Vitamin B12 Inhibits Progression of Hypercholesterolemia and Atherosclerosis in Rabbits Fed a High Cholesterol Diet
The present study was undertaken to examine the effect of vitamin B12 on serum cholesterol levels and development of aortic atherosclerosis in New Zealand White male rabbits fed a high cholesterol diet. Twenty rabbits were divided into 4 groups matched for their baseline serum cholesterol values. Groups 1 and 2 received a normal diet, whereas groups 3 and 4 had cholesterol mixed with their chow. After 5 weeks, the serum cholesterol of groups 3 and 4 increased by approximately 12 fold compared to groups 1 and 2. At that point, vitamin B12 was administered in the drinking water (1000 micrograms/l) to rabbits in groups 2 and 4. At week 8, the Vitamin B12 dose was increased to 2400 micrograms/l for group 4. At 12 weeks into the study, rabbits in group 4 (high cholesterol diet plus vitamin B12) had a serum cholesterol level of 919 +/- 270 mg/dl while those of group 3 (high cholesterol diet) had a serum cholesterol level of 1417 +/- 250 mg/dl. At the end of the study, rabbit aortas were excised, fixed, and stained with fat-red-B, a dye for lipid. Comparison of the aortas of rabbits that received the lipid rich diet revealed that animals given additional vitamin B12 had significantly decreased surface area of fat deposition. These data suggest the potential role for vitamin B12 as a safe and inexpensive pharmacological intervention for the modification of the progression of human atherosclerosis.
- Uemura K, Pisa, Z. Trends in cardiovascular diease mortality in industrialized countries since 1950. World Health Statistics Quarterly 41(3-4):155-178; 1988.
- Moore S. Blood vessels and lymphatics. In: Damjanov I, Linder J, eds. Anderson's Pathology, 10th edition. Missouri: Mosby Year Book, Inc.; 1996.
- Moore S, Alavi MZ. Vessel wall matrix : An overview. In: Woodford, Davignon and Sniderman, eds. Atherosclerosis X. Amsterdam: Elsevier; 1995; 369-372.
- Ross R. Cell biology of atherosclerosis. Annual Review of Physiology 57: 791-804; 1995.
- Parasad C, Chandra R.K. Atherosclerosis : A paediatric problem? Nutrition Research 11:1-5; 1990.
- Strong JP. The natural history of atherosclerosis in childhood. Annals of the New York Acadamy of Sciences 623:9-15; 1991.
- Reeder BA, Dagenais GR, Johansen H, et al. Cardiovascular disease in Canada 1993. Heart and Stroke Foundation of Canada Report; 1993.
- Stary HC, Blankenhorn, DH, Chandler AB, et al. A definition of the intima of human arteries and of its atherosclerosis-prone regions. Arteriosclerosis and Thrombosis 12(1): 120-134; 1992.
- Getz GS. An overview of atherosclerosis: A look to the future. Toxicologic Pathology 18(4 pt 1): 623-635; 1990.
- Bierman L. Atherosclerosis and Other Forms of Arteriosclerosis. In: Wilson JD, Braunwald E, Isselbacher KJ, et al., eds. Harrison's Principles of Internal Medicine, 12th edition. New York: McGraw-Hill Inc.; 1991: 992-1001.
- Mayes, PA. Cholesterol Synthesis, Transport and Excretion. In: Murray RK, Granner DK, Mayes PA, Rodwell VW, eds. Harper's Biochemistry, 23rd edition. Norwalk, Connecticut: Appleton and Lange; 1993: 266-277.
- Goldstein JL, Brown MS. Familial hypercholesterolemia: A genetic regulatory defect in cholesterol metabolism. American Journal of Medicine 58(2): 147-150; 1975.
- Brown MS, Goldstein JL. A receptor-mediated pathway for cholesterol homeostasis. Science 232 (4746): 34-47; 1986.
- Hegele RA. The pathogenesis of atherosclerosis. Clinica Chimica Acta 246(1-2): 21-38; 1996.
- Malinow MR. Hyperhomocyst(e)inemia. A common and easily reversible risk factor for occlusive atherosclerosis. Circulation 81(6): 2004-2006; 1990.
- Clarke R, Daly L, Robinson K, et al. Hyperhomocysteinemia: an independant risk factor for vascular disease. New England Journal of Medicine 324(17): 1149-1155; 1991.
- Ueland PM, Refsum H, Brattstrom L. Plasma homocysteine and cardiovascular disease. In : Francis BR, ed. Atherosclerotic cardiovascular disease, hemostasis, and endothelial function. New York: Marcel Dekker; 1992.
- Kang SS, Wong PW, Malinow MR. Hyperhomocyst(e)inemia as a risk factor for occlusive vascular disease. Annual Review of Nutrition 12:279-298; 1992.
- Genest J Jr, Malinow MR. Homocyst(e)ine and coronary artery disease. Current Opinion in Lipidology 3:295-299;1992.
- Stampfer MJ, Malinow MR, Willet WC, et al. A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in US physicians. JAMA 268(7): 877-881; 1992.
- Fortin LJ, Genest J Jr. Measurement of homocyst(e)ine in the prediction of arteriosclerosis. Clinical Biochemistry 28(2): 155-162; 1995.
- Harker LA, Ross R, Slichter SJ, et al. Homocysteine induced atherosclerosis: The role of endothelial cell injury and platelet response in its genesis. Journal of Clinical Investigation 58(3): 731-741; 1976.
- Wall RT, Harlan JM, Harker LA, et al. Homocysteine-induced endothelial cell injury in vitro: a model for the study of vascular injury. Thrombosis Research 18(1-2):113-121; 1980.
- Harker LA, Harlan JM, Ross R. Effect of sulfinpyrazone on homocysteine induced endothelial injury and arteriosclerosis in baboons. Circulation Research 53(6): 731-739; 1983.
- Elian KM. Plasma homocysteine and vascular disease. McGill Journal of Medicine 2(2): 107-112; 1996.
- Brattstrom L, Israelsson B, Lindgarde F, Hultberg, B. Higher total plasma homocysteine in vitamin B12 deficiency than in heterozygosity for homocystinuria due to cystathionine beta-synthase deficiency Metabolism: Clinical and Experimental 37(2):175-178; 1988.
- Jacobsen DW, Gatautis VJ, Green R, et al. Rapid HPLC determination of total homocysteine and other thiols in serum and plasma: sex differences and correlation with cobalamin and folate concentrations in healthy subjects. Clinical Chemistry 40(6):873-881; 1994.
- Selhub J, Jacques PF, Wilson, PW, et al. Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. JAMA; 270(22): 2693-2698; 1993.
- Pancharuniti N, Lewis CA, Sauberlich HE, et al. Plasma homocyst(e)ine, folate, and vitamin B12 concentrations and risk for early-onset coronary artery disease. American Journal of Clinical Nutrition 59(4):940-948; 1994.
- Ubbink JB, Vermaak WJH, van der Merwe A, et al. Vitamin B12, Vitamin B6, and folate nutritional status in men with hyperhomocysteinemia. American Journal of Clinical Nutrition 57(1):47-53; 1993.
- Dalery K, Lussier-Cacan S, Selhub J, et al. Homocysteine and coronary artery disease in French Canadian subjects: relation with vitamins B12, B6, pyridoxal phosphate and folate. American Journal of Cardiology 75 (16): 1107-1111; 1995.
- Malinow MR. Plasma homocyst(e)ine and arterial occlusive diseases: A mini-review. Clinical Chemistry 41(1): 173-176; 1995.
- Alavi MZ, Galis Z, Li ZH, Moore S. Dietary alterations of plasma lipoproteins influence their interactions with proteoglycan enriched extracts from neointima of normal and injured aorta of rabbit. Clinical and Investigative Medicine 14(5): 419-431; 1991.
- Allain CC, Poon LS, Chan CS, et al. Enzymatic determination of total serum cholesterol. Clinical Chemistry 20(4): 470-475; 1974.
- Murphy-Chutorian DR, Wexman MP, Grieco AJ, et al. Methionine intolerance: a possible risk factor for coronary artery disease. Journal of the American College of Cardiology 6(4):725-730; 1985.
- Malinow MR, Kang SS, Taylor LM, et al. Prevalence of hyperhomocyst(e)inemia in patients with peripheral arterial occlusive disease. Circulation 79(6):1180-1188; 1989.