Why do some dietary migraine patients claim they get headaches from placebos?

Clin Exp Allergy. 2000 May;30(5):739-43. doi: 10.1046/j.1365-2222.2000.00783.x.


Background: In six double-blind studies involving 182 tests of dietary migraine patients sensitive to tyramine and beta-phenylethylamine, 18% reported headaches from placebos which were all concealed in gelatin capsules.

Objective: The purpose of this research was to test a hypothesis: gelatin is partially hydrolysed animal protein; (partially) hydrolysed vegetable protein (PHVP) is known to cause migraine; perhaps the gelatin caused some of the headaches.

Method: The author tested this hypothesis on himself because he suffers from dietary migraine. He proved this in a double-blind test with tyramine hydrochloride (TYH). The amount required for the test was so small (1 mg) that it was tasteless and capsules were unnecessary. The author then undertook tests with a capsule, PHVP, monosodium glutamate (MSG) aspartame (a dipeptide) and TYH, adjusting quantities to give a moderate headache. Samples were mixed with foods to simulate normal eating: the capsule with potato chips, aspartame with orange juice and the rest with cottage cheese or ricotta cheese. Times were measured from ingestion (1) to start of the headache and (2) to maximum headache intensity. Each experiment was repeated three times. The headaches were relieved with caffeine.

Results: Of eight double-blind test samples, the author identified correctly the two placebos and five of the six samples containing tyramine. Quantities giving moderate headaches were: 1 gelatin capsule, 400 mg MSG, 118 mg PHVP, 4.0 mg aspartame and 1.0 mg TYH. Typical times for the three repetitions of the two time periods were 8, 9 and 11 and 17, 19 and 22 min.

Conclusions: Capsules may give headaches to dietary migraine patients that are similar to those from foods. This would explain some of the headaches of patients from placebos. The double-blind test and the repeatability of the time measurements demonstrated the validity of the experiments.

MeSH terms

  • Analgesics / administration & dosage
  • Capsules / administration & dosage
  • Capsules / adverse effects
  • Diet / adverse effects*
  • Double-Blind Method
  • Gelatin / adverse effects
  • Humans
  • Male
  • Migraine Disorders / drug therapy
  • Migraine Disorders / etiology*
  • Phenethylamines / administration & dosage
  • Phenethylamines / adverse effects
  • Placebos / adverse effects*
  • Tyramine / administration & dosage
  • Tyramine / adverse effects


  • Analgesics
  • Capsules
  • Phenethylamines
  • Placebos
  • phenethylamine
  • Gelatin
  • Tyramine