A diet lower in vegetable oil and higher in fatty fish reduce migraine headaches


A diet higher in fatty fish helped frequent migraine sufferers reduce their monthly number of headaches and intensity of pain compared to participants on a diet higher in vegetable-based fats and oils, according to a new study.

The findings by a team of researchers from the National Institute on Aging (NIA) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA), parts of the National Institutes of Health; and the University of North Carolina (UNC) at Chapel Hill, were published in the July 3 issue of The BMJ.

This study of 182 adults with frequent migraines expanded on the team’s previous work on the impact of linoleic acid and chronic pain. Linoleic acid is a polyunsaturated fatty acid commonly derived in the American diet from corn, soybean, and other similar oils, as well as some nuts and seeds.

The team’s previous smaller studies explored if linoleic acid inflamed migraine-related pain processing tissues and pathways in the trigeminal nerve, the largest and most complex of the body’s 12 cranial nerves.

They found that a diet lower in linoleic acid and higher in levels of omega-3 fatty acids (like those found in fish and shellfish) could soothe this pain pathway inflammation.

In a 16-week dietary intervention, participants were randomly assigned to one of three healthy diet plans. Participants all received meal kits that included fish, vegetables, hummus, salads, and breakfast items. One group received meals that had high levels of fatty fish or oils from fatty fish and lowered linoleic acid.

A second group received meals that had high levels of fatty fish and higher linoleic acid. The third group received meals with high linoleic acid and lower levels of fatty fish to mimic average U.S. intakes.

During the intervention period, participants monitored their number of migraine days, duration, and intensity, along with how their headaches affected their abilities to function at work, school, and in their social lives, and how often they needed to take pain medications.

When the study began, participants averaged more than 16 headache days per month, over five hours of migraine pain per headache day, and had baseline scores showing a severe impact on quality of life despite using multiple headache medications.

The diet lower in vegetable oil and higher in fatty fish produced between 30% and 40% reductions in total headache hours per day, severe headache hours per day, and overall headache days per month compared to the control group. Blood samples from this group of participants also had lower levels of pain-related lipids.

Despite the reduction in headache frequency and pain, these same participants reported only minor improvements in migraine-related overall quality of life compared to other groups in the study.

Migraine, a neurological disease, ranks among the most common causes of chronic pain, lost work time, and lowered quality of life. More than 4 million people worldwide have chronic migraine (at least 15 migraine days per month) and over 90% of sufferers are unable to work or function normally during an attack, which can last anywhere from four hours to three days.

Women between the ages of 18 and 44 are especially prone to migraines, and an estimated 18% of all American women are affected. Current medications for migraine usually offer only partial relief and can have negative side effects including sedation, and the possibility of dependence or addiction.

“This research found intriguing evidence that dietary changes have potential for improving a very debilitating chronic pain condition like migraine without the related downsides of often prescribed medications,” said Luigi Ferrucci, M.D., Ph.D., scientific director of NIA.

The NIH team was led by Chris Ramsden, a clinical investigator in the NIA and NIAAA intramural research programs, and UNC adjunct faculty member. Ramsden and his team specialize in the study of lipids – fatty acid compounds found in many natural oils—and their role in aging, especially chronic pain and neurodegenerative conditions.

The UNC team was led by Doug Mann, M.D., of the Department of Neurology, and Kim Faurot, Ph.D., of the Program on Integrative Medicine. Meal plans were designed by Beth MacIntosh, M.P.H., of UNC Healthcare’s Department of Nutrition and Food Services.

“Changes in diet could offer some relief for the millions of Americans who suffer from migraine pain,” said Ramsden. “It’s further evidence that the foods we eat can influence pain pathways.”

The researchers noted that these findings serve as validation that diet-based interventions increasing omega-3 fats while reducing linoleic acid sources show better promise for helping people with migraines reduce the number and impact of headache days than fish-oil based supplements, while reducing the need for pain medications.

They hope to continue to expand this work to study effects of diet on other chronic pain conditions.

Omega-3 (or ω-3) is the name for long-chain polyunsaturated fatty acids (PUFAs).[1] Among PUFAs properties, the most relevant are represented by antioxidant,[2] anti-inflammatory,[3] and neuroprotective effects.[4] FAs are key components of nutrition, play a primary role in the lipid composition of cell membranes,[5] and their metabolites are crucial as cell signaling molecules.[6] The main FAs present in the brain and nervous system are long-chain PUFAs.[7,8]

The physiological functions of Omega-3 FAs in the nervous system include the maintenance of membrane fluidity and synapse integrity[9] and endogenous derivatives of Omega-3 FAs, act as anti-inflammatory mediators.[10]

Eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) are the most important long-chain omega-3 FAs, however, their endogenous formation can be not sufficient for physiological necessities.[11] They are structurally and functionally distinct from omega-6 PUFAs, and inflammatory cells contain high proportions of the omega-6 PUFAs and low proportions of omega-3 PUFAs.[1,12,13]

In general, lipids derived from omega-6 FAs show pro-nociceptive properties, while mediators derived from omega-3 FAs have anti-nociceptive properties, with some exceptions.[14] Moreover, omega-3 interferes with the conversion of omega-6 to eicosanoids, thus reducing the production of prostaglandins and leukotrienes.[12,15]

Omega-3 and omega-6 FAs modulate inflammation, and pain-related biochemical pathways,[16] in particular, omega-3 FAs intake have been associated with decreased concentration of C-reactive protein (CRP), pro-inflammatory eicosanoids, cytokines, chemokines, and other inflammatory biomarkers.[17]

In recent years, PUFAs were recommended to treat systemic pathological conditions,[18] and administration of omega-3 PUFAs has been proposed for the treatment neurological diseases such as hyperactive disorder, attention deficit,[19] Alzheimer,[20] depression,[21] neurodegenerative diseases,[22] and spinal cord injury.[23]

These FAs mediate numerous physiological functions and have therapeutic potential for neuro-traumatic conditions[24] and omega-3 FAs intake provide relief from neuropathic pain caused by diabetic neuropathy.[25] In addition, patients affected by cervical radiculopathy and thoracic outlet syndrome reported long term significant pain attenuation with high oral doses of omega-3 FAs.[26] More recently, analgesia with omega-3 FAs in chronic headache has also been observed.[27]


Migraine is a common chronic neurological disease, characterized by frequent attacks of disrupting pain, commonly associated with depression, anxiety, hypertension, stroke, and cardiovascular diseases.[28] Even in its episodic form migraine can evolve in a chronic condition.[29] Factors that could contribute to its pathogenesis are menstrual cycle, pregnancy, lifestyle, diet, and chronic stress.[30]

Etiology of migraine is still not completely known, even if genetics and environmental factors could play a central role[31] and current opinion states that neurogenic inflammation contributes to migraine pathogenesis.[32] It is well known that in a neuro-inflammatory condition, increased neuronal activity leads to the release of inflammatory mediators such as the cytokine tumor necrosis factor (TNF)-α.[33]

Phases of attack migraine are also frequently associated with higher serum levels of glutamate, magnesium deficiency, monoaminergic pathway and mitochondrial disorders, calcitonin gene related peptide (CGRP) release.[34,35] Cytokines, by increasing membrane permeability and through cell-to-cell interactions, have a significant role in the inflammatory process of the central nervous system (CNS) and generation of pain.[36]

In migraine patients, vascular dysfunction is generated by increased production of adhesion molecules and, during attacks, is sustained by increased concentrations of pro-inflammatory cytokines.[34] Expression of pro-inflammatory cytokines, adhesion molecules, and activation of microglia, contribute to generate and sustain inflammation and neuropathic pain.[37,38] Human and experimental pre-clinical research also highlighted the role of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), confirming that they contribute to sustaining inflammation and neurogenic pain in migraine.[39]

Migraine is a neurovascular disorder[40] affecting approximately 11% of the population worldwide[41] and classified among the 10 most prevalent incapacitating diseases.[42] It is a common disorder even at early ages with the prevalence of 10.6% in children 5 to 15 years old.[43] The mean age of onset of migraine symptoms is about 7 years in boys and approximately 10.9 years in girls.[44] Migraine attacks may have a negatively impact the quality of life of children,[45] moreover, recurrent headaches can worsen daily activities even during adolescence.[46]

The role of fatty acids in neuroinflammation

Neurogenic inflammation plays a crucial role in the pathogenesis and progression of migraine,[47] and also leads to the sensitization and activation of perivascular meningeal afferent nerves.[48] Moreover, the activated glia is responsible for producing pro-inflammatory cytokines and mediators capable of damaging the blood–brain barrier.

FAs modulation of membrane proteins related to ion channels including the transient receptor potential family, could be responsible for omega-3 analgesic properties. Changes in lipid composition in the microenvironment influence the physiological function of membrane proteins related to cellular signaling processes,[49] especially those involving G-proteins.[50] On this basis, membrane-lipid supplementation can also be employed in the prevention or the treatment of many health problems as it is for vascular diseases and cancer pathologies.[51,52]

PUFAs produce self-mediated (i.e., acting as peroxisome proliferator-activated receptor alpha ligands) biological effects and effects mediated by their bioactive metabolites.[53,54] These bioactive compounds are specialized mediators such as epoxides, electrophilic oxo-derivatives, ethanolamines, acylglycerols, acrylamides of amino acids or neurotransmitters, and fatty acyl esters of hydroxyl fatty acids (FAHFAs),[7,55–58] exerting mostly anti-inflammatory effects.[59]

The production of pro-inflammatory proteins, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6, and IL-8 in various cell types, including endothelial cells, monocytes, macrophages, and dendritic cells is inhibited by PUFAs.[17] Moreover, PUFAs regulate the severity of inflammatory diseases and reduce neurogenic pain.[60,61] In the light of the concepts expressed above, the authors collected clinical studies carried out with omega-3 FAs, alone or in association, with the aim to evaluate the state of the art of their use in migraine therapy.

reference link : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7572026/

More information: Dietary alteration of n-3 and n-6 fatty acids for headache reduction in adults with migraine: randomized controlled trial, The BMJ, DOI: 10.1136/bmj.n1448, www.bmj.com/content/374/bmj.n1448


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