Essential fatty acids (EFAs) are required in the diet as they can not be synthesized by humans from the shorter chain fatty acid, oleic acid (C18:1). The omega-6 fatty acid linoleic acid (C18:2n-6, LA) found in many vegetable oils such as soy and corn oils, and the omega-3 fatty acid alpha-linolenic (C18:3n-3, ALA) are EFAs. ALA is found in the highest concentration in flaxseed oil (55-57% of total fatty acids). LA and ALA are components of cellular membranes and act to increase membrane fluidity. These fatty acids are necessary for cell membrane function, as well as for the proper functioning of the brain and nervous system (1).
ALA is converted by a series of alternating desaturations and elongations to the long-chain polyunsaturated fatty acids (PUFA) omega-3 fatty acids, eicosapentaenoic acid (EPA), docoapentaenoic acid (DPA) and to a limited extent, docosahexaenoic acid (DHA), both found in fish oil. LA is converted to long-chain omega-6 fatty acids in particular arachidonic acid (AA), also by a series of desaturations and elongations.
There is debate about the optimal dietary ratio and the absolute dietary amounts of LA and ALA to promote an efficient conversion of ALA to EPA and DHA, which have implications for human health. Early estimates of the amount of ALA converted to EPA ranged from 0.2% to 8% (1,2), with young women showing a conversion rate as high as 21% (3). Conversion of ALA to DPA is estimated to range from 0.13% to 6% (3). Conversion of ALA to DHA was reported to be limited in humans, with studies showing a conversion rate of about 0.05% (3,4) to as high as 4% (5). A conversion rate of 9% was reported in young women (3).
Barceló-Coblijn, et al. have argued that conversion and conservation of ALA may be efficient in developing neural tissue and in very active tissues such as retina which actively recycles DHA (6). Further, the conversion of ALA to EPA and DHA appears to be dependent on the tissue and phospholipid class, with significant accumulation of ALA, DPA and EPA, but not DHA, in the heart and liver phospholipids of rats fed flax oil. Additionally, diets enriched in either flax or fish oil diets increased phospholipid DHA mass in the brains of rats. In all tissues, both oils decreased the AA mass, although the effect was more marked in the fish oil than in the flax oil group. This study was not able to identify the origin of the DHA in the rats fed the flax oil diet, that is, whether it was imported from the blood as preformed DHA or synthesized in the brain from plasma-derived ALA. However, some studies demonstrate minimal elongation and desaturation of ALA in the plasma, with conversion limited to EPA and DPA (3,7,8) and thus suggesting that ALA, DPA and EPA are taken up by the brain and converted to DHA.
In twenty humans who received supplementation with either fish oil (1296 mg EPA and 864 mg DHA/day) or flaxseed oil (3510 mg ALA; 900 mg LA/day) for 8 weeks, erythrocyte membrane EPA and DHA increased 300% and 42%, respectively following fish oil (9). Flaxseed oil supplementation increased erythrocyte membrane EPA to 133% and DPA to 120% of baseline. The rapid conversion between EPA and DPA indicates the possibility that DPA can be a potential storage form for EPA. ALA supplementation enriches EPA and DPA composition in erythrocyte membranes which may act to sustain a constant supply of EPA to body tissues.
The relationship between the dietary intake of ALA and changes in membrane EPA is positive and linear over intakes of ALA between 2 and 10 g but may be influenced by several factors especially dietary intakes of LA. In a study of 22 healthy men, an LA rich diet (10.5% energy) reduced the EPA content of plasma phospholipids significantly after four weeks compared with a low LA diet (3.8% energy), even though both diets contained the same amount of ALA (1.1% energy) (10).
A recent study published in flaxresearch.com compared the effects of a low-LA/high-ALA (loLA/hiALA) diet with a high-LA/low-ALA (hiLA/loALA) diet on fatty acid concentrations in red blood cells (RBCs) (11). Both diets were fed for two weeks to fifteen healthy men (mean age 26.1 ± 4.5 years) with a low initial EPA/DHA status (EPA + DHA% of total fatty acids in RBC at baseline: 4.03 ± 0.17). A nine-week wash-out phase between the diets which had LA/ALA ratios of 0.56 ± 0.27 : 1 and 25.6 ± 2.41 : 1. Following the loLA/hiALA diet, ALA and EPA concentrations and EPA + DHA increased, whereas LA concentrations decreased. The DHA concentration was unaffected. The hiLA/loALA diet led to slightly decreased EPA concentrations, while all other fatty acid concentrations remained constant. These results suggest that ALA supplementation combined with a reduced LA intake (loLA/hiALA diet) may be more effective at increasing EPA blood concentrations.
The cumulative data suggest that both the total PUFA content and the balance of LA to ALA consumed are critical determinants of long chain omega-3 PUFA status. Thus, it is important to pay close attention to the complete fatty acid profile of the diet, in particular, the balance of omega-6 and omega-3 fats, when evaluating its potential health benefits. Ensuring an adequate omega-3 FA status in individuals is increasingly seen as important for optimizing long-term health outcomes.
High dietary intakes of omega-6 FAs through vegetable oils, spreads and processed foods in many developed countries have made an intake of ALA essential to large numbers of people if they are to improve their omega-3 PUFA status.
The importance of ALA in contributing to EPA requirements is obvious when considering that the average EPA+DHA intake is roughly 100 – 135mg/day (12). These intake levels have really not changed over the last decade despite an abundance of consumer encouraging the consumption of fish and fish oils for numerous health conditions.
References
- Davis, B.C., Kris-Etherton, PM. 2003. Achieving optimal essential fatty acid status in vegetarians: current knowledge and practical implications. J. Clin. Nutr. 78(Suppl): 640S-660S.
- Burdge, G.C., P.C. Calder. Conversion of α-linolenic acid to longer-chain polyunsaturated fatty acids in human adults. Nutr. Dev. 2005. 45: 581-597.
- Burdge, G.C. Metabolism of α-linolenic acid in humans. Prostaglandins Leukot. Essent. Fatty Acids. 75:161-168.
- Pawlosky, R.J., J.R. Hibbeln, J.A. Novotny, N. Salem Jr. Physiological compartmental analysis of α-linolenic acid metabolism in adult humans. Lipid Res. 2001. 42: 1257-1265.
- Emken EA. Influence of linoleic acid on conversion of linolenic acid to omega-3 fatty acids in humans. In: Proceedings from the Scientific Conference on Omega-3 Fatty Acids in Nutrition, Vascular Biology, and Medicine, American Heart Association, Dallas, TX, 1995. pp. 9-18.
- Barceló-Coblijn, G., L.W. Collison, A. Jolly, et al. Dietary a-Linolenic Acid Increases Brain but Not Heart and Liver Docosahexaenoic Acid Levels. Lipids. 2005, 40, 787–798.
- de Groot, R.H.M., G. Hornstra, A.C. van Houwelingen, F. Roumen. Effect of a-Linolenic Acid Supplementation During Pregnancy on Maternal and Neonatal Polyunsaturated Fatty Acid Status and Pregnancy Outcome. Am J. Clin. Nutr. 2004, 79, 251–260.
- Zhao, G., T.D. Etherton, K.R. Martin; J, et al. Dietary α-linolenic acid reduces inflammatory and lipid cardiovascular risk factors in hypercholesterolemic men and women. Nutr. 2004, 134, 2991-2997.
- Cao, J., K.A. Schwichtenberg, N.Q. Hanson, M.Y. Tsai. Incorporation and Clearance of Omega-3 Fatty Acids in Erythrocyte Membranes and Plasma Phospholipids. Clinical Chemistry. 2006, 52, 12, 2265–2272.
- Zhao, G., T.D. Etherton, K.R., Martin, et al.. Dietary alpha-linolenic acid inhibits proinflammatory cytokine production by peripheral blood mononuclear cells in hypercholesterolemic subjects. J. Clin. Nutr. 2007, 85, 385 – 391.
- Greupner, T. Kutzner, L. Pagenkopf, S. et al. 2018. Effects of a low and a high dietary LA/ALA ratio on long-chain PUFA concentrations in red blood cells. doi: 10.1039/c8fo00735g.
- Harris, WS, Mozaffarian, D., Lefevre, M., et al. Towards Establishing Dietary Reference Intakes for Eicosapentaenoic and Docosahexaenoic Acids. J Nutr. Feb 25:084S.