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Do omega-3 fatty acids provide real hope or mere hype?

In the early 1970s, studies of Inuit people in Greenland credited their low incidence of cardiovascular disease to their fishy diet. The status of fish as a healthy food soared and supplements of the long-chain omega-3 fatty acids found in fish began to appear in pharmacies.

The initial results of many observational studies looked promising and before long, omega-3s were the ‘in’ supplement. Enthusiastic promotions extended beyond cardiovascular disease to claim benefits for almost every part of the body, including the heart, lungs, skin, eyes, bones, brain and bowel.

Sellers of the supplements and popular diet books recommended omega-3s for those with diabetes, some cancers and various inflammatory conditions (including osteoarthritis). Omega-3s were also promoted for those with mental health and cognitive issues including ADHD, as well as autism spectrum disorder and behavioural problems in children; and depression, dementia and cognitive decline in older people.

With such a litany of claims, displays of omega-3 supplements soon dominated the pharmaceutical aisle in supermarkets, occupying positions of prominence in pharmacies and healthfood shops. Eventually, with the advent of the internet and e-commerce, online sales of the supplement also took off. Meanwhile, food technologists achieved some success in removing the fishy flavour from fish oil, enabl­ing omega-3s to be found in some brands of milk, cheese, yoghurt, breads, breakfast cereals and eggs.

Researchers began clinical trials to substantiate the claims being made about omega-3s. The results are now coming in and while there is some evidence backing their use, this is failing to fulfil many of the key promises.

So called wonder foods
Dietary ‘all-purpose cures’ have a history of failing to live up to expectations. In the 1950s, extravagant claims were made for the five wonder foods: brewer’s yeast, blackstrap molasses, yoghurt, skim milk and wheatgerm. Yoghurt, skim milk and wheatgerm are now regarded as healthy foods, but the claims of an association with eternal youth and good health have disappeared along with the tooth-rotting molasses. Vitamin E supplements suffered a great blow when clinical trials failed to sustain the hype surrounding them.

Oat bran, the darling of the 1980s, appeared in biscuits, desserts, pasta, breads and breakfast cereals, but fell out of favour — as did wheat bran. Oat bran is enjoying a small revival now that the popular (but unbalanced) Dukan diet promotes it. Currently, some claims for low glycaemic index foods extend beyond the evidence, and food companies are clamouring for permission to add vitamin D to a range of foods — along with claims that extend beyond its proven benefits for bone health.

Returning to fish, there is no doubt that seafood should form part of a balanced diet. Dietary guidelines around the world continue to recommend 1-2 fish meals a week. The omega-3 fatty acids in fish are partly responsible, backed by the high nutrient content of fish and the benefits of substituting fish for large servings of red meat. Sadly, however, there is not enough fish in the world to meet these dietary recommendations. Even in Australia, we import up to 70% of the seafood we consume, and often these products have lower levels of omega-3 fatty acids than the seafood we export. This has given rise to greater interest in omega-3 supplements.

The value of omega-3s
Contrary to popular belief (reinforced by PR companies), ‘omega-3’ is not a single entity; there are many omega-3 fatty polyunsaturated fatty acids. The most common are:

• Alpha linolenic acid — an 18-carbon chain with three double bonds found in seeds such as linseeds, chia, canola and walnuts.
• Eicosapentaenoic acid (EPA) — a 20-carbon chain with five double bonds, found in fish, especially those from cold waters.
• Docosahexaenoic acid (DHA) — a 22-carbon chain with six double bonds, also found in fish, with those from Australian waters being an excellent source.
• Docosapentaenoic acid (DPA) — a 22-carbon chain with five double bonds, found in meat from grass-fed animals.

In general, fish deserves its status as a healthy choice, and analyses of all seafood from Australian waters show they have sufficient omega-3 fatty acids to be officially classed as a “good source”.¹ Some fish, such as swordfish, salmon, mackerel, oreo, gemfish, bonito, mullet, herring, warehou and blue eye are especially good sources.

The mechanisms that explain some of the benefits of omega-3 fatty acids are clear. The longer-chain omega-3s with more than 20 carbon atoms exhibit anti-inflammatory and anti-clotting effects.

The mechanisms have been well summarised.² In keeping with these effects, some clinical trials have shown benefits for rheumatoid arthritis, inflammatory bowel disease and asthma, although confirmation of some of the claimed benefits remain elusive.

For example, a recent meta-analysis failed to find benefits for omega-3 supplements in IBD and results vary for asthma.³ Benefits for rheumatoid arthritis withstand scrutiny, although not so the popular extension of this to the more common osteoarthritis.

Clinical trials show that omega-3 supplements of fish oils reduce triglyceride levels with the two major long-chain omega-3s, EPA and DHA, having similar effects. However, more is not better and high doses of DHA can raise LDL cholesterol levels, as well as HDL cholesterol. EPA has little effect on either LDL or HDL.⁴

Cardiovascular disease
Interestingly, some of the new, longer-term trials of omega-3 supplements are not backing earlier assumptions for heart—health benefits. For example, the Canadian ORIGIN trial of 12,536 people with, or at high risk of, diabetes found no advantages for those given omega-3 supplements.⁵

Triglyceride levels were reduced, but there was no effect on cardiovascular deaths (or deaths from any cause) and no significant effect on the rates of major vascular events or death from arrhythmia.

Several meta-analyses have also failed to back the use of omega-3 fatty acids to prevent sudden death in patients with cardiovascular disease or reduce rates of overall cardiovascular events, all-cause mortality, sudden cardiac death, myocardial infarction, congestive heart failure or transient ischaemic attack and stroke.^6,7

These results contrast with the earlier results from the GISSI Prevenzione Heart failure trial, which reported that supplements of fish oil reduced fatal cardiovascular disease by 10% among people with chronic congestive heart failure.^8,9 It’s possible that the lack of effect in the more recent trials is due to the current widespread use of statins. The take-home message is that omega-3 supplements may not have any benefits for cardiovascular disease, but it remains sens­ible to include fish or seafood in the weekly diet.

After five years of follow-up, the randomised SU.FOL.OM3 trial (Supplementation with Folate, Vitamins B6 and B12, and/or Omega-3 Fatty Acids) found no cancer benefits from the vitamins or omega-3 supplements.¹⁰

Neither were any links noted between fish and pancreatic cancer in nine independent cohorts, which included 3082 events among 1,209,265 participants (with a mean follow-up of nine years) and 10 independent case—control studies including 2514 cases and 18,779 controls.¹¹

However, one review of fish consumption and colorectal cancer risk did report a reduction in risk among those who consumed fish.¹¹ This may have reflected an inverse consumption between fish and red meat.

The brain
Since essential omega-3 fatty acids are required for brain structure, it is not surprising that studies have also examined their role in behaviour, mood changes, depression and dementia.

Again, the results of recent randomised double blind controlled trials have been disappointing. A major review from the UK identified seven relevant trials, four among cognitively healthy older people, and three among individuals with pre-existing cognitive decline or dementia. There was no evidence to support the routine use of long chain omega-3 supplements for the prevention or amelioration of cognitive decline in later life.¹²

Noting that a higher intake of omega-3 fatty acids had been linked with a reduction in Alzheimer’s disease, a Canadian meta-analysis of 10 randomised controlled trials reported that omega-3 supplements had no effect on composite memory or benefits for Alzheimer’s. However, this analysis did detect a slight improvement in attention and processing speed in those with cognitive impairment but no dementia^.13

Noting that a higher intake of omega-3 fatty acids had been linked with a reduction in Alzheimer’s disease, a Canadian meta-analysis of 10 randomised controlled trials reported that omega-3 supplements had no effect on composite memory or benefits for Alzheimer’s. However, this analysis did detect a slight improvement in attention and processing speed in those with cognitive impairment but no dementia.

Another Cochrane report from the London School of Hygiene and Tropical Medicine looked at the evidence that fish oil could help prevent typical cognitive decline in people over the age of 60. Three randomised controlled trials involving over 3536 people found no difference in results of learning and memory tests.¹⁴

The SU.FOL.OM3 trial mentioned earlier also checked for symptoms of depression in survivors of cardiovascular disease. After 4.7 years, the B vitamins had no effect on depressive symptoms, but men receiving omega-3 supplements had a 28% increase in their depressive symptoms, a point the researchers felt merited more study.¹⁵

A Spanish meta-analysis of 38 studies using omega-3 supplements also issued a note of caution. In 23 studies that examined prevention or treatment of depression, six of which looked at perinatal depression and nine of which examined ADHD, the researchers noted that some studies only recorded benefits with low doses. They warned that excessive omega-3 fatty acids might be associated with a greater risk of peroxidation events and therefore neuropsychiatric deterioration. For this reason, the appropriate dose needs to be determined.¹⁶

Another Cochrane review of ADHD identified eight trials that used either omega-3 and/or omega-6 fatty acid supplements. There were no statistically significant differences in teacher or parent-rated ADHD symptoms, including inattention or hyperactivity—impulsivity.¹⁷

The take-home message
Omega-3 supplements are not snake oil, but neither are they universal saviours. Including fish (and other seafood) in your diet makes good sense. It is also unlikely that fish oil supplements, taken in their usual doses, will do harm.

However, the extremely unstable nature of these highly unsaturated fatty acids makes them vulnerable to oxidation. Our noses tell us when fish is ‘off’ and unfit for consumption. Equal olfactory attention needs to be paid to fish oil supplements — and their source. Be especially careful with online sales or products from small companies without adequate laboratory and delivery standards.

Dr Stanton (PhD Hon) is a leading nutritionist.

References:

1. Nichols PD, et al. Seafood the Good Food (Volumes I and II). CSIRO and Fisheries Research and Development Corporation, 1998, 2002.
2. Calder PC. Omega-3 polyunsaturated fatty acids and inflammatory processes: Nutrition or pharmacology? British Journal of Clinical Pharmacology 2012; online.
3. British Journal of Nutrition 2012; 107 Suppl 2:S240-52.
4. Current Atherosclerosis Reports 2011; 13:474-83.
5. New England Journal of Medicine 2012; 367:309-18.
6. Cardiovascular Drugs and Therapy 2011; 25:259-65.
7. Archives of Internal Medicine 2012; 172:686-94.
8. Lancet 1999; 354:447-55.
9. Lancet 2007; 369:1090-8.
10. Archives of Internal Medicine 2012; 172:540-47.
11. Journal of Nutrition 2012; 142:1067-73.
12. American Journal of Medicine 2012; 125:551-5 and Neurobiology of Aging 2012; 33:1482.
13. British Journal of Nutrition 2012; 107 Suppl 2:S152-58.
14. Cochrane Database of Systematic Reviews 2012; Issue 6, CD005379.
15. American Journal of Clinical Nutrition 2012; 96:208-14.
16. British Journal of Nutrition 2012; 107 Suppl 2:S261-70.
17. Cochrane Database of Systematic Reviews 2012; Issue 7, CD007986.