The Chemical Mysteries of Fatty Acids: From the Balance of Omega-3 and Omega-6 to the Powerful Antithrombotic Effect of EPA

Saturated fatty acids are those in which all the carbon atoms in a chain are saturated with hydrogen. Unsaturated fatty acids, on the other hand, have some adjacent carbon atoms bonded together by double bonds, thus not fully bonded to hydrogen atoms. This double bond bonding between carbon atoms is called double bond bonding or unsaturated bonding. Fatty acids with one unsaturated bond are called monounsaturated fatty acids, and those with two or more unsaturated bonds are called polyunsaturated fatty acids.

The human body can synthesize saturated fatty acids and monounsaturated fatty acids, but not polyunsaturated fatty acids. Polyunsaturated fatty acids must be obtained from food and are therefore called essential fatty acids. Essential fatty acids that humans must obtain from external sources are divided into two categories: ω-3 and ω-6. "ω" is the last letter of the Greek alphabet, thus meaning "terminal." ω-3 fatty acids are those with unsaturated bonds appearing at the third carbon atom from the end of the protein, while ω-6 fatty acids are those with unsaturated bonds appearing at the sixth carbon atom from the end of the protein.

In the human body, omega-3 unsaturated fatty acids can be converted into other omega-3 unsaturated fatty acids, but they cannot be converted into omega-6 unsaturated fatty acids. Similarly, omega-6 unsaturated fatty acids cannot be converted into omega-3 unsaturated fatty acids. In short, fatty acids comprise three series that cannot be interconverted. Among plant-based fats, there is one essential fatty acid that the human body cannot synthesize-linoleic acid (omega-6).

Linoleic acid is a very important nutrient that, in the human body, is converted into local hormones and prostaglandins (PGs) that maintain normal tissue and cell function through important fatty acids such as gamma-linolenic acid (GLA) and arachidonic acid (AA). However, sometimes linoleic acid cannot be successfully converted into gamma-linolenic acid. Infants, the elderly, and the infirm cannot synthesize gamma-linolenic acid adequately. Especially now, due to excessive intake of animal fats and excessive alcohol consumption, as well as deficiencies in minerals and vitamin B₆ from processed foods, and insulin deficiency due to diabetes, the number of people unable to synthesize gamma-linolenic acid adequately is increasing.

Therefore, it is necessary to supplement gamma-linolenic acid (GLA) directly from the outside. Currently, universities and some research institutions are paying close attention to this multifunctional GLA and are conducting research. Under natural conditions, GLA is only found in breast milk and evening primrose seed oil from certain limited regions (Japanese evening primrose seed oil does not contain GLA). The Chemical Technology Research Institute of the Ministry of International Trade and Industry (MITI) has developed a production technology for GLA using natural sugars such as glucose as the main raw material and through microbial fermentation.

Glucose is fed to a filamentous bacterium, which accumulates an oil containing gamma-linolenic acid within its cells. By squeezing out the cells and removing water and protein, the gamma-linolenic acid-containing oil is obtained. Idemitsu Petrochemicals has successfully mass-produced a 99% pure gamma-linolenic acid monoester using this technology. People who drink excessively, have unbalanced diets, or are physically weak are less able to synthesize prostaglandins effectively.

Furthermore, frequently consuming processed foods or foods with added preservatives, colorings, and other chemical additives can inhibit prostaglandin biosynthesis. For these individuals, regular supplementation with gamma-linolenic acid (GLA) is necessary. GLA has a significant therapeutic effect on atopic dermatitis. However, it's important to note that excessive intake of omega-6 fatty acids is harmful and must be balanced with omega-3 unsaturated fatty acids such as EPA. Recently, the number of people suffering from hypertension and arteriosclerosis has been increasing.

The top three causes of death in Japan are cancer, stroke, and heart disease. High blood pressure and arteriosclerosis are major contributing factors to these two diseases, after cancer. Therefore, preventing high blood pressure and arteriosclerosis is of great significance for maintaining and improving health. Recently, there has been attention regarding the excessive consumption of animal-based foods, leading to calls for "eating more plant-based foods." However, it's easy to understand that these two aspects are relative and should not be overcorrected.

It is incorrect to treat fish, an important food for the Japanese, in the same way as other animal-based foods. According to research from researchers worldwide, fish contains substances such as vitamin E, and its effectiveness in preventing high blood pressure and arteriosclerosis is superior to that of vegetable oils. Research has focused on the functional substance EPA (a omega-3 series unsaturated fatty acid). This research was initiated by a health survey of the Inuit people, whose main diet consists of fish and seals.

Dr. Dejaberg of Olboa Hospital in Denmark, during an epidemiological survey of Eskimos, discovered that Eskimos suffered from far fewer adult-onset diseases such as arteriosclerosis, cerebral thrombosis, and myocardial infarction than the local Danish population, whose diet is primarily meat-based. For example, myocardial infarction accounts for over 40% of deaths in Denmark, while among Eskimos, even focusing solely on those over 61 years of age, only 3.6% suffered from myocardial infarction.

Based on the results of their dietary studies, it was found that EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), contained in the oil of their staple food, fish, are effective substances in preventing myocardial infarction. A research team led by Professor Takashi Yoshida of the Second Department of Internal Medicine, Chiba University School of Medicine, conducted clinical and epidemiological studies on EPA. They selected 42 fishermen and 130 mountain farmers living along the coast of Chiba Prefecture, all aged 40 and including both men and women, and conducted a three-month follow-up survey on their dietary habits.

According to the survey results, fishermen consume an average of 2.5 times more fish, such as sardines, than farmers. Every 100 grams of fish contains approximately 1 gram of EPA. Fishermen consume 2.5 grams of EPA daily, while farmers consume only 0.9 grams, making the former 2.7 times the latter. In terms of the fatty acid composition (EPA and AA) in the blood, fishermen have 3.8%, while farmers have 2.3%, with fishermen having a higher proportion. Fishermen's platelet aggregation ability is one-third that of farmers, therefore their blood is less prone to clotting.

In the surveyed fishing villages, the mortality rate from myocardial infarction or cerebral thrombosis was approximately two-thirds of that in the rural areas surveyed. This survey was conducted over three years. In years with low fish catches, fishermen showed decreased EPA levels in their blood and increased platelet aggregation, suggesting a close relationship with fish consumption. Based on these epidemiological findings, the research team conducted various clinical trials using refined EPA extracted from sardine oil and presented the results at the Japanese Society for Arteriosclerosis.

Professor Takashi Yoshida's research team administered EPA orally to 172 men and women suffering from conditions such as myocardial infarction, arteriosclerosis, angina pectoris, diabetes, and hyperlipidemia, all of which are prone to causing thrombosis, for 16 consecutive weeks. Their results, taking 27 men who took 3 grams of EPA orally daily for four weeks as an example, showed that the ratio of EPA to AA in their blood approximately doubled. Further experiments confirmed a decrease in blood cholesterol and inhibition of platelet aggregation.

Professor Takashi Yoshida believes that "in platelets, arachidonic acid (AA) is converted into fatty acids, which can harden the coronary arteries that pump blood to the heart. Taking EPA can reduce AA in platelets, thus effectively preventing adult-onset diseases such as myocardial infarction and cerebral thrombosis." EPA and DHA in fish oil, like linoleic acid in vegetable oils, are unsaturated fatty acids that improve blood flow, but this effect of EPA and DHA is much stronger than that of linoleic acid.

Fish living in cold seawater do not have their blood clot even at very low temperatures, mainly due to substances like EPA. EPA has a strong anticoagulant effect. The main functions of EPA include: ① inhibiting blood clotting (preventing platelet aggregation and thrombus formation); ② lowering blood cholesterol levels (cholesterol adhering to blood vessels can lead to arteriosclerosis, while EPA can remove cholesterol from blood vessels, and its effect is stronger than oleic acid); ③ lowering triglycerides (triglycerides are also a cause of arteriosclerosis).

DHA also has the following effects: ① inhibiting blood clotting, but its effect is weaker than EPA; ② lowering blood cholesterol levels, its effect is stronger than EPA. The effects of DHA and EPA complement each other, and their combined effect far exceeds that of linoleic acid, especially in preventing arteriosclerosis, hypertension, and thrombosis, which is unparalleled by other health foods. Based on these facts, food manufacturers and food research institutes are actively dedicated to researching and developing EPA mass production technologies and striving to commercialize it.

Kazuyoshi Yazawa, a researcher at the Sagami Central Chemical Research Institute, was the first in the world to develop a highly efficient technology for culturing bacteria isolated from fish to produce EPA, and plans to commercialize it. Nippon Suisan, in collaboration with Mochida Pharmaceutical, established the world's first technology for applying EPA to pharmaceuticals, with approval expected in 1990. Furthermore, Nippon Suisan has developed EPA-enriched nutritional supplements, and functional foods such as hamburgers and condiments are being commercialized.