Folate Associated with Chromosomal Abnormalities in Men's Sperm

24/03/08 Researchers have found an association between a vitamin found in leafy green vegetables, fruit and pulses and levels of chromosomal abnormalities in men's sperm. Men who consumed high levels of folate (a water-soluble B vitamin that occurs naturally in food) and folic acid (the synthetic form of the vitamin) tended to have lower levels of abnormal sperm where a chromosome had been lost or gained (known as aneuploidy).

Writing in Europe's leading reproductive medicine journal, Human Reproduction Thursday 20 March, the authors say estimates suggest that between 1-4% of sperm in a healthy man have some type of aneuploidy, but there are large variations among individuals, the mechanisms are poorly understood and little is known about the effects of men's diet on their sperm. In the first study of its kind to investigate the relationship between sperm aneuploidy and paternal diet, they analysed sperm samples from 89 healthy, non-smoking men and questioned them about their daily total intake (from diet and from vitamin supplements) of zinc, folate, vitamin C, vitamin E and beta-carotene.

One of the principal investigators of the study, Brenda Eskenazi, Professor of Maternal and Child Health and Epidemiology and Director of the Center for Children's Environmental Health at the School of Public Health, University of California, Berkeley, USA, said: "We found a statistically significant association between high folate intake and lower sperm aneuploidy: there was increasing benefit with increasing intake, and men in the upper 25th percentile who had the highest intake of folate between 722-1150 micrograms, had 20-30% lower frequencies of several types of aneuploidy compared with men with a lower intake.

"However, this study cannot prove that high folate intake caused the lower sperm aneuploidy levels, only that there is an association. This is the first study of its kind and the results indicate the need for further research, especially a randomised controlled trial, on this topic."

The researchers found no consistent associations between intakes of zinc and the other vitamins and sperm aneuploidy.

Prof Eskenazi said: "While the importance of maternal diet on reproduction, especially folate intake, is well known, the results of our study suggest the importance of studying paternal nutrition when considering male-mediated developmental consequences. In previous studies, we and others have shown that paternal micronutrient intake may contribute to successful conceptions by improving the quality of the sperm. This study is the first to suggest that paternal diet may play a role after conception in the development of healthy offspring."

The current recommended daily intake (RDA) for men aged over 19 is 400 micrograms, and the authors say that if other studies confirm their findings of the link between folate intake and aneuploidy, then a possible intervention would be to increase the RDA for men considering becoming fathers for at least three months before trying to conceive in order to reduce the risk of chromosomal abnormalities in their children.

Ms Suzanne Young, a researcher in Prof Eskenazi's group and the study co-ordinator, said: "Increasing folate intake can be as simple as taking a vitamin supplement with at least 400 micrograms of folate or eating breakfast cereal fortified with 100% of the RDA for folic acid. In addition, green leafy vegetables, such as spinach, can have up to 100 micrograms of folate per serving."

Disentangling the effects of folate from other micronutrients (e.g. the other vitamins) can be difficult, but the authors think they have succeeded in doing this by looking at several different nutrients in statistical analyses. Ms Young said: "The results of the different analyses were different, which gave us some confidence that we could look at the effect of these micronutrients separately. The definitive way to answer this question would be with a randomised control trial with folate supplementation."