Can the ketogenic diet help prevent migraine headaches?
Migraine headaches are characterized by recurrent episodes of moderate to severe throbbing pain that are typically associated with nausea, vomiting, along with light and sound sensitivity. Currently, it is estimated that between 12-14% of the population, or over 37 million people in the United States suffer from migraine headaches. Migraines are more common in females of childbearing age. One out of four women will have a migraine sometime during their lives. Despite the fact that it is the 3rd most prevalent and the 6th most disabling illness in the world, there are still very few effective treatment options.
As a headache specialist I am always looking for better treatment options for migraine headaches. For those who know me, know that I prefer conservative treatment options, such as exercise or dietary changes. For the past two years I have been doing research on all the potential neurological benefits of ketones and the ketogenic diet (KD).
The ketogenic diet mimics fasting by restricting the amount of carbohydrates that are eaten. This triggers the break down of fats, producing ketones. Research has shown that ketones have many beneficial effects both for the brain and the body. Specifically, research has shown that ketones decrease inflammation, decrease brain cortical excitability, improves mitochondria function, and decrease the amount of reactive oxygen species (ROS) thus reducing oxidative stress.
So why would the ketogenic diet or having ketones potentially help with migraine headaches?
Ketogenic diet has been used since the 1920’s for treatment for epilepsy. Many of the same medications are used to treat both conditions. Specifically, the anti-seizure medications, Topamax and Depakote are also used to prevent migraine headaches. Both migraine headaches and seizures involve paroxysmal excitability of the brain. So measures that decrease this excitability may improve both conditions. Ketones have been found to decrease the levels of the excitatory neurotransmitter glutamate. (Stafstrom, C. 2016) Decreasing glutamate levels decreases cortical excitability and decreases central sensitization. Central sensitization is a condition of the nervous system that is associated with the development and maintenance of chronic pain syndromes such as chronic migraine headaches and fibromyalgia.(Pomeror, 2017)
Decreased cortical excitability has also been shown in rat models looking at cortical spreading depression (CSD). CSD is a wave of cortical excitability that is thought to correlate with migraine aura and may be a trigger for the start of a migraine. (Stafstrom, C. 2016) It has been shown that rats treated with a KD had decreased CSD. (Di Lorenzo C. , 2015) Why CSD occurs is unclear but one hypothesis is that it is due to dysfunctional mitochondria. Mitochondria are where the cells produce ATP needed for cellular energy. When the mitochondria are dysfunctional, this lead to decreased ATP production. This decreased ATP then increases the occurrence of CSD and potentially migraines. (Sparaco, 2006) Thus, another reason ketones may be beneficial in preventing migraines is that ketones have been shown to improve mitochondrial function. (Di Lorenzo C. , 2013)
Another reason that ketones or being on the KD would be helpful in prevention of migraines is because of the anti-inflammatory effect of ketones. Neuroinflammation is inflammation medicated by the release of neuropeptides of the nerve fibers in the brain. It is the physiological mechanism of a migraine attacks. Indirect evidence that inflammation is the mediator of a migraine attack is during a migraine attack is based on the increased levels of inflammatory peptides during a migraine and the fact that non-steroidal anti-inflammatory drugs are often effective treatment for acute migraine headache.(Pietrobon, 2013)
There are several different mechanisms for the anti-inflammatory effects of ketones. First of all, compared to glucose metabolism, ketone metabolism produces fewer reactive oxygen species (ROS). ROS contribute to inflammation. Secondarily, the neurotransmitter Adenosine is increased with the KD. Adenosine has been shown to decreases both central and peripheral inflammatory. (Masino, 2013) (Dupuis, 2016) Lastly, ketones have been shown to block the NLRP3 inflammasome. Activation of NLRP3 inflammasome leads to the release of pro-inflammatory cytokines. (Youm, 2015)
So what does this mean clinically? Can the KD decrease the frequency of migraine headaches?
The first report of using the KD for migraine was in 1928. That study, 9 of the 28 patients reported some improvement, despite the fact that there was low compliance with the diet. (Stafstrom, 2016) More recently a larger observational study was done in 96 obese females. In this study, the females were randomized to either eat a KD or standard diet (SD) for 1 month. During the month on the ketogenic diet, there was a significant decrease in the frequency of migraine, the number of days with migraine, and medications used to treat migraine headaches. After that month all were transitioned back to a SD, during which their headaches again worsened. (Di Lorenzo C. , 2015)
So, if you have migraine headaches, and would like to try something conservative as a means to decreasing the frequencies of your headaches consider starting a ketogenic diet. If starting making this significant dietary changes scares you, consider jumping in the easy way by starting a ketone supplement*. Other benefits that you might notice when you have ketones in your system include fat loss, improved energy, and improved mental focus. When was the last time you heard those ‘side effects’ when discussing medication options for migraines?!?
Di Lorenzo, C. (2013). Diet transiently improves migraine in two twin sisters: possible role of ketogensis. Functional Neurology, 28 (4), 305-308.
Di Lorenzo, C. (2015). Migraine improvement during short lasting ketogenesis: a proof of concept study. European Journal of Neurology, 22, 170-177.
Dupuis, N. P. (2016). Anti-inflammatory Effects of a Ketogenic Diet. In S. Masino (Ed.), Ketogenic Diet and Metabolic Therapies (pp. 147-155).
Masino, S. (2013). Ketogenic Diet and Pian. Journal of Child Neurology, 28 (8), 993-1001.
Pietrobon, D. M. (2013). Pathophysiology of Migraine. Annual Review of Physiology, 75, 365-91.
Pomeror, J. L. (2017). Ketamine Infusion for Treatment Refractory Headache. Headache, 57 (2), 276-282.
Sparaco, M. (2006). Mitochondrial dysfunction and migraine: evidence and hypotheses. Cephalalgia, 361-372.
Stafstrom, C. (2016). Dietary Therapy for Neurolgical Disorders. In S. A. Masino (Ed.), Ketogenic Diet and Metabolic Therapies. Oxford.
Stafstrom, C. (2012). The ketogenic diet as a treatment paradigm for diverse neurological disorders. Frontiers in Pharmacology, 3, 1-8.
Youm, Y.-H. (2015). Ketone body Beta Hydroxybutrate blocks the the NLRP3 inflammasome-mediated inflammatory disease. Nature Medicine, 21, 263-269.
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