A recent study published in the journal Nutrients explored the link between three ketogenic diets (KD) and migraine symptoms. Preliminary results suggested that all the three diets are associated with reductions in the frequency and intensity of migraines. Migraineurs also reported feeling less fatigue than they did before adopting the diet.

Study: The Effect of Three Different Ketogenic Diet Protocols on Migraine and Fatigue in Chronic and High-Frequency Episodic Migraine: A Pilot Study. Image Credit: SewCreamStudio / Shutterstock

Chronic and frequent sufferers know that migraines can be incapacitating. They affect the central nervous system and can involve several autonomic, neurological, and gastrointestinal symptoms. Migraine headaches are associated with many issues: nausea, vomiting, blurry vision, congestion, diarrhea, and abdominal cramps. Migraineurs are often diagnosed with fatigue, depression, and concentration impairment as a result of their condition. The impact of migraines goes beyond the episodes themselves, affecting work productivity, social activities, and quality of life.

Diet modifications have been studied as a possible treatment for migraines. KD treatments, which were initially developed to treat childhood epilepsy, involve decreasing the consumption of carbohydrates and limiting the consumption of proteins. Caloric requirements are maintained through lipid consumption. These protocols aim to induce ketone production in the body, raising the brain’s ATP/ADP ratio. Previous studies found that KD protocols could effectively treat migraines, but whether they could reduce fatigue was not explored.

“This study aims to quantify the fatigue of chronic and high-frequency episodic migraineurs before and after diet therapy.”

About the study

A team of Italian researchers offered KD therapies as a preventative measure for migraineurs. They recruited 76 participants who had been clinically diagnosed with either chronic or high-frequency episodic migraines. These patients were interested in exploring alternative migraine therapies over conventional treatments. They were treated with KD protocols between January 2020 and December 2022 at a nutritional outpatient clinic in Udine, Italy.

All participants were over 18 years old with a body mass index (BMI) of less than 18 kg/m². Researchers included individuals who were not pregnant or breastfeeding, not suffering any intellectual impairments, and had not previously undergone surgery. Participants did not have any physical or mental conditions other than anxiety disorder or major depressive disorder. All participants had compiled three-month headache diaries before they began the KD treatment; these were used as a retrospective source of data.

At the beginning of the study, researchers calculated scores based on self-reported questionnaires for the Fatigue Severity Scale (FSS), Migraine Disability Questionnaire (MIDAS), and Headache Impact Test (HIT-6) from all the participants. A score of over 4 on the FSS scale meant the participant was pathologically fatigued.

A nutritionist collected anthropometric data and calculated the fat mass (FM), free-fat mass (FFM), and BMI. The same measurements were reassessed after three months of implementing a KD diet, the adherence to which was also assessed by the nutritionist.

The diet a participant was prescribed was based on their BMI. Patients with a BMI of 18.5-24.9 kg/m² were asked to follow the 2:1 KD, consuming 1600-2300 Kcal daily. The low-glycemic-index diet (LGID), which involves consuming 1300-1500 Kcal per day, was prescribed to participants with a BMI of 25-29.9 kg/m², who could be classified as overweight. Participants with a BMI of over 30 kg/m² were asked to follow a very low-calorie ketogenic diet (VLCKD) with a caloric intake of 600-800 Kcal per day to promote weight loss.

The primary research objective was to compare fatigue levels before and after three months of following a KD regimen. Researchers also examined the effect of the diet on migraine frequency and intensity, as well as migraine-associated disability and quality of life. Finally, they calculated correlations between fatigue reductions and reductions in migraine frequencies, intensities, BMI, and other factors.

Findings

Participants were, on average, 46 years old, and a majority (>80%) were women. About 60% were chronic migraine sufferers, while the others had high-frequency episodic migraines. On average, they had the condition for slightly over 22 years. Twenty-one participants followed the 2:1 KD treatment, 41 underwent the LGID treatment, and 14 were prescribed the VLCKD treatment.

At the beginning of the treatment, 66% of the participants reported having pathologic fatigue, indicated by an FSS score >4. However, three months after the treatment began, mean fatigue scores declined significantly. The total fatigue score decreased from 4.9 to 3.9, and all three diets showed a positive effect on fatigue.

The diets also reduced the frequency of migraine days per month from 18 to 8 days and the intensity of attacks from 8.1 to 5.3. MIDAS scores also declined from 76 to 37, while the HIT-6 score decreased from 65 to 54. Fat mass and BMI decreased while free-fat mass was preserved. Researchers found that the decrease in fatigue was positively associated with the decline in the MIDAS and HIT-6 scores.

New treatments can often have severe side effects, but in this case, adverse effects were relatively mild. Some patients reported diarrhea, mild constipation, abdominal pain, and nausea. To check for other adverse effects, researchers conducted blood tests after three months of the treatment and found no signs of high cholesterol or elevated uric acid levels.

Conclusions

In this pilot study, researchers found promising evidence that KD therapies can effectively prevent migraine frequency and intensity while also reducing fatigue and improving quality of life. However, the team noted that further studies with larger sample sizes are required to validate these findings. They also acknowledged that the study was not a double-blinded study; they could, therefore, not exclude the possibility that their results were due to the placebo effect. Despite these limitations, the encouraging findings of this pilot study will inform future explorations into effective treatments for chronic and frequent migraine attacks.

Journal reference:

• Tereshko, Y., Bello, S.D., Lorenzo, C.D., Pittino, A., Filippi, F., Belgrado, E. Lettieri, C., Merlino, G., Gigli, G.L., Valente, M. The Effect of Three Different Ketogenic Diet Protocols on Migraine and Fatigue in Chronic and High-Frequency Episodic Migraine: A Pilot Study. Nutrients (2023). https://doi.org/10.3390/nu15204334, https://www.mdpi.com/2072-6643/15/20/4334