Low unesterified: Esterified eicosapentaenoic acid (EPA) plasma concentration ratio is associated with bipolar disorder episodes, and omega-3 plasma concentrations are altered by treatment

Bipolar Disorders

Volumn 17, Issue 7, 2015, Pages 729-742

  Saunders, Erika F H ^a,b,c   Reider, Aubrey ^a   Singh, Gagan ^a   Gelenberg, Alan J ^a   Rapoport, Stanley I ^d  

^a PENN STATE MILTON S HERSHEY MEDICAL CENTER   (United States)

^b UNIVERSITY OF MICHIGAN HEALTH SYSTEM   (United States)

^c UNIVERSITY OF MICHIGAN   (United States)

^d NATIONAL INSTITUTE ON AGING   (United States)

Author keywords

Bipolar disorder; Eicosapentaenoic acid; Inflammation; Omega 3

Indexed keywords

ANTIDEPRESSANT AGENT; ARACHIDONIC ACID; ARIPIPRAZOLE; BIOLOGICAL MARKER; CARBAMAZEPINE; DOCOSAHEXAENOIC ACID; HALOPERIDOL; ICOSAPENTAENOIC ACID; LAMOTRIGINE; LINOLEIC ACID; LINOLENIC ACID; LITHIUM SALT; MOOD STABILIZER; NEUROLEPTIC AGENT; OLANZAPINE; OMEGA 3 FATTY ACID; OMEGA 6 FATTY ACID; PERPHENAZINE; QUETIAPINE; RISPERIDONE; SEDATIVE AGENT; VALPROIC ACID; MONOUNSATURATED FATTY ACID; PALMITOLEIC ACID; TRANQUILIZER;

ADULT; ARTICLE; BIPOLAR I DISORDER; BIPOLAR II DISORDER; BLOOD BRAIN BARRIER; CLINICAL ARTICLE; CLINICAL EFFECTIVENESS; CONTROLLED STUDY; DEPRESSION; DISEASE SEVERITY; ETHNICITY; FEMALE; FOLLOW UP; HUMAN; LIPID BLOOD LEVEL; LIPID METABOLISM; MALE; MANIA; OBSERVATIONAL STUDY; PANIC; PARALLEL DESIGN; PRIORITY JOURNAL; PSYCHOSIS; BEHAVIOR; BIPOLAR DISORDER; BLOOD; DRUG EFFECTS; LONGITUDINAL STUDY; METABOLISM; MIDDLE AGED; PHYSIOLOGY; PSYCHOLOGY; SEVERITY OF ILLNESS INDEX; STATISTICS; SUICIDE; SYNAPTIC TRANSMISSION;

ADULT; ANTIDEPRESSIVE AGENTS; ANTIMANIC AGENTS; ARACHIDONIC ACID; BEHAVIORAL SYMPTOMS; BIOMARKERS; BIPOLAR DISORDER; EICOSAPENTAENOIC ACID; FATTY ACIDS, MONOUNSATURATED; FATTY ACIDS, OMEGA-3; FATTY ACIDS, OMEGA-6; FEMALE; HUMANS; LONGITUDINAL STUDIES; MALE; MIDDLE AGED; SEVERITY OF ILLNESS INDEX; STATISTICS AS TOPIC; SUICIDE; SYNAPTIC TRANSMISSION;

EID: 84945263490     PISSN: 13985647     EISSN: 13995618     Source Type: Journal    
DOI: 10.1111/bdi.12337     Document Type: Article

References (103)

1. Merikangas KR, Akiskal HS, Angst J et al. Lifetime and 12-month prevalence of bipolar spectrum disorder in the National Comorbidity Survey replication. Arch Gen Psychiatry 2007; 64: 543-552.
2. Craddock N, Sklar P. Genetics of bipolar disorder. Lancet 2013; 381: 1654-1662.
3. Goodwin FK, Jamison KR. Manic-Depressive Illness: Bipolar Disorders and Recurrent Depression. New York: Oxford University Press, 2007: 1262.
4. American Psychiatric Association. DSM-5 Task Force. Diagnostic and Statistical Manual of Mental Disorders: DSM-5, 5th edn. Washington, DC: American Psychiatric Association, 2013: 947.
5. Ghaemi SN, Bauer M, Cassidy F et al. Diagnostic guidelines for bipolar disorder: a summary of the International Society for Bipolar Disorders Diagnostic Guidelines Task Force Report. Bipolar Disord 2008; 10: 117-128.
6. Tohen M, Frank E, Bowden CL et al. The International Society for Bipolar Disorders (ISBD) Task Force report on the nomenclature of course and outcome in bipolar disorders. Bipolar Disord 2009; 11: 453-473.
7. Vieta E, Suppes T. Bipolar II disorder: arguments for and against a distinct diagnostic entity. Bipolar Disord 2008; 10: 163-178.
8. Hibbeln JR, Palmer JW, Davis JM. Are disturbances in lipid-protein interactions by phospholipase-A2 a predisposing factor in affective illness? Biol Psychiatry 1989; 25: 945-961.
9. Allison JH, Stewart MA. Reduced brain inositol in lithium-treated rats. Nature 1971; 233: 267-268.
10. Svennerholm L. Distribution and fatty acid composition of phosphoglycerides in normal human brain. J Lipid Res 1968; 9: 570-579.
11. Rapoport SI. Brain arachidonic and docosahexaenoic acid cascades are selectively altered by drugs, diet and disease. Prostaglandins Leukot Essent Fatty Acids 2008; 79: 153-156.
12. Rapoport SI. Lithium and the other mood stabilizers effective in bipolar disorder target the rat brain arachidonic acid cascade. ACS Chem Neurosci 2014; 5: 459-467.
13. Rapoport SI, Basselin M, Kim HW, Rao JS. Bipolar disorder and mechanisms of action of mood stabilizers. Brain Res Rev 2009; 61: 185-209.
14. Rapoport SI, Bosetti F. Do lithium and anticonvulsants target the brain arachidonic acid cascade in bipolar disorder? Arch Gen Psychiatry 2002; 59: 592-596.
15. Freeman MP. Omega-3 fatty acids and perinatal depression: a review of the literature and recommendations for future research. Prostaglandins Leukot Essent Fatty Acids 2006; 75: 291-297.
16. Noaghiul S, Hibbeln JR. Cross-national comparisons of seafood consumption and rates of bipolar disorders. Am J Psychiatry 2003; 160: 2222-2227.
17. Sublette ME, Bosetti F, DeMar JC et al. Plasma free polyunsaturated fatty acid levels are associated with symptom severity in acute mania. Bipolar Disord 2007; 9: 759-765.
18. Chiu CC, Huang SY, Su KP et al. Polyunsaturated fatty acid deficit in patients with bipolar mania. Eur Neuropsychopharmacol 2003; 13: 99-103.
19. McNamara RK, Jandacek R, Rider T, Tso P, Dwivedi Y, Pandey GN. Selective deficits in erythrocyte docosahexaenoic acid composition in adult patients with bipolar disorder and major depressive disorder. J Affect Disord 2010; 126: 303-311.
20. Evans SJ, Kamali M, Prossin AR et al. Association of plasma omega-3 and omega-6 lipids with burden of disease measures in bipolar subjects. J Psychiatr Res 2012; 46: 1435-1441.
21. Evans SJ, Prossin AR, Harrington GJ et al. Fats and factors: lipid profiles associate with personality factors and suicidal history in bipolar subjects. PLoS ONE 2012; 7: e29297.
22. Purdon D, Arai T, Rapoport S. No evidence for direct incorporation of esterified palmitic acid from plasma into brain lipids of awake adult rat. J Lipid Res 1997; 38: 526-530.
23. Ouellet M, Emond V, Chen CT et al. Diffusion of docosahexaenoic and eicosapentaenoic acids through the blood-brain barrier: an in situ cerebral perfusion study. Neurochem Int 2009; 55: 476-482.
24. Sheehan DV, Lecrubier Y, Sheehan KH et al. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 1998; 59 (Suppl. 20): 22-33.
25. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960; 23: 56-62.
26. Altman EG, Hedeker DR, Janicak PG, Peterson JL, Davis JM. The Clinician-Administered Rating Scale for Mania (CARS-M): development, reliability, and validity. Biol Psychiatry 1994; 36: 124-134.
27. Sublette ME, Segal-Isaacson CJ, Cooper TB et al. Validation of a food frequency questionnaire to assess intake of n-3 polyunsaturated fatty acids in subjects with and without major depressive disorder. J Am Diet Assoc 2011; 111: 117-123.e1-2.
28. NIAAA Alcohol Facts and Statistics [webpage]. National Institute on Alcohol Abuse and Alcoholism, 2015. Available from: http://www.niaaa.nih.gov/alcohol-health/overview-alcohol-consumption/alcohol-facts-and-statistics [accessed July 2015].
29. Folch J, Lees M, Sloan Stanley GH. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 1957; 226: 497-509.
30. Breckenridge WC, Kuksis A. Specific distribution of short-chain fatty acids in molecular distillates of bovine milk fat. J Lipid Res 1968; 9: 388-393.
31. Makrides M, Neumann MA, Byard RW, Simmer K, Gibson RA. Fatty acid composition of brain, retina, and erythrocytes in breast- and formula-fed infants. Am J Clin Nutr 1994; 60: 189-194.
32. DeMar JC Jr, Ma K, Bell JM, Rapoport SI. Half-lives of docosahexaenoic acid in rat brain phospholipids are prolonged by 15 weeks of nutritional deprivation of n-3 polyunsaturated fatty acids. J Neurochem 2004; 91: 1125-1137.
33. Serhan CN. Novel chemical mediators in the resolution of inflammation: resolvins and protectins. Anesthesiol Clin 2006; 24: 341-364.
34. Ramsden CE, Mann JD, Faurot KR et al. Low omega-6 vs. low omega-6 plus high omega-3 dietary intervention for chronic daily headache: protocol for a randomized clinical trial. Trials 2011; 12: 97.
35. Perneger TV. What's wrong with Bonferroni adjustments. BMJ 1998; 316: 1236-1238.
36. Sublette ME, Ellis SP, Geant AL, Mann JJ. Meta-analysis of the effects of eicosapentaenoic acid (EPA) in clinical trials in depression. J Clin Psychiatry 2011; 72: 1577-1584.
37. Sarris J, Mischoulon D, Schweitzer I. Omega-3 for bipolar disorder: meta-analyses of use in mania and bipolar depression. J Clin Psychiatry 2012; 73: 81-86.
38. Evans SJ, Ringrose RN, Harrington GJ, Mancuso P, Burant CF, McInnis MG. Dietary intake and plasma metabolomic analysis of polyunsaturated fatty acids in bipolar subjects reveal dysregulation of linoleic acid metabolism. J Psychiatr Res 2014; 57: 58-64.
39. Grosso G, Pajak A, Marventano S et al. Role of omega-3 fatty acids in the treatment of depressive disorders: a comprehensive meta-analysis of randomized clinical trials. PLoS ONE 2014; 9: e96905.
40. Brooks JD, Milne GL, Yin H, Sanchez SC, Porter NA, Morrow JD. Formation of highly reactive cyclopentenone isoprostane compounds (A3/J3-isoprostanes) in vivo from eicosapentaenoic acid. J Biol Chem 2008; 283: 12043-12055.
41. Arita M, Yoshida M, Hong S et al. Resolvin E1, an endogenous lipid mediator derived from omega-3 eicosapentaenoic acid, protects against 2, 4, 6-trinitrobenzene sulfonic acid-induced colitis. Proc Natl Acad Sci USA 2005; 102: 7671-7676.
42. Jeng JY, Lee WH, Tsai YH, Chen CY, Chao SY, Hsieh RH. Functional modulation of mitochondria by eicosapentaenoic acid provides protection against ceramide toxicity to C6 glioma cells. J Agric Food Chem 2009; 57: 11455-11462.
43. Leroy C, Tricot S, Lacour B, Grynberg A. Protective effect of eicosapentaenoic acid on palmitate-induced apoptosis in neonatal cardiomyocytes. Biochim Biophys Acta 2008; 1781: 685-693.
44. Yamagata K, Tagami M, Takenaga F, Yamori Y, Nara Y, Itoh S. Polyunsaturated fatty acids induce tight junctions to form in brain capillary endothelial cells. Neuroscience 2003; 116: 649-656.
45. Omura M, Kobayashi S, Mizukami Y et al. Eicosapentaenoic acid (EPA) induces Ca(2+)-independent activation and translocation of endothelial nitric oxide synthase and endothelium-dependent vasorelaxation. FEBS Lett 2001; 487: 361-366.
46. Igarashi M, Chang L, Ma K, Rapoport SI. Kinetics of eicosapentaenoic acid in brain, heart and liver of conscious rats fed a high n-3 PUFA containing diet. Prostaglandins Leukot Essent Fatty Acids 2013; 89: 403-412.
47. Oldendorf WH, Brown WJ. Greater number of capillary endothelial cell mitochondria in brain than in muscle. Proc Soc Exp Biol Med 1975; 149: 736-738.
48. Goldstein BI, Young LT. Toward clinically applicable biomarkers in bipolar disorder: focus on BDNF, inflammatory markers, and endothelial function. Curr Psychiatry Rep 2013; 15: 425.
49. Pomponi M, Janiri L, La Torre G et al. Plasma levels of n-3 fatty acids in bipolar patients: deficit restricted to DHA. J Psychiatr Res 2013; 47: 337-342.
50. Smith QR, Nagura H. Fatty acid uptake and incorporation in brain: studies with the perfusion model. J Mol Neurosci 2001; 16: 167-172.
51. Robinson PJ, Noronha J, DeGeorge JJ, Freed LM, Nariai T, Rapoport SI. A quantitative method for measuring regional in vivo fatty-acid incorporation into and turnover within brain phospholipids: review and critical analysis. Brain Res Brain Res Rev 1992; 17: 187-214.
52. Dawson E, Gill M, Curtis D et al. Genetic association between alleles of pancreatic phospholipase A2 gene and bipolar affective disorder. Psychiatr Genet 1995; 5: 177-180.
53. Jacobsen NJ, Franks EK, Owen MJ, Craddock NJ. Mutational analysis of phospholipase A2A: a positional candidate susceptibility gene for bipolar disorder. Mol Psychiatry 1999; 4: 274-279.
54. Ikenaga EH, Talib LL, Ferreira AS, Machado-Vieira R, Forlenza OV, Gattaz WF. Reduced activities of phospholipases A2 in platelets of drug-naïve bipolar disorder patients. Bipolar Disord 2015; 17: 97-101.
55. Meira-Lima I, Jardim D, Junqueira R, Ikenaga E, Vallada H. Allelic association study between phospholipase A2 genes and bipolar affective disorder. Bipolar Disord 2003; 5: 295-299.
56. Noponen M, Sanfilipo M, Samanich K et al. Elevated PLA2 activity in schizophrenics and other psychiatric patients. Biol Psychiatry 1993; 34: 641-649.
57. Ross BM, Hughes B, Kish SJ, Warsh JJ. Serum calcium-independent phospholipase A2 activity in bipolar affective disorder. Bipolar Disord 2006; 8: 265-270.
58. Kim HW, Rapoport SI, Rao JS. Altered arachidonic acid cascade enzymes in postmortem brain from bipolar disorder patients. Mol Psychiatry 2011; 16: 419-428.
59. Tremblay BL, Cormier H, Rudkowska I, Lemieux S, Couture P, Vohl MC. Association between polymorphisms in phospholipase A2 genes and the plasma triglyceride response to an n-3 PUFA supplementation: a clinical trial. Lipids Health Dis 2015; 14: 12.
60. Igarashi M, DeMar JC Jr, Ma K, Chang L, Bell JM, Rapoport SI. Upregulated liver conversion of alpha-linolenic acid to docosahexaenoic acid in rats on a 15 week n-3 PUFA-deficient diet. J Lipid Res 2007; 48: 152-164.
61. McNamara RK, Jandacek R, Rider T, Tso P, Cole-Strauss A, Lipton JW. Differential effects of antipsychotic medications on polyunsaturated fatty acid biosynthesis in rats: relationship with liver delta6-desaturase expression. Schizophr Res 2011; 129: 57-65.
62. MacKinnon DF, Zamoiski R. Panic comorbidity with bipolar disorder: what is the manic-panic connection? Bipolar Disord 2006; 8: 648-664.
63. 2 challenge? J Psychopharmacol 2003; 17: 252-259.
64. Bunney WE Jr, Goodwin FK, Murphy DL, House KM, Gordon EK. The "switch process" in manic-depressive illness. II. Relationship to catecholamines, REM sleep, and drugs. Arch Gen Psychiatry 1972; 27: 304-309.
65. Joyce PR, Fergusson DM, Woollard G, Abbott RM, Horwood LJ, Upton J. Urinary catecholamines and plasma hormones predict mood state in rapid cycling bipolar affective disorder. J Affect Disord 1995; 33: 233-243.
66. Joesting JJ, Moon ML, Gainey SJ, Tisza BL, Blevins NA, Freund GG. Fasting induces IL-1 resistance and free-fatty acid-mediated up-regulation of IL-1R2 and IL-1RA. Front Immunol 2014; 5: 315.
67. Moon ML, Joesting JJ, Lawson MA et al. The saturated fatty acid, palmitic acid, induces anxiety-like behavior in mice. Metabolism 2014; 63: 1131-1140.
68. Ramsden CE, Faurot KR, Zamora D et al. Targeted alteration of dietary n-3 and n-6 fatty acids for the treatment of chronic headaches: a randomized trial. Pain 2013; 154: 2441-2451.
69. Osher Y, Bersudsky Y, Belmaker RH. Omega-3 eicosapentaenoic acid in bipolar depression: report of a small open-label study. J Clin Psychiatry 2005; 66: 726-729.
70. Sagduyu K, Dokucu ME, Eddy BA, Craigen G, Baldassano CF, Yildiz A. Omega-3 fatty acids decreased irritability of patients with bipolar disorder in an add-on, open label study. Nutr J 2005; 4: 6.
71. Wozniak J, Biederman J, Mick E et al. Omega-3 fatty acid monotherapy for pediatric bipolar disorder: a prospective open-label trial. Eur Neuropsychopharmacol 2007; 17: 440-447.
72. Clayton EH, Hanstock TL, Hirneth SJ, Kable CJ, Garg ML, Hazell PL. Reduced mania and depression in juvenile bipolar disorder associated with long-chain omega-3 polyunsaturated fatty acid supplementation. Eur J Clin Nutr 2009; 63: 1037-1040.
73. Stoll AL, Severus WE, Freeman MP et al. Omega 3 fatty acids in bipolar disorder: a preliminary double-blind, placebo-controlled trial. Arch Gen Psychiatry 1999; 56: 407-412.
74. Frangou S, Lewis M, McCrone P. Efficacy of ethyl-eicosapentaenoic acid in bipolar depression: randomised double-blind placebo-controlled study. Br J Psychiatry 2006; 188: 46-50.
75. Chiu CC, Huang SY, Chen CC, Su KP. Omega-3 fatty acids are more beneficial in the depressive phase than in the manic phase in patients with bipolar I disorder. J Clin Psychiatry 2005; 66: 1613-1614.
76. Keck PE Jr, Mintz J, McElroy SL et al. Double-blind, randomized, placebo-controlled trials of ethyl-eicosapentanoate in the treatment of bipolar depression and rapid cycling bipolar disorder. Biol Psychiatry 2006; 60: 1020-1022.
77. Frangou S, Lewis M, Wollard J, Simmons A. Preliminary in vivo evidence of increased N-acetyl-aspartate following eicosapentanoic acid treatment in patients with bipolar disorder. J Psychopharmacol 2007; 21: 435-439.
78. Gracious BL, Chirieac MC, Costescu S, Finucane TL, Youngstrom EA, Hibbeln JR. Randomized, placebo-controlled trial of flax oil in pediatric bipolar disorder. Bipolar Disord 2010; 12: 142-154.
79. Murphy BL, Stoll AL, Harris PQ et al. Omega-3 fatty acid treatment, with or without cytidine, fails to show therapeutic properties in bipolar disorder: a double-blind, randomized add-on clinical trial. J Clin Psychopharmacol 2012; 32: 699-703.
80. Ross BM, Seguin J, Sieswerda LE. Omega-3 fatty acids as treatments for mental illness: which disorder and which fatty acid? Lipids Health Dis 2007; 6: 21.
81. Martins JG. EPA but not DHA appears to be responsible for the efficacy of omega-3 long chain polyunsaturated fatty acid supplementation in depression: evidence from a meta-analysis of randomized controlled trials. J Am Coll Nutr 2009; 28: 525-542.
82. Martins JG, Bentsen H, Puri BK. Eicosapentaenoic acid appears to be the key omega-3 fatty acid component associated with efficacy in major depressive disorder: a critique of Bloch and Hannestad and updated meta-analysis. Mol Psychiatry 2012; 17: 1144-1149.
83. Appleton KM, Rogers PJ, Ness AR. Updated systematic review and meta-analysis of the effects of n-3 long-chain polyunsaturated fatty acids on depressed mood. Am J Clin Nutr 2010; 91: 757-770.
84. Lin PY, Mischoulon D, Freeman MP et al. Are omega-3 fatty acids antidepressants or just mood-improving agents? The effect depends upon diagnosis, supplement preparation, and severity of depression. Mol Psychiatry 2012; 17: 1161-1163.
85. Blasbalg TL, Hibbeln JR, Ramsden CE, Majchrzak SF, Rawlings RR. Changes in consumption of omega-3 and omega-6 fatty acids in the United States during the 20th century. Am J Clin Nutr 2011; 93: 950-962.
86. Ramsden CE, Ringel A, Feldstein AE et al. Lowering dietary linoleic acid reduces bioactive oxidized linoleic acid metabolites in humans. Prostaglandins Leukot Essent Fatty Acids 2012; 87: 135-141.
87. Igarashi M, Gao F, Kim HW, Ma K, Bell JM, Rapoport SI. Dietary n-6 PUFA deprivation for 15 weeks reduces arachidonic acid concentrations while increasing n-3 PUFA concentrations in organs of post-weaning male rats. Biochim Biophys Acta 2009; 1791: 132-139.
88. Baptista T, Uzcategui E, Arape Y et al. Migraine life-time prevalence in mental disorders: concurrent comparisons with first-degree relatives and the general population. Invest Clin 2012; 53: 38-51.
89. Ortiz A, Cervantes P, Zlotnik G et al. Cross-prevalence of migraine and bipolar disorder. Bipolar Disord 2010; 12: 397-403.
90. Dilsaver SC, Benazzi F, Oedegaard KJ, Fasmer OB, Akiskal HS. Is a family history of bipolar disorder a risk factor for migraine among affectively ill patients? Psychopathology 2009; 42: 119-123.
91. McIntyre RS, Konarski JZ, Wilkins K, Bouffard B, Soczynska JK, Kennedy SH. The prevalence and impact of migraine headache in bipolar disorder: results from the Canadian Community Health Survey. Headache 2006; 46: 973-982.
92. McIntyre RS, Konarski JZ, Soczynska JK et al. Medical comorbidity in bipolar disorder: implications for functional outcomes and health service utilization. Psychiatr Serv 2006; 57: 1140-1144.
93. Fasmer OB. The prevalence of migraine in patients with bipolar and unipolar affective disorders. Cephalalgia 2001; 21: 894-899.
94. Fasmer OB, Oedegaard KJ. Clinical characteristics of patients with major affective disorders and comorbid migraine. World J Biol Psychiatry 2001; 2: 149-155.
95. Saunders EF, Nazir R, Kamali M et al. Gender differences, clinical correlates, and longitudinal outcome of bipolar disorder with comorbid migraine. J Clin Psychiatry 2014; 75: 512-519.
96. Antonova M, Wienecke T, Olesen J, Ashina M. Prostaglandin E(2) induces immediate migraine-like attack in migraine patients without aura. Cephalalgia 2012; 32: 822-833.
97. Moskowitz MA, Buzzi MG. Migraine general aspects. Handb Clin Neurol 2010; 97: 253-266.
98. Buzzi MG, Moskowitz MA. The pathophysiology of migraine: year 2005. J Headache Pain 2005; 6: 105-111.
99. Buzzi MG, Moskowitz MA. The trigemino-vascular system and migraine. Pathol Biol (Paris) 1992; 40: 313-317.
100. BALANCE Investigators and collaborators, Geddes JR, Goodwin GM et al. Lithium plus valproate combination therapy versus monotherapy for relapse prevention in bipolar I disorder (BALANCE): a randomised open-label trial. Lancet 2010; 375: 385-395.
101. Linde M, Mulleners WM, Chronicle EP, McCrory DC. Valproate (valproic acid or sodium valproate or a combination of the two) for the prophylaxis of episodic migraine in adults. Cochrane Database Syst Rev 2013; 6: CD010611.
102. Taha AY, Cheon Y, Faurot KF et al. Dietary omega-6 fatty acid lowering increases bioavailability of omega-3 polyunsaturated fatty acids in human plasma lipid pools. Prostaglandins Leukot Essent Fatty Acids 2014; 90: 151-157.
103. MacIntosh BA, Ramsden CE, Faurot KR et al. Low-n-6 and low-n-6 plus high-n-3 diets for use in clinical research. Br J Nutr 2013; 110: 559-568.