Omega 3 fatty acids
The evidence supporting the use of recommended amounts of EPA and DHA in fish oil supplementation has been well documented in multiple epidemiologic studies and randomized controlled trials.
Harris et al. reviewed 25 trials which evaluated the risk of coronary heart disease (CHD) events as a result of in-vivo levels of Omega-3 PUFA. (1) They demonstrated that a reduction in major CV events correlated inversely with the tissue levels of EPA and particularly DHA.
Three major trials have documented the efficacy of Omega-3 PUFA for the primary endpoint of secondary prevention of CHD. DART (Diet and Reinfarction Trial) is a randomized trial on 2,033 men with recent MI. (2) Omega-3 PUFA was administered in either the form of oily fish or fish oil capsules. The results showed that a 2-year all cause mortality was reduced in the study group by 29% with the benefit almost entirely attributable to a reduction in CHD mortality. Also demonstrated within this study was the fact that the subgroup who consumed only fish oil capsules as opposed to increasing fish consumption, showed a more remarkable reduction in CV events.
The GISI study (3) randomized 11,323 post-MI patients to one capsules per day of Omega-3 PUFA, providing 850mg EPA/DHA. At the end of year one, patients had a 21 and 30% reduction in total and CV mortality respectively. This study also demonstrated that after only four months there was a 45% reduction in sudden cardiac death.
More recently, the JELIS trial (4) studied 18,645 patients with hypercholesterolemia (14,981 in primary prevention, 3,664 in secondary prevention) of which 70% were women. The patients were randomized to statin alone or statin with highly purified EPA 1,800/day. At the end of five years, those randomized to EPA had a 19% reduction in major CV events.
The mechanism of action of Omega-3 PUFA appears to be the enrichment of membrane phospholipids. (5) Also, Omega-3 PUFA reduces blood pressure, increases vasodilation, improves arterial and endothelial function and reduces platelet aggregation. (6)
Rheumatoid Arthritis (RA)
Fish oil supplementation between 2,800 and 3,000 EPA + DHA per day at a ratio of 2:1 in conjunction with conventional therapy is considered efficacious for rheumatoid arthritis according to Health Canada's Natural Health Products Directorate (NHPD). (7)
In a study by Kremer et al., 66 RA patients were entered into a double-blind placebo controlled trial of fish oil while taking diclofenac. (8) Patients took either 130mg/kg/day of Omega-3 PUFA or 9 capsules/day of corn oil. The results showed that the fish oil group had significant decreases in tender joints, duration of morning stiffness and overall evaluation of global arthritis activity. In the corn oil group, no changes from baseline were observed. After discontinuing diclofenac, the fish oil group retained significance in the decrease in tender joints, demonstrating that some patients are able to discontinue NSAIDs without a disease flare. IL-1 beta also decreased significantly from baseline through weeks 12 and 22 in patients consuming fish oil.
In another double-blind study, Cleland et al. compared a fish oil supplement (18g/day) with an olive oil supplement for 12 weeks. (9) Production of leukotriene B4 by isolated neutrophils stimulated in vitro was reduced by 30% in the fish oil group and unchanged in the olive oil treated group.
Cognitive Health and/or Brain Function
NHPD requires a minimum of 1.5 – 3.0 g of EPA +DHA per day including at least 1.0g of EPA per day (at a ratio of 1.75:1 or 2:1) to support mood balance.(7)
Evidence from epidemiological, laboratory and clinical studies suggest that Omega-3 PUFA may influence both the vulnerability and outcome in depressive disorders. (10) Although the influence of Omega-3 fatty acids is not completely understood, the possible mechanisms of action include the importance of Omega-3 fatty acids as a component of CNS membrane phospholipid acyl chains. They are critical to the structure and function of neuronal membranes. (11)
Another area where Omega-3 fatty acids influence major depression is on the cytokine modulation.These cytokines, including interleukin-1 beta, -2 and -6 interferon-gamma, and tumor necrosis factor alpha, can have direct and indirect effects on the CNS. (12). Research has shown that elevations of IL-1B, and TNFa are associated with the severity of depression. (13)
Although Vitamin D has long been known for its role in reducing the risk of bone fracture and tooth formation, more recent research has focused on areas such as autoimmune diseases, cardiovascular disease, type 2 diabetes and cancer. (14)
A meta-analysis of 18 randomized controlled trials involving over 57 thousand patients taking between 300 and 2000IU Vitamin D daily, concluded that supplementation decreased total mortality. (15)
The most recent research has focused on the effects of Vitamin D3 on immune cells. In particular, Interleukin-17 secreting T cells (Th17) have been widely implicated in the development of autoimmune diseases. (16) T cell differentiation is important to both immunity and autoimmunity. The inflammatory cytokines are important factors to decide whether regulatory T cells or Th17 cells are produced. In vitro experiments conducted by Jeffery et al. demonstrated that Vitamin D3 exerted direct effects on T cells and inhibited IL-17 production.(17) These results were also observed in-vivo by Tang et al.. (18) Although preliminary, these data do show promise in this area for future clinical trials.