Is an “Epigenetic Diet” for Migraines Justified? The Case of Folate and DNA Methylation

Abstract

Migraines are a common disease with limited treatment options and some dietary factors are recognized to trigger headaches. Although migraine pathogenesis is not completely known, aberrant DNA methylation has been reported to be associated with its occurrence. Folate, an essential micronutrient involved in one-carbon metabolism and DNA methylation, was shown to have beneficial effects on migraines. Moreover, the variability of the methylenetetrahydrofolate reductase gene, important in both folate metabolism and migraine pathogenesis, modulates the beneficial effects of folate for migraines. Therefore, migraine could be targeted by a folate-rich, DNA methylation-directed diet, but there are no data showing that beneficial effects of folate consumption result from its epigenetic action. Furthermore, contrary to epigenetic drugs, epigenetic diets contain many compounds, some yet unidentified, with poorly known or completely unknown potential to interfere with the epigenetic action of the main dietary components. The application of epigenetic diets for migraines and other diseases requires its personalization to the epigenetic profile of a patient, which is largely unknown. Results obtained so far do not warrant the recommendation of any epigenetic diet as effective in migraine prevention and therapy. Further studies including a folate-rich diet fortified with valproic acid, another modifier of epigenetic profile effective in migraine prophylaxis, may help to clarify this issue.

Nutrition in Cancer Therapy in the Elderly—An Epigenetic Connection?

“…Although an "epigenetic diet" is sometimes defined as a diet affecting the epigenome, in fact, a diet that would not affect the epigenetic profile would be very sophisticated, if possible, at all. As we concluded in our previous work, an "epigenetic diet" is a rather misleading term, as it is hardly possible to find a diet that would not affect the epigenome [112]. Instead, three kinds of diet can be considered to amend the needs of elderly patients undergoing cancer therapy.…”

Migraine and Diet

“…Using electronic diaries as part of an app in which it can be determined statistically whether headache is associated with some dietary components might be helpful [ 18 ]. The downside of an elimination diet is the long-term negative effect of undernutrition—a form of malnutrition—which is characterized as the inadequate intake of protein, energy, and micronutrients and may result in disorders including psychological problems or infection [ 25 , 26 ].…”

“…In theory, for migraine, such an intervention would mean that a dietary component can block mechanisms underlying migraine or promote prevention mechanisms. This assumption has raised a question on the existence and potential benefits of an epigenetic diet for migraine [ 26 ]. This hypothesis has mainly been formed following recent advanced studies in the pathogenesis of migraine with a focus on epigenetics [ 35 , 36 ], where aberrant DNA methylation has been found to be associated with the occurrence of migraine [ 37 ].…”

“…Folate, which is involved in DNA methylation and has previously been shown to be beneficial in migraine, has captured further attention in the context of an epigenetic diet for migraine [ 26 , 43 ]. Recently, it has been proposed that defining a diet, which can target DNA methylation—for example, a folate-rich diet—could potentially provide a future direction for migraine-related epigenetic dietary studies [ 26 , 44 ]. Further investigation is required to provide evidence on the potential dietary components, which may interfere with the epigenetics of migraine [ 37 , 45 , 46 ].…”

“…In addition, one must consider that other elements of the cellular epigenetic profile, such as histone modification and the action of non-coding RNAs (ncRNAs) [ 36 ], in addition to DNA methylation, can be modified by dietary components, resulting in the alteration of proteins or RNA products. This field is open for investigation, but issues related to bioavailability and final biological effects, synergistic or inhibitory effects when used alone or in combination with other substances, tissue-specific absorption, individual features of consumers, and the role of sex and other body characteristics must be taken into consideration, as these factors alone or in combination can alter the outcome [ 26 , 37 ]. In addition, migraine comorbidities, such as depression and epilepsy, must be taken into account.…”