Reprinted from Network News, No. 4
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
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
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
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
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.
[Reprinted from Network News, No. 4