Genetic polymorphisms and folate status.

Moderate hyperhomocysteinemia-induced low folate status is an independent risk factor for cardiovascular disease, dementia, and depression. Folate is an essential cofactor in the one-carbon metabolism pathway and is necessary in amino acid metabolism, purine and thymidylate synthesis, and DNA methylation. In the folate cycle and homocysteine metabolism, folate, vitamin B12, vitamin B6, and vitamin B2 are important cofactors. Many enzymes are involved in folate transport and uptake, the folate pathway, and homocysteine (Hcy) metabolism, and various polymorphisms have been documented in these enzymes. Serum folate and total Hcy (tHcy) levels are influenced by folate intake and genetic polymorphisms in 5,10-methylenetertahydrofolate reductase (MTHFR) such as C677T. The prevalence of the MTHFR 677TT genotype varies across ethnic groups and regions, with a frequency of approximately 15% in Japanese populations. Individuals with the TT genotype have significantly higher tHcy levels and lower folate levels in serum than those with the CT and TT genotypes. However, administration of folic acid has been shown to eliminate these differences. Moreover, data have suggested that interventions based on genotype may be effective for motivating individuals to change their lifestyle and improve their nutrition status. Accordingly, in this review, we discuss the effects of MTHFR C677T polymorphisms on serum tHcy and folate levels with folic acid intervention and evaluate approaches for overcoming folic acid deficiency and related symptoms.

Medical cost savings in Sakado City and worldwide achieved by preventing disease by folic acid fortification.

The introduction of mandatory fortification of grains with folate in 1998 in the United States resulted in 767 fewer spina bifida cases annually and a cost saving of $603 million per year. However, far more significant medical cost savings result from preventing common diseases, including myocardial infarction, stroke, dementia and osteoporosis. A cost-effectiveness analysis showed a gain of 266 649 quality-adjusted life-years and $3.6 billion saved annually, mainly due to the reduction of cardiac infarction. The recommended folate intake in Japan is 240 µg/day whereas it is 400 µg/day internationally. Our Sakado Folate Project targeted individuals with genetic polymorphism of methylenetetrahydrofolate reductase or with hyperhomocysteinemia. Using, for example, folate-fortified rice, resulted in an increase in serum folate and a decrease in serum homocysteine in the participants, and reduced medical costs were achieved by decreasing myocardial infarction, stroke, dementia and fracture. Due to the small population of Sakado City (approximately 101 000) and small number of births (693) in 2015, a decrease in spina bifida could not be confirmed but there was a significant decrease in the number of very low birthweight infants. The genome notification of subjects was effective in motivating intake of folate, but the increase in serum folate (from 17.4 to 22.5 nmol/L, 129%) was less than that observed following compulsory folic acid fortification of cereals in the USA (from 12.1 to 30.2 nmol/L, 149.6%). Mandatory folic acid fortification is cheap in decreasing medical costs and is thus recommended in Japan.

Influences of stearidonic acid-enriched soybean oil on the blood and organ biochemical parameters in rats.

In this study, we administered various diets of stearidonic acid (SDA, 18:4n-3) soybean oil to rats and examined the subsequent blood and organ biochemical parameters. Male Wistar rats (seven rats/group, six groups total) were fed diets supplemented with a test oil for 4 weeks. Diets containing test oils were: FFC diet (fish-oil-free control diet), C diet (control group, assuming a Japanese diet), SDA25 diet (25% 18:4n-3 soybean oil in the C diet), SDA50 (50% 18:4n-3 soybean oil in the C diet), ALA diet (34% flaxseed oil in the C diet), and EPA+DHA diet (34% fish oil in the C diet). The intake of 18:4n-3 showed increased relative efficiency of 20:5n-3 accretions in serum and liver triacylglycerol and significantly decreased the serum triacylglycerol level in rats. The results suggested that the consumption of 18:4n-3 soybean oil may modify the lipid and fatty acid profiles of body fats, even when EPA and DHA derived from fish is consumed.

A high accumulation of hair minerals in Mongolian people: 2(nd) report; influence of manganese, iron, lead, cadmium and aluminum to oxidative stress, Parkinsonism and arthritis.

UNLABELLED: It was previously reported that the hair of Mongolian people showed very high accumulation of manganese (Mn), which may increase oxidative stress. This study (2(nd) report), indicated that not only Mn but other minerals had also accumulated at high levels in hair. It describes the influence of these minerals on oxidative stress, Parkinson's disease-like symptom (Parkinsonism) and arthritis, these diseases being prevalent in Mongolia. METHODS: 299 subjects were enrolled (including 21; Parkinsonism and 25; arthritis) from Ulaanbaatar and 5 other areas in Mongolia. Oxidative stress was evaluated by measuring the level of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG). The minerals accumulated in scalp hair were measured by the inductively coupled plasma mass spectrometry method. As a control, 81 healthy Japanese subjects were enrolled. RESULTS: Mongolian subjects showed high accumulated levels of Mn, iron, lead, cadmium and aluminum accumulations in hair, as compared with Japanese subjects. These levels were correlated with urinary 8-OHdG levels. The subjects with Parkinsonism and arthritis demonstrated higher levels in these minerals than healthy subjects. CONCLUSION: High accumulations of these minerals may increase oxidative stress in Mongolian people, and induce Parkinsonism and arthritis through the high oxidative stress. The high accumulations of these minerals may be induced by eating large amounts of sheep meat. In addition, sandy wind pollution may also contribute to it.

Levels of plasma insulin, leptin and adiponectin, and activities of key enzymes in carbohydrate metabolism in skeletal muscle and liver in fasted ICR mice fed dietary n-3 polyunsaturated fatty acids.

The aim of this study was to clarify the mechanisms related to plasma glucose concentration in mice fed a diet rich in n-3 polyunsaturated fatty acids (n-3 PUFAs). Male Crlj:CD-1 (ICR) mice were fed experimental diets containing 6% lard (LD), 6% fish oil (FO) or 4.1% lard plus 1.5% docosahexaenoic acid ethyl ester and 0.4% eicosapentaenoic acid ethyl ester (DE) for 12 weeks. There were no marked differences in plasma glucose and insulin concentration changes on glucose tolerance test between the three dietary groups. At the end of the feeding trial, plasma glucose concentration was significantly lower in fasted mice in the FO group than in those in the LD group (P<.005). Plasma adiponectin concentration was significantly higher in the FO group than in the LD group (P<.05). Hexokinase, phosphofructokinase, glucose-6-phosphate dehydrogenase and glycerophosphate dehydrogenase activities in skeletal muscle tended to be lower in the FO group than in the LD group, while there were no differences in glucokinase and phosphofructokinase activities in liver between the three dietary groups. However, hepatic glycerophosphate dehydrogenase activity was 53-fold and 4.2-fold higher in the FO group than in the LD and DE groups, respectively (P<.0005 and P<.05, respectively). These results suggest that the reduction in plasma glucose concentration in mice fed n-3 PUFAs is mainly caused by acceleration of glucose uptake and glycerol synthesis in the liver rather than in the skeletal muscle.

Comparison of electrocardiogram findings and lifestyles between urbanized people and ger-living people in Ulaanbaatar, Mongolia.

In Ulaanbaatar, lifestyles differ between urbanized people (group A) and ger (tent)-living people (group B). Group A earn high annual incomes and live in houses or apartments. Group B (who had moved to Ulaanbaatar from nomadic areas) earn low incomes and live in narrow gers. In 2002, we investigated daily food intake, health status, and electrocardiogram (ECG) in these groups. In total, 256 subjects (group A, 142; group B, 114) were enrolled. Group A ate meat, vegetables, and fruits high enough by a Western style. Group B consumed meat but ate only small amounts of vegetables and fruits. They took a lot of fat, however, the serum lipid levels of them were not so high. The fat source as energy was plant oil for cooking rather than meat. Several abnormal ECG findings including left ventricular hypertrophy (LVH) were found in 32 (22.5%) of group A and 50 (43.9%) of group B (P < 0.001). LVH was also found more in group B than in group A. LVH in group A males was accompanied by high body weight (BW), hypertension, and high LDL-cholesterol, whereas LVH in group B males seemed to be related to an unbalanced diet, high salt intake, smoking, and some low socio-economic problems. In order to promote health condition, such risk factors should securely be eliminated from the lifestyles.

Gene-nutrient and gene-gene interactions of controlled folate intake by Japanese women.

Elevated serum total homocysteine (tHcy) levels are associated with increased risk for cardiovascular disease and dementia. The prevalence rates of homozygous mutants among Japanese women (n = 300) were 17.3%, 1.3%, 18.6%, and 5.3% for methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, reduced folate carrier (RFC-1) A80G, and methionine synthase (MS) A2756G, respectively. The tHcy value was significantly lower (p < 0.001) in young women with CC or CT of MTHFR than with TT (10.9+/-4.7 micromol/L) (n =250). Diversities of serum folate and tHcy in women with 23 combinations of different alleles at low folate intake converged to the highest (34.0+/-8.6 nmol/L) and lowest (7.6+/-1.5 micromol/L) levels, respectively, after folic acid (400 microg/day) supplementation. In the regression equation ( y= ax + b) of serum folate ( y nmol/L) plotted against mean folate intake ( x microg/day), the values of "a" were 0.032, 0.037, and 0.045 for individuals with CC, CT, and TT alleles, respectively, of MTHFR.