‘It is far more than just a headache. Not being taken seriously is having a significant impact on the lives of those with the condition.’ - says Robert Music, the chief executive of The Migraine Trust. Millions suffer from migraine, which is not merely a bad headache, but causes a serious limitation on the quality of life. Current medications can alleviate symptoms, but certain supplements have also been proven to be effective adjunctive treatments. Newest research focuses on the benefits of antioxidants, such as vitamin E, alpha-lipoic acid, and carotenoids.

What is migraine?

It is a common misconception that migraine is merely a bad headache. But this throbbing, pulsing, pounding, dull headache is usually one-sided, and its intensity ranges from mild to severe. Besides the pain, it also affects movements and is accompanied by extreme sensitivity to even normal light and sounds. These episodes, called migraine attacks, can force someone to stay in bed for days, limit their ability to work, participate in daily activities, and enjoy social gatherings. It is a huge economic and personal burden, which is very common – 12% of the population experiences it. But its distribution is uneven; 17% of people assigned female at birth (AFAB) suffer from it, while 6% of people assigned male at birth (AMAB) have migraine attacks in their lives.

A migraine attack has four phases (prodrome phase, aura, headache attack, and postdrome phase) with their own typical symptoms, such as mood changes, vision changes, nausea, or fatigue. But the experienced symptoms are different for each person, as well as the frequency of migraine attacks. Most patients suffer from 2-4 episodes per month, each episode can last from hours to days, and common painkillers cannot provide relief for the different forms of migraine. 

Migraine has various subtypes. Migraine without aura gets diagnosed in 75% of the cases, which is characterised by recurrent headache attacks, lasting 4-72 hours, with pain that is usually one-sided, pulsating, and moderate to severe in intensity. It worsens with physical activity and is associated with nausea, light and sound sensitivity. Migraines with aura are recurrent, fully reversible attacks lasting for only minutes. They are typically accompanied by one-sided symptoms such as visual, sensory, speech, language and motor disturbances. 

Understanding migraine

The biological reason behind migraine attacks is that specific nerves in the blood vessels send pain signals to the brain, which releases inflammatory substances into the head, nerves and blood vessels. But why it happens remains unclear. The possible explanation lies in a combination of genetic and environmental factors.

It is known that those who have relatives with migraine have a three times higher risk of this condition than those who have unaffected family members. Research also identified that more genes play a role in migraine, but the exact inheritance pattern is unidentified. This background is even more complicated by the fact that environmental factors are also strong triggers of migraine attacks. Stress, hormonal changes, certain medications, changes in sleep schedule, weather conditions, too much physical activity, and exposure to bright lights, loud noises, or strong odours also induce or worsen migraine. Besides these factors, food and drinks can also trigger attacks: aged cheese, alcohol, caffeine, chocolate, food additives, processed or cured meat (hot dogs, pepperoni), and fermented food can all act as triggers.

Research suggests that these environmental factors can lead to oxidative stress in the body, which eventually can lead to migraine.¹

Figure: Migraine and its triggers (Created by Anna Petschner Biorender.com)

Oxidative stress, antioxidants, and their role in migraine

Oxidative stress is an imbalance between two types of molecules in the body: fewer antioxidants and more free radicals (or oxidants). In this case, too many free radicals circulate in the body, which are merely byproducts of the food digestion process. Certain habits and environments, such as smoking, exposure to sunshine, and air pollution, can increase the number of oxidants in the blood. These molecules at low or moderate levels are useful, for example, they contribute to the normal function of the immune system, but in higher concentrations, they cause harm to the body.

Free radical levels can be lowered with antioxidants. These are substances that bind the harmful chemical compounds and convert them to harmless ones. One type of them is enzymatic antioxidants, such as catalase, superoxide dismutase, and glutathione peroxidase.¹ The other type is called nonenzymatic antioxidants, like glutathione and coenzyme Q10, which can be found in fruits, vegetables, and whole grains.¹ 

Increased level of free radicals is proven to contribute to the development of chronic diseases, such as cancer, atherosclerosis, and Alzheimer’s disease. Studies show that oxidative stress can also be responsible for migraine attacks.^2,3,4 Some patients have lower levels of enzymatic antioxidants; thus, the free radicals can cause harm in the body and brain, inducing inflammation.¹ Other results show that migraine patients have lower levels of non-enzymatic antioxidants than healthy people, which contributes to a higher frequency of headaches and migraine attacks.^5,6,7 Decreased antioxidant concentration (such as vitamin A, C, E, selenium, zinc and carotenoids) is also associated with increased intensity of headaches.^8,9 Therefore, researches support that an antioxidant-rich diet can help reduce the frequency and intensity of migraine attacks and improve patients’ quality of life of patients.¹⁰

With antioxidants against migraine

Vitamin E

Vitamin E is a collective name for a group of fat-soluble chemical compounds with antioxidant effects. Although different forms exist, we associate vitamin E with one specific form that the human body can use, the alpha-tocopherol. It can be found in nuts, seeds, vegetable oils, and some green leafy vegetables. A large amount of alpha-tocopherol can be found in foods like:

• Sunflower seeds
• Almonds
• Sunflower oil
• Hazelnuts
• Peanuts and peanut butter
• Spinach
• Broccoli
• Soybean oil
• Kiwifruit
• Mango
• Tomato

Vitamin E intake is essential for healthy skin, eyes, and helps to maintain the immune system’s function. Lack of it can lead to coronary heart disease, cancer, eye disorders and cognitive decline. Research suggests that vitamin E also affects migraines. In a study, increased vitamin E intake was examined in people AFAB who suffer from menstrual migraine. This form of migraine occurs before or during the menstrual cycle. Patients who regularly took vitamin E supplements reported lower pain severity and better quality of life, because the pain limited their daily activities less. It was also observed that nausea and extreme light and sound sensitivity had reduced.¹¹ Different studies found similar results, but with a combination of vitamins or pine bark extract that led to less severe migraine symptoms.^12,13 

Alpha-lipoic acid

Alpha-lipoic acid (ALA) is a powerful antioxidant that, unlike others, is water- and fat-soluble. In small amounts, the body can also produce it, but it is also available in red meat, beets, carrots, potatoes, spinach and broccoli. It is proven to be beneficial in oxidative-stress-related diseases, like radiation injury or ischemia. It is also suggested that it can help treat diabetic neuropathy, a type of nerve damage due to the high blood sugar level that harms the small blood vessels around nerves. Besides its overall positive effect on the human body, it also plays a role in migraine. Study suggests that ALA can improve the oxidative, inflammatory and mood conditions of patients living with episodic migraine.¹⁴ Another research drew a similar conclusion, that taking ALA supplement was able to reduce the severity and frequency of migraine symptoms, although it did not affect the duration of migraine pain.¹⁵ These findings can provide a new adjunctive migraine treatment. 

Carotenoids

Carotenoids are naturally occurring pigments with the colour of yellow, orange and red. They share similarities in their chemical structure, but represent a large group of different substances. The human body cannot synthesise them; it only has access to them via food sources, fruits, vegetables, algae, insects, and fungi. 

Table 1. Carotenoids and their food sources.¹⁶

In general, carotenoids have an important antioxidant effect but can also have individual health benefits. For example, the human body is able to produce vitamin A (retinol) from β-carotene, which vitamin supports the normal function of the immune system, helps vision in dim light, and keeps the skin healthy. Other carotenoids, lutein and zeaxanthin, constitute macular pigment in the eye, essential to the sharp, central vision. Additionally, lutein can also reduce the progression of age-related eye diseases and cataracts.¹⁷ Carotenoids can also have a positive effect on migraine patients. A study shows that people with higher concentrations of certain carotenoids in the blood (α-carotene, β-carotene, β-cryptoxanthin, lutein/zeaxanthin) are less likely to have migraines.¹⁸ However, it is important to note that this underlying mechanism is not entirely known. Another recent study shows that consuming more carotenoids or vitamin A is not necessarily a solution for migraine. They revealed that certain genes with a role in retinoic acid signalling, which is how the body uses vitamin A, are different in migraine patients. Researchers found that migraine patients had reduced enzyme production from the CYP26B1 gene and other gene variants of LRP1 than healthy people. These findings paint a more complex picture of the role of vitamin A and its metabolism in migraine patients, and can open a way to new treatments and medications.¹⁹

Summary

Migraine affects more than 10% of the population and creates a huge personal, social and economic burden. Its underlying mechanism is not entirely understood, but oxidative stress can play a role in the frequency and intensity of migraine attacks. Besides medication, new studies also focus on reducing oxidative stress with the help of antioxidants. Vitamin E, alpha-lipoic acid and carotenoids are amongst the candidates of potential new adjunctive treatments. They not only can ease the migraine symptoms, but this research can also contribute to a better understanding of the genetic and environmental factors behind the disease that can lead to new drug treatments.