Diagnosing Essential Fatty Acid Deficiency

In his letter about our study published in Circulation 3 years ago,^R1 Dr Siguel raises essentially two concerns: (1) how to assay blood for essential fatty acid deficiency and (2) whether low-fat diets cause essential fatty acid deficiency. Both are addressed separately below.

There are two essential fatty acids, linoleic acid and alpha-linolenic acid, required for synthesis for arachinoids, eicosanoids, prostaglandins, thromboxanes, and leukotrienes that are important for cell membrane function.^R2R3R4 With essential fatty acid deficiencies, an “abnormal” intermediate, eicosatrienoic acid (20:3ω9), accumulates and the “normal” intermediate metabolite, arachidonic or an eicosatetranoic acid (20:4ω6), decreases such that the triene to tetraene ratio (20:3ω9/20:4ω6) or the T/T ratio increases.^R2R3R4

Current texts of nutrition indicate that a T/T ratio of ≥0.4 is associated with clinical linoleic acid deficiency,^R3R4 a criterion used in our 1993 study. Table 3 (page 666) of Dr Siguel’s 1987 study in the journal Metabolism shows an average T/T ratio of 0.45 in six patients with clinical essential fatty acid deficiency as the result of malabsorption syndromes or prolonged fat-free parenteral alimentation.^R5 A normal reference group had a T/T ratio of 0.008, and a subset of subjects from the Framingham Study had values of 0.014. A patient with essential fatty acid deficiency corrected to a T/T ratio of 0.02, in the normal range, after intravenous infusion of adequate essential fatty acids.

In his second 1987 study,^R6 Dr Siguel reports a T/T ratio in a normal reference group as 0.013±0.006. In 10 patients with clinical malabsorption syndromes, the T/T ratio was 0.30±0.61, with a value of P=.06 for the difference, not statistically significant at the .05 level. The normal T/T ratio in older literature is reported as 0.1±0.07.^R6 On the basis of these data, Dr Siguel claims in his letter that “measures of T/T currently in use were in error by a factor ≥10.” With his average value of the T/T ratio of 0.45^R5 and 0.3^R6 in patients with essential fatty acid deficiency by new technology^R5 compared with 0.4 used traditionally,^R3R4 his basis for this claim is questionable, particularly since his own value of 0.3 was not significantly different from his reference group at the P=.05 level of probability.^R6 His normal reference values for the T/T ratio of 0.013 compared with older literature of 0.1^R6 do not redefine the criteria for clinical fatty deficiency, which are 0.3 to 0.45 by his own numbers, the same as traditionally used. Therefore, the criteria for our 1993 article in Circulation are the same as those traditionally used^R3R4 and consistent with Dr Siguel’s own data.^R5R6

In a publication of 1994,^R7 Dr Siguel proposed a new intermediate stage of essential fatty acid insufficiency (as opposed to deficiency) with a number of other end point measures proposed as being more sensitive than the T/T ratio as indicators of essential fatty acid insufficiency. On the basis of fatty acid analyses in 47 patients with documented coronary artery disease, he reasoned that excessive dietary levels of saturated fatty acids saturate or disturb the transport of essential fatty acids, thereby producing a possible abnormal T/T ratio or other proposed biochemical markers of possible essential fatty acid deficiency despite apparently relatively normal diets in these patients. In this study,^R7 the T/T ratio in the normal reference population was 0.013±0.001 and in the coronary artery disease patients was 0.016±0.001, a statistically significant difference of unclear biological importance, particularly in view of a T/T ratio of 0.3±0.61 in patients with clinical essential fatty acid deficiency that was not significantly different from normal at the P=.05 level in his previous study.^R6 By his T/T ratio criteria in the 1994 study,^R7 5 of 47 patients were claimed to have deficiency of essential fatty acids without reference to the type of diet the patients were on. Dr Siguel then extrapolated this point of view to the more extended hypothesis that a low-fat diet causing essential fatty acid insufficiency may increase the risk of coronary artery disease.^R7

In a 1996 study^R8 and in his letter, this point of view is still further extrapolated to the more extended hypothesis that low-fat diets cause essential fatty acid deficiency and heart disease and that “billions of dollars are now spent on drug treatments and surgical procedures for conditions like high blood pressure, abnormal cholesterol ratios, and coronary artery disease, which respond quite well to correction of PUFA abnormalities.” His letter goes on to indict the low-fat food industry and “public health organizations” and concludes that “failure to diagnose and treat PUFA abnormalities can cause unnecessary premature death,” where “correcting PUFA abnormalities” apparently does not mean low-fat food or cholesterol-lowering drugs. The data documenting these extended hypotheses are not reported, to my knowledge. In fact, high intake of linoleic acid of >12% of calories reportedly decreases HDL cholesterol that is associated with higher risk of atherosclerosis.^R3R9R10

Reading the 1987^R5R6 and 1994^R7 articles of Dr Siguel suggests that he knows a great deal about measuring fatty acids and about their possible interactions, with thoughtful, provocative hypotheses about their potential biological importance. However, his own data do not support the claim of an error by a factor of 10 in the criteria of the T/T ratio indicating clinical essential fatty acid deficiency. His data actually support the current traditional criteria. The reader and Dr Siguel need to clearly separate documented criteria and conditions for clinical essential fatty acid deficiency supported by Dr Siguel’s own data^R5R6 from a hypothesized, intermediate stage of essential fatty acid insufficiency in free-living people on undefined diets, on the basis of changes in fatty acid ratios of unknown significance, without defined clinical abnormalities, due to a hypothesized adverse effect on lipid profiles, by an undefined level of dietary polyunsaturated fatty acids.^R7R8 These latter provocative hypotheses are just that—unconfirmed hypotheses. Furthermore, these hypotheses involve the effects of substantial amounts of dietary polyunsaturated fatty acids, particularly linoleic acid and alpha-linolenic acid, on lipid metabolism, not clinical deficiency of these essential fatty acids in the diet of well individuals without malabsorption syndromes or parenteral alimentation.

As to the second issue, do low fat-diets cause essential fatty acid deficiency? The Recommended Dietary Allowances (RDA) published by the National Research Council do not make recommendations on minimum daily requirements of essential fatty acids. The reason is a lack of data and the difficulty of identifying essential fatty acid deficiency in a free-living population other than patients with malabsorption syndromes or total parenteral alimentation. The United Kingdom Reference Nutrient Intakes suggest minimum consumption of 1% of calories from linoleic acid and 0.2% from alpha-linolenic acid.^R3R4 For a 1500-calorie diet commonly needed to achieve lean body habitus, ≈1.67 g of linoleic acid and 0.33 g of alpha-linolenic acid would be minimum requirements on the basis of these criteria. For an 1800-calorie diet, 2 g of linoleic acid and 0.4 g of alpha-linolenic acid would be the minimal requirements by these criteria.

Soybean oil, walnut oil, corn oil, grapeseed, sunflower, and cottonseed oil contain >50% linoleic acid. Soybean oil, walnut oil, canola, and rapeseed oil contain 7% to 11%, and linseed oil contains 53% alpha-linoleic acid.^{R11R12R13R14R15} Only soybean and walnut oils have significant balanced amounts of both linoleic acid and alpha-linolenic acid in proportion to their essential requirements. Alternatively, the compounds synthesized from alpha-linolenic acid, docosahexanoic (DHA) and eicosapentenoic (EPA), can be acquired from seafood, specifically omega-3 fish oil. In view of the ubiquity of the two essential fatty acids in Western diets, essential fatty acid deficiency is considered rare in free-living adults if it occurs at all,^R3R4 being seen only and uncommonly in severe malnutrition, untreated malabsorption syndromes or prolonged incomplete fat-free intravenous alimentation.

However, I have seen 14 lean patients on self-imposed, well-documented diets of <5% of calories as fat for 1 to 3 years (less than my guidelines of 10% of calories as fat) who had clinical symptoms consistent with essential fatty acid deficiency. These symptoms included mild but definite temporary recent memory loss, difficulty concentrating, episodic somnolence during the day, visual scotoma, decreased visual acuity, and/or sexual dysfunction. One, several, or all of these symptoms first appeared on very low-fat diets and reverted to normal on increasing sources rich in essential fatty acids. In addition to these symptoms, 4 of these 14 subjects had their first episode of atrial fibrillation or tachyarrhythmia without alcohol exposure or identifiable cause and without recurrence after increasing essential fatty acid intake. Nine of these subjects had their first episode of overt vasovagal syncope preceded by symptoms of similar but less severe vasovagal reactions, all of which disappeared on increasing sources of essential fatty acids without other identifiable changes in food, weight, or medications. Two individuals developed flaking, soft nails that became normal after increased intake of essential fatty acid sources. None had the typical fatigue, elevated triglycerides, and low HDL commonly caused by excess carbohydrate and inadequate protein previously discussed in “Letters to the Editor” of JAMA in response to Dr Siguel.^R16 Therefore, clinically relevant essential fatty acid deficiency may occur in otherwise well-nourished, active, well individuals on very low-fat diets of <5% of calories as fat. Any treatment powerful enough to heal is also powerful enough to harm if misused or if its side effects are not understood. Very-low-fat food also has similar beneficial or bad potential and must be implemented properly with no less than 10% of calories as fat.

For individuals adherent to very-low-fat foods, I recommend specific sources of essential fatty acids. Soybean oil contains 51% linoleic acid and 6.8% alpha-linolenic acid.^{R11R12R13R14R15} One teaspoon of soybean oil containing ≈4.7 g of oil provides 2.4 g of linoleic acid and 0.38 g of alpha-linolenic acid, the minimum requirements to prevent clinical essential fatty acid deficiency on the basis of the criteria of the United Kingdom Reference Nutrient Intakes^R3R4 and consistent with discussion of the recommended dietary allowances of the US National Research Council.^R2 One form of soybean oil is soya lecithin,^R15 containing 1.2 g of oil per capsule, so that 4 capsules per day would provide this minimum requirement.

One teaspoon of walnut oil provides 2.4 g of linoleic acid and 0.25 g of alpha-linolenic acid. One to two teaspoons of walnut oil ingested per day provide the minimal requirements for essential fatty acids. It is the only oil besides soybean oil with balanced equivalent amounts of both linoleic and alpha linolenic acids in approximate proportion to their essential requirements.

One teaspoon of corn oil, grapeseed, sunflower, or cottonseed oil provides the same amount or more of linoleic acid, since all contain >50% linoleic acid. However, these oils lack the alpha-linolenic acid. Alpha-linolenic acid can be obtained from a teaspoon of linseed oil, rapeseed oil, or canola oil, containing ≈2.4, 0.5, and 0.5 g of alpha-linolenic acid, respectively. Alternatively, instead of alpha-linolenic acid, fish consumption or fish oil could be used as sources of EPA and DHA instead of oils containing alpha-linolenic acid from which the body synthesizes these compounds.

In the study by Siscovick et al,^R17 quoted by Dr Siguel, one fish meal per week consisting of 5.5 g of N-3 fatty acids per month was associated with a 50% decrease in risk of primary cardiac arrest in patients without known heart disease after adjustment for confounding other risk factors. This level of intake is the equivalent of only 0.2 g of fish oil per day, not the “high intakes” of PUFA that Dr Siguel recommends in his 1996 study^R8 and implies in his letter. Although the Siscovick study^R17 has limitations, it suggests that very small amounts of fatty acids may be beneficial.

To keep this discussion with Dr Siguel in perspective, it is important to emphasize that low-fat or very-low-fat food, with adequate essential fatty acids, protein, and other nutrients and cholesterol-lowering drugs have been documented to stabilize or partially reverse coronary and cerebrovascular atherosclerosis with a profound decrease in cardiac and cerebrovascular events. Inadequate lowering of dietary fat or serum cholesterol in the management of patients with coronary artery disease because of extended, unvalidated hypotheses about potential essential fatty acid deficiency could be detrimental to optimal patient management.