Wednesday December 11 2013
Folic acid is found in asparagus, brown rice and Brussels sprouts
“Dad's diet before conception plays crucial role in long-term health of offspring,” reports the Mail Online, recommending that prospective dads “stick to greens and avoid junk”. But while a healthy diet is never going to hurt, the study it is reporting on involved mice, not men.
The research in question indicated that feeding male mice a folate deficient diet caused harm to the health of their offspring. For example, there was a higher chance of them being born with birth defects. The deficient diet led to a pattern of chemical changes in the DNA of the father that was passed on to their offspring. This suggested a possible mechanism by which the harm was caused.
The study authors also suggested this may increase the risk of chronic conditions such as diabetes, autism, schizophrenia and cancer. However, this link was not certain or proven, and remains somewhat speculative. Whether similar effects would be seen in men is also not known.
Still the association, even if unproven, is plausible. Pregnant women are currently recommended to take folic acid supplements during the first 12 weeks of pregnancy as this can reduce the risk of birth defects in the child.
Although this was animal research, the results appear to be compatible with the general public health advice to follow a balanced and varied diet containing lots of different fruit and vegetables.
While such a diet may not guarantee any future children’s good health; it will certainly improve your own.
Where did the story come from?
The study was carried out by researchers from Canada and was funded by The Natural Sciences and Research Council of Canada, the Canadian Institute of Health Research, and Genome Quebec, a public-private sector partnership that backs genetic research development in Quebec.
The study was published in the peer-reviewed science journal Nature Communications. The study was published as an open-access article meaning it is free to all to view and download.
Generally the UK media’s reporting was poor. The Mail Online took half a page before mentioning the study was in mice and did not mention that this substantially limited its applicability to humans. The Daily Express coverage was minimal and made no mention of mice at all. Both may have misled readers into thinking the research was in humans and both overemphasised the importance of the research to people. Some even gave dietary advice to “stick to greens and avoid junk”.
While this is good general health advice in principle, advising people on dietary changes based on early research in a small group of mice is not a sensible idea and is potentially harmful.
What kind of research was this?
This was a laboratory study using mice.
Observational studies indicate that a father’s diet can influence the health of his child or children.
One of the mechanisms for this, the research proposes, is genetic. Differences in diet can influence the chemical regulation of genetic material, and this regulation pattern can be passed on to the children via the sperm. The study of the pattern of chemical changes to DNA and how these are inherited is a fast growing field called “epigenomics”.
The research focused on the dietary influence of folate, also known as folic acid and vitamin B. Generally speaking, people get enough folate from their diet, but not having enough – called folate deficiency – causes the body to produce abnormally large red blood cells that cannot function properly.
In pregnant women folate deficiency can increase the risk of birth defects such as spinal bifida.
Folic acid is found in small amounts in many foods, including broccoli, spinach, brown rice and Brussels sprouts, explaining some of the media references to eating more green vegetables. Folate deficiency is most commonly seen in people who have a poor or restricted dietary intake, the elderly and those with digestive conditions affecting the body’s ability to absorb nutrients from their food (such as coeliac disease).
This research looked to see if the same might occur in men and used mice to investigate this theory from a largely genetic point of view.
A lot of early genetic studies first occur in mice because their genetics is well understood and can be manipulated experimentally. The aim is to give clues to how genetics might work in humans, as mice and men share many common genetic features due to their common mammalian ancestry. However, often things found to work in mice do not work when tested in humans; this is because sometimes even small differences between mice and men prove crucial.
Consequently, we should be cautious in assuming that results in mice will automatically apply to humans. Some do, some don’t; the best way to tell is to perform research in humans.
What did the research involve?
Two groups of mice were fed either a diet deficient in folate or a diet sufficient in folate throughout their life.
The researchers analysed the chemical patterns on the DNA of each of the adult male mice and whether these patterns were passed on to their offspring. They were particularly interested in chemical patterns affecting genes known to be important in infant development and disease. The males on the different diets were assessed for “reproductive fitness” by assessing the health of their offspring and their breeding behaviour.
The main analysis looked at whether the different diets affected the chemical patterns on the DNA, to what extent these changes were passed on to the offspring, and what potential effect these had on the health of the offspring.
What were the basic results?
The study tested a range of genetic, cellular and behavioural aspects of the mice to establish any significant differences between mice on the folate deficient diet compared with those on the folate sufficient diet. Many measures have no significant effect. However, a handful did show diet-related differences. The main findings based on these results were:
- The different folate diets did not affect the ability of the male mice to make sperm, their overall sperm counts, or the extent to which DNA in their sperm was damaged and repaired.
- However, the fertility of the male mice fed a folate deficient diet was lower (pregnancy rate of 52.38%) than those on a folate sufficient diet (85%), despite no observable differences in mating behaviour.
- Embryo length or weight were not affected by the different diets.
- Pre-implantation loss of the embryo was not affected by the different diets, but post-implantation loss was higher in the folate deficient group.
- Developmental abnormalities were observed at a high rate in foetuses fathered by male mice on folate deficient diets.
- Abnormalities were 27% in offspring fathered by mice on the folate deficient diet, compared to 3% on the folate sufficient diet.
- The recorded abnormalities included head and facial defects, abnormal sternum (breast bone) development, abnormal placental development, and a build-up of fluid on the brain. Other limb, muscle and bone defects were also observed and further analysis showed some of these were due to the bones not hardening correctly and a delay in the development of digits in the offspring.
- Abnormalities observed in the folate sufficient fathered offspring were minor and included a “runt” (the human equivalent would be failure to thrive) and skin discolouration.
The researchers then looked at whether the folate deficient diet had led to the inheritance of chemical DNA changes in their offspring that were linked to the malformations described above.
- They observed a number of patterns of chemical modifications to DNA that were inherited.
- They reported the differences were related to genes implicated in the development of the central nervous system, kidneys, spleen and muscle tissue and chronic diseases such as diabetes, autism, schizophrenia and cancer.
How did the researchers interpret the results?
The researchers’ interpreted their findings as identifying regions of the sperm DNA that are environmentally programmed by factors in the diet, specifically folate.
They said they had demonstrated that a father’s folate deficient diet “altered the sperm epigenome and that these changes were associated to genes implicated in development and chronic disease” and that these offspring “may be at increased risk for later chronic diseases such as diabetes and cancer”.
This research demonstrated that a folate deficient diet given to male mice led to a higher rate of birth abnormalities in their offspring than male mice on a folate sufficient diet. There were a number of chemical patterns on the DNA of the folate deficient mouse fathers that appeared to be inherited by their offspring. These patterns affected DNA regions that the researchers say, may affect rates of chronic disease.
There are a number of large limitations to this research.
- The research was on a small group of mice and not people. So, this doesn’t provide sufficient evidence on which to base any new dietary recommendations. Common sense advice would be to recommend men do not follow a folate deficient diet, instead following a balanced and varied diet containing lots of fruit and vegetables. But this advice is based on a large volume of evidence in humans indicating this diet reduces risks of disease, rather than this mouse study. A separate issue is whether a closer look is needed at the association between male folate levels and birth defects, which seemed to be the strongest link found in the mice study. This may be an area where further research could lead to specific folate recommendations for men in the future, but this is purely speculative at this stage.
- The link between the changes in genes and chronic disease is not certain. The researchers did not look at whether the mice offspring got any diseases. They instead looked at chemical patterns on their DNA and estimated what disease they might get. Consequently, this makes their conclusion that the inherited genetic patterns cause chronic disease a lot less reliable and clear.
This research indicated that feeding male mice a folate deficient diet can cause harm to the health of newborn mice. The deficient diet led to a pattern of chemical changes in the DNA of the father that was passed on to their offspring. This suggested a possible mechanism by which the harm was caused; however this link is not certain.
The bottom line is that this research is compatible with the general public health advice to follow a balanced and varied diet containing lots of different fruit and vegetables. While it does not provide solid enough evidence to warrant dietary guidance itself, it does highlight a potential and unproven health risk that is worthy of further study. That is whether folate deficiency in men could have any effect on sperm DNA and so potentially affect their children.
If you are a man planning a family, factors that may help boost your fertility levels include:
- quitting smoking if you smoke
- achieving or maintaining a healthy weight
- drinking sensibly
All three factors can help improve your sperm quality.
Read more about pre-conception advice.
Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.