White adipose tissue configures body fat, while brown adipose tissue (brown fat: BAT) is the only cell in the human body engaged in specialized in heat production. Loss and depression of BAT, which actively consume fat (triacylglyceride), have been shown to cause lifestyle-related diseases such as obesity and diabetes associated with it. Food and nutrition ingredients play a dominant role in BAT thermogenesis and energy metabolism. Especially, some ingredients activate BAT via the transient receptor potential-sympathetic nervous system. These results are expected to apply on anti-obesity treatment. This article reviews the major advances in the field of diet-induced thermogenesis and food ingredients.
In this review, we described two clinical trials that verified new nutritional functions of n-3 fatty acids in the ophthalmologic field. Firstly, we evaluated the efficacy of fish oil supplementation for subjects with dry eye in a randomized controlled trial. Fish oil group subjects (n = 15) ingested fish oil capsules containing eicosapentaenoic acid (EPA, 1245 mg/day) and docosahexaenoic acid (DHA, 540 mg/day) for 12 weeks. Placebo group subjects (n = 12) ingested placebo capsules. The subjective symptoms of "eye pain", the index of tear stability, and the deficits of mucin layer in the fish oil group were significantly improved, compared to those of the placebo group. These results suggest that fish oil supplementation may be effective in the treatment of dry eye. Secondly, we examined the effects of dietary supplementation with a combination of fish oil, bilberry extract, and lutein on subjective symptoms of asthenopia in humans in a randomized controlled trial. Active group subjects (n = 11) ingested a supplement containing n-3 fatty acid-rich fish oil (DHA 783 mg/day, EPA 162 mg/day), bilberry extract (anthocyanidin 59 mg/day), and lutein (17.5 mg/day) for 4 weeks. Placebo group subjects (n = 9) ingested placebo capsules. Asthenopia symptoms such as "stiff shoulder, low back pain", "frustration", "dry-eye", and "stuffy head" and a score of mental fatigue were improved in the Active group. These results suggest that dietary supplementation with the combination of n-3 fatty acid-rich fish oil, bilberry extract, and lutein improves subjective symptoms of asthenopia and mental fatigue in humans.
Krill Oil (K-Oil), extracted from Antarctic krill (Euphausia Superba Dana), has a unique chemical composition. It is rich in n-3 highly unsaturated fatty acid (n-3HUFA) that combined with phospholipids, especially with phosphatidylcholine (PC), rather than fish oil that combined with triglyceride. As a new n-3HUFA source, K-Oil has been reported to have many effects on physiological function in recent studies. In this paper, the results of the functional research on K-Oil are introduced.
The structure of lipids deeply relates to its health function and metabolism. This type of study has been carried out using radio or stable isotope labeled lipids so far. Particularly, the method using deuterium (2H) labeled fatty acid and mass spectrometry developed by Emken et al. is excellent. However, the method cannot compare the migration and metabolism of labeled fatty acids, namely the front and back of fatty acid metabolism. In this paper, migration and metabolism of 2H and carbon thirteen (13C) labeled odd- and even-numbered fatty acids were examined using mice. The results revealed that the odd-numbered fatty acids were accumulated to the body fat. It was thought that low beta-oxidizability of odd-numbered fatty acid causes the result. The expired carbon dioxide (CO2) after administration of stable labeled fatty acid to mice was also examined using IR-MS. The carbon locating at carbonyl group in fatty acid firstly changed to CO2 and fatty acid labeled carbonyl with 13C forms 13CO2. IR-MS can quantify the amount of 13CO2 in expiration. The results also indicated low beta-oxidizability of odd-numbered fatty acid. The health functions of n-3 type fatty acids were compared among EPA (C20:5n-3), DPA (C22:5n-3), and DHA (C22:6n-3) to understand the relationship between the structure of fatty acid and health function. As the results, both numbers of double bonds and carbon numbers related to the health functions. Consequently, DPA expressed the medium health function among them in all the measurement parameters such as adiponectin, lipid profiles in blood and liver, etc.
Cancer is a major cause of mortality worldwide, and epidemiological studies have shown the influence of lifestyle -related factors, mainly nutritional factors, on its development. Compared with Western countries, Japan has had a low incidence of nutritionally related cancer, e.g., colon, breast, and prostate cancer, and a high incidence of gastric cancer. However, the dietary habits and lifestyle of Japanese have changed markedly, and the incidence of nutritionally related cancer is rapidly approaching that of Western countries. Among dietary factors, a high intake of fat is clearly associated with an increased risk of colon and breast cancer in epidemiological and experimental animal studies. Furthermore, the effects of the type of fatty acids have also been investigated in several rodent colon and breast cancer models. In general, linoleic acid enhances whereas n-3 fatty acids decrease chemical-induced colon and breast carcinogenesis. However, regarding the protective effects of n-3 polyunsaturated fatty acids on colon and breast cancer, evidence from human epidemiological studies is inconsistent. Null findings of epidemiological studies could result from several factors, and one of the important factors influencing the inconsistent results of epidemiological studies between dietary fatty acids and colon and breast cancer may be the length of follow-up. Some studies showed that a temporal change in fat intake coincided with the incidence of colon and breast cancer approximately 15 to 25 years later. It may be important to improve the Westernized dietary habits of young Japanese generations to protect against nutritionally related cancer.
Recently, numerous studies have shown a hypolipidemic effect of docosahexaenoic acid (DHA, C22:6n-3) and eicosapentaenoic acid (EPA, C20:5n-3), which are commonly described as omega-3 fatty acids; however, in most cases, DHA and EPA are ingested as capsules, pills, or health supplements with little chance of being prepared in tasty foods eaten on a daily basis. We planned to develop fish sausage, which is recognized as a healthy food that is high in protein and low in lipids, supplemented with DHA and EPA to allow the claim of lowering serum triglycerides for the prevention of lifestyle related diseases. Based on clinical data, the fish sausage (containing 850 mg DHA and 200 mg EPA) was validated as a food for a specific health use in 2005 by the Ministry of Health, Labour and Welfare, following further validation of 9 sausage series. The impact of this permission to label the DHA sausage had an influence not only in food markets but also in the medical industry. In postmenopausal women, hyperlipidemia conditions are generally partially managed, but rarely return to normal levels, even with hypolipidemic drugs. In a sample of postmenopausal women, dietary DHA and EPA supplementation was administered once a day for 1 month with continuing administration of statins. Lipid levels returned to normal levels, including lowering of remnant-like particle (RLP)-cholesterol as well as normalization of triglyceride levels.Concerning the effects in the central nervous system, DHA was studied mechanically in the enhancement of long-term potentiation (LTP) in vitro and was investigated in a rat model of Alzheimer's disease, but there have been few clinical trials to examine the effects of DHA in mild dementia in Japanese. A 2-year randomized, double-blind, placebo-controlled trial aimed at examining the effects of daily dietary DHA and EPA supplementation on cognitive function in healthy elderly Japanese. The Mini Mental State Examination (MMSE) sub item "Language: copying" and Frontal Assessment Battery (FAB) sub item "Conflicting instructions" scores were significantly greater in the treatment group. Long-term daily dietary DHA and EPA supplementation seems to have beneficial effects for age-related cognitive decline in otherwise healthy elderly Japanese with very mild dementia. We would like to develop a line of processed foods rich in DHA, which are effective for the maintenance of human health, particularly relating to the central nervous system and cardiovascular stability.
Much attention has recently been poured on the physiological role of lysoglycerophospholipids that are liberated together with free fatty acids from diradyl-phospholipids in biomembranes. Their metabolic abnormalities that contribute to the progression of life-style related diseases including atherosclerosis have been suggested. In the lumen of digestive tube, both dietary and endogenously secreted phospholipids decomposed to physiologically active lysophosphatidic acid that acts as a signaling molecule to protect the digestive mucosa from harmful stresses. In this review, recent studies on potential protective roles of lysophosphatidic acid on the pathogenesis of periodontitis and gastric ulcer have been presented. In addition, the nutritional value of dietary phospholipids has been re-evaluated from this novel viewpoint.
The theory that prenatal and infant undernutrition and fetal growth retardation can be risk factors for lifestyle diseases in adulthood.called the developmental origins of health and disease.has been accepted worldwide. Nutritional status during pregnancy has a profound effect on infants' health and disease later in life. Since the birth weight declines are notable in Japan recently, it is important to take in enough calories and nutrients for both fetuses and mothers. However, there is little evidence concerning lipid nutritional management during pregnancy that considers the infants' future health. Our studies on cholesterol and trans fatty acids have been conducted so far and the results suggested that maternal dietary fat intake influences the development of fetuses. There seems to be insufficient evidence to determine the quality and quantity of dietary fats in pregnancy. Further investigations are needed to define appropriate dietary fat intakes during pregnancy.
The risk chart of NIPPON DATA80 showing the absolute mortality from coronary heart disease (CHD) is the only chart of this type widely used in the medical field in Japan. In this chart, there are 240 frames for men with casual blood glucose of ≥200 mg/dL (the right side of the chart); these frames are separated according to smoking status, age, systolic blood pressure, and total cholesterol. The absolute CHD mortality during 10 years in these 240 frames ranges from <0.5% to ≥10% (more than 20 times difference). However, we estimated that there were only 5 CHD deaths at most in these 240 diabetic frames during the study period of NIPPON DATA80. The left (non-diabetic; another 240 frames) part of the chart was adopted for the Guidelines by Japan Atherosclerosis Society after excluding 60 frames for those in their 70s (180 frames as a whole), but those 180 frames were estimated to have only 35 CHD deaths despite the risk difference being more than 10. Furthermore, statistical values such as p value and confidence interval were not found either in the paper introducing the risk chart or in the referred paper for methodology. We, therefore, could not statistically estimate appropriateness of the risk chart. In conclusion, the NIPPON DATA80 risk chart for CHD mortality is not suitable for guidelines or education.
Previous cholesterol guidelines for the prevention of CHD were based on "the lower, the better" hypothesis, setting upper LDL-C limits and treating patients to maintain their cholesterol levels below the targets, as seen in the ATP 3 issued from the National Heart, Lung, and Blood Institute (NHLBI) and that issued from the Japan Atherosclerosis Society (JAS GL). We published a new cholesterol guideline for longevity (JSLN GL 2010), in which evidence was presented that a high cholesterol level is not a causative factor of CHD but is a predictor of longevity among general populations over 40-50 years of age. Recently, a long-waited revision of the ATP 3 was published from the NHLBI in conjunction with the American College of Cardiology and the American Heart Association (ACC/AHA GL 2013), in which "setting targets to treating patients with statins" and "the lower, the better hypothesis" were abandoned because of the lack of clinical evidence. However, both the JAS GL 2012 and ACC/AHA GL 2013 brought about estimated 10-year CHD (ASCVD) risk mainly based on NIPPON DATA 80 and NHLBI-supported studies, respectively, resulting in increased estimated number of subjects to be treated with statins. Here, we point out that the estimated 10-year risks are not usable because they are not evidence-based. Moreover, we summarize biochemical mechanisms underlying the statin actions to increase heart failure, diabetes mellitus and other diseases after long-term treatments. The cases for which statins, all mitochondrion-toxic, are applicable should be extremely restricted.