Therapeutic efficacy of N-3 polyunsaturated fatty acid
in experimental Crohn's disease.
Shoda R: Division of Gastroenterology, International Medical Center of Japan, Tokyo, Japan; Matsueda K, Yamato S, Umeda N
J Gastroenterol 1995 Nov 30 Suppl 8:98-101
We investigated the therapeutic efficacy of
n-3 polyunsaturated fatty acids (PUFAs) on trinitro-benzene sulfonic acid (TNBS)-induced colitis in the rats, which condition is considered an experimental Crohn's disease (CD).
In rats with TNBS-induced colitis, feeding with an elemental diet (ED) plus 2% n-3 PUEA-rich perilla oil significantly suppressed plasma leukotriene (LT) B4 and ulcer index
compared to that in rats fed with ED plus 2% n-6 PUFA-rich safflower oil (34.2 +/- 12.3 s 63.8 +/- 13.2 pg/ml and 8.8 +/- 12.1 vs 66.4 +/- 33.1, P < 0.01, respectively).
Moreover, the plasma LTB4 and the ulcer index were significantly correlated (P < 0.05). Feeding with ED plus 2% alpha-linolenic acid (A-LA)-rich vegetable oil significantly
reduced plasma LTB4 and colonic weight compared to that in rats fed with ED plus 2% eicosapentaenoic acid (EPA)/docosahexaenonic acid (DHA)-rich fish oil in this model (61.6 +/-
10.5 vs 85.0 +/- 20.9 pg/ml and 0.83 +/- 0.13 vs 0.96 +/- 0.08g, P < 0.05, respectively). This study suggested that dietary fat manipulation with perilla oil can reduce colonic
damage and that this is correlated with the suppression of plasma LTB4. The therapeutic efficacy of A-LA in controlling intestinal inflammation in experimental CD may be
superior to that of EPA and DHA.
n-3 fatty acids and the immune system in autoimmunity.
Ergas D: Department of Internal Medicine B, Kaplan Medical Center, Rehovot, Israel; Eilat E, Mendlovic S, Sthoeger ZM
Isr Med Assoc J 2002 Jan 4:34-8
In short-term studies, both in animals and in humans, fish oil seems to
exert anti-inflammatory effects. However, these effects may vanish during long-term treatment. There is a possibility that in autoimmune diseases, supplementation of dietary n-3
fatty acids might lead to a decrease in the number of autoreactive T cells via apoptosis, as demonstrated in (NZBXNZW) F1 lupus mice . Thus, the "fade away" effect might be
due to regrowth of pathogenic autoreactive cells. In animal models of autoimmune diseases, diets high in n-3 fatty acids from fish oil increase survival and reduce disease
severity in spontaneous autoantibody-mediated disease, while n-6 linoleic acid-rich diets appear to increase disease severity. The situation in human disease is probably more
complex. Some of the discrepancy between studies can be attributed to methodologic problems. The effect of fish oil is dose, time and disease-dependent. Since the
anti-inflammatory effects depend on the balance between n-3 and n-6 fatty acids, the relative proportion of EPA and DHA and possibly co-treatment with dietary vitamin E, the
dose/effect ratio may vary between individuals. Furthermore, some animal studies demonstrating efficacy used very high doses that may be incompatible with human consumption.
It seems that fish oil is only mildly effective in acute inflammation. In those chronic inflammatory disorders where it was found to be effective, several weeks are
necessary to exhibit results. Yet, this mild anti-inflammatory effect, possibly through downregulation of pro-inflammatory cytokine production, leads to striking
therapeutic improvement in critically ill patients.Fish oil supplementation seems advantageous especially in acute and chronic disorders
where inappropriate activation of the immune system occurs. Fish oil has only a mild effect on active inflammation of diseases such as rheumatoid arthritis, SLE
and Crohn's disease, but it could prevent relapse (in some of the studies). In diseases where the inflammation is mild, such as IgA nephropathy, fish oil may slow or even prevent
disease progression. The above could explain the observation in some populations of a decreased incidence of inflammatory and autoimmune diseases , since the constant
consumption of n-3 fatty acids could suppress any autoreactive (or hyper-reactive) T cells. However, if there is already an existing disease, increased consumption might not be
beneficial over a long period. Therefore, the use of n-3 fatty acids can be recommended to the general healthy population, not only to
prevent atherosclerosis but possibly also to reduce the risk of autoimmunity.
Essential fatty acids in health and chronic disease.
Simopoulos AP: Center for Genetics, Nutrition and Health, Washington, DC
Am J Clin Nutr 1999 Sep 70:560S-569S
Human beings evolved consuming a diet that contained about equal amounts
of n-3 and n-6 essential fatty acids. Over the past 100-150 y there has been an enormous increase in the consumption of n-6 fatty acids due to the increased intake of
vegetable oils from corn, sunflower seeds, safflower seeds, cottonseed, and soybeans. Today, in Western diets, the ratio of n-6 to n-3 fatty acids ranges from
approximately 20-30:1 instead of the traditional range of 1-2:1. Studies indicate that a high intake of n-6 fatty acids shifts the physiologic state to one that is
prothrombotic and proaggregatory, characterized by increases in blood viscosity, vasospasm, and vasoconstriction and decreases in bleeding time. n-3 Fatty acids, however, have
antiinflammatory, antithrombotic, antiarrhythmic, hypolipidemic, and vasodilatory properties. These beneficial effects of n-3 fatty acids have been shown in the secondary
prevention of coronary heart disease, hypertension, type 2 diabetes, and, in some patients with renal disease, rheumatoid arthritis, ulcerative colitis, Crohn disease, and chronic
obstructive pulmonary disease. Most of the studies were carried out with fish oils [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)]. However, alpha-linolenic acid,
found in green leafy vegetables, flaxseed, rapeseed, and walnuts, desaturates and elongates in the human body to EPA and DHA and by itself may have beneficial effects in health
and in the control of chronic diseases.