Benefit-Risk Assessment of Fish Oil in Preventing Cardiovascular Disease.

Cardiovascular disease (CVD) is a preventable disease, which combines two general processes: chronic vascular inflammation and acute thrombosis. Both are amplified with positive feedback signals by n-6 eicosanoids derived from food-based n-6 highly unsaturated fatty acids (n-6 HUFA). This amplification is lessened by competing actions of n-3 HUFA. Death results from fatal interactions of the vascular wall with platelets and clotting proteins. The benefits of fish oil interventions are confounded by complex details in pharmacokinetics, pharmacodynamics, adverse events, timescale factors, topology, financial incentives and people's sense of cause and effect. Two basic aspects of n-3 HUFA that are overlooked in CVD dynamics are saturable, hyperbolic responses of the enzymes continually supplying n-6 HUFA and hard-to-control positive feedback receptor signals by excessive n-6 HUFA-based mediators. Multiple feedback loops in inflammation and thrombosis have diverse mediators, and reducing one mediator that occurs above its rate-limiting levels may not reduce the pathophysiology. Clinicians have developed some successful interventions that decrease CVD deaths in the form of secondary prevention. However, the current high CVD prevalence in the USA remains unchanged, and successful primary prevention of CVD remains uncertain. This review weighs the available evidence to help clinicians, the biomedical community and the public put the use of fish oil supplements into a balanced perspective.

Historical perspectives on the impact of n-3 and n-6 nutrients on health.

Current public advice from the Food and Nutrition Board (FNB) about essential fatty acids (EFA) has limited quantitative details about three processes: (1) similar dynamics for n-3 linolenic and n-6 linoleic polyunsaturated fatty acids (PUFA) in maintaining 20- and 22-carbon n-3 and n-6 highly unsaturated fatty acids (HUFA) in tissues; (2) different dynamics for tissue n-3 and n-6 HUFA during formation and action of hormone-like eicosanoids; (3) simultaneous formation of non-esterified fatty acids (NEFA) and low density lipoprotein (LDL) from very low density lipoprotein (VLDL) formed from excess food energy and secreted by the liver. This report reviews evidence that public health may benefit from advice to eat less n-6 nutrients, more n-3 nutrients and fewer calories per meal. Explicit data for linoleic acid fit an Estimated Average Requirement (EAR) near 0.1 percent of daily food energy (en%) meeting needs of half the individuals in a group, a Recommended Dietary Allowance (RDA) near 0.5 en% meeting needs of 97-98 percent of individuals, and a Tolerable Upper Intake Level (UL) near 2 en% having no likely risk of adverse health effects. Quantitative tools help design and monitor explicit interventions that could beneficially replace imprecise advice on "healthy foods" with explicit preventive nutrition.

Prevent the cause, not just the symptoms.

If people stay healthy, less health care treatments need to be paid. Alternatively, health care treatments are uneconomical and unethical when they only remove signs and symptoms and leave the primary cause neglected and unchanged to cause future harm. Neglected preventable causes continue to cause massive health-related financial loss in the US. Monitoring imbalances of omega-3 and omega-6 hormone precursors in individuals can increase awareness and motivation for making efforts to prevent this pervasive diet-related cause of dysfunction, disease and financial loss. We now have low-cost tools for individuals to monitor their balance of omega-3 and omega-6 hormone precursors and to identify and choose foods that will maintain a desired balance and a desired quality of life.

False profits and silent partners in health care.

Traditional health care services have focused more on treatment of signs and symptoms of cardiovascular disease rather than on prevention of primary causal factors. This bias created a nation with increasing numbers of older people paying for increasing treatment costs. Treatment-oriented clinicians, drug companies and hospitals take a major proportion of ever-increasing health care dollars. Without prevention, American families gain little long-term relief from the highest health care treatment costs in the world. A lack of public accountability for valid surrogate endpoints continues to drain funds for treatments that do not remove underlying primary causes. It seems unethical and uneconomical to withhold community-wide primary prevention advice and only attend to people with clinical signs of disease. Also, treatments that remove a sign or symptom without removing the primary cause unethically set a sense of improved health while leaving unchanged the cause to continue harming future generations. A good alternative would be long-term primary prevention that removes primary causal factors and prevents the onset of signs and symptoms of disease. Health insurance companies could be effective partners with corporate and individual subscribers by diverting resources toward preventing proved primary causes of disease. A chain of molecular events that causally connects modifiable food choices to many health disorders has a measurable mediator: the proportions of omega-3 and omega-6 in tissue highly unsaturated fatty acids (HUFA). Health risk assessment can monitor the diet-based proportions of tissue HUFA which influence hundreds of vital physiologic events. Many financial losses will likely be decreased by primary prevention advice to choose foods that increase intakes of omega-3 fats, decrease intakes of omega-6 fats and include fewer calories per meal.