Plasma carotenoid response to chronic intake of selected foods and beta-carotene supplements in men.

We determined serial changes in four major plasma carotenoid fractions (alpha-carotene, beta-carotene, lutein/zeaxanthin, and lycopene) in 30 men consuming defined daily doses of carotenoids from foods (broccoli, carrots, or tomato juice) or from purified beta-carotene in capsules (12 or 30 mg) for 6 wk while fed a controlled diet. Compared with baseline, beta-carotene increased in the 30- and 12-mg-capsule and carrot groups whereas alpha-carotene increased in the carrot group and lutein increased in the broccoli group. Lower lutein concentrations in recipients of beta-carotene capsules suggested an interaction between these two carotenoids. Lycopene declined in all groups except the tomato-juice group. Total carotenoid concentration changes only reflected the large increases in beta-carotene concentrations and not the smaller changes observed in other individual carotenoids. Overall, purified beta-carotene produced a greater plasma response than did similar quantities of carotenoids from foods sources. However, some foods increased plasma concentrations of certain carotenoids.

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.

Are the recommended allowances for dietary antioxidants adequate?

Recommended dietary allowances are standards for maintaining health. Claims that intakes substantially above the allowances may provide protection from xenobiotics and prevent diseases, including cancer, are examined critically for five nutrients that have antioxidant potential. Major criticism is directed at the failure of epidemiologists to recognize that for many of these nutrients, metabolic differences among individuals preclude a direct relationship between dietary intake and plasma or tissue concentration. Also, the fact that no differences in disease incidence have been described within various species of animals that have markedly different metabolic patterns for some of these nutrients has not been considered. It is concluded that the experimental and epidemiological evidence to data that increased intakes of certain nutrients will have beneficial effects on human health are tenuous.

The effect of neomycin on plasma alpha tocopherol levels in type II hyperlipoproteinemia.

Use of oral neomycin as a hypocholesterolemic agent was found to decrease plasma alpha tocopherol levels during a 9-month, randomized, crossover placebo-controlled clinical trial with controlled diet. Pooled data from each treatment sequence showed a placebo alpha-tocopherol level of 1,896 +/- 643 micrograms/dl, and a neomycin alpha-tocopherol concentration of 1,449 +/- 451 micrograms/dl (p less than .01). When all subjects were on neomycin simultaneously, the level increased to 1,665 +/- 614 micrograms/dl (p less than .05 from placebo). Normal plasma alpha-tocopherol ranges from 400-1,000 micrograms/dl. Neomycin treatment reduces but does not normalize elevated levels of alpha-tocopherol found in Type II hyperlipoproteinemia.

Linoleic acid absorption from lipid supplements in patients with cystic fibrosis with pancreatic insufficiency and in control subjects.

To determine the relative role of malabsorption as the cause of decreased linoleic acid in blood and tissue lipids of patients with cystic fibrosis (CF) and pancreatic insufficiency, the increase in plasma linoleic acid was determined after ingestion of various lipid supplements. CF patients with documented pancreatic insufficiency and normal control subjects were given each of four different lipid supplements on separate days (a minimum of 3 days apart). The supplements were commercial safflower oil, Microlipid, Captex 810D, and Captex 810B. Fasting subjects consumed 36 g of lipid in a milk shake containing 15 g of protein and 45 g of carbohydrate. Plasma samples obtained at 0, 2, 4, 6, and 8 h after the meal showed that CF patients absorbed linoleic acid from all of the lipid preparations tested when administered with their regular dose of pancreatic enzyme supplement. The mean maximal increase in percent plasma linoleic acid in CF patients was not different from controls after ingestion of safflower oil, Microlipid, and Captex 810B. With Captex 810D the CF patients had a significantly higher increase in percent plasma linoleic acid than controls, 6.75% vs. 2.27%, respectively, at 2 h (p less than 0.01), and 11.10% vs. 4.65% at 8 h (p less than 0.01). The CF patients also appeared to absorb the Captex products faster than controls, suggesting that presence of medium chain length fatty acids in these structured lipids facilitated their utilization by CF patients. The results indicate that malabsorption alone cannot account for the inadequate or marginal essential fatty acid status of CF patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Lipofuscin accumulation in extraocular muscle of rats deficient in vitamins E and A.

The influences of vitamin E and A deficiencies on the formation of lipofuscin in two different muscle fiber types of the extraocular muscle were tested. Weanling female albino rats (Sprague-Dawley) were divided into three groups and fed purified diets that were adequate or deficient in vitamin E and A: +E, +A; -E, +A; and -E, -A. After 35 weeks on this diet, the animals were killed for analysis of extraocular muscle. When examined by fluorescence microscopy, the extraocular muscle of the (-E, +A) rats showed more lipofuscin-specific fluorescence than the (+E, +A) and (-E, -A) rats. Lipofuscin was then further analyzed by electron microscopy (EM), using morphometric analysis. By this high-resolution technique, the increased lipofuscin of the (-E, +A) extraocular muscle was seen to be confined mostly to the type I fibers. The type II fibers were quite insensitive to vitamin E deficiency: in type II fibers, the (-E, +A) and (-E, -A) muscle showed very small amounts of lipofuscin, and the (+E, +A) showed none at all. Vitamin A has an influence on vitamin E-deficiency and appears to be involved in the formation of lipofuscin in type I muscle fibers of the extraocular muscle.

Multilayer cannula for long-term infusion of unrestrained rats.

A multilayer cannula was constructed from a long, thin inner cannula of siliconized rubber tubing with an outer collar of siliconized rubber tubing held in place by three "rubber bands" made from the same tubing as the collar. This multilayer cannula has been used for long term infusion studies of unrestrained rats and has several advantages over those described in the literature. It is easily secured into place without bending near the entry to the vein, or constricting the lumen. The use of a collar also insures that the correct length of cannula is inserted into the vein of the size rat being used.

Deficiencies of vitamins E and A in the rat: lipofuscin accumulation in the choroid.

The effects of vitamin E and A deficiencies on the formation of lipofuscin in the melanocytes and fibroblasts of the choroidal stroma and in the endothelial cells of the choriocapillaris were studied. Weanling female albino rats (Sprague-Dawley) were divided into three groups and fed purified diets adequate or deficient in vitamins E and A: +E, +A; -E, -A. After 35 weeks, vitamin E deficient rats (-E, +A) exhibited increased lipofuscin-specific autofluorescence in the choroid compared to the controls (+E, +A). By electron microscopy and morphometric methods the choroidal stroma of vitamin E deficient rats displayed an increase in lipofuscin content as measured by the number of lipofuscin granules and their size, if compared with the controls. However, in vitamin E deficiency, only animals with a supply of vitamin A (-E, +A) showed higher amounts of lipofuscin in the choroidal stroma; animals deficient in both vitamins (-E, -A) stayed on the same level as the controls (+E, +A). In the endothelial cells of the choriocapillaris, on the other hand, no significant increases in lipofuscin content were observed in either group of vitamin E deficient animals (-E, +A), (-E, -A). Apparently vitamin E deficiency affects the choroid by increasing lipofuscin formation only in the melanocytes and fibroblasts. Vitamin A appears to play a role in lipofuscin formation.

Lipofuscin accumulation resulting from senescence and vitamin E deficiency: spectral properties and tissue distribution.

The corrected fluorescence emission spectra and tissue distributions of the autofluorescent pigments which accumulate during normal aging and as a consequence of vitamin E deficiency were studied in albino rats. In the retinal pigment epithelium, both the age-related pigment (lipofuscin) and the pigment related to vitamin E deficiency had essentially identical emission spectra. Peak emission occurred from 590 to 650 nm. Young animals which had been kept on a vitamin E deficient diet for 17 weeks after weaning showed significant accumulations of autofluorescent pigment in uterus, duodenum, and retinal pigment epithelium, but not in the spinal cord or inferior olivary nucleus of the brain. Old animals (96 weeks) fed a commercial diet with adequate vitamin E had accumulated lipofuscin in the retinal pigment epithelium, spinal cord gray matter, and inferior olivary nucleus, but not in the duodenum or uterus. Thus, while the auto-fluorescent pigments related to aging and vitamin E deficiency have similar properties, their tissue distributions are quite different.

Cellular localization of liver vitamin A in rats given total parenteral nutrition (TPN) solutions intravenously or orally.

The cellular localization of liver vitamin A was determined in rats, depleted of retinol, whose vitamin A stores were repleted orally or by total parenteral nutrition (TPN) to determine if the route of vitamin administration affected storage location. Solutions containing dispersions of retinyl palmitate were infused into the TPN group and fed orally to controls for 5 days. The site of liver vitamin A storage was determined by correlating vitamin A-specific autofluorescence in frozen sections with the presence of lipid droplets in oil red O preparations, in 1-micron Epon sections and in sections prepared for electron microscopy. Both the vitamin A autofluorescence and oil red O staining were concentrated along the sinusoids in rats both infused with TPN solution and orally fed. Examination of thin sections at higher magnification showed that most of the lipid droplets containing vitamin A were localized near the sinusoidal side of the parenchymal cell cytoplasm, corresponding to the vitamin A autofluorescence and oil red O distribution. There were very few lipid droplets in the stellate cells and none in the Kupffer cells. The results indicate that vitamin A infused in TPN solutions is stored in the same cellular location as orally ingested vitamin A.

Tissue storage of vitamins A and E in rats drinking or infused with total parenteral nutrition solutions.

The total parenteral nutrition (TPN) rat and its sham-operated control were used as a model to compare the metabolism and storage of vitamins A and E when they are administered intravenously or orally. Male Fisher rats were depleted of both vitamins for several months with a diet free of vitamins A or E, but containing retinoic acid for growth. TPN solutions containing aqueous dispersions of retinol, retinyl palmitate and dl-alpha-tocopheryl acetate were infused at 2.3 ml/h into the jugular veins of 10 TPN rats. Eight sham-operated control rats drank similar volumes from food cups. TPN rats received 115.3 +/- 4.5 (mean +/- SEM) micrograms of retinol equivalents and 2.2 +/- 0.2 mg of alpha-tocopherol equivalents per day; controls received 146.4 +/- 16.5 micrograms and 2.1 +/- 0.3 mg, respectively. After 7 days the animals were fasted overnight and killed. Plasma levels of retinol were 27.8 +/- 1.5 micrograms/dl for TPN rats, and 27.4 +/- 1.2 for controls. Plasma alpha-tocopherol was 1909 +/- 183 micrograms/dl for TPN rats and 1063 +/- 77 for controls. The only forms of the vitamins found in plasma after overnight fasting were unesterified retinol and unesterified alpha-tocopherol. Sham-operated control rats stored amounts of vitamins A and E similar to values reported in the literature for fed animals. TPN rats stored more of both vitamins than controls in liver, heart, and spleen, but not in testes. The enhanced liver vitamin storage by TPN rats did not appear to be due to a slight increase in lipid content. The results indicate that both vitamins A and E infused in TPN solutions maintain blood levels and are stored in tissues.

Intrinsic, light-independent, regional differences in photoreceptor cell degeneration in vitamin A-deficient rat retinas.

The retinas of retinol-deficient rats reared in darkness or cyclic light were examined to determine whether regional degeneration of photoreceptor cells was induced by environmental lighting or resulted from intrinsic differences between ocular hemispheres. Weanling male Sprague-Dawley rats were fed a retinol-adequate or retinol-deficient diet and were reared in either cyclic light or darkness through 29 weeks. The nasal retinal quadrants were examined by light microscopy and the number of photoreceptor nuclei was counted in a 630 micron segment beginning 200 micron from the optic nerve. Retinol-deficient rats reared in darkness for 29 weeks lost 24% of their photoreceptors in the inferior nasal quadrant but only 11% in the superior nasal quadrant. Deficient rats reared in cyclic light for 29 weeks lost 39% of their photoreceptor cells in the inferior nasal quadrant and only 16% in the superior nasal quadrant. Photoreceptor cells degenerated faster in the inferior nasal quadrant than in the superior nasal quadrant in darkness or cyclic light. These results indicate that regional differences in rate of photoreceptor cell loss in retinol-deficient rats are not induced by the lighting conditions but occur as a result of intrinsic differences between the ocular hemispheres.