Exclusive breastfeeding during the 40-day rest period and at six months in Lebanon: a cross-sectional study.

BACKGROUND: Exclusive breastfeeding is recommended for the first 6 months of life with well-established benefits to the mother and child. The traditional practice of the 40-day rest period helps establish and maintain exclusive breastfeeding. This study aims to estimate the prevalence and examine the factors associated with exclusive breastfeeding at 40 days and at 6 months in Lebanon. METHODS: A cross-sectional survey was conducted in 2011-2012 as part of the "Early Life Nutrition and Health in Lebanon" study. A nationally representative sample of 1005 children aged five years or younger and their mothers was drawn from households using a stratified cluster sampling design. Trained nutritionists interviewed eligible mothers about sociodemographic characteristics of the household and maternal and child characteristics including infant feeding practices. Anthropometric measurements of the mother and child were collected. Multinomial logistic regression analysis was conducted to examine the characteristics associated with exclusive breastfeeding. RESULTS: The prevalence of exclusive breastfeeding was 41.5% at 40 days and 12.3% at 6 months. Children in families with three or more children had higher odds of exclusive breastfeeding for 40 days (Adjusted Odds Ratio [AOR] 1.76, 95% Confidence Interval [CI] 1.19, 2.60). Children in families owning two or more cars had lower odds of exclusive breastfeeding for 40 days (AOR 0.45, 95% CI 0.24, 0.83) and at 6 months (AOR 0.32, 95% CI 0.14, 0.77). Similarly, children delivered via Caesarian section had lower odds of exclusive breastfeeding for 40 days (AOR 0.49, 95% CI 0.34, 0.71) and at 6 months (AOR 0.39, 95% CI 0.24, 0.65). The odds of exclusive breastfeeding for 6 months were lower among children of overweight (AOR 0.50, 95% CI 0.26, 0.95) or obese (AOR 0.56, 95% CI 0.32, 0.98) mothers. CONCLUSIONS: The association between higher socio-economic status, as reflected by car ownership, and C-section delivery with lower odds of exclusive breastfeeding persisted across the first 6 months in Lebanon. Future research should investigate the factors associated with exclusive breastfeeding in prospective cohort studies and help to better understand the cultural practice of the 40-day rest period in relation to breastfeeding.

Genetic, epigenetic and genomic mechanisms of methionine dependency of cancer and tumor-initiating cells: What could we learn from folate and methionine cycles.

Methionine-dependency is a common feature of cancer cells, which cannot proliferate without constant inputs of exogenous methionine even in the presence of its precursor, homocysteine. The endogenous synthesis of methionine is catalyzed by methionine synthase, which transfers the methyl group of 5-methyltetrahydrofolate (5-methylTHF) to homocysteine in the presence of vitamin B12 (cobalamin, cbl). Diverse mechanisms can produce it, including somatic mutations, aberrant DNA methylation (epimutations) and altered expression of genes. Around twenty somatic mutations have been reported as a cause of methionine dependency. Some of them are contributors but not sufficient on their own to cause methionine dependency. Epigenetic invalidation of MMACHC gene expression triggers methionine dependency of the MeWo-LC1 melanoma cancer cell line. This epimutation is generated by aberrant antisense transcription of the adjacent gene PRDX1. Methionine dependency involves the abnormal expression of 1-CM genes in cancer stem cells. It is related to an increased demand for methionine and SAM, which is not compensated by the increased production of formate by glycine decarboxylase pathway in lung cancer tumor spheres. Tumor spheres of glioblastoma U251 are methionine-dependent through disruption of folate metabolism. The rescue of the growth of glioblastoma stem cells by folate shows the considerable importance to evaluate the influence of supplements and dietary intake of folate on the risk of tumor development, in particular in countries subjected to mandatory food fortification in folic acid. Dietary methionine restriction or the use of methioninase represent promising anticancer therapeutic strategies that deserve to be explored in combination with chemotherapy.

Folate can promote the methionine-dependent reprogramming of glioblastoma cells towards pluripotency.

Methionine dependency of tumor growth, although not well-understood, is detectable by 11C-methionine positron emission tomography and may contribute to the aggressivity of glioblastomas (GBM) and meningiomas. Cytosolic folate cycle is required for methionine synthesis. Its dysregulation may influence cell reprogramming towards pluripotency. We evaluated methionine-dependent growth of monolayer (ML) cells and stem cell-like tumor spheres (TS) derived from 4 GBM (U251, U87, LN299, T98G) and 1 meningioma (IOMM-LEE) cell lines. Our data showed that for all cell lines studied, exogenous methionine is required for TS formation but not for ML cells proliferation. Furthermore, for GBM cell lines, regardless of the addition of folate cycle substrates (folic acid and formate), the level of 3 folate isoforms, 5-methytetrahydrofolate, 5,10-methenyltetrahydrofolate, and 10-formyltetrahydrofolate, were all downregulated in TS relative to ML cells. Unlike GBM cell lines, in IOMM-LEE cells, 5-methyltetrahydrofolate was actually more elevated in TS than ML, and only 5,10-methenyltetrahydrofolate and 10-formyltetrahydrofolate were downregulated. The functional significance of this variation in folate cycle repression was revealed by the finding that Folic Acid and 5-methyltetrahydrofolate promote the growth of U251 TS but not IOMM-LEE TS. Transcriptome-wide sequencing of U251 cells revealed that DHFR, SHMT1, and MTHFD1 were downregulated in TS vs ML, in concordance with the low activity cytosolic folate cycle observed in U251 TS. In conclusion, we found that a repressed cytosolic folate cycle underlies the methionine dependency of GBM and meningioma cell lines and that 5-methyltetrahydrofolate is a key metabolic switch for glioblastoma TS formation. The finding that folic acid facilitates TS formation, although requiring further validation in diseased human tissues, incites to investigate whether excessive folate intake could promote cancer stem cells formation in GBM patients.