In recent medical journal article researchers have highlighted significant advancements in the treatment of migraines. Specifically, they focused on disease classification, as well as progress in clinical and dietary interventions aimed at reducing the frequency, pain, and severity of migraine attacks.
Their research delves into the advancements in the study of Calcitonin Gene-Related Peptides (CGRP) and the role of CGRP antagonists in treating migraines. Additionally, they emphasize the role of diets such as ketogenic and low glycemic diets in treating the disease. Their findings suggest that CGRP receptor antagonists, in combination with changes in diet and physical activity, can significantly increase the number of migraine-free days for patients suffering from this condition.
In a review titled „CGRP Antagonism and Ketogenic Diets in Migraine Treatment,“ they further highlight the potential benefits of these interventions. Image credit: Krakenimages.com/Shutterstock.
Migraines: A Brief Overview
„Migraine“ refers to a group of chronic neurological conditions characterized by recurring episodes of moderate to severe throbbing and pulsating pain on one side of the head. It is often accompanied by nausea and increased sensitivity to light and sound. While adolescents are most commonly affected, cases have also been reported in some children. Individuals over 50 have a lower risk of migraines. It is more prevalent in women, affecting 12-14% of females compared to 6-8% of males. Women also generally experience more pronounced symptoms and longer attack durations than their male counterparts.
The condition is typically preceded by blurred vision, loss of motor control, and speech difficulties, which prompted the World Health Organization (WHO) to rank it as the seventh-largest disease worldwide, especially affecting women. To date, no cures for the disease have been discovered, with clinical interventions primarily aimed at managing the frequency and severity of the condition. Recent research has also explored factors (triggers) contributing to the disease, identifying five main trigger groups: hormonal factors (especially in women), dietary factors, environmental triggers, psychological factors (stress), and others. Understanding the interplay of these factors and developing individualized patient interventions to address them can drastically reduce the diminishing quality of life experienced by patients.
Classification and Diagnosis of Migraines
Migraines were first classified in 1988 by the International Headache Society (IHS), representing a breakthrough in disease management by allowing the use of common terminologies in medical and scientific research. The latest edition, called the „International Classification of Headache Disorders (ICHD-3rd Edition Beta-Version, ICHD-3),“ has been part of the World Health Organization’s (WHO) International Classification of Diseases (ICD-11) since its publication in 2018. The conventional migraine classification recognizes over 300 distinct headache types, hierarchically grouped into 14 classes, each with a higher diagnostic accuracy than the previous one. Groups one to four are used to diagnose primary headaches, usually with a genetic basis. Groups 5 to 12 are used to diagnose migraines occurring as comorbidities in other diseases, while groups 13 and 14 are used to identify secondary headaches caused by non-genetic factors such as head trauma, psychiatric disorders, hormonal imbalances, and substance abuse. Surprisingly, despite decades of research in this area, there is still a lack of clinical diagnostic tests for migraines, with diagnosis limited to screening for associated symptoms.
Therapeutic Interventions for Migraines
Traditional clinical migraine interventions (medications) aim to reduce attack frequency by treating migraine-associated pathologies, focusing on groups 5 to 12 of the aforementioned classification. For example, beta-blockers are used to treat migraine as a side effect of existing heart diseases, under the assumption that improvements in the cardiovascular system would lead to positive migraine outcomes. Interventions focusing on managing attacks once they occur are treated on a case-by-case basis, based on the severity of the attack – mild attacks are treated with pain medications (such as ibuprofen), while the most severe attacks require the use of combinations of antiemetics and triptan medications in addition to intravenous fluids to counterbalance fluid loss due to vomiting. Notably, none of the conventional medications used for migraines have been specifically developed for them, resulting in their low effectiveness (at best a 50% reduction in attack frequency and severity).
Fortunately, recent research has identified the role of Calcitonin Gene-Related Peptide (CGRP) receptors in migraine pathology. CGRP belongs to a family of G protein-coupled receptors (GPCRs) and is predominantly expressed in trigeminal nerve ganglia. The discovery of these receptors and their connection to migraines led to the rapid development of CGRP antagonists and, more recently, of monoclonal anti-CGRP antibodies, novel medications that are usually injected subcutaneously to block CGRP receptors, significantly improving migraine outcomes. Olcegepant was the first CGRP antagonist specifically developed for migraines, but its large volume required frequent intravenous administration. Telcagepant was later developed as an oral alternative to Olcegepant. Unfortunately, these medications, like all subsequent CGRP antagonists, had the notable side effect of causing milder migraine-like headaches in patients. In contrast, breakthroughs in monoclonal antibody research have led to the development of monoclonal anti-CGRP antibodies, which have proven to be safe and free of side effects even with extended use, surpassing CGRP antagonists in treatment efficacy. „These antibodies have a rapid onset of action, providing the intended treatment benefits quickly, even in patients who have not responded to previous preventive treatments or are using oral preventive treatments concurrently. They are administered monthly or in some cases quarterly, through subcutaneous or intramuscular injection.“ Studies have shown that therapy with monoclonal antibodies can lead to a 50% reduction in migraine frequency, significantly less severe attacks, and a general improvement in patients‘ quality of life.
Recently, bioprospection is investigating the benefits of toxins derived from arthropods and snakes as future anti-migraine interventions due to the vasoconstrictive and anti-inflammatory properties of their peptides.
Can Diet Play a Role?
Research has shown a strong correlation between food and different types of migraines, where some foods and diets increase migraine risk, while others prevent or treat the disease. Coffee is a prime example of the rule „Everything in moderation“ – its excessive consumption has been shown to have a migraine-inducing effect, while its controlled consumption is one of the most well-known natural methods of treating attacks. Foods rich in complex carbohydrates, fiber, and minerals (especially calcium and magnesium) have proven helpful in treating the condition. Recent reports attest to the effectiveness of Zingiber officinale (ginger) and Cannabis sativa (cannabis) as side-effect-free natural alternatives to migraine medications.
„In 1983, researchers at the Hospital for Sick Children in London reported the results of their observations on 88 children suffering from severe and frequent migraine crises who began an elimination diet. Of these 88 children, 78 fully recovered, and 4 markedly improved. In the same study, some children who also suffered from seizures found that they no longer experienced seizure episodes. The researchers then started reintroducing various foods into their diets and found that for all but eight children, the reoccurrence of migraine attacks was triggered by these foods. Subsequent trials using blinded foods resulted in most children becoming asymptomatic again when avoiding the trigger foods. While trigger foods vary from patient to patient, the most common culprits are dairy products, chocolate, eggs, meat, wheat, nuts, and certain fruits and vegetables (such as tomatoes, onions, corn, bananas, and apples). However, the worst and almost ubiquitous triggers are alcoholic beverages, especially red wine.“
In contrast, research by the Dietary Approaches to Stop Hypertension (DASH) organization has shown that in adults, migraines can be controlled by sodium abstinence (<2400 mg/day) and increased calcium and magnesium intake. Building on this work, clinical studies have shown that diets such as the Mediterranean diet, rich in plant-based foods and healthy fats, can significantly reduce the frequency and duration of attacks through their connection with the gut microbiome. The ketogenic diet (Keto) is a low-carbohydrate, high-fat diet originally developed in the 1920s for the treatment of childhood epilepsy but has proven surprisingly effective in other conditions, including migraines. "This diet is safe, when supervised by a trained professional, and has negligibly short- to medium-term side effects. Although the ketogenic diet was successfully used in 1928 to treat migraine patients, this strategy has only gained momentum in recent years, initially with case studies, then with clinical trials." Remarkably, the ketogenic diet led to complete cessation of migraines in some clinically tested patients, highlighting its potential as a promising intervention. In conclusion, researchers have made substantial progress in identifying and developing innovative treatments for migraines, focusing on pharmaceutical and dietary interventions. The integration of these novel approaches with traditional methods and a personalized approach to addressing individual patient triggers holds great promise for improving the quality of life for those suffering from migraines.