The effects of high concentrations of folic acid, methionine and vitamin B12 by male rodents were found to transfer to some degree to the next generation.
The team have pointed to these nutrients as sources of methyl donors. Tiny tags attached to the DNA that control the activity of genes can be altered by an excess of methyl tags in the diet.
The findings may be of relevance to countries like the UK, where fortifying foods with folic acid has been a popular strategy in reducing the risk of neural tube defects in foetuses.
In addition to this, methyl donors such as vitamin B12 are present in vitamin supplements and added to diverse foods including energy drinks.
"Methyl donor deficiencies are well known to have adverse health consequences that can be prevented with dietary supplements,” said Dr Dan Ehninger, research group leader at the German Center for Neurodegenerative Diseases.
“However, our study suggests that excessive consumption may be associated with adverse effects as well."
Meddling with mice
Along with colleagues at the Helmholtz Zentrum München and the Federal Institute for Drugs and Medical Devices, male mice were placed on a diet that promoted methyl group metabolism.
This diet contained high concentrations of methionine, folic acid, vitamin B12, choline, betaine and zinc. The study group was joined by another group of male rats raised on a standard diet.
After six weeks, the male mice were mated with female mice and their offspring were monitored.
Results found the offspring of the male mice fed with methyl donors performed poorly in a selection of learning and memory assessments.
"We were able to show that even a transient change in the paternal diet can cause impaired learning skills in offspring. This affected in particular the ability to properly learn a spatial navigation task," explained Dr Ehninger.
Brain structure had also been fundamentally altered, the team discovered, as nerve connections in the hippocampus reacted slowly to electrical stimuli.
The team believed the nerves’ ability to adapt, or its neuronal plasticity, had been impaired in the offspring mice.
Researchers identified the gene known as ‘Kcnmb2’ as a possible cause of neuroplasticity that was downregulated in these offspring.
Paternal influence
Child development is known to be affected by the mother's pre-pregnant diet and lifestyle. What is not so well known are the effects of environmental factors that fathers are exposed to.
A growing literature collection has demonstrated the inheritance of altered metabolic traits is heavily influenced by paternal diet in animals.
For example, paternal deficiency in dietary folate has been shown to induce birth defects in mouse offspring.
Dietary intake of methyl donors is subject to substantial variability within human populations such as seasonal food availability, which is sufficient enough to alter genome-wide methylation patterns.
Countries like Switzerland have fortification programs designed to enforce folic acid supplementation.
The country currently has around 250 food products, which are voluntarily fortified with folic acid.
“A growing number of foods in certain countries are being fortified with methyl donors such as folic acid, increased comprehension of dietary methyl donor influences is warranted to prevent neurocognitive and metabolic alterations in subsequent generations,” the study said.
“Taken together, our study identified adverse effects of a paternal methyl donor-rich diet (MD) on cognitive and neural functions in offspring animals, raising the possibility that paternal dietary factors may be relevant causal factors for mental health issues in the subsequent generation.”
Source: Molecular Psychiatry
Published online ahead of print: DOI: 10.1038/MP.2017.53
“A paternal methyl donor-rich diet altered cognitive and neural functions in offspring mice.”
Authors: D Ehninger et al.