Omega 3 fatty acid hypothesis

Professor Basant Puri of Imperial College London has theorized that some of the symptoms of ME/CFS are caused by improper fatty acid metabolism and can be ameliorated by supplementation with high dose eicosapentaenoic acid (EPA) and evening primrose oil, a source of gamma-Linolenic acid (GLA).

Mechanism
Puri theorizes that a persistent, low grade viral infection blocks the delta-6-desaturase enzyme, which is required for generating the long chain Omega-3 and Omega-6 polyunsaturated fatty acids such as DGLA, arachidonic acid and EPA. This in itself will cause a variety of symptoms including sleep disturbances and improper immune responses.

Moreover, EPA, a long chain Omega 3 acid, is both directly antiviral and a precursor to interferons, are themselves antiviral.

These fatty acids are also precursors to eicosanoids, signaling molecules that regulate growth during and after physical activity, inflammation or immunity after the intake of toxic compounds and pathogens, and act as messengers in the central nervous system.

Finally, deficiencies in arachidonic acid and docosahexaeonic acid have deltetirious effects on cell membranes. They lose their normal flexibility and become more rigid, which effects the protein receptor molecules and disrupts cell signaling. This causes cognitive impairment.

Puri points to increased choline in specific areas of the brains of CFS patients, including the occipital cortex and basal ganglia as evidence of unspecified alterations in fatty acid metabolism. However, these are all extremely small studies.

Treatment
Puri recommends treatment with evening primrose oil, a source of GLA, and high dose EPA without DHA, such as VegEPA.

EPA competes directly with AA for the phospholipase A2 enzyme in the production of inflammatory eicosanoids while DHA does not. DHA has little effect on cellular inflammation.

Fatty acid status in CFS patients
A study of twenty-two patients (defined using the CDC criteria) and twelve controls found that CFS patients has significantly lower levels of EPA/AA and Omega3/Omega 6 (ω3/ω6) ratios owing to substantially increased levels of Omega 6 fatty acids (but not lower Omega 3s). These ratios correlated with some of the items on the FibroFatigue scale such as pain, fatigue, and memory deficits. The study also found significant correlations between the ω3/ω6 ratio and lowered serum zinc levels and lowered mitogen-stimulated CD69 expression on CD3+, CD3+CD4+, and CD3+CD8+ T cells.

Relationship with Zinc
Zinc plays an important role in desaturase enzymes.

Effects of fatty acid treatment
The evidence for fatty acid treatment is mixed, owing in part to varying research criteria and incomparable treatments.

A double-blind, placebo-controlled study of 63 patients with postviral fatigue syndrome found the 85% of patients found improvement at three months on Efamol Marine, a high Omega-6 formulation of evening primrose oil and fish oil (linoleic acid: 58%, GLA: 7.2%, EPA: 3.6%, and DHA: 2.4%). An attempt to replicate the study using Efamol Marine and the Oxford Criteria found no effect.

In a small case study of four patients diagnosed by the Fukuda criteria, Puri found that high dose EPA was associated with significant improvement after 12 weeks of treatment.

Fatty acids and viruses
In vitro studies have found polyunsaturated fatty acids kill Epstein Barr Virus. and herpes simplex virus. PUFAs inactivated lipid-enveloped viruses