Treating FSF - MSM, Colchicine & Other Supplements

posted: by: Dr. Linda Tintle Tags: "Clinic Specials" "News" 

Methylsulfonylmethane – MSM – (or dimethyl sulfone) is a metabolite of DMSO (dimethyl sulfoxide).  It has been reported in the scientific literature to aid in reducing the effects of osteoarthritis and seasonal allergic rhinitis in humans.  It appears to have anti-inflammatory action but measurable parameters of inflammation were not reduced in patients reporting improvement with the compound (i.e. no one knows how it works).  It may have anti-cancer effects as well but results are preliminary.  I have seen it referred to as antioxidant but I have not found support for that statement.  (It may be, but I was not able to uncover support for its action against free radicals.)  The problem with MSM is that there is a paucity of evidence for or against it.

My opinion - this is a supplement that may help and can’t hurt if used cautiously.  It has been reported to cause loose stools if amounts larger than can be absorbed are administered and dosages should be adjusted if the patient has diarrhea.

Dosages vary widely.  The most common dose recommended by alternative veterinary health professionals is 500mg/50 lbs.  I have seen anecdotal reports of recommendations as high as 88mg/kg TID for a dog by veterinarians (this would be 1760 mg three times a day!) and in one human study the patients were given 3000 mg twice daily for 12 wks.  A widely available veterinary supplement for arthritis that includes MSM would give a dose of 500-1000mg MSM/day (Glycoflex III) to a Shar-Pei size dog.

This is an interesting graphic from a company promoting an alternative to MSM and Sam-e but it does elucidate the pathway that might be responsible for MSM’s anti-inflammatory effects:

MSM graphi

This also illustrates why molybdenum should also be supplemented when MSM is given at high doses (I would suggest supplementation with 50-75 micrograms/day if dose of MSM > 1000 mg/day).

Familial Shar-pei Fever (FSF) is an autoinflammatory syndrome (not autoimmune).  The underlying genetic defect is most likely a disruption in how the messengers of inflammation are controlled which causes chronic elevations of these mediators in the bloodstream.  It is a periodic fever syndrome that is characterized by apparently random inflammatory events with fever, sometimes with joint swelling, that usually last 24-36 hrs.

The chronic inflammation puts them at risk for developing reactive systemic amyloidosis which can lead to early death from kidney failure.  Not every dog with FSF will develop amyloidosis but the fevers are a warning that they are at high risk.  Shar-Pei with FSF CAN live to over 10 yrs of age.  My mom’s Shar-Pei died of cancer at age 12 ½ yrs with lifelong intermittent FSF fevers.  By doing everything you can to reduce their chronic inflammation and monitor their disease, you can help them live their best possible lives - however long that may be.

It is the background levels of chronic inflammation that predispose FSF patients to amyloidosis – whether or not they have 0, 1 or hundreds of fevers.  The fever event is a marker, a great big waving red flag, that they have this underlying autoinflammatory syndrome.

So, right now,  I think a very good case could be made for giving a Shar-Pei with the autoinflammatory syndrome FSF the following:

Curcumin with bioperine
Alpha-lipoic acid
MSM (& molybdenum if given at high doses)
B-complex vitamins including B12, B6 and folate
Vitamin E & Selenium
Omega 3 essential fatty acids (n-3 PUFA)

Feed a good quality diet and avoid rancid polyunsaturated, hydrogenated or trans- fats.  Rancid fatty acids and oxidized cholesterol in cell membranes has been linked to deposition of amyloidosis in current research which is why this list is heavy on antioxidants as well as anti-inflammatory agents.

As with all nutritional supplements, the quality is very important.  Sometimes you get what (little) you pay for.  Do your homework before purchasing.

Colchicine treats the underlying pathology by blocking the movement of neutrophils (one of the white blood cells), decreasing levels of cytokines (the messengers of inflammation) and by blocking acute inflammation prevents the formation of amyloid protein (a waste by-product of inflammation).  In humans, it has proven to be safe in infants, pregnant women and when given lifelong.  Treatment is for life.  I have been using the drug since 1993 and have had individual patients on the drug safely for over 10 yrs.  Some dogs cannot tolerate colchicine without chronic diarrhea and they are given smaller amounts or none if it is severe.  I do believe this drug is prolonging the lives of dogs predisposed to amyloidosis and decreasing the severity and frequency of fever events in most patients.

My current recommended treatment is 0.025-0.03 mg/kg of colchicine twice daily.  I recommend that the dog start on a low dose and try to gradually increase to the maximum recommended amount or the most of that that they can tolerate without gastrointestinal upset (usually diarrhea) twice daily.  For most average wt. Shar-Pei, this is one X 0.6 mg tablet twice daily.  Colchicine is a potent drug but it accumulates in white blood cells (the desired target for treatment) and GI signs occur long before other serious side-effects appear.  I have never seen evidence of any damage from colchicine except for a transient treatable diarrhea that goes away when the drug is withdrawn in sensitive patients.

Colchicine can lower levels of vitamin B12 (cobalamin) in the body and some Shar-Pei are already deficient in vitamin B12 so B-complex supplementation is important.  Vitamin B12 deficiency has been reported to cause chronic diarrhea and low-grade anemia in some Shar-Pei.

I treat the fever events with 50% dipyrone injectable (usually 1.0 ml under the skin) (a drug available to veterinarians through compounding pharmacists that has been shown to block IL-1-beta induced fever), or Metacam (an NSAID) by weight per package insert instructions.  Some fevers are very serious and can require emergency veterinary treatment if they approach or exceed 106 degrees F.  You will need to discuss treatment with your veterinarian because treating the fever as early as possible in the inflammatory cascade can often stop it from becoming life-threatening and it is best to have medication available on-hand at home.
Shar-Pei with FSF should get regular and routine monitoring of first morning urine and a CBC, chemistry profile and T4.  A dilute urine can often be the first sign of kidney trouble and should be repeated to see if the dog has a consistently low specific gravity.  FSF patients should be checked and tests run whenever they are not eating well or at all, if they are vomiting, having diarrhea for more than a few days or acting sick in any way – if they are just “not right”.  The bare minimum is annually in the healthy active young dog and many dogs should be checked more often.

Owners should consult with their veterinarians about the appropriateness of treatment for their individual dog before starting any new product.  Permission to cross-post and forward this material in its entirety is given.

August 26, 2006

Dr. Linda Tintle
Wurtsboro Veterinary Clinic
163 Sullivan Street, PO Box 910
Wurtsboro, New York 12790