Ketogenic Diet

Summary:
A very low-carbohydrate, high-fat diet that shifts the body’s primary fuel from glucose to ketones. It has shown promise in reducing migraine frequency, likely via effects on mitochondrial function and inflammation.

Biological Plausibility

Ketones enhance mitochondrial energy efficiency, reduce reactive oxygen species, and suppress cortical spreading depression—mechanisms all implicated in migraine. The diet also reduces insulin and glutamate, which modulate pain and cortical excitability.

Evidence

Open-label and crossover studies suggest significant reductions in migraine frequency, particularly in overweight individuals and those with metabolic comorbidities. While RCTs are limited, mechanistic data and clinical observations are strong.

Effect Size

Typical reduction of 2–4 migraine days/month. Some patients report a 50–75% reduction in frequency within 1–2 months of achieving ketosis.

⚠️ Risk

GI side effects are common early on (constipation, nausea). Risk of nutritional deficiencies exists without proper guidance. Requires careful planning.

Cost

$

Scores

  • Benefit: 4
  • Burden: 3
  • Ratio: 1.33

Clinical Takeaways

  • Highly effective in motivated patients who can maintain nutritional ketosis.
  • Should be guided by a provider experienced in ketogenic therapy.
  • May be particularly helpful for those with PCOS, insulin resistance, or epilepsy.

Key References

  • Di Lorenzo C, et al. *Migraine improvement during short-lasting ketogenesis: a proof-of-concept study.* Eur J Neurol. 2015.
  • Ruskin DN, et al. *Ketogenic diets and migraine: mechanisms and potential clinical relevance.* Front Neurosci. 2021.
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