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Homocyst(e)ine Accumulation in Pigs Fed Diets Deficient in Vitamin B-6: Relationship to Atherosclerosis¹

Departments of Nutritional Sciences and Meat & Animal Science, University of Wisconsin, Madison, WI 53706

The early onset of atherosclerotic lesions in homocystinuric individuals has implicated homocyst(e)ine in the development of atherosclerosis. Two trials were conducted in which diets totally or partially deficient in vitamin B-6 were fed to pigs to investigate the accumulation of homocyst(e)ine in the plasma and the development of vascular lesions. In one trial plasma free homocyst(e)ine levels were 179 and 43 µmol/liter in deficient and adequate pigs, respectively, on day 24, while cysteine levels were 39 and 155 µmol/liter. The concentration of plasma protein-bound homocysteine and cysteine reflected the plasma-free values. Because pigs deficient in pyridoxine could be used only over short time intervals, pigs in trial 2 received 0, 0.03, 0.3 or 3 mg (i.e., 0, 2, 20 or 200% of allowance) of supplemental pyridoxine · HCl per kilogram diet. After 12 weeks pigs deficient and adequate in vitamin B-6 were injected intravenously with Evan's blue dye and the vascular trunk perfused with 2% glutaraldehyde. The aorta and major organs were removed and examined for vascular lesions. Grossly no significant lesions were seen. Light microscopy revealed occasional foci of intimal degeneration and mural thickening in the renal arterioles of pigs deficient in vitamin B-6. An area of focal medial necrosis was observed in one of the pigs deficient in vitamin B-6. Pigs fed diets containing 0.03 mg pyridoxine · HCl per kilogram diet had homocyst(e)ine concentrations not different from pigs fed diets with no added pyridoxine. Animals fed diets containing 0.3 mg pyridoxine · HCl per kilogram had homocyst(e)ine concentrations slightly higher than controls fed 3.0 mg/kg. Feed intake and weight gain increased with increasing pyridoxine in the diet. Swine offer an excellent vascular model for humans. Diets partially deficient in vitamin B-6 which cause the homocyst(e)ine concentration to increase, but allow better growth and feed consumption than diets totally deficient in pyridoxine, could be fed to pigs to study homocyst(e)ine-induced vascular damage over extended period of time.

KEY WORDS: • homocysteine • atherosclerosis • vitamin B-6

¹ Research supported in part by the College of Agricultural and Life Sciences and project number 133-C706 from the Food Research Institute, 1925 Willow Drive, Madison, WI 53706. This is paper number 828 from the Department of Meat and Animal Science.

² Present address: Dr. L. A. Smolin, Harbor-UCLA Medical Center, CSC Box 16, 1000 W. Carson St., Torrance, CA 90509.

³ Reprint requests should be sent to N. J. Benevenga, University of Wisconsin-Madison, Room 1156 Animal Sciences Building, 1675 Observatory Drive, Madison, WI 53706, phone (608)-263-4313.

Manuscript received 29 April 1983.

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