Wednesday, December 14, 2005

Biochemical and health details of omega-3 fatty acids.

Animal cell membranes consist of fatty materials of which fatty acids are vital membrane components. Some of these fats cannot be made in the body they include fatty acids called LA and ALA that we need in our diet. LA and ALA are used to make several other important compounds in the body that include polyunsaturated fatty acids (usually called PUFAs) and other molecules such as prostaglandins used as special hormone like messengers. EPA and DHA are the main PUFAs made by the body from essential fatty acids in the diet, but we can also get them directly from fish oil, which is good because is seems the body is inefficient at converting vegetable sources of LA and ALA into EPA DHA and, and are also be used to make other molecules with highly specialized roles a hormone like signal compounds (e.g. prostaglandins, arachidonic acid). We can get the LA and ALA from vegetable oils like linseed oil. PUFAs like EPA and DHA are involved in numerous health benefits such as less heart trouble; it’s really worth waiting till the Pundit's explains them more fully in a coming post as part of the story behind new GM oilseeds that are being developed by many companies.

It the meantime here's some comments from two recent scientific papers I have read to partly document my remarks.

Paper 1. The biochemical details.

Molecules of Interest: Eicosapentaenoic acid: biosynthetic routes and the potential for synthesis in transgenic plants.

Olga V. Sayanova, Johnathan A. Napier* Rothamsted Research, Harpenden, Herts AL5 2JQ, UK

Accepted 9 October 2003

This review is dedicated to the memory of Dr. David Horrobin (1939–2003).

Phytochemistry 65 (2004) 147–158

Long chain polyunsaturated fatty acids are now known to play important roles in human health. In particular, eicosapentaenoic acid (20:5delta 5,8,11,14,17; n-3: EPA) is implicated as a protective agent in a range of pathologies such as cardiovascular disease and Metabolic Syndrome (Syndrome X). Eicosapentaenoic acid is currently sourced from fish oils, the presence of this fatty acid being due to the dietary piscine consumption of EPA-synthesising micro-algae. The biosynthetic pathway of EPA has been elucidated, and contains several alternative metabolic routes. Progress in using ‘‘reverse engineering’’ to transgenically mobilize the trait(s) for EPA are considered. In particular, the prospect of producing this important polyunsaturated fatty acid in transgenic oilseeds is highlighted, as is the urgent need for a sustainable replacement for diminishing fish stocks.

Animal cell membranes primarily consist of a bilayer of phospholipids and cholesterol with imbedded proteins that act as receptors, transporters and enzymes.The phospholipid fatty acid composition determines thephysical and functional properties of cell membranesand has important implications for cell integrity and growth, inflammation and immunity. This is defined by the fatty acids esterified to the glycerol backbones, with chain length and unsaturation acting as key determinants.The role(s) of 20-carbon (C20) polyunsaturated fatty acids (PUFAs) with methylene interrupted double bonds have been the recent focus of intensive research on fatty acid functionality. For the purpose of this review, PUFAs are defined as containing three or more double bonds on a fatty acid chain of 18 or more carbons. PUFAs can be further classified into two families (n-6 or n-3), depending on the position of the last double bond proximal to the methyl end of the fatty acid. These n-6 and n-3 fatty acids (also sometimes called omega-3 and omega-6 fatty acids) are derived from the essential fatty acids (EFA) linoleic acid (LA, 18:2_9,12) and a-linolenic acid (ALA, 18:3delta9,12,15), respectively. Both of these precursor fatty acids are synthesized by plants, but not mammals; therefore they are essential dietary components of all mammals and hence their designation as EFAs. Through a series of acyl desaturation and elongation reactions, LA is metabolized to arachidonic acid (AA, 20:4delta 5,8,11,14; n-6) and ALA is metabolized to eicosapentanoic acid (EPA, 20:5delta 5,8,11,14,17; n-3) and docosahexaenoic acid (DHA, 22:6delta 4,7,10,13,16,19).

Thus the n-6 (LA) and n-3 (ALA) EFAs yield two different distinct classes of C20+ PUFAs and these two families are not normally interconvertible. This is highlighted by the fact that they are metabolically and functionally distinct, having opposing physiological functions. PUFAs play key roles in cellular and tissue metabolism, including the regulation of membrane fluidity, electron and oxygen transport, as well as thermal adaptation. They are also implicated in prevention and modulation of certain pathological conditions such as obesity and cardiovascular diseases which now appear common in Western society.

Second Paper:

Usefulness of omega-3 Fatty acids and the prevention of coronary heart disease. Harper CR, Jacobson TA. Am J Cardiol. 2005 Dec 1;96(11):1521-9.

Department of Medicine, Emory University School of Medicine, Atlanta, Georgia.

Clinical trial evidence exists that supports a role for the omega-3 polyunsaturated fatty acids in coronary heart disease prevention. However, the results from these clinical trials have varied and were conducted in diverse population groups using several different types of omega-3 polyunsaturated fatty acids, including eicosapentaenoic acid, docosahexaenoic acid, and alpha-linolenic acid (ALA). Thus, we systematically reviewed previously published reports assessing the different types of omega-3 polyunsaturated fatty acid interventions and cardiovascular outcomes. Fourteen randomized clinical trials were included in the review. Six trials were included with fish oil, with 1 large trial (10,000 patients) dominating the analysis. In aggregate, the fish oil trials demonstrated a reduction in total mortality and sudden death without a clinically significant reduction in nonfatal myocardial infarction. The 6 trials with ALA supplements or an ALA-enriched diet were of poorer design than the fish oil trials and had limited power. Many of the trials with ALA involved other changes in dietary components. In aggregate, the ALA trials demonstrated possible benefits in reducing sudden death and nonfatal myocardial infarction, but with wider confidence intervals than in the fish oil trials. In conclusion, the evidence suggests a role for fish oil eicosapentaenoic acid, docosahexaenoic acid) or fish in secondary prevention because recent clinical trial data have demonstrated a significant reduction in total mortality, coronary heart disease death, and sudden death. The data on ALA have been limited by studies of smaller sample size and limited quality.

1 comment:

Anonymous said...

While the role of n-3 PUFA and fish oils remains controversial in the area of cardiovascular disease, the role in IgA nephropathy is even more uncertain. Any thoughts out there on whether we should be using these agents in IgA Nephropathy?