Kynurenine pathway pathologies: Do nicotinamide and other pathway co-factors have a therapeutic role in reduction of symptom severity, including chronic fatigue syndrome (CFS) and fibromyalgia (FM)

International Journal of Tryptophan Research

Volumn 6, Issue SUPPL.1, 2013, Pages 39-45

  Blankfield, Adele ^a  

^a NONE

Author keywords

Chronic fatigue syndrome; Fibromyalgia; Mental status; Neurology; Nicotinamide; Nutrition; Pernicious anaemia; Psychiatry; Tryptophan; Vitamin B 12

Indexed keywords

EID: 84882617989     PISSN: None     EISSN: 11786469     Source Type: Journal    
DOI: 10.4137/IJTR.S11193     Document Type: Article

References (86)

1. Chen V, Guillemin GJ. Kynurenine pathway metabolites in human disease and healthy states. Int J Tryptophan Res. 2009;2:1-19.
2. Blankfield A. Kynurenine pathway hypothesis: the nature of the chronic fatigue syndrome (CFS) revisited. Int J Tryptophan Res. 2011;4: 47-8.
3. Blankfield A. A brief historic overview of Clinical Disorders associated with Tryptophan: The Relevance to Chronic Fatigue Syndrome (CFS) and Fibromyalgia (FM). Int J Tryptophan Res. 2012;5:27-32.
4. Solomon S. Clinical Neurology and Pathophysiology. In: Freedman AM, Kaplan HI, Sadock BJ, editors. Comprehensive Textbook of Psychiatry, 2nd ed. Baltimore Williams and Wilkens; 1975.
5. David AS, Wessely S, Pelosi AJ. Postviral Fatigue Syndrome: time for a new approach. Brit Med J. Mar 5, 1988;296(6623):696-9.
6. Singer A, Thompson S, Kraiuhin C, et al. An investigation of patients presenting with multiple physical complaints using the illness. Behaviour questionnaire. Psychother Psychosom. 1987;47(3-4):181-9.
7. Zonderman AB, Heft MW, Costa PT Jr. Does the illness behavior questionnaire measure abnormal illness behaviour? Health Psychol. 1985;4(5):425-36.
8. Pilowsky I. Abnormal illness behaviours and their treatments. Med J Aust. 1990;153:346-8.
9. Lipowski ZJ. Somatization: Medicines unsolved problem. Psychosomatics. 1987;28(6):294-7.
10. Kate N, Grover S, Agarwal M. Does B-12 deficiency lead to lack of treatment response to conventional antidepressants? Psychiatry (Edgmont). 2010;7(11):42-4.
11. Deahl MP. Physical illness and depression: the effects of acute physical illness on the mental state of psychiatric inpatients. Acta Psychiatrica Scand. 1990;81(1):83-6.
12. Tripathi AK, Verma SP, Kimanshu. Acute psychosis: A presentation of cyanocobalamin deficiency megaloblastic anaemia. Indian J Haematol Blood Transfus. 2010;26(3):99-100.
13. Jenkins AP, Treasure J, Thompson RPH. Crohn's disease presenting as anorexia nervosa. Brit Med J. 1988;296(6623):699-700.
14. Hall RCW, Gardner ER, Stickney SK, LeCann AF, Popkin MK. Physical Illness Manifesting as psychiatric Disease II. Analysis of a state hospital inpatient population. Arch Gen Psychiatry. 1980;37(9):989-95.
15. Middleton J. Pellagra and the blues song 'Cornbread, meat and black molasses'. JR Soc Med. 2008;101(11):569-70.
16. Bender DA. Biochemistry of tryptophan in health and disease. Molec Aspects Med. 1982;6(2):101-97.
17. Bender DA. Introduction to Nutrition and Metabolism, 4th ed. Boca Raton: CRC Press; 2008.
18. Stone TW. Kynurenines in the CNS: from endogenous obscurity to therapeutic importance. Prog Neurobiol. 2001;64(2):185-218.
19. Houtkooper RH, Canto C, Wanders RJ, Auwerx J. The secret life of NAD+: An old metabolite controlling new metabolic signaling pathways. Endocr Rev. 2010;31(2):194-223.
20. Sauve AA. NAD+ and Vitamin B3: From metabolism to therapies. J Pharmacol Exp Ther. 2008;324(3):883-93.
21. Murray MG. Nicotinamide: An oral antimicrobial agent with activity against both mycobacterium tuberculosis and human immunodeficiency virus. Clin Infect Dis. 2003;36(4):453-60.
22. Braidy N, Grant R, Brew J, Adams S, Jayasena T, Guillemin GJ. Effects of kynurenine pathway metabolites on intracellular NAD+ synthesis and cell death in human primary astrocytes and neurons. Int J Tryptophan Res. 2009;2:63-9.
23. Braidy N, Guillemin GJ, Grant R. Effects of kynurenine pathway inhibition on NAD+ metabolism and cell viability in human primary astrocytes and neurons. Int J Tryptophan Res. 2011;4:29-37.
24. Bellac CL, Coimbra RS, Christen S, Leib SL. Inhibition of the kynurenine- NAD+ pathway leads to energy failure and exacerbates apoptosis in pneumococcal meningitis. J Neuropathol Exp Neurol. 2010;69(11):1096-104.
25. Murray MF, Langan M, MacGregor RR. Increased plasma tryptophan in HIV-infected patients treated with pharmacologic doses of nicotinamide. Nutrition. 2001;17(7-8):654-6.
26. Murray MF. Tryptophan depletion and HIV infection: a metabolic link to pathogenesis. Lancet Infect Dis. 2003;3(10):644-52.
27. Surjana D, Halliday GM, Damian DL. Role of nicotinamide in DNA damage, mutagenesis and DNA repair. J Nucleic Acids. 2010;2010:157591.
28. Kirkland JB. Niacin status and treatment-related leukemogenesis. Mol Cancer Ther. 2009;8(4):725-32.
29. Audrito V, Vaisitti T, Ross D, et al. Nicotinamide blocks proliferation and induces apoptosis of chronic lymphocytic leukemia cells through activation of the p53/miR-34a/SIRT 1. Tumour suppressor network. Cancer Res. 2011;71(13):4473-83.
30. Inculet RI, Norton JA, Nichoalds, Maher MM, White DE, Brennan MF. Water-soluble vitamins in cancer patients on parental nutrition: a prospective study. J Parenter Enteral Nutr. 1987;11(3):243-9.
31. Werbach MR. Nutritional strategies for treating chronic fatigue syndrome. Altern Med Rev. 2000;5(2):93-108.
32. Ledochowski M, Propst T, Fuchs D. The role of psychological and biological factors in post-infective gut dysfunction. Gut. 2000;46(1):140-1.
33. Monteiro AM, Coutinho H, Janz GJ, deLoureiro JA. Endemic pellagra in northern Portugal. J Hygiene. 2009;44(6):518-25.
34. Robertson EE. Organic disorders. In: Forrest A, Affleck J, Zealley A, editors. Companion to Psychiatric Studies, 2nd ed. Edinburgh, Churchill, Livingstone; 1978.
35. Vannucchi H, Moreno FS, Amarante AR, et al. Plasma amino acid patterns in alcoholic pellagra patients. Alcohol Alcohol. 1991;26(4):431-6.
36. Creeke PI, Dibari F, Cheung E, van den Briel T, Kyroussis E, Seal AJ. Whole blood NAD and NADP concentrations are not depressed in subjects with clinical pellagra. J Nutr. 2007;137(9):2013-7.
37. Hortin GL, Landt M, Powderly WG. Changes in plasma amino acid concentrations in response to HIV-1 infection. Clin Chem. 1994;40(5):785-9.
38. Trusswell AS, Hansen JK, Wannenburg P. Plasma tryptophan and other amino acids in pellagra. Am J Clin Nutr. 1968;21(11):1314-20.
39. Brown RR, Ozaki Y, Datta SP, Borden EC, Sondel PM, Malone DG. Implications of interferon-induced tryptophan catabolism in cancer, auto-immune diseases and AIDS. Adv Exp Med Biol. 1991;294:425-35.
40. Mason JB. Nutrition in Gastroenterology. In: Feldman M, Friedman LS, Brandt LH, editors. Sleisenger and Fortran's Gastrointestinal and Liver disease; Pathophysiology, Diagnosis, Manage Merit, 8th ed. Philadelphia: Saunders Elsevier; 2008.
41. Russell IJ, editor. The fibromyalgia syndrome: A Clinical Case Definition for Practitioners. J Musculoskeletal Pain. Haworth Medical Press. 2003;11(4).
42. Oshikoya KA, Senbanjo IO. Pathophysiological changes that affect drug disposition in protein-energy malnourished children. Nutr Metab. 2009;6:50-5.
43. Zangerle R, Widner B, Quirchmair G, Neurauter G, Sarcletti M, Fuchs D. Effective antiviral therapy reduces degradation of tryptophan in patients with HIV-1 infection. Clin Immunol. Sep 2002;104(3):242-7.
44. Dhaliwal W, Shawa T, Khanam M, et al. Intestinal antimicrobial gene-expression: Impact of micronutrients in malnourished adults during a randomized trial. J Infect Dis. 2010;202(6):971-8.
45. Rossini M, Di Munno O, Valentini G, et al. Double-blind, multicentre trial comparing acetyl L-carnitine with placebo in the treatment of fibromyalgia patients. Clin Exp Rheumatol. 2007;25(2):182-8.
46. Santaella ML, Font I, Didier OM. Comparison of oral nictotinamide adenine dinucleotide (NADH) versus conventional therapy for chronic fatigue syndrome. Health Sci J. 2004;23(2):89-93.
47. Torpy D. Chronic Fatigue Syndrome, Chap 33b. In: Adrenal Physiology and Diseases. http://www.endotext.org/adrenal/adrenal33b.
48. Nicolson GL, Gan R, Haier J. Multiple co-infections (Mycoplasma, Chlamydia, human herpes virus-6) in blood of chronic fatigue syndrome patients: association with signs and symptoms. APMIS. 2003;111(5):557-66.
49. Kerr JR, Barah F, Mattey DL, et al. Circulating tumor necrosis factor-alpha and interferon-gamma are detectable during acute and convalescent parvovirus B19 infection and are associated with prolonged and chronic fatigue. J Gen Virol. 2001;82(Pt 12):301-19.
50. Kerr JR, Gough J, Richards SCM, et al. Antibody to Parvovirus B19 non-structural protein is associated with chronic arthralgia in patients with chronic fatigue syndrome/myalgic encephalitis [CFS/ME]. J Gen Virol. 2010;91(Pt 4):893-7.
51. Carmel R, Watkins D, Goodman SI, Rosenblatt DS. Hereditary defect of cobalamin metabolism (cblG mutation) presenting as a neurologic disorder in adulthood. N Engl J Med. 1988;318(26):1738-41.
52. Taghizadeh M. Megaloblastic Anemias. In: Harmening D, editor. Clinical Hematology and Fundamentals of Hemostasis, 5th ed. Philadelphia: FA Davis & Co; 2009.
53. Stopler S. Medical Nutrition Therapy for Anemia (Chap 34). In: Mahan LK, Escott-Stump S, editors. Krause's Food, Nutrition and Diet Therapy, 11th ed. Philadelphia: Saunders Elsevier; 2004.
54. Komaroff AL, Cho T. Role of infection and neurological dysfunction in chronic fatigue syndrome. Semin Neurol. 2011;31(3):325-37.
55. Caro XJ, Winter EF, Dumas AJ. A subset of fibromyalgia patients have findings suggestive of chronic inflammatory demyelinating polyneuropathy and appear to respond to IVIg. Rheumatology. 2008;47(2):208-11.
56. Carmel R, Melayk S, James SJ. Cobalamin deficiency with and without neurological abnormalities: differences in homocysteine and methionine metabolism. Blood. 2003;101(8):3302-8.
57. Lindenbaum J, Healton EB, Savage DG, et al. Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis. N Engl J Med. 1988;318(26):1720-8.
58. Savage DG, Lindenbaum J. Neurological complications of acquired cobalamin deficiency: clinical aspects. Baillieres Clin Haematol. 1995;8(3):657-78.
59. Toru S, Yokota T, Inaba A, et al. Autonomic dysfunction and orthostatic hypotention caused by vitamin B-12 deficiency. J Neurol Neurosurg Psychiatry. Jun 1999;66(6):804-5.
60. Fitzgerald P, Cassidy EM, Clarke G, et al. Tryptophan catabolism in females with irritable bowel syndrome: relationship to interferon-gamma, severity of symptoms and psychiatric co-morbidity. Neurogastroenterol Motil. 2008;20(12):1291-7.
61. Hashimoto T, Perlot T, Rehman A, et al. ACE 2 links amino acid malnutrition to microbial ecology and intestinal inflammation. Letter Nature. 2012;487(7408):477-81.
62. Tamura J, Kubota K, Murakami H, et al. Immunomodulation by vitamin B-12; augmentation of CD8+ T lymphocytes and natural killer (NK) cell activity in vitamin B-12-deficient patients by methyl B-12 treatment. Clin Exp Immunol. 1999;116(1):28-32.
63. Kannan R, Ng MJM. Cutaneous lesions and vitamin B-12 deficiency. An often-forgotten link. Can Fam Physician. 2008;54(4):529-32.
64. Carlson TH. Laboratory Data in Nutrition Assessment (Chap. 18). In: Mahan LK, Escott-Stumps, editors. Krause's Food, Nutrition and Diet Therapy, 11th ed. Philadelphia: Saunders Elsevier, 2004.
65. Regland B, Anderson M, Abrahamsson L, Bagby J, Dyrehag LE, Gottfries CG. Increased concentrations of homocysteine in the cerebrospinal fluid in patients with fibromyalgia and chronic fatigue syndrome. Scand J Rheumatol. 1997;26(4):301-7.
66. Lapp CW. Using vitamin B-12 for the management of chronic fatigue syndrome (CFS). Feb 25, 2000. http://www.ProHealth.com.
67. Myhill S. Diagnosing and treating chronic fatigue syndrome (CPS). 2009. Self-published. http://www.drmyhill.co.uk.
68. Markus CR, Oliver B, de Haan EH. Whey protein rich in alpha-lactalbumin increases the ratio of plasma tryptophan to the sum of the other large neutral amino acids and improves cognitive performance in stress-vulnerable subject. Am J Clin Nutr. 2002;75(6):1051-6.
69. Schrocksnadl K, Wirleitner B, Winkler C, Fuchs D. Monitoring tryptophan metabolism in chronic immune activation. Clin Chim Acta. 2006; 364(1-2):82-90.
70. Jensen GL, Mirtallo J, Compher C, et al. Adult starvation and disease-related malnutrition: a proposal for etiology-based diagnosis in the clinical practice setting from the International Consensus Guideline Committee. Clinical Nutrition. 2010;29(2):151-3.
71. Munoz-Hoyos A, Molina-Carballo A, Macias M. Comparison between tryptophan methoxyindole and kynurenine metabolic pathways in normal and preterm neonates and in neonates with acute fetal distress. Eur J Endocrinol. 1998;139(1):89-95.
72. de Betue CT, van Waardenburg DA, Deutz NE, et al. Increased protein-energy intake promotes anabolism in critically ill infants with viral bronchiolitis: a double-blind randomized controlled trial. Arch Dis Child. 2011;96(9):817-22.
73. Manary MJ, Yarasheski KE, Hart CA, Broadhead RL. Plasma urea appearance rate is lower when children with Kwashiorkor are fed egg-white-Tryptophan rather than milk protein. J Nutr. 2000;130(2):183-8.
74. Abassy AS, Zeitoun MM, Hassanein EA, et al. Studies on tryptophan metabolism in protein-calorie malnutrition. Transactions of the Royal Society of Tropical Medicine and Hygiene. 1970;64(1):148-55.
75. Metwalli OM, Shukry AS, Ghali I, Shukry I, Ismail S, El-Bishlawi A. Studies of tryptophan metabolism in protein-energy malnutrition (PEM). Gaz Egypt Paediatr Assoc. 1977;26(1):57-66.
76. Iyer SS, Chatrow JH, Tan WG, et al. Protein energy malnutrition impairs homeostatic proliferation of memory CD8 T cells. J Immunol. 2012;188(1): 77-84.
77. Sauerwein RW, Mulder JA, Mulder L, et al. Inflammatory mediators in children with protein-energy malnutrition. Am J Clin Nutr. 1997;65(5):1534-9.
78. Thumham DI, Mburu ASW, Mwaniki DL, DeWagt A. Micronutrients in childhood and the influence of subclinical inflammation. Proc Nutr Soc. 2005;64(4):502-9.
79. Karl A, Staehler M, Bauer R, et al. Malnutrition and clinical outcome in urological patients. Eur J Med Res. 2011;16(10):469-72.
80. Utaka S, Avesani CM, Draibe SA, Kamimura MA, Andreoni S, Cuppari L. Inflammation is associated with increased energy expenditure in patients with chronic kidney disease. Am J Clin Nutr. 2005;82(4):801-5.
81. Greenberg DB. Neurasthenia in the 1890s: Chronic mononucleosis, chronic fatigue syndrome, and anxiety and depressive disorders. Psychosomatics. 1990;31(2):129-37.
82. Hickie I, Davenport T, Wakefield D, et al. Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study. BMJ. 2006;333(7568):575.
83. Dreizen S, McCredie KB, Keating MJ, Andersson B. Nutritional deficiencies in patients receiving cancer chemotherapy. Postgrad Med. 1990; 87(1):163-70.
84. Vella A, Farrugia G. D-Lactic acidosis: pathological consequence of saprophytism. Mayo Clic Proc. 1998;73(5):451-6.
85. Sheedy JR, Wettenhall REH, Scanlon D, et al. Increased D-lactic acid intestinal bacteria in patients with chronic fatigue syndrome. In Vivo. 2009;23(4):621-8.
86. Evengard B, Nord CE, Sullivan A. Patients with chronic fatigue syndrome have higher numbers of anaerobic bacteria in the intestine compared to healthy subjects. Eur Soc Clin Microbiol Infect Dis. 2007;17:S340.