Methylmercury (MeHg) and persistent organic pollutants (POPs), such as dioxins and polychlorinated biphenyl (PCB), are bioaccumulative chemicals that are considered to be toxic contaminants. Recent studies raise health concern for the toxic effects of combined exposure to these chemicals on child development. These environmental contaminants are found in fish and seafood. On the other hand, fish consumption is largely recognized as beneficial for brain development of children during the gestation period and early infancy. Long-chain omega-3 polyunsaturated fatty acids (omega-3 PUFA) are believed to be responsible for these beneficial effects. In this context, the balance of toxicological and nutritional aspects of fish consumption is highlighted. The aim of this article is to review the negative health effects of the exposures to MeHg, PCB, and dioxins. Current epidemiological evidence, including the three studies performed in Japan, suggests that perinatal exposure to the chemicals can adversely influence child development. This article also reviews the advisories issued by the Japanese governmental agencies. Although several environmental chemicals are demonstrated to be toxic even at the levels observed in Japanese pregnant women, exposure standards are still under active debate. Furthermore, because of lack of epidemiological evidence on the beneficial effects of omega-3 PUFA on child development, the recommendation on fish consumption remains largely undetermined.
PC-DHA, docosahexaenoic (DHA) acid conjugated phosphatidylcholine, has two functional structures in one molecule. One is DHA and another is choline. PC-DHA is a practical transporter of DHA and choline. As lysophospholipids can pass through blood-brain barrier, it is suggested that PC-DHA transports DHA and choline to the brain. Thus, it is assumed that this transportation influences cognition, sleep, lipid metabolism, and circadian rhythm. We report here in the influence of sleep and the metabolic syndrome with PC-DHA. It was found that %SREM, the relative amount of REM sleep in a given sleep period , increased significantly (25～35% from the baseline) over a 3-month administration period. This increase in %SREM disappeared during the washout session. These results suggest that PC-DHA increases REM sleep to an optimal amount, and may contribute to stabilizing sleep structure. In addition, PC-DHA can prevent or alleviate obesity-related disorders through the suppression of fatty acid synthesis, enhancement of fatty acid beta-oxidation, and increase in the serum adiponectin level in OLETF rats.
Arachidonic acid (ARA) is converted to eicosanoids with diverse physiological activities, which are essential for the maintenance of growth and reproductive physiology of mammals. However, excessive and unbalanced productions of eicosanoids from ARA are known to be causative of inflammation-related diseases including cancer, atherosclerotic diseases and allergic diseases, which are currently prevailing in the elderly in Japan. Omega 3 fatty acids can suppress excessive productions of eicosanoids from ARA, thereby serving to prevent these diseases. These interpretations are based on the results from nutritional, pharmacological and biotechnological studies performed worldwide. Therefore, it was a big surprise for us when a leading Japanese food company began to sell an ARA-containing supplement. With a Health and Labour Sciences Research Grant from the Ministry of Health, Labour and Welfare, Japan, members of the committee of Japan Society for Lipid Nutrition performed a series of research on the safety and efficacy of ARA containing microbial oil to find little evidence to support the health benefits. Moreover, teratogenicity in the eye of a mouse strain was noted at 0.6 energy % ARA, together with cancer promoting activities, which are crucial as a supplement for elderly people. These safety issues need to be solved before supplementing humans with the ARA oil.
Human type 1 diabetes is an autoimmune disease resulting from T-cell-mediated destruction of pancreatic islet beta cells. Maternal environment has been suggested to be important in the development of diabetes. In this study, to investigate the effect of maternal nutrition, in particular the essential fatty acid (EFA) ratio (n-6/n-3) and composition, on the development of type 1 diabetes in the offspring, we prepared different kinds of chows with different n-6/n-3 ratios, and provided them to pregnant and lactating mothers and post-weaning female offspring of non-obese diabetic (NOD) mice, a type 1 diabetes model. The EFA ratio in breast milk and serum of NOD dams became nearly the same as that of the maternal diet. Overt diabetes was not suppressed in the offspring from dams provided with a diet with an n-6/n-3 ratio of 14.5 during gestation and lactation, but it was strongly suppressed in those from dams provided with a diet with an n-6/n-3 ratio of 3.0 during the same period. At 2 and 4 weeks after birth, insulin autoantibodies (IAA) were detected in the offspring from dams provided with a diet with an n-6/n-3 ratio of 14.5, and not detected in those from dams provided with a diet with an n-6/n-3 ratio of 3.0. These findings suggest that n-6/n-3 ratio of the maternal diet during gestation and lactation rather than that of the diet intake by offspring after weaning strongly affects the development of overt diabetes in NOD mice.
Docosahexaenoic acid (DHA, 22:6 n-3) was characteristically the major fatty acid of all the major lipid classes of all organs of highly migratory fish species, such as Thunnus spp. The mean DHA content of the various organs accounted for more than 20% of the total fatty acids (TFA). These values differed markedly from the fatty acid profile of other fish species, because the fatty acid composition of other species is variable and the DHA content is less than 20% of TFA. In particular, the levels of DHA of the triacylglycerols (TAG) of all their organs comprised up to 20% of TFA, even though it is a neutral lipid. In contrast, the major fatty acids present in C. phaseoliformis lipids belong to the n-4 family non-methylene interrupted polyunsaturated fatty acids (NMI-PUFA): 20:3 n-4,7,15, 20:4 n-1,4,7,15, and 21:3 n-4,7,16, and two Bathymodiolus mussels contained high levels of methylene interrupted PUFA: 20:3 n-4,7,10, 20:4 n-1,4,7,10, and 21:3 n-4,7,10. Such special kinds of novel fatty acids are assimilated by symbiotic chemosynthetic bacteria, which use geothermal energy and minerals from the hydrothermal and cold-seep vents. Highly migratory fishes are a good dietary source of n-3 PUFA, such as DHA, and deep-sea bivalves have the possibility of synthesizing other physiologically active fatty acids. All marine animals might be good sources of such fatty acids as ingredients of functional foods.
In mammals, arachidonic acid (ARA) and docosahexaenoic acid (DHA) play important physiological roles as precursors of eicosanoids and docosanoids, respectively. However, a full scope of the function of these fatty acids is yet to be elucidated. A major obstacle is endogenous synthesis of ARA and DHA from precursors. It is not possible to create ARA deficiency by dietary manipulation without depleting linoleic acid, which is an essential component of skin ceramides. Also, DHA deficiency cannot be created without a compensatory increase in 22:5 n-6. To overcome these obstacles, mice lacking the Fads2 gene that encodes the first step of ARA and DHA synthesis were created. When Fads2-null mice were fed a diet lacking ARA and DHA but containing sufficient linoleic and alpha-linolenic acid, they exhibited previously undocumented phenotypes. The Fads2-null mice developed ulcerative dermatitis after 4 months of age, which was distinct from dry, scaly dermatitis observed in classic linoleic acid deficiency. Fads2-null males exhibited complete arrest of sperm development at the stage of acrosome biogenesis. Intestinal ulcer was observed at duodenum and the ileo-cecal junction. In liver, lipid droplets were primarily localized in a periportal area. Dietary ARA prevented dermatitis and intestinal ulcer, whereas dietary DHA was ineffective. The male fertility and sperm formation were fully recovered by dietary DHA, whereas ARA was only partially effective. Either ARA or DHA supplementation prevented fatty liver. Although some of these phenotypes are likely due to reduced eicosanoid formation, the exact mechanism is yet to be elucidated.
The n-3 fatty acids, especially, docosahexaenoic acid (DHA) cannot be synthesized in mammals, although there are nutritionally essential polyunsaturated fatty acids. Therefore, it is necessary to take some food containing DHA or its precursor. Many animal studies have reported that the dietary n-3 fatty acid deprivation produces a loss of brain function. Recently, several reports have been presented concerning various mental functions including mood disorders under the n-3 fatty acid deficiency. In this study, the focus is on the decrease of the emotional function under the n-3 fatty acid deficiency and the incorporation of DHA into the fetal brain in n-3 fatty acid deficiency pregnant mice. Using the novelty suppressed feeding paradigm, n-3 fatty acid deficient or adequate mice were measured for the anxiety level under two kinds of breeding conditions (group housed or isolation stress). The n-3 fatty acid deficient mice indicated an increase of anxiety and were enhanced anxiety level by the chronic mild stress of social isolation. On the other hand, the incorporation of DHA into the fetal brain in the n-3 fatty acid deficient pregnant mice after switching to the n-3 fatty acid adequate diet was measured. Alpha-linolenic acid in the n-3 fatty acid adequate diet was supplied into fetus by the mother via the placenta after being metabolized to DHA. A nutritional intervention with n-3 fatty acid adequate diet can nearly but incompletely rescue the mouse fetal DHA deficiency, if begun at the time of conception but that the third trimester is too late.
On September 8, 2012, the panel discussion “The Rethinking of Cholesterol Issues” was held in Sagamihara City, Japan. This paper is the summary of that panel discussion. Four discussants expressed their skeptical views against the cholesterol hypothesis. The whole discussion will be freely seen on the net. Also a similar editorial written by the four discussants will be published in English (Ann Nutr Metab 2013;62:32-36, a free PDF file is already available on the internet). Because Japan Atherosclerosis Society Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2012 (JASG 2012) has recently been published, the main part of this paper is focused on serious flaws found in JASG 2012. Dr Harumi Okuyama discusses the differences between JASG 2012 and our guidelines indicating that high cholesterol levels are a good index of longevity; the most important point is that the statin trials that have been performed after 2004, when the new EU law regulating clinical trials became in effect, are all negative. Dr Yoichi Ogushi claims that JASG 2012 intentionally omits some good aspects of cholesterol; cholesterol is a negative risk factor of stroke. His own data also show that cholesterol is good for stroke. He also claims that to properly treat patients with diabetes, we need to reject the cholesterol hypothesis and to reduce carbohydrate rather than cholesterol. Dr Tomohito Hamazaki points out unforgivable flaws in JASG 2012. It does not disclose any COI. It does not contain any relationship between cholesterol levels and all-cause mortality in Japan. Pharmaceutical companies spend 600 billion yen (7 billion US$) per year for advertisement in Japan. This works as “devil’s insurance” (withdrawal of advertisement is a real threat to the mass media). The last discussant, Dr Rokuro Hama, explains the mistake made by JAS (liver disease causes both death and depression of cholesterol levels, and low cholesterol levels are not the cause of death). Hepatitis C virus (HCV) enters hepatic cells via LDL receptors, and low cholesterol levels are one of the major risk factors of HCV infection and chronic hepatitis. Hence, death from liver disease could be the result of low cholesterol levels.