What are omega-3 polyunsaturated fatty acids (PUFAs), and where are they found?
Omega-3 PUFAs are referred to as essential fatty acids because they cannot be made endogenously in the body and thus must be obtained through the diet. There are three types which are commonly found in the North American diet; these are listed below.
Type: Alpha-linolenic acid (ALA) 18:3n-3
- Dietary Sources: Flaxseeds/Flaxseed Oil, Canola Oil, English Walnuts, Soybeans
Type: Eicosapentaenoic acid (EPA) 20:5n-3
- Dietary Sources: Fish/Fish Oils, Marine Sources, Algal Oils
Type: Docosapentaenoic acid (DHA) 22:6n-3
- Dietary Sources: Fish/Fish Oils, Marine Sources, Algal Oils
Generally speaking, the Western daily diet offers an intake of EPA and DHA which falls short of recommended levels. Vegetable oils rich in omega-6 fatty acids are much more popular within this diet, largely outnumbering omega-3 fatty acids for structural places in biological membranes and pathways. Many experts indicate that a healthy ratio of omega-6/omega-3 intake should be approximately 4:1. However, it has been estimated that a traditional Western diet provides a ratio in excess of this amount of up to 15:1. More often than not, this imbalance generates a state of inflammation which can accelerate atherosclerotic development.
What are the benefits of higher intakes of EPA and DHA?
Several studies have indicated an inverse relationship between the consumption of fish containing the omega-3 fatty acids as EPA AND DHA and the risk of CVD and cardiac death. Low blood levels of specific omega-3 fatty acids have been associated with an 80% greater risk of sudden cardiac death. Roughly half of all sudden cardiac deaths occur in patients with no prior history of cardiovascular disease.
A review article of 65 intervention trials indicated that patients with fasting triglyceride levels of 1.70-2.82 mmol/L (i.e. those with borderline to high levels) taking 3 grams of supplemental EPA + DHA over a period of approximately 4 weeks reduced these levels by 25-30%. Reductions in TGs are generally attributed to decreased TG synthesis and increased TG clearance. This reduction in levels of fasting TGs also lowers the TG: HDL-C ratio – which has been implicated as a highly potent risk factor for development of cardiovascular disease. These trends have led to encouragement of omega-3 intake by the American Heart Association and the Canadian Cardiovascular Society to effectively manage hypertriglyceridemia.
When levels of PUFAs in red blood cell membranes are increased, the viscosity of blood is reduced – there-by leading to an anticoagulative effect. Omega-3 PUFAs are associated with reductions in blood platelet reactivity, and some evidence suggests a stabilizing influence of fish-derived omega-3 fatty acids on pre-existing atherosclerotic plaques. Supplementation with long-chain omega-3 fatty acids has also been a safe and effective adjunct therapy to ASA and statin treatments. Favorable effects of long-chain omega-3 fatty acids are also demonstrated in postprandial lipemia, heart rate variability, arterial compliance, and heart rhythm.
What are the current recommended intake levels?
Dieticians of North America, 2007
- Subject Group: Healthy Adults
- Daily Dose (EPA + DHA): 500mg
FDA, 2007 (Upper Safety Limit)
- Subject Group: Most Adults
- Daily Dose (EPA + DHA): 3000mg
Health Canada, 2009 (Safe Rangers)
- Subject Group: Children 1-8 years
- Daily Dose (EPA + DHA): 100-1500mg
- Subject Group: Adolescents 9-13 years
- Daily Dose (EPA + DHA): 100-2000mg
- Subject Group: Adolescents 14-18 years
- Daily Dose (EPA + DHA): 100-2500mg
- Subject Group: Adults (incl.pregnant/ brestfeeding women) 18 years+
- Daily Dose (EPA + DHA): 100-3000mg
American Heart Association, 2011
- Subject Group: Adults with CHD
- Daily Dose (EPA + DHA): 900-1000mg
- Subject Group: Adults with high triglycerides (i.e. 2.26 – 5.63 mmol/L)
- Daily Dose (EPA + DHA): 1000-2000mg
- Subject Group: Adults with very high triglycerides (i.e., ≥ 5.65 mmol/L)
- Daily Dose (EPA + DHA): ≥2000mg
Are there any risks associated with omega-3 intake?
Patients who may have fish allergies should consider speaking with their pharmacist to determine which omega-3 supplement is desirable. Many supplements are essentially devoid of protein (which is more likely the culprit allergen). There are also DHA supplements derived from algal sources, and these may be of note for patients who prefer a vegan or vegetarian diet.
Tolerable Upper Limit
The FDA (US) and Health Canada consider up to 3 grams of (EPA plus DHA) to be generally safe for most people. This includes dietary sources. There are no risk information statements from either Health Canada or the FDA regarding cautions, contraindications, or known adverse reactions.
A handful of isolated reports on this issue indicate that certain patients taking relatively high amounts of anticoagulants with blood thinners such as warfarin and heparin have experienced adverse events if they also take high doses of omega 3 fatty acid supplements. This combination has in some cases led to abnormal coagulation profiles (e.g., increased bleeding times), which are restored to desired therapeutic ranges when omega 3 PUFAs are withdrawn. It can be pointed out that patients have been on such anticoagulants as part of their prescribed regimens while enrolled in clinical trials which have suggested beneficial effects of DHA/EPA supplementation of 900 mg/day following a myocardial infarction such as in the GISSI Prevencione trial. It is noteworthy that many trials investigating benefits of n-3 PUFA supplementation have included patients on these anticoagulants as part of their prescribed regimens, with no adverse events related to this type of combination.
Supplemental DHA has proven safe during pregnancy and lactation, and whereas intakes in a typical North American diet are roughly 80 mg/day, a minimal intake of 200 mg/day has been recommended by the FAO/WHO to support optimal delivery of DHA and its provision for brain development and visual acuity for the baby. Often, intakes during pregnancy in Japan approach 1000 mg per day, with no evidence for any harmful effects to the baby.
How do I know what to recommend to my patients?
Canola Oil Vs. Fish Oil Supplements?
While ALA is more easily obtained in the diet through some types of vegetable oil, conversion of ALA in the body to its longer chain counterparts EPA and DHA is extremely inefficient. It is therefore of utmost importance to obtain the latter two directly. Generally speaking, 2-3 servings of fatty fish per week may be enough to reach a daily target of 200-300 mg per day, when averaged throughout the week. Marine sources of omega-3 PUFAs are almost completely digested, with a bioavailability nearing 80-90%. Cooking does not generate significant decreases in these levels. Patients who do not wish to eat fish may choose to investigate EPA/DHA supplements. This market has now developed algal sources of DHA for patients who are averse to animal sources of omega-3s.
Comment on Omega 3:6:9 Supplements
Many people ask about the popular omega 3:6:9 supplements available on pharmacy shelves. These contain a mixture of omega-3, omega-6, and omega-9 fatty acids. Omega-9 fatty acids are not essential – the human body has a high capacity to synthesize them through existing metabolic pathways. They are also highly common in a typical North American diet. Like omega-3 PUFAs, some omega-6 PUFAs are considered essential and must be obtained from the diet. Omega-6 fatty acids are consumed with vegetable sources which are highly common in the typical North American diet. In fact, whereas the daily recommended intake of omega 6 is approximately 2-4 grams per day, many people in Westernized areas consume up to 15-20 grams per day. Omega-3 fatty acids are commonly under-consumed in these same populations.
Comment on Recommended Ratio of EPA to DHA in Supplements
Although two large-scale clinical trials investigated the effects of EPA supplementation on cardiovascular events and related mortality, the vast majority of studies which have evaluated and supported the benefits of consuming omega-3 fatty acids have used mixtures of EPA and DHA omega-3 fatty acids. It has been recommended that at least one third of a combination supplement be represented by either EPA or DHA. This translates to a recommended EPA: DHA ratio ranging from 2:1 on one extreme all the way to 1:2 on the other. Many of the studies looking exclusively at DHA have focused on a structure-function relationship for optimal neuronal and visual functioning in infants, since this particular fatty acid accumulates rapidly in the brain and eye tissues during infant development.
The 1999 Fatty Acid Workshop in Bethesda indicated that at least one third of target intakes of 650 mg/day by healthy adults be represented exclusively by either EPA or DHA. Supplemental omega-3 has a better absorption across the intestinal wall when taken with meals
Comment on Form of Omega-3 Supplements
Some comparative studies have shown either minimal or no significant differences in the bioavailability of the triglyceride versus ethyl ester forms; though others have demonstrated that the TG form is more readily absorbed. The triglyceride form lends to the term “natural” on labels, whereas the ethyl ester form is produced when processing to concentrate the omega-3 contents.
Ensuring Supplemental Safety
IFOS Program: Omega-3 and whole fish products are tested through certified and accredited reference laboratory partners. This International Fish Oil Standards program is world-renowned and has tested a number of brand names for polychlorinated biphenyls (PCBs), mercury, heavy metal, and oxidation levels in accordance with Council for Responsible Nutrition’s voluntary monograph on omega-3 products and safety standards for human consumption. Dioxin and Furan levels are tested against the World Health Organization’s standard and omega-3 concentration is tested and compared with the product label claim. Patients can browse a detailed list of these products – including batch numbers and expiry dates – at the website: ifosprogram.com/IFOS/ConsumerReport.aspx
How do I know what to recommend to my patients?
Why test these levels?
Individual differences exist in the ability to absorb and metabolize these essential fatty acids. Even if the omega-3 intake were known, each person is metabolically unique, with idiosyncrasies in digestion, absorption, tissue distribution, and cellular metabolism. Body weight and individual variations such as the in vivo conversion of ALA into EPA and DHA as well as the intake of n-6 fatty acids can also influence tissue levels. These factors conspire together to produce different levels in people all consuming the same amount of EPA + DHA. The levels of EPA + DHA in fish and seafood vary dramatically even between a given species which greatly affects the Omega Profile. Knowledge of baseline levels will help guide a physician’s recommendations – not surprisingly, lower baseline levels may require a larger dose. Subsequent measurements of levels provide assessment of changes in risk as a function of intake. When the daily oral intake of EPA/DHA is increased, it takes about 4-6 weeks for the blood levels to approach reaching the new higher level.
The Omega Profile Difference
The Omega Profile is a way to provide a tangible measure of benefit for these patients. It may also serve as a measure of compliance to prescribed nutritional modifications. Provision of this information will help to reinforce patient autonomy and beneficial lifestyle changes. The Omega Profile is the only diagnostic test currently available which directly correlates blood levels to established targets in the scientific literature.
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