Doses Of Beta-carotene Research Articles

Enhancement of sow reproductive performance by β-carotene or vitamin A3

Two experiments were conducted at separate commercial farms. In Exp. 1, all primiparous sows and an equal number of multiparous sows weaned each week were randomly assigned to one of four treatment groups. Treatments consisted of one i.m. injection on the day of weaning of 0, 50, 100, or 200 mg of beta-carotene. Sows were checked for estrus with boars once daily and mated at first estrus after weaning. A sample of sows (n = 100) was selected for determination of plasma beta-carotene and vitamin A. Blood samples were obtained from another group (n = 120) 14 d after injection to determine plasma progesterone. In Exp. 2, treatments consisted of i.m. injection of 200 mg of beta-carotene, 50,000 IU of vitamin A, or vehicle on the day of weaning, on the day of mating, and on d 7 after mating. In both experiments, the sow diet was supplemented with 11,000 IU/kg of vitamin A. In Exp. 1, there was no effect of dose of beta-carotene on the interval from weaning to estrus or on the repeat service rate. There was a dose x parity interaction on the number of pigs born dead (P < .01) and born alive (P < .10), because treatment with beta-carotene did not affect reproduction in primiparous sows, but litters subsequently farrowed by multiparous sows had more pigs born alive and fewer pigs born dead. There was a dose x day interaction (P < .05) on plasma beta-carotene; beta-carotene was elevated on d 6 and 13 after injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Uptake of orally administered beta-carotene by blood plasma, leukocytes, and lipoproteins in calves.

The uptake of beta-carotene by blood cells, plasma, and lipoproteins was studied in bull calves that were orally administered a single (Exp. 1; n = 18 Angus calves) or multiple (Exp. 2; n = 16 Holstein calves) doses of beta-carotene. Administration of beta-carotene increased plasma beta-carotene and the amount of beta-carotene associated with each lipoprotein fraction. Before beta-carotene treatment, the total amount of beta-carotene associated with the high-density lipoprotein (HDL) was three- to fourfold higher than the amount associated with low-density lipoprotein (LDL) and fivefold higher than the amount associated with very-low-density lipoprotein (VLDL). The relative increase in total beta-carotene associated with the lipoproteins was greater for LDL than for HDL or VLDL. Orally administered beta-carotene increased the uptake of beta-carotene by lymphocytes. Subcellular fractions of blood lymphocytes isolated from animals fed beta-carotene revealed that beta-carotene was taken up in significant amounts by the mitochondrial, nuclear, and microsomal fractions. The profile of beta-carotene uptake by these subcellular fractions did not mirror that observed in plasma. In contrast, beta-carotene was not detectable in blood neutrophils and erythrocytes in either beta-carotene-supplemented or unsupplemented calves. Treatment did not influence the concentrations of retinol or alpha-tocopherol in plasma, lipoproteins, lymphocytes, neutrophils, or erythrocytes. These data revealed the presence of beta-carotene in bovine lymphocyte subcellular fractions and suggest a possible physiological role of beta-carotene in these cells.

Beta-carotene accumulation in serum and skin

The accumulation of beta-carotene in serum and skin was evaluated in human volunteers. A single 51-mg dose of beta-carotene given in the absence of dietary fat resulted in no detectable change in serum beta-carotene. The same dose administered with 200 g fat increased serum beta-carotene 2.5-fold at 40 h. Similarly, administering beta-carotene daily in three divided doses with meals raised the serum beta-carotene concentration three times as high compared with the same total dose administered once a day; both regimens had the same time constant for serum accumulation; 9-10 d. Remittance measurements of skin color demonstrated that the accumulation of beta-carotene in skin was delayed by up to 2 wk compared with serum accumulation. These data indicate that beta-carotene absorption requires dietary fat and is enhanced by administering with meals but there is a long time constant for serum (10 d) and tissue (several weeks) accumulation.

β‐Carotene decreases markers of lipid peroxidation in healthy volunteers

We previously showed that daily intake of beta-carotene, a nontoxic antioxidant, reduces lipid peroxidation as assessed by serum lipid peroxide levels. An alternative method to detect lipid peroxidation is the measurement of pentane in breath. Pentane is a five-carbon hydrocarbon that is released when an omega-6 unsaturated fatty acid undergoes peroxidation. The aim of this study was to see whether graded doses of beta-carotene would affect breath pentane excretion in normal subjects placed on a carotenoid-free liquid diet for two weeks. The subjects were then repleted with either 15 (n = 7) or 120 mg (n = 8) of beta-carotene daily for four weeks while continuing the same diet. Serum beta-carotene and breath pentane were measured before and after beta-carotene refeeding. Lipid peroxidation, as assessed by gas-chromatographic measurement of breath pentane, was significantly (p < 0.05) reduced by daily supplements of 120 mg beta-carotene (from 3.7 +/- 0.9 to 2.2 +/- 1.4 nmol/l). However, the decline in pentane exhalation observed with the 15-mg beta-carotene dose did not achieve statistical significance (p = 0.13).

Distribution of orally administered β-carotene among lipoproteins in healthy men

Plasma and lipoprotein concentrations of beta-carotene (BC) were measured in men for 10 d after an oral dose of BC (120 mg) (experimental subjects, n = 11) or no BC (control subjects, n = 5). Lipoproteins were separated by sequential ultracentrifugation and BC was measured by HPLC. Plasma and lipoprotein BC concentrations in control subjects were steady. In experimental subjects, plasma BC content increased by 6 h postdosing (P less than 0.015), peaked at 24 h (P less than 0.05), and returned to baseline by 7 d. Maintenance of plasma BC concentrations suggests homeostatic control. Of the 11 experimental subjects, only 4 had a plasma response. Early increases in the BC content of chylomicrons, very-low-density lipoproteins, and intermediate-density lipoproteins. Intestinal input accounts for early rises in circulating BC concentrations whereas hepatic secretion is the source of later increases. Among all of the lipoproteins, transfer of BC may occur.

Interaction of ethanol with beta-carotene: delayed blood clearance and enhanced hepatotoxicity.

Because we had found that ethanol interacts with retinol, we investigated whether it also affects its precursor, beta-carotene. In 14 baboons fed ethanol (50% of total energy) for 2 to 5 yr with a standard amount of beta-carotene (one 200-gm carrot/day), levels of beta-carotene were much higher than in controls fed isocaloric carbohydrate, both in plasma (122.5 +/- 30.9 nmol/dl vs. 6.3 +/- 1.4 nmol/dl; p less than 0.005) and in liver (7.9 +/- 1.1 nmol/gm vs. 1.8 +/- 0.5 nmol/gm; p less than 0.001). Even 20 days after withdrawal of the carrots, plasma beta-carotene levels remained higher in alcohol-fed baboons than in controls (10.1 +/- 3.8 nmol/dl vs. less than 0.1 nmol/dl). Next, the diet was supplemented with beta-carotene beadlets: in four pairs of baboons given a low dose of beta-carotene (3 mg/1,000 kcal), plasma levels were significantly higher in alcohol-fed animals than in controls, even when expressed per cholesterol (although the latter increased with alcohol intake). Seven pairs of animals were given a higher dose (30 mg/1,000 kcal) of beta-carotene for 1 mo, followed, in four pairs, by 45 mg for another month. On cessation of beta-carotene treatment, plasma levels decreased more slowly in the alcohol-fed baboons than in the controls. Percutaneous liver biopsy specimens revealed that liver concentrations of beta-carotene correlated with plasma levels but were higher in the alcohol-fed baboons than in the control baboons, whereas the beta-carotene-induced increase in liver retinoids was lower (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

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β-Carotene Uptake and Tissue Distribution in Ferrets (Mustela putorius furo)

Ferrets accumulate beta-carotene in liver and adipose tissue after chronic feeding. This study was designed to further evaluate the time course of uptake and depletion of beta-carotene in ferret serum and tissues. Male ferrets (n = 15; 1000-1200 g) were given a single dose of beta-carotene (10 mg/kg body wt) with a meal. Animals were killed at various time points over an 11-d period. Blood and tissue samples were extracted and analyzed for beta-carotene by HPLC. Peak serum beta-carotene levels (0.68 +/- 0.18 mumol/L) were observed 8 h after the test meal. beta-Carotene was essentially cleared from the blood by 76 h. Peak beta-carotene concentrations (nmol/g) were observed between 8 and 16 h after ingestion for liver (1.20 +/- 0.04), lung (0.042 +/- 0.012), kidney (0.090 +/- 0.015) and spleen (0.076 +/- 0.012). Ferret liver also seemed to contain a variety of other polar and nonpolar carotenoids. Ferrets were shown to absorb beta-carotene from a meal and have a consistent serum response pattern. Absorbed beta-carotene is differentially distributed in a variety of tissues. The ferret seems to be a useful model for the study of beta-carotene absorption and metabolism.

Plasma response to oral beta-carotene in Guatemalan schoolchildren

The response to oral doses of beta-carotene (0 mg, n = 10; 15 mg, n = 20; and 30 mg, n = 21) was studied in 51 Guatemalan children aged 8-15 y, with mean fasting plasma retinol concentrations of 1.72 +/- 0.38 mumol/L. Beta-carotene was delivered with a chocolate drink containing 8.4 g fat. Serial blood sampling was performed at intervals up to 48 h. Circulating retinol concentrations remained relatively constant. The maximum increases in plasma beta-carotene after the 30- and 15-mg doses for all subjects occurred at 24 h and were 0.29 and 0.23 mumol/L, respectively. Time of maximum increase for individuals varied and average maxima over the 48-h period for individuals were 0.13 and 0.26 mumol/L for the 15- and 30-mg-treatment groups, respectively. Increased plasma beta-carotene concentrations were not predicted by recent intake of dietary vitamin A, fasting plasma concentrations, or anthropometric measurements.

Serum time curve characteristics of a fixed dose of beta-carotene in young and old men.

The present study was designed to evaluate age-related differences in serum beta-carotene time curve response characteristics when a beta-carotene dose was given in conjunction with 1500 kcal over the course of a day. On two consecutive days, seven old (73 +/- 4 years) and six young (24 +/- 1 years) men were each fed three 500-kcal meals of an isotonic liquid formula diet containing only trace amounts of beta-carotene. On the first day of testing, no supplemental beta-carotene was given (baseline day). A 15 mg dose of beta-carotene was fed with the morning meal on the second day (test dose day). Fasting blood and hourly blood samples were obtained for 8 consecutive hours on both days. Additional blood was drawn 24 and 48 hours after the test beta-carotene dose. There were no statistical differences in baseline beta-carotene concentrations between the two age groups tested, but, because of high individual variability, serum time curve characteristics were adjusted for fasting beta-carotene levels. After adjustment, the postdose serum beta-carotene response was two to three times greater (p less than or equal to 0.04) in young subjects, as evaluated by peak concentration, area under the curve, or ascending slope of the serum response curve. Examination of factors besides age group that may have accounted for these results suggests that the serum response of the elderly may be more a function of body composition and/or serum lipid patterns than of age per se. However, in the present US population, it may not be valid to control for these factors, which are both closely related to aging.

Spirulina as a source of vitamin A

Experiments were carried out to assess spirulina fusiformis-a blue green algae as a source of vitamin A in rats. In one experiment, the control rats were fed synthetic vitamin A and the experimental rats spirulina as the sole source of vitamin A. The liver vitamin A concentration of spirulina-fed rats of both sexes was found to be significantly higher than that of the control rats. In another experiment the absorption of carotenes from the solvent extract of spirulina and their availability (vitamin A value) as judged by the levels of vitamin A and carotene in plasma and liver were compared with those of synthetic beta-carotene or vitamin A in male rats. The absorption of beta-carotene from spirulina extract tended to be lower than that of crystalline beta-carotene at doses of 550 and 1100 micrograms of beta-carotene. The difference became insignificant at lower beta-carotene dose of 275 micrograms. Spirulina carotene-fed rats did not show a strict dose related increase in the liver or serum vitamin A concentration. The liver vitamin A storage and plasma levels of vitamin A of spirulina carotene-fed rats was much higher than expected. The results of the two studies reported suggest that the algae spirulina can be a valuable source of vitamin A.

Beta-carotene's effects on serum lipoproteins and immunologic indices in humans

Doses of beta-carotene for cancer-prevention trials have been chosen based on epidemiologic data. Mechanisms of the putative antineoplastic effects by beta-carotene are unknown but may involve modulation of the immune system. We measured plasma carotenoid concentrations and selected immunologic indices at baseline and at 2 and 4 wk in 50 healthy humans (5 groups of 10 each) ingesting 0, 15, 45, 180, or 300 mg beta-carotene/d for 1 mo in this randomized placebo-controlled, open-label, parallel study. Plasma beta-carotene concentrations were markedly increased by 2 wk and were correlated with dose. Beta-carotene concentrations plateaued between 2 and 4 wk except for the 300-mg group. Thus, we developed a dose-concentration curve to optimize beta-carotene-dose selection to achieve target plasma concentrations. We were unable to identify any effects of beta-carotene ingestion on the immunologic indices studied, but modest increases in high-density-lipoprotein cholesterol were observed in all beta-carotene-treated groups.

Dietary lipid level and the availability ofβ‐carotene ofdunaliella‐bardawilin rats

High plasma and tissue levels of beta-carotene have been implicated to be inversely related to the incidence of some types of cancer. Previous studies indicated that the availability of the natural beta-carotene isomer mixture of Dunaliella bardawil was severalfold higher than that of synthetic all-trans beta-carotene. This study illustrated that this higher availability, as expressed by hepatic and plasma beta-carotene, can be further enhanced by increased dietary lipid level. For 12 days, weanling male and female rats were fed diets containing either 0.1% all-trans beta-carotene or spray-dried Dunaliella bardawil having an equal level of the beta-carotene isomer mixture. The diets contained 5 or 15% soybean oil. The rise in dietary fat resulted in a marked increase in plasma and liver beta-carotene, with the Dunaliella isomer mixture being more effective. Higher levels were found in female than in male animals. These findings may be relevant when a high dose of beta-carotene is considered as a potential anticancer agent.

Plasma concentrations of carotenoids after large doses of beta-carotene

Plasma concentrations of beta-carotene were determined in healthy men ingesting 180 mg beta-carotene/d during studies on the effects of beta-carotene on sunburn prevention. This dose is also used in the treatment of light-sensitive skin diseases. beta-carotene concentrations were found to reach a plateau in 1.5 to 4 wk, although there was much individual variation in the actual serum concentrations achieved. Carotenodermia was present in most subjects. No evidence of toxicity was found, confirming the findings of previous photosensitivity-prevention studies, which also reported no significant toxicity attributable to beta-carotene.

Normal serum response to oral beta-carotene in humans.

This study was performed to determine (1) the normal serum response to a single oral dose of beta-carotene (BC), (2) the effect of meal timing and serum response to meal lipids on serum BC, (3) the effect of administered BC on other serum carotenoids and retinoids, and (4) the relationship of body composition to serum BC response. Subjects consumed one BC dose with a liquid 500 kcal BC-free diet; fasting and hourly venous blood was collected for 8 hours and again at 24 hours. A second liquid BC-free meal was consumed 4 hours post-dosing; this midday meal was omitted in some subjects. Serum BC levels rose and peaked initially at 5 hours, but continued to be absorbed in most subjects, remaining significantly elevated at 24 hours as compared to baseline values (p less than 0.001), independent of BC dose. The area under the BC absorption curve (8-hr AUC) increased linearly with BC dose and correlated positively with peak serum triglycerides (TG) after a meal (n = 26 tests, r = 0.56, p less than 0.003). Omission of the midday meal significantly delayed the initial BC peak to 7 hours (p less than 0.0004). Serum levels of retinol, alpha-carotene, cryptoxanthin, lycopene, and lutein remained unchanged. Serum retinyl esters did not rise in all subjects following BC intake; when it did, retinyl esters rose and peaked concomitantly with BC, but declined within 8 hours. There was no correlation between the initial serum BC, peak BC, 24-hr BC, 8-hr AUC, or peak serum TG and the percentage of body fat. We conclude that: (1) the timing of the serum response to oral BC is independent of dose, (2) the serum BC response is greater in those with a greater serum triglyceride response to meal lipids, (3) BC at the doses given does not alter the levels of other serum carotenoids, and (4) there is no correlation between the serum BC parameters measured and adiposity.

Plasma carotenoids in normal men after a single ingestion of vegetables or purified beta-carotene

Changes in seven plasma carotenoids were measured in 30 men for 11 d after ingesting a single dose of pure beta-carotene or a high carotenoid vegetable. A controlled, low-carotenoid diet was fed in a crossover design. Maximum plasma concentrations of beta-carotene occurred 24-48 h after dosing with beta-carotene (12 or 30 mg) or carrots (270 g). A large intake of broccoli (600 g) or tomato juice (180 g) did not change any plasma carotenoids. We concluded that 1) normal subjects vary widely, three to fourfold, in efficiency of carotenoid absorption; 2) peak plasma response to beta-carotene in a capsule occurs at 24-48 h; 3) a large single intake of carrots produces a small increase in plasma beta-carotene but single intakes of broccoli or tomato juice do not change plasma carotenoids; and 4) plasma response to pure beta-carotene is greater than the response to a similar amount of beta-carotene in carrots.

Enhancing the carotenoid content of atherosclerotic plaque: Implications for laser therapy

Selective laser ablation of human atherosclerotic plaque is possible because endogenous carotenoid pigments found in atherosclerotic plaque confer a twofold preferential absorption of laser radiation at 450 to 500 nm. In this study, patients with carotid endarterectomy were pretreated with oral beta carotene to determine if the carotenoid content and therefore laser selectivity of plaque could be increased in vivo. Beta carotene—treated patients had a significant, nearly twofold increase in their plaque carotenoid concentration, which increased from 0.22 to 0.40 μg beta carotene/mg cholesterol. These results suggest that selective ablation of atherosclerotic plaque may be enhanced by pretreating patients with doses of oral beta carotene for short periods of time.

Serum level changes after administration of a pharmacologic dose of beta-carotene

Results from a pilot study to assess the feasibility of conducting a full-scale lung-cancer-prevention trial using pharmacologic beta-carotene are reported. Participants in the study were randomized in a double-blind fashion to receive either 15 mg orally of beta-carotene or placebo daily. Findings for the first 300 men to complete 1 y on study are presented. After 10 mo of treatment, serum levels in the placebo group showed essentially no change whereas levels in the treated group increased almost 10-fold after 4 mo of treatment. The relationship between change in serum levels are evaluated in regard to body mass index, alcohol consumption, amount of smoking, lipids, and other variables. The results to date clearly indicate that substantial serum response can be achieved with only 15 mg/d and that with this dosage no skin discoloration or other toxicities are observed.

Bioavailability of beta-carotene in humans

Normal healthy volunteers were studied after they ingested various beta-carotene doses. Daily administration of 15 or 45 mg beta-carotene resulted in significant increase in plasma beta-carotene levels. The extent of increase and the pattern of plasma beta-carotene levels showed substantial interindividual variation. Absorption of beta-carotene was affected by dietary fat concentration. Individuals placed on a high-fat diet showed significant increases in plasma beta-carotene as compared with those placed on a low-fat diet. Pharmacological doses of beta-carotene (45 and 90 mg) were used in intermittent schedules (5-6 d intervals) without altering the steady state of beta-carotene plasma levels. Yellowing of the skin occasionally occurred during daily dosing with 45 mg beta-carotene without evidence of toxicity. The observed individual variation in bioavailability of beta-carotene raises questions regarding clinical use of this micronutrient. It appears that determination of target plasma beta-carotene concentrations is essential for effective use of this compound in prevention or treatment.

Photoprotection by carotenoids

Carotenoid pigments have been found to have a protective function against photosensitization in green plants. This protective ability has been exploited in the administration of high doses of beta-carotene to patients with erythropoietic protoporphyria to ameliorate the photosensitivity associated with this disease. The carotenoids seem to exert their light-protective function by quenching excited species such as singlet oxygen and free radicals.