Yazawa: The dietary life of Japanese people is very healthy, and that has been the case for well over 20 years. Why is that? Does fish have anything to do with it? These notions were the starting point of my research. I finally had the idea that EPA and DHA would be the reason. I am originally a researcher in microbiology, having an interest in ocean microbes, and have worked to discover its effective use and novel resources. It has been known that microalgae and seaweeds produce these substances. I envisaged that bacteria and marine bacteria, which are in the area of my research, might make these compounds, so I started this study 12 years ago.

I have so far succeeded in producing EPA from Escherichia coli (or E. coli) bacteria after cloning the gene for an enzyme that biosynthesizes EPA. If such a gene was also introduced into other microbes, or into plants, vegetables, fruits, or finally cereals, for production, I believe that it could lead to the development of a new food. People that do not take fish, or those who live in a region where there is no habit of eating fish, could take EPA by eating such vegetables and cereals. We may be able to expect the arrival of such a time.

――DHA has been added to many kinds of ordinary foods such as ham and beverages lately. It has been given attention, not only for use in food, since it is said it may improve dementia.

Yazawa: I have carried out studies on the physiological functions and pharmacological actions of EPA and DHA. I had noted that a lot of DHA was contained in the head regions of fish six years ago, and I reported this observation at an academic conference. Subsequently, I received inquiries from some pharmaceutical companies and health food manufacturers. What has happened since then is that recognition of the name 'DHA' has increased rapidly; health foods including this substance have come to be sold in the market; and now, it is even added to baby formulas.

These days, high purity DHA is available at low cost, with which many kinds of researches are conducted. In a joint study conducted by the Department of Psychiatry of Gunma University and second internal medicine of Chiba University, a capsule containing DHA with the purity of DHA increased by 50% was administered to dementia patients. As a result, improvement in dementia or slowing of the development of the illness was confirmed. Of course, there are no side effects.

――Please tell us what EPA and DHA are, and how they differ in terms of functions.

Yazawa: EPA has been studied for more than 20 years, and DHA came to be researched on about a decade later. It was already known that DHA works on the central nervous system. In the brain, the blood brain barrier does not allow EPA to go through, whereas DHA can pass through it. Actually, DHA is detected at a level of 20-25% in the fatty acid composition of the brain while EPA is hardly detectable. Moreover, DHA is present at a level of 60% in retinal cells in the optic nerves of the eye, while EPA can scarcely be found. So DHA is commonly seen in the nervous system.

DHA is an essential element, especially for the development of the brain and optic nerves of fetuses and breast-fed babies. Its deficiency causes various disorders, which has been known well. So it is necessary for pregnant mothers to take a lot of DHA through having powdered milk supplemented with the compound. As for cancer prevention, EPA works on this to a certain extent, but DHA suppresses precancerous conditions in a much clearer way than EPA, slowing the timing of the manifestation of cancers. Further, when a patient has cancer, as opposed to a precancerous condition, it is expected that DHA will help to restrain its development considerably. As a result of their relation with lipids, EPA lowers neutral fat by about 25% on average while it lessens cholesterol level by only a few percent. In contrast, DHA easily brings cholesterol down by 10%. However, it does not work much to reduce neutral fat. Hence, it is thought that these compounds have different actions respectively in bringing down the levels of neutral fat and cholesterol. It is claimed that EPA is converted into DHA in the body. So the actions of EPA might be the same as those of DHA in some cases. This subject is still at the research stage. These are the main differences between the substances known so far.

――It appears that DHA has more pharmacological actions than EPA. Could you explain this point more specifically?

Yazawa: There are two major pharmacological actions of DHA: One is a physicochemical action that comes from its structure; and, the other is a biochemical effect of inhibiting enzymes.

The physicochemical action is that DHA enters into phospholipid in cell membranes so as to raise the fluidity of the membrane. As a result, cells of vessel walls get softer, controlling the elevation of blood pressure; the substance enters into the membranes of erythrocytes, enhancing deformability of red blood cells and preventing formation of blood clots; the blood circulation is also improved, which increases oxygen delivery. In addition, when DHA enters into the phospholipid membranes of synapses in brain cells, the synthesis of acetylcholine is increased there, or the activity of acetylcholine receptors are enhanced, improving the apparent activity of the receptors although there is no change in their numbers. It is thought that DHA works by improving the physicochemical properties of cell membranes.

There are LDL cholesterol receptors in the liver that have functions such as metabolizing 'bad' cholesterol in blood, taking the cholesterol into hepatocytes, converting it into bile acid so as to eliminate it through the gall bladder, and finally excreting it in the feces. DHA does not change the number of receptors for LDL, but there is a report that it apparently activates the receptors by 25%. Regarding the mechanism of reducing the level of cholesterol, it is thought that this has something to do with DHA's physicochemical properties, in particular that it is absorbed into cell membrane phospholipid.

It is also believed that there would be another activity relating to prevention of atopic disease, anti-inflammatory action and cancer prevention. This mechanism includes suppression of cyclooxygenase or lipoxygenase in general, and action in inhibiting enzymes such as cellular phospholipase A2, which is a biochemical action. So it is already thought to a certain extent that there would be such a mechanism as suppression of inflammation and cancer through enzyme inhibition, similar to that of non-steroidal anti-inflammatory drugs.

――Please tell us the effect which we can expect most through taking DHA.

Yazawa: Most of the clinical data describes effects relevant to diseases of the central nervous system, such as improvement in treating senile dementia and delaying its development. The next largest volume of published data is on cancer prevention. Its effect against cancer is clear through animal experiments. I believe that clinical trials in man will start soon. To ascertain the effect of cancer prevention, such clinical trials would take a long time, but an epidemiological survey surely indicates a potential as such. The one that comes in third place is anti-inflammatory action. The mechanism is nearly the same as that of cancer prevention. In any case, its action to suppress a group of inflammatory diseases including allergy has become much clearer than before. So the appearance of an anti-inflammatory agent with mild efficacy and without side effects can also be expected. These are the three effects for which we can have particular expectations. If there is something more to add, lowering cholesterol and blood pressure can also be expected through activating blood circulation and respective receptors.

――What is the recommended intake level of DHA?

Yazawa: If a patient wants to improve an illness after it progressed, it is suggested to take around 2g a day. If one does not feel well, the recommended amount is 1g a day. For maintaining good daily health, the dose suggested is 0.5g a day. The frequency of fish intake per week by typical Japanese living in urban areas would be about 5 or 6 times in 21 meals. On this basis, DHA intake would be approximately 400mg. If 500mg of DHA is taken additionally, it makes almost 1g. From the standpoint of maintaining health, the objective could be achieved to a certain extent with this dose. From an epidemiological viewpoint, Japanese people used to take far more DHA than 2g per day as they used to eat much more fish than now. Thanks to that habit, the facts are that the number of individuals with senile dementia was very small; that those with cancer was also small; and, that those with hay fever was insignificant. So it is expected that DHA will contribute a lot to society from the point of view of preventive medicine, in an age when the number of senior citizens will increase in the future.

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