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CGRP antagonists and dietary changes show promise for migraine treatment

In a recent article published within the journal Medicina, researchers review advancements in migraine therapy, specifically the classification of the disease and the clinical and food regimen intervention advancements geared toward significantly reducing the frequency, pain, and severity of attacks. They highlight progress in calcitonin gene-related peptide (CGRP) research and the role of CGRP antagonists in treating the disease. They further reveal the role of diets similar to ketogenic- and low-glycemic diets in disease management. Their findings indicate that CGRP receptor antagonists, together with dietary and physical activity modifications, can substantially increase the variety of migraine-free monthly days for patients of the disease.



Review: CGRP Antagonism and Ketogenic Weight loss plan within the Treatment of Migraine. Image Credit: Krakenimages.com / Shutterstock

Migraine – A Transient Overview

‘Migraine’ refers to a bunch of chronic neurological conditions characterised by recurrent attacks of moderate to severe throbbing and pulsating pain on one side of the pinnacle. It is usually accompanied by nausea and increased sensitivity to light and sound. It mostly affects adolescents, though it has been reported in some children. People older than 50 are at a lower risk for migraines.

Migraine is more prevalent in women, affecting 12-14% of the sex as compared to 6-8% of men. Moreover, women generally suffer from more pronounced symptoms and longer attack durations than their male counterparts. The condition is generally preceded by blurred vision, lack of motor control, and difficulty speaking, which, when paired with its direct symptoms, has led the World Health Organization (WHO) to rate it because the seventh most disabling disease globally or third if just including women.

Hitherto, no cures for the condition have been discovered, with clinical interventions primarily geared toward managing the disease’s frequency and severity. Recent research has moreover explored the aspects (triggers) contributing to the disease and has identified five macro-groups – 1. Hormonal aspects (especially in women), 2. Dietary aspects, 3. Environmental triggers, 4. Psychological aspects (stress), and 5. Others. Understanding the interplay between these aspects and developing patient-personalized interventions geared toward managing them may drastically reduce the losses in quality of life currently experienced by patients.

Migraine classification and diagnoses

Migraines were initially classified by the International Headache Society (IHS) in 1988, representing a breakthrough in disease management because it allowed, for the primary time, using common terminologies in medical and scientific research. The most recent edition, titled “International Classification of Headache Disorders (ICHD-Third edition beta version, called ICHD-3),” has formed an element of the WHO’s International Classification of Diseases (ICD-11) since its publication in 2018.

Conventional migraine classification recognizes greater than 300 unique sorts of headaches, that are classified in a hierarchical fashion into 14 groups, with each group having higher diagnostic accuracy than the previous one. Groups one through 4 are used for diagnosing primary headaches, normally having a genetic basis. Groups 5 through 12 are used to diagnose migraines that arise as comorbidities in other diseases. Finally, groups 13 and 14 are used to discover secondary headaches that occur as a consequence of non-genetic aspects, similar to head trauma, psychiatric disorders, hormonal imbalances, and substance abuse.

Surprisingly, despite a long time of research in the sector, there stays an absence of clinical diagnostic tests for migraine, with diagnosis restricted to screening of symptoms related to the disease.

Therapeutic interventions against migraines

Traditionally, clinical migraine interventions (drugs) have been geared toward reducing attack frequency via the treatment of migraine-associated pathologies and have hence focused on groups 5 through 12 of the classification mentioned above. For instance, within the case of migraines as a side-effect of preexisting heart conditions, beta-blockers are used to treat these heart problems on the idea that cardiovascular improvements would cascade to useful migraine outcomes.

Interventions focused 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 painkillers (similar to ibuprofen), while most severe ones involve using mixtures of antiemetic and triptan drugs alongside intravenous fluids to compensate for those lost through vomiting. Notably, not one of the medications conventionally used were developed against migraines, leading to their low efficacy (best-case scenario – a 50% reduction in attack frequency and severity).

Encouragingly, recent research has identified the role of the calcitonin gene-related peptide (CGRP) receptor in migraine pathology. CGRP belongs to a family (B) of G-protein-coupled receptors (GPCRs) and is predominantly expressed in trigeminal neural ganglions. The invention of those receptors and elucidation of their association with migraines has allowed for the rapid development of CGRP antagonists and, more recently, anti-CGRP monoclonal antibodies, novel drugs normally injected subcutaneously that block CGRP receptors, substantially improving migraine outcomes.

Olcegepant was the primary CGRP antagonist developed specifically against migraines, but given its large volume, it required frequent intravenous administration. Telcagepant was subsequently developed as an oral alternative to Olcegepant. Unfortunately, like all CGRP antagonists that followed, these drugs had the notable side effect of causing milder migraine-like headaches in patients. In contrast, breakthroughs in monoclonal antibody research allowed for the event of anti-CGRP monoclonal antibodies, which have been demonstrated to be secure and side-effect-free even on prolonged use while outperforming CGRP antagonists in treatment efficacy.

“These antibodies exhibit a rapid onset of effect. They will quickly provide the intended treatment advantages, even in patients who haven’t responded to previous preventive treatments or are concurrently using oral preventive treatments. Their administration is monthly, or in some cases quarterly, through subcutaneous or intramuscular intravenous injection.”

Research has presented that monoclonal antibody therapy can lead to a 50% reduction in migraine frequency, substantially reduced attack severity, and overall improvements in patients’ quality of life. Most recently, bioprospecting is exploring the utility of arthropod- and snake-derived venoms as future anti-migraine interventions, given the vasoconstrictory and anti inflammatory properties of their peptides.

Can food regimen play a job?

Research has revealed a powerful association between food and various sorts of migraine, with some foods and diets increasing migraine risk while others prevent or manage the condition. Coffee forms a chief example of the “the whole lot sparsely” rule – its excessive use has been found to have a migraine-inducing effect, while its controlled use is one in all the best-known natural management practices against attacks.

Foods wealthy in complex carbohydrates, fibers, and minerals (specifically calcium and magnesium) have proven helpful in treating the condition, with recent reports highlighting the efficacy of Zingiber officinale (ginger) and Cannabis sativa (cannabis) as side-effect-free natural alternatives to anti-migraine drugs.

“In 1983, researchers from the Hospital for Sick Children in London reported the outcomes of their observations on 88 children with severe and frequent migraine crises who had began an elimination food regimen. Of those 88 children, 78 recovered completely and 4 improved significantly. In the identical study, some children who also had seizures noticed that they now not experienced seizure episodes. Researchers then began reintroducing various foods into the food regimen and located that these triggered the resumption of migraine attacks in all but 8 of the kids. In subsequent trials using disguised foods, a lot of the children became asymptomatic again when the foods that triggered the seizures were avoided.”

While trigger foods vary from patient to patient, essentially the most common culprits are dairy products, chocolate, eggs, meat, wheat, nuts, and specific fruit and veggies (tomatoes, onions, corn, bananas, and apples). The worst and almost ubiquitous triggers, nevertheless, are alcoholic beverages, especially red wine. In contrast, research by the Dietary Approaches to Stop Hypertension (DASH) has revealed that adult migraines may be managed via sodium abstinence (< 2400 mg/day) and increased calcium and magnesium intake. Constructing on this work, clinical trials have depicted that diets similar to the Mediterranean food regimen, wealthy in plant-based foods and healthy fats, can significantly reduce attack frequency and duration through their association with the gut microbiome.

The ketogenic food regimen (keto) is a low-carb, high-fat food regimen initially developed within the Nineteen Twenties to treat childhood epilepsy but has been found surprisingly useful against other pathologies, including migraine.

“This food regimen is secure when performed under the supervision of a trained skilled and has negligible unwanted effects within the short to medium term. Although the ketogenic food regimen has been used to successfully treat migraine victims as early as 1928, only in recent times has this strategy returned to the forefront, first with individual case studies, then with clinical studies.”

Remarkably, the ketogenic food regimen has resulted in the whole lack of migraines in some clinically tested patients, highlighting its utility as a secure behavioral modification against the disease. Unfortunately, research has not yet unraveled the mechanism by which this dietary pattern alters migraine pathology.

Conclusions

The current review paints an outline of conventional and up to date advances in anti-migraine research. It explores the classification of the disease, therapeutic interventions geared toward managing the chronic condition, and the influence of food as either trigger or cure against migraines. The work highlights the advantages of anti-CGRP monoclonal antibodies and diets similar to the Mediterranean and ketogenic diets as secure and efficient interventions that may improve patient’s quality of life and, in some cases, halt migraine altogether.

Journal reference:

  • Finelli, F., Catalano, A., De Lisa, M., Ferraro, G. A., Genovese, S., Giuzio, F., Salvia, R., Scieuzo, C., Sinicropi, M. S., Svolacchia, F., Vassallo, A., Santarsiere, A., & Saturnino, C. (2023). CGRP Antagonism and Ketogenic Weight loss plan within the Treatment of Migraine. Medicina, 60(1), 163, DOI – 10.3390/medicina60010163,  https://www.mdpi.com/1648-9144/60/1/163
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