Assessment of total body stores of vitamin A in Guatemalan elderly by the deuterated-retinol-dilution method.

BACKGROUND: Deuterated retinol dilution (DRD) gives quantitative estimates of total body stores of vitamin A. OBJECTIVES: In elderly people, we studied 1) the time when an oral dose of deuterated vitamin A equilibrates with body stores, 2) whether serum ratios of deuterated to nondeuterated retinol (D:H) at 3 or 6 d postdosing predicted body stores, and 3) the ability of DRD to detect changes in the size of the body vitamin A pool. DESIGN: A 10-mg oral dose of [2H4]retinyl acetate was administered to 60-81-y-old Guatemalans (n = 47); percentage enrichment of serum retinol with deuterated retinol was determined at 1-3 time points per subject at 3, 6, 7, 14, 20, 21, and 54 d. In subjects from whom blood was obtained at 3 and 21 d (n = 15) and at 6 and 20 d (n = 9), total body stores were calculated by using the formula of Furr et al (Am J Clin Nutr 1989;49:713-6) with 21- or 20-d data and correlated with serum D:H at 3 or 6 d postdosing. Nine subjects received diets containing 982+/-20 microg RE (x+/-SEM) plus 800 microg RE as retinyl acetate supplements for 32 d. DRD, serum retinol, and relative dose response were used to assess vitamin A status before and after the intervention. RESULTS: Deuterated retinol equilibrated with the body pool by 20 d postdosing. Vitamin A supplementation for 32 d increased body stores, although unexplained exaggerated increases were seen in some subjects. An inverse linear relation was found between estimates of body stores and serum D:H at 3 d postdosing (r = -0.75, P = 0.002); at 6 d postdosing, the correlation was weaker. CONCLUSIONS: DRD can detect changes in total body stores of vitamin A, although factors affecting serum D:H need to be elucidated. Serum D:H 3 d postdosing might be used as an early indicator of total body stores of vitamin A, although a predictive equation will need to be developed.

Short- and long-term beta-carotene supplementation do not influence T cell-mediated immunity in healthy elderly persons.

Supplementation of healthy elderly persons with beta-carotene has been considered a way to enhance immune responses. In study 1 the short-term effect of beta-carotene (90 mg/d for 3 wk) on immunity was assessed in a randomized, double-blind, placebo-controlled longitudinal comparison of healthy elderly women. In study 2 the long-term effect of beta-carotene (50 mg every other day for 10-12 y) on immunity was assessed in a randomized, double-blind, placebo-controlled longitudinal comparison of men enrolled in the Physicians' Health Study. Subjects from both studies taking active supplements had significantly greater plasma beta-carotene concentrations than did subjects taking placebo. The pre- to postintervention change in delayed-type hypersensitivity skin test responses between beta-carotene and placebo groups in the short-term study was not significantly different, nor was the response between treatment groups in the long-term study. There were no significant effects due to beta-carotene supplementation on in vitro lymphocyte proliferation, production of interleukin 2, or production of prostaglandin E2 as a result of short- or long-term beta-carotene supplementation. In addition, there were no differences in the profiles of lymphocyte subsets [total T cells (CD3+), T helper cells (CD4+), T cytotoxic-suppressor cells (CD8+), and B cells (CD19+)] due to short- or long-term beta-carotene supplementation, nor were there differences in percentages of CD16+ natural killer cells or activated lymphocytes (cells expressing interleukin 2 transferrin receptor) due to long-term beta-carotene supplementation. Consistent results from these two trials show that beta-carotene supplementation did not have an enhancing or suppressive effect on T cell-mediated immunity of healthy elderly.

Importance of adequate vitamin A status during iron supplementation.

Nutritional deficiencies, including iron deficiency, may promote infection by lowering the body's resistance to infectious diseases. However, it has been shown that administration of iron in developing countries can result in increased morbidity, because pathogenic bacteria may compete effectively for iron in the circulation, resulting in an exacerbation of existing infections. Improved vitamin A status may protect against this potentially harmful effect of iron supplementation in environments where infections are highly prevalent.

Effect of beta-carotene supplementation on the concentrations and distribution of carotenoids, vitamin E, vitamin A, and cholesterol in plasma lipoprotein and non-lipoprotein fractions in healthy older women.

OBJECTIVE: We studied the effect of beta-carotene supplementation on the concentrations and distribution in plasma lipoprotein and non-lipoprotein fractions of carotenoids, alpha-tocopherol, retinol, and cholesterol. METHODS: Ten women ingested either 90 mg of beta-carotene or placebo daily for 3 weeks while residing in their homes and eating their usual meals. Carotenoids (beta-carotene, lycopene, lutein/zeaxanthin), retinol, alpha-tocopherol, and cholesterol were measured in plasma lipoprotein and non-lipoprotein fractions before and after treatment. RESULTS: In the beta-carotene-supplemented group, total plasma beta-carotene increased 14-fold from 0.48 +/- 0.13 to 6.83 +/- 2.12 mumol/L (p = 0.04). Although the greatest increase in beta-carotene was in low-density-lipoproteins (LDL), the magnitude of increase was similar in LDL, high-density-lipoproteins (HDL), and very-low-density-lipoproteins (VLDL). Thus, the relative distribution of beta-carotene in lipoproteins was unchanged: approximately 71% was in LDL, approximately 15% in HDL and approximately 12% in VLDL, before and after beta-carotene supplementation. There were no changes in amounts and distribution in lipoproteins of the other carotenoids, alpha-tocopherol, and cholesterol. There was no change in the amount of retinol in lipoprotein-deficient plasma. There were no changes in total plasma triglycerides. Significant positive correlations were found between LDL- or VLDL-cholesterol and alpha-tocopherol in LDL or VLDL, respectively; between LDL- or VLDL-cholesterol and lutein/zeaxanthin in LDL or VLDL, respectively; and between HDL-cholesterol and beta-carotene in HDL. CONCLUSIONS: beta-Carotene supplementation (90 mg/day for 3 weeks) in healthy older women results in an enrichment of all plasma lipoprotein fractions with beta-carotene, but does not alter the relative distribution of beta-carotene in lipoproteins. beta-Carotene supplementation has no effect on the amounts and relative distribution of lycopene, lutein/zeaxanthin, and alpha-tocopherol in lipoproteins, or of retinol in the non-lipoprotein fraction of plasma. Short-term beta-carotene supplementation has no effect on the concentrations of plasma total triglycerides, total cholesterol, HDL-, LDL-, and VLDL-cholesterol.

Relation between beta-carotene intake and plasma and adipose tissue concentrations of carotenoids and retinoids.

We evaluated the relation between beta-carotene intake and plasma and adipose tissue concentrations of carotenoids and retinoids. In Study 1, beta-carotene intakes were significantly greater in vegetarians than in nonvegetarians. Plasma concentrations of beta-carotene were also significantly higher in vegetarians than in nonvegetarians but only after two nonvegetarians with excessive intake of carrots were omitted. Plasma retinoid (retinol, retinyl esters, and retinoic acid) concentrations were not different between the two groups. In Study 2, female subjects ingested a daily placebo or 90 mg beta-carotene for 3 wk. In the group fed beta-carotene, plasma beta-carotene concentrations were significantly increased from baseline at 1, 2, and 3 wk. No beta-carotene changes were observed in the placebo-fed group. Plasma retinoid concentrations did not change in either group. In Study 3, adipose tissue beta-carotene and retinoid concentrations were measured in men after an oral beta-carotene dose (120 mg, experimental subjects) or no beta-carotene (control subjects). In the experimental subjects, adipose beta-carotene concentrations increased from baseline at 5 and 10 d postdosing. The control group's adipose tissue beta-carotene concentration did not change over a 10-d period. Changes in retinoids in adipose tissue were not significant in either group. In conclusion, dietary and supplemental beta-carotene increased plasma beta-carotene concentrations but had no effect on plasma retinoid concentrations. There may be little tissue metabolism of beta-carotene to retinoids. Therefore, the anticarcinogenic effect of beta-carotene, if any, may be due to properties of the molecule itself.

Skin lycopene is destroyed preferentially over beta-carotene during ultraviolet irradiation in humans.

This placebo-controlled study examined in healthy women the effects of ingestion of a single large dose of beta-carotene (120 mg) on the concentrations of beta-carotene and lycopene in plasma and skin, and the effects of UV light exposure on the concentrations of beta-carotene and lycopene in the skin. Ingestion of beta-carotene increased plasma beta-carotene concentration by 127%, from 0.26 +/- 0.06 (mean +/- SEM) to 0.59 +/- 0.07 mumol/L after 1 d, and the level remained elevated at 0.54 +/- 0.11 mumol/L after 5 d. beta-Carotene in skin, analyzed after 6 d, increased by 23%, from 1.41 +/- 0.74 to 1.74 +/- 0.72 nmol/g. beta-Carotene ingestion had no effect on the lycopene concentrations of plasma (0.37 +/- 0.11 mumol/L) or skin (1.60 +/- 0.62 nmol/g). A single exposure of a small area of one volar forearm to a dose of solar-simulated light (three times the individually determined minimal erythema dose) resulted in 31 to 46% reductions in skin lycopene concentration compared with an adjacent non-exposed area. The same UV dose did not result in significant changes in skin beta-carotene concentration. We conclude that a single 120-mg dose of beta-carotene increases plasma and skin beta-carotene concentrations and has no effect on plasma and skin lycopene concentrations. The amounts of lycopene in plasma and skin are comparable to or even greater than those of beta-carotene. When skin is subjected to UV light stress, more skin lycopene is destroyed compared with beta-carotene, suggesting a role of lycopene in mitigating oxidative damage in tissues.

Effect of beta-carotene supplementation on the human sunburn reaction.

Beta-carotene, a quencher of excited species such as singlet oxygen and free radicals, has been reported to protect against cutaneous photodamage, including sunburn acutely and photocarcinogenesis chronically. The present double blind placebo-controlled study examines the effect of beta-carotene supplementation on the human sunburn response and specifically on the induction of sunburn cells at the time of peak reaction intensity (24 h) after a single solar simulated light exposure 3 times the individually determined minimal erythema dose (MED). Administered orally either as a single 120 mg dose to dietarily restricted subjects or for 23 d as a daily 90 mg supplement to subjects on standard diets, beta-carotene increased plasma and skin levels of beta-carotene compared to both pretreatment levels and placebo-treated controls, but provided no clinically or histologically detectable protection against a 3 MED sunburn reaction. Thus, these data suggest that oral beta-carotene supplementation is unlikely to modify the severity of cutaneous photodamage in normal individuals to a clinically meaningful degree.

Beta-carotene supplementation increases antioxidant capacity of plasma in older women.

The antioxidant effect of dietary beta-carotene supplementation on the peroxidation potential of plasma was investigated in a randomized double-blind, placebo-controlled study. Twelve healthy women (62-80 y) supplemented their usual daily diet with 90 mg of beta-carotene (n = 6) or placebo (n = 6) capsules for 3 wk. Plasma concentrations of beta-carotene, alpha- and gamma-tocopherol, ascorbate, urate, bilirubin and in vitro production of phosphatidylcholine hydroperoxides (PC-OOH) and utilization of plasma antioxidants in the presence of 50 mmol/L 2,2'-azobis (2-aminopropane) hydrochloride (AAPH), a free radical generator, at 37 degrees C were measured before and after dietary treatment. Plasma beta-carotene increased from 0.76 +/- 0.16 to 6.45 +/- 1.16 micromol/L (P < 0.05) in supplemented but not placebo-treated subjects. The plasma concentrations of other antioxidants did not change significantly in either group. beta-Carotene supplementation did not affect basal levels of plasma PC-OOH as measured by HPLC post-column chemiluminescence but did affect AAPH-induced production of PC-OOH. Before supplementation, the induction period of plasma PC-OOH production was 2.4 +/- 0.4 h, with levels reaching 5.39 +/- 1.50 micromol/L after 6 h of incubation. After supplementation, the induction period increased significantly to 4.2 +/- 0.4 h (P < 0.01), with a lower PC-OOH production of 2.16 +/- 0.90 micromol/L after 6 h (P < 0.05). In this system, plasma ascorbate concentrations were depleted first, followed by loss of bilirubin and alpha-tocopherol and then by the sequential loss of gamma-tocopherol, urate and beta-carotene. These results indicate that beta-carotene supplementation increases the plasma antioxidant capacity of older women.

Beta-carotene, retinol and retinyl ester concentrations in serum and selected tissues of ferrets fed beta-carotene.

The concentrations of beta-carotene, retinol and retinyl esters in serum and selected tissues of ferrets fed diets supplemented with beta-carotene (80 micrograms/g wet diet) for 3 wk were determined. The initial concentration of serum beta-carotene was 0.011 +/- 0.006 mumol/L (mean +/- SEM); at the end of the experimental period it was 5.75 +/- 1.60 mumol/L. No significant differences in serum retinol and total retinyl esters were observed between beta-carotene-fed and control ferrets that had been fed an unsupplemented diet. The predominant retinyl esters in serum were retinyl stearate (53%) and retinyl palmitate (35%). Of the tissues analyzed after beta-carotene feeding, the liver contained the highest concentration of beta-carotene (78.8 +/- 18.8 nmol/g). Other tissues that contained beta-carotene in amounts ranging from 17 to 20 nmol/g were adrenals, small intestine, stomach and colon; lesser amounts (6.9 nmol/g) were found in kidneys. Amounts ranging from 1.2 to 2.3 nmol/g were found in muscle, bladder, adipose tissue, lungs and skin; only 0.37 and 0.34 nmol/g were present in brain and eyes, respectively. Thus, like humans, ferrets have the capacity to absorb intact beta-carotene and to store this compound in tissues, especially the liver. However, compared with humans, ferrets have elevated concentrations of retinyl esters in serum, liver and other tissues.