Examine.

com
Joint Health
Supplement Guide

Written by Michael Hull, MSc, and Wyatt Brown

Edited by Pierre-Alexandre Sicart, PhD
Reviewed by Kamal Patel, MPH, MBA, PhD(c), and the Examine.com team
Updated April 2020
Table of Contents
Medical Disclaimer

How to Use This Guide

Introduction

Combos

Core Supplements

Primary Options

Secondary Options

Unproven Supplements

Inadvisable Supplements

FAQ

References

Bios

2
Medical Disclaimer
This guide is a general-health document for adults 18 or over. Its aim is strictly educational. It does
not constitute medical advice. Please consult a medical or health professional before you begin
any exercise-, nutrition-, or supplementation-related program, or if you have questions about your
health.

This guide is based on scientific studies, but individual results do vary. If you engage in any activity
or take any product mentioned herein, you do so of your own free will, and you knowingly and
voluntarily accept the risks. While we mention major known interactions, it is possible for any
supplement to interact with other supplements, with foods and pharmaceuticals, and with particular
health conditions.

Examine.com does not assume liability for any actions undertaken after visiting these pages, and
does not assume liability if one misuses supplements. Examine.com and its Editors do not ensure
that unforeseen side effects will not occur even at the proper dosages, and thereby does not
assume liability for any side effects from supplements or practices hosted under the domain of
Examine.com.

Examine.com does not make any representations, recommend or endorse any specific tests,
products, procedures, opinions, or other information that may be mentioned on the website.
Reliance on any information provided by Examine.com, Examine.com employees, guest writers,
editors, and invitees of Examine.com, or other visitors to Examine.com is solely at your own risk.

3
How to Use This Guide
The Examine.com team has been publishing research on nutrition and supplementation since
March 2011. Drawing from all we’ve learned, we’ve designed this Supplement Guide with two aims
in mind: helping you decide which supplements are right for you, based on the scientific evidence,
and helping you integrate these supplements into synergistic combos.

Core supplements have the best safety-efficacy profile. When used responsibly, they are the
supplements most likely to help and not cause side effects.

Primary options may provide substantial benefit, but only in the right context. A primary option is
not for everyone, but if you read the entry and find that you meet the criteria, consider adding the
supplement to your combo.

Secondary options have less evidence for their effects. They could work or be a waste of money.
Keep them in mind, but think twice before adding them to your combo.

Unproven supplements are backed by tradition or by mechanistic, animal, epidemiological, or

anecdotal evidence, but not yet by convincing human trials. At this point, they are not good
candidates for your combo.

Inadvisable supplements are either potentially dangerous or simply ineffective, marketing claims
notwithstanding. Do not add them to your combo. At best, they’ll be a waste of money; at worst,
they can cause you harm.

Now that you’ve learned of various supplements worthy of your consideration, you’ll learn to
integrate them into synergistic combos. You’ll discover a core combo (composed of the core
supplements) and several specialized combos (composed of primary and secondary options). Each
specialized combo is optimized for a specific population. The simplest way to formulate your own
combo is to combine the core combo with the specialized combo that best fits your situation,
needs, and primary health goal.

Then comes the FAQ, in which we cover common questions that may arise when selecting and
combining supplements. With all this, you should be able to identify and assemble the supplement
combo best suited to your objective.

4
Introduction
If you’re reading this, you probably have joint issues that refuse to go away; you’re still looking for a
solution. The first thing you should know is that you’re not alone — weird, stubborn joint pains are
common.

Digging Deeper: Weird joint pain 101

Why do some cases of joint pain resolve quickly, whereas others worsen or stay the same?
Unfortunately, that topic isn’t well understood,[1] and individual cases seldom get solved
within the fifteen minutes of a medical appointment.

Try physical therapy and anti-inflammatories (e.g., NSAIDs); if neither helps, consider
surgery. Such is the traditional approach to joint pain; it is simplistic and fraught with
problems, of which we’ll mention only a couple:

• Lasting joint pain can often be blamed on inflammatory tendonitis, and physicians
may not look any further. Yet it could also be caused by non-inflammatory
tendinosis[2] (if, for example, the tendon tissue has degenerated past the point of
having an inflammatory response to injury).

• Several joint surgeries have recently been found to be much less effective than
assumed, prompting guidelines against surgery as a primary option.[3]

It’s your body, so don’t be afraid to ask a ton of questions. Weird joint pain is worth digging
into, possibly through second opinions along with self-education. It may stem from a
condition as common (yet complex and difficult to treat) as fibromyalgia,[4] or as rare as
Fabry disease.[5] Or it could just be an old injury that hasn’t healed due to diet or lifestyle
factors. The only way to find out is to keep exploring.

Common doesn’t mean simple. I can’t stress enough how complex joint health is. It’s not like fat
loss, which, although complicated in practice, nonetheless has a basic formula underlying any
successful strategy:

• Take in less energy than you expend.

5
To address joint pain, there’s no formula, and the “strategy” tends to look like this:

• Just keep trying. Don’t fall for snake oil. Or at least not too often.

After being hyper-focused on my own joint issues for many years, then working with patients,
running a Meetup group on chronic pain, and answering hundreds of emails from fellow sufferers, I
have a takeaway: joint pain really sucks. Okay, fine, here’s another takeaway: you can reduce joint
pain, even if you think you’ve tried everything, but it really helps to understand a bit about joint-pain
physiology and why the best treatment plans aren’t very simple.

The reason joint issues are so complex is actually quite interesting. There are many ways you can
damage your joints: by forcing past their range of motion (e.g., by tearing your ACL), by routinely
messing up their surroundings (e.g., by letting your bad posture compress one of the shoulder
joints), or through more insidious processes (e.g., wear and tear from aging or disease). The
multiplicity of possible causes, which often intersect, makes addressing joint pain difficult, as does
the complexity of the joint tissue itself. Here we highlight just a few components of articular
cartilage:

What is cartilage

Yet when your joints work smoothly, you don’t think about them at all. It’s only when they stop
working well, and keep not working, that you can’t stop thinking about them. And that’s where much

6
of the problem lies.

We humans, with our relatively defenseless bodies, must employ a fairly robust alarm system to
warn our big brain that it is indirectly in danger (for our distant ancestors, a damaged joint could
easily be a death knell). Pain is a helpful signal when it works correctly: it helps us live out our long
human lifespans. It follows that, to ensure its survival, your body can become “better and better” at
experiencing pain; in other words, your nervous system lowers the threshold over which signals are
interpreted as painful (through varied mechanisms, notably central sensitization[6]).

Humans respond to pain so differently from most other mammals that painkillers that work in
animal studies often fail in human studies.[7] In humans, we observe a pretty clear dichotomy: acute
pain (from overexerting yourself at the gym, for instance) responds well to medication and other
interventions. Chronic pain, sadly, does not.[8]

If that were the only sticking point, joint-pain treatment would be merely difficult. But joint-pain
complexities don’t stop there. Why did Tiger Woods pile up so many injuries after his first one?
Why do patients often develop multiple chronic conditions, with triads such as arthritic joints plus
fibromyalgia plus depression? Here are three common reasons:

• Fear of reinjury. If you get hurt, and your lifts go down (or race times get worse, or what
have you), a bunch of things can change at once.[9] You start to compensate for the injured
joint; you start to resent rehab and physical therapy; and if the pain doesn’t go away, you
slowly start to shy away from physical activity. In other words, you start a cycle whereby
other joints get injured and you become overall less fit.

• Sleep issues. To those who haven’t been sleeping well for months or even years, “sleep
issues” is a grating euphemism. Pain can be a sleep bulldozer, with studies showing that
over half of joint-pain sufferers also suffer from disturbed sleep.[10] Sleep problems tend to
worsen with joint-pain severity, so a nagging knee injury could be merely annoying, but
severe knee arthritis could stop sleep in its tracks.[11]

• The perfect storm. Let’s say you’re heading for the Olympics and wish to set up the
optimal conditions to net you a gold medal. Everything you want to ensure (good sleep,
support from family and friends, mental and physical well-being) is the opposite of what
you’ll get with chronic joint pain. Disturbed sleep is often the catalyst of this perfect
storm:[12] you wake up tired, your pain sensitivity is higher, your family and friends can’t
relate to you and sometimes get secretly annoyed, and your body feels like a sack of crap.
Repeat this cycle for a few days and it’s hard to climb out of the pain hole.

We’ve established that having chronic joint pain means turning into Sisyphus: you keep trying to
roll that pain boulder up the hill, but it’s too dang heavy. Disturbed sleep, failed treatments, fat gain
and muscle loss … these are hard to overcome.

7
Luckily, thousands of studies on joint pain are here to help you. Before we distill them into tips,
however, we need to review three very important points.

First, remember that no single study will be a lightning bolt that decimates your pain. There are a
thousand and one different causes for joint pain, and only snake oil therapies would claim to
address them all. In fact, the term “snake oil” was originally used for a literal snake oil therapy for
joint pain used in Traditional Chinese Medicine (TCM).

Digging Deeper: A unified theory of

pain?
A few academics have proposed unified theories of pain, centered around areas such as
inflammation or the nervous system.[13] Similarly, a plethora of researchers, academic and
not, will tell you there’s a simple, single cause behind most of your health issues — some
claim that, when it comes to osteoarthritis, nightshade vegetables are the main culprit;
others, that gluten is to blame for many of today’s pains and ailments; and yet others, that
those pains and ailments derive from our lack of direct contact with the bare earth.[14]

Common nightshade vegetables and herbs

Ashwagandha Goji berry Potatoes

(excluding sweet potatoes)

Cayenne pepper Paprika Tobacco

Eggplants Peppers/Chili peppers Tomatoes/Tomatillos

Reference: USDA Plants Database. Accessed September 12, 2020.

It’s certainly tempting to believe that one’s health issues all share a single cause, since it
would mean that addressing that one cause would, in one stroke, make it all better. But, as
implied by the very number of conflicting opinions on the nature of that cause, reality is …
messier.

Yes, on the theoretical side, it’s interesting to tie together various pain mechanisms; but

8
 the factors involved (dietary, environmental, psychological …) are simply too diverse to be
distilled into one neat system. And yes, on the practical side, single triggers such as gluten
might be at the root of multiple health issues — in some individuals. But even if you belong
to the minority of people whom gluten adversely affect, embarking on a gluten-free diet isn’t
likely to make all your ills magically disappear.

Too bad, too. If chronic pain could be traced down to one cause, it would be quite easier to
treat!

Second, remember that you will not see immediate benefits from most therapies. Joint pain takes a
while to resolve, and “a while” could range from a couple of weeks to many months.

Third, remember that the benefits you experience might be hard to assess. This isn’t like muscle
gain or fat loss, where you can track pounds or see those biceps veins become more prominent;
you won’t have an easy way to quantify pain, and some days will be worse than others due to
factors you can only guess at.

And now onto the “tips” (a term which greatly undersells what they are; they should rather be called
Very Important Pointers That Will Help If You Follow Them).

• Follow the sun. You will never hear about a huge randomized trial on the effect of sun
exposure on pain — or on any other condition, for that matter. There’s simply no financial
incentive, since you can’t patent the sun. That being said, circadian rhythm may just be the
most important factor in treating pain. Sunlight may decrease pain after joint surgery,[15] and
UV tanning beds have been shown to decrease pain from fibromyalgia.[16] These clues are
just two out of many pointing to a simple message: get as much natural light as you can
during the day, and as little artificial bright light as you can at night.

• Keep a healthy weight. This one especially matters if you have knee pain. When you walk,
each 0.5 kg (1 lb) of excess weight becomes about 1.8 kg (4 lb) of extra load on your
knees. If you’re just 4.5 kg (10 lb) overweight, that’s 18 kg (40 lb) of extra load per step —
and 21,772 kg (48,000 lb) of cumulative load per 1.6 km (1 mile, assuming 1,200 steps).
Ouch.[17]

• Train your brain. You may think your pain is in your knee, but it’s not. It’s in your brain and
nervous system. Signals going up to the brain and back down to the joint modify what you
feel, so that a damaged joint painful to one person may hardly be felt by another.[18] While
you can’t “think away” your joint pain, mindfulness meditation appears to reduce pain.[19] It
may sound hokey, but something as minor as positive thinking might train your brain to

9
 perceive pain differently.

• Help your gut bacteria help you. No probiotic has ever been shown to universally relieve
pain. That’s probably because different people have such different microbiomes, and
because there’s only so much one single strain can do when living among hundreds others
in your gut. Still, certain bacterial strains have shown benefit for specific painful conditions,
such as rheumatoid arthritis.[20] Taking probiotics matters less than generally caring for your
gut, though, such as by avoiding too much processed junk food.[21][22] By decreasing the
chance of your immune system activating inappropriately, a happy gut microbiome leads to
less pain over time.

Pain science undergoes major new developments seemingly every few months. Despite this,
chronic pain not only persists, but more and more people have joint pain each year. Don’t fall for
this common trap: trying quick fix after quick fix and wasting a lot of money along the way.

A wise strategy for dealing with recalcitrant joint pain is to act slowly and mindfully: figure out which
treatments are most likely to net some benefit, pick a couple, and stick with them for at least a few
weeks. It’s easy to try some hyped-up treatment and then be disappointed when it doesn’t work. It’s
harder to try, over weeks and months, to make your brain and gut happier, to get more sunshine,
and to take just a supplement or two from those presented in this guide. But joint pain is a unique
enemy, and to combat it, you need a uniquely wise strategy. Best of luck.

Kamal Patel, Co-founder and Director

MBA, MPH, PhD(c) in Nutrition

10
Combos

In this section you’ll learn to integrate various supplements into

synergistic combos. You’ll discover a core combo (composed of
the core supplements) and several specialized combos (composed
of primary and secondary options). Each specialized combo is
optimized for a specific population. The simplest way to formulate
your own combo is to combine the core combo with the specialized
combo that best fits your situation, needs, and primary health goal.

Core Combo
Joint pain is caused by a variety of factors. Since no supplement can address all of them, there is
no core supplement in this guide.

Specialized Combos

Tip: Try one combo alone for a few

weeks
Taking too many supplements at once may prevent you from determining which ones are
truly working. Start with just one of the combos suggested here for a couple of weeks before
you consider making any modification, such as adding another supplement, altering a
supplements dosage, or incorporating the supplements from an additional combo.

When adding another supplement to your regimen, be methodical. For example, you may
wish to take all the supplements from two combos. Select the combo that you wish to try

11
 first and take this for a couple of weeks. Then, add one supplement from the second combo
and wait another week to see how it affects you. Continue this process until you’ve added all
the supplements you wish to.

If a supplement appears in two combos you wish to combine, don’t stack the doses; instead,
combine the ranges. For instance, if the range is 2–4 mg in one combo and 3–6 mg in the
other, your new range becomes 2–6 mg. Always start with the lower end of the range —
especially in this case, since the reason why one of the ranges has a lower ceiling in one
combo may be due to a synergy with another supplement in the same combo. Reading
through the full supplement entry may help you decide which dose to aim for, but if you’re
not sure, lower is usually safer.

For people with osteoarthritis

Each day, with food, take 1.2 g of chondroitin sulfate, 1.5 g of glucosamine sulfate, 100–200 mg of
Pycnogenol, and some collagen in the form of undenatured type-II collagen (40 mg), hydrolyzed
collagen (10 g), or gelatin (10–15 g).

After one month, add either Boswellia serrata or curcumin to your regimen. If your condition doesn’t
improve, switch to the other plant extract. If your situation improves with either extract, wait for it to
stabilize, then add the other extract; if your condition improves some more, you can keep taking
both extracts.

Studies on Boswellia serrata tend to use one of two patented extracts: 5-Loxin and Aflapin. To
supplement either, take 100–250 mg once a day. Alternatively, you can try taking 1,800 mg of the
plant’s gum oleoresin three times a day (i.e., 5,400 mg/day).

Curcumin is a component of turmeric (Curcuma longa). Its bioavailability can be greatly increased
by taking it with piperine (a black pepper extract) or by combining it with lipids (BCM-95, Meriva).
To supplement curcumin with piperine, take 500 mg of the former with 20 mg of the latter, thrice a
day (i.e., 1.5 g of curcumin and 60 mg of piperine per day). To supplement BCM-95 or Meriva, take
500 mg twice a day (i.e., 1 g/day).

For people with rheumatoid arthritis

Get 3 g of combined EPA and DHA per day by eating fatty fish (e.g., 200 g of salmon) or by taking
fish oil softgels (with food, to reduce the chance of fishy burps). Vegans and vegetarians have the

12
option of taking algal oil softgels.

In addition, take 40 mg of undenatured type-II collagen once a day.

For people at risk of complex regional pain syndrome

(CRPS)
Take 500 mg of vitamin C once a day, ideally in the morning.

For people with joint pain related to athletics

Try the “rheumatoid arthritis” combo, above. You can choose to replace the undenatured type-II
collagen (40 mg) by some hydrolyzed collagen (10 g) or some gelatin (10–15 g).

Cissus quadrangularis is a popular option among athletes, but further research needs to confirm its
benefits before it can be included in this specialized combo.

Remember that supplementation should not serve as primary treatment for injuries. It can be
used as ancillary treatment and to alleviate the pain while tending to an injury, but alleviating the
pain in order to continue exercising will only worsen the injury.

For people with joint pain unrelated to a disease or to

athletics
Try the “rheumatoid arthritis” combo, above. You can choose to replace the undenatured type-II
collagen (40 mg) by some hydrolyzed collagen (10 g) or some gelatin (10–15 g).

If your pain persists, add the “osteoarthritis” combo, above. Although collagen is a supplement in
both specialized combos, taking both specialized combos doesn’t mean doubling the collagen
dose.

Other options
MSM (3–6 g/day) can be added to any combo that includes chondroitin, glucosamine, or Boswellia
serrata.

13
Core Supplements

Core supplements have the best safety-efficacy profile. When

used responsibly, they are the supplements most likely to help and
not cause side effects.

Joint pain is caused by a variety of factors. Since no supplement can address all of them, there is
no core supplement.

14
Primary Options

Primary options may provide substantial benefit, but only in the

right context. A primary option is not for everyone, but if you read
the entry and find that you meet the criteria, consider adding the
supplement to your combo.

Boswellia Serrata
What makes Boswellia serrata a primary option
Boswellia serrata is a plant used in Ayurvedic medicine notably to alleviate joint pain. Research
suggests that it could be as effective as some pharmaceuticals for the purpose of alleviating joint
pain and improving knee flexibility in people with osteoarthritis. More evidence is needed before it
can be recommended for people with rheumatoid arthritis.

What is osteoarthritis?

15
In Ayurvedic medicine, Boswellia serrata is often used alongside Curcuma longa (turmeric), a plant
rich in curcumin. Further research is needed to determine whether these two supplements actually
have synergistic properties.

How to take Boswellia serrata

Studies on Boswellia serrata tend to use one of two patented extracts: 5-Loxin and Aflapin. To
supplement either, take 100–250 mg once a day with food. Alternatively, you can try taking 1,800
mg of the plant’s gum oleoresin three times a day (i.e., 5,400 mg/day).

Like curcumin, Boswellia serrata has been combined with lipids to increase its bioavailability (the
same company that makes Meriva for curcumin makes Casperome for Boswellia serrata), but
further research is needed to determine a dosage for joint health.

Tip: Why don’t you recommend

brands or specific products?
For two reasons:

• We don’t test physical products. What our researchers do — all day, every day — is
analyze peer-reviewed studies on supplements and nutrition.

• We go to great lengths to protect our integrity. As you’ve probably noticed, we don’t

sell supplements, or even show ads from supplement companies, even though
either option would generate a lot more money than our Supplement Guides ever
will — and for a lot less work, too.

If we recommended any brands or specific products, our integrity would be called into
question, so … we can’t do it. That being said, in the interest of keeping you safe, we drew
a short list of steps you should take if a product has caught your interest.

16
Chondroitin
What makes chondroitin a primary option
Studies on knee osteoarthritis suggest that supplementation of chondroitin (a component of
cartilage) can reduce water retention in inflamed joints, improve mobility, and reduce pain.[23] Its
anti-inflammatory effects[24] could be occurring through inhibition of the protein complex NF-κB,
which regulates a host of inflammatory responses.[24]

Putative inflammatory interplay between the synovium

and cartilage

Adapted from Lovu et al. Osteoarthritis Cartilage. 2008.[24]

Like collagen and glucosamine, chondroitin is a component of cartilage, and there is some

17
evidence that it may reduce cartilage loss. With regard to joint pain and mobility, chondroitin and
glucosamine show modest benefits in many studies; by contrast, collagen, curcumin, and Boswellia
serrata show greater benefits, but studies are much fewer.

Orally supplementing with chondroitin is relatively safe.[25] Yet chondroitin and glucosamine may
have anticoagulant properties. This could be a problem for people taking blood thinners, be they
antiplatelet agents (such as aspirin) or anticoagulants (such as warfarin/Coumadin and
acenocoumarol/Sintrom).

While there is good evidence that suggests chondroitin could slow the progress of osteoarthritis, its
efficacy is not a settled matter. Some researchers have suggested that the question of efficacy may
be, in part, due to poor quality control in chondroitin supplements.[26] Some formulations of
chondroitin sulfate could have dosing variations, contaminants, or composition differences. Using
pharmaceutical-grade chondroitin, whose purity and dose is vetted, may be more effective.[27][28]

How to take chondroitin

Take 600–1,200 mg of chondroitin sulfate per day, with food. Within this range, higher doses tend
to be more effective.

Talk to your physician to see if a pharmaceutical-grade chondroitin is a viable treatment option for
your circumstances.

Current evidence suggests that chondroitin and glucosamine may be synergistic.

Collagen
What makes collagen a primary option
Collagen amounts to 25–35% of total protein in mammals, which makes it the most abundant
protein in our bodies.

The collagen in joint cartilage is 80–90% type-II collagen. Current research suggests that
undenatured type-II collagen (UC-II) may reduce swelling, joint pain, and stiffness in cases of
moderate-to-severe osteoarthritis and both juvenile and adult-onset rheumatoid arthritis.

How cartilage degrades in osteoarthritis vs.

18
 rheumatoid arthritis

Adapted from Smolen and Aletaha. Nat Rev Rheumatol. 2015.[29]

Collagen can be freed from the skins, bones, and other connective tissues of animals through
prolonged boiling; the resulting glutinous substance is called gelatin. In effect, gelatin is collagen
broken down into individual strands of protein (partial hydrolysis). Hydrolyzed collagen (HC) is
collagen further broken down into peptides (total hydrolysis). Gelatin dissolves only in hot water;
HC dissolves also in cool water.

Both HC and gelatin appear to reduce pain from osteoarthritis, but HC may be more bioavailable.
Most gelatin on the market (and probably most HC) is type-I collagen extracted from the skins and
bones of pigs and cows. Studies seldom see fit to specify the type(s) of collagen in their HC or
gelatin, however, so it is unclear if selecting a product made of type-II collagen would be more
beneficial to joint health.

As with chondroitin and glucosamine, two other components of cartilage, there is some evidence
that collagen may reduce cartilage loss.

19
How to take collagen
To supplement undenatured type-II collagen (UC-II), take 40 mg/day of a UC-II cartilage
supplement, which will yield 10 mg/day of native type-II collagen.

To supplement hydrolyzed collagen (also known as collagen hydrolysate), take 10 g/day.

To supplement gelatin, take 10–15 g/day. Keep in mind that, whereas true gelatin is pure collagen
(thus pure protein), the dessert called gelatin often has very little collagen in it.

In one study, gelatin increased collagen synthesis when taken after a bout of exercise, but more
research is needed to confirm this benefit and see if it extends to other forms of collagen.

Curcumin
What makes curcumin a primary option
Curcumin is a component of turmeric (Curcuma longa). It can inhibit the cyclooxygenase (COX)
enzymes and thus reduce inflammation in the body, so its action is similar to that of nonsteroidal
anti-inflammatory drugs (NSAIDs).[30]

Many studies looking at the effects of curcumin and turmeric on osteoarthritis symptoms have been
conducted.[31][32][33][34][35][36][37][38][39][40][41][42][43] Most of the higher-quality studies have found a
positive effect on overall symptoms, particularly pain, and also physical function and the effects
tends to be medium-large. One important caveat is that many of the studies were funded by
industry, and thus may be at a higher risk for bias towards positive findings, though non-industry-
funded studies have been largely positive as well.

Curcumin’s effects on patients with osteoarthritis

20
Reference: Belcaro et al. Altern Med Rev. 2010.[32]

Some athletes use curcumin to fight muscle inflammation. In theory, curcumin should have effects
similar in nature and potency to those of aspirin, and rodent studies are promising, but human
studies are needed for confirmation.

In Ayurvedic medicine, Curcuma longa is often used alongside Boswellia serrata. Further research
is needed to determine whether these two supplements actually have synergistic properties.

21
How to take curcumin
By itself, curcumin is poorly absorbed. Among the methods devised to address the issue, the two
most common (and most often tested) are to pair curcumin with piperine (a black pepper extract) or
to combine it with lipids (BCM-95®, Meriva® …).

To supplement curcumin with piperine, take 500 mg of the former with 20 mg of the latter, thrice a
day (i.e., 1,500 mg of curcumin and 60 mg of piperine per day).

To supplement BCM-95®, a patented combination of curcumin and essential oils, take 500 mg
twice a day (i.e., 1,000 mg/day).

To supplement Meriva®, a patented combination of curcumin and soy lecithin, take 200–500 mg
twice a day (i.e., 400–1,000 mg/day).

Curcumin is usually taken together with food.

Fish Oil
What makes fish oil a primary option
Essential fatty acids (EFAs) are polyunsaturated fatty acids (PUFAs) your body needs and cannot
produce. There are only two kinds of EFAs: linoleic acid (LA) and alpha-linolenic acid (ALA).
Neither is very active, so your body transforms the former notably into arachidonic acid (AA) and
the latter into eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). LA and AA are
omega-6 fatty acids, whereas ALA, EPA, and DHA are omega-3 fatty acids. EPA and DHA make
for most of the PUFAs in fish oil.

Fish oil has immunosuppressive properties, so it can benefit people with rheumatoid arthritis. It has
also been shown to alleviate work-related joint pain (i.e., pain not associated with a disease such
as osteoarthritis or rheumatism). As such, it is frequently supplemented by athletes. Early studies
on fish oil and athletes were disappointing, but later studies (which used much higher dosages)
have been encouraging.

22
 Digging Deeper: Oxidized fish oil
Fish oil can go rancid and oxidize when exposed to oxygen, heat, or light. These oils are
particularly susceptible to oxidation because of their very-long-chain polyunsaturated fatty
acids. The oxidation level is measured using three values.

1. Peroxide value (PV)

2. Anisidine value (AV)

3. Total oxidation value (TOTOX)

The PV is a measure of primary oxidation products (peroxides) and AV a measure of

secondary oxidation (aldehydes and ketones). The TOTOX value is calculated using the
formula AV + 2PV. The lower the TOTOX value, the better the oil quality will be. The Global
Organization for EPA and DHA Omega-3 recommends a TOTOX value of no more than 26.

Oxidation of fish oils may be more common than you suspect. One 2015 study found that
nearly 50% of commercial fish oils exceeded the maximum recommended TOTOX value.[44]
while others have found good compliance with TOTOX limits.[45][46] Taken together, the
divergent results demonstrate just how widely the quality of commercially available fish oil
supplement can be.

Evidence for the health effects of consuming oxidized fish oils is a bit mixed though. For
healthy individuals, it would appear that there is a lack of obvious short-term health damage
from consuming oxidized fish oil. One study showed no difference in circulating levels of
oxidized LDL or inflammatory markers after seven weeks of oxidized fish oil
supplementation.[47]

However, in people with high levels of cholesterol and triglycerides, consumption of highly
oxidized fish oils can minimize its efficiency at improving metabolic markers like fasting
glucose, total cholesterol, and triglycerides.[48]

How to take fish oil

Get 3 g of combined EPA and DHA per day by eating fatty fish (e.g., 200 g of salmon) or by taking
fish oil softgels (with food, to reduce the chance of fishy burps). Vegans and vegetarians have the
option of taking algal oil softgels.

23
Glucosamine
What makes glucosamine a primary option
For the treatment of knee osteoarthritis, there are more trials on glucosamine (a component of
cartilage) than on any other supplement. Pooled results show a reduction in pain and an
improvement in function — both modest on average, but with important interindividual variability. In
some people, glucosamine relieves pain as well as acetaminophen (Tylenol), a pharmaceutical
painkiller. In others, alas, it has no effect. People taking glucosamine should monitor their
symptoms to better assess if this supplement works for them.

Like collagen and chondroitin, glucosamine is a component of cartilage, and there is some
evidence that it may reduce cartilage loss. With regard to joint pain and mobility, glucosamine and
chondroitin show modest benefits in many studies; by contrast, collagen, curcumin, and Boswellia
serrata show greater benefits, but studies are much fewer.

Glucosamine’s cartilage-preserving effects

Glucosamine and chondroitin may have anticoagulant properties. This could be a problem for
people taking blood thinners, be they antiplatelet agents (such as aspirin) or anticoagulants (such
as warfarin/Coumadin and acenocoumarol/Sintrom).

24
How to take glucosamine
Take 1.5 g of crystalline glucosamine sulfate (a stabilized form of glucosamine sulfate).

Glucosamine sulfate sodium chloride is the best-studied form of crystalline glucosamine sulfate,
but preliminary evidence suggests that glucosamine sulfate potassium chloride may be equally
efficacious.

Studies do not support the use of other types of glucosamine sulfate. Studies do not support the
use of glucosamine hydrochloride.

Current evidence suggests that glucosamine and chondroitin may be synergistic.

25
Secondary Options

Secondary options have less evidence for their effects. They

could work or be a waste of money. Keep them in mind, but think
twice before adding them to your combo.

Cissus Quadrangularis
What makes Cissus quadrangularis a secondary option
Cissus quadrangularis has long been used in Ayurvedic medicine to promote bone healing and
relieve joint pain. Its benefits may stem from its anti-inflammatory properties and its ability to induce
growth factors in connective tissues.

Today, Cissus quadrangularis is often supplemented by athletes (particularly martial artists) to

relieve joint pain.[49] Much more research is needed to confirm this effect, but preliminary evidence
is promising.

Supplementation, however, should not serve as primary treatment for injuries. It can be used to
alleviate the pain while tending to an injury, but alleviating the pain in order to continue exercising
will only worsen the injury.

How to take Cissus quadrangularis

Take a Cissus quadrangularis extract standardized to 2.5% ketosteroid. Start with 300–600 mg/day.
Over a month, increase your daily dosage until pain disappears or you reach 3,200 mg/day.

Cissus quadrangularis may have muscle-relaxing properties, so it should be taken after a workout
or before bed.

26
MSM
What makes MSM a secondary option
Methylsulfonylmethane (MSM) is the oxidized form of dimethyl sulfoxide (DMSO). Both are
chemically similar sulfur compounds, but MSM is prefered over DMSO because it is more stable,
does not smell as bad, and does not cause skin irritations. MSM can be found in foods (such as
coffee, corn, tomatoes, or tea), but only in tiny amounts.

In people with knee osteoarthritis, MSM supplementation may improve physical functioning, but
results are mixed with regard to reductions in pain, swelling, or stiffness.

Basic knee anatomy

27
How to take MSM
The best study on MSM used 1,125 mg three times a day (i.e., 3,375 mg/day). There is no proven
benefit to taking more than 6 g per day.

MSM has been tested with Boswellia serrata, with glucosamine, and with a combination of
glucosamine and chondroitin. In each case, the addition of MSM seems to add a slight benefit, but
further research is needed for confirmation.

28
Pycnogenol
What makes Pycnogenol a secondary option
The flavonoids called procyanidins can improve blood flow and reduce inflammation. Pycnogenol is
a patented pine bark extract standardized to 65–75% procyanidin; there is preliminary evidence
that it can benefit people with osteoarthritis, but further research is needed for confirmation.

Grape seed extracts are rich in procyanidins and cheaper than pine bark extracts, but their benefits
to joint health have never been directly demonstrated.

How to take Pycnogenol

To supplement Pycnogenol, take 100–200 mg once a day with a meal.

Maximum benefit is usually experienced after three months of continuous supplementation.

Vitamin C
What makes vitamin C a secondary option
Vitamin C is necessary for collagen formation, so having low levels of vitamin C can be detrimental
to joint health. In people whose levels are normal, however, supplemental vitamin C has little effect
on joint disorders, with one exception: It can help prevent complex regional pain syndrome (CRPS),
a painful chronic condition characterized by swollen joints and by changes in skin and hair quality.
CRPS can be caused by orthopedic surgery or a joint injury.

Vitamin C may reduce the effectiveness of some HIV medications. Moreover, since it can increase
the absorption of iron and aluminum, it should not be supplemented within several hours of
aluminum-based antacids (Amphojel, AlternaGEL, Alu-Cap, Alu-Tab, Dialume).

How to take vitamin C

People at risk of CRPS can take 500 mg of vitamin C once a day, ideally in the morning.

People with joint pain not associated with CRPS can also take 500 mg of vitamin C once a day, but

29
if the pain has not lessened after two months, supplementation need not be continued.

Further research is needed to determine if vitamin C is better absorbed with food.

The Recommended Dietary Allowance (RDA) for vitamin C for adults ranges from 75–120 mg per
day.[50] While 500 mg/day dose discussed here exceeds that, it is still well under vitamin C’s
Tolerable Upper Intake Level (UL) of 2,000 mg/day.

Tolerable Upper Intake Level (UL) for vitamin C (mg)

AGE MALE FEMALE PREGNANT LACTATING

0–12 months * * — —

1–3 years 400 400 — —

4–8 years 650 650 — —

9–13 years 1,200 1,200 — —

14–18 years 1,800 1,800 1,800 1,800

>18 years 2,000 2,000 2,000 2,000

* Formula and food should be the only sources of vitamin C for infants.
Reference: Institute of Medicine. Vitamin C (chapter 5 in Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and
Carotenoids. The National Academies Press. 2000. DOI:10.17226/9810)

30
Unproven Supplements

Unproven supplements are backed by tradition or by

mechanistic, animal, epidemiological, or anecdotal evidence, but
not yet by convincing human trials. At this point, they are not good
candidates for your combo.

CBD (cannabidiol)
CBD (cannabidiol) is the second most abundant cannabinoid in cannabis (aka marijuana), after
THC (tetrahydrocannabinol).[51] Isolated CBD is typically used medicinally, not recreationally, with
the four most commonly targeted conditions being pain, anxiety, depression, and sleep
disorders.[52]

The Arthritis Foundation is a United States-based advocacy group. One of their aims is to provide
evidence-based resources for people with arthritis. A recent survey they conducted found that 30%
of the respondents used cannabidiol (CBD) and close to 80% were considering using it or have
used it previously.

The large and growing interest in CBD prompted The Arthritis Foundation to release a set of
expert-reviewed guidelines for people with arthritis who are interested in using CBD. The key
takeaways are summarized below. Another review by the National Academies of Sciences,
Engineering, and Medicine also found studies on CBD and arthritis were very limited at the
moment.[53]

Key takeaways from The Arthritis Foundation’s CBD

guidelines

31
Reference: Arthritis.org

32
Inadvisable Supplements

Inadvisable supplements are either potentially dangerous or

simply ineffective, marketing claims notwithstanding. Do not add
them to your combo. At best, they’ll be a waste of money; at worst,
they can cause you harm.

Thunder God Vine

What makes thunder god vine an unproven
supplement

Caution: This supplement has the

potential to harm your health
Please read the following section carefully. Examine.com advises against adding this
supplement to your regimen.

Thunder god vine (Tripterygium wilfordii) is used in Traditional Chinese Medicine to treat a wide
range of conditions. By decreasing the number of white blood cells, it reduces inflammation (and
thus pain) around the joints, but it also makes the body more susceptible to infection, leading to
sickness and potentially death.

Though it appears to be effective at treating rheumatoid arthritis, thunder god vine is not safe
and should not be supplemented.

Adverse effects of thunder god vine

33
34
FAQ
Q. What about the supplements not covered in this
guide?
Our guides are regularly updated, often with new supplements. We prioritize assessing (and
reassessing) the most popular of them and those most likely to work. However, if there is a specific
supplement you’d like to see covered in a future update, please let us know by filling out this
survey.

Q. Can I add a supplement not covered in this guide to

my combo?
Supplement with your current combo for a few weeks before attempting any change. Talk to your
physician and research each potential addition. Check for known negative interactions with other
supplements and pharmaceuticals in your current combo, but also for synergies. If two
supplements are synergistic or additive in their effects, you might want to use lower doses of each.

Q. Can I modify the recommended doses?

If a supplement has a recommended dose range, stay within that range. If a supplement has a
precise recommended dose, stay within 10% of that dose. Taking more than recommended could
be counterproductive or even dangerous. Taking less could render the supplement ineffective, yet
starting with half the regular dose could be prudent — especially if you know you tend to react
strongly to supplements or pharmaceuticals.

Q. At what time should I take my supplements?

The answer is provided in the “How to take” section of a supplement entry whenever the evidence
permits. Too often, however, the evidence is either mixed or absent. Starting with half the regular
dose can help minimize the harm a supplement may cause when taken during the day (e.g.,
fatigue) or in the evening (e.g., insomnia).

35
Q. Should I take my supplements with or without food?
The answer is provided in the “How to take” section of a supplement entry whenever the evidence
permits. Too often, however, the evidence is either mixed or absent. Besides, a supplement’s
digestion, absorption, and metabolism can be affected differently by different foods. Fat-soluble
vitamins (A, D, E, K), for instance, are better absorbed with a small meal containing fat than with a
large meal containing little to no fat.

Q. What are DRI, RDA, AI, and UL?

The Dietary Reference Intakes (DRIs) is a system of nutrition recommendations designed by the
Institute of Medicine (a US institution now known as the Health and Medicine Division). RDA, AI,
and UL are part of this system.

• Contrary to what the name suggests, a Recommended Dietary Allowance (RDA) doesn’t
represent an ideal amount; it represents the minimum you need in order to avoid deficiency-
related health issues. More precisely, it represents an amount just large enough to meet the
minimum requirements of 97.5% of healthy males and females over all ages — which
implies that the RDA is too low for 2.5% of healthy people.

• The Adequate Intake (AI) is like the RDA, except that the number is more uncertain.

• The Tolerable Upper Intake Level (UL) is the maximum safe amount. More precisely, it is
the maximum daily amount deemed to be safe for 97.5% of healthy males and females over
all ages — which implies that the UL is too high for 2.5% of healthy people.

As a general rule, a healthy diet should include at least the RDA of each nutrient — but less than
this nutrient’s UL. This rule has many exceptions, though. For instance, people who sweat more
need more salt (i.e., sodium), whereas people who take metformin (a diabetes medicine) need
more vitamin B12.

Moreover, the DRIs are based on the median weight of adults and children in the United States.
Everything else being equal (notably age, sex, and percentage of body fat), you likely need a
lesser amount of nutrients if you weigh less, and vice versa if you weigh more. The numbers,
however, are not proportional — if only because the brains of two people of very different weights
have very similar needs. So you can’t just double your RDIs for each nutrient if you weigh twice as
much as the median adult of your age and sex (even if we overlook that people weighing the same
can differ in many respects, notably body fat).

Q. What's the difference between osteoarthritis and

36
rheumatoid arthritis?
Osteoarthritis is caused by a progressive loss of cartilage that leads to joint inflammation via bone-
on-bone rubbing, whereas rheumatoid arthritis is an autoimmune inflammatory disease that targets
and degrades joint tissue.

Q. What are the risk factors for osteoarthritis?

Distinct risk factors for osteoarthritis, summarized below, include genetic susceptibility,
morphological variations in bones and joints, traumatic joint injury, excessive joint stress, aging,
and obesity.[54] Obesity is a major risk factor for osteoarthritis of the knee,[55] and weight loss can
lead to improvements in the condition,[56] though more long-term studies are warranted.

Exercise can be useful for reducing pain and improving joint function,[57][58] though exercising with
sore joints can be difficult, and not all forms of exercise are suitable for every patient.[59]

Pharmaceutically, treatment mostly revolves around the use of nonsteroidal anti-inflammatories

(NSAIDs). While effective in reducing pain,[60] these drugs aren’t without their adverse effects,
which can include an increased risk of stroke and heart attack.[61][62]

Osteoarthritis risk factors

37
Reference: Allen and Golightly. Curr Opin Rheumatol. 2015.[54]

Q. Will supplementing or consuming turmeric yield the

same benefits as curcumin supplementation?
Curcumin is the active ingredient in turmeric that yields many of the benefits currently seen, but
both are poorly absorbed in the gastrointestinal tract and usually require some enhancement to
increase bioavailability.[63] Typically, a compound found in black pepper, known as piperine, is
supplemented alongside curcumin to increase this bioavailability.[64] Other products increase
bioavailability by using specialized formulations, such as the use of nanotechnology or a blend of
essential oils.

It is unlikely, though, that simply consuming turmeric in small amounts through the diet will yield the
same benefits as supplementing large doses of curcumin, due to the small dosage and poor
bioavailability. It is also worth noting that turmeric has been found in some studies to be
contaminated with heavy metals like lead.[65]

Q. What about essential nutrients? I don’t see many in

this guide.
It’s plausible that some essential nutrients would be relevant to osteoarthritis, but evidence is
sparse.

Calcium fructoborate, a form of boron, has shown potent reductions in circulating inflammatory
cytokines associated with osteoarthritis in a handful of small trials,[66] and in osteoarthritis
patients.[67] Although its impact on osteoarthritis-specific endpoints has yet to be studied in
humans, at least one study in dogs suggests an improvement in physical function.[68]

Vitamin K is also plausible[69], but not well-studied. It would be beneficial to see studies of common
nutrient deficiencies in osteoarthritis and more trials on plausible supplements in the future, though
there isn’t very much information at present.

Q. Will using CBD alone increase my appetite?

In short, probably not. THC, one of cannabis's main active ingredients, is primarily responsible for
the appetite-stimulating effects of cannabis. THC can interact with receptors in the body that can, in
turn, increase appetite. The method of consumption can affect how THC influences food choice
and overall food intake, as can the amount and nature of the products consumed concurrently.

38
However, some products labeled “CBD only” or “0 THC” may still have high enough amounts of
THC to cause an effect. Be conscious of who your source is if you chose to use CBD products.

How cannabis increases appetite

References: Cota et al. Int J Obes Relat Metab Disord. 2003.[70] ● Patel and Cone. Nature. 2015.[71]

Q. What can I do to help prevent my fish oils from

oxidizing?
Since fish oil is primarily polyunsaturated fat, it is prone to becoming rancid and oxidizing.
Oxidation largely depends on exposure to heat, light, and oxygen. The addition of antioxidants to
the final product can reduce the rate of oxidation during storage. Vitamin E is typically used, but

39
there’s a lot of research on other antioxidants like carnosic acid suggesting they might be
superior.[72]

Part of the responsibility for ensuring fish oil remains unoxidized is on the buyer. Exposure of fish
oil to light, heat, and oxygen accelerates the oxidation of the oil, with the magnitude of damage
depending on the length and degree of exposure. Once you buy the supplement, it is prudent to
store it in a cool place away from light, such as the fridge.

If you buy oil in a bottle, the bottle should be tinted to prevent light from getting through and small
enough that you can work through it in a month or two. After all, oxygen gets in the bottle every
time you open it. Some fish oil bottles come with a pump, which can help reduce oxygen exposure.
Buying capsules instead of bottles can also help prevent oxidation.

Q. How do NSAIDs provide pain relief?

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to relieve pain or a fever.
Common forms include aspirin (Advil), ibuprofen (Motrin), and naproxen (Aleve, Naprosyn) but they
all work through a similar mechanism: they block an enzyme called cyclooxygenase (COX).[73] But
there’s a twist! This enzyme comes in two major forms: COX-1 and COX-2.

• COX-1 is involved in the production of prostaglandins, which perform many functions in the
body, including maintaining good kidney function and producing the protective layer of the
gastrointestinal (GI) tract.

• COX-2 produces molecules responsible for pain and inflammation, so that’s the one to
target if you want to reduce these effects.

Most NSAIDs nonselectively target both COXs, which explains their infamous GI adverse effects.
However, the NSAID celecoxib (Celebrex) binds more to COX-2 than COX-1, so it can target pain
and inflammation with fewer adverse effects, at least in theory. In reality, the advantages of
celecoxib are not so clear-cut. A recent review found that the relative harm and benefit of celecoxib
for people with osteoarthritis are hard to assess, partially because of the general scarcity and
possible bias of evidence due to industry involvement.[74]

40
References

41
 1. ^ Mifflin KA, Kerr BJ. The transition from acute to chronic pain: understanding how
different biological systems interact. Can J Anaesth. (2014)
2. ^ Kaeding C, Best TM. Tendinosis: pathophysiology and nonoperative treatment.
Sports Health. (2009)
3. ^ Siemieniuk RAC, et al. Arthroscopic surgery for degenerative knee arthritis and
meniscal tears: a clinical practice guideline. Br J Sports Med. (2018)
4. ^ Queiroz LP. Worldwide epidemiology of fibromyalgia. Curr Pain Headache Rep.
(2013)
5. ^ Politei J, et al. When arthralgia is not arthritis. Eur J Rheumatol. (2016)
6. ^ Woolf CJ. Central sensitization: implications for the diagnosis and treatment of
pain. Pain. (2011)
7. ^ Joshi SK, Honore P. Animal models of pain for drug discovery. Expert Opin Drug
Discov. (2006)
8. ^ Wang CK, Myunghae Hah J, Carroll I. Factors contributing to pain chronicity. Curr
Pain Headache Rep. (2009)
9. ^ Hsu CJ, et al. Fear of Reinjury in Athletes. Sports Health. (2017)
10. ^ Blay SL, Andreoli SB, Gastal FL. Chronic painful physical conditions, disturbed
sleep and psychiatric morbidity: results from an elderly survey. Ann Clin Psychiatry.
(2007)
11. ^ Sasaki E, et al. Nocturnal knee pain increases with the severity of knee
osteoarthritis, disturbing patient sleep quality. Arthritis Care Res (Hoboken). (2014)
12. ^ Irwin MR, et al. Sleep loss exacerbates fatigue, depression, and pain in rheumatoid
arthritis. Sleep. (2012)
13. ^ Apkarian AV, Baliki MN, Geha PY. Towards a theory of chronic pain. Prog
Neurobiol. (2009)
14. ^ Chevalier G, et al. Earthing: health implications of reconnecting the human body to
the Earth's surface electrons. J Environ Public Health. (2012)
15. ^ Walch JM, et al. The effect of sunlight on postoperative analgesic medication use: a
prospective study of patients undergoing spinal surgery. Psychosom Med. (2005)
16. ^ Taylor SL, et al. Pilot study of the effect of ultraviolet light on pain and mood in
fibromyalgia syndrome. J Altern Complement Med. (2009)
17. ^ Messier SP, et al. Weight loss reduces knee-joint loads in overweight and obese
older adults with knee osteoarthritis. Arthritis Rheum. (2005)
18. ^ Apkarian AV, et al. Human brain mechanisms of pain perception and regulation in
health and disease. Eur J Pain. (2005)
19. ^ la Cour P, Petersen M. Effects of mindfulness meditation on chronic pain: a

42
 randomized controlled trial. Pain Med. (2015)
20. ^ Zamani B, et al. Clinical and metabolic response to probiotic supplementation in
patients with rheumatoid arthritis: a randomized, double-blind, placebo-controlled trial.
Int J Rheum Dis. (2016)
21. ^ Brown K, et al. Diet-induced dysbiosis of the intestinal microbiota and the effects on
immunity and disease. Nutrients. (2012)
22. ^ Spreadbury I. Comparison with ancestral diets suggests dense acellular
carbohydrates promote an inflammatory microbiota, and may be the primary dietary
cause of leptin resistance and obesity. Diabetes Metab Syndr Obes. (2012)
23. ^ Singh JA, et al. Chondroitin for osteoarthritis. Cochrane Database Syst Rev. (2015)
24. ^ a b c Iovu M, Dumais G, du Souich P. Anti-inflammatory activity of chondroitin
sulfate. Osteoarthritis Cartilage. (2008)
25. ^ Fardellone P, et al. Comparative efficacy and safety study of two chondroitin sulfate
preparations from different origin (avian and bovine) in symptomatic osteoarthritis of
the knee. Open Rheumatol J. (2013)
26. ^ Martel-Pelletier J, et al. Discrepancies in composition and biological effects of
different formulations of chondroitin sulfate. Molecules. (2015)
27. ^ Honvo G, Bruyère O, Reginster JY. Update on the role of pharmaceutical-grade
chondroitin sulfate in the symptomatic management of knee osteoarthritis. Aging Clin
Exp Res. (2019)
28. ^ Pelletier JP, et al. Chondroitin sulfate efficacy versus celecoxib on knee
osteoarthritis structural changes using magnetic resonance imaging: a 2-year
multicentre exploratory study. Arthritis Res Ther. (2016)
29. ^ Smolen JS, Aletaha D. Rheumatoid arthritis therapy reappraisal: strategies,
opportunities and challenges. Nat Rev Rheumatol. (2015)
30. ^ Hewlings SJ, Kalman DS. Curcumin: A Review of Its' Effects on Human Health.
Foods. (2017)
31. ^ Panahi Y, et al. Curcuminoid treatment for knee osteoarthritis: a randomized
double-blind placebo-controlled trial. Phytother Res. (2014)
32. ^ a b Belcaro G, et al. Efficacy and safety of Meriva®, a curcumin-
phosphatidylcholine complex, during extended administration in osteoarthritis
patients. Altern Med Rev. (2010)
33. ^ Belcaro G, et al. Product-evaluation registry of Meriva®, a curcumin-
phosphatidylcholine complex, for the complementary management of osteoarthritis.
Panminerva Med. (2010)
34. ^ Kuptniratsaikul V, et al. Efficacy and safety of Curcuma domestica extracts in
patients with knee osteoarthritis. J Altern Complement Med. (2009)

43
35. ^ Madhu K, Chanda K, Saji MJ. Safety and efficacy of Curcuma longa extract in the
treatment of painful knee osteoarthritis: a randomized placebo-controlled trial.
Inflammopharmacology. (2013)
36. ^ Nakagawa Y, et al. Short-term effects of highly-bioavailable curcumin for treating
knee osteoarthritis: a randomized, double-blind, placebo-controlled prospective study.
J Orthop Sci. (2014)
37. ^ Haroyan A, et al. Efficacy and safety of curcumin and its combination with boswellic
acid in osteoarthritis: a comparative, randomized, double-blind, placebo-controlled
study. BMC Complement Altern Med. (2018)
38. ^ Kuptniratsaikul V, et al. Efficacy and safety of Curcuma domestica extracts
compared with ibuprofen in patients with knee osteoarthritis: a multicenter study. Clin
Interv Aging. (2014)
39. ^ Panda SK, et al. A Randomized, Double Blind, Placebo Controlled, Parallel-Group
Study to Evaluate the Safety and Efficacy of Curene® versus Placebo in Reducing
Symptoms of Knee OA. Biomed Res Int. (2018)
40. ^ Pinsornsak P, Niempoog S. The efficacy of Curcuma Longa L. extract as an
adjuvant therapy in primary knee osteoarthritis: a randomized control trial. J Med
Assoc Thai. (2012)
41. ^ Shep D, et al. Safety and efficacy of curcumin versus diclofenac in knee
osteoarthritis: a randomized open-label parallel-arm study. Trials. (2019)
42. ^ Srivastava S, et al. Curcuma longa extract reduces inflammatory and oxidative
stress biomarkers in osteoarthritis of knee: a four-month, double-blind, randomized,
placebo-controlled trial. Inflammopharmacology. (2016)
43. ^ Henrotin Y, et al. Bio-optimized Curcuma longa extract is efficient on knee
osteoarthritis pain: a double-blind multicenter randomized placebo controlled three-
arm study. Arthritis Res Ther. (2019)
44. ^ Albert BB, et al. Fish oil supplements in New Zealand are highly oxidised and do
not meet label content of n-3 PUFA. Sci Rep. (2015)
45. ^ Bannenberg G, et al. Omega-3 Long-Chain Polyunsaturated Fatty Acid Content
and Oxidation State of Fish Oil Supplements in New Zealand. Sci Rep. (2017)
46. ^ Bengtson Nash SM, Schlabach M, Nichols PD. A nutritional-toxicological
assessment of Antarctic krill oil versus fish oil dietary supplements. Nutrients. (2014)
47. ^ Ottestad I, et al. Intake of oxidised fish oil does not affect circulating levels of
oxidised LDL or inflammatory markers in healthy subjects. Nutr Metab Cardiovasc
Dis. (2013)
48. ^ García-Hernández VM, et al. Effect of omega-3 dietary supplements with different
oxidation levels in the lipidic profile of women: a randomized controlled trial. Int J Food
Sci Nutr. (2013)

44
49. ^ Bloomer RJ, et al. Cissus quadrangularis reduces joint pain in exercise-trained
men: A pilot study. Phys Sportsmed. (2013)
50. ^ Institute of Medicine (US) Panel on Dietary Antioxidants and Related Compounds.
Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids.
51. ^ Andre CM, Hausman JF, Guerriero G. Cannabis sativa: The Plant of the Thousand
and One Molecules. Front Plant Sci. (2016)
52. ^ Corroon J, Phillips JA. A Cross-Sectional Study of Cannabidiol Users. Cannabis
Cannabinoid Res. (2018)
53. ^ National Academies of Sciences, et al. The Health Effects of Cannabis and
Cannabinoids: The Current State of Evidence and Recommendations for Research.
54. ^ a b Allen KD, Golightly YM. State of the evidence. Curr Opin Rheumatol. (2015)
55. ^ Bliddal H, Leeds AR, Christensen R. Osteoarthritis, obesity and weight loss:
evidence, hypotheses and horizons - a scoping review. Obes Rev. (2014)
56. ^ Christensen R, et al. Effect of weight reduction in obese patients diagnosed with
knee osteoarthritis: a systematic review and meta-analysis. Ann Rheum Dis. (2007)
57. ^ Iwamoto J, et al. RETRACTED ARTICLE. World J Orthop. (2011)
58. ^ Uthman OA, et al. Exercise for lower limb osteoarthritis: systematic review
incorporating trial sequential analysis and network meta-analysis. Br J Sports Med.
(2014)
59. ^ Wang Y, et al. Is physical activity a risk factor for primary knee or hip replacement
due to osteoarthritis? A prospective cohort study. J Rheumatol. (2011)
60. ^ da Costa BR, et al. Effectiveness of non-steroidal anti-inflammatory drugs for the
treatment of pain in knee and hip osteoarthritis: a network meta-analysis. Lancet.
(2017)
61. ^ Machado GC, et al. Efficacy and safety of paracetamol for spinal pain and
osteoarthritis: systematic review and meta-analysis of randomised placebo controlled
trials. BMJ. (2015)
62. ^ Trelle S, et al. Cardiovascular safety of non-steroidal anti-inflammatory drugs:
network meta-analysis. BMJ. (2011)
63. ^ Anand P, et al. Bioavailability of curcumin: problems and promises. Mol Pharm.
(2007)
64. ^ Shoba G, et al. Influence of piperine on the pharmacokinetics of curcumin in
animals and human volunteers. Planta Med. (1998)
65. ^ Forsyth JE, et al. Turmeric means "yellow" in Bengali: Lead chromate pigments
added to turmeric threaten public health across Bangladesh. Environ Res. (2019)
66. ^ Mogoşanu GD, et al. Calcium Fructoborate for Bone and Cardiovascular Health.
Biol Trace Elem Res. (2016)

45
67. ^ Scorei R, et al. A double-blind, placebo-controlled pilot study to evaluate the effect
of calcium fructoborate on systemic inflammation and dyslipidemia markers for
middle-aged people with primary osteoarthritis. Biol Trace Elem Res. (2011)
68. ^ Price AK, et al. Effects of dietary calcium fructoborate supplementation on joint
comfort and flexibility and serum inflammatory markers in dogs with osteoarthritis. J
Anim Sci. (2017)
69. ^ Rayman M. Diet, nutrition and osteoarthritis. BMC Musculoskelet Disord.. (2015)
70. ^ Cota D, et al. Endogenous cannabinoid system as a modulator of food intake. Int J
Obes Relat Metab Disord. (2003)
71. ^ Patel S, Cone RD. Neuroscience: a cellular basis for the munchies. Nature. (2015)
72. ^ Wang H, et al. Oxidative stability of fish oil supplemented with carnosic acid
compared with synthetic antioxidants during long-term storage. Food Chem. (2011)
73. ^ Vane JR, Botting RM. Mechanism of action of nonsteroidal anti-inflammatory drugs.
Am J Med. (1998)
74. ^ Puljak L, et al. Celecoxib for osteoarthritis. Cochrane Database Syst Rev. (2017)

46
Bios

Michael Hull
Senior research manager ● MSc in human nutrition

Michael received a BSc in exercise science with a minor in

nutrition from George Mason University (where he mentored
under GMU’s resident sports dietitian, Deanna Busteed, MS,
RD, CSSD), then an MSc in human nutrition from McGill
University. His master’s thesis examined how modifiable lifestyle
factors can potentially predict vitamin D status. As a full-time
senior researcher at Examine.com, he primarily writes and
updates the Supplement Guides, maintains the company’s
database of supplement studies, and blogs about various health
topics. When not working for Examine.com, he enjoys finding
ways of using technology to further science communication.

Wyatt Brown
Researcher

Searching for ways to improve his health and frequently

confused by the conflicting messages from publications and
popular authors, Wyatt dove head first into the scientific
research and became fascinated by its logic and methods.
Contributing to his most respected website has only intensified
his interest and motivated him to pursue an education in
nutrition.

47
 Kamal Patel
Co-founder and director ● MBA, MPH, PhD(c) in nutrition

Kamal Patel is cofounder and director of Examine.com. He holds

two master’s degrees from the Johns Hopkins University, in
business and in public health, and is on hiatus from a PhD in
nutrition for which he’s investigated the link between diet and
chronic pain. He’s published peer-reviewed articles on vitamin D
and calcium, as well as on a variety of clinical research topics.
He’s also been involved in research on fructose and liver health,
on nutrition in low-income areas, and on mindfulness meditation.

Pierre-Alexandre Sicart
Resident copy editor ● AA in English, PhD in French
literature

Pierre-Alexandre holds graduate degrees from New York

University, the University of Toulouse II, and the University of St
Andrews. At NYU, he was MVP then captain of the Taekwondo
Club, president of the Karate Club, and founder of the Martial
Arts Club. After graduation, he wrote a grammar book, then
found himself working as assistant professor of French in
Taiwan. After some years enjoying the best foods in Asia, he
moved back to France to freelance as a writer, translator, and
copy editor. He’s Examine.com’s resident copy editor and has
been overseeing our Supplement Guides since 2016.

... and the rest of the team!

With degrees in nutrition, exercise science, medical science, public health, pharmacology,
toxicology, microbiology, biophysics, biomedical science, neuroscience, chemistry, and more, the
members of our team are all accredited experts, but with very different backgrounds, so that when
we review the evidence, we get the full picture.

48