Arachidonic acid (20:4n-6, ARA), which is one of the n-6 essential fatty acids, has been accumulated about 10% of the total fatty acids in a rodent brain. We investigated the effects in the brain function after chronic supplementation of ARA. The chronic supplementation of ARA increased motor activity, and reduced the total time which is the time until taking the diet, in the radial maze test as the spatial cognitive function test, although ARA did not indicate severe toxicity. A decrease in brain function was also observed in the rota-rod test as the motor coordination test. In the fatty acid composition of brain, we detected the increase of the total n-6 fatty acids and the decrease of DHA as the n-3 fatty acid in the ARA supplementation group, but there were no differences in saturated and monounsaturated fatty acids. This change of the n-3 Def group was more remarkable than that of the n-3 Adq group. Therefore, the chronic supplementation of ARA should be careful because there is a risk of deterioration of brain function based on the enhancement in n-3 fatty acids deficiency.

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Statins have been recognized clinically to raise blood glucose and glycated protein (HbA1c) levels enhancing the development of insulin resistance. However, most clinicians appear to adopt the interpretation that the benefit (prevention of CHD) outweighs the risk (new-onset of diabetes mellitus). Consistently, "Japan Atherosclerosis Society Guidelines for the Prevention of Atherosclerotic Cardiovascular Diseases 2012" recommends diabetics to maintain LDL-C levels below 120 mg/dL; 40 mg/dL lower than the value for those without risky complications. This recommendation necessitates many diabetics to use statins. However, we pointed out that statins exhibited no significant benefit for the prevention of CHD in the trials performed by scientists independent of industries after 2004, when a new regulation on clinical trials took effect in EU (Cholesterol Guidelines for Longevity, 2010). Here, we reviewed clinical evidence that statins could induce diabetes mellitus, and biochemical evidence that statins are toxic to mitochondria; they suppress electron transport and ATP generation through decreased prenyl-intermediate levels. They also inhibit seleno-protein synthesis and dolichol-mediated glycation of insulin receptor leading to insulin resistance and cardiac failure, similarly to the case of Se-deficiency. These mechanisms of statin actions are consistent with clinically observed decreases in blood ketone body, mitochondrial dysfunctions and enhanced glucose intolerance. Based on these lines of evidence, we urgently propose that statins are contraindicant to diabetics and their prescription should be restricted to special cases* for which medical doctors rationally decide to be necessary.

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