Alpha-linolenic acid in the treatment of rheumatoid arthritis. A double-blind, placebo-controlled and randomized study: flaxseed vs. safflower seed

Source

Nordström, D.C.E., Honkanen, V.E.A., Nasu, Y, Antila, E., Friman, C., and Konttinen, Y.T. Rheumatol Int. 14:231-234.

Abstract

Rheumatoid arthritis (RA) is an inflammatory disease characterized by tissue destruction and pain, and pro-inflammatory metabolites of arachidonic acid, such as leukotriene B4 and prostaglandin E2. Dietary supplementation with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has been used to decrease the amount of AA relative to EPA and DHA, which forms non- or anti-inflammatory eicosanoids LTB5 and PGI3. The clinical benefits of EPA and DHA are well-documented. However, they are expensive compared to their precursor alpha-linolenic acid (ALA) found in flax seed oil, and thus nutritional supplementation with flax seed oil could be a rational alternative. ALA may be beneficial by conversion into EPA and DHA and by competing with linoleic acid (LA) for the delta-6-desaturase (D6D) enzyme, both of which could effectively diminish AA and inflammation caused by its metabolites. ALA could also decrease production of pro-inflammatory prostanoids and leukotrienes. In this study, 22 patients aged 34 to 72 years with RA were randomly assigned to a treatment or placebo (control) group. The treatment group received 30 g of flax seed oil (32% ALA) while the control group received 30 g of safflower oil (33% LA). Clinical assessment measured joint involvement by swelling or limitation of movement, subjective pain measurement and laboratory parameters such as sedimentation rate. After 3.2 months of supplementation, serum ALA levels and bleeding time was increased in the treated group, confirming patient compliance. The increase in bleeding time has been considered to be due to a rapid change in lipid mediators, including the pro-aggregatory thromboxane A2. Contrary to expectations, none of the clinical parameters nor the patients’ condition improved in the treated group. It is possible that this short-term supplementation study of only 3 months was not enough to significantly affect the ALA:LA ratio, which is supported by the observation that although ALA levels increased, there was no effect on EPA, DHA, AA or other fatty acids. Furthermore, the conversion of ALA to EPA and DHA may be dependent on other nutrients such as vitamin E and zinc. Zinc controls D6D activity, by catalyzing the first step from ALA to EPA and LA to gamma-linolenic acid (GLA). The RA patients in this study had low zinc levels. Low conversion of ALA to EPA and DHA, together with a low ALA:LA ratio might explain why a short-term ALA supplementation did not alter the RA disease activity.