Authors:
This work was supported in part by NUTREK, Inc., and the National Center for Nutrition and Fatty Acid Research, Inc.
Chronic intestinal disorders cause malabsorption and nutritional losses through diarrhea. One would be expect that patients with these disorders would have essential fatty acid deficiency (EFAD). However, such deficiency has not been found in patients treated by their gastroenterologists in the usual manner.
We evaluated the plasma fatty acid patterns of 56 reference or control subjects with no known disease, and 47 patients with chronic intestinal disorders (mostly Crohn's disease). We used high resolution capillary column gas-liquid chromatography with a long column.
Patients exhibited a shift in fatty acid metabolism which is similar to the one Dr. Siguel has shown to be associated with EFAD. Compared with control subjects, patients had:
In other studies conducted by Dr. Siguel, most of the patients with chronic intestinal malabsorption had significant EFA abnormalities.
On various indices of EFA status, the patients were between patients with severe whole body EFAD and healthy subjects. This is the condition or state which Dr. Siguel named Absolute EFA Insufficiency. We recommend that patients with chronic intestinal disease be evaluated for likely EFA deficiencies and imbalances. When an abnormality is found, patients should be treated with substantial amounts of supplements rich in EFAs, such as oral vegetable and fish oils. If this is not enough, due to fat malabsorption, it will be necessary to use intravenous lipids.
Patients with chronic intestinal disorders have (in percents) the plasma fatty acid pattern characteristic of Absolute EFAD. The condition of Absolute EFAD is often characterized by:
Our data indicate that normal T/T ratios are about one tenth of the previous detection limit, and ratios in patients with chronic intestinal disorders are an average of 50% higher than subjects without disease.
Absolute EFA insufficiency may cause significant abnormalities of eicosanoid metabolism. These abnormalities would be a contributory factor to the so-called "systemic" consequences of intestinal disease. EFA abnormalities also produce subtle clinical symptoms which the patient may not notice, such as increased platelet aggregation and suboptimal cell function, including reduced cell life.
In my clinical experience, the most significant factors accounting for EFA status are: individual variability; treatment effects often due to unknown interactions of a multitude of drugs; exercise; disease activity (which fluctuates and is difficult to assess); and large variabilities in dietary intake (these are practically impossible to measure reliably, because people substantially change their dietary intake of EFAs almost every week. Also, EFA composition of food depends on actual oil used in the food (often unknown) and method of food preparation). For these reasons, it is practically impossible, in our clinical experience, to predict EFA status from clinical observations. It is practically useless to assess intake of EFAs by dietary questionnaires in these patients.
In subjects on intravenous feeding or at risk for hypercoagulability (i.e., abnormal antithrombin III level, Protein C deficiency, Protein S deficiency, thrombocytosis, or history of thrombosis), we recommend that physicians screen for low w3 or 20:5w3/20:4w6 levels as an additional risk factor. Based on the test results, an appropriate diet should be followed to correct EFA abnormalities.
With increasing deficiency of EFAs, there is enhanced formation of derivatives of linoleic acid and oleic acid. EFAD subjects compensate by producing more MUFAs and actively converting w6 EFAs to their derivatives to attempt to maintain plasma levels of w6 EFA derivatives. A similar phenomena was found in patients with coronary artery disease (reported by Siguel in Metabolism, 1995). We propose that increased pathway activity helps to regulate the amount of EFA derivatives available for cell function, and substitutes EFAs with MUFAs in an attempt to maintain membrane fluidity (a MUFA is closer to a PUFA than is a SFA).
We know from theoretical reasons and our data (unpublished) that total plasma fatty acid concentration is highly correlated with the sum of the concentrations of cholesterol and triglycerides. The patients reported in this study had low total plasma fatty acid concentrations. For well fed patients with cholesterol and triglycerides within the average population ranges, plasma fatty acid concentrations will be within average population ranges. In this case, we must use percents for the diagnosis of EFA status. In contrast, patients with CAD have elevated plasma concentrations of total fatty acids and normal to elevated plasma concentrations of PUFA with decreased PUFA percent. Here, the percents of EFAs are also critical for diagnosis.
Variations in concentrations of fatty acids are, by themselves, less significant indicators of EFAD than are percents, because the concentrations depend on total plasma lipid levels and thus depend on total cholesterol and triglyceride levels. A patient may have mildly elevated plasma lipids which result in EFA concentrations within reference values, but the percent of EFAs would be low and the percent or concentration of 20:3w9 would be increased. The best diagnosis is achieved by the concurrent analyses of concentrations, percents of fatty acids, and ratios of fatty acids using two dimensional (or higher dimensional) plots. Concurrent analyses of several variables also identifies patients with a partial block in the conversion of EFAs to their derivatives (reduced derivatives in the presence of adequate precursors), impaired utilization (increased 16:1w7 and 20:3w9 in the presence of normal to elevated concentrations of EFAs), and other metabolic abnormalities, or suboptimal proportion of eicosanoid precursors (w3 vs w6 levels).
Our research indicates that EFA Insufficiency is not only a consequence of chronic intestinal disease, but is a contributing factor to its pathology. There are several physiological mechanisms which explain the role of EFAs in the pathology of Crohn's disease.
The EFAs must be obtained from the diet. Dietary intake data cannot accurately measure fatty acid intake (due to conversions of glucose and protein to saturated fatty acids, or changes in fatty acid structure caused by food processing such as trans fatty acid formation). In a given patient, it is practically impossible to determine whether EFA abnormalities are caused by insufficient EFA intake, malabsorption, increased demand for fatty acids, excess saturated fatty acids, or an imbalance of w3 vs w6 fatty acids. We recommend that fatty acid profiles be incorporated in indices of intestinal disease activity. In cystic fibrosis, the disease contributes to EFAD, and EFAD is a primary contributor to many of the systemic consequences of the disease.
EFAs and EFA derivatives have been proposed for the treatment of a variety of diseases. The extent of the deficiency in individual fatty acids provides clues to determine whether to use foods high in w3 or w6 fatty acids. Correction of fatty acid imbalances may improve the disease. To determine whether a patient with EFAD or EFA insufficiency needs intravenous lipids, one can supplement the diet with w3 and w6 fatty acids, using 2 tablespoons of soybean or flax seed oil per day for several weeks (together with about 100 IU of vitamin E/day per tablespoon of oil), and test again for plasma fatty acid composition in about three months. Patients who can not tolerate the oils (i.e., due to severely increased diarrhea even with drugs such as Questran) or who do not show a consistent increase in PUFAs will require periodic infusions of intravenous lipids. The frequency and formula for such lipids is determined by monitoring of the fatty acid profile. Dr. Siguel has published an article in the Arch of Path and Lab Medicine showing that fatty acid testing is cost effective to determine the need for intravenous lipids, which are very expensive.
A 50% elevation in cholesterol is a sign of pathology. A 50% elevation in blood pressure is serious. We propose that a 50% elevation in the T/T ratio or 16:1w7 is a risk factor and indicator of serious pathology. There is little doubt that significant EFAD should be treated. In our clinical experience, we found that EFA abnormalities are probably the single most important nutritional deficiency overlooked in patients with intestinal disease. See data presented at ASPEN 1995. When treatment is recommended, we use a diet that will bring the plasma fatty acid profile of a patient closer to the profile of a healthy control population. Such a diet requires a mixture of oil supplements optimized for each patient. The optimal mixture can be formulated with safflower and sunflower oil (rich in w6), soybean oil (rich in w6 and w3) and flax seed oil (mostly w3). Sequential fatty acid profiles can assess whether oral EFA supplements are sufficient, or if intravenous lipids are needed.
Optimal diagnosis requires a concurrent evaluation of concentrations of fatty acids in plasma, and concentrations in lipoproteins (known as percents of fatty acids).
See the published articles for
graphs, tables and references. Key definitions.
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© 1998 Edward N. Siguel. All rights reserved |
modified 9/16/98 |