Five studies addressed the effect of low-fat diets as means of migraine/headache prophylaxis [
78‐
82]. In 1999, a trial conducted to assess the role of fat-reduced diet for migraine control in 54 adults. Patients were instructed to restrict their fat intake to less than 20 g/d for 12 weeks, after 28 days of run-in period. They reported a notable reduction in headache frequency, intensity, and need for abortive medication [
78]. An open-label, randomized cross-over trial investigated the effect of a diet change in comparison with a placebo supplement on migraine patients. For the first 16-week duration, 42 individuals were randomly allocated in
intervention group (who were prescribed a low-fat vegan diet for 4 weeks, followed by elimination diet for 4 weeks, followed by reintroduction diet for the last 8 weeks group,
n = 21) or
placebo group (who were supplemented with 10 mcg alpha-linolenic acid + 10 mcg vitamin E as placebo,
n = 21). Then after a 4-week washout period was considered and the studied subjects in either group crossed over to the other group. A decrease in headache intensity, frequency, and use of abortive medication were observed following the intervention; However, in the mentioned trial, details regarding dietary fat composition were not noted [
79]. In another cross-over study on 63 adults with episodic or chronic migraine, low lipid diet (< 20% of total daily energy intake) for 3 months significantly reduced frequency and severity of headache attacks. In this study, participants did not reduce total fat intake to less than 45 g/d and used olive oil as the main source of fat intake [
80]. Additionally, based on the theory of the probable effects of different fat types on headache characteristics, a randomized study assessed the effect of omega-3 and omega-6 intake. Fifty-five adults with CM were either reduced omega-6 fats intake or reduced omega-6 fats along with increased omega-three consumption. After 12 weeks, individuals on high omega-3 combined with low omega-6 diet showed a higher headache improvement compared to headache patients on the reduced omega-6 diet [
81]. In another randomized double-blind controlled trial on 80 patients with EM, effect of omega-3 supplementation (2500 mg/d) was compared with either nano-curcumin (80 mg/d) or placebo. After 2 months of supplementation, combination of nano-curcumin and ω-3 fatty acids lowered the expression of TNF-α mRNA and serum level of TNF-α. Headache frequency was also reduced in all treatment groups (incl. Nano-curcumin, omega-3, and combination of omega-3/nano-curcumin), with two-fold higher effect in combination group [
82].