Possible Implications Of Observations In Rat In Human Behavior

Rudin (1981) described a causal relationship between ALA deficiency and neurotic disorders in humans. Psychoses and neuroses of some pellagra cases unresponsive to multivitamin therapy have been treated effectively with linseed oil enriched with ALA. In 1982, Holman described numbness, paraesthesia, weakness, inability to walk, pain in the legs, and blurring of vision in a 6-yr-old girl under total parenteral nutrition taking safflower oil as the source of essential fatty acid. When the regimen was changed to an emulsion containing ALA, the neurological symptoms disappeared, and the amount of ALA required was estimated to be 0.54 en%.

In schizophrenia, the severity was reported to be less in patients taking more n-3 fatty acids, and supplementation of fish oil was effective in improving the symptoms (Peet, 1995, 1996). It was reported that the levels of polyunsaturated fatty acids such as LA (n-6), ARA (n-6) and DHA (n-3) are lower in plasma and red cell lipids in schizophrenic patients (Yao, 1994; Kaiya, 1991; Mahadik, 1996), suggesting enhanced oxidative injury, although their causal relationship has yet to be elucidated. In depression, the ARA/EPA ratio in blood showed positive correlation with clinical symptoms of depression (Adams, 1996; Maes, 1996). Hibbeln (1995a, 1995b) pointed out that DHA plays a role in mental function and depression, revealing a highly negative correlation between average fish intake and incidence of depression among countries. Based on these observations, some clinical trials have been started, aiming at suppressing the symptoms of depression. Recently, Hamazaki (1996) reported the results of a double-blind test in medical students that "aggressiveness against others" was suppressed by supplementing DHA ethyl ester. This study also revealed that the medical students used to take a much lower amount of DHA (0.2 g/d) than the average Japanese.

In classical lipid nutrition for the prevention of atherosclerosis and related diseases, hypercholesterolemia and animal fat were considered to be the major risk factors and high-LA vegetable oils were recommended. Although this recommendation was found to be ineffective (Multiple Risk Factor Intervention Trial Research Group, 1982) and even to be risky for atherosclerosis-related diseases, an increase in the incidence of violent death was observed to be associated with it (Strandberg, 1991; Muldoon, 1990 ). The plasma cholesterol level does not decrease significantly after prolonged dietary recommendations to raise the vegetable oil/animal fat ratio (or P/S ratio) of food; the hypocholesterolemic effect of dietary LA was found to be only transient (Okuyama, 1997, 2000). Therefore, it is not cholesterol that is associated with the increase in the incidence of violent death; rather, the increased intake of LA and the elevated n-6/n-3 ratio are likely to be the cause, in view of the results of animal experiments described earlier. Similarly, those who have experienced a heart attack have been noted to have a characteristic behavioral pattern called the Type A behavior pattern (TABP), and the causal relationship between heart attack and TABP has been studied by a group of scientists. Again, "increased intake of LA and elevated n-6/n-3 ratio," but not hypercholesterolemia, are probably the major risk factors for both heart attack and TABP (Okuyama, 1997, 2000).

Attention-deficit hyperactive disorder (ADHD) is known to be typical among atopic patients (Stevens, 1995, 1996). Atopic dermatitis is treated effectively with steroidal anti-inflammatory drugs and other antiallergic drugs that exert their effects mainly by inhibiting the cascade of LA ^ ARA ^ lipid mediators of allergic, inflammatory reactions ^ receptors (LA cascade). Clinically, decreasing the intake of LA and increasing the intake of n-3 fatty acids that are competitive effectors of the LA cascade and partial agonists for the lipid mediator receptors were shown to be effective for the prevention of atopic dermatitis (Kato, 2000) and other allergic hyperreactivities (Ashida, 1997). In rodents suffering from n-3 fatty acid deficiency, the observed decrease in the feedback suppression of negative responses in the brightness-discrimination learning test (Fig. 3) and the increase in anxiety in the elevated plus-maze test (Nakashima, 1993) appear to have characteristics common to ADHD in atopic children. Here, again, we would like to emphasize that both allergic hyperreactivities and behavioral anomalies such as ADHD as well as some pathological states of the brain (Yoshida, 1998) could be the result of an enhancement of the LA cascade (ie., the result of the increase in the intake of LA and the elevated n-6/n-3 ratio of dietary fat and oils.

Along with the Westernization of the dietary habits in Japan and possibly among urban dwellers in developing countries, the disease pattern has also been Westernized: an increase in the incidence of cancers of Western type, thrombotic diseases, and other inflammatory diseases. It is also a serious concern for the Japanese that changes in behavioral patterns may be occurring among young Japanese, following those of younger populations in Western industrialized countries. These changes in disease pattern and behavioral pattern could well be the result of the enhancement of the LA cascade resulting from the increase in the intake of LA and the elevated n-6/n-3 ratio of tissue phospholipids.

Simply applying the results shown in Table 2 to humans, 1.6 en% DHA in the Saf-DHA diet is not the amount easily ingested by people in industrialized countries; even the average Japanese takes less than 1 en% as EPA+DHA. Thus, it is important to reduce the intake of competing n-6 fatty acids, essentially LA that is present in most vegetable oil and oil products, and increase the intake of n-3 fatty acids such as ALA, EPA, and DHA present in seafood and vegetables. The essential amount of LA in humans is roughly 1 en%, but average people in industrialized countries are ingesting more than 6 en% LA.

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