This blog post discusses how the ketogenic diet has improved my personal battle with migraine headaches. It is a n=1 anecdotal story. The results have been so positive that I decided to share. This is not intended to be personal medical advice. If you are suffering from frequent headaches, please seek medical attention.
Migraine headaches have plagued me since I was in High School. My migraines start with a visual aura (scintillating scotoma) 15-20 minutes prior to the onset of the headache. The aura is severely debilitating as it prevents me from being able to read. As you can imagine, this is highly problematic in the middle of a busy clinic! The aura is then followed by a severe global headache, fatigue, with a sense of mild cognitive slowing. Obviously this is a huge problem not just for my own quality of life, but also as a productive sports medicine physician.
The frequency of my migraines was 1-2 times a week during college and medical school. I was able to persevere regardless, but this problem added a layer of difficulty. During residency I noted that the migraines often had a pattern, consistently hitting in the late morning. This made hospital rounds particularly challenging. I also noted that many of my migraines occurred soon after a hypoglycemic episode, which also had a similar timing.
In addition to migraine headaches, I have always been prone to severe hypoglycemic episodes. I remember MANY times experiencing this as a child. I would be outside playing basketball or something, and then it would hit. I would start felling light headed, shaky, anxious, unable to think straight and I was STARVING. This prompted me to immediately consume large amounts of…whatever food I could get my hands on. Often spoonfuls of peanut butter would do the trick. These episodes started to happen with clockwork regularity in the late mornings during medical school and residency. Frequently, if the episode was severe enough, a migraine would hit once the hypoglycemia was resolved. At the time, I was typically eating breakfast around 6AM, which consisted of some type of whole grain cereal or bagels with cream cheese or peanut butter. I would be okay until about 10-11AM and then I would start to experience hypoglycemic symptoms. My strategy was to plan ahead and bring a snack to consume around 10AM. This would usually stave off a hypoglycemic attack.
Due to the early start times of inpatient rounds in residency, I often skipped breakfast in the morning merely due to being rushed. Unexpectedly, I noted that on days when I skipped breakfast, I consistently had higher energy levels, better concentration and no hypoglycemic episodes. Clearly I had been experiencing reactive hypoglecemia. I also noted that my migraines rarely struck at that typical late morning period.
Around this time, my wife, who is also a physician and was going through her residency, discovered the paleo diet and convinced me to give it a go. We were eating pretty low carb at the time, though I am unsure if I was consistently in ketosis. I did find, however, that my hypoglycemic episodes dramatically reduced in frequency, as did my migraines with this low carb approach. I also experienced dramatic improvements in my cognition! This significantly boosted my quality of life and productivity in my last 2 years in residency.
Even after cleaning up my diet I was still having occasional migraines (about 1 per month), so I decided to get things dialed in even further and went into full blown ketosis (during fellowship training). I have since been utilizing a modified ketogenic diet with some MCT oil supplementation and moderate protein intake. I use a blood ketone meter to confirm that I am eating to stay in consistent ketosis. My migraine frequency is now nearly non-existent and I couldn’t be happier!
There is a lot of ongoing research looking at the pathophysiology of Migraines. Our general current understanding is that it is due to an imbalance between the brain’s excitatory and inhibitory pathways leading to activation of the Trigemino-vascular pain pathway. This broad process is associated with several underlying mechanisms, many of which can theoretically be addressed by ketosis.
Metabolic Pathways / Mitochondria: Migraine headaches appear to be linked to metabolic / mitochondrial dysfunction (1, 2). This idea is further supported by the fact that supplementing with metabolic / mitochondrial enhancers, such as Co Enzyme Q10 and Riboflavin has been shown to provide benefit for migraine patients (3, 4). For further discussion on this topic, please see my blog posts on neutraceuticals for concussions (another metabolic disorder). The Ketogenic diet can significantly improve brain metabolism, as ketones can more efficiency produce ATP than pure glucose driven metabolism (5, 6, 7, 8, 9, 10, 11).
Migraine patients also appear to be more susceptible to oxidative stress at baseline (28) and the ketogenic diet seems to improve this (12, 13) by increasing the NAD+/NADH ratio (29, 30).
Inflammatory Pathways: Inflammation appears to play a primary role in the pathophysiology of migraine headaches (14, 15) and the Ketogenic diet has been shown to protect against neuroinflammation (16, 17).
Excitatory/Inhibitory Neurotransmission: An imbalance between glutamate (excitatory pathways) and glutamine/GABA (inhibitory pathways) plays a pivotal role in causing migraines. It appears that the ketogenic diet can potentially help restore this balance (18, 19, 20).
Cortical Spreading Depression: Migraines have been linked to what’s called cortical spreading depression and ketosis has been shown to mitigate this as well. (21).
Upon briefly reviewing the literature, there is certainly mechanistic logic giving ketosis the potential to be a powerful tool in managing certain types of migraines.
Here are a couple of studies looking at the effects of a ketogenic diet on migraine patients…
In THIS study (22), the ketogenic diet reduced migraine frequency and duration and improved the lack of cortical habituation to repetitive visual and somatosensory stimuli (commonly seen in migraine patients) measured by evoked potentials. Habituation is intended to protect the brain against cortical over excitability (23) so lack of this ability is thought to play a role in migraine development. Neuron excitability depends on energy metabolism, and it appears that people who experience frequent migraines have some dysfunction in this regard (24, 25). The above mentioned metabolic improvements associated with being in ketosis likely plays a large role in these observed improvements.
In THIS (26) study, Ketogenesis reduced migraine frequency. This improvement partially went away when the ketogenic diet was discontinued.
THIS (27) paper is a case report, and discusses two twin sisters who were obese both with frequent debilitating migraines. They both underwent a ketogenic diet for weight loss and incidentally noted a complete reduction of their migraines. When they stopped the ketogenic diet the migraines returned regardless of the improved obesity.
Clearly, the utilization of ketosis for treating migraines needs to be researched much more thoroughly and taken seriously. This blog post is merely my own personal story and the Ketogenic Diet may not be as effective for other folks. I do believe that this can be a highly effective tool to have in the tool box, and the results in my personal case have been worthy of sharing.
Thanks for reading!
1. Montagna P, Cortelli P, Monari L et al (2004) 31P-magnetic resonance spectroscopy in migraine without aura. Neurology 44(4):666–669
2. Di Lorenzo C, Pierelli F, Coppola G et al (2009) Mitochondrial DNA haplogroups influence the therapeutic response to riboflavin in migraineurs. Neurology 72:1588–1594
3. Schoenen J, Jacquy J, Lenaerts M. Effectiveness of high-dose riboflavin in migraine prophylaxis. A randomized controlled trial. Neurology 1998; 50: 466–470.
4. Sandor PS, Di Clemente L, Coppola G, et al. Efficacy of coenzyme Q10 in migraine prophylaxis: a randomized controlled trial. Neurology 2005; 64: 713–715.
5. Bough K, Wetherington J, Hassel B et al (2006) Mitochondrial biogenesis in the anticonvulsant mechanism of the ketogenic diet. Ann Neurol 60:223–235
6. DeVivo D, Leckie M, Ferrendelli J, McDougal D. Chronic ketosis and cerebral metabolism. Ann Neurol 1978; 3: 331–337.
7. Bough K, Wetherington J, Hassel B et al (2006) Mitochondrial biogenesis in the anticonvulsant mechanism of the ketogenic diet. Ann Neurol 60:223–235
8. Bough K. Energy metabolism as part of the anticonvul- sant mechanism of the ketogenic diet. Epilepsia 2008; 8: 91–93.
9. Cullingford T, Eagles D, Sato H. The ketogenic dietupregulates expression of the gene encoding the key ketogenic enzyme mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase in rat brain. Epilepsy Res 2002; 49: 99–107.
10. Prins, M.L. and J.H. Matsumoto, The collective therapeutic potential of cerebral ketone metabolism in traumatic brain injury. Journal of Lipid Research, 2014. 55(12): p. 2450-2457
11. Veech, R.L., et al., Ketone Bodies, Potential Therapeutic Uses. IUBMB Life, 2001. 51(4): p. 241
12. Kim D, Davis L, Sullivan P et al (2007) Ketone bodies are protective against oxidative stress in neocortical neurons. J Neurochem 101:1316–1326
13. Maalouf M, Sullivan P, Davis L et al (2007) Ketones inhibit mitochondrial production of reactive oxygen species production following glutamate excitotoxicity by increasing NADH oxidation. Neuroscience 145:256–264.
14. Vecchia D, Pietrobon D (2008) Migraine: a disorder of brain excitatory–inhibitory balance? Trends Neurosci 8:507–520
15. Waeber C, Moskowitz MA (2005) Migraine as an inflammatory disorder. Neurology 64:S9–S15
16. Jeong EA, Jeon BT, Shin HJ et al (2011) Ketogenic diet-induced peroxisome proliferator-activated receptor-c activation decreases neuroinflammation in the mouse hippocampus after kainic acid-induced seizures. Exp Neurol 232(2):195–202
17. Cullingford T. The ketogenic diet; fatty acids, fatty acid-activated receptors and neurological disorders. Prostaglandins Leukot Essent Fatty Acids 2004; 70: 253–264
18. Yudkoff M, Daikhin Y, Horyn O, Nissim I (2008) Ketosis and brain handling of glutamate, glutamine, and GABA. Epilepsia 8:73–75
19. Hartman AL, Gasior M, Vining EP, Rogawski MA. The neuropharmacology of the ketogenic diet. PediatrNeurol 2007; 36: 281–292.
20. Suzuki Y, Takahashi H, Fukuda M, et al. Beta-hydroxybutyrate alters GABA-transaminase activity in cultured astrocytes. Brain Res 2009; 1268: 17–23.
21. de Almeida Rabello Oliveira M, da Rocha Ataı`de T, de Oliveira S et al (2008) Effects of short-term and long-term treatment with medium- and long-chain triglycerides ketogenic diet on cortical spreading depression in young rats. Neurosci Lett 434:66–70
22. Di Lorenzo et al. Cortical functional correlates of responsiveness to short-lasting preventive intervention with ketogenic diet in migraine: a multimodal evoked potentials study. J Headache Pain. 2016;17:58
23. Schoenen J (1996) Deficient habituation of evoked cortical potentials in migraine: a link between brain biology, behavior and trigeminovascular activation? Biomed Pharmacother = Biomédecine pharmacothérapie 50:71–78
24. Barbiroli B, Montagna P, Cortelli P et al (1992) Abnormal brain and muscle energy metabolism shown by 31P magnetic resonance spectroscopy in patients affected by migraine with aura. Neurology 42:1209–1214
25. Sándor P, Dydak U, Schoenen J et al (2005) MR-spectroscopic imaging during visual stimulation in subgroups of migraine with aura. Cephalalgia 25:507–518
26. Di Lorenzo et al. Migraine improvement during short lasting ketogenesis: a proof-of-
concept study. European J. of Neurology. 2014. 170-177.
27. Di Lorenzo et al. Diet transiently improves migraine in two twin
sisters: possible role of ketogenesis? Functional Neurology 2013; 28(4): 305-308
28. Borkum JM (2016) Migraine triggers and oxidative stress: a narrative review and synthesis. Headache 56(1):12–35
29. Kim D, Davis L, Sullivan P, et al. Ketone bodies are protective against oxidative stress in neocortical neurons. J Neurochem 2007; 101: 1316–1326.
30. Maalouf M, Sullivan P, Davis L, Kim D, Rho J. Ketones inhibit mitochondrial production of reactive oxygen species production following glutamate excitotoxicity by increasing NADH oxidation. Neuroscience 2007; 145: 256–264.