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Methodologic challenges in designing clinical studies to measure differences in the bioequivalence of n-3 fatty acids

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Vascular Biochemistry

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Abstract

Although epidemiologic studies suggest a role for alpha-linolenic acid (ALA) in the prevention of coronary heart disease and certain types of cancer, the findings of clinical studies suggest that ALA is inferior biologically to the n-3 long-chain fatty acids because its bioconversion to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is limited in humans and because the magnitude of its biologic effects is smaller than that of EPA and DHA. This paper reviews several methodologic issues that may confound the findings of clinical studies and complicate our interpretations of them: the ALA and EPA + DHA dietary enrichment levels; the choice of tissue; the choice of lipid species; and the method of reporting fatty acid composition. Although the ALA enrichment levels used in most clinical studies can be achieved by consuming ground flaxseed, flaxseed oil, canola oil and other ALA-rich plants as part of a typical dietary pattern, the EPA + DHA enrichment levels are not practical and can only be obtained from fish oil supplements. The lack of consistency in the choice of lipids species and the reporting of data makes it difficult to compare outcomes across studies. The choice of tissue (blood) for analysis is a limitation that probably cannot be overcome. The use of practical ALA and EPA+ DHA dietary enrichment levels and some standardization of clinical study design would allow for greater comparisons of outcomes across studies and ensure a more realistic analysis of how individual n-3 fatty acids differ in their biologic effects in humans. (Mol Cell Biochem 246: 83–90, 2003)

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Reference

  1. Gerster H: Can adults adequately convert a-linolenic acid (18:3n3) to eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3)? Internat J Vit Nutr Res 68: 159–173, 1998

    CAS  Google Scholar 

  2. Adam O, Wolfram G, Miner N: Effect of a-linolenic acid in the human diet on linoleic acid metabolism and prostaglandin biosynthesis. J Lipid Res 27: 421–426, 1986

    PubMed  CAS  Google Scholar 

  3. Dyerberg J, Bang HO, Aagaard O: a-Linolenic acid and eicosapentaenoic acid (letter). Lancet i: 199, 1980

    Google Scholar 

  4. McKeigue P: Diets for secondary prevention of coronary heart disease: Can linolenic acid substitute for oily fish (commentary)? Lancet 343: 1445, 1994

    Article  PubMed  CAS  Google Scholar 

  5. DeLany JP, Windhauser MM, Champagne CM, Bray GA: Differential oxidation of individual dietary fatty acids in humans. Am J Clin Nutr 72: 905–911, 2000

    PubMed  CAS  Google Scholar 

  6. Vermunt SHF, Mensink RP, Simonis MMG, Hornstra G: Effects of dietary a-linolenic acid on the conversion and oxidation of “C-a-linolenic acid. Lipids 35: 137–142, 2000

    Article  PubMed  CAS  Google Scholar 

  7. Cunnane SC: The Canadian Society for Nutritional Sciences 1995 Young Scientist Award Lecture: Recent studies on the synthesis, (3-oxidation, and deficiency of linoleate and a-linolenate: Are essential fatty acids more aptly named indispensable or conditionally dispensable fatty acids? Can J Physiol Pharmacol 74: 629–639, 1996

    Article  PubMed  CAS  Google Scholar 

  8. Garg ML, Thomson ABR, Clandinin MT: Interactions of saturated, n6 and n-3 polyunsaturated fatty acids to modulate arachidonic acid metabolism. J Lipid Res 31: 271–277, 1990

    PubMed  CAS  Google Scholar 

  9. Layne KS, Goh YK, Jumpsen JA, Ryan EA, Chow P, Clandinin MT: Normal subjects consuming physiological levels of 18:3(n-3) and 20:5 (n-3) from flaxseed or fish oils have characteristic differences in plasma lipid and lipoprotein fatty acid levels. J Nutr 126: 2130–2140, 1996

    PubMed  CAS  Google Scholar 

  10. Garg ML, Thomson ABR, Clandinin MT: Effect of dietary cholesterol and/or 0)3 fatty acids on lipid composition and A5-desaturase activity of rat liver microsomes. J Nutr 118: 661–668, 1988

    PubMed  CAS  Google Scholar 

  11. Leikin AI, Brenner RR: Cholesterol-induced microsomal changes modulate desaturase activities. Biochim Biophys Acta 922: 294–303, 1987

    Article  PubMed  CAS  Google Scholar 

  12. van Houwelingen AC, Hornstra G:Transfatty acids in early human development. World Rev Nutr Diet 75: 175–178, 1994

    Google Scholar 

  13. Emken EA, Adlof RO, Gulley RM: Dietary linoleic acid influences desaturation and acylation of deuterium-labeled linoleic and linolenic acids in young adult males. Biochim Biophys Acta 1213: 277–288, 1994

    Article  PubMed  CAS  Google Scholar 

  14. Emken EA, Adlof RO, Duval SM, Nelson GJ: Effect of dietary docosahexaenoic acid on desaturation and uptake in vivo of isotope-labeled oleic, linoleic and linolenit acids by male subjects. Lipids 34: 785–791, 1999

    Article  PubMed  CAS  Google Scholar 

  15. Vermunt SHF, Mensink RP, Simonis AMG, Hornstra G: Effects of age and dietary n-3 fatty acids on the metabolism of [13 C]-a-linolenic acid. Lipids 34: S 127, 1999

    Article  Google Scholar 

  16. Cunnane SC, Ganguli S, Menard C, Liede AC, Hamadeh MJ, Chen Z-Y, Wolever TMS, Jenkins DJA: High a-linolenic acid flaxseed (Linum usitatissimum): Some nutritional properties in humans. Br J Nutr 69: 443–453, 1993

    Article  PubMed  CAS  Google Scholar 

  17. Pawlosky RJ, Hibbeln JR, Novotny JA, Salem N Jr: Physiological compartmental analysis of a-linolenic acid metabolism in adult humans. J Lipid Res 42: 1257–1265, 2001

    PubMed  CAS  Google Scholar 

  18. Simopoulos AP, Leaf A, Salem N Jr: Workshop on the essentiality of and recommended dietary intakes for omega-6 and omega-3 fatty acids. Nutr Today 35: 166–167, 2000

    Article  Google Scholar 

  19. de Lorgeril M, Salen P, Martin J-L, Monjaud I, Boucher P, Mamelle N: Mediterranean dietary pattern in a randomized trial: Prolonged survival and possible reduced cancer rate. Arch Intern Med 158: 1181–1187, 1998

    Article  PubMed  Google Scholar 

  20. Ascherio A, Rimm EB, Giovannucci EL, Spiegelman D, Stampfer M, Willett WC: Dietary fat and risk of coronary heart disease in men: Cohort follow up study in the United States. Br Med J 313: 8490. 1996

    Google Scholar 

  21. Dolecek TA: Epidemiological evidence of relationships between dietary polyunsaturated fatty acids and mortality in the Multiple Risk Factor Intervention Trial. Proc Soc Exp Biol Med 200: 177–182, 1992

    PubMed  CAS  Google Scholar 

  22. Hu FB, Stampfer MJ, Manson JE, Rimm EB, Wolk A, Colditz GA, Hennekens CH, Willett WC: Dietary intake of a-linolenic acid and risk of fatal ischemic heart disease among women. Am J Clin Nutr 69: 890–897, 1999

    PubMed  CAS  Google Scholar 

  23. de Lorgeril M, Renaud S, Mamelle N, Salen P, Martin J-L, Monjaud I, Guidollet J, Touboul P, Delaye J: Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease. Lancet 343: 1454–1459. 1994

    Article  PubMed  Google Scholar 

  24. de Lorgeril M, Salen P, Martin J-L, Monjaud I, Delaye J, Mamelle N: Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: Final report of the Lyon Diet Heart Study. Circulation 99: 779–785, 1999

    Article  PubMed  Google Scholar 

  25. Simon JA, Fong J, Bernert JT Jr, Browner WS: Serum fatty acids and the risk of stroke. Stroke 26: 778–782, 1995

    Article  PubMed  CAS  Google Scholar 

  26. Chan JK, McDonald BE, Gerrard JM, Bruce VM, Weaver BJ, Holub BJ: Effect of dietary a-linolenic acid and its ratio to linoleic acid on platelet and plasma fatty acids and thrombogenesis. Lipids 28: 811–817, 1993

    Article  PubMed  CAS  Google Scholar 

  27. Goh YK, Jumpsen JA, Ryan EA, Clandinin MT: Effect of (03 fatty acid on plasma lipids, cholesterol and lipoprotein fatty acid content in NIDDM patients. Diabetologia 40: 45–52, 1997

    Article  PubMed  CAS  Google Scholar 

  28. Indu M, Ghafoorunissa: n-3 Fatty acids in Indian diets: Comparison of the effects of precursor (alpha-linolenic acid) vs product (long chain n-3 polyunsaturated fatty acids). Nutr Res 12: 569–582, 1992

    Article  CAS  Google Scholar 

  29. Kwon J-S, Snook JT, Wardlaw GM, Hwang DH: Effects of diets high in saturated fatty acids, canola oil, or safflower oil on platelet function, thromboxane B, formation, and fatty acid composition of platelet phospholipids. Am J Clin Nutr 54: 351–358, 1991

    PubMed  CAS  Google Scholar 

  30. Mantzioris E, James MJ, Gibson RA, Cleland LG: Dietary substitution with an a-linolenic acid-rich vegetable oil increases eicosapentaenoic acid concentrations in tissues. Am J Clin Nutr 59: 1304–1309, 1994

    PubMed  CAS  Google Scholar 

  31. Sanders TAB, Roshanai F: The influence of different types of 0)3 polyunsaturated fatty acids on blood lipids and platelet function in healthy volunteers. Clin Sci 64: 91–99, 1983

    PubMed  CAS  Google Scholar 

  32. Caughey GE, Mantzioris E, Gibson RA, Cleland LG, James MJ: The effect on human tumor necrosis factor a and interleukin 1 p production of diets enriched in n-3 fatty acids from vegetable oil or fish oil. Am J Clin Nutr 63: 116–122, 1996

    PubMed  CAS  Google Scholar 

  33. McDonald BE, Gerrard JM, Bruce VM, Corner EJ: Comparison of the effect of canola oil and sunflower oil on plasma lipids and lipoproteins and onin vivothromboxane A, and prostacyclin production in healthy young men. Am J Clin Nutr 50: 1382–1388, 1989

    PubMed  CAS  Google Scholar 

  34. Abbey M, Clifton P, Kestin M, Belling B, Nestel P: Effect of fish oil on lipoproteins, lecithin:cholesterol acyltransferase, and lipid transfer protein activity in humans. Arteriosclerosis 10: 85–94, 1990

    Article  PubMed  CAS  Google Scholar 

  35. Bierenbaum ML, Reichstein R, Watkins TR: Reducing atherogenic risk in hyperlipidemic humans with flax seed supplementation: A preliminary report. J Am Coll Nutr 12: 501–504, 1993

    PubMed  CAS  Google Scholar 

  36. Chan JK, Bruce VM, McDonald BE: Dietary a-linolenic acid is as effective as oleic acid and linoleic acid in lowering blood cholesterol in normolipidemic men. Am J Clin Nutr 53: 1230–1234. 1991

    PubMed  CAS  Google Scholar 

  37. Clandinin MT, Foxwell A, Goh YK, Layne K, Jumpsen JA: Omega-3 fatty acid intake results in a relationship between the fatty acid composition of LDL cholesterol ester and LDL cholesterol content in humans. Biochim Biophys Acta 1346: 247–252. 1997

    Article  PubMed  CAS  Google Scholar 

  38. Kelley DS, Branch LB, Love JE, Taylor PC, Rivera YM, Iacono JM: Dietary a-linolenic acid and immunocompetence in humans. Am J Clin Nutr 53: 40–46, 1991

    PubMed  CAS  Google Scholar 

  39. Freese R, Mutanen M: α-Linolenic acid and marine long-chain n3 fatty acids differ only slightly in their effects on hemostatic factors in healthy subjects. Am J Clin Nutr 66: 591–598. 1997

    PubMed  CAS  Google Scholar 

  40. Kestin M, Clifton P, Belling GB, Neste] PJ: n-3 Fatty acids of marine origin lower systolic blood pressure and triglycerides but raise LDL cholesterol compared with n-3 and n-6 fatty acids from plants. Am J Clin Nutr 51: 1028–1034, 1990

    PubMed  CAS  Google Scholar 

  41. Nestel PJ, Pomeroy SE, Sasahara T, Yamashita T. Liang YL, Dart AM, Jennings GL, Abbey M, Cameron JD: Arterial compliance in obese subjects is improved with dietary plant n-3 fatty acid from flaxseed oil despite increased LDL oxidizability. Arterioscler Thromb Vase Biol 17: 1163–1170. 1997

    Article  CAS  Google Scholar 

  42. Singer P, Wirth M, Berger I: A possible contribution of decrease in free fatty acids to low serum triglyceride levels after diets supplemented with n-6 and n-3 polyunsaturated fatty acids. Atherosclerosis 83: 167–175, 1990

    Article  PubMed  CAS  Google Scholar 

  43. Uauy R, Hoffman DR: Essential fat requirements of preterm infants. Am J Clin Nutr 71(suppl): 245S–250S, 2000

    PubMed  CAS  Google Scholar 

  44. Gibson RA, Makrides M: n-3 Polyunsaturated fatty acid requirements of term infants. Am J Clin Nutr 71(suppl): 251S–255S. 2000

    PubMed  CAS  Google Scholar 

  45. Allman-Farinelli MA, Hall D, Kingham K, Pang D, Petocz P. Favaloro EJ: Comparison of the effects of two low fat diets with different a-linolenic:linoleic acid ratios on coagulation and fibrinolysis. Atherosclerosis 142: 159–168, 1999

    Article  PubMed  CAS  Google Scholar 

  46. Corner EJ, Bruce VM, McDonald BE: Accumulation of eicosapentaenoic acid in plasma phospholipids of subjects fed canola oil. Lipids 25: 598–601, 1990

    Article  PubMed  CAS  Google Scholar 

  47. Freese R, Mutanen M, Valsta LM, Salminen I: Comparison of the effects of two diets rich in monounsaturated fatty acids differing in their linoleic/a-linolenic acid ratio on platelet aggregation. Thromb Haemostas 71: 73–77, 1994

    CAS  Google Scholar 

  48. Li D, Mann NJ, Sinclair AJ: Comparison of n-3 polyunsaturated fatty acids from vegetable oils, meat, and fish in raising platelet eicosapentaenoic acid levels in humans. Lipids 34: 5309, 1999

    Article  Google Scholar 

  49. Kelley DS, Nelson GJ, Love JE, Branch LB, Taylor PC, Schmidt PC, Mackey BE, Iacono JM: Dietary a-linolenic acid alters tissue fatty acid composition, but not blood lipids, lipoproteins or coagulation status in humans. Lipids 28: 533–537, 1993

    Article  PubMed  CAS  Google Scholar 

  50. Jones PJH, Lichtenstein AH, Schaefer EJ, Namchuk GL: Effect of dietary fat selection on plasma cholesterol synthesis in older, moderately hypercholesterolemic humans. Arterioscler Thromb 14: 542–548, 1994

    Article  PubMed  CAS  Google Scholar 

  51. Lichtenstein AH, Ausman LM, Carrasco W, Jenner JL, Gualtieri LJ, Goldin BR, Ordovas JM, Schaefer EJ: Effects of canola, corn. and olive oils on fasting and postprandial plasma lipoproteins in humans as part of a National Cholesterol Education Program step 2 diet. Arterioscler Thromb 13: 1533–1542, 1993

    Article  PubMed  CAS  Google Scholar 

  52. Cunnane SC, Hamadeh MJ, Liede AC, Thompson LU, Wolever TMS, Jenkins DJA: Nutritional attributes of traditional flaxseed in healthy young adults. Am J Clin Nutr 61: 62–68, 1995

    PubMed  CAS  Google Scholar 

  53. Matheson B, Walker KZ, Taylor DM, Peterkin R, Lugg D, O’Dea K: Effect on serum lipids of monounsaturated oil and margarine in the diet of an Antarctic Expedition. Am J Clin Nutr 63: 933–938, 1996

    PubMed  CAS  Google Scholar 

  54. Bierenbaum ML, Reichstein RP, Watkins TR, Maginnis WP, Geller M: Effects of canola oil on serum lipids in humans. J Am Coll Nutr 10: 228–233, 1991

    PubMed  CAS  Google Scholar 

  55. Mantzioris E, Cleland LG, Gibson RA, Neumann MA, Demasi M, James MJ: Biochemical effects of a diet containing foods enriched with n-3 fatty acids. Am J Clin Nutr 72: 42–48, 2000

    PubMed  CAS  Google Scholar 

  56. Connor WE, Bendich A. eds: Highly unsaturated fatty acids in nutrition and disease prevention. Am J Clin Nutr 71 (suppl): 169S–398S. 2000

    Google Scholar 

  57. Harris WS: n-3 Fatty acids and serum lipoproteins: Human studies. Am J Clin Nutr 65 (suppl): 1645S–1654S, 1997

    PubMed  CAS  Google Scholar 

  58. Blok WL, Katan MB, van der Meer JWM: Modulation of inflammation and cytokine production by dietary (n-3) fatty acids. J Nutr 126: 1515–1533, 1996

    PubMed  CAS  Google Scholar 

  59. GISSI-Prevenzione Investigators: Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: Results of the GISSI-Prevenzione trial. Lancet 354: 447–455, 1999

    Google Scholar 

  60. Foulon T, Richard M-J, Payen N, Bourrain J-L, Beani J-C, Laporte F. Hadjian A: Effects of fish oil fatty acids on plasma lipids and lipoproteins and oxidant-antioxidant imbalance in healthy subjects. Scand J Clin Lab Invest 59: 239–248, 1999

    Article  PubMed  CAS  Google Scholar 

  61. US Department of Agriculture, Agricultural Research Service: Nutrient database for standard reference, release 14, 2001. Available online athttp://www.nal.usda.gov/fnic

  62. Food Surveys Research Group, Beltsville Human Nutrition Research Center, Agricultural Research Service, US Department of Agriculture: Intakes of 19 individual fatty acids: Results from the 1994–96 Continuing Survey of Food Intakes by Individuals. Available online athttp://www.barc.usda.gov/bhnrc/foodsurvey/home.htm

  63. Krauss RM, Eckel RH, Howard B, Appel LJ, Daniels SR, Deckelbaum RJ, Erdman JW Jr, Kris-Etherton P, Goldberg IJ, Kotchen TA, Lichtenstein AK Mitch WE. Mullis R, Robinson K, Wylie-Rosett J, St Jeor S, Suttie J, Tribble DL, Bazzarre TL: AHA dietary guidelines: Revision 2000: A statement for healthcare professionals from the Nutrition Committee of the American Heart Association. Circulation 102: 2296–2311, 2000

    Article  Google Scholar 

  64. Abedin L. Lien EL, Vingrys AJ, Sinclair AJ: The effects of dietary α-linolenic acid compared with docosahexaenoic acid on brain, retina, liver, and heart in the guinea pig. Lipids 34: 475–482, 1999

    Article  PubMed  CAS  Google Scholar 

  65. Berger A, Gershwin ME, German JB: Effects of various dietary fats on cardiolipin acyl composition during ontogeny of mice. Lipids 27: 605–612, 1992

    Article  PubMed  CAS  Google Scholar 

  66. Cleland LG, Gibson RA, Hawkes JS, James MJ: Comparison of cell membrane phospholipid fatty acids in five rat strains fed four test diets. Lipids 25: 559–564, 1990

    Article  PubMed  CAS  Google Scholar 

  67. Greiner RCS, Winter.17 Nathanielsz PW, Brenna JT: Brain docosahexaenoate accretion in fetal baboons: Bioequivalence of dietary a-linolenic and docosahexaenoic acids. Pediatr Res 42: 826–834, 1997

    Article  PubMed  CAS  Google Scholar 

  68. Makrides M. Neumann MA, Gibson RA: Is dietary docosahexaenoic acid essential for term ‘infants? Lipids 31: 115–119, 1996

    Article  PubMed  CAS  Google Scholar 

  69. Farquharson J. Jamieson EC, Abbasi KA, Patrick WJA, Logan RW, Cockburn F: Effect of diet on the fatty acid composition of the major phospholopids of infant cerebral cortex. Arch Dis Child 72: 198–203, 1995

    Article  PubMed  CAS  Google Scholar 

  70. Farquharson J. Cockburn F, Patrick WA, Jamieson EC, Logan RW: Infant cerebral cortex phospholipid fatty-acid composition and diet. Lancet 340: 810–813, 1992

    Article  PubMed  CAS  Google Scholar 

  71. Seidelin KN, Myrup B, Fischer-Hansen B: n-3 Fatty acids in adipose tissue and coronary artery disease are inversely related. Am J Clin Nutr 55: 1117–1119, 1992

    PubMed  CAS  Google Scholar 

  72. Conquer JA, Martin JB, Tummon I, Watson L, Tekpetey F: Fatty acid analysis of blood serum, seminal plasma, and spermatozoa of normozoospermic vs. asthenozoospermic males. Lipids 34: 793–799, 1999

    Article  PubMed  CAS  Google Scholar 

  73. Conquer JA, Martin JB, Tummon I, Watson L, Tekpetey F: Effect of DHA supplementation on DHA status and sperm motility in asthenozoospermic males. Lipids 35: 149–154, 2000

    Article  PubMed  CAS  Google Scholar 

  74. Christophe A, Zalata A, Mahmoud A, Combaire F: Fatty acid composition of sperm phospholipids and its nutritional implications. Middle East Fertil Soc J 3: 46–53, 1998

    Google Scholar 

  75. Kang JX, Leaf A: Antiarrhythmic effects of polyunsaturated fatty acids: Recent studies. Circulation 94: 1774–1780, 1996

    Article  PubMed  CAS  Google Scholar 

  76. Billman GE, Kang JX, Leaf A: Prevention of ischemia-induced cardiac sudden death by n-3 polyunsaturated fatty acids in dogs. Lipids 32: 1161–1168, 1997

    Article  PubMed  CAS  Google Scholar 

  77. Billman GE, Kang JX, Leaf A: Prevention of sudden cardiac death by dietary pure o)-3 polyunsaturated fatty acids in dogs. Circulation 99: 2452–2457, 1999

    Article  PubMed  CAS  Google Scholar 

  78. Lands WEM, Libelt B, Morris A, Kramer NC, Prewitt TE, Bowen P, Schmeisser D, Davidson MH, Burns JH: Maintenance of lower proportions of (n-6) eicosanoid precursors in phospholipids of human plasma in response to added dietary (n-3) fatty acids. Biochim Biophys Acta 1180: 147–162, 1992

    Article  PubMed  CAS  Google Scholar 

  79. Lands WEM: Review: Stories about acyl chains. Biochim Biophys Acta 1483: 1–15, 2000

    Article  PubMed  CAS  Google Scholar 

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  1. Mainstream Nutrition, Toronto, Canada

    Diane H. Morris

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  1. Research Center, St. Boniface General Hospital, 351 Tache Avenue, Winnipeg, Manitoba, R2H 2A6, Canada

    Peter Zahradka

  2. Institute of Cardiovascular Sciences, St. Boniface General Hospital, 351 Tache Avenue, Winnipeg, Manitoba, R2H 2A6, Canada

    Jeffrey Wigle

  3. Division of Stroke & Vascular Disease, St. Boniface General Hospital Research Center, Canada

    Grant N. Pierce

  4. Faculty of Medicine, University of Manitoba, R2H 2A6, Winnipeg, Manitoba, Canada

    Grant N. Pierce

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Morris, D.H. (2003). Methodologic challenges in designing clinical studies to measure differences in the bioequivalence of n-3 fatty acids. In: Zahradka, P., Wigle, J., Pierce, G.N. (eds) Vascular Biochemistry. Molecular and Cellular Biochemistry: An International Journal for Chemical Biology in Health and Disease, vol 41. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0298-2_12

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