The cutting edge technology that allows Genova Diagnotics to measure fatty acids in membrane phospholipids has become available only within the past couple of years. Serum fatty acids were simply not reliable indicators of true fatty acid status, and so physicians and researchers were limited to a shotgun approach of giving various oils in gross amounts (fish oil, flax oil, EPO, etc.) and then watching for clinical improvement. Today, however, Genova Diagnotics' Essential and Metabolic Fatty Acids Analysis offers physicians a precise assessment of 24 individual fatty acids and 17 of the important ratios (such as the ones influencing chronic inflammatory states), as well as percent distributions of fat families, including the omega-3 and omega-6 fatty acids.
For determination of red blood cell (RBC) fatty acids, a fasting whole blood sample is required. The blood sample is sent whole to the laboratory, where it is analyzed. The determination of fatty acids is then analyzed by computer, and each fatty acid quantity is presented as a percentage of the total fatty acids in the cell membrane.
Changes in the modern diet are largely responsible for the increasing incidence of EFA imbalances and deficiencies. The ratio of omega-6 to omega-3 fats has changed dramatically due to the widespread use of vegetable oils (mostly n-6 fats) in cooking and to the processing of oils to alter omega-3 fats to improve shelf life and eliminate their stronger taste (just think of the distinctive tastes of cod liver or flax oil). In fact, historical estimates place the ratio of n-6 to n-3 oils at nearly 1:1 for prehistoric humans, but by the turn of the 20th century, the ratio had increased to about 4:1. Current estimates for Americans place the ratio in the range of 20:1 to 25:1!1 The sharp rise is due to increased vegetable oil consumption: from 2 lbs per year in 1909 to 25 lbs per year in 1985!2 The ideal dietary ratio should probably be in the range of 3:1 to 5:1, with a minimum of 1% of our daily calories coming from omega-3 oils.3 A recent study looked at 8 essential fatty acid metabolites in 847 consecutive patients, aged 50-70. 322 of those tested had at least one EFA outside the normal range, and of those 322 patients, 57% had at least two abnormal values, and 7% had 5-7 fatty acid deviations. General trends observed included an increase in abnormals with age, and increases in heart disease and cancer patients.4
Over the course of a month recently, GSDL received 168 patient samples for fatty acid analysis. We limited the search to include the 12 most clinically important metabolites, rather than the full 30 we measure. All 168 of the tests had at least one analyte outside the reference range. 68% of the test samples had moderate imbalances (1 or 2 important fatty acids out of the reference range) while 32% had severe imbalances (3-12 analytes out of range). While these figures do not reflect the general population, they are probably fairly indicative of a typical patient population.5
Fatty acid imbalances are commonly seen in patients with any chronic inflammatory condition (arthritis, atherosclerosis, eczema, allergies, irritable bowel disease, autoimmune diseases), in patients with behavior and neuropsychological disturbances (senile dementia, ADHD, aggressive and anti-social tendencies, depression, paresthesias), and in pregnant and lactating women. Both the clinical picture and the laboratory picture nearly always improve with accurate and judicious supplementation of appropriate essential fatty acids.
Fatty acids are hydrocarbons of varying length with a carboxyl group (-COOH) at one end and a methyl group (-CH3) at the other. Fatty acids are stored in plants and animals as triglycerides, that is, three fatty acids attached to a glycerol backbone. The vast majority of dietary fats are found in the form of triglycerides. Triglycerides can come directly from the diet or can be made endogenously by the body from excess dietary carbohydrates or proteins. Triglycerides are stored in adipose tissue and act as a reservoir of caloric energy. Most of the fatty acids used for membrane structures are in the form of phospholipids, not triglycerides. A phospholipid also has a glycerol backbone, with two fatty acids and a highly polar base molecule attached in the third position. That base molecule is usually inositol, serine, ethanolamine, or choline. Phospholipids allow for the formation of a lipid bi-layer, with the non-polar fatty acids portion migrating towards the center and the polar bases forming a polar outer and inner layer of the membrane, that allows interface with the aqueous medium inside and outside the cell. The types of fatty acids used to make phospholipids are heavily influenced by the types of dietary fats eaten.
There are several ways to classify fatty acids. The two most frequently used classification systems are 1) type of saturation (saturated, monounsaturated, polyunsaturated, and trans fats), and 2) families of fats, based on physical structure (omega-3 , omega-6 , omega-9, etc.). Biochemically, fats within a certain family behave similarly in the body, as do fats with the same degree of saturation. For example, polyunsaturated fats are very susceptible to oxidative damage, most saturated fats raise serum cholesterol levels, omega-3 fats make cell membranes more fluid and therefore more permeable, etc. Of the two parent essential fatty acids, both are polyunsaturated. Linoleic acid (LA) is an omega-6 (n-6) oil, and linolenic acid (ALA) is an omega-3 (n-3) oil.
Both LA and ALA are transformed by the body into longer and even more polyunsaturated fatty acids using the same cellular enzymes. Three of these metabolites have 20 carbons and are very important physiolog-ically: di-homo gamma linolenic acid (DGLA), arachidonic acid (AA), and eicosapentaenoic acid (EPA). The body uses these 20- carbon fats to make compounds known as eicosanoids (eicosa is the Greek word for 20) using either the cycloxygenase enzyme to make prostaglandins or thromboxanes or the lipoxygenase enzymes to make leukotrienes. Eicosanoid is the general term to include all prostaglandins, thromboxanes and leukotrienes. Eicosanoids are short-lived, local-acting hormones that affect many aspects of physiological function at the cellular level.
In terms of membrane structure, the longer and more polyunsaturated fatty acids play the more critical roles in maintaining membrane structure and function. Eicosapentaenoic acid (EPA, 20:5 n-3) is elongated and desaturated even further to produce docosahexaenoic acid (DHA, 22:6 n-3) which is a critical EFA for increasing membrane fluidity and permeability. This allows for proper cell receptor function as well as regulation of nutrient and waste product flow into and out of cells and organelles (see Figure 3). DHA is the longest and most highly polyunsaturated fatty acid in membranes. It is found in highest concentration in the membranes of nerve cells, in the retina, and in the testes.
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