B vitamins vital before conception: study
to have fatter male offspring at greater risk of high blood
pressure, suggests new research with sheep.
The findings are important for species with two legs, since the pre- and post-natal development of sheep is approximately the same as humans, state the researchers in the prestigious journal Proceedings of the National Academy of Sciences. By depriving female sheep of vitamins B12, folate and the amino acid methionine, researchers from the University of Nottingham set about testing their hypothesis that this could lead to changes to DNA in the pre-ovulatory egg or the embryo before implantation in the uterus. The importance of B vitamins, particularly folate, in foetal development is well established. The new study expands our understanding of the potential of pre-conception diets to influence the health of offspring. "The data provide the first evidence that clinically relevant reductions in specific dietary inputs to the methionine/folate cycles during the periconceptional period can lead to widespread epigenetic alterations to DNA methylation in offspring, and modify adult health-related phenotypes," wrote lead author Kevin Sinclair. The authors explain that DNA methylation is key to the maintenance of gene silencing. The process relies on a dietary supply of methyl groups, as provided by B vitamins. Fifty female sheep were split into two groups, with half the sheep fed a balanced diet and the other half fed a diet produce vitamin B deficiencies for eight weeks before artificial insemination and six days after. Six days after insemination, Sinclair and co-workers transferred the vitamin-deficient sheep's embryos to sheep fed the balanced diet. While no effects of this intervention were the chances of conceiving or the birth weight of the offspring, they did see effects when the offspring reached adulthood, compared to offspring of mothers fed the balanced diet. "This modest early dietary intervention led to adult offspring that were both heavier and fatter, elicited altered immune responses to antigenic challenge, were insulin - resistant, and had elevated blood pressure - effects that were most obvious in males," wrote Sinclair. Indeed, the male offspring of B-deprived sheep were 25 per cent fatter than their controlled counterparts. In addition, an analysis of the DNA of the vitamin B-deprived offsprings showed gene irregularities, which were again more pronounced in males. Being the first study to report these observations, and being based in animals, further research is needed to explore the significance of B-vitamins in the diet before conception. Currently, supplementation with folate and folic acid - the synthetic, bioavailable form of folate - is recommended to all women of child-bearing age since most neural tube defects (NTDs), including spina bifida and anencephaly, occur within the first 22 to 28 days of pregnancy, when the mother-to-be is not aware she is even pregnant. Folic acid supplements after this time are too late to prevent neural tube defects and therefore fail to benefit women with unplanned pregnancies - more than half of all pregnancies in the US. This connection between folate deficiency in early pregnancy and an increased risk of NTDs led to the 1998 introduction of public health measures in the US and Canada, where all grain products are fortified with folic acid. While preliminary evidence indicates that the measure is having an effect with a reported 15 to 50 per cent reduction in NTD incidence, parallel measures in European countries, including the UK and Ireland, are still on the table. Earlier this year an epidemiological study report that high levels of vitamin B6 prior to falling pregnant may boost conception rates and reduce the odds of losing the baby during early pregnancy (American Journal of Epidemiology, Vol. 166, pp 304-312). Source: Proceedings of the National Academy of Sciences 4 December 2007, Volume 104, Number 49, Pages 19351-19356 "DNA methylation, insulin resistance, and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine status," Authors: Kevin D. Sinclair, C. Allegrucci, R. Singh, D.S. Gardner, S. Sebastian, J. Bispham, A. Thurston, J.F. Huntley, W.D. Rees, C.A. Maloney, R.G. Lea, J. Craigon, T.G. McEvoy, L.E. Young