Complimentary and alternative medications (CAMs) in RA

Brad Butt Managing partner

Cooleman Court Pharmacy WESTON

Objectives

• Which CAMs are our patients seeking information on

• What evidence is there for their use• Possible interactions – disease

state/medication

CAMs in RA

• Fish oils– Trend towards Krill oil

• Tumeric/curcumin• Others…

Fish Oils

• EPH/DHA is the key – polyunsaturated 3 fatty acids.

• Flaxseed oil – ALA 5-10% EPA and 1-5% DHA only1&2

• Quality – TGA v GOED (global organisation for EPA and DHA 3)

Inflammatory cascade

TGA v GOED table

Fish oils benefits

• Anti-inflammatory effect – complex!– PG/TXA/LT – signalling molecules in inflammation• Arachidonic acid (AA) is the major substrate for their

synthesis3-5

– EPA/DHA leads to reduced conversion of AA– Decreases leukocyte chemotaxis reduced pro-

inflammatory cytokines (TNF and IL subtypes) 6-7

– 3.8g EPA + 2g DHA 10 capsules daily

Fish oil benefits

• Anti depressant effect– Evidence for EPA/DHA in major depressive

episodes• Meta analysis – 15 randomised, double blind, placebo

controlled trials (916 patients) at doses up to 2200mg EPA/DHA per day concluded effective against primary depression8

Fish oil precautions

• Recent clinical studies show no increase in bleed risk; even in patients on aspirin and warfarin with doses up to 7g/day of EPA/DHA9

– Should be done under medical supervision1

• Doses <12g/day need medical supervision1

• Hypomania can occur with fish oil in bipolar patients10

• Seafood allergy theoretically problematic

Krill oil – fad or not?

• Krill oil has been hugely popular– Comprehensively out sells fish oil– There is a lack of good clinical evidence– Doses need to be in excess of 1500mg daily• 1500mg krill oil 226mg EPA 122mg DHA

– General feel is that evidence is for fish oils so recommend fish oil at appropriate dose first for best results

Curcumin/Tumeric

• May assist with the down regulation of inflammatory mediators

• Reduces joint inflammation in RA• Symptomatically works quickly• Lack of large clinical trials– COX2 inhibition believed to be MOA– Less GIT/BP issues associated with curcumin (v

NSAID)

Curcumin pathway

Curcumin precautions

• Bile duct obstruction• Anti coagulants• Can reduce BGL – hypoglycaema risk• May increase stomach acid secretion

Others

• Glucosaime– Minimum 4 week time to effect– Shell fish allergy precaution– 1500mg daily required– +/- condroitin/MSN

• Green lipped muscle extract– Anti-inflammatory effect– Small evidence for use

Others

• St Johns Wart– Used for depression– Effect similar to a SSRI– Variability between brands/batches as plant

derived – numerous environmental factors may affect outcome of dose

– Many interactions with other Rx medications– Reasonable evidence for its use/effect

References1. McCusker MM, Grant-Kels JM. Healing fats of the skin: the structural and immunologic roles of the

omega-6 and omega-3 fatty acids. Clin Dermatol 2010;28(4):440-451. 2. Braun L, Cohen M. Herbs and natural supplements: an evidence-based guide, 3rd ed. Sydney: Churchill

Livingstone Elsevier, 2010.3. Silva V, Barazzoni R, Singer P. Biomarkers of fsh oil omega-3 polyunsaturated fatty acids intake in humans.

Nutr Clin Pract 2014;29(1):63-72.4. Calviello G, Su HM, Weylandt KH, et al. Experimental evidence of w-3 polyunsaturated fatty acid

modulation of infammatory cytokines and bioactive lipid mediators: their potential role in infammatory, neurodegenerative, and neoplastic diseases. Biomed Res Int 2013;2013:743171.

5. Calder PC. n-3 fatty acids, infammation and immunity: new mechanisms to explain old actions. Proc Nutr Soc 2013;72(3):326-336

6. Calder PC. n-3 polyunsaturated fatty acids, infammation, and infammatory diseases. Am J Clin Nutr 2006;83(Suppl):1505S-1519S

7. Galarraga B, Ho M, Youssef HM, et al. Cod liver oil (n-3 fatty acids) as an non-steroidal anti-infammatory drug sparing agent in rheumatoid arthritis. Rheumatology 2008;47(5):665-669.

8. Sublette ME, Ellis SP, Geant AL, et al. Meta-analysis of the effects of eicosapentaenoic acid (EPA) in clinical trials in depression. J Clin Psychiatry 2011;72(12):1577-1584.

9. Harris WS. Expert opinion: omega-3 fatty acids and bleeding-cause for concern? Am J Cardiol 2007;99(6A):44C-46C.

10. Bays HE. Safety considerations with omega-3 fatty acid therapy. Am J Cardiol 2007;99(6A):35C-43C.