Headache is defined as any type of pain localized in the region of the head. The international classification of headache disorders divides headache disorders into three main groups: primary headache which is of unidentified etiology, secondary headache with evident cause of the headache and neuropathies, and facial pains and other headaches [1]. Headaches are among the most common neurological complaints today; however, the treatment of these conditions has been a problem of physicians for decades. Current epidemiologic data estimates that prevalence of headache throughout lifetime is 96%, with a female predominance, although gender dominance depends also on the headache type. Tension-type headache is the most common headache type with a prevalence of approximately 40% whilst the prevalence of migraine is about 10% [2]. Headaches still represent a significant health burden worldwide. Migraine, which caused 45.1 million YLDs, was estimated to have a very high disability weight, much higher than tension-type headache which was estimated to 7.2 million YLDs globally in 2016 [3]. Headache disorders are associated with impaired quality of life, substantial loss of productivity, and high economic costs worldwide. Headache has been ranked as the second leading cause of years lived with disability according to The Global Burden of Disease study [4].

Magnesium has been extensively studied for its potential benefits in acute treatment and prophylaxis of migraine [17]. The ion exerts effects multiple factors believed to be involved in migraine pathophysiology including vascular, neurogenic inflammation and oxidative stress mechanisms. Magnesium has been shown to decrease CGRP and substance P levels thereby lessening the vasodilation and nociceptive transmission [18]. Serotonin released from platelets during a migraine attack is also a potent cerebral vasoconstrictor. Mg²⁺ acting as a calcium antagonist, may block serotonin-induced vasoconstriction and promote vasodilation by blocking calcium sensitive potassium channels on smooth muscle cells [19]. Maybe most importantly, Mg²⁺ ions influence glutamatergic transmission via NMDA receptor blocking and thus help regulate glutamate excitotoxicity and cortical spreading depression [20]. Magnesium, alongside riboflavin and coenzyme Q10 is proposed to improve mitochondrial function and reduce brain energy deficit and oxidative stress in migraine [21]. Multiple studies have found decreased levels of serum magnesium in patients suffering from migraine and tension type headache, therefore supplementation with this ion may prove beneficial [22,23,24]. There are different options for treatment with magnesium, the most common being oral supplementation. Products containing magnesium differ in chemical composition (e.g., magnesium oxide, magnesium citrate) and bioavailability which is important for the therapeutic effects. Magnesium supplementation efficacy is considered level B (probably effective and should be considered for migraine prevention) by the American Headache Society and the American Academy of Neurology [25] and is endorsed by European treatment guidelines for migraine [26], with common recommendations being 400–600 mg of oral magnesium daily. Increased dietary intake of magnesium-rich foods such as oats, whole-grain flour, brown rice, almonds, and pumpkin seeds is also encouraged [27].

Riboflavin (vitamin B2) is a water soluble vitamin that plays an important role in many biochemical processes including synthesis and recycling of niacin and folate, metabolism of fatty acids in brain lipids and nerve myelination and heme protein synthesis [28]. Most importantly, it is a precursor to two coenzymes, flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) which are key actors in the electron transport chain and antioxidative function in the cell. While there is no strong evidence of riboflavin deficiency in migraine patients, several studies have shown its potential benefits in migraine prophylaxis, probably via mitigating oxidative stress [29,30,31]. Riboflavin is currently classified as a level B medication for migraine prevention by the American Academy of Neurology [32], the recommended dose being 400 mg oral daily supplementation.

Feverfew (Tanacetum parthenium) has been used for centuries in folk medicine as treatment for fevers, headaches, toothaches and other conditions. Feverfew is a perennial herbaceous plant, originating from the mountainous regions of the Balkans but has been widely cultivated in many regions in the world for its medicinal properties. The plant contains different active compounds, among which sesquiterpene lactones-parthenolides are thought to be the most important. Parthenolides act on platelets, inhibiting their aggregation and release of serotonin. The anti-inflammatory function, through the inhibition of prostaglandin and phospholipase A, is also suggested as a mechanism of action [33]. While there is mixed evidence for its effectiveness, some studies have shown a reduction in migraine frequency in patients treated with feverfew extract [34].

Common dietary products can play a role in the occurrence of headaches, so dietary regimes that limit the use of certain foods are often useful in therapy. Caffeine, even though it is used as an adjuvant to analgesics (such as acetaminophen or ibuprofen), may cause recurrent headaches if taken excessively. Consuming more than 100 mg of caffeine (in medications or drinks) is a known risk factor for chronic headache [35]. Dietary triggers are established phenomena in migraines. The most common culprits are alcohol, tyramine-rich foods such as aged cheese or cured meat, artificial sweeteners, and flavor enhancers like monosodium glutamate (MSG) and nitrites and nitrates used as preservatives in plenty of foods [36]. Studies in children have shown that the “elimination” or oligoantigenic diets with witch certain substances are excluded from consumption may be effective in migraine prophylaxis [37]. There is evidence that obesity may be associated with migraines, potentially through mechanisms involving adipose tissue inflammatory mediators [38,39], hence there is significant improvement in some patient groups who undergo weight loss programs [40]. Further dietary interventions may include a low-carbohydrate, high-fat ketogenic diet (KD) to help in migraine treatment. The classic KD consists of 4 g of fat for 1 g of carbohydrates and proteins combined, replacing the main caloric source of carbohydrates for fats [41]. Most of the 10 selected studies in the recent systematic review [41] reported that KD reduced the number and severity of migraine attacks in adolescents and adults, with few reported adverse effects. The evidence on the effectiveness of the KD is low, so whether the final effect is due to the treatment remains still inconclusive and needs further research aimed to identify specific groups that could benefit from KD as a complementary therapeutic route to the drug treatment of migraine [42].