Hyperhomocysteinaemia (HHcy) is associated with all-cause mortality in some disease states. However, the correlation between HHcy and the risk of mortality in the general population has rarely been researched. We aimed to evaluate the association between HHcy and all-cause and cause-specific mortality among adults in the USA. This study analysed data from the National Health and Nutrition Examination Survey database (1999–2002 survey cycle). A multivariable Cox regression model was built to evaluate the correlation between HHcy and all-cause and cause-specific mortality. Smooth curve fitting was used to analyse their dose-dependent relationship. A total of 8442 adults aged 18–70 years were included in this study. After a median follow-up period of 14·7 years, 1007 (11·9 %) deaths occurred including 197 CVD-related deaths, 255 cancer-related deaths and fifty-eight respiratory disease deaths. The participants with HHcy had a 93 % increased risk of all-cause mortality (hazard ratio (HR) 1·93; 95 % CI (1·48, 2·51)), 160 % increased risk of CVD mortality (HR 2·60; 95 % CI (1·52, 4·45)) and 82 % increased risk of cancer mortality (HR 1·82; 95 % CI (1·03, 3·21)) compared with those without HHcy. For unmeasured confounding, E-value analysis proved to be robust. In conclusion, HHcy was associated with high risk of all-cause and cause-specific (CVD, cancer) mortality among adults aged below 70 years.

No risk assessment tools for the efficacy of folic acid treatment for hyperhomocysteinaemia (HHcy) have been developed. We aimed to use two common genetic risk score (GRS) methods to construct prediction models for the efficacy of folic acid therapy on HHcy, and the best gene–environment prediction model was screened out. A prospective cohort study enrolling 638 HHcy patients was performed. We used a logistic regression model to estimate the associations of two GRS methods with the efficacy. Performances were compared using area under the receiver operating characteristic curve (AUC). The simple count genetic risk score (SC-GRS) and weighted genetic risk score (wGRS) were found to be independently associated with the efficacy of folic acid treatment for HHcy. Using the SC-GRS, per risk allele increased with a 1·46-fold increased failure risk (P < 0·001) after adjustment for traditional risk factors, including age, sex, BMI, smoking, alcohol consumption, history of diabetes, history of hypertension, history of hyperlipidaemia, history of stroke and history of CHD. When used the wGRS, the association was strengthened (OR = 2·08, P < 0·001). Addition of the SC-GRS and wGRS to the traditional risk model significantly improved the predictive ability by AUC (0·859). A precise gene–environment predictive model with good performance was developed for predicting the treatment failure rate of folic acid therapy for HHcy.

Studies on the nutritional status of vegetarians in Spain are lacking. Prevention of vitamin B12 deficiency is the main concern, as dietary sources are of animal origin. The present study aimed to evaluate vitamin B12 and folate status of Spanish vegetarians using classical markers and functional markers. Participants were adult and healthy lacto-ovo vegetarians (forty-nine subjects) and vegans (fifty-four subjects) who underwent blood analyses and completed a FFQ. Serum vitamin B12, homocysteine (Hcy), methylmalonic acid (MMA), erythrocyte folate and haematological parameters were determined. The effects of the type of plant-based diet, and the intake of supplements and foods were studied by a FFQ. Mean erythrocyte folate was 1704 (sd 609) nmol/l. Clinical or subclinical vitamin B12 deficiency was detected in 11 % of the subjects (MMA>271 nmol/l) and 33 % of the participants showed hyperhomocysteinaemia (Hcy>15 µmol/l). Regarding plant-based diet type, significantly higher Hcy was observed in lacto-ovo vegetarians compared with vegans (P = 0·019). Moreover, use of vitamin B12 supplements involved an improvement of vitamin B12 status but further increase in erythrocyte folate (P = 0·024). Consumption of yoghurts was weakly associated with serum vitamin B12 adequacy (P = 0·049) and that of eggs with lower Hcy (P = 0·030). In conclusion, Spanish vegetarians present high folate status but vitamin B12 subclinical deficiency was demonstrated using functional markers. The lack of influence of dietary sources on functional markers and the strong effect of vitamin B12 supplement intake emphasise the need of cobalamin supplementation in both lacto-ovo vegetarians and vegans.

The aim of this study is to analyse the efficacy rate of folate for the treatment of hyperhomocysteinaemia (HHcy) and to explore how folate metabolism-related gene polymorphisms change its efficacy. This study also explored the effects of gene–gene and gene–environment interactions on the efficacy of folate. A prospective cohort study enrolling HHcy patients was performed. The subjects were treated with oral folate (5 mg/d) for 90 d. We analysed the efficacy rate of folate for the treatment of HHcy by measuring homocysteine (Hcy) levels after treatment. Unconditioned logistic regression was conducted to analyse the association between SNP and the efficacy of folic acid therapy for HHcy. The efficacy rate of folate therapy for HHcy was 56·41 %. The MTHFR rs1801133 CT genotype, TT genotype and T allele; the MTHFR rs1801131 AC genotype, CC genotype and C allele; the MTRR rs1801394 GA genotype, GG genotype and G allele; and the MTRR rs162036 AG genotype and AG+GG genotypes were associated with the efficacy of folic acid therapy for HHcy (P<0·05). No association was seen between other SNP and the efficacy of folic acid. The optimal model of gene–gene interactions was a two-factor interaction model including rs1801133 and rs1801394. The optimal model of gene–environment interaction was a three-factor interaction model including history of hypertension, history of CHD and rs1801133. Folate supplementation can effectively decrease Hcy level. However, almost half of HHcy patients failed to reach the normal range. The efficacy of folate therapy may be genetically regulated.

There is increasing evidence documenting gene-by-environment (G × E) interactions for CVD related traits. However, the underlying mechanisms are still unclear. DNA methylation may represent one of such potential mechanisms. The objective of this review paper is to summarise the current evidence supporting the interplay among DNA methylation, genetic variants, and environmental factors, specifically (1) the association between SNP and DNA methylation; (2) the role that DNA methylation plays in G × E interactions. The current evidence supports the notion that genotype-dependent methylation may account, in part, for the mechanisms underlying observed G × E interactions in loci such as APOE, IL6 and ATP-binding cassette A1. However, these findings should be validated using intervention studies with high level of scientific evidence. The ultimate goal is to apply the knowledge and the technology generated by this research towards genetically based strategies for the development of personalised nutrition and medicine.

The aim of the present study was to investigate the prevalence of hyperhomocysteinaemia (HHCY; total plasma homocysteine (tHcy) concentration >15 μmol/l) and its major determinants in healthy Chinese northerners. A descriptive and cross-sectional study was conducted in Shaanxi Province, China. The study sample included 2645 participants (1042 men and 1603 women) aged >20 years. Demographic characteristics and lifestyle factors were assessed via questionnaire interviews and physical examination. Plasma levels of homocysteine and folate and methylenetetrahydrofolate reductase (MTHFR) gene polymorphism were determined according to standard methods. The prevalence of HHCY was 67·7 % (81·4 % in men and 58·8 % in women). The geometric mean of tHcy concentration was 19·1 μmol/l. The OR of HHCY were 0·44 (95 % CI 0·34, 0·57) for women v. men; 1·95 (95 % CI 1·41, 2·70), 1·41 (95 % CI 1·05, 1·88) and 0·76 (95 % CI 0·64, 0·89) for participants with smoking and alcohol drinking cessation and improved physical activity levels, respectively; 0·25 (95 % CI 0·17, 0·38), 0·33 (95 % CI 0·22, 0·49) and 0·56 (95 % CI 0·36, 0·88) for participants with an education level of elementary school, secondary school and university v. illiterate, respectively; 1·41 (95 % CI 1·13, 1·75) and 3·05 (95 % CI 2·35, 3·97) for participants with CT and TT v. CC genotype at MTHFR 677C → T polymorphism, respectively. These results demonstrate that the prevalence of HHCY is considerably high in Chinese northerners, especially in TT subjects, suggesting that implementation of tHcy-lowering strategies, such as lifestyle changes, is necessary.

There is strong evidence indicating that elevated plasma total homocysteine (tHcy) levels are a major independent biomarker and/or a contributor to chronic conditions, such as CVD. A deficiency of vitamin B12 can elevate homocysteine. Vegetarians are a group of the population who are potentially at greater risk of vitamin B12 deficiency than omnivores. This is the first systematic review and meta-analysis to appraise a range of studies that compared the homocysteine and vitamin B12 levels of vegetarians and omnivores. The search methods employed identified 443 entries, from which, by screening using set inclusion and exclusion criteria, six eligible cohort case studies and eleven cross-sectional studies from 1999 to 2010 were revealed, which compared concentrations of plasma tHcy and serum vitamin B12 of omnivores, lactovegetarians or lacto-ovovegetarians and vegans. Of the identified seventeen studies (3230 participants), only two studies reported that vegan concentrations of plasma tHcy and serum vitamin B12 did not differ from omnivores. The present study confirmed that an inverse relationship exists between plasma tHcy and serum vitamin B12, from which it can be concluded that the usual dietary source of vitamin B12 is animal products and those who choose to omit or restrict these products are destined to become vitamin B12 deficient. At present, the available supplement, which is usually used for fortification of food, is the unreliable cyanocobalamin. A well-designed study is needed to investigate a reliable and suitable supplement to normalise the elevated plasma tHcy of a high majority of vegetarians. This would fill the gaps in the present nutritional scientific knowledge.

The association of plasma phospholipid (PL) fatty acid composition with plasma homocysteine (Hcy) in Chinese vegetarians is not understood. The main aim of the present study was to investigate the plasma PL fatty acid status, and its association with plasma Hcy in Chinese vegetarians and omnivores. A total of 103 male vegetarians and 128 male omnivores were recruited in Linyin Temple, Hangzhou. Plasma Hcy and PL fatty acid concentrations were determined by standard methods. Compared with omnivores, plasma PL n-3 PUFA (P< 0·001), 22 : 6n-3 (P< 0·001), 22 : 5n-6 (P= 0·021), 22 : 2n-6 (P< 0·001) and SFA (P= 0·017) were significantly lower, while plasma PL n-6 PUFA (P= 0·007) and total PUFA (P< 0·001) were significantly higher in vegetarians. The prevalence of hyperhomocysteinaemia (HHcy) in vegetarians (26·47 %) was significantly higher than that in omnivores (13·28 %). In vegetarians, plasma PL 22 : 6n-3 (r − 0·257, P= 0·046) was significantly negatively associated with plasma Hcy. In omnivores, plasma PL 18 : 1n-7 (r 0·237, P= 0·030) was significantly positively associated with plasma Hcy. Plasma PL 22 : 6n-3 (r − 0·217, P= 0·048) was negatively associated with plasma Hcy in omnivores. Plasma PL SFA were positively associated with the prevalence of HHcy. It would seem appropriate for vegetarians to increase their dietary n-3 PUFA and decrease dietary SFA, and thus reduce the risk of HHcy.

We aimed to investigate the prevalence of hyperhomocysteinaemia (total plasma homocysteine (tHcy) ≥ 10 μmol/l) and its major determinants in rural Chinese hypertensive patients. A cross-sectional investigation was carried out in Lianyungang of Jiangsu province, China. This analysis included 13 946 hypertensive adults. The prevalence of hyperhomocysteinaemia was 51·6 % (42·7 % in women and 65·6 % in men). The OR of hyperhomocysteinaemia were 1·52 (95 % CI 1·39, 1·67) and 2·32 (95 % CI 2·07, 2·61) for participants aged 55–65 and 65–75 v. 45–55 years; 1·27 (95 % CI 1·18, 1·37) for participants with a BMI ≥ 25 v. < 25 kg/m2; 1·14 (95 % CI 1·06, 1·23) for participants with v. without antihypertensive treatment; 1·09 (95 % CI 1·00, 1·18) for residents inland v. coastal; 0·89 (95 % CI 0·82, 0·97) and 0·83 (95 % CI 0·74, 0·92) for participants with moderate and high v. low physical activity levels; 1·54 (95 % CI 1·41, 1·68) and 2·47 (95 % CI 2·17, 2·81) for participants with a glomerular filtration rate 60–90 and < 60 v. ≥ 90 ml/min per 1·73 m2; and 1·20 (95 % CI 1·07, 1·35) and 3·81 (95 % CI 3·33, 4·36) for participants with CT and TT v. CC genotype at methylenetetrahydrofolate reductase 677C>T polymorphism, respectively. Furthermore, higher tHcy concentrations were observed in smokers of both sexes (men: geometric mean 12·1 (interquartile range (IQR) 9·2–14·5) v. 11·9 (IQR 9·3–14·0) μmol/l, P= 0·005; women: geometric mean 10·3 (IQR 8·3–13·0) v. 9·6 (IQR 7·8–11·6) μmol/l, P= 0·010), and only in males with hypertension grade 3 (v. grade 1 or controlled blood pressure) (geometric mean 12·1 (IQR 9·2–14·4) v. 11·7 (IQR 9·2–14·0), P= 0·016) and in male non-drinkers (yes v. no) (geometric mean 12·3 (IQR 9·4–14·8) v. 11·7 (IQR 9·1–13·9), P= 0·014). In conclusion, there was a high prevalence of hyperhomocysteinaemia in Chinese hypertensive adults, particularly in the inlanders, who may benefit greatly from tHcy-lowering strategies, such as folic acid supplementation and lifestyle change.