Supplements For Pain - PHP

Supplements for Pain & Healing: Science vs Hype 09/12/2022, 20:09
Vitamins, Minerals &

Supplements for Pain &
Healing
Critical analysis of most popular “nutraceuticals” — food-

like pseudo-medicines taken for medicinal purposes,
especially glucosamine and creatine, mostly as they
relate to pain, arthritis, and recovery from exercise and
injury
Paul Ingraham • Jun 23, 2022 • 95m read
Article Summary −
Many nutritional supplements, vitamins, and minerals, are taken like drugs as a treatment for muscles and
joints and aches and pains: the “nutraceuticals,” like glucosamine, creatine, curcumin, protein powders, and
several others. Most are considered either anti-inflammatory and/or something that promotes tissue
repair/growth. But most make little sense as pain treatments even in principle, and supplement science in
general has been extremely disappointing and even ominous, due to the discovery of risks and serious
problems with quality control in a virtually unregulated industry that is just as profitable as “Big Pharma,”
and more corrupt by many measures (even just on the basis of the massive involvement multi-level
marketing, a fundamentally fraudulent business model).
Glucosamine (taken mainly for arthritis) is the most popular supplement, and has been slammed by multiple
large and decisively negative trials. Creatine is actually effective, but mainly for muscle fatigue resistance for
intense weightlifting — probably irrelevant to pain. There are some rays of hope for Vitamin D, magnesium,
curcumin, and omega-3 fatty acids. Probiotics for dysbiosis are interesting and have some real potential
principle, but in practice don’t seem to be doing much for most pain patients.
But there isn’t one single supplement that is clearly beneficial for any common kind of pain. But I explore the
https://www.painscience.com/articles/supplements-for-pain.php 1
science and the safety of every popular option, and some more obscure ones too.
tap to collapse
Arthritis is not caused by a lack of glucosamine. And it isn’t

treated by them either. If you think they’re helping you, that’s the
placebo talking.
People take many nutritional supplements because they are supposed to be “good for” muscles
and joints, aches and pains, arthritis, and recovery from exercise and injury. These vitamins,
minerals, and other assorted nutrients aren’t considered pain-killers — like ibuprofen — but people
take them for pain anyway. They aren’t performance-enhancing “drugs,” but athletes and
bodybuilders take them almost like drugs to enhance their performance… and people hope that
anything that might enhance performance will also help the body with anything that ails it.
There is some good news here and there, but supplement science is almost entirely discouraging, not
“promising,” and there are major concerns about contamination and side effects in any case.
This article covers creatine, vitamin D, chondroitin sulfate, magnesium, glucosamine, whey,
collagen, glutamine, BCAAs, curcumin, bromelain, caffeine, Protandim, and fish oil. Hot takes and
table of contents below.
Supplement science from 10,000 feet: the big picture in a paragraph

All the best-selling supplements have been studied and tested thoroughly over the years, and the
results have been almost perfectly discouraging, particularly for the average healthy person with
no particular problem to solve. 1 New science is showing that even basic vitamin supplementation
with staples like calcium may have more risks 2 and fewer benefits 3 than anyone suspected.
Americans who use supplements don’t live any longer. 4 They have been shown to be healthier by
some measures, but likely just because people with healthier lifestyles tend to take supplements. 5
And that was the basis for this excellent advice:
Be the kind of person who takes supplements — then skip the
supplements.
~ Michael Pollan, Food Rules: An Eater’s Manual
None of this is surprising, because supplementation has never really been a plausible upgrade from
good nutrition. The inevitable words “good for” betray a suspicious lack of biological specificity
that plagues the topic: it is usually unclear just how supplements are supposed to be “good for”
anything, and the more specific claims we see often just don’t make much sense. Many of them boil
down to a shamefully simplistic more-is-better rationale.
And for pain, the focus of this article? Alas, in a whole world full of supplements, there isn’t
compelling evidence that any supplement is helpful for any kind of significant chronic pain or rehab
challenge. In twenty years of study, I have never encountered an important exception. That doesn’t
mean that there’s literally nothing worth trying — there are interesting possibilities, like vitamin D
deficiency. But there’s not a single proven pain-fighter in the entire supplement armamentarium.
Warning: contaminated supplements are common!

Contaminated supplements are a thing. 6 The problem is so serious that it’s responsible for a huge
rise in supplement-related calls to poison centers. 7 In 2018 the Clean Label Project found 64
percent of a popular supplement category had detectable levels of arsenic, a third tested positive
for lead, 17% had cadmium, and more and worse.
One major pharmacy is now testing products themselves to protect their customers (and
reputation). A huge and totally unregulated industry is selling to legions of credulous people who
are knee-jerk cynical about Big Pharma but never question the scruples of supplement sellers. What
could possibly go wrong? Poisoning — that’s what!
Adulteration is another major concern: shady supplement makers spike their products with actual
drugs to win fans… in shocking numbers. 8 9 10 Who needs placebo when your customers can
“swear by” your product because it has actual pharmaceutical effects?
Dr William Osler once said, “One of the first duties of the physician is to educate the
masses not to take medicine.” This sage advice coupled with the adage “first, do no
harm” seems appropriate when discussing the use of dietary supplements with our
patients and athletes due to their limited efficacy and known safety risks.
Adulterated evidence of supplement adulteration?

The most popular citation to support the belief the supplements are contaminated/adulterated has come
under fire. Jonathan Jarry regarding the allegations: “…the lead researcher’s data seem to be missing,
fraudulent or plagiarized. The paper was widely cited and it became one of those easy-to-grab bits of
evidence that skeptics love to pull out.”
I avoided citing this famous paper … but only because I somehow missed it. If I had known about it, I
probably would have cited it! The last time I looked at supplement adulteration/contamination, I did think
that the data was a bit thin. I don’t really doubt that some supplements are adulterated and contaminated, but
it may not be as common and serious a problem as skeptics would “like” to believe. I will look closer and
update this page soon.
For the record (and unsurprisingly), the researcher accused of cooking the data has denied all wrongdoing.
Supplement science highlights (and table of contents)
A appears with any supplement that has some kind of legitimate, significant good news about it — something about it that
probably does actually help some people. And for the ones that are particularly dubious or problematic? Each item has a link to
Examine.com (which has lots of science about most of these), or another key source.
Fish oil (omega-3 fatty acids) — Fish is a fine source of omega-3 fatty acids, which seem to be
linked to healthiness, a little, maybe, but it’s just not as clear as everyone seems to think. Actual fish
is likely better than fish oil pills, and perhaps slightly anti-inflammatory — though probably just
because it’s not poor nutrition (which is inflammatory). EXAMINE.COM
Glucosamine and chondroitin sulfate — Both similar and known for being good for cartilage.
Glucosamine is a building block of proteins and fats, especially in cell walls. Benefits for
osteoarthritis possibly real but definitely trivial. Possibly toxic to pancreas. Chondroitin sulfate is a
component of cartilage, taken for arthritis, largely ineffectively, and fairly safe — but with multiple
rare and minor side effects. EXAMINE.COM
Creatine — A form of stored energy for muscles, primarily used by athletes and bodybuilders.
The most legitimate sports supplement with some verified benefits, but largely irrelevant to
pain/recovery. Quite safe; may cause insomnia. EXAMINE.COM
Whey protein — Prized by athletes as a convenient protein source to aid in building muscle, which
does work, plus some wild speculation that it also has anti-inflammatory properties, all unproven.
Numerous side effects and safety concerns, surprisingly. EXAMINE.COM
Glutamine & Arginine — Amino acids (protein building blocks), mainly stored in muscle, taken by
athletes to aid recovery from intense exertion and injury, also given to seriously sick/injured people.
More drug-like and broadly plausible benefits for performance and recovery, but barely studied.
Long lists of possible side effects and numerous safety concerns! EXAMINE.COM
Collagen — Extremely abundant proteinaceous connective tissue ingredient (we are never
“deficient” in it), popular for arthritis and touted as anti-inflammatory. Implausible. With scanty
mixed evidence of any benefit. Probably very safe, though, so at least there’s that! EXAMINE.COM
Curcumin — Curcumin is the biologically active part of turmeric with many claimed health
benefits, but mainly anti-inflammatory. Mildly promising evidence for some kinds of pain, but even
if it works your mileage may vary due to very complex bioavailability issues. Possibly safe, minor
digestive side effects most likely. EXAMINE.COM
Bromelain — A pineapple enzyme, better known as a meat tenderizer, that may also have anti-
inflammatory properties — just an experimental drug that’s never been properly tested. Safety
profile basically unknown; minor digestive side effects most likely. EXAMINE.COM
Caffeine — The most popular drug in the world is a proven mild pain-killer and performance
booster, but caffeine abuse — which is common, of course — is a plausible risk factor for chronic pain.
EXAMINE.COM
Protandim — Patented “blend of phytonutrients” from a multi-level marketing company that

touts anti-aging and anti-inflammatory effects, classic too-good-to-be-true stuff. Barely studied, and
no human studies related to pain at all. Safety? That’s a blank slate. ScienceBasedMedicine.org
Tart cherry juice — A source of antioxidants and believed to be good for recovery from intense
exercise, slightly supported by a couple small trials only. Possible sleep aid, oddly. Likely quite safe,
of course — it’s just fruit juice. EXAMINE.COM
Vitamin D — Vitamin D deficiency is probably more common than once suspected and may cause
or aggravate chronic pain. While evidence that supplementation can correct it is scanty, it’s probably
a worthwhile experimental medicine for chronic pain patients, because it’s cheap. But don’t
“mega”-dose, that’s nonsense. And its ability to prevent muscle or bone loss in healthy older people
is very much in doubt. EXAMINE.COM
Magnesium — Magnesium is one of the essential minerals, widely used in biology, so deficiency
has many possible effects, but most notably it makes nerves a wee bit trigger happy. Despite its
importance, deficiencies may be both common and related to pain — but also probably better fixed
with diet. For chronic pain patients, it isn’t a ridiculous supplementation option. EXAMINE.COM
Branched-chain amino acids — The BCAAs are three of the essential amino acids, and yet another
alleged recovery aid, better than the other amino acids at promoting protein synthesis. Preliminary
evidence was promising (isn’t it always?), but hasn’t been replicated (is it ever?). Several known
side effects: disorientation (!) and substantial indigestion. EXAMINE.COM
The last two sections are visible to logged-in PainSci members only. Members can login
to get all the details and with citations.
Coenzyme Q10 (CoQ10) [MEMBERS] — An obscure nutrient and antioxidant (with all that implies), but
also famed for relieving the muscle aching side effect of the statins (the cholesterol drugs). The
science is sketchy, however: it’s not clear that CoQ10 can solve the problem … or even that there is a
problem to solve.
Probiotics [MEMBERS] — We do now know that gut health affects entire bodies. But do probiotics
actually make guts healthier? And solve real health problems? Perhaps, but we are also clearly
meddling with forces we do not yet understand, and meanwhile the supplements industry is
cashing in on the hope. Probiotics for pain patients are still almost perfectly experimental.
Some other topics:
Do supplements show promise for pain patients in general?

Anti-inflammatory nutrition vs. supplements
Ergo-what? Performance, fatigue, and pain
But it worked for me! The role of anecdotes and testimonials
Big Suppla: Large supplement corporations are not only just as bad or worse than the
pharmaceutical ones, many of them are the same corporations
The Multi-Level Marketing Connection: Supplements and Fraud
“Big Suppla” is now evidence-based debunking
What about cannabis? Almost a “supplement,” but not quite. See Marijuana for Pain
And how about just nutrition itself? I discuss the idea of “anti-inflammatory nutrition” below, and
also in an article dedicated to inflammation: Chronic, Subtle, Systemic Inflammation.
Looking for something else?

You’re next stop is definitely Examine.com — by far the best and largest source of science-based critical
analysis of nutrition and supplements. This article delivers my unique take on many popular supplements
related to pain, but that’s the tip of the supplements iceberg, and Examine has vastly more good quality
information that I can provide here. They have a great subscription service that delivers a personalized
selection of study summaries to your inbox — highly recommended for those that need help drinking from
the firehose of nutrition science.
Arthritis and exercise soreness are the focus of a great deal of supplement
research
The more you read on this page, the more you might notice a pattern: again and again, the research
is about arthritis or exercise soreness. They are good proxies for lots of other kinds of pain. They are
very common, and anything good for those things might be useful for other kinds of pain, too.
You can only take that so far, though. There are many causes of pain, more than most people
realize, and pain is weird — volatile, complex, and deeply baked into our biology. A “broad
spectrum” pain-killer is impossible in principle: anything that works for one kind of pain is always
likely to fail with a bunch of others. A basic truth about pain is that the only way to treat it is to take
the person out of the equation — anaesthesia. As long as you are still conscious, there are still ways
that you can hurt, no matter what you eat (or don’t).
Do supplements show promise for pain patients in general? More detail now
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. 11 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. Generally
speaking, nutraceuticals fail the “impress me” test.
And that squares nicely with the anecdotal evidence, Only one of them (creatine)
which is hardly impressive either, despite great
commercial success and lots of enthusiasm. 12
is a clear winner. Not one
other is definitely helpful.
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.
Survey says most people don’t care what the science says: most people won’t quit
taking supplements no matter what
In 2013, Blendon et al found that only about a quarter of surveyed supplement users would quit
taking a supplement if it was shown to be ineffective. 13 Faith in supplements is a freight train that
probably cannot be stopped in anything less than a generation. When you consider what the
evidence is up against — people’s hopes and fears — perhaps it’s remarkable and even
encouraging that as many as 25% of people said they would lay off a supplement if it was proven to
be useless. And presumably some percentage could be swayed by enough of the right kind of
evidence and rhetoric, which hopefully means there is some damned point to our blogging!
You can’t reason people out of anything they didn’t reason themselves into. They’re taking
supplements not because it makes sense, but because life — even for the healthy and wealthy — is
often tiresome and difficult and discouraging and maybe, just maybe, supplements will make it all a
little easier. Unless you can offer something that actually can, you’re not going to convince people to
stop spending a little of their discretionary income on that gamble.
Anti-inflammatory nutrition versus supplements
Many supplements are touted to be “anti-inflammatory,” but loose usage has rendered this concept
almost as meaningless as “detoxification.” Inflammation is synonymous with immune system
activity, and “immunology is where intuition goes to die.” 14 Inflammation is not one thing, but a
huge family of overlapping and interacting processes. It’s not that we want less inflammation in
our lives — it’s that we want a dynamical and dazzlingly complex balance of just the right types of
inflammation in the right places, times, and amounts… all of which is a constantly moving target,
as it strongly interacts with variables like your gut microbiome.
Based on the complexity alone, anti-inflammatory claims are broadly implausible. Any one
substance is less likely to “fix” an inflammation problem than any one wrench is going to fix a
broken down car.
There’s a lot of overlap between the idea of anti-inflammatory supplements and an anti-
inflammatory diet. I think most people imagine that an inflammatory diet contains special foods —
“super” foods, even — that have anti-inflammatory properties. And to whatever degree you accept
that, then why not just eat whatever makes those foods special? Why bother with the food?
Because there mostly is no such thing as special anti-

inflammatory ingredients — either as part of food, or
isolated as a nutritional supplement. An anti-
inflammatory diet is just a diet that avoids foods that
Any one substance is less
are pro-inflammatory… which is mostly just an likely to “fix” an
obviously unhealthy diet, because being unfit is
inflammatory. So what’s an anti-inflammatory diet? inflammation problem than
Just a diet that isn’t terrible.
any one wrench is going to
A few foods do seem to have some anti-inflammatory
properties, but it’s quite rare, and they seem to be fix a broken down car.
hard to extract and isolate. The main example of this
is fish…
Omega-3 fatty acids, and fish versus fish oil pills
Fish is the best dietary source of omega-3 fatty acids, which might be a valuable class of nutrients.
The conventional wisdom for years is that they are “heart healthy” and more, and maybe it’s even
true, though Heaven help you if you try to actually find “proof” of that. Perhaps they are useful for
athletic performance and recovery, but that’s seriously uncertain. And maybe omega-3 fatty acids
are valuable on their own (fish oil in a pill), and maybe they aren’t. Some details…
Fish oil has perhaps shown some potential to aid with recovery from exercise. 15 A 2020 review of
more evidence like that is clearly bullish: the authors “identified evidence” that fish oil can improve
performance: “enhanced endurance, markers of functional response to exercise, enhanced recovery
or neuroprotection.” 16 They also emphasized that the data is mixed and mediocre, and it all could
so easily just be a cherry-picking expedition (seriously, anyone can “identify evidence” supporting
anything these days). There’s no way to know if their optimism is trustworthy without more and
better data and backup from other experts, but more data almost always leeds to more
contradictions. Case in point…
Extracting and isolating omega-3 fatty acids and putting them in a pill might undermine their
power to protect us from disease, but there’s no way to be sure. This body of evidence is much
more substantial — dozens of studies, including some huge ones — and yet still extremely complex
and inconsistent, with major trials and reviews pointing each way: some show that fish is better
than fish pills, 17 while others show that they are both protective against disease. 18 But good luck
finding a study that shows that supplements are better than fish! And the uncertainty only
punctuates that fish oil on its own isn’t exactly guaranteed to do the job. Trying to actually prove
that either fish or fish oil protects from disease is nearly impossible — the variables are nearly
infinite. Wake me up in fifty years when science has sorted it all out.
Meanwhile, I suggest erring on the side of fish. This is an important general principle. Food is
probably the best source of nutrients. Not extracted and purified molecules. No one’s actually
surprised by that, right? Right?
You: This one barely tested supplement will restore balance to my body!
Your body:
Hat tip to science journalist Peter Brannen for the good

joke. His original tweet version has 19.5K likes and
counting.
Glucosamine — leading by example?
Glucosamine has long been the king of the supplement hill, and so you’d hope it was also the best
— if any supplements work, it had better be this one. It is known as being “good for cartilage,” and
is mostly used to treat osteoarthritis (especially hips and knees) via alleged anti-inflammatory and
other happy effects on cartilage. It doesn’t really, and neither does its cousin chondroitin sulfate —
not enough that even the largest trials can produce an uncontroversial result anyway. But let’s look
at them earnestly a bit anyway, starting with some chemistry:
Glucosamine is an abundant monosaccharide — and amino sugar — and a building block of

proteins and fats, especially in cell walls. It is made commercially by extracting it from crustacean
exoskeletons. Shrimp shell!
Chondroitin sulfate is major component of cartilage, and it has much in common with glucosamine
(they are often sold together). It is chemically complex, and it’s almost impossible to know what
you’re really getting.
Both of these substances are “building block” supplements, which are all based on the idea that
consuming the ingredients of a given tissue will enable the body to repair that tissue more
effectively. But arthritis isn’t caused by a deficiency of the molecules it is made from. Even if it was,
a deficiency is unlikely without a pathological cause: these are extremely abundant molecules in the
human body, which our biology churns out by the billions from other more basic ingredients. 19
Eating a few extra is like trying to make the Atlantic
saltier by sweating in it.
Glucosamine supplementation has been mostly

Eating a few extra
bashed by science continuously for at least twenty glucosamine molecules is like
years now. 20 21 It bombed two particularly good
tests in 2010, 22 23 showing benefits for trying to make the Atlantic
osteoarthritis that are possibly real but barely
clinically significant, like “taking a car from 40mpg to saltier by sweating in it.
42mpg” (Examine.com editor Sol Orwell’s analogy).
Plus another flunk from a huge 2010 meta-analysis of
3800 patients. 24 A major 2015 report on knee osteoarthritis treatments declared it to be particularly
useless (along with chondroitin sulfate). 25 A 2018 meta-analyses (pooled data study) in
Rheumatology International was decisively negative. 26 JAMA’s big 2018 meta-analysis took a more
nuanced approach, focusing on long-term results (arguably the only results that matter for
arthritis), and concluding that — despite mountains of data from forty-seven randomized controlled
trials, including more than 22,000 patients — there was still “uncertainty” around the size of any
benefit and the conclusion was an eye-roll inducing “we need more data.” 27
Do we really, though? If you can’t find a signal in that much data, there isn’t anything interesting to
find. If these substances were even remotely useful, don’t you think it would be just a teensy bit
more obvious? 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?
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.
Are there technically positive studies? Of course! It’s the 21st Century — you can’t swing a dead cat
without hitting a positive study about practically anything. In this case, most are based on ideas
like “maybe specific kinds of patients” or “maybe a specific type of glucosamine.” Some of these
trials have yielded what appear to be “promising” results — that no one else ever seems to be able
to confirm, and which have little relevance to the consumer. Let’s just say for the sake of argument
that there actually is a particular combination of patient and chemistry where it works. Literally no
one knows if they are that person, or how to know that they are getting that product. For the
average consumer, it’s a meaningless signal, completely lost in the noise of science and marketing.
Not that any of the evidence will actually stop people from “believing” in glucosamine and buying
it in bulk! Glucosamine bottlers really appreciate everyone’s continued gullibility.
P.S. on chondroitin sulfate

The science is basically identical, and indeed there’s a bunch of overlap in the research. All
scientific papers about chondroitin sulfate are good examples of no clear good news. A good
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. 28 In the context of the body of evidence, it’s really quite silly to write a summary that
sounds so positive. Although it’s an aging reference, it was and remains perfectly cromulent: the
New England Journal of Medicine slammed chondroitin sulfate hard back in 2006. 29
Ergo-what? Performance, fatigue, and pain
Ergogenic aids improve physical or mental performance: stronger, faster, better in some way. Comic
books are full of super-soldier serums, the ultimate fictional example. In real life, anabolic steroids
are the most classic way to effectively cheat at sports — nothing else delivers an unfair advantage
quite like that. Most ergogenic aids are less impressive, but the hope is that anything that can
enhance performance is also a kind of medicine — that improvement is improvement, whether
you’re starting from a healthy state or a messed up one. 30
From stimulants like caffeine and cocaine to nutritional fuels like creatine, performance can be
boosted — but usually not much, and often with a price. There ain’t no such thing as a free lunch,
and better lunches usually cost more. They should be used with caution. 31
What about pain? Can a proven performance booster help pain? Perhaps. We know that perception
can change both pain and power. 32 But what we all really want something that we can swallow —
a pain-killer from the supplement store.
All the supplements that allegedly boost performance also have a bit of a reputation of being good
for pain, and precious little evidence. But a link remains plausible in special cases. The largest
subcategory of performance boosting is improved fatigue resistance and recovery, which in turn
may overlap with healing — much of which is just recovery from the effects of acute physical
stress. 33 And that in turn may have some relevance to pain, because that which makes us tired
may also make us hurt. 34 Ever have a hard time telling the difference between pain and fatigue?
They might have some biology in common.
But if any ergogenic aid can treat pain, it has yet to be proven. Creatine is probably the best hope
there is.
Creatine: the most evidence-based common supplement
Creatine is the standard bearer for supplements that aid exercise recovery, and might by extension
have other health benefits including less pain. It is by far the most popular supplement that
actually does what it says on the tin: creatine really does fight muscle fatigue, a benefit that is mainly of
interest to people who use their muscles intensely. Bodybuilders take creatine so they can lift
longer. Muscle cells take longer to tire out when they have extra creatine in their little cellular
pantries. It’s an “energy intermediate,” a molecule that is part of the metabolic recipe for
replenishing the fuel molecule, adenosine triphosphate (ATP is one of the greatest hits of organic
chemistry).
The stuff clearly works on almost everyone, 35 and it

is perhaps the only popular supplement that does. A recovered creatine skeptic — One of the biggest
Examine.com’s mighty creatine page is extremely mind-changes I’ve ever had as a science writer was
thorough and balanced. If you want all the creatine about creatine. It was a victim of careless cynicism
science, just go there: about the industry. I didn’t take it seriously, didn’t look
at it closely enough, and tarred it with the same brush
Creatine is among the most well-researched and as other much less useful products. The good folks at
effective supplements. It can help with exercise Examine.com turned me around on this topic. They
used evidence on me, and it worked.
performance by rapidly producing energy
during intense activity. So, creatine, I’m sorry I misjudged you. You seem like a
stand-up nutraceutical.
For balance, I will point out that some researchers
have some reservations — but, notably, they still
acknowledge the benefits for muscle recovery. They just aren’t sure if it translates to measurable
benefits for anyone but bodybuilders. 36
Currently, the scientific literature supports creatine supplementation for increased

performance in short-duration, maximal-intensity resistance training. Whether these
effects of creatine supplementation lead to improved performance on the field of play
remains unknown.
Going beyond sports to other medical benefits is even more of a reach, but there is some evidence
that creatine is useful for some other conditions. 37 Certainly not osteoarthritis, that most universal
of painful conditions, and a good proxy for many others. 38
But muscular dystrophy is a very interesting positive example. There’s a common form of muscular
dystrophy that routinely goes undiagnosed, and yet causes excessive muscle fatigue and
soreness. 39 It’s a subtle and specific cause of pain that might actually respond well to creatine,
even if you have no idea why. 40 But it’s also a perfect example of why a supplement like creatine
might help one person’s pain but not most others.
Another intriguing example of the same type: creatine supplementation might relieve a painful side
effect of a common class of drug, the cholesterol-lowering “statins” for heart disease prevention
(like Lipitor). 41 There’s little direct evidence of this so far, but it’s plausible. 42 If this effect exists,
it’s great for a specific group of patients.
But there isn’t a shred of evidence that creatine’s fatigue fighting benefits have the slightest
relevance to pain in general, or any common kind of chronic pain.
Creatine is super safe, too!

Creatine also appears to be one of the safest of all supplements: “The only consistently reported
side effect from creatine supplementation that has been described in the literature has been weight
gain.” 43
Creatine may give some people trouble with their sleep, and that happened to me (see my
insomnia article for the story). But I suspect this isn’t a major issue for many people: it doesn’t get a
mention in the scientific literature. It’s just a side effect some people report that I seemed to
experience myself.
Whey protein (AKA protein powder, protein shakes)
Whey powder is what’s in those large buckets you see in supplement stores that seem to cater
mainly to bodybuilders, although also very popular with the aspirational market: people who buy
it optimistically thinking they will do enough weightlifting to need it, making it one the best-selling
of all the non-vitamin supplements (collagen is the other big one). The idea is that it’s a convenient
source of fairly pure protein, like egg whites but cheaper and nicer when blended with blueberries.
It’s a mixture of globular proteins isolated from whey, the liquid material created as a by-product of
cheese production. It is prized by athletes as a protein source to aid in building muscle. There is no
controversy regarding bodybuilding benefits, but it’s also not doing anything special: it is literally
just a more convenient way to eat the large amounts of protein needed by anyone doing a lot of
weightlifting.
There is also a lot of wild speculation that it also has anti-inflammatory properties, and/or some
other good-for-pain effect. I have had any number of people write to me over the years to tell me
that eating a lot of protein (in whey or other forms) had cured their chronic pain. There is exactly
zero real data about this — just anecdata.
Despite the fact that it’s basically just protein, there are actually several side effects and safety
concerns about whey powder. Glucoasmine is probably safe at recommended doses, but pancreatic
damage is possible with more 44 These products also routinely contain added sugar — a
nutritional hazard. And there’s also the contamination issue with all supplements, which definitely
applies to this huge category. In 2018 the Clean Label Project screened 134 products for 130 types of
toxins and found that many protein powders contained heavy metals, bisphenol-A (BPA),
pesticides, or other contaminants. One protein powder contained 25 times the allowed limit of BPA.
Horrifying.
Maybe stick to egg whites and skinless chicken breasts?
Bromelain, the lesser known pineapple-derived anti-inflammatory

nutraceutical that has been in research limbo for ages
Bromelain is worthy of a 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 might have the potential to be used as a
substitute for anti-inflammatory drugs. It’s a substance with potentially anti-inflammatory
properties that just happens to come from pineapple in the same way that aspirin comes from
willow bark. But for now — and probably forever — it’s something you get from the supplement
store, not the drugstore.
In 2004, Brien et al reviewed a dozen early studies of bromelain research in Evidence-based

Complementary & Alternative Medicine. 45 Despite a blatant conflict of interest — Brien works for a
bromelain bottler — the review seems balanced, 46 and the authors do not fail to point out
weaknesses in the evidence (lots) or concerns about adverse effects (definitely possible). Their
conclusion is cautiously positive (surprise surprise), and seems to be justified by the evidence
reviewed. “The currently available data do indicate the potential of bromelain in treating
osteoarthritis.”
However — and this is critical — we already have medications that do “something” to help people
with painful osteoarthritis. To qualify as a replacement for existing medications, bromelain 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. And proving fewer side
effects is tricky — a high bar to clear, requiring multiple large trials. 47
This was not even remotely established in 2004. How about fifteen years later?
2021 bromelain science update: no news is bad news

Almost nothing has happened scientifically with bromelain since 2004. Just a single study strikes
me as legit enough to be worth citing, and only barely: it’s just a pilot study… and negative. It
showed that bromelain was no better than existing medications for arthritis. 48
Other than that, there are just a handful of minor

clinical trials of bromelain, many of them blatant
junk science, plus the usual cart-before-horse papers,
with no horse in sight. 49 There’s not even enough
There are just a handful of
for systematic review or meta-analysis, and indeed minor clinical trials of
there haven’t been any — not even the seemingly
inevitable garbage-in-garbage-out reviews with bromelain, many of them
“more study needed” conclusions. This substance is
still so unstudied that it doesn’t even really qualify blatant junk science, plus the
for “promising” status.
usual cart-before-horse
In short, there really isn’t any bromelain research
worth discussing. There is just a remote possibility papers, with no horse in
that pineapples contain a molecule that is not only as
useful as existing anti-inflammatory drugs but also
sight.
has fewer side effects. Literally every single existing
anti-inflammatory drug has a unique batch of side effects — so what are the odds that bromelain is
both efficacious and safer? Not great.
And yet it’s been in stores the whole time, unproven and unregulated. What could possibly go
wrong?
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 — a performance booster — and, for once, the
evidence actually supports popular belief (also true of creatine and several other ergogenic aids,
because performance is actually relatively easy to trivially boost). It doesn’t even matter how much
of it you drink normally: you’ll get a boost from caffeine whether you guzzle the stuff every day, or
never touch it. 50
I’ve played a lot of ultimate with players who are younger, fitter, and more talented than I am.
Truly, 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”
(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 swill 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.” 51 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 abuse — vicious cycle of self-medication, caffeine every morning, alcohol every night, very
common — could well 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, and even a short-
term reliever of pain, but probably also a long-term aggravator of pain when chronically abused. 52
Bottom line: caffeine is a known mild analgesic and ergogenic aid, but caffeine abuse — which is
super common — is a plausible risk factor for chronic pain.
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.
(P.S. It also doesn’t dehydrate you. That’s a silly myth. 53 )
Energy drinks — Everyman’s ergogenic aid

The most ubiquitous of the ergogenic aids are the energy drinks, like Red Bull, Full Throttle, or Rockstar.
Virtually every imaginable and claimed ergogenic aid has been put into drink form for you — Red Bull
“Vitalizes Body and Mind” and their website is festooned with athletic imagery. But almost all of them
mainly rely on caffeine for the real effect. Pharmacist and writer Scott Gavura cuts energy drinks down to size:
Despite the impressive lists of ingredients and slick marketing, these products are essentially
caffeine delivery vehicles, most of which come loaded with sugar.
Although caffeine can actually boost performance in some ways, technically it’s “just” a stimulant, not a true
ergogenic aid: that is, it makes us feel like we have more energy rather than actually having it. Cocaine and
other narcotic amphetamines do the same thing, only more so, infamously making people overconfident
about abilities that have not actually changed.
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 lasts 3–4 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 doctor about this
one day, he recommended that I try arginine supplementation. Why?
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 of the non-essential amino acids in the body, much of which is
stored in muscle. Both glutamine and arginine get depleted in people recovering from major injury
and illness, in which case they are regarded as “conditionally essential” — that is, they are essential
during emergencies, when there’s lots of tissue rebuilding going on. For this reason, glutamine is
used medically to treat the critically ill (controversially, but it’s used; 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 — “I worked out so hard it’s like an emergency!” — 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, 54 and therefore it
is also a bit unlikely that they can benefit from supplementation for this reason. And if they can’t
get depleted, we probably can’t either.
There are other possible reasons. 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, 55
such as stimulation of growth hormone production, 56 or dilating blood vessels. 57 Guessing
about how this stuff works out in the real world is
basically gambling with your biochemistry, though.
The state of the clinical research for arginine and Guessing about how this stuff
glutamine supplementation is predictably poor. Their works out in the real world is
use can only be faith-based, not evidence-based. I
spent about a half hour poking around for basically gambling with your
glutamine/arginine science on the web and PubMed,
and determined only that they are nearly unstudied biochemistry
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 citing any research). I couldn’t find any thorough critical analysis of either
(although MayoClinic.com has dry summaries for both). I found one good-news study, but it’s
weak sauce. 58
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 substances do for something as trivial as a little bit of muscle soreness after
exercise.
Meanwhile, there are safety concerns for chronic supplementation of either. For glutamine
“neurological effects were the most frequently observed,” 59 and arginine is “associated with death
in certain groups of heart patients.”
Death. Now there’s a side effect. Remember: gambling with biochemistry.
Branched-chain amino acids: leucine, isoleucine, valine
And sneezy and happy and dopey…
The branched-chain amino acids (BCAAs, or just “protein supplements”) are three of the six
essential amino acids in human physiology and they are widely believed to be more important to
recovery than the other amino acids for more or less the same reasons (like the non-essential
glutamine and arginine, see above): that is, people hope they are better at promoting protein
synthesis, and therefore may help muscle growth/repair after exercise, and that in turn might — in
theory — also reduce soreness, aid recovery, and generally make muscles better.
For several years there was a lot of excitement (and protein supplement sales) on the strength of
promising preliminary evidence about BCAAs… which then failed to be replicated. Yet another
case of “promising” research that went nowhere. Recent trials and reviews of this topic are mostly
negative. 60 61 62
Fedewa et al is the only recent review to claim victory: “A large decrease in
DOMS occurs following BCAA supplementation after exercise compared to a placebo
supplement.” 63
There’s always the possibility that certain people, with just-so biology, are benefitting way more
than others. But clearly its benefit for the average human is not robust enough to be easily
confirmed. The BCAAs are on even thinner scientific ice than glutamie and arginine. So really very
thin indeed.
Collagen: ever so slightly good for arthritis, maybe
Collagen — you’re basically made of the stuff. It is an extremely abundant proteinacious building
block of connective tissue, currently popular as an arthritis treatment in the form of products like
Genacol, and also used extensively for skin and nail health. There are a bunch of different forms
from various animals sources — pig, cow, fish, shark! The evidence supporting this bazillion-dollar
industry is, as usual, embarrassingly weak. A 2019 review described the science as “controversial”
and “minimal” — but also “promising”! 64
Will a Jello diet help your joints? It’s a short leap of faith from skin health to the health of other
important tissues, like cartilage, where there is more hope and even less evidence.
The skeptical perspective is straightforward and predictable: eating collagen is probably mostly or
entirely useless. Assuming extra collagen is helpful in any way, it is probably impossible to get it by
eating it in the form of a supplement. 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.
But evidence! And complexity! Nothing in biology is ever simple. Exactly what kind of collagen
may be important, and there’s just enough smoke in the evidence to wonder if there could possibly
be a fire here somewhere. There are a bunch of positive studies, but are they positive enough for any
sensible person to care? The damned-with-faint-praise problem is substantial. The only major recent
scientific review of collagen for arthritis does indeed seem to bring good tidings, but how good? The
authors summarize the improvements detected by trials as “significant,” but that’s a classic bit of
spin and a well-known science foul: they mean statistically significant, which is not the same thing
as important or major. 65
In fact the improvements were right around the threshold of clinical significance. 66 As Scott says
in a much more recent article: “There are inconsistent signs of benefit and of unclear clinical
importance with collagen hydrolysate.” Yup.
Medical science tends to produce “promising” results

that are later overturned by more and better data. Attack on the sharks — Another major concern
about collagen is the extensive slaughter of sharks to
And then there’s safety: eating pure collagen isn’t meet the demand — an environmental cost that is
harmless. It’s a weird non-food that can definitely far too high for such dubious benefits. Not all Type II
mess with people There’s almost no hard data about collagen comes from sharks, but that’s where far too
it, but lots of anecdata and concerns in principle from much of it comes from.
healthcare professionals. Allergic reactions,
hypercalcemia, insomnia, depression, kidney stones, constipation and diarrhea… all possible. This
kind of supplementing could absolutely backfire for pain patients.
Remember: like most of the supplements, collagen is a natural part of part of food. Extracting and
isolating it and consuming it in quantities far beyond what you’d ever get from a normal diet is not
what nature intended.
Turmeric and curcumin: not just tasty
Curcumin is a spice. It’s the interesting molecule in the bright orange South Indian spice, turmeric,
a flamboyant cousin of ginger. There are also other similar molecules (the “curcuminoids”), which
are polyphenols, huge category of molecules that is associated with astringency and the healthiness
of many foods: some fruits and most berries, especially grapes and therefore also wine, plus
chocolate and tea. Polyphenols are so diverse and complex that it doesn’t really make sense to
think of them as “healthy” and more than you’d think that all snacks are healthy. For instance, they
may or may not be “antioxidants,” which in turn are also extremely complex and may or may not
actually be healthy.
Is curcumin an antioxidant? Healthy? Good for pain? Yes, probably, and perhaps.
According to Examine.com, “Supplementation of curcumin reliably reduces markers of

inflammation and increases the levels of endogenous antioxidants in the body.” Does that translate
to benefits for a good proxy for all kinds of pain, like arthritis? As usual, the answer is a bit “meh”
— yet another case of “promising” data that doesn’t pass the “impress me” test. From a 2017
review:
Curcuminoids may have some beneficial effects on knee pain and quality of life in
patients with knee OA. However, they are less effective at relieving pain compared
with ibuprofen. Curcuminoids appear safe on the short-term, and may reduce the need
for rescue medication. Published RCTs vary in reporting quality, are characterized by
small sample sizes, and have all been conducted in Asia.
Less than ibuprofen, eh? Well, I like curry anyway…
In a 2015 study, “curcumin caused moderate to large reductions in pain” in 17 men with extremely
sore leg muscles. 67 It also helped some aspects of strength loss. The effect size here actually does
impress me, and these results constitute the only really good science news about any kind of
treatment for exercise soreness, by the way. Now it just needs to be replicated! And it still hasn’t.
Good and promising news, but simply unverified, and there are about a thousand ways that one
study can be wrong.
There is a complication with curcumin that drives up the cost and risk of wasting your money:
although curcumin is widely available, unfortunately it is poorly absorbed without other agents
such as black pepper extract (e.g. piperine). Most bottles advertise one method or another of
enhancing absorption, and some of them use it to justify a much higher price point, but it’s hard to
know (maybe impossible) how well any of them actually work. Just be aware that straight
curcumin may not be effective.
As always, anything that can have a positive effect can also have a negative effect. Curcumin isn’t
likely to cause anything worse than indigestion for most people, but it does have some odd
interactions with common drugs that many aging people take: it can actually boost the effect of
diabetes meds and blood thinners (including aspirin); and it can cancel the benefits of antacids.
Tart cherry juice
There’s just enough good news about black cherry juice to justify talking about it. Just.
Recovery from intense exercise can probably be at least partially enhanced with, of all things, tart
cherry juice. It’s the antioxidants, see. (That word makes me a little suspicious.) Cherry juice, it
seems, is chock-a-block with them and other “anti-inflammatory agents.” None of these things
have proven to be especially helpful for muscle soreness before. But the cherry cocktail is special,
because apparently if you give cherry juice to several young men and then make them exercise
their biceps viciously, they experience a statistically significant 22% less strength loss 68 than their
poor peers who got fake cherry juice: black cherry Kool-Aid. 69
That’s the good news: black cherry juice made a modest but clear and worthwhile difference for
those guys in that test. The bad news? It had no effect whatsoever on the symptom everyone
actually cares about: the pain. “Relaxed elbow angle and muscle tenderness were not different
between trials.”
I was going to run to the store to buy some cherry juice when I read that. Now I think I’ll just walk.
Can tart cherry juice help you sleep?
Probably not much, if at all. Supposedly the stuff contains melatonin, or melatonin precursors (and
I won’t even bother going down that rabbit hole; it’s doomed to be a moot point anyway). For
context, you should know that your guide is a hard-core insomniac: I have a bonified life-altering
sleep disorder, narcolepsy, and narcoleptics have as much trouble staying asleep as we do staying
awake. My wife, struggling with her own sleep issues, brought home some tart cherry juice — hard
to find and not cheap — because a friend told her it was good for insomnia. Millions have heard
the same, because the mere existence of what looks like a positive study is all the internet needs to
justify a kajillion blog posts declaring that cherries can slay our insomnia demons.
The reality is that there are just a handful of pilot studies (I could find only 3 in the last decade)
with technically positive but pathetically underwhelming results. 70 71 72 There is effectively no
actual science here. The onlys tory here is yet another supplement hype case study.
Vitamin D
Vitamin D deficiency is probably more common than once suspected — at least 1 in 20 people in
the lowest estimates, 73 and possibly many more. 74 It can also cause subtle widespread pain that
may be misdiagnosed as fibromyalgia and/or chronic fatigue
syndrome, including symptoms like muscle and bone aching, 75
fatigue and weakness, lower pain threshold, and more acute soreness
after exercise that is slower to resolve.
If there’s only one supplement you’re taking for your

health and your diet is decent, it should probably be
Vitamin D.
~ Herman Gill, Examine.com editor Michele Blackwell on Unsplash
(Vitamin D reference page)
However, vitamin D supplementation in healthy people is dubious at best. Major reviews have
declared it to be nearly useless. 76 77 Debate rages on, of course, but there is plenty of evidence to
support “reasonable doubt.”
I’ve covered this important topic in much greater detail in a separate article: Vitamin D for Pain.
Magnesium
Magnesium is one of the essential minerals — “life finds a way,” but not without a good supply of
Mg it doesn’t! We use a lot of the stuff: it’s one of the big three mineral nutrients, along with sodium
and potassium. If it’s missing, blood pressure rises, glucose tolerance drops, and our nerves get just
a wee bit trigger happy. Interestingly, fixing an magnesium deficiency is actually sedating! It
literally calms your nerves… and that could certainly be relevant to chronic pain. Most plausibly, it
makes some sense in principle that it be helpful for cramping and/or neuropathy (pain originating
from insult to the nervous system itself).
Despite its biological importance and being readily available in food, deficiencies seem to be both
surprisingly common and possibly related to pain. 78 It may also “hide” from routine blood
tests. 79
Magnesium in roughly the same category as vitamin D deficiency and pain: it might matter to a lot
of people, especially pain patients, and supplementing is quite safe. In the extremely scammy
world of supplements and nutraceuticals, vitamin D and magnesium both stand out as being less
lame — especially for chronic pain patients.
Not that it has actually been studied properly, of course! It is merely plausible, and there are some
encouraging hints (especially for neuropathic pain specifically). But the science is woefully
incomplete, and what little there is to cite mostly just punctuates that. 80 81 To date, I am aware of
just one promising test of magnesium supplementation for any somewhat common kind of pain,
but it’s focused on back pain with a clear neuropathic component 82 — good to know, but just one
study, and most kinds of pain are neuropathic.
Magnesium for cramps

Cramps are not clearly caused by electrolyte loss from dehydration. 83 84
If electrolyte loss caused cramps, we would fully expect supplementation to help — and people
sure do. But this wildly popular belief remains ignored by science. The well-respected publisher of
pooled data reviews, The Cochrane Collaboration, simply had no data to pool on this topic. 85 The
data on magnesium for cramps due to pregnancy and disease is almost as scarce and mixed. For
common unexplained cramping in adults (e.g. foot cramps in the night), there was just enough data
to conclude that magnesium is “unlikely” to help.
Eating your magnesium

Unlike with vitamin D, it’s downright easy to get enough magnesium from a reasonably healthy
diet. Despite this, Mg deficiency is common even in wealthy places because grains and meat are
poor sources, and the good sources are not nearly as popular: salad, basically. Leafy greens and
nuts/seeds, especially spinach and pumpkin seeds. And potatoes are also a decent source, which is
hardly a hardship. Anyone with a magnesium deficiency can suck it up and eat a nutty salad a
couple times a week — or potato salad! — and Bob’s your uncle. So just eat it.
See dietary sources of magnesium.
How come you’re always such a fussy young man?

Don’t want no Captain Crunch, don’t want no Raisin Bran
Well, don’t you know that other kids are starving in Japan?
So eat it, just eat it
~ Weird Al Yankovic, “Just Eat it”
Bathing in magnesium
Epsom salts baths are basically magnesium baths — is like going a half hour out of your way to
buy stale bread from a corner store when you live next to a good bakery. Nevertheless, Epsom salts
are extremely popular and widely regarded as a good method of supplementing magnesium.
Which is why I cover this topic in substantial detail detail in my article about Epsom salts.
But it worked for me! The role of anecdotes and testimonials
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. Consider the startling way that placebo worked just as well
as intravenous magnesium as a back pain treatment *at least two weeks* of a six month trial. 86 No
one could be blamed for misinterpreting that as a full-blown success.
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 seem 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.
Big Suppla: Large supplement corporations are not only just as bad or worse
than the pharmaceutical one, many of them are the same corporations
Cranking about Big Pharma while giving the supplements industry a free pass really chaps my
arse.
It’s not that the pharmaceutical industry is innocent — certainly not! Scandals galore! Seriously
major issues, even! (See Bad Pharma, by one of my favourite authors.) But paranoia about Big
Pharma has reached a fever pitch that isn’t even remotely proportionate to the problem, and the
most shrill critics seem unable to comprehend that the supplements industry — let’s call them “Big
Suppla” — is both insanely profitable and much more unregulated and corrupt.
The double standard is maddening.
It’s also critical to understand that Big Suppla is Big Pharma. There’s huge overlap. Pharmaceutical
companies own most of the big supplement companies now, and use them to produce massively
profitable products with near-zero regulation. A substantial percentage of the profits generated by
supplements are going straight into Big Pharma’s pockets.
A 2010 study in the British Medical Journal (which scientifically slams the dynamic duo of
supplements, glucosamine and chondroitin) noted that studies funded by Big Suppla tend to
produce results that were — here’s a shocker — biased in favour of supplements! 87
And the supplement companies that are not owned by Big Pharma? Many of the biggest are far
worse than Big Pharma: the deeply scammy multi-level marketers. More on those below.
“Big Suppla” is now evidence-based debunking

The term “Big Suppla” is intended to be a witty delivery mechanism for this debunking truth
bomb. It’s quite clever. If Suppla is just as Big as Pharma… well, the whole point is that the
implication is so clear that no further explanation is even required.
But does that reach people? Is it an effective debunking strategy? Someone actually tested this, and
the results were positive, huzzah! Minds were changed! This is a great relief for me to hear, because
I started deploying “Big Suppla” in about 2006. Mijatović et al tested the effect of this terminology
by giving about 250 people three different kinds of information about the supplements industry: 88
Neutral information was just the origins of the words “supplements” and “alternative.”
Big Suppla information framed the industry as “powerful, profit-oriented, and unregulated.” Which
it actually is.
Baby Suppla information portrayed the supplements industry as a virtue-motivated underdog.
Which it definitely is not.
The test results were better than science communicators could have hoped for. Not only did the
“Big Suppla” framing change minds, it even worked on some of the hardest targets: subjects who
were prone to conspiratorial thinking. Those people were more likely to be keen on supplements to
begin with, but they were still persuaded by “Big Suppla.” Perhaps it’s because this debunking
method exploits the “follow the money” trope that practically defines conspiratorial thinking.
Will the real underdog please stand up?

Skeptics and debunkers do a lot of joking about how we’re in the wrong line of work, because it
would obviously be so much easier to get rich if only we were willing to just lie, tell people
whatever they want to hear, and sell easy solutions to hard problems. Which is exactly what the
bad guys do. For instance, Alex Jones' Infowars Store — dominated by supplements and survival
gear — Made $165 Million Over 3 Years (HuffPost.com). But Alex Jones constantly told his
followers things like, “As much begging as I do, we can barely pay the bills.”
That would be a lie even if he’d only made one million dollars, instead of one hundred sixty-five
million.
Defy that lie! Tell the truth: false hope and fear are highly profitable, while truth and realism are the
actual underdogs.
The Multi-Level Marketing Connection: Supplements and Fraud
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 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. They are technically legal, but they
shouldn’t be. As with supplements themselves,
legality is a poor guideline — many scams are legal!
MLMs are technically legal,
It says something about supplements that they are so
routinely sold by such scammy methods. Probably
but they shouldn’t be. As with
every imaginable product has been sold via MLMs, supplements themselves,
but supplements and snake oils are that industry’s
favourite product category by far. legality is a poor guideline —
Alternative medicine practitioners are juicy targets many scams are legal!
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.
Protandim: The most prominent MLM-powered supplement
Protandim is a patented “blend of phytonutrients” from a multi-level marketing company, with

slick marketing emphasizing anti-aging effects: “the only supplement clinically proven to reduce
oxidative stress by 40%, slowing down the rate of cell aging to the level of a 20 year old.” Anti-
aging claims should always set off every caveat emptor alarm you’ve got. The product allegedly
treats pain and inflammation via antioxidant effects and “activating” the Nrf2 protein (regarded as
the “master activator” of antioxidant gene expression). The biology of antioxidants is dizzyingly
complex, and only large, high-quality human clinical trials can establish the efficacy of any product
that tries to “hack” it.
There have been a handful of test-tube and animal studies, no human studies related to pain at all,
and only two human studies — both irrelevant, both negative. In 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!” (Dr. Hall has written quite a bit about Protandim on
ScienceBasedMedicine.org over the years. 89 )
Protandim proponents believe there’s lots of supporting research, but of course that’s what they all
say. And the FDA disagrees.
Potential side effects are unstudied and unknown — another red flag for anything that allegedly
has potent benefits.
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Information is Beautiful
Here’s a great way to conclude this tour of nutraceuticals: InformationIsBeautiful.net publishes a
brilliant, beautiful and interactive visualization of the popularity and effectiveness of popular
dietary supplements, which they have kept up-to-date since 2009. It’s a really 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, it’s an extremely interesting (and pretty)
visualization:
Rather a lot of products are below the “worth it” line! There are also many above the “worth it” line,
but please notice that few of those have anything to do with body pain. Just cannabis (and feverfew
for migraine)… and cannabis only barely, and even that’s debatable and highly complex (see
Marijuana for Pain). Although I mostly agree with what I see here, I think — as always — that
evidence is given too much credit for being “promising” when it’s actually really weak sauce.
About Paul Ingraham

I am a science writer in Vancouver, Canada. I was a Registered Massage Therapist for a decade and the assistant editor of
ScienceBasedMedicine.org for several years. I’ve had many injuries as a runner and ultimate player, and I’ve been a chronic pain
patient myself since 2015. Full bio. See you on Facebook or Twitter, or subscribe:
Related Reading
Chronic, Subtle, Systemic Inflammation — One possible sneaky cause of puzzling chronic pain
Anxiety & Chronic Pain — A self-help guide for people who worry and hurt This article covers
prebiotics and turmeric/curcumin, which both show some minor potential as treatments for anxiety.
Other pain medications:
The Science of Pain-Killers — A user’s guide to over-the-counter analgesics like acetaminophen,
ibuprofen, and more
Voltaren Gel: Does It Work? — The science of the topical pain-killers, which can be effective
without dosing your entire system
Opioids for Chronic Aches & Pains — The nuclear option: Oxycontin, codeine and other opioids for
musculoskeletal problems like neck and back pain
Does Epsom Salt Work? — The science and mythology of Epsom salt bathing for recovery from
muscle pain, soreness, or injury
Marijuana for Pain — The hype versus the science! What does the evidence actually show about
cannabis and chronic pain?
Vitamin D for Pain — Is it safe and reasonable for chronic pain patients to take higher doses of
Vitamin D? And just how high is safe?
Does Arnica Gel Work for Pain? — A detailed review of popular homeopathic (diluted) herbal
creams and gels like Traumeel, used for muscle pain, joint pain, sports injuries, bruising, and post-
surgical inflammation
Homeopathy Schmomeopathy — Homeopathy is not a natural or herbal remedy: it’s a magical idea
with no possible basis in reality
Muscle relaxants — This topic is covered in several of my books in detail — low back pain, neck
pain, trigger points, frozen shoulder, headaches. There is also condensed (but free) information
about them in Cramps, Spasms, Tremors & Twitches.
What’s new in this article?
35 updates have been logged for this article since publication (2010). All PainScience.com updates
are logged to show a long term commitment to quality, accuracy, and currency. more
Jun 23, 2022 — Added a section about probiotics and the microbiome. Can gel caps full of “good bacteria” treat
pain outside the gut?
June — Added a section about Coenzyme Q10 and statin-associated myalgia (SAM).
March — Added a section, “‘Big Suppla’ is now evidence-based debunking.”
February — Added important disclaimer about adulteration and contamination, regarding concerns about the
accuracy of a key paper on that topic.
2021 — Substantive science update on the efficacy of treating pain with magnesium.
2021 — Added warning about the slaughter of sharks required for collagen production.
2021 — Added minor new citation and commentary: “Survey says most people don’t care what the science says.”
2021 — Several miscellaneous edits after promoting the rebooted version of this article. Most notably, I added
some safety information about curcumin, and a full-blown science update about tart cherry juice for insomnia,
but there have been many other minor changes.
2021 — Tied up some loose ends and corrected a bunch of minor errors that crept in during the wave of recent
updates. Page is in great shape now, I think. The main thing missing? Some popular supplements! Mostly in the
vitamins/minerals category. I will chip away at them over time, of course.
2021 — Many minor improvements to the topics of Glutamine and arginine, branched-chain amino acids, and
collagen.
2021 — Science and citation update on the topic of supplement contamination and adulteration.
2021 — A thorough science update on bromelain — such as it is. More like an update on the lack of science. But the
section is much more informative now, even if disappointingly so.
2021 — Complete overhaul of everything about ergogenic aids in general, their possible relevance to pain, and
creatine as the primary example — still actually effective for muscle fatigue (hooray, something that works!), but
probably not for pain.
2021 — Revision and science updates for the glucosamine and chondroitin section. I was particularly exasperated
by and sassy about these embarrassingly unimpressive supplements.
2021 — Added an adapted version of Peter Brannen’s highly relevant joke about the simplicity of supplementation
versus the complexity of metabolic pathways.
2021 — Rewrote the fish oil section, with significant science updates.
2021 — Major reorganization of the article to make it more useful and comprehensive. Added topics, removed
others. A variety of other science updates to come.
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.
2021 — Proofreading and editorial polish: corrected about 20 minor errors.
2020 — Minor science update, a couple new citations, and a new section about anti-inflammatory nutrition.
2017 — Added a small but important public service announcement about supplement contamination, based on
Rao et al.
2017 — Added a citation about the effect of caffeine on performance.
2017 — Added a footnote about the (lack) of evidence concerning the long term effects ogf caffeine on pain.
2016 — Added new section about vitamin D.
2016 — Added a mobile-only article summary.
2016 — Minor science update about glucosamine.
2012 — Turned around on creatine. That stuff seems to work as advertised.
2012 — Added a reference to a new Protandim study, only the second ever in humans … and it’s irrelevant and
negative.
2011 — Added collagen, and some comments about bioavailability.
2011 — A couple more references for arginine and glutamine. Also: improvements to layout of main supplements
table.
2011 — Extensive upgrades and expansion of information about glutamine and arginine.
2011 — Added reference information about Protandim, and “bottle of hope” image.
2011 — Added more evidence of underwhelming benefit to chondroitin sulfate.
2011 — Added more information about the connection between nutraceuticals multi-level marketing.
2011 — Added “safety” column and data to main chart.
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.
2010 — Publication.
Notes
1. Rodriguez NR, DiMarco NM, Langley S, et al. Position of the American Dietetic Association, Dietitians of Canada, and the
American College of Sports Medicine: Nutrition and athletic performance. J Am Diet Assoc. 2009 Mar;109(3):509–27.
PubMed #19278045 ❐
This is a dense paper on how nutrition can enhance athletic performance. It describes in great detail the position of the
American Dietetic Association, Dietitians of Canada, and the American College of Sports Medicine, so it’s very “official” (for
whatever it’s worth). Some highlights:
they endorse sports drinks (which badly undermines the credibility of these recommendations, because sports drinks are
ridiculous, please see Wagner)
energy and macronutrient needs, especially carbohydrate and protein, must be met when exercising hard
vitamin and mineral supplements are not needed if adequate energy to maintain body weight is consumed from a variety of
foods
ergogenic aids are poorly regulated and should be used with caution
And of course they recommend the services of a “qualified sports dietitian and in particular in the United States, a Board
Certified Specialist in Sports Dietetics.”
2. See Do calcium supplements cause heart attacks?
3. Warensjö E, Byberg L, Melhus H, et al. Dietary calcium intake and risk of fracture and osteoporosis: prospective longitudinal
cohort study. BMJ. 2011;342:d1473. PubMed #21610048 ❐ PainSci #55295 ❐
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 interest 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.
4. Chen F, Du M, Blumberg JB, et al. Association Among Dietary Supplement Use, Nutrient Intake, and Mortality Among U.S.
Adults: A Cohort Study. Ann Intern Med. 2019 May;170(9):604–613. PubMed #30959527 ❐ PainSci #52693 ❐
5. This is the “healthy user effect.” See Who takes dietary supplements, and why?
6. White CM. Dietary Supplements Pose Real Dangers to Patients. Ann Pharmacother. 2020 08;54(8):815–819.
PubMed #31973570 ❐ “Microbial and heavy metal contamination, adulteration with synthetic drugs (including drugs
banned from the United States), substituting herbs, and fraudulently specifying ingredients on the label have all occurred.”
7. Rao N, Spiller HA, Hodges NL, et al. An Increase in Dietary Supplement Exposures Reported to US Poison Control Centers.
J Med Toxicol. 2017 Jul. PubMed #28741126 ❐
8. Martínez-Sanz JM, Sospedra I, Ortiz CM, et al. Intended or Unintended Doping? A Review of the Presence of Doping
Substances in Dietary Supplements Used in Sports. Nutrients. 2017 Oct;9(10). PubMed #28976928 ❐ PainSci #51803 ❐
Substances prohibited by WADA were found in most of the supplements analyzed in this review. Some of them were
prohormones and/or stimulants. With rates of contamination between 12 and 58%, non-intentional doping is a point to
take into account before establishing a supplementation program.
9. Walpurgis K, Thomas A, Geyer H, Mareck U, Thevis M. Dietary Supplement and Food Contaminations and Their
Implications for Doping Controls. Foods. 2020 Jul;9(8). PubMed #32727139 ❐ PainSci #51802 ❐
Even though controversial positions concerning the effectiveness of dietary supplements in healthy subjects exist, they
are frequently used by athletes, anticipating positive effects on health, recovery, and performance. However, most
supplement users are unaware of the fact that the administration of such products can be associated with unforeseeable
health risks and AAFs in sports. In particular anabolic androgenic steroids (AAS) and stimulants have been frequently
found as undeclared ingredients of dietary supplements, either as a result of cross-contaminations due to substandard
manufacturing practices and missing quality controls or an intentional admixture to increase the effectiveness of the
preparations.
10. Mathews NM. Prohibited Contaminants in Dietary Supplements. Sports Health. 2018;10(1):19–30. PubMed #28850291 ❐
PainSci #51800 ❐
Poor manufacturing processes and intentional contamination with many banned substances continue to occur in dietary
supplements sold in the United States. Certain sectors, such as weight loss and muscle-building supplements, pose a
greater threat because they are more likely to be contaminated. Athletes will continue to be at risk for adverse events
and failed doping tests due to contaminated dietary supplements until legislation changes how they are regulated.
11. 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.
12. 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.)
13. Blendon RJ, Benson JM, Botta MD, Weldon KJ. Users' views of dietary supplements. JAMA Intern Med. 2013 Jan;173(1):74–6.
PubMed #23403846 ❐
Blendon et al. did a survey of 1579 adults looking for users of dietary supplements (but not vitamins or mineral): 38% of
those took some supplement in the past two years, and 13% took a supplement regularly, with fish oil topping the chart.
Their reasons for taking supplements included: “to feel better” (41%), “improve energy levels” (41%), “boost your immune
system” (36%), “digestive issues” (28%), and “lower cholesterol” (21%). Incredibly, only a quarter of them thought they
would pass on supplement if a trial concluded it was ineffective.
14. www.theatlantic.com [Internet]. Yong E. The Pandemic's Biggest Mystery Is Our Own Immune System - The Atlantic; 2021
May 18 [cited 21 May 18].
An extremely well-written piece bout the bewildering complexity of the immune system in the context of the COVID
pandemic. As rich an article as it is, I primarily cite it for the useful sentiment baked right into the title: that immunology is
so complex that even the most educated guesses about how it works are routinely wrong or incomplete.
15. Tsuchiya Y, Yanagimoto K, Nakazato K, Hayamizu K, Ochi E. Eicosapentaenoic and docosahexaenoic acids-rich fish oil
supplementation attenuates strength loss and limited joint range of motion after eccentric contractions: a randomized,
double-blind, placebo-controlled, parallel-group trial. Eur J Appl Physiol. 2016 Jun;116(6):1179–88. PubMed #27085996 ❐ A
small 2016 test of the effect of eight weeks of fish oil supplementation on recovery from weight lifting in 24 men. The
researchers measured outcomes in many ways. Although they observed some benefits, the results were modest, and only for
range of motion and strength, not for pain (or several other measures, such as various blood test results). There were an
assortment of isolated minor wins for fish oil — e.g. less pain on day 3 after the exercise — but that’s to be expected in any
set of data (especially when it comes from a group of subjects this small).
16. Thielecke F, Blannin A. Omega-3 Fatty Acids for Sport Performance-Are They Equally Beneficial for Athletes and Amateurs?
A Narrative Review. Nutrients. 2020 Nov;12(12). PubMed #33266318 ❐ PainSci #51787 ❐
17. Chowdhury R, Stevens S, Gorman D, et al. Association between fish consumption, long chain omega 3 fatty acids, and risk
of cerebrovascular disease: systematic review and meta-analysis. BMJ. 2012 Oct;345:e6698. PubMed #23112118 ❐
PainSci #51781 ❐ This review compared many trials of eating fish to many trials of eating fish oil, finding that fish on a plate
is measurably better. Based on the data they crunched, eating actual fish twice week reduces stroke risk by about 6%
compared to fish oil supplements (which showed a benefit, technically, but a statistically insignificant one). Maybe omega-3
fatty acids just don’t have the same effect in isolation. Or maybe eating more fish just displaces less healthy foods? There are
a couple of very beefy paragraphs in the paper discussing all the possible explanations for the difference. Or maybe the data
is just misleading! See next reference to Chen et al!
18. Chen C, Huang H, Dai QQ, et al. Fish consumption, long-chain omega-3 fatty acids intake and risk of stroke: An updated
systematic review and meta-analysis. Asia Pac J Clin Nutr. 2021;30(1):140–152. PubMed #33787050 ❐ Chen et al. is a very
similar study to Chowdhury et al… but they did not find a difference between fish and fish oil. D’oh!
19. 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.’”
20. 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.
21. Towheed TE, Maxwell L, Anastassiades TP, et al. Glucosamine therapy for treating osteoarthritis. Coch. 2005;(2):CD002946.
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 others 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.
22. Wilkens P, Scheel IB, Grundnes O, Hellum C, Storheim K. Effect of Glucosamine on Pain-Related Disability in Patients With
Chronic Low Back Pain and Degenerative Lumbar Osteoarthritis: A Randomized Controlled Trial. JAMA. 2010 Jul
7;304(1):45–52. PubMed #20606148 ❐ PainSci #55639 ❐
This straightforward and good quality test of glucosamine for low back pain — the first of its kind — found no therapeutic
benefit 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.” They tested 250 adults who’d had low back pain for more than 6 months, and
degenerative lumbar osteoarthritis.
Almost 30% of patients had mild side effects, and 10 patients withdrew because of them, but there were no serious
problems.
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.
23. Sawitzke AD, Shi H, Finco MF, 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
Aug;69(8):1459–64. PubMed #20525840 ❐ PainSci #54963 ❐
Even though knee osteoarthritis makes many lives miserable, long-term studies of treatment options are surprisingly few.
This badly needed and good quality experiment compared the efficacy and safety of the two most popular supplements for
pain — glucosamine, chrondroitin sulphate — as well as the painkiller celecoxib. They were pitted against each other, a
supplement combination, and a placebo, in several hundred patients for two years (valuable long-term data that didn’t
really exist before).
Alas, 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 most popular supplements are totally bogus.
But safe! “All of the tested therapies appeared to be generally safe and well tolerated over a two-year period.”
24. Wandel S, Jüni P, Tendal B, et al. Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee:
network meta-analysis. BMJ. 2010 Sep 16;341:c4675. PubMed #20847017 ❐ PainSci #55001 ❐
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.”
25. American Academy of Orthopaedic Surgeons. Treatment of Osteoarthritis of the Knee – 2nd Edition. AAOS.org. 2013.
PainSci #54555 ❐ They also slammed acupuncture, “lube jobs” (injection of joint lubricant), and surgical lavage and
debridement.
26. Simental-Mendía M, Sánchez-García A, Vilchez-Cavazos F, et al. Effect of glucosamine and chondroitin sulfate in
symptomatic knee osteoarthritis: a systematic review and meta-analysis of randomized placebo-controlled trials. Rheumatol
Int. 2018 Aug;38(8):1413–1428. PubMed #29947998 ❐
27. Gregori D, Giacovelli G, Minto C, et al. Association of Pharmacological Treatments With Long-term Pain Control in Patients
With Knee Osteoarthritis: A Systematic Review and Meta-analysis. JAMA. 2018 12;320(24):2564–2579. PubMed #30575881 ❐
PainSci #51785 ❐
28. Gabay C, Medinger-Sadowski C, Gascon D, Kolo F, Finckh A. Symptomatic effects of chondroitin 4 and chondroitin 6 sulfate
on hand osteoarthritis: a randomized, double-blind, placebo-controlled clinical trial at a single center. Arthritis Rheum. 2011
Sep 6;63(9). PubMed #21898340 ❐
29. Clegg DO, Reda DJ, Harris CL, et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee
osteoarthritis. N Engl J Med. 2006 Feb;354(8):795–808. PubMed #16495392 ❐
This is one of 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.
30. Maybe 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. Recovery from exercise may have a lot in common biologically with healing from an injury. Maybe.
31. Rodriguez NR, DiMarco NM, Langley S, et al. Position of the American Dietetic Association, Dietitians of Canada, and the
American College of Sports Medicine: Nutrition and athletic performance. J Am Diet Assoc. 2009 Mar;109(3):509–27.
PubMed #19278045 ❐
This is a dense paper on how nutrition can enhance athletic performance. It describes in great detail the position of the
American Dietetic Association, Dietitians of Canada, and the American College of Sports Medicine, so it’s very “official” (for
whatever it’s worth). Some highlights:
they endorse sports drinks (which badly undermines the credibility of these recommendations, because sports drinks are
ridiculous, please see Wagner)
energy and macronutrient needs, especially carbohydrate and protein, must be met when exercising hard
vitamin and mineral supplements are not needed if adequate energy to maintain body weight is consumed from a variety of
foods
ergogenic aids are poorly regulated and should be used with caution
And of course they recommend the services of a “qualified sports dietitian and in particular in the United States, a Board
Certified Specialist in Sports Dietetics.”
32. There are many fascinating examples of super-human performance and freakish immunity to pain during emergencies,
tragedies, and other exceptional circumstances. These effects by and large cannot be harnessed, but they do at least
demonstrate that both performance and pain can dance to the same tune. Pain is weird, volatile and quirky, and so is
performance.
33. And maybe the only difference between some performance boosters and “medicine” is where you started. If you were
healthy to begin with, it’s a performance booster. If you were injured, it’s a medicine. Maybe 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. Recovery from
exercise may have a lot in common biologically with healing from an injury. Maybe.
34. For instance, exercise soreness and fatigue are almost synonymous — sore muscles are also tired and weak. The everything-
hurts fragility of the seriously sick and injured blends seamlessly with being tired, and the same blend of sensitization and
exhaustion probably has less obvious causes too. Fibromyalgia is defined by unexplained pain and fatigue, and many people
with severe chronic fatigue also have a lot of pain.
35. It’s important to acknowledge that some people do not respond to creatine. There are non-responders to every drug, even
the most effective drugs ever developed.
36. Butts J, Jacobs B, Silvis M. Creatine Use in Sports. Sports Health. 2018;10(1):31–34. PubMed #29059531 ❐ PainSci #51778 ❐
37. Balestrino M, Adriano E. Beyond sports: Efficacy and safety of creatine supplementation in pathological or
paraphysiological conditions of brain and muscle. Med Res Rev. 2019 11;39(6):2427–2459. PubMed #31012130 ❐
38. Cornish SM, Peeler JD. No effect of creatine monohydrate supplementation on inflammatory and cartilage degradation
biomarkers in individuals with knee osteoarthritis. Nutr Res. 2018 03;51:57–66. PubMed #29673544 ❐
Creatine for osteoarthritis hasn’t been studied much, because it’s not what it’s supposedly good for, not what it “says on the
tin.” But these researchers were looking for a link between and ergogenic aid and pain, exactly what this article is all about.
They “hypothesized that supplementing with creatine monohydrate for 12 weeks would lower biomarkers of inflammation
and cartilage degradation in patients with knee osteoarthritis when compared to placebo.” But they found nothing: not a
single difference in anything they measured. Not inflammation, not cartilage condition, not functionality, not strength, and
not how the subjects felt about their knees. Absolutely bupkis. A disappointing result, but kudos to them (and the journal)
for just reporting a negative result, without any annoying attempt to spin it as positive (shockingly rare restraint).
A little extra colour: this is a decisively negative study, but that didn’t stop some other researchers for citing it as if it was
positive! A particularly extreme example of a bogus citation, in a paper that seemed to be pure creatine propaganda, in a
journal that might be terrible — probably unethical, maybe outright fraudulent.
39. Facioscapulohumeral Muscular Dystrophy (FSHD) is a common, mild form of muscular dystrophy that primarily affects the
muscles of the shoulder and face. I have a good friend with this condition, and it’s endlessly useful as a fascinating example
of a subtle pathology that can be a surprising cause of unexplained pain. For more information, see 35 Surprising Causes of
Pain.
40. Pearlman JP, Fielding RA. Creatine monohydrate as a therapeutic aid in muscular dystrophy. Nutr Rev. 2006 Feb;64(2 Pt
1):80–8. PubMed #16536185 ❐
41. Statins are important and widely used drugs, and their deleterious effect on muscle is controversially but widely considered
a diagnosable condition: statin myalgia, or statin-associated muscle symptoms (SAMS). See Stasi.
42. Balestrino M, Adriano E. Creatine as a Candidate to Prevent Statin Myopathy. Biomolecules. 2019 09;9(9).
PubMed #31533334 ❐ PainSci #51779 ❐
43. Kreider RB, Kalman DS, Antonio J, et al. International Society of Sports Nutrition position stand: safety and efficacy of
creatine supplementation in exercise, sport, and medicine. J Int Soc Sports Nutr. 2017;14:18. PubMed #28615996 ❐
PainSci #51782 ❐
44. 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.”
45. Brien S, Lewith G, Walker A, Hicks SM, Middleton D. Bromelain as a Treatment for Osteoarthritis: a Review of Clinical
Studies. Evidence-based Complementary & Alternative Medicine. 2004 Dec;1(3):251–257. PubMed #15841258 ❐
PainSci #55428 ❐
46. So there’s a conflict of interest (COI) — so what? Historically, the worst science has often been funded by people with a
strong stake in the results. But it’s not always a deal-breaker. The same bias that can compromise science often comes from
the same enthusiasm needed to pay for it in the first place! It’s not reasonable to expect science to only ever be done by
people without *any* skin in the game. Dispassionate objectivity in science is largely a myth. (Journalism too, by the way.)
The severity and relevance of a COI has to be evaluated on a case-by-case basis.
47. 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!
48. Kasemsuk T, Saengpetch N, Sibmooh N, Unchern S. Improved WOMAC score following 16-week treatment with bromelain
for knee osteoarthritis. Clin Rheumatol. 2016 Oct;35(10):2531–40. PubMed #27470088 ❐ It’s noteworthy than bromelain
appeared to match the benefits of diclofenac, which is an efficacious drug with notoriously severe side effects. But this study
was just too small to clearly establish its efficacy or it’s relative safety. At best, this trial is a reason to do a better trial.
49. Well-designed clinical trials are expensive and time-consuming. Cart-before-horse basic science papers are something you
bang off in a weekend and pad your resumé with, so they exist in huge numbers: jargon-riddled speculation about why
[insert molecule] might be useful, because that’s way easier than testing it to see if it actually is.
50. Gonçalves Ld, Painelli Vd, Yamaguchi G, et al. Dispelling the myth that habitual caffeine consumption influences the
performance response to acute caffeine supplementation. J Appl Physiol (1985). 2017 May:jap.00260.2017.
PubMed #28495846 ❐
This trial demonstrated that caffeine supplementation boosts athletic performance even if you are used to its effects. Forty
endurance cyclists were divided into groups of low, moderate, and highly daily caffeine intake. They all did three cycling
tests after drinking caffeine, a placebo, or nothing at all. Performance on caffeine was clearly best across the board for all
participants, regardless of typical caffeine intake.
51. Hogervorst E, Bandelow S, Schmitt J, et al. Caffeine Improves Physical and Cognitive Performance during Exhaustive
Exercise. Medicine & Science in Sports & Exercise. 2008 Oct;40(10):1841–1851. PainSci #56104 ❐
52. To be clear, my statements about the role of caffeine in chronic pain here are unsupported speculation, whereas the short-term
pain-relieving effects of caffeine are quite clear and evidence-based. And there’s no conflict between what we know about
the short effects and what I suspect about the long term effects. It can be “all of the above”! Caffeine can be good for pain in
the short term and bad for it in the long term. (Just like booze. We can draw a strong analogy to alcohol, which definitely
relieves pain in a meaningful way ... for as long as you’re drunk! It’s the original anaesthetic. But at the same time, we know
with extremely high confidence that the stuff is a nasty poison and downright terrible for you when habitually consumed
for a long time.)
53. Killer SC, Blannin AK, Jeukendrup AE. No evidence of dehydration with moderate daily coffee intake: a counterbalanced
cross-over study in a free-living population. PLoS One. 2014;9(1):e84154. PubMed #24416202 ❐ PainSci #53892 ❐
Many people believe that coffee is dehydrating. To test this popular idea, 50 men drank four cups (200ml) of either coffee or
water each day for three days while their diet and activity were controlled. There were no differences in their body mass,
urine volume, and signs of hydration in the blood and urine (pee clarity, basically). If you can drink almost a litre of coffee a
day and have no measurable effect on hydration, then it is not “dehydrating” to any meaningful degree. The authors
reasonably concluded that coffee “provides similar hydrating qualities to water.”
54. Rogero MM, Tirapegui J, Pedrosa RG, Castro IA, Pires IS. Effect of alanyl-glutamine supplementation on plasma and tissue
glutamine concentrations in rats submitted to exhaustive exercise. Nutrition. 2006 May;22(5):564–71. PubMed #16472983 ❐
55. Cruzat VF, Rogero MM, Tirapegui J. 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
Jan;28(1):24–30. 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.
56. Merimee TJ, Rabinowtitz D, Fineberg SE. Arginine-initiated release of human growth hormone. Factors modifying the
response in normal man. N Engl J Med. 1969 Jun;280(26):1434–8. PubMed #5786514 ❐ PainSci #55053 ❐
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.
57. Willoughby DS, Boucher T, Reid J, Skelton G, Clark M. 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 Aug;21(4):291–9. 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.
58. Tajari SN, Rezaeee M, Gheidi N. Assessment of the effect of L-glutamine supplementation on DOMS. Br J Sports Med.
2010;44. PubMed #23997909 ❐ PainSci #54728 ❐
“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.
59. Garlick PJ. Assessment of the safety of glutamine and other amino acids. J Nutr. 2001 Sep;131(9 Suppl):2556S–61S.
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
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.
60. Pasiakos SM, Lieberman HR, McLellan TM. Effects of protein supplements on muscle damage, soreness and recovery of
muscle function and physical performance: a systematic review. Sports Med. 2014 May;44(5):655–70. PubMed #24435468 ❐
61. VanDusseldorp TA, Escobar KA, Johnson KE, et al. Effect of Branched-Chain Amino Acid Supplementation on Recovery
Following Acute Eccentric Exercise. Nutrients. 2018 Oct;10(10). PubMed #30275356 ❐ PainSci #52500 ❐
62. Estoche JM, Jacinto JL, Roveratti MC, et al. Branched-chain amino acids do not improve muscle recovery from resistance
exercise in untrained young adults. Amino Acids. 2019 Sep;51(9):1387–1395. PubMed #31468208 ❐ )
63. Fedewa MV, Spencer SO, Williams TD, Becker ZE, Fuqua CA. Effect of branched-Chain Amino Acid Supplementation on
Muscle Soreness following Exercise: A Meta-Analysis. Int J Vitam Nutr Res. 2019 Nov;89(5-6):348–356. PubMed #30938579 ❐
64. 30681787 “The use of collagen supplementation in dermatology remains controversial due to the lack of regulation on
quality and quantity of ingredients in over-the-counter collagen supplements, as well as minimal peer-reviewed literature
on the subject.” But “Preliminary results are promising”!
65. The word “significant” in scientific abstracts is routinely misleading. It does not mean that the results are large or
meaningful, and in fact is used to hide precisely the opposite. When only “significance” is mentioned, it almost invariably
refers to the notoriously problematic “p-value,” a technically-true distraction from the more meaningful truth of a tiny
“effect size”: results that are not actually impressive. This practice has been considered bad form by experts for decades, but
is still extremely common. See Statistical Significance Abuse: A lot of research makes scientific evidence seem more
“significant” than it is.
66. García-Coronado JM, Martínez-Olvera L, Elizondo-Omaña RE, et al. Effect of collagen supplementation on osteoarthritis
symptoms: a meta-analysis of randomized placebo-controlled trials. Int Orthop. 2019 03;43(3):531–538. PubMed #30368550 ❐
67. Nicol LM, Rowlands DS, Fazakerly R, Kellett J. Curcumin supplementation likely attenuates delayed onset muscle soreness
(DOMS). Eur J Appl Physiol. 2015 Mar. PubMed #25795285 ❐
68. Connolly DA, McHugh MP, Padilla-Zakour OI, Carlson L, Sayers SP. Efficacy of a tart cherry juice blend in preventing the
symptoms of muscle damage. Br J Sports Med. 2006 Aug;40(8):679–83; discussion 683. PubMed #16790484 ❐
PainSci #53887 ❐
69. I don’t think black cherry Kool-Aid would fool me. I’m not sure it would fool anyone!
70. Howatson G, Bell PG, Tallent J, et al. Effect of tart cherry juice (Prunus cerasus) on melatonin levels and enhanced sleep
quality. Eur J Nutr. 2012 Dec;51(8):909–16. PubMed #22038497 ❐
A small pilot trial of tart cherries for insomnia in 20 subjects, comparing to a placebo and measuring sleep quality and
melatonin levels. The conclusion is positive, but the data is mediocre at best: small effects that are barely statistically
significant. It's not a negative study, but it's not exactly a convincing positive either.
71. Losso JN, Finley JW, Karki N, et al. Pilot Study of the Tart Cherry Juice for the Treatment of Insomnia and Investigation of
Mechanisms. Am J Ther. 2018;25(2):e194–e201. PubMed #28901958 ❐ PainSci #52136 ❐
A pilot study with 8 subjects. Microscopic! Powerless to actually prove anything. But, for what very little it's worth…
technically positive, showing a decent boost to sleep duration (and nothing else they measured).
72. Pigeon WR, Carr M, Gorman C, Perlis ML. Effects of a tart cherry juice beverage on the sleep of older adults with insomnia:
a pilot study. J Med Food. 2010 Jun;13(3):579–83. PubMed #20438325 ❐ PainSci #52142 ❐
A teensy pilot study of 15 people, comparing a tart cherry juice blend to placebo, showing barely-there improvements in
insomnia. “Effect sizes were moderate and in some cases negligible. … considerably less than those for evidence-based
treatments of insomnia: hypnotic agents and cognitive-behavioral therapies for insomnia.”
73. Manson JE, Patsy M B, Rosen CJ, Taylor CL. Vitamin D Deficiency — Is There Really a Pandemic? N Engl J Med. 2016 Nov
10;375(19):1817–1820. PubMed #27959647 ❐
ABSTRACT
The claim that large proportions of North American and other populations are deficient in vitamin D is based on misinterpretation
and misapplication of the Institute of Medicine reference values for nutrients — misunderstandings that can adversely affect
patient care.
74. Holick MF, Chen TC. Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr. 2008
Apr;87(4):1080S–6S. PubMed #18400738 ❐ PainSci #55028 ❐
75. Bone aching is caused by osteomalacia, which is bone weakening specifically caused by malfunctioning bone building
biology. The Mayo Clinic describes osteomalacia symptoms like so: “The dull, aching pain associated with osteomalacia
most commonly affects the lower back, pelvis, hips, legs and ribs. The pain may be worse at night, or when you’re putting
weight on affected bones.”
76. Bolland MJ, Grey A, Avenell A. Effects of vitamin D supplementation on musculoskeletal health: a systematic review, meta-
analysis, and trial sequential analysis. Lancet Diabetes Endocrinol. 2018 11;6(11):847–858. PubMed #30293909 ❐
77. Bislev LS, Grove-Laugesen D, Rejnmark L. Vitamin D and Muscle Health: A Systematic Review and Meta-analysis of
Randomized Placebo-Controlled Trials. J Bone Miner Res. 2021 09;36(9):1651–1660. PubMed #34405916 ❐
78. Tai YT, Tong CV. The Perilous PPI: Proton Pump Inhibitor as a Cause of Clinically Significant Hypomagnesaemia. J ASEAN
Fed Endocr Soc. 2020;35(1):109–113. PubMed #33442177 ❐ PainSci #52188 ❐ It may be a side effect of the extremely common
proton pump inhibitor drugs for heartburn and acid reflux, but the prevalence of the side effect is unknown. There have
been more than a couple dozen case reports of serious hypomagnesaemia over the last twenty years, and those are generally
the tip of an iceberg.
79. This is uncertain. Some experts claim it. For instance, Mauskop et al point out that most magnesium isn’t stored in the blood,
but rather in the bones and other tissue reservoirs. That premise is probably true, but does it follow that blood levels are
therefore “inaccurate” for detecting deficiency? Not necessarily, and I have been unable to find direct empirical support for
it. This might true and important, or it might not.
80. Tarleton EK, Kennedy AG, Rose GL, Littenberg B. Relationship between Magnesium Intake and Chronic Pain in U.S. Adults.
Nutrients. 2020 Jul;12(7). PubMed #32708577 ❐ PainSci #52160 ❐
81. Banerjee S, Jones S. Magnesium as an Alternative or Adjunct to Opioids for Migraine and Chronic Pain: A Review of the
Clinical Effectiveness and Guidelines. CADTH Rapid Response Reports. 2017 Apr. PubMed #29334449 ❐
This paper concluded in 2016 that “magnesium appears to have an analgesic effect.” Great! But don’t read the fine print if
you want to hang on to that good feeling. Their own summary of findings doesn’t seem to back up the optimism. They
clearly state that conclusions were “not possible” for migraine … that the evidence is conflicting for a rather exotic kind of
chronic pain (complex regional pain syndrome) … and they mention only a single trial showing a benefit for back pain (with
intravenous supplementation, no less, and for back pain complicated by neuropathy; see Yousef).
And that’s just all they wrote about the data. If there is enough evidence to justify “magnesium appears to have an analgesic
effect,” it is not reported in this paper.
82. Yousef AA, Al-deeb AE. A double-blinded randomised controlled study of the value of sequential intravenous and oral
magnesium therapy in patients with chronic low back pain with a neuropathic component. Anaesthesia. 2013 Mar;68(3):260–
6. PubMed #23384256 ❐ PainSci #52166 ❐
This is one of the only good quality trials of magnesium supplementation for body pain. However, crucially, they studied
only back pain with a neuropathic component. 40 patients were given a placebo, and their progress over 6 months was
compared to 40 more who got intravenous magnesium for two weeks, then oral for another month.
The patients who got magnesium clearly did better in the long run.
Both groups did great at first, more than halving their pain. If stopped there, the study would have shown that magnesium
was no better than a placebo. But then the placebo group's numbers rebounded, while the magnesium folks stayed
low… for six months. The improvement wasn’t huge, but it wasn’t small either. I wouldn’t turn it down.
This is a clearly positive result on its face — which is such a rarity in this field that it’s cause for too-good-to-be-true concern.
It is “just one study,” with unknown flaws, and unreplicated.
This experiment just cannot tell us anything about the effect of magnesium on the most common kinds of pain, which are
mostly not neuropathic. Back pain without neuropathy is a good proxy for many other kinds of pain; back pain with
neuropathy is more about neuropathy than “back pain.”
But, for whatever it’s worth, it is indeed a properly positive result — and that’s more than we can say for a great many other
trials of any intervention for any kind of back pain.
83. Minetto MA, Holobar A, Botter A, Farina D. Origin and Development of Muscle Cramps. Exerc Sport Sci Rev. 2013
Jan;41(1):3–10. PubMed #23038243 ❐ PainSci #54733 ❐ “Dehydration (and/or cramps, motor unit action potentials, motor
neurons electrolyte depletion) often is given as an explanation for muscle cramps occurring in workers and athletes,
although this claim is not supported by scientific evidence .” And indeed it is contradicted by some good science — see next
note.
84. Schwellnus MP, Drew N, Collins M. Increased running speed and previous cramps rather than dehydration or serum
sodium changes predict exercise-associated muscle cramping: a prospective cohort study in 210 Ironman triathletes. Br J
Sports Med. 2011 Jun;45(8):650–6. PubMed #21148567 ❐
Blood samples from 210 Ironman triathletes were checked for electrolytes and other signs of hydration status. 43 had
suffered cramps. There were no significant differences between the crampers and the non-crampers in any of the pre-testing
or post-testing. Dehydration and electrolyte shortage don’t cause cramps — intense effort does. “The results from this study
add to the evidence that dehydration and altered serum electrolyte balance are not causes for exercise-associated muscle
cramps.” This is a nice myth-mangler of a paper.
85. Garrison SR, Korownyk CS, Kolber MR, et al. Magnesium for skeletal muscle cramps. Cochrane Database Syst Rev. 2020
09;9:CD009402. PubMed #32956536 ❐ PainSci #52162 ❐
86. In Yousef et al, previously referenced, both the placebo and magnesium groups experienced equally dramatic benefits at the
2-week point — a good demonstration of how a placebo can easily resemble a robust therapeutic effect and for a
surprisingly long time. In this case, the placebo effect had dried up by six weeks while the benefit of magnesium persisted
— but we have no idea if that same benefit will happen in other conditions. And we can certainly count on a placebo effect.
87. Wandel S, Jüni P, Tendal B, et al. Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee:
network meta-analysis. BMJ. 2010 Sep 16;341:c4675. PubMed #20847017 ❐ PainSci #55001 ❐
88. Mijatović N, Šljivić J, Tošić N, et al. Big Suppla: Challenging the Common View of the Supplements and Herbs Industry
Affects the Willingness to Try and Recommend Their Products. Studia Psychologica. 2022 Mar;64(1):91–103.
PainSci #51970 ❐
89. ScienceBasedMedicine.org [Internet]. Hall H. Pursued by Protandim Proselytizers; 2011 Oct 11 [cited 12 Mar 16].
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.”
90. Lalani SR, Vladutiu GD, Plunkett K, et al. Isolated mitochondrial myopathy associated with muscle coenzyme Q10
deficiency. Arch Neurol. 2005 Feb;62(2):317–20. PubMed #15710863 ❐
91. Taylor BA, Lorson L, White CM, Thompson PD. A randomized trial of coenzyme Q10 in patients with confirmed statin
myopathy. Atherosclerosis. 2015 Feb;238(2):329–35. PubMed #25545331 ❐ PainSci #52036 ❐ “CoQ10 supplementation does
not reduce muscle pain in patients with statin myalgia.”
92. Banach M, Serban C, Sahebkar A, et al. Effects of coenzyme Q10 on statin-induced myopathy: a meta-analysis of randomized
controlled trials. Mayo Clin Proc. 2015 Jan;90(1):24–34. PubMed #25440725 ❐ “The results of this meta-analysis of available
randomized controlled trials do not suggest any significant benefit of CoQ10 supplementation in improving statin-induced
myopathy.”
93. Di Stasi SL, Macleod TD, Winters JD, Binder-Macleod SA. Effects of Statins on Skeletal Muscle: A Perspective for Physical
Therapists. Phys Ther. 2010 Aug. PubMed #20688875 ❐
94. “Rhabdo” is a nasty but also very interesting condition. I discuss it in detail in Poisoned by Massage.
95. Mammen AL. Statin-Associated Autoimmune Myopathy. N Engl J Med. 2016 Feb;374(7):664–9. PubMed #26886523 ❐
96. Regarding classification, professionals should take a look at a great 2004 interview with Eliot A. Brinton, MD: “There are 4
interrelated terms for muscle problems that can occur with statins. Unfortunately, they are often confused even by
healthcare professionals … .” (Technical note: this document is freely available, but direct linking will hit a paywall.
Medscape only reveals the whole thing to people arriving from a Google search. Simply search for do a Google search for it
to get around the paywall.)
97. Ganga HV, Slim HB, Thompson PD. A systematic review of statin-induced muscle problems in clinical trials. Am Heart J.
2014 Jul;168(1):6–15. PubMed #24952854 ❐
In this review of several statin trials, only slightly more patients had pain on statins than without (placebo): just 12.7%,
compared to 12.4%. You could conclude from this data that there actually is no such thing as statin mylagia! But it probably
is a real phenomenon, which is highly plausible based on the existence of rarer but very severe side effects on muscle (see
Mammen or Statin Therapy). We don’t have very good data about it, it’s mostly not severe, and it’s hard to distinguish from
the “background noise” of many other common causes of musculoskeletal pain.
98. Cholesterol Treatment Trialists' Collaboration. Effect of statin therapy on muscle symptoms: an individual participant data
meta-analysis of large-scale, randomised, double-blind trials. Lancet. 2022 Aug. PubMed #36049498 ❐
In this huge review of 19 placebo controlled trials of the side effects of statins, following over 30,000 patients for about 4
years on average, there was no major difference in the rate of muscle pain and weakness. There was a modest signal in the
first year, and for more intensive statin therapy: slightly more myopathy, mostly mild. Only about 1 in 15 cases of statin-
induced myopathy reported by patients were actually related to statins, according to this data. The researchers concluded:
“Statin therapy caused a small excess of mostly mild muscle pain. Most (>90%) of all reports of muscle symptoms by
participants allocated statin therapy were not due to the statin. The small risks of muscle symptoms are much lower
than the known cardiovascular benefits.”
99. Gupta A, Thompson D, Whitehouse A, et al. Adverse events associated with unblinded, but not with blinded, statin therapy
in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid-Lowering Arm (ASCOT-LLA): a randomised double-blind
placebo-controlled trial and its non-randomised non-blind extension phase. Lancet. 2017 Jun;389(10088):2473–2481.
PubMed #28476288 ❐
This study was designed to test the existence of the phenomenon of statin myalgia. Taking statins did not increase pain in
patients when they were unaware that they were taking them. This suggests that statin myalgia is something people get because
they are afraid of it, not because it’s a real side effect. As the authors concluded:
These analyses illustrate the so-called nocebo effect, with an excess rate of muscle-related AE reports only when
patients and their doctors were aware that statin therapy was being used and not when its use was blinded. These
results will help assure both physicians and patients that most AEs associated with statins are not causally related to
use of the drug and should help counter the adverse effect on public health of exaggerated claims about statin-related
side-effects .
100. Michalska-Kasiczak M, Sahebkar A, Mikhailidis DP, et al. Analysis of vitamin D levels in patients with and without statin-
associated myalgia - a systematic review and meta-analysis of 7 studies with 2420 patients. Int J Cardiol. 2015 Jan;178:111–6.
PubMed #25464233 ❐
101. Sender R, Fuchs S, Milo R. Revised Estimates for the Number of Human and Bacteria Cells in the Body. PLoS Biol. 2016
08;14(8):e1002533. PubMed #27541692 ❐ PainSci #52035 ❐
You may have heard that the human body is infested with ten times as more bacterial hitchhikers than the number of our
own cells, and even that they have equal mass. Happily, no, we are not quite that disgusting. There’s “only” about the same
number of bacteria as the headcount for our own cells, and — because bacteria are quite a bit smaller than our cells — they
weigh just a couple hundred grams on average.
102. Ruth Ley, commenting on the 10th anniversary of the Human Microbiome Project (HMP, see Human Microbiome Project
Consortium), for Nature.com:
“The result the first comprehensive catalogue of a healthy US human microbiome: a full list of the genes in the microbes
in the gut. The HMP showed that the gut’s cellular organisms consist of thousands of species, with a genetic footprint 150 times
the size of the human genome. Eventually, this abundance led biologists to view the microbiome as an environmentally
acquired ‘second genome’, hidden in the human host.”
103. Lindsay, Bethany. “Naturopaths ‘not bound by science,’ lawyer argues in B.C. hearing on fecal transplants for autism..”
CBC.com. Jun 29, 2022.
“Klop’s three nephews were the business’s only donors at the time of the complaint and clarified that the lab was in a
ground-level unit of the building where the boys lived.”
104. Lynch SV, Pedersen O. The Human Intestinal Microbiome in Health and Disease. N Engl J Med. 2016 Dec;375(24):2369–2379.
PubMed #27974040 ❐
105. Lynch SV, Ng SC, Shanahan F, Tilg H. Translating the gut microbiome: ready for the clinic? Nat Rev Gastroenterol Hepatol.
2019 11;16(11):656–661. PubMed #31562390 ❐
106. Bastian H. "They would say that, wouldn't they?" A reader's guide to author and sponsor biases in clinical research. J R Soc
Med. 2006 Dec;99(12):611–4. PubMed #17139062 ❐ PainSci #51373 ❐
The full quote:
“A promising treatment is often in fact merely the larval stage of a disappointing one. At least a third of influential trials
suggesting benefit may either ultimately be contradicted or turn out to have exaggerated effectiveness.”
107. Ma P, Mo R, Liao H, et al. Gut microbiota depletion by antibiotics ameliorates somatic neuropathic pain induced by nerve
injury, chemotherapy, and diabetes in mice. J Neuroinflammation. 2022 Jun;19(1):169. PubMed #35764988 ❐
108. Anything good for your general health has the potential to help chronic pain. The specific cause of chronic pain may often
be less important than general sensitivity and biological vulnerability to any pain. The biggest risk factors for pain chronicity
are things like poor health, fitness, and socioeconomic status, inequality… and they overshadow common scapegoats like
poor posture, spinal degeneration, or even repetitive strain injury. How can nothing in particular make us hurt? Because
pain is weird, a generally oversensitive alarm system that can produce false alarms even at the best of times, and probably
more of them when your system is under strain. See Vulnerability to Chronic Pain: Chronic pain often has more to do with
general biological vulnerabilities than specific tissue problems.
109. Mohammed AT, Khattab M, Ahmed AM, et al. The therapeutic effect of probiotics on rheumatoid arthritis: a systematic
review and meta-analysis of randomized control trials. Clin Rheumatol. 2017 Dec;36(12):2697–2707. PubMed #28914373 ❐
110. Sanchez P, Letarouilly JG, Nguyen Y, et al. Efficacy of Probiotics in Rheumatoid Arthritis and Spondyloarthritis: A
Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients. 2022 Jan;14(2). PubMed #35057535 ❐
PainSci #52051 ❐
111. The NIH says that “some probiotic products have been reported to contain microorganisms other than those listed on the
label. In some instances, these contaminants may pose serious health risks.”
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Supplements for Pain & Healing: Science vs Hype 09/12/2022, 20:09

Vitamins, Minerals &

Critical analysis of most popular “nutraceuticals” — food-

Paul Ingraham • Jun 23, 2022 • 95m read

Arthritis is not caused by a lack of glucosamine. And it isn’t

Supplement science from 10,000 feet: the big picture in a paragraph

Warning: contaminated supplements are common!

Adulterated evidence of supplement adulteration?

Supplement science highlights (and table of contents)

Protandim — Patented “blend of phytonutrients” from a multi-level marketing company that

Some other topics:

Do supplements show promise for pain patients in general?

Looking for something else?

Anti-inflammatory nutrition versus supplements

Because there mostly is no such thing as special anti-

Omega-3 fatty acids, and fish versus fish oil pills

Hat tip to science journalist Peter Brannen for the good

Glucosamine — leading by example?

Glucosamine is an abundant monosaccharide — and amino sugar — and a building block of

Glucosamine supplementation has been mostly

P.S. on chondroitin sulfate

Ergo-what? Performance, fatigue, and pain

Creatine: the most evidence-based common supplement

The stuff clearly works on almost everyone, 35 and it

Currently, the scientific literature supports creatine supplementation for increased

Creatine is super safe, too!

Whey protein (AKA protein powder, protein shakes)

Maybe stick to egg whites and skinless chicken breasts?

Bromelain, the lesser known pineapple-derived anti-inflammatory

In 2004, Brien et al reviewed a dozen early studies of bromelain research in Evidence-based

2021 bromelain science update: no news is bad news

Other than that, there are just a handful of minor

Caffeine improves physical and cognitive performance during exhaustive

Caffeine to the rescue!

(P.S. It also doesn’t dehydrate you. That’s a silly myth. 53 )

Energy drinks — Everyman’s ergogenic aid

Glutamine and arginine for exercise recovery and soreness? Faith-based

Death. Now there’s a side effect. Remember: gambling with biochemistry.

Branched-chain amino acids: leucine, isoleucine, valine

And sneezy and happy and dopey…

Collagen: ever so slightly good for arthritis, maybe

Medical science tends to produce “promising” results

Turmeric and curcumin: not just tasty

According to Examine.com, “Supplementation of curcumin reliably reduces markers of

Less than ibuprofen, eh? Well, I like curry anyway…

Tart cherry juice

Can tart cherry juice help you sleep?

If there’s only one supplement you’re taking for your

Magnesium for cramps

Eating your magnesium

See dietary sources of magnesium.

How come you’re always such a fussy young man?

But it worked for me! The role of anecdotes and testimonials

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

The double standard is maddening.

“Big Suppla” is now evidence-based debunking

Will the real underdog please stand up?

The Multi-Level Marketing Connection: Supplements and Fraud

Protandim: The most prominent MLM-powered supplement

Protandim is a patented “blend of phytonutrients” from a multi-level marketing company, with

1. Coenzyme Q10 (~600 words)

→ access to many members-only sections of articles +

Buy PainSci Membership $6/month or $60/year USD