Extensive studies in animal models indicate that subclinical
ascorbic acid deficiency impairs the conversion of
cholesterol to
bile acid, elevates plasma
cholesterol levels, and predisposes to development of
cholesterol cholelithiasis. The present study was designed to see if this is also true in man. Five normal volunteers were hospitalized in a metabolic ward and placed on a controlled diet containing 3-4 mg of
ascorbic acid each day.
Ascorbic acid supplementation was given as follows: control period I (days 1-33), 75 mg/day; deficient period (days 34-96), 0 mg/day; and repletion period (days 97-101), 1000 mg/day. In addition, three of the subjects were studied during a second control period (days 102-139) during which they were given 75 mg/day of
ascorbic acid. Ascorbate levels at the end of both control periods were 0.87-1.34 mg/dl in plasma and 19.4-29.5 micrograms/10(8) cells in leukocytes. At the end of the deficient period these levels were 0.09-0.15 mg/dl in plasma and 6.2-10.0 micrograms/10(8) cells in leukocytes, levels approaching those seen in
scurvy. There was no effect of
ascorbic acid deficiency on plasma
cholesterol and
triglycerides; plasma
cholesterol in high, very low, and
low density lipoprotein fractions; biliary
lipid composition and saturation index of gallbladder bile; synthesis, fractional turnover, or pool size of either cholic or chenodeoxycholic
acids; output of fecal
acid or neutral
sterols; and fecal
sterol balance. Total
bile acid pool size calculated by the one-sample technique was reduced 11% in the deficient period compared to control period I (P less than 0.005), and increased to 98.7% of the baseline levels in control period II. However, total
bile acid pool calculated by the Lindstedt method did not change during deficiency. These data demonstrate that short-term subclinical
ascorbic acid deficiency near the scorbutic range has no significant effect on
bile acid and
cholesterol metabolism in man.