Existing data on folate status and hepatocellular carcinoma (HCC) prognosis are scarce. We prospectively examined whether serum folate concentrations at diagnosis were associated with liver cancer-specific survival (LCSS) and overall survival (OS) among 982 patients with newly diagnosed, previously untreated HCC, who were enrolled in the Guangdong Liver Cancer Cohort (GLCC) study between September 2013 and February 2017. Serum folate concentrations were measured using chemiluminescent microparticle immunoassay. Cox proportional hazards models were performed to estimate hazard ratios (HR) and 95 % CI by sex-specific quartile of serum folate. Compared with patients in the third quartile of serum folate, patients in the lowest quartile had significantly inferior LCSS (HR = 1·48; 95 % CI 1·05, 2·09) and OS (HR = 1·43; 95 % CI 1·03, 1·99) after adjustment for non-clinical and clinical prognostic factors. The associations were not significantly modified by sex, age at diagnosis, alcohol drinking status and Barcelona Clinic Liver Cancer (BCLC) stage. However, there were statistically significant interactions on both multiplicative and additive scale between serum folate and C-reactive protein (CRP) levels or smoking status and the associations of lower serum folate with worse LCSS and OS were only evident among patients with CRP > 3·0 mg/l or current smokers. An inverse association with LCSS were also observed among patients with liver damage score ≥3. These results suggest that lower serum folate concentrations at diagnosis are independently associated with worse HCC survival, most prominently among patients with systemic inflammation and current smokers. A future trial of folate supplementation seems to be promising in HCC patients with lower folate status.

Several studies have described a positive association between elevated BMI and birth defects risk. Data on plasma concentration of folate in pregnant women with obesity have shown values far below those recommended, regardless of diet, while folate levels should increase before pregnancy to reduce neural tube defects. We report a descriptive review of the most recent studies (from 2005 to 2015) to evaluate folate status through a population of women of childbearing age affected by obesity. The literature contains few studies, which present conflicting results regarding folate status in non-pregnant women of childbearing age affected by obesity, and it appears that there is a modification in folate metabolism, with a reduction in plasma folate levels and an increase in erythrocyte folate uptake. In conclusion, the folate status in women of childbearing age should be assessed by both plasma and erythrocyte levels to start a personalised and more adequate supplementation before conception. Further studies need to be conducted in a larger population, which take into account variables that can affect folate metabolism, such as dietary intake, lifestyle and genetic factors, oral contraceptives or other drug use, previous weight-loss programmes, or a history of bariatric surgery.

The International Clearinghouse for Birth Defects, Surveillance and Research reports a rise in the prevalence rate of spina bifida in Japan. We determined first-trimester folate status of Hokkaido women and identified potential predictors. Participants were 15 266 pregnant women of the Hokkaido Study on Environment and Children’s Health Cohort. Data were extracted from self-reported questionnaires and biochemical assay results. Demographic determinants of low folate status were younger maternal age (adjusted OR (AOR) 1·48; 95 % CI 1·32, 1·66), lower educational level (AOR 1·27; 95 % CI 1·17, 1·39) and lower annual income (AOR 1·11; 95 % CI 1·01, 1·22). Plasma cotinine concentrations of 1·19–65·21 nmol/l increased the risk of low folate status (AOR 1·20; 95 % CI 1·10, 1·31) and concentrations >65·21 nmol/l further increased the risk (AOR 1·91; 95 % CI 1·70, 2·14). The most favourable predictor was use of folic acid (FA) supplements (AOR 0·19; 95 % CI 0·17, 0·22). Certain socio-demographic factors influence folate status among pregnant Japanese women. Modifiable negative and positive predictors were active and passive tobacco smoking and use of FA supplements. Avoiding both active and passive tobacco smoking and using FA supplements could improve the folate status of Japanese women.

Fortification of select grain products with folic acid and periconceptional supplementation recommendations in Canada and the USA have improved folate status, and have been associated with a reduced risk of neural tube defects. In the present study, we aimed to conduct a comparison of erythrocyte folate concentrations from the 2007–9 Canadian Health Measures Survey (CHMS) and the 2007–8 US National Health and Nutrition Examination Survey (NHANES). Erythrocyte folate concentration was assessed in participants aged 6–79 years (CHMS, n 5248; NHANES, n 7070). To account for different folate assays employed – Immulite 2000 immunoassay (CHMS) and microbiological assay (NHANES) – a conversion equation was generated (n 152 adults) to adjust the CHMS data. t Tests were used to examine country differences. Median Canadian erythrocyte folate concentrations (method-adjusted) were lower than those of Americans (988 and 1100 nmol/l, respectively), but unadjusted median Canadian erythrocyte folate concentrations were higher (1250 nmol/l). The upper 95 % CI boundary of the method-adjusted Canadian erythrocyte folate distribution overlapped that of the American erythrocyte folate concentrations, while the lower 95 % CI boundary of the method-adjusted Canadian erythrocyte folate data was below the American distribution. In summary, the fact that erythrocyte folate concentrations were either higher or lower in Canadians compared with Americans, depending on whether an adjustment was made to account for assay differences, suggests that caution must be exercised in evaluating erythrocyte folate data from different countries because analytical methods are not readily comparable. Furthermore, we cannot unequivocally conclude that there are true differences in erythrocyte folate concentrations between the Canadian and American populations in the post-fortification era.

Previous studies with folate/methyl-deficient rat models proposed the role of folate deficiency in hepatocarcinogenesis and tumour progression. We investigated the relationship between folate status and tumour progression in patients with hepatocellular carcinoma (HCC). Ninety HCC patients (age 62 (sd 10) years) recruited through the Department of Internal Medicine, Chi-Mei Hospital, participated in this cross-sectional study. According to the clinical criteria, 44 % showed marginal folate deficiency (serum folate 7–14 nmol/l; folate intake 278 (sd 212) μg/d), and 16 % were folate deficient ( < 7 nmol/l; 207 (sd 113) μg/d). Serum folate showed inverse correlations with three elements of tumour progression: tumour size (r − 0·29; P = 0·005), tumour multiplicity (r − 0·24; P = 0·018) and metastasis (r − 0·39; P = 0·0001). When HCC progression was categorised into stages I to IV, serum folate decreased as HCC stage progressed (stage I, 24·5 (sd 11·5); stage IV, 10·3 (sd 3·3) nmol/l; P = 0·032). After adjustment for age, sex, lifestyle and dietary factors, patients with low blood folate status (serum folate < 14 nmol/l) had increased risks for advanced tumour progression in large tumours (OR 7·1 (95 % CI 2·27, 21·9); P = 0·0007), tumour multiplicity (OR 3·2 (95 % CI 1·07, 3·51); P = 0·004) and metastasis (OR 4·5 (95 % CI 1·11, 18·4); P = 0·03) relative to those with normal folate status. Further controlling for liver injury, tumour proliferation and tumour stage, however, negated the effect of folate on advanced tumour progression. The data thus suggest that low blood folate status could be a risk factor for tumour progression, which is modulated by clinical lesions present in HCC patients. Future studies with larger sample sizes are warranted to explore the joint effects of low folate and hepatic lesions in human HCC malignancy.