Nobody Dies of Arthritis

directly.  But in practice, the pain of arthritis limits activity and discourages exercise.  The chronic pain of arthritis wears people down, contributing to depression, which is a substantial mortality risk factor.  Limitations on mobility combined with disspiriting effects of pain can destroy the will to live.  There is no cure for arthritis yet, but anti-inflammatories can slow its progress, and one Swiss company claims a cure in the pipeline.


The “commonsense” view of osteoarthritis is that the cartilage that lubricates our joints gradually wears down over time, and when we are old, bone grinds against bone.  Ouch!  In fact, the commonsense view became the medical view which dominated for many years.  But is it really so commonsensical?  Wearing down of the lubricant cartrilage takes place in the course of hours and days, and, in young people, it is rebuilt and replaced as fast as it is worn away.  (Even the association of extreme exertion with early-onset arthritis (Sandy Koufax’s elbow, : Shaquille O’Neal’s foot) is an effect of chronic inflammation rather than physical wear.)  Thirty-year-olds don’t have more arthritis than ten-year olds, but by sixty, almost everyone has symptoms of enlarged joints, degenerated disks or lumbar pain.  What happens over decades is not explained by the sum of tiny deficits in repair from day to day.  Rather it is changes in the metabolism (initiated by epigenetics, and mediated by signal molecules in the blood) that causes a slowing of regeneration and an acceleration of inflammatory damage.

Historically, the medical community distinguishes rheumatoid arthritis–an autoimmune disease–from osteoarthritis, which is accumulated wear on joints.  The emerging view, however, is that there is no fundamental distinction between them, and that the same metabolic forces are at play in both.  The symptoms were always the same, but the distinction was based etiology: osteoarthritis is almost universal in older people, whereas rheumatoid arthritis is traceable to trauma or an autoimmune condition.  We know now that autoimmunity is part of human aging, an icon of the self-destruction program coded in our genes.

Spinal stenosis is a particularly painful and debilitating complication of arthritis in the spine.  Inflamed bone grows until it impinges on the spinal cord, generating numbness or referred pain in the legs and compromising movement.  Fibromyalgia seems to be a generalized inflammation of joints and muscles.

 

What can be done?

Exercise may be the best treatment.  The cruel paradox is that arthritis makes exercise much less appealing, and so a vicious cycle begins.

“Patients’ fear for disease aggravation and an indefensible traditional approach of rheumatology health professionals to recommend exercise restriction may account for the inactive lifestyle of this population. It is now established that well-designed physical exercise programmes promote prolonged improvements without inducing harmful effects on disease activity and joint damage.” [ref]

Exercise may hurt, but you won’t hurt yourself with exercise.  Cycling and water aerobics are often suggested, not because they are inherently better for arthritis, but because people experience less discomfort and are more likely to stick with the program.

There is no cure for arthritis, but all the emerging anti-aging technologies are expected to slow or turn back the arthritis clock.

I’ve recommended vitamin D for many reasons, especially lowering risk of cancer and preserving the immune system.  In this study, vitamin D supplementation lowered incidence of arthritis by 1/3.  This study found that people with high circulating levels of vitamin D in the blood had risk of arthritis lower by 2/3.  Depending on your metabolism, you may need to take jumbo doses of vitamin D (10,000 – 30,000 IU) to get your blood level up above 90, which I think is ideal. (Here’s a study that looked for a protective effect of vitamin D and didn’t find any. Here’s another study that finds more tentative evidence of a benefit from high blod levels of vitamin D.)

Arthritis may also be one more reason to keep your magnesium intake high.

Glucosamine supplements have been used for more than 20 years, and are well-researched.  On average, they are marginally effective, if taken in sufficient quantity of 3 or more g per day.  Response varies with the individual, and glucosamine is well worth trying.  One study has found a lower all-cause mortality rate in people who take glucosamine.

A dark horse worth trying is boron, a trace mineral for which there is indirect evidence for a powerful benefit [ref].

S-adenasyl methionine (SAMe) is a pro-hormone, sold by prescription in Europe, where it is used as a treatment for arthritis.  Here’s a study that found SAMe worked as well as Celebrex.  My opinion is that SAMe is worth trying, despite thin evidence, because side-effects of SAMe are likely to be salutory.

A study with krill oil produced the best reported results.  Over the first month of treatment with 300mg/day, patients reported substantially less pain and more mobility, and their subjective experience was corroborated by a 30% drop in C-Reactive Protein (CRP) in their blood (a marker of inflammation).

Boswellia is a resin from the sap of a tree, classically known as frankincense.  It is well-known for anti-inflammatory effect, and there are four well-controlled studies that show objective and subjective benefits [1, 2, 3, 4].  (References collected by Examine.com)

Curcumin (from turmeric) is the best known of the herbal anti-inflammatories.  In clinical trials, it has been found to be effective, but not a magic bullet, comparable in benefit to ibuprofen.  Getting an adequate dose absorbed into the bloodstream is always an issue.

Nigella sativa produced benefits for some patients.  It is a tasty black seed, used in rye bread and middle-eastern cooking, known variously as charnoushka, kalonji, or black cumin seed (no relation to cumin).

Here is a review of many herbal anti-inflammatories, with explanation of the role of the signaling by NFkB as a bad actor.  (Full text available from ResearchGate.)  This team of distinguished Indian-Americans, with thousands of publications among them, highlights curcumin, resveratrol, tea polyphenols, genistein (soy), quercetin (onions), silymarin, guggulsterone  boswellia and ashwagandha.  Here is their table, including other candidates that have shown some promise in at least one study.

Herbs4Arthritis

 

Drugs

NSAIDs are effective.  Aspirin and ibuprofen are safe but of small benefit.  COX2 inhibitors (e.g. Celebrex=celecoxib)  are more effective but raise the risk of heart disease.  For some, the tradeoff may be worthwhile.  Celebrex has been marketed by Pfizer for about 20 years, and has been the subject of commercial law suits unrelated to safety.

Steroids (esp dexamethasone) work temporarily and make you feel good for awhile, but are not a long-term solution because of side-effects from upset stomach to diabetes to depression.

Humira, Remicade, and Enbrel are more recent entries into the arthritis marketplace.  They all target tumor necrosis factor (TNF) cytokines, they are all fantastically expensive, and clinical data is yet thin.  Talk to your insurance company.

 

On the horizon

Two years ago, there was a report from a Swiss pharmaceutical claiming a cure for arthritis in mice.  They combined dexamethasone with targeted immunotherapy, paradoxically using the immune system itself to attack inflamed sites [ref].  Interleukin4 is fantastically expensive, probably one motive for modifying the molecule with an antibody that would seek out inflamed target cells, so the dose can be reduced.  (Of course, lowered dosage also means fewer side-effects.)  The journal article and news reports from 2014 indicated that trials in humans were imminent, but I have been unable to find evidence that this has come to fruition yet.  While you’re waiting, you might write to scientists at ETH, which is a sort of Swiss MIT.

 

The Bottom Line

As with so many aging conditions, there is no miracle cure, but there are lots of possibilities for treatments that have great benefit for a few, and small benefit for others.  Until we have personalized medicine based on your genetic and epigenetic profile, there is no substitute for personal experimentation.  Many of the recommendations above have beneficial side-effects, or none.  Try them freely, singly or in pairs.  On for a month – off for a month – on for a month – off for a month, keeping a diary of symptoms.  This is a time-consuming exercise, to be sure, but the potential benefit is huge.  Don’t give up if the first few treatments that you try don’t seem to be working; that’s all in the nature of the game.  We’re looking for the treatment that resonates with your metabolism, and you’ll know it when you find it if you can remain objective and scientific.  (That’s the purpose of the diary.)

23 thoughts on “Nobody Dies of Arthritis

  1. Great post Josh and an issue that certainly needs more attention. We’ve come a long way in our understanding of cellular aging, but the very protein that makes up most of our bodies is still poorly understood. Why is it that the body stops replacing damaged collagen in cartilage right after childhood and pretty much wears out what is left once we reach 40+? E.g. collagen in our tendons and skin is still repaired in old age albeit at a much slower pace and with significantly reduced quality. What’s the purpose of cellular immortality, if we are wheelchairbound anyway.

  2. Nice and true with the one exception of, “Cycling and water aerobics are often suggested, not because they are inherently better for arthritis, but because people experience less discomfort and are more likely to stick with the program.”
    Now people may indeed enjoy water aerobics or cycling more than running for example (which most people hate, but if you were a runner you get to love), but the reason it’s used is because the majority of people in old and late middle age are obese or at least overweight and the pressure on their arthritic joints would do more damage than the exercise was worth (and of course they no longer have the muscle to easily move their bulk), unless they are sitting (which only exerts the weight of their legs on their ankles and only the force they can exert, (not so much), on their knees) or supported by water (which will keep a high percentage fat person nicely buoyed, again removing the weight on joints factor).

  3. Josh, I am too am reading your book…Nice to see the thoughts of the blog mulled over, thought through, put down on paper..

    • But I have been wondering about the behaviour of predators such as foxes and wild dogs here in Australia. Whena fox or dog launches an attack on sheep or chooks ( chickens ), they nearly always quickly kill as many as they can and take home just one prey. Now this goes against your hypothesis of predators taking out the old and unfit to ensure that there are prey in the future for descendants.

      This behaviour actually guarantees that the humans involved will try to kill the foxes or wild dogs..

  4. Yes Josh-Exercise- 2b or not 2b? If you listed all the benefits both mental and physical of intelligently done intence exercise its staggering.
    Arthritis is toast with a hiiit workout. Both getting out of breath(amazing) and working the type 2b muscle fibers – the answe is yes, 2b.
    I train seniors in the gym and witnessed its effects again and again. I hesitate to use the word panacea but darn it- it fits. Nothing else can influence stem cells, prolong and reverse teleomere shortening and increase and strengthen mitochondria. Joint movement improves because in reality it must-Exercise forces the body to change. Animals don’t get stronger in the gym. They get stronger adapting to what happened in the gym. The conservation of energy is a law of the Universe. Nothing biological or chemical will expend more energy than it has to. What animal would run lift and work hard// unless it had to? Anti inflammatory oils spices and food should be avoided after intense brief exercise. You’ve talked about this Josh they muffle the hermetic response. BUT they need to be in the diet. Just not immediately post workout. Forced response. Goodbye arthritis

  5. Just to expand a little on your discussion of biologics, there are far more biologics on the market now than the few you mention. Some target the T cells, but others work on the B cells and Interleukin 6 for example. There is a tremendous amount of evidence today on the effectiveness of these drugs in Rheumatoid Arthritis and many – perhaps all – of the 150+ other auto-immune arthritis diseases, such as Ankylosing Spondylitis, Juvenile Idiopathic Arthritis, Psoriatic Arthritis, to name but a few. Although some patients have to try several different biologics till they find the one that works for them. most patients put onto biologics say, “I have got my life back.” They are still very expensive, but biosimilars are now coming onto the market that show the same effects as the originals, so we can look forward to a significant drop in price from now on.
    On a different tack, there has been a fairly recent study (approx.two years ago) on behalf of the NHS in the UK of 35 000 people with osteoarthritis, examining the effect of glucosamine on osteoarthritis The conclusion was that it has no effect at all and it has consequently been removed from the NHS schedule of drugs.
    I very much enjoy your posts as there is always something of value to read and mull over. I edit the Arthritis Foundation of South Africa’s magazine ‘Joint Ability,’ and would like to publish this article in part in our next issue, duly acknowledged of course, if that’s OK with you.
    Aletta

  6. I am following your advice on vitamin d and immediate improvement in arthritic pain. I have avoided before because of alleged reverse hormesis effect from any vitamin supplementation – see Getting Stronger.
    Will try krill oil next.

    • Wow – that’s inspiring to hear that it has made a big difference from the start
      It’s the antioxidant vitamins that interfere with hormesis – mostly the alpha form of vit E and vit A. I’m of two minds on vit C.
      But for vit D, I’d say, get as much as you can. Here’s a book that is overhyped but contains a lot of stories about vit D successes, with a smattering of biochem: https://www.amazon.com/Miraculous-Results-Extremely-Sunshine-Experiment/dp/1491243821/
      – Josh

      • Thanks for the tip.
        Yes I was pretty amazed. I’ve had neck pain from double whiplash, worsening over the last 2 years, and this is 90% improved since taking 5000 IU of D3 after reading your blog this week. I had previously dropped multii-vit supplements about 7 years ago as I believed it was contrary to hormesis.
        I am a big advocate of HIIT and Tabata training, but it’s hard to exercise your neck…
        I mentioned Todd’s excellent hormesis blog at http://gettingstronger.org/ – I’ve been following his detailed advice on resolving myopia and it is working (basically using plus lenses for reading a few times a day)
        Thanks again Josh

      • Years ago I read a lot of papers on inflammation and cytokines. IIRC, when a cell receives an inflammatory cytokine like IL6, it will express various genes in response. One gene is the Vitamin D receptor (VDR), of which there are various polymorphisms in the population.

        It the cell gets its vitamin D, it sort of settles down, but if not it too expresses genes for inflammatory cytokines and thus passes along the signal for inflammation response to adjacent cells. Thus Vitamin D is a sort of chain breaker or modulator.

        I don’t know whether it was ever settled whether the VDR receptor polymorphisms affect function. But it is possible some people would need more D than others.

        These inflammatory cytokines are also mitogens — stimulate cell division — so this may explain why higher vitamin D is associated with longer telomeres and lower cancer rates.

    • Josh there are several mentions on the Amazon site of combining K2 with D3 for maximum absorption – do you have a view on that? Thanks.

  7. I am happy to have found your site. The content of your articles speaks of an open and intelligent , critical mind.
    I am a Dutch woman, living half of the year in the beautiful countrysite of France.
    Being in the countryside and not in the city always makes me feel much better.
    My problem is neck pain. I use a lot of the supplements you describe.
    What I think really helped me are proteolytic enzymes. Since I use these and take care of my posture, I have nearly no pain any more.
    Do you have an opinion on proteolytic enzymes ?
    kind regards, Emilie

    • Emilie –
      I don’t know anything about protease supplements, but I can imagine that some stomachs don’t digest proteins well, and the un-denatured proteins can then cause immune reactions. So I’m glad to suggest protease supplements (as well as papaya and pineapple) for people who suspect that they are not properly digesting proteins. (Other indications include bloating, gas and constipation.)
      – Josh

  8. A little late on this blog, but felt I had to comment on the treatment of autoimmune disease with a generic pharmaceutical which has been around for quite some time. The drug, naltrexone, historically in indicated for narcotic antagonism and overdose. Currently, clinicians around the world are prescribing low dose naltrexone (LDN) orally for autoimmune disorders and other diseases. Briefly, LDN blocks opiate receptors which causes an upregulation in the production of endorphins which act in an immunomodulary way to correct immune system malfunction. The book (below) addresses the detailed mechanisms of the pharmacological basis of LDN.

    I came across “The LDN Book” in a journal book review, Wise Traditions – The Weston A Price Foundation – Spring 2016. “The LDN Book” is edited by Linda Elsgood (copyright 2016) consists of several chapters written by specialists in their field of autoimmune disease, cancer, and other diseases.

    Fascinating story of how Dr. Bernard Bihari, working in NYC in 1985, did studies with HIV/AIDS patients and found that LDN prevented the gradual destruciton of the immune system.

    I have had personal experience with a family member who had a severe reaction to one of the biologicals for plaque psoriasis and has responded quite well with LDN. After one month symptoms resolved and remain resolved for the las six months.

    Finding a practitioner who is familiar with LDN is somewhat of a challenge. However, contacting a compounding pharmacy and asking if they compound LDN and who in community is prescribing the drug is the best approach. There are several centers throughout the US that are quite involved in the use of LDN.

    Big Pharma will probably not get involved in LDN as there is little financial incentive to do so. Some small generic companies may eventually participate.

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