Omega-3 fatty acids are essential nutrients, which have to be provided with the diet. Medium chain omega-3 fatty acids from seeds are converted to the long-chain fatty acids, however, based on new data from clinical studies the conversion rate is low indicating that marine omega-3 fatty acids are the preferred fatty acids for prevention and treatment of cardiovascular disease. Morten Bryhn reports.
Long-chain omega-3 fatty acids are important structural components of cell membranes and they are also utilised as raw material for production of local acting hormones.
Docosahexaenoic acid (DHA) is the longest of the marine omega-3 fatty acids with 22 carbon atoms and 6 double bonds. DHA is enriched in brain tissue and in rhodopsin in the retina of the eye. The reason for the local enrichment of DHA in the brain and the specific function of this fatty acid is not fully elucidated.
However, newborn babies deprived of DHA does not obtain the same visual acuity and intellectual functions as children given mothers milk.
Even if the effects of DHA in the brain is not fully elucidated, it is known that patients with cognitive defects have less DHA in red blood cell membranes and patients with Alzheimer's dementia have significantly less DHA in the brain tissue compared with normal age-matched controls.
DHA is even important for normal production of sperms and since DHA is enriched in the myocardium as well as in lung tissue we will very soon know that this marine fatty acid has a series of vital functions and that deprivation may cause disease and malfunction.
Omega-3 fatty acids are essential fatty acids meaning that they have to be provided by food. However, till now it has been generally accepted that the medium chain alfa-linolenic acid (ALA) from linseed or flaxseed can be easily converted to eicosapentaenoic acid (EPA) and DHA, the marine omega-3 fatty acids, meaning that intake of fish is not absolutely necessary. The conversion of ALA to EPA and DHA is described in Sprecher's Pathway (Fig. 1).
The rate limiting step is the delta-6 desaturation and this enzyme as well as delta-5 desaturase may be subjected to different capacities in different species. Until now we have had information mainly from rodents but recently there has been three publications addressing this issue in humans and there has also been issued a consensus report from the UK Food Standard Agency. These reports and the implications of the conclusions will be discussed.
The first study of two from the Institution of Human Nutrition in Southampton examined the capacity for conversion of ALA to EPA and DHA in young men(1). Emulsified ALA tagged with the radioactive isotope carbon 13 was given in addition to a habitual diet. Approximately 33 per cent of administered radio labelled ALA was recovered as CO2 on breath over the first24 hours.
The time scale of conversion of ALA to EPA indicated that the liver was the main site of desaturation and elongation, which has been shown previously in animals.
However, there was no enrichment of DHA in total plasma to be recorded at any time point up to 21 days. The distribution of total plasma omega-3 fatty acids over this time period was 84 per cent ALA, 7.9 per cent EPA and 0 per cent DHA.
The authors concluded that even if some ALA seems to be converted into EPA the extent of DHA synthesis is likely to be of negligible biological significance.
A conversion of ALA to DHA in tissues where the fatty acid was not released into plasma could, however, not be excluded.
The nutritional demands for DHA in healthy adults are likely to be modest and the need for DHA may be satisfied by existing pools of DHA within the body or preferably by eating fatty fish.
Since, however, elderly people with cognition defects have low levels of DHA in red blood cells membranes, it seems that these pools will have to be continuously replenished in order to counteract a negative balance.
The second study from Southampton was performed in women of reproductive age with the same methodological set-up as in the previous study(2). The results were slightly different compared to what was found in men since the extent of ALA conversion to DHA was greater in the women.
A direct comparison is difficult due to methodological reasons, but in this study the fractional excursions of labelled fatty acids in total plasma lipids was 21 per cent for EPA and9.2 per cent for DHA.
These data suggest greater synthesis of both EPA and DHA in women compared with men. It has been shown previously that estrogens used for anticonception increase the conversion of ALA to DHA(3).
The capacity to regulate ALA conversion by the action of sex hormones may contribute to the higher DHA concentration in women. This may be important during pregnancy and lactation in order to provide the foetus with sufficient DHA for brain development and maturisation.
However, a study from Oregon Health and Science University could not find any increase of DHA in lactating women given flaxseed oil, which is rich in ALA(4). Seven lactating women were given this oil providing a daily intake of 10.7g ALA. Breast milk and plasma ALA and EPA increased significantly while no increase was observed for DHA. The authors concluded that flaxseed oil supplementation would not be an adequate method of increasing the availability of DHA for the developing infant.
A workshop initiated by the UK Food Standards Agency with the aim of reviewing current research investigated whether ALA was as beneficial to cardiovascular health as the omega-3 fatty acids from marine sources(5).
The conclusions from the studies presented was that ALA supplementation either as flaxseed oil or as fortified food such as margarine could increase the levels of ALA and EPA, but hardly any, if at all, DHA. The studies presented suggested little, if any, benefit of ALA on risk factors for cardiovascular disease. The effects previously observed with supplementation of marine omega-3 fatty acids were not replicated by ALA supplementation.
The workshop had reservations about the evidence suggesting beneficial effect of ALA on the secondary prevention of coronary heart disease, and felt it was still needed to be established.
The industry in the US with commercial interest in the commercialisation of flaxseed crop has during many years been heavily promoting the use of ALA as a fully substitute for the marine omega-3 fatty acids, claiming that conversion from ALA to EPA and DHA is efficient and reliable.
Data on conversion from ALA to EPA and DHA has been based on studies in rodents but the yield of the Sprecher's pathway from ALA to EPA, and even more important DHA, is probably very different between species, not least between men and mice. In the promotion of food products and food supplements containing ALA data from studies on EPA and DHA have been extensively used. Now it seems that this arguments are not valid based on recent studies in humans.
Even if conversion from ALA to EPA may be effective to a certain extent, DHA has to be provided either by eating fatty fish or by taking marine omega-3 dietary supplements. The claimed net effects of providing ALA on primary prevention and secondary prevention against cardio vascular disease seems to be non-existing and further large clinical studies will have to be presented before health claims of flaxseed and linseed oils can bewarranted.
Morten Bryhn, MD, Ph D, is with Pronova Biocare AS, Lysaker, Norway. www.pronovabiocare.com
References: 1. Burdge GC, Jones AE and Wooton SA. Eicosapentaenoic and docosapentaenoic acids are the principal products of alfa-linolenic acid metabolism in young men. Br J of Nutr 2002;88:355-363; 2. Burdge GC and Wooton SA. Conversion of alfa-linolenic acid to eicosapentaenoic, docosapentaenoic and docosahexaenoic acids in young women. Br J of Nutr 2002;88:411-420; 3. Silfverstolpe G, Johnson P, Samsice G, et al. Effects induced by two different estrogens on serum individual phospholipid and serum lecitin fatty acid composition. Hormone and Metabol Res 1981;13:141-145; 4. Francois CA, Connor SL, Bolewicz LC, et al. Supplementing lactating women with flaxseed oil does not increase docosahexaenoic acid in their milk. Am J Clin Nutr 2003;77:226-233; 5. Sanderson P, Finnegan YE, Williams CM, et al. UK Food Standards Agency alfa-linolenic acid workshop report. Br J of Nutr 2002;88:573-579.
