The acute and chronic toxic effects of vitamin A

Lipoproteins, nutrition, and heart disease

Background Although studies in animals and epidemiologic studies have indicated that a high vitamin A intake is associated with increased bone fragility, no biologic marker of vitamin A status has thus far been used to assess the risk of fractures in humans. Methods We enrolled 2322 men, 49 to 51 years of age, in a population-based, longitudinal cohort study. Serum retinol and beta carotene were analyzed in samples obtained at enrollment. Fractures were documented in 266 men during 30 years of follow-up. Cox regression analysis was used to determine the risk of fracture according to the serum retinol level. Results The risk of fracture was highest among men with the highest levels of serum retinol. Multivariate analysis of the risk of fracture in the highest quintile for serum retinol (>75.62 μg per deciliter [2.64 μmol per liter]) as compared with the middle quintile (62.16 to 67.60 μg per deciliter [2.17 to 2.36 μmol per liter]) showed that the rate ratio was 1.64 (95 percent confidence interval, 1.12 t...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa021171

Serum retinol levels and the risk of fracture.

AGA Technical Review on the Evaluation and Management of Chronic Diarrhea

Differential effects of saturated and monounsaturated fatty acids on postprandial lipemia and incretin responses in healthy subjects

We investigated postprandial vitamin A metabolism by measuring retinyl ester, triglyceride, and apolipoprotein (apo)B-48 in the plasma lipoproteins of human subjects before and after fat-feeding. Following a 14-hour fast, eight healthy subjects (two men, six women, 28 to 79 years) were given a fat-rich meal (1 g fat/kg body weight) containing vitamin A (40 retinol equivalents per kilogram body weight). Blood was collected every 3 hours for 12 hours and lipoproteins were isolated by sequential ultracentrifugation. Mean plasma retinyl ester concentration peaked 6 hours after the fat-rich meal, whereas mean plasma triglyceride peaked at 3 hours. Data obtained from hourly samples in 3 subjects showed that changes in the postprandial plasma concentration of retinyl ester occurred 1 to 2 hours after changes in the plasma triglyceride concentration. In triglyceride-rich lipoproteins (TRL) of d less than 1.006 g/mL, retinyl ester similarly peaked at 6 hours, whereas triglyceride as well as apoB-48 peaked at 3 hours. Although retinyl esters were found mainly in TRL in the initial postprandial period (84%, 3 hours; 83%, 6 hours), in fasting and postprandial plasma, particularly 9 or more hours after fat-feeding, a large percentage of plasma retinyl esters were in low-density lipoproteins (LDL) (44%, fasting; 9%, 3 hours; 9%, 6 hours; 19%, 9 hours; 32%, 12 hours). A small percentage of retinyl esters were also found in postprandial high-density lipoproteins (HDL) (2% to 7%). ApoB-48 was not detected in LDL of fasting or postprandial plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Postprandial plasma vitamin A metabolism in humans: a reassessment of the use of plasma retinyl esters as markers for intestinally derived chylomicrons and their remnants.

Postprandial vitamin A and intestinal lipoprotein metabolism was studied in 86 healthy men and women, aged 19-76 yr. Three independent experiments were carried out. In the first experiment, a supplement dose of vitamin A (3,000 retinol equivalents [RE]) was given without a meal to 59 subjects, aged 22-76 yr. In the second experiment, 20 RE/kg body wt was given with a fat-rich meal (1 g fat/kg body wt) to seven younger subjects (aged less than 50 yr) and seven older subjects (aged greater than or equal to 50 yr). In both experiments, postprandial plasma retinyl ester response increased significantly with advancing age (P less than 0.05). In the third experiment, retinyl ester-rich plasma was infused intravenously into nine young adult subjects (aged 18-30 yr) and nine elderly subjects (aged greater than or equal to 60 yr), and the rate of retinyl ester disappearance from plasma during the subsequent 3 h was determined. Mean (+/- SE) plasma retinyl ester residence time was 31 +/- 4 min in the young adult subjects vs. 57 +/- 8 min in the elderly subjects (P less than 0.05). These data are consistent with the concept that increased postprandial plasma retinyl ester concentrations in older subjects are due to delayed plasma clearance of retinyl esters in triglyceride-rich lipoproteins of intestinal origin.

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Postprandial plasma retinyl ester response is greater in older subjects compared with younger subjects. Evidence for delayed plasma clearance of intestinal lipoproteins.

https://www.gastrojournal.org/article/0016-5085(89)90527-1/pdf

Effect of age on tests of intestinal and hepatic function in healthy humans.

We studied intestinal function and hepatic microsomal phase I monooxygenase function in healthy, free-living subjects, aged 19-91 yr. In subjects (n = 114) given a diet including 100 g/day of fat, fecal fat in a 72-h collection did not increase with advancing age. D-Xylose excretion (n = 54) following a 25-g oral load significantly declined with increasing age, but a concomitant decline in creatinine clearance suggested a decrease in renal function rather than an absorptive defect. Furthermore, there was no evidence for an age-associated increase in bile salt deconjugation by intestinal bacteria as shown by the glycocholate breath test (n = 60). Finally, there was no evidence for a decrease in hepatic microsomal function with advancing age as measured by the aminopyrine breath test (n = 60). We conclude that digestive/absorptive and hepatic microsomal phase I monooxygenase function are well preserved in healthy humans throughout life.

Stephen D. Krasinski

Papers

Postprandial plasma vitamin A metabolism in humans: a reassessment of the use of plasma retinyl esters as markers for intestinally derived chylomicrons and their remnants.

Postprandial plasma retinyl ester response is greater in older subjects compared with younger subjects. Evidence for delayed plasma clearance of intestinal lipoproteins.

Effect of age on tests of intestinal and hepatic function in healthy humans.

Effect of Age on Tests of Intestinal and Hepatic Function in Healthy Humans