The Belly and the Brain: Weight Management and Headache

Obesity is a complex condition extending beyond metabolic complications and has been shown to lead to neurologic disorders.¹ The prevalence of obesity is high, especially in the United States. Between August 2021 and 2023, 40.3% of Americans had a body mass index (BMI) ≥30. The rates of obesity have been stable for the past 10 years, but the prevalence of class 3 obesity (BMI ≥40) has risen.² Integrating weight management into neurology care can provide a holistic approach to preventing and treating obesity-related neurologic disorders. Recognizing individuals with neurologic disorders who can benefit from weight management is essential, but the conversation is often challenging to weave into a typical appointment.

A long-established link has been recognized between headaches—most notably, migraine and idiopathic intracranial hypertension (IIH)—and obesity. A wealth of research has established that weight loss can be effective at reducing headaches, but many of these studies focused on bariatric surgery outcomes.³ There is a paucity of literature assessing headache as relates to nonsurgical weight management. Clinical observations suggest that headaches can be improved through dietary and pharmaceutical weight management. This area has advanced at a rapid pace due to new medications and increased public interest.

We performed a literature search using Google Scholar and PubMed with the keywords migraine, IIH, bariatric surgery, gastric banding, gastric sleeve, gastric bypass, weight loss medications, glucagon-like peptide 1 receptor agonists (GLP-1 RAs), lipase inhibitors, and sympathomimetic amines. Single case reports, pilot studies, animal studies, and literature reviews were excluded. The purpose of this article is to review the evidence regarding weight loss and headache management to guide decision making within a neurology practice. 

Migraines and Obesity 

Obesity was associated with a 27% increased risk of migraine with the association being particularly strong in women and younger individuals, according to a meta-analysis by Gelaye et al.⁴ Clinical studies have observed that reducing adipose tissue through weight loss can improve migraine. Bond et al⁵ reported that individuals undergoing bariatric surgery experienced a significant reduction in migraine days after surgery, suggesting a causal relationship among excess fat, inflammation, and migraine.

Adipose tissue, especially visceral fat, functions as an active endocrine organ. In individuals with obesity, this tissue expands and begins to produce excessive amounts of cytokines, which are proteins critical in regulating the immune system and inflammation. The overproduction of cytokines, such as tumor necrosis factor–α and interleukin-6, creates a state of chronic low-grade inflammation. These cytokines may cross the blood–brain barrier, intensifying neurogenic inflammation in the brain. Chronic exposure to these cytokines can increase neuronal excitability and lower the threshold for pain, making individuals susceptible to migraine triggers. Inflammation may enhance the release of calcitonin gene-related peptide, a molecule heavily implicated in migraine pathophysiology.

Idiopathic Intracranial Hypertension and Obesity

IIH is a condition marked by increased cerebrospinal fluid (CSF) pressure without an identifiable underlying cause. The diagnostic criterion for IIH in adults is a CSF opening pressure >20 mmHg.⁶ Its association with obesity has been linked to several proposed mechanisms. One involves increased venous pressure; excess body weight can raise intrathoracic pressure, which in turn elevates venous pressure and ultimately leads to higher CSF pressure. In addition, the choroid plexus and adipose tissue both produce tryptase, which can induce mast cell activation, ultimately leading to increased intracranial pressure. Hormonal factors may play a role because estrogen, progesterone, and testosterone have been shown to affect CSF secretion rates, potentially contributing to IIH development in individuals with obesity.

Nonidiopathic causes of intracranial hypertension include cerebral venous stenosis and cerebral venous sinus thrombosis. Stenotic vessels likely predispose to and lower the threshold for developing increased ICP, especially in these circumstances (ie, cerebral venous stenosis, cerebral venous sinus thrombosis). Venous stenting can be an effective treatment in this situation.⁷ A dynamic relationship also exists between obesity and cerebral venous sinus thrombosis. Obesity leads to a hypercoagulable state, increasing the risk of deep vein thrombosis and cerebral venous sinus thrombosis. This risk is elevated in women, but has not been seen in men. The risk is increased further in women taking oral contraceptives. 

Weight Management and Headache

Weight loss treatment options range from lifestyle modifications to medical and surgical interventions, although combination approaches are frequently used. Sustainable weight loss begins with reshaping everyday habits; with a healthful diet having paramount importance. While these changes require commitment, they lay the foundation for lasting success. There is a paucity of literature dedicated to the assessment of weight management as a treatment for headache. The following is a review of weight loss strategies with evidence related to headache management.

Diet, Exercise, and Headache

Weight loss has previously been associated with reductions in headache frequency, duration, pain, and disability, but there is limited evidence suggesting a direct link between headache and weight loss diets.⁸ A 2020 systematic review found that dietary interventions such as low-fat and elimination diets were associated with a reduced frequency of migraine attacks, but the review did not assess weight loss.⁹ One prospective study assessed pediatric weight loss by diet and exercise and found significant reductions in weight and migraine frequency.¹⁰ A small retrospective observational study found that participants on the ketogenic diet had a reduction in monthly migraine days along with reduced body weight and BMI.¹¹ Evidence suggests that dietary weight loss may improve headache, but further research is needed to assess both dietary and exercise weight loss interventions for headache.¹²

A reduced-calorie diet creates the deficit needed for body fat loss. There are multiple strategies to accomplish this, and the best strategies often focus on lean proteins and vegetables. A review by Aaseth et al¹³ described common weight loss diets and their efficacy, summarized in Table 1. In the United States, commercial weight loss programs providing counseling and low-calorie meal replacements (eg, Weight Watchers, Jenny Craig) are popular, and a 2015 meta-analysis found that users had improved sustained weight loss when compared with control participants.¹⁴

The specific style of eating, such as food choices and meal timing, is less important than the overall nutritional content of the diet. Effective diets ultimately work by reducing caloric intake, limiting the content that sustains excess body fat. The long-term success of any dietary approach depends largely on adherence. Too often, a weight loss diet is abandoned prematurely because an individual may not realize they are effectively maintaining a lower weight. Strengthening nutritional and dietary education empowers individuals, allowing them to be better equipped to maintain sustainable eating patterns over time.

Physical activity can promote calorie reduction, build muscle, and heighten metabolism. For individuals with obesity however, exercise capacity can be limited by comorbidites associated with excess weight. Direct evidence for exercise-induced weight loss without caloric restriction is heterogeneous and variable.¹⁵ Aerobic exercise has been found to be more effective than anaerobic for weight reduction, when combined with dietary interventions.^15a Exercise can also lead to changes in body composition, which is distinct from weight loss. Research has suggested that exercise is unlikely to result in substantial weight loss unless paired with caloric restriction. Exercise should be recommended as it helps achieve weight loss goals and longitudinally maintains optimal patient health.¹⁵

Pharmaceutical Interventions and Headache

Standard migraine medication prescriptions include abortive and preventive treatments. Abortive treatments include triptans, CGRP antagonists, NSAIDs, and antiemetics.^15b Preventive treatments include beta-blockers, antiepileptics, calcium channel blockers, antidepressants, and CGRP antagonists.^15b Many migraine medications can have side effects causing changes in weight; this should be taken into consideration when tailoring a care plan for a migraine patient. 

Preventative migraine medications like amitriptyline, propranolol, and divalproex sodium have been associated with variable amounts of weight gain.^15c Therefore, selecting an alternative medication is advised for individuals who require weight management. Conversely, topiramate and atogepant (Qulipta; AbbVie, North Chicago, IL) have been associated with varying degrees of weight loss.^15c,15d These 2 medications may be preferred for preventive migraine care when patients are seeking to manage weight. It is important to note that while topiramate and atogepant have weight loss as a side effect, they are not FDA–indicated/approved for weight loss and should not be used solely for weight management. However, topiramate is currently used in combination with phentermine as an FDA-approved therapy for weight loss.

Three main classes of weight loss medications have been approved by the Food and Drug Administration (FDA): lipase inhibitors, which block fat absorption; GLP-1 RAs, which perform hormonal appetite control; and sympathomimetic amines, which act through short-term appetite suppression. Combination therapies use multitargeted approaches. Within these classes, there are 6 FDA-approved weight loss medications: liraglutide, semaglutide, tirzepatide, orlistat, naltrexone/bupropion, and phentermine/topiramate.^17,18

We performed a literature review to assess weight loss outcomes in studies mentioning these classes of medications, including primary results presented by class and adverse side effects. The mechanisms of action, results, and considerations for these drugs are detailed in Table 2. Other medications within these classes have demonstrated weight loss efficacy but are not FDA approved for weight loss (eg, medications approved for diabetes that can induce weight loss) and therefore are not included in the table.

A 2024 review and meta-analysis¹⁶ assessed the overall efficacy of these weight loss medications. When compared with placebo, liraglutide resulted in a 4.7% increase in weight loss, semaglutide in 11.4%, tirzepatide in 12.4%, orlistat in 3.1%, naltrexone/bupropion in 4.1%, and phentermine/topiramate in 8.0%. Orlistat works best with fat-rich diets, but the adverse gastrointestinal effects (including oily fecal spotting and oily discharge) can be a drawback for use.¹⁶ Liraglutide, semaglutide, and tirzepatide, initially designed to treat type 2 diabetes, are extremely effective weight loss medications.¹⁶ Despite their weight loss efficacy, these medications can have high costs and side effects. Common side effects associated with these GLP-1 RAs include multiple gastrointestinal issues such as nausea, diarrhea, vomiting, and constipation as well as headache.¹⁶ Naltrexone/bupropion and phentermine/topiramate are more cost-effective weight loss options but have somewhat reduced efficacy in comparison. Headache was reported as an adverse event during treatment with liraglutide, semaglutide, phentermine/topiramate, and naltrexone/bupropion, though it was not a severe adverse event.

There is limited evidence suggesting an association between weight loss medication use and migraine or IIH headache relief. Searches for orlistat, naltrexone/bupropion, or phentermine/topiramate and migraine or IIH headache relief yielded no results. Emerging evidence was found assessing the GLP-1 RAs liraglutide, semaglutide, and tirzepatide and the effects on associated IIH symptoms (Table 3). The GLP-1 RA exenatide was included in Table 3 despite lacking an indication for weight loss, given the evidence presented by Mitchell et al.²⁷

Improvements in IIH resulted in reduction in monthly headache days, papilledema risk, and ICP. Two of the 4 trials were retrospective and included <40 participants. For most of these studies, inclusion criteria varied for BMI ranging anywhere from ≥25 to ≤47. The improvement of IIH with GLP-1 RAs is promising, but prospective, randomized controlled trials with larger cohorts are needed. Nonetheless, these medications provide the opportunity for a less invasive treatment option for individuals with IIH. No migraine-specific studies evaluating these weight loss medications have been published.

Surgical Interventions and Headache

Surgical intervention is typically reserved for individuals with BMI ≥40 or with BMI ≥35 with related health issues (BMI ≥30 is also sometimes accepted). Bariatric surgery physically alters how and where the body processes food. The 3 main types of bariatric surgery include gastric banding, gastric sleeve (sleeve gastrectomy), and gastric bypass (Roux-en-Y). The procedures, their outcomes, and considerations are detailed in Table 4.

Some of the studies that evaluated bariatric surgery and migraine/IIH improvement are summarized in Table 5. Gastric banding was associated with lower migraine frequency, duration, pain, and medication use during migraine attacks. Gastric sleeve was associated with a reduction in migraine duration and an increase in migraine-free days. Gastric bypass was associated with improvement of migraine in 89% of individuals. In a study assessing all 3 bariatric surgeries, ICP was significantly decreased for individuals with IIH, and there was a significant improvement in quality of life. However, due to the invasive and irreversible nature of weight loss surgeries (with the exception of gastric band surgery), along with the associated risks and the availability of new medication options, surgery is reserved as a final option. Consulting with a bariatric surgeon early, however, could decrease the time to surgery for an individual who may ultimately need surgical treatment.

Approach

Fundamentally and physiologically, weight loss is achieved through the creation of a caloric deficit. In practice, effective weight management typically involves a combination of therapeutic strategies, beginning with dietary modifications and lifestyle changes, including exercise and behavioral counseling. Lifestyle changes should be the first step and should be evaluated for effectiveness, as insurance carriers often require documentation of a successful attempt at weight loss before approving pharmaceutical or surgical treatments. There are also state-specific insurance hurdles in obtaining medication and surgical coverage, which usually require a specific BMI and/or pre-existing comorbid condition. In certain urgent neurologic situations, immediate pharmaceutical treatment or surgical consultation may be necessary, as in severe presentations of IIH.

GLP-1 RAs provide the most potent and sustained appetite suppression, making them highly sought after by patients. However, they are expensive and often difficult to obtain through insurance. Phentermine-associated medications, which are more affordable and accessible, offer short-term appetite control. Naltrexone/bupropion can be particularly beneficial for people struggling with cravings or eating triggered by boredom or stress. Orlistat is generally the least favored option due to its side effect profile, and its benefit is reduced if an individual is already following a low-fat diet, although gastrointestinal side effects may persist. There is a paucity of clinical evidence assessing the association between weight loss medications and migraine headache. Literature exists for IIH headache, but larger-scale, prospective randomized controlled studies are needed to help develop and establish a dosing protocol and better understand the safety and efficacy of these medications in this population.

Within the past 15 years, research has established a connection between bariatric surgery and relief of headache associated with migraine and IIH. Significant reductions in migraine were observed for individuals who underwent the different types of bariatric surgery. Despite the association between headache improvement and weight loss after bariatric surgery, there is a significant risk associated with invasive surgical procedures, which should be evaluated on a case-by-case basis. There has been a substantial decline in studies evaluating bariatric surgery since the advent of the new, effective, less-invasive weight loss medicines.

Although there is no standardized step-by-step, evidence-based medicine protocol on how to instruct a patient with migraine through a weight loss journey, standard clinical practice suggests a multimodal approach. Typically, patients are initially evaluated for comorbid risk factors in addition to their migraine/IIH profile. Setting realistic weight management goals can be beneficial for long-term success. Initial attempts should be made to tailor prevention and acute migraine/IIH treatment to help and not hinder weight management. Concurrently, clinicians should present dietary and lifestyle modifications through nutrition and exercise counseling to establish a healthy foundation. Ideally, these core weight management practices are tailored and revised for individuals at each office visit. Similarly, headache profile should be evaluated at each appointment through standardized headache assessment tools and physical examination.

If these methods prove to be unsuccessful with either weight loss or headache relief, pharmaceutical therapies can be considered to augment weight loss and should be combined with core weight management practices. In more severe or urgent situations, such as with severe IIH, surgical intervention for weight loss is a possible treatment option. If the patient is an appropriate candidate, referral to a specialist can be considered. Core weight management practices are still recommended as most insurances require demonstration of a concerted effort and some weight loss success before approval for surgery.

Conclusion

There is no universal path to weight loss success or headache freedom. Lifestyle changes remain an essential first step in sustained improvement in weight management and headache. Pharmaceutical treatments offer added appetite suppression for those in need of more weight loss support, whereas surgical procedures are reserved for more challenging cases. Ultimately, the best treatment choice depends on individual goals, medical history, side effect tolerance, and available resources. Weight loss as a treatment for neurologic conditions, such as migraine and IIH, is often achieved through a combination of therapies fostered by supportive counseling from a clinician. Weight remains a sensitive topic to broach for both the neurology clinician and patient; however, this conversation can lead to a life-altering journey if approached with sensitivity, compassion, and understanding. Weight loss language should be chosen intentionally and sensitively, because more outdated terms can connote negativity and lead to resistance. Partnering with an individual on their weight loss process can allow for greater success. There is an ongoing need for evidence-based research on the connection between weight reduction and headache amelioration, as well as guidelines for weight management within headache practice.