Table 1 LARGE trial inclusion and exclusion criteria

1. Migraine (with or without aura) diagnosed at least 1 year ago

2. Migraine onset occurred before 50 years of age

3. Adult males and females, aged 18–80 years (inclusive) at screening

4. 2–6 migraine episodes and fewer than 6 ‘other’ headache types per month, averaged over the previous 3 months

5. Able to differentiate between migraine and ‘other’ headache types

6. Able to commit to taking oral capsules once a day for 14 weeks

7. Able to fill out paper daily migraine diary over 14 weeks

1. Taking medications/drugs that affect vascular tone or blood pressure

2. Continuous residual headaches

3. Headache disorder or facial pain disorder other than migraine

4. Change in migraine treatment in previous 3 months

5. Taking > 2 migraine-prevention drugs

6. L-arginine tablets or aged garlic extracts in previous 3 months

7. Possibility of pregnancy or breastfeeding during study

8. Adverse reactions to food containing L-arginine or garlic

9. Clinical reports of kidney/liver dysfunction

10. Known risks of bleeding or coagulopathy, or currently on blood-thinning medications

11. Cancer, haemochromatosis or diabetes

12. Severe psychiatric disorder or other neurological disorders

13. Acute/chronic pain disorders, infections, cardiovascular or cerebrovascular disease

14. Poorly controlled depression or anxiety

15. Antipsychotic or antidepressant medications/drugs over past 3 months

16. Low blood pressure or complications arising from it

17. Diagnoses other than migraine as primary cause of headaches

18. Changes in digestive system over past few months

19. Headaches cause fainting or other medical emergencies

20. Substance abuse/dependence/addiction in previous 3 months

21. Procedure or injection to treat migraine over past 3 months

22. Implanted or external nerve stimulator to treat migraines

23. Pain medications on most days a week for headaches

24. Opioid medications each day for chronic pain

25. History of overusing medications

26. History of eye pathology, surface disorder, surgery (except cataract extraction), or injury

27. Difficulty seeing clearly (with glasses or contact lenses, if required)

28. History of diabetes, hypertension, collagen vascular disease, vasculitis, or renal disease/failure

29. Smoke > 1 pack of cigarettes a day

30. Disorders of the optic nerve or retina

31. Reasons that retinae may not be clearly viewed

32. Poor image perception due to cataract or unstable fixation

33. Anaemia or iron deficiency

34. Participation in concurrent research trial