FISH OIL

Reprinted from Network News, No. 4 (November 1994)

Last month, the Mayo Clinic published a headline-making study on treating IgA Nephropathy with Omega-3 fish oil.

Omega-3 fish oil provides essential fatty acids that cannot be made by our bodies but must be supplied by our diet. These include linoleic and linolenic acids, which are found in black currant, borage, primrose and flax oils as well as fish, EPA (eicosapentaenoic acid), and DHA (docosahexanenoic acid).

In recent years, there have been investigations of the usefulness of Omega-3 fatty acids in treating ulcerative colitis, hypertension, psoriasis, rheumatoid arthritis, and autoimmune diseases like systemic lupus erythematosus. Researchers have looked at fish oil's potential role in lowering blood lipid levels of patients on dialysis or at risk of accelerated coronary disease, or in preventing restenosis in the arteries of those who have undergone angioplasty to open clogged vessels.

The rationale for using fish oil in treating IgA Nephropathy is that, among other things, Omega-3 fatty acids affect the production of eicosanoids, cytokines, and thromboxane A2, all of which are believed to have a role in injuring the glomeruli.

Unfortunately, studies of fish oil and IgAN have been small and the results conflicting. The Mayo Clinic study, which used different nephrology centers to follow over 100 patients (half of whom received olive-oil placebo) was by far the largest, and patients were tracked for roughly two years, or until their serum creatinine concentration increased by 50%, indicating significant loss of renal function.

What the Mayo Clinic found--and why the results are so encouraging--was that the kidneys of those in the fish-oil group functioned better longer than those in the placebo group. Only 6% of the fish-oil patients suffered an increase of 50% or more in their serum creatinine, whereas 33% of the placebo patients did. Whether hypertension was present or absent, whether serum creatinine was elevated or not at the study's start, whether proteinuria was below or above 3.5 g/24 hours, patients receiving fish oil consistently showed less decline in function than did those receiving the placebo.¹

Despite this great news, however, there are some caveats that anyone thinking of going on fish oil needs to know:

1) Other studies of fish oil, whether on animals or humans, report conflicting results. A Canadian study of rats who had most of their kidneys removed concluded that animals fed both a low-protein diet and fish oil supplements "significantly preserved" their kidney function, in contrast to rats fed either alone, or fed a regular lab diet. The low-protein diet reduced mesangial expansion, while the fish oil prevented formation of fibrin within the glomeruli; together they worked to prevent glomerulosclerosis (scarring of the glomeruli).² On the other hand, Italian researchers treating patients with proteinuria found a low-fat, low-protein vegetarian soy-based diet to be effective in reducing protein loss and blood lipids. Adding fish oil brought about a slight lowering of diastolic blood pressure, but not much else.³ A Swedish study found no difference between fish oil and corn oil placebo in treating IgAN patients who had proteinuria and "moderately reduced" kidney function. In fact, the patients on fish oil showed a decline in renal function that was not reflected in those on placebo.⁴ The Mayo Clinic study notes these and other adverse reports, but says that they may be due to differences in the disease itself, including its rate of progression, or in the patient populations studied. At any rate, it is not clear which patients are likely to benefit from fish oil or what stages of IgAN it might help. A person's reaction to fish oil may be as idiosyncratic as his reaction to a prescription drug.

2) The fish oil used in the Mayo study was a high-quality product supplied by special arrangement with the National Marine Fisheries Service. Commercially-available fish oils may be of lesser quality. For the highest EPA and DHA content, Omega-3 fish oils should be prepared from fatty cold-water fish. If the fish used are small and fairly low down on the food chain, heavy metal contamination should not pose a problem. Unfortunately, it's not easy to find out the source of commercial oils. Nor is it clear that fish oils are being tested for possible heavy metal contamination. Todd Putzbach, a technical representative of Thompson, one of many companies distributing MaxEPA fish oil in the U. S., claims that fish oil is tested; but representatives of the Food & Drug Administration's Center for Food Safety and Applied Nutrition do not believe that fish oils are routinely tested or that any laws require their testing.⁵ If testing is being done, it may be spot-testing on a voluntary basis by the companies. Heavy metal contamination may not indeed be a problem in fish oil--but if you're consuming megadoses of the stuff, you'd better be sure of that.

3) Animal studies of fish oil have noted negative as well as positive effects. In one, rats fed fish oil developed proteinuria and reduced glomerular filtration rate. Reviewers speculated that incorporating these highly unsaturated fatty acids into the rats' kidney membranes may have resulted in the formation of free radicals, which in turn damaged the kidneys.⁶ The possibility of further damage to kidneys by free radicals liberated from fish oil's fatty acids has not been studied in the human kidney, to the best of my knowledge. Many commercial fish oils are fortified with small amounts of Vitamin E, an anti-oxidant, presumably to prevent free radical formation through oxidation.

4) There may be problems tolerating megadoses of fish oil, especially on the part of children. In large doses it can cause diarrhea; at just about any dosage level there can be an unpleasant fishy aftertaste, even if attempts are made to camouflage the fishiness with other flavorings. Consider whether the needed essential fatty acids might be supplied in part by other sources, such as black currant oil, borage oil, or the herb purslane.

5) There can be adverse effects. Increases in blood glucose levels have been reported in non-insulin dependent diabetics, and nutritional guides like the popular Prescription for Nutritional Healing recommend that all diabetics stay away from fish oil. (On the other hand, a recent Massachusetts study and an Italian review both concluded Omega-3 fish oil could be of benefit to diabetics with high cardiovascular risk factors.⁷ The Network has a report of one case of acute renal failure precipitated by fish oil in a patient subject to constant macrohematuria. Because fish oil decreases the blood's ability to clot and increases bleeding time, megadoses may not be a good idea in heavily hematuric patients.

1. JV Donadio, et al., "A controlled trial of fish oil in IgA Nephropathy," New England Journal of Medicine, v. 331, no. 18 (November 3, 1994), pp. 1194-99.

2. WF Clark, et al., "Dietary protein restriction versus fish oil supplementation in the chronic remnant nephron model," Clinical Nephrology, v. 39, no. 6 (June 1993), pp. 295-304.

3. MG Gentile, et al., "Treatment of proteinuric patients with a vegetarian soy diet and fish oil," Clinical Nephrology, v. 40, no. 6 (December 1993), pp. 315-20.

4. EE Pettersson, et al., "Treatment of IgA Nephropathy with Omega-3 polyunsaturated fatty acids," Clinical Nephrology, v. 41, no. 4 (April 1994), pp. 183-90.

5. Telephone interviews, November 16 & 18, 1994.

6. JL Logan, et al., "Dietary fish oil interferes with arachidonic acid metabolism in rats: correlations with renal physiology," Metabolism, v. 41, pp. 382-89, cited in Pettersson, op. cit.

7. L Axelrod, et al., "Effects of a small quantity of Omega-3 fatty acids on cardiovascular risk factors in NIDDM," Diabetes Care, v. 17, no. 1 (January 1994), pp. 37-44; I Nosari, et al., [Use of Omega-3 in diabetic patients (in Italian)], Clinica Terapeutica, v. 144, no. 3 (March 1993), pp. 213-21.

[Reprinted from Network News, No. 4 (November 1994)]