.

Friday, March 16, 2012 — Added a reference to a new Protandim study, only the second ever in humans … and it’s irrelevant and negative.

Thursday, November 10, 2011 — Added collagen, and some comments about bioavailability.

Friday, October 28, 2011 — A couple more references for arginine and glutamine. Also: improvements to layout of main supplements table.

Friday, 21 October, 2011 — Extensive upgrades and expansion of information about glutamine and arginine.

Tuesday, October 11, 2011 — Added reference information about Protandim, and “bottle of hope” image.

Thursday, September 15, 2011 — Added more evidence of underwhelming benefit to chondroitin sulfate.

Thursday, August 26, 2011 — Added more information about the connection between nutraceuticals multi-level marketing.

Thursday, August 26, 2011 — Added “safety” column and data to main chart.

Saturday, May 28, 2011 — Added Protandim. Plus new section, “But it worked for me!” Includes a link to a terrific video: The Strange Powers of the Placebo Effect 2:57

January 2010 — Extensive upgrades before promoting this article for the first time.

Notes

  1. See Do calcium supplements cause heart attacks? BACK TO TEXT
  2. Warensjö et al. Dietary calcium intake and risk of fracture and osteoporosis: prospective longitudinal cohort study. British Medical Journal. 2011. PubMed #21610048.

    Does long-term supplementation with calcium reduce the risk of fractures? The answer, based on this study, appears to be no: "Gradual increases in dietary calcium intake above the first quintile in our female population were not associated with further reductions in fracture risk or osteoporosis." My am interested in this evidence is mainly because it’s a good example of how supplements continue to turn out to be less useful than we all hoped in the 20th Century.

    BACK TO TEXT
  3. In his 2007 book Snake Oil Science, R. Barker Bausell examined all the research evidence. He analyzed the strengths and weaknesses of a Cochrane Review of glucosamine with 2570, a NEJM study with 1583 patients, and an Annals of Internal Medicine study of 222 patients. Based on these large tests, Bausell concluded that glucosamine is ineffective. BACK TO TEXT
  4. Towheed et al. Glucosamine therapy for treating osteoarthritis. Cochrane Database of Systematic Reviews. 2005. PubMed #15846645.

    This prominent Cochrane review — #4 in mid-2012 — concludes that glucosamine “failed to show benefit in pain and WOMAC function” with one kind of glucosamine product (non-Rotta), but succeeded with another (Rotta), coming dangerously close to cherry-picking favourable results. Maybe glucosamine of one sort works while other do not, and maybe the authors simply wanted good news and found it in some of the data. For a good taste of how conflicting and confused the evidence still is, read the introduction to his 2009 update — it starts out very positive, but then proceeds with a litany of caveats that makes one doubt the enthusiastic opening statements.

    BACK TO TEXT
  5. Wilkens et al. Effect of Glucosamine on Pain-Related Disability in Patients With Chronic Low Back Pain and Degenerative Lumbar Osteoarthritis: A Randomized Controlled Trial. Journal of the American Medical Association. 2010.

    This straightforward test of glucosamine for low back pain found no therapeutic effect by any measure: “Our findings suggest that glucosamine is not associated with a significant difference in pain-related disability, low back and leg pain, health-related quality of life, global perceived effect of treatment.” Although statistically insignificant, disability was actually greater in those who took glucosamine, and “approximately 30% of the patients reported mild adverse events.”

    See also Dr. Harriet Hall’s analysis. She writes: “[This study is] well-designed, randomized and double blind, with 250 subjects, a low drop-out rate, a 6 month duration with a one year follow-up, appropriate clinical criteria for improvement (disability, pain, quality of life, use of rescue medications), intention-to-treat analysis, and even an “exit poll” to insure that blinding had been effective, that patients couldn’t guess which group they were in. It used the doses of glucosamine sulfate that had been called for by critics of previous studies. It was done in Norway, where glucosamine is a prescription drug (in the US it is marketed as a diet supplement under DSHEA regulations so there is a greater possibility of dosage variations and impurities); it was independently funded, with no involvement of industry.”

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  6. Sawitzke et al. Clinical efficacy and safety of glucosamine, chondroitin sulphate, their combination, celecoxib or placebo taken to treat osteoarthritis of the knee: 2-year results from GAIT. Ann Rheum Dis. 2010. PubMed #20525840.

    Even though osteoarthritis in the knee causes severe pain and dysfunction for many older adults, long-term studies of treatment are few and far between. This research evaluated the efficacy and safety of two popular “supplements_for_pain” — glucosamine, chrondroitin sulphate — as well as the painkiller celecoxib by comparing them to a placebo in over 600 patients over 2 years. None of the treatments worked — less than 2% of patients enjoyed even a 20% improvement. The study authors conclude: “..no treatment achieved a clinically important difference in … pain or function as compared with placebo.” As well, adverse reactions were similar in all groups; serious adverse reactions were rare for all treatments. This adds considerable weight to the already substantial evidence that the popular supplements_for_pain are ineffective.

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  7. Wikipedia: “Clinical studies have consistently reported that glucosamine appears safe. However, a recent Université Laval study shows that people taking glucosamine tend to go beyond recommended guidelines, as they do not feel any positive effects from the drug. Beyond recommended dosages, researchers found in preliminary studies that glucosamine may damage pancreatic cells, possibly increasing the risk of developing diabetes.” BACK TO TEXT
  8. All scientific papers about chondroitin sulfate are good examples of “no clear good news,” but a good recent example is an experiment by Gabay et al, who somewhat absurdly concluded that chondroitin sulfate “improves hand pain” — which was technically true, but the improvement was rather trivial. In the context of the body of evidence, it’s really quite silly to write a summary that sounds so positive. BACK TO TEXT
  9. Clegg et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. New England Journal of Medicine. 2006. PubMed #16495392.

    This is one the largest and best designed studies of glucosamine and chrondroitin sulfate to date. More than 1500 patients were treated for six months. The results were trivial. “Overall, glucosamine and chrondroitin sulfate were not significantly better than placebo in reducing knee pain,” and the painkiller celecoxib produced better results.

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  10. After griping to my doctor about how much post-exercise muscle soreness I suffer from, he enthusiastically recommended that I “try” glutamine and arginine supplementation. The rationale for this really does not go any deeper than the fact that amino acids are required by the body for tissue repair and growth. There is exactly no specific evidence that they help in the context of ordinary exercise recovery. BACK TO TEXT
  11. Cruzat et al. Effects of supplementation with free glutamine and the dipeptide alanyl-glutamine on parameters of muscle damage and inflammation in rats submitted to prolonged exercise. Cell Biochem Funct. 2010. PubMed #19885855.

    This is a study of rats showing some signs that glutamine supplementation might have some biological effects that would reduce muscle soreness, namely it “may attenuate inflammation biomarkers after periods of training.” It is an example of basic science with possible clinical relevance. However, it is a long way from this evidence to anything like proof that amino acid supplementation actually reduces post-exercise muscle soreness in humans.

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  12. Merimee et al. Arginine-initiated release of human growth hormone. Factors modifying the response in normal man. New England Journal of Medicine. 1969. PubMed #5786514.

    Some ancient, basic physiology science demonstrating that arginine supplementation may stimulated production of growth hormone — which is still used by as a rationale for arginine supplementation for bodybuilders to this day.

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  13. Willoughby et al. Effects of 7 days of arginine-alpha-ketoglutarate supplementation on blood flow, plasma L-arginine, nitric oxide metabolites, and asymmetric dimethyl arginine after resistance exercise. Int J Sport Nutr Exerc Metab. 2011. PubMed #21813912.

    A small study showing that arginine supplementation increased the amount of arginine in the blood, but changes in circulatory function were simply due to exercise — that is, they also occurred in people who took only a placebo.

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  14. Garlick. Assessment of the safety of glutamine and other amino acids. J Nutr. 2001. PubMed #11533313.

    Four studies of the safety of glutamine supplementation in a medical context found that it was “safe in adults and in preterm infants,” but that data was not relevant to concerns about “chronic consumption by healthy subjects.” The authors attempted reviewed more literature on high dietary intake of proteins and amino acids in general, and found more problems, particularly neurological damage in preterm infants. Infants are particularly sensitive to neurological effects, so if they have problems, it certainly means trouble for adults too — just less dramatically. “Because glutamine is metabolized to glutamate and ammonia, both of which have neurological effects, psychological and behavioral testing may be especially important.” In other words, a high dietary intake of glutamine may mess with your head.

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  15. MayoClinic.org. Arginine. BACK TO TEXT
  16. I spent about a half hour poking around for glutamine science on the web and PubMed, and determined only that it is virtually unstudied in the context of athletic performance, and 99% of glutamine search results are places to buy the stuff, with another .9% being blog posts enthusiastically recommending it because “research has shown” that it works (without mentioning what research). I was unable to find any thorough critical analysis. (Absurdly, this thumbnail sketch of the topic, barely referenced itself, is actually more substantial than anything I found.) BACK TO TEXT
  17. Pharmacist Scott Gavura for ScienceBasedMedicine.org: From a dietary perspective, your body doesn’t care (and can’t tell) if you ate a collagen supplement, cheese, quinoa, beef, or chick peas — they’re all sources of protein, and indistinguishable by the time they hit the bloodstream. The body doesn’t treat amino acids derived from collagen any differently than any other protein source. For this reason, the idea that collagen supplementation can be an effective treatment for joint pain, osteoarthritis, or any other condition, is highly implausible, if not impossible in principle.” BACK TO TEXT
  18. Pursued by Protandim Proselytizers. Hall. ScienceBasedMedicine.org. 2011.

    Dr. Harriet Hall once again summarizes the (lack) of evidence that Protandim helps people. There’s still only one human trial of this stuff … and still none that have anything to do with pain.

    Note that there have been no human clinical studies since the one in 2006. The newer studies are just more animal and laboratory studies, so they do nothing to change my previous conclusion. If I were a mouse being artificially induced to develop skin cancer in a lab study, I might seriously consider taking Protandim. But so far, the only study in humans measured increased antioxidant levels by a blood test but did not even attempt to assess whether those increases corresponded to any measurable clinical benefit, for cancer or for anything else.

    Dr. Hall also shares some of her contents of her mail bag about this stuff. It’s illuminating, and good for a chuckle. Note that Dr. Hall also has a concurrent article about antioxidants in the print issue (Volume 16 Number 4) of Skeptic Magazine, “Complexities of Antioxidants.”

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  19. In Mar 2012, Dr. Hall reported on a new human study of Protandim, but still not a trial and almost comically irrelevant … and negative: “Protandim was significantly (p<0.01) worse than placebo. No wonder [Protandim fans] are not bragging about this study!” BACK TO TEXT
  20. This is why many drugs have to be injected: because digestion destroys them, you have to put them right into the blood stream so that they can be used by the body. Some substances can be eaten and absorbed, but many can’t. “Bioavailability” is a significant problem with the logic of several popular nutraceuticals. BACK TO TEXT
  21. For instance, glucosamine isn’t curing anyone’s back pain. I’ve been working in this field a long time, and I have yet to meet the patient who has told me “hey, glucosamine really did the trick! My pain is gone!” Not one. You get “glucosamine took the edge off a little … maybe” and “I think it’s helping” and “I’m pretty sure,” but there were 5 other possibilities at the same time and the patient is back in trouble a month later. Another example: lots of people claim that they “can’t live without” their glucosamine for their bum knee, but I have yet to meet one who actually no longer had any significant knee pain.

    This is a common, odd thing about human nature: people paradoxically tend to brag about a treatment for a problem that isn’t actually solved; if it were solved, they probably wouldn’t even be thinking or talking about it. People without knee pain don’t run around saying, “I used to have knee pain, but now I take glucosamine and I never have the slightest problem.” This is exactly like victims of faith healers who are actually still sick but nevertheless believe they were healed — they rationalize the cognitive dissonance away by claiming that God is simply testing them. This is beautifully explained and illustrated in Radiolab’s signature storytelling style in this episode about placebo, and James Randi and Banachek give another amazing example talking about their adventures debunking faith healer Peter Popoff (interview in this Skeptics Guide to the Universe Episode.) BACK TO TEXT

  22. Dr. Harriet Hall on ScienceBasedMedicine.org: “The amount of glucosamine in the typical supplement dose is on the order of 1/1000th or 1/10,000th of the available glucosamine in the body, most of which is produced by the body itself. [Dr. Wallace Sampson] says, ‘Glucosamine is not an essential nutrient like a vitamin or an essential amino acid, for which small amounts make a large difference. How much difference could that small additional amount make? If glucosamine or chondroitin worked, this would be a medical first and worthy of a Nobel. It probably cannot work.’” BACK TO TEXT
  23. Wandel et al. Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysis. British Medical Journal. 2010. PubMed #20847017.

    This is a large scale analysis of ten of the largest, best trials of glucosamine and chondroitin, compared with placebo in over 3800 patients. No effect at all was found. Neither one, on its own or in combination, could outperform placebo. Pain was not reduced. Cartilage was not restored.

    Predictably, experiments funded by the supplements industry — “Big Suppla”! — produced results biased somewhat in favour of supplements, but even those were still statistically insignificant.

    The authors concluded: “Compared with placebo, glucosamine, chondroitin … do not reduce joint pain or have an impact on narrowing of joint space. Health authorities and health insurers should not cover the costs of these preparations, and new prescriptions … should be discouraged.”

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  24. The conventional pain-killer celecoxib did not have any effect either. BACK TO TEXT
  25. Brien et al. Bromelain as a Treatment for Osteoarthritis: a Review of Clinical Studies. Evidence-based Complementary & Alternative Medicine. 2004. PubMed #15841258. BACK TO TEXT
  26. Hogervorst et al. Caffeine Improves Physical and Cognitive Performance during Exhaustive Exercise. Medicine & Science in Sports & Exercise. 2008. BACK TO TEXT
  27. Killer et al. No evidence of dehydration with moderate daily coffee intake: a counterbalanced cross-over study in a free-living population. PLoS ONE. 2014. PubMed #24416202. BACK TO TEXT
  28. Rogero et al. Effect of alanyl-glutamine supplementation on plasma and tissue glutamine concentrations in rats submitted to exhaustive exercise. Nutrition. 2006. PubMed #16472983. BACK TO TEXT
  29. Namdar et al. Assessment of the effect of L-glutamine supplementation on DOMS. British Journal of Sports Medicine. 2010.

    “These results suggest that L-glutamine supplementation attenuates DOMS effects, muscle damage and downfall of performance in flexor of hip.” However, it’s a weak study, and I don’t think the results do much more than “suggest”: it was a small experiment, and they measured range of motion only (not pain or strength, both of which would have been better choices — DOMS does not particularly limit range of motion, just makes it uncomfortable). Nevertheless, this is a shred of evidence that glutamine might, possibly, help with DOMS a little.

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