by Dr. Neville Wilson
Health conscious consumers of Omega-3 have been stunned by the recent implementation of a “cost saving strategy” which includes the removal of omega-3 from the list of reimbursable health products.
Patients who have been receiving prescribed omega-3 (EPA / DHA ), for a variety of legitimate medical indications, and health protective reasons, have been informed by their pharmacists that they are now responsible for meeting the costs of these prescribed nutrients.
The Irish Medicines Board (IMB), in support of a state strategy to save €26.5 million, has endorsed the HSE decision to deprive large sections of the Irish population of this widely tested and well proven health supportive agent.
The unprecedented move to discontinue state funding for prescription omega 3 (Omacor, or Morepa) was prompted by a dubious finding from a recently conducted Greek study, concluding that “there is insufficient evidence” for the use of omega 3 as a preventative strategy in patients with established heart disease.
The study was a meta-analysis, which is a systematic review of pre-selected clinical trials, and a statistical analysis of their collective outcomes, and reported in a recent edition of JAMA. (1)
The Greek researchers looked at 20 selected studies, involving 68,680 randomised patients, and tabulated the associations of omega-3 with reported deaths from heart attacks, death from all causes, stroke and sudden death.
Their conclusion was a “lack of association” between omega-3 and prevention of these cardiovascular outcomes.
This conclusion flies in the face of several hundred well conducted studies, over several decades, documenting the protective and survival benefits for healthy persons, as well as for those at risk of a recurrent heart attack.
A marked decrease in the risk for heart attack among fish oil consumers was noted by Bang and Dyberg more than 30 years ago, (2) (3) and confirmed by several subsequent investigators in Japan, Holland, Norway and the USA, and more than 25 trials have confirmed the positive association between increased tissue levels of EPA/DHA and reductions in major cardiovascular events. (4)
More recently, an extensive review of the positive health benefits of omega-3 prompted an eminent American cardiologist, Dr. Carl Lavie, to say, “ physicians are not as familiar with omega-3 as they are with statins…..as they should be”, and as a therapeutic agent, omega-3 “should be promoted to clinicians” (5 )
The most compelling evidence for the cardiovascular benefits of omega-3 PUFA comes from 4 large controlled trials of nearly 40,000 participants randomized to receive eicosapentanoic acid (EPA), with or without docosahexanoic acid (DHA), in studies of patients in primary prevention, after myocardial infarction, and with heart failure.
The first randomized controlled trial (RCT) which demonstrated the benefits of omega-3 was conducted in1989 at the University of Wales, known as the Diet & Reinfarction Trial (DART). In this study 2033 men with a history of a prior heart attack, receiving a diet of fish, or supplemented fish oil, experienced a 29% reduction in death after 2 years of dietary intervention. (6)
The landmark Gissi-Prevenzione trial conducted in 1999, and involving 11,323 patients who had previously suffered a heart attack, reported a dramatic 30% reduction in death from heart attack, and 45% reduction in sudden death at the conclusion of the 4 year study. (7)
A Harvard University study in 2002 reported a 80% reduction in risk for sudden cardiac death for those who had high levels of serum EPA and DHA, compared to those with low levels. (8)
In a large Japanese Trial (JELIS) 18, 645 subjects were randomized to 2 groups, one with a statin, and the other a statin plus purified EPA 1800 gms. (9)
After 5 years of observation the group using EPA and low dose stain had a 19% greater reduction in cardiovascular events than the group using only statins. There were no cases of sudden death reported.
The mechanisms whereby EPA & DHA exert their protective health benefits are well documented, (and confirmed in JELIS) demonstrating that they have anti-platelet, anti-inflammatory and triglyceride lowering effects (10), produce vaso-dilation and reduce blood pressure (11), improve arterial endothelial function (12), have anti-arrhythmic effects and can improve heart failure and reduce sudden cardiac death (13), suppress the production of pro- inflammatory cytokines (14) and offer benefit to obese patients by increasing adiponectin levels, reducing inflammation and improving insulin sensitivity. (15)
At the cellular level EPA & DHA confer cardiovascular benefits through enrichment and protection of cellular membrane phospholipids. (16)
The relevance of the recently reported Greek meta-analysis as a therapeutic guide for clinicians, has been called into question by the Council for Responsible Nutrition (CRN) and other influential bodies, on the grounds that small, short term studies were selected, while the longer and larger studies that showed a positive role for omega-3 were excluded.
The meta-analysis included trials in which patients were likely to be using cocktails of platelet, cholesterol and blood pressure lowering drugs, making it impossible to attribute outcomes solely to their omega 3 intake.
The “cherry-picking” of under- powered studies, while ignoring well powered studies, therefore served to produce a predictable outcome, and questions may be raised as to what the underlying motive was in conducting such a limited analysis.
Meta-analyses are considered to be a poor substitute for a prospective randomized trial, and lack of evidence from such a review does not prove lack of benefit.
Since these findings are in conflict with the epidemiological and observational evidence, and the outcomes of large randomized controlled trials which show the benefits of EPA and DHA in primary and secondary care, their relevance for clinical guidelines or therapeutic recommendation must be discounted.
To withhold supplemental fish oil from deserving patients on the basis of such a flawed meta-analysis is unjustifiable and clinically irresponsible, and represents a retrogressive move at a time when the quality of healthcare needs to be maximized.
In the best health interests of our young and elderly patients, and all those at risk, the hasty decision to withhold marine-3 fish oils from deserving patients should be reversed with immediate effect.
Dr. Neville Wilson.
Medical Director,
The Leinster Clinic,
Maynooth.
22 September, 2012.
REFERENCES:
1. JAMA 2012; 308 (10): 1024-1033
2. Bang et al, Acta Med Scandinavia 192, 1972, 85-94
3. Dyberg et al, Am J Clin Nutr 28, 1975, 958-966
4. Harris et al, Atherosclerosis 193, 2007, 170.
5. J Am Coll Cardiol, Aug 11, 2009; 54: 585-594
6. Lancet 1989 Sept 30, 2 (8666): 757-61 (DART)
7. Lancet 1999 Aug 7: 354(9177): 447-55 (GISSI)
8. New Eng J Med 2002 April 11, 346; (5) 113-8
9. Am Heart J 2003; 146: 613-620
10. Lancet 3161, 2003; 477-484
11. Am J Cardiol 97, 2006, 1127-1130
12. Circ 88, 1993, 11251-11285
13. JAMA 296, 2006, 1885-1899
14. Am J Clin Nutr 85, 2007, 385-391
15. Art Thromb Vasc Biol 27, 2007: 1918-1925
