Effects of chronic β‐carotene supplementation on vitamin K status in adults

Plasma vitamin K concentrations and prothrombin coagulation activity were determined in 26 normal adults who had received daily (S‐carotene supplementation (0,15,30, or 60 mg) for six months. Neither plasma vitamin K nor coagulation activity were significantly decreased at any supplementation level. Thus, chronic β‐carotene supplementation, even at high daily doses, is not expected to result in clinical vitamin K deficiency. The data suggest separate mechanisms for intestinal absorption of β‐carotene and vitamin K.     

Serum retinoic acid levels in patients with resected benign and malignant colonic neoplasias on β‐carotene supplementation

To determine whether patients with colon cancer metabolize β‐carotene differently from benign colon polyp patients, a normal control group (n = 13) and groups of resected colon polyp patients (n = 29) or resected colon cancer patients (Dukes A and BI, n = 21) were supplemented with placebo or β‐carotene (30 mglday) taken with their morning meals for three months. Serum samples at zero and three months of the study were anlayzed blindly for retinoic acid and β‐carotene. The results showed that β‐carotene levels in the serum of colon polyp and colon cancer groups were 8‐ to 12‐fold higher than in the untreated control or the placebo‐treated groups. The benign polyp subjects (n = 17) receiving β‐carotene showed a significant rise in serum trans‐retinoic acid at three months compared with Time 0. The trans‐retinoic acid values from the colon cancer group receiving β‐carotene (n = 11) or placebo (n = 10) were significantly lower than the values from the β‐carotene‐supplemented colon polyp group. It appears that trans‐retinoic acid levels in response to β‐carotene supplementation are different between treated cancer and benign patients because of different body demands for retinoic acid.     

Influence of dietary spices on the in vivo absorption of ingested β-carotene in experimental rats

Animal studies were conducted to evaluate the influence of dietary spice compounds, piperine, capsaicin and ginger, on the absorption of orally administered β-carotene and its conversion to vitamin A. In rats maintained on these spice-containing diets for 8 weeks, concentrations of β-carotene and retinol were determined in the serum, liver and intestine 4 h after a single oral administration of β-carotene. β-Carotene concentration was significantly increased in the serum, liver and intestine of piperine- and ginger-fed rats, suggesting improved absorption of β-carotene. However, retinol concentration was not significantly changed in these animals, suggesting that the bioconversion of β-carotene to vitamin A was not similarly influenced. Between the two enzymes involved in the bioconversion of β-carotene to vitamin A, the activity of intestinal and hepatic β-carotene 15,15'-dioxygenase was either unaffected or lowered by these spice treatments. The activity of intestinal and hepatic retinal reductase was unaffected by the dietary spices. Activities of these two enzymes involved in the bioconversion of β-carotene to retinal were inhibited by the test spices in vitro, thus corroborating with the in vivo observation. Although the bioconversion of β-carotene was not promoted, increased absorption and tissue levels of β-carotene by the dietary spices may contribute to a higher antioxidant protection.     

The effect of different levels of dietary ß‐carotene on DMBA‐induced salivary gland tumors

Different levels of ß‐carotene (0, 5, 25, 125, and 250 mg/kg diet) were tested for their chemoprevention effects using 9,10‐dimethyl‐1,2‐benzanthracene‐induced salivary gland tumor model in rats. Tumor incidence and tumor weights were slightly lower in rats fed diets supplemented with 25 mg or more ß‐carotene/kg diet. Hepatic vitamin A and ß‐carotene levels were increased in a dose‐dependent fashion, reaching a plateau at 125 mg ß‐carotene/kg diet. In plasma, ß‐carotene concentrations were also increased with an increase in dietary ß‐carotene. Vitamin A levels in plasma were not affected. The normal salivary glands had higher concentrations of ß‐carotene than did the tumors. The results suggest that the decreases in tumor incidence and tumor weight may be related to the increase in plasma and tissue levels of ß‐carotene as a result of feeding high levels of ß‐carotene.     

Effect of vitamin e on rat hepatic cytochrome p‐450 activity

Hepatic cytochrome P‐450 activity has been shown to be affected by various dietary factors including vitamin E. However, reports of the effect of dietary vitamin E on cytochrome P‐450 activity have been inconsistent. The aim of the present study was to investigate the influence of dietary vitamin E on rat hepatic cytochrome P‐450 activity. Three groups of six male weanling Sprague‐Dawley rats were fed semipurified diets containing 0, 100, or 1,500 ppm vitamin E for eight weeks. Vitamin E was given in the form of a‐tocopheryl acetate. Dietary vitamin E significantly affected liver vitamin E content (p < 0.05) but had no effect on rat hepatic total P‐450 content, N‐nitrosodimethylamine demethylase, and NADPH‐cytochrome‐P‐450 reductase activities. Hepatic pentoxyresorufin O‐dealkylase and glu‐tathione S‐transferase activities were significantly greater in rats fed 100 and 1,500 ppm vitamin E than in rats fed no vitamin E (p < 0.05). Dietary vitamin E induced changes in hepatic phospholipid fatty acid composition. Hepatic phos‐pholipid linoleate was significantly greater in rats fed 0 and 1,500 ppm vitamin E than in rats fed 100 ppm vitamin E (p < 0.05). Hepatic phospholipid eicosapentaenoate was increased significantly by dietary vitamin E (p< 0.05). Hepatic thiobarbituric acid‐reactive substance was significantly greater in rats fed no vitamin E than in rats fed 100 and 1,500 ppm vitamin E (p < 0.05). The results suggest that vitamin E may influence cytochrome P‐450 IIB1 enzyme activity and may affect hepatic phospholipid fatty acid composition.     

In vivo and in vitro effects of β‐carotene and algae extracts in murine tumor models

Abstract

Phycotene, an algae extract with known antineoplastic activity, was demonstrated to prolong, but not sustain, an increased survival rate in a murine fibrosarcoma model when it was combined with immunotherapy. It was further shown that splenocytes from phycotene and β‐carotene‐treated survivors could not confer protection to a fresh tumor cell challenge in virgin mice after adoptive transfer. In a series of cytotoxicity assays, phycotene combined with immunization was demonstrated to enhance cell‐mediated and complement‐dependent cytotoxicity in the first 14–21 days. However, after 21 days, the phycotene and immunization groups exhibited a decreased ability to mediate immune cytotoxicity compared with immunization‐only controls. This may serve to explain the in vivo findings that while survival was increased early on in active immunization and phycotene‐treated mice, it eventually dropped to the level of the active immunization controls.     

The influence of different levels of dietary fat on the incidence and growth of mnu‐induced mammary carcinoma in rats

This study describes the influence of isocalorically fed diets (containing different amounts of fat) on tumor incidence and parameters of fat metabolism in female Sprague‐Dawley rats. Comparisons are made between rats induced with methylnitrosourea (25 mg/kg body wt) and untreated controls (Group I). The animals received either control diets (3.9% fat by weight, Groups I and II) or fat‐enriched diets (10.7%, GroupIII; 15.6%, Group IV; 21.4%, Group V) over a period of 180 days. At the termination of the experiment, intake of the diet containing 10.7% fat by weight (24% fat per total calories) was associated with the highest tumor incidence. Comparing the different diets, liver lipid concentrations in the individual groups increased with increasing dietary fat, whereas the total lipid in plasma decreased. During the feed‐ingperiod, total lipid of the liver and plasma, and plasma cholesterol, increased in all groups, but triglycerides of plasma decreased. However, when plasma cholesterol and triglycerides were calculated as a relative amount of total lipid in plasma, cholesterol was found to be significantly decreased in Groups III and IV, and triglycerides were increased in Group III but decreased significantly in Groups I, II, and Vat the end of the experiment.     

Development and relative validity of a food frequency questionnaire for the estimation of intake of retinol and β‐carotene

The aim of this study was to develop and validate a semiquantitative food frequency questionnaire to classify individuals according to their intakes of retinol and β‐carotene. Food items for the questionnaire were selected both on the basis of their contribution to total population intake of retinol and β‐carotene and on the proportion of between‐person variation explained, which was as calculated from data of two study populations in the Netherlands. Thus, 15 products containing retinol and 15 products containing β‐carotene were selected. These contributed over 90% to the total intake and explained 99% of the variation of retinol and β‐carotene, respectively. The questionnaire was validated against a dietary history in a population of 82 women (aged 30–49 years). The time elapsed between the two interviews was (on average) 25 days. Spearman rank‐order correlation coefficients comparing the questionnaire with the dietary history were 054, 0.59, and 0.64 for retinol, β‐carotene, and total vitamin A, respectively. The proportion of exact agreement in the two extreme categories of vitamin A intake, based on quintiles, was 56%. The corresponding gross misclassification (from 1 extreme category into the opposite) was 3%. These data indicate that a very short questionnaire can classify subjects into categories according to their vitamin A intake.     

GLV supplements increased plasma β–carotene, vitamin C, zinc and hemoglobin in young healthy adults

Summary Background Green leafy vegetables (GLV) are rich sources of β–carotene, iron and other micronutrients. Our in vitro studies have demonstrated good antioxidant potential in GLV. Moreover linkages of GLV intakes with plasma retinol and ascorbic acid were seen in apparently healthy Indians. Aim of the study To investigate the effect of GLV as a natural fortificant of multiple micronutrients through a prospective human trial. Methods Short–term (0–4 h) response (AUC) of single dose of 7.9 mg β–carotene and 130 mg ascorbic acid through a spinach–carrot meal against the standard meal without GLV plus10 mg β–carotene and 150 mg ascorbic acid tablets was studied in two groups of 4 young volunteers each. In the second trial of 3 weeks' supplementation, 5 groups of young adults (n = 40) were given either 100 g GLV/day alone or with tablets of vitamin E (100 mg/day), or C (100 mg/day) or more oil (5 g/day) or non–GLV meal with tablet of β–carotene (10 mg/day). Hemoglobin (Hb), plasma β–carotene, zinc, vitamin C, glucose, and triglycerides were measured. Results In a postprandial response, AUC were comparable in both GLV and standard meals for β–carotene and ascorbic acid. In case of triglycerides and glucose AUC the GLV meal showed a better recovery to the baseline value after 4 hours than the standard meal. Three weeks' supplementation of GLV with more oil resulted in significant increase of plasma β–carotene (51%) and Hb (9%). GLV with vitamin E showed a significant increase in plasma β–carotene (40%), Hb (8%) and plasma vitamin C (6%). Supplementing β–carotene without GLV significantly increased Hb (11%), plasma zinc (14%) in addition to β–carotene. Multiple regression analyses weighted for energy intake indicated a significant association of percent increase in Hb with intakes of iron, riboflavin, folic acid, β–carotene, copper, phytate and fiber (p < 0.01), percent change in plasma zinc with intakes of zinc, β–carotene, vitamin C, riboflavin, copper, iron, and thiamin (p < 0.01), percent change in vitamin C with intakes of vitamin C, vitamin E, niacin, riboflavin, thiamin, β–carotene, zinc, phytate and fiber (p < 0.05) and percent change in plasma β–carotene with intakes of β–carotene, thiamin, folic acid, zinc, phytate and tannins (p < 0.05). Conclusion Using 100 g GLV/day with 10 g oil could be a single moderate strategy for supplementation of iron, β–carotene, ascorbic acid and zinc.     

Taurocholate stimulates the absorption and biotransformation of β‐carotene in intact and lymph duct‐cannulated ferrets

We have determined the influence of dietary taurocholate and β‐carotene on the absorption and biotransformation of newly administered β‐[¹⁴C]carotene. Male ferrets were fed the control or β‐carotene diet (0.05% β‐carotene wt/wt) with and without taurocholate (1% wt/wt) for four weeks, and then the absorption and biotransformation of newly administered β‐[¹⁴C]carotene was measured after eight hours in intact or thoracic lymph duct‐cannulated animals. Percent recovery of β‐[¹⁴C]carotene in the liver was increased 3.6‐fold (p < 0.05) in the taurocholate‐fedferrets regardless of whether they were fed the control or β‐carotene diet. Percent recovery of labeled vitamin A in the liver was also increased by the same magnitude (p < 0.05). These results were confirmed in thoracic lymph duct‐cannulated ferrets. The recoveries of β‐carotene label in the lymph were comparable to the corresponding values in livers of intact animals. The recovery of β‐carotene label in the liver was 50% (p < 0.05) higher in β‐carotene‐fed than in control animals. Taurocholate stimulates intestinal absorption of newly administered β‐[¹⁴C]carotene and its metabolic conversion to ¹⁴C‐labeled vitamin A (retinol + retinyl ester) 3.6‐fold. β‐Carotene absorption is as efficient in thoracic lymph duct‐cannulated ferrets as in intact animals. Prior β‐carotene feeding also stimulates the absorption of newly administered β‐carotene by 50%.     

Effects of a soy milk supplement on plasma cholesterol levels and oxidative DNA damage in men – a pilot study

Summary Background: Phytoestrogens are a major component of Asian diets and may be protective against certain hormone-dependent cancers (breast and prostate) and coronary heart disease. They may also have antioxidant function in scavenging potentially harmful free radicals and thus decreasing oxidative attack on DNA. Aims of the study: A pilot study to determine the effects of a phytoestrogen supplement, in the form of soy milk, on plasma LDL and HDL cholesterol levels and DNA damage in men. Methods: Ten healthy men participated in the study and were assigned to one of three groups consuming 1 litre of either soy milk, rice dream (vegetable protein control) or semi-skimmed cow's milk (animal protein control) each day for 4 weeks. Results: The soy supplement caused significant increases in plasma genistein and daidzein concentrations despite considerable interindividual variation (P<0.001). Supplementation with soy resulted in a decrease in oxidative damage to DNA bases detected using the comet assay compared with controls (P<0.05). However, there was no significant effect of the soy supplement on plasma cholesterol or triglyceride levels in comparison with control groups. Conclusions: A 4 week soy milk supplementation in healthy volunteers does not alter serum cholesterol levels but can have a protective effect against oxidative DNA damage in lymphocytes. Received: 29 December 1998, Accepted: 24 March 1999     

Effect of chronic ethanol consumption and moderate or high fat diet upon tissue distribution of vitamin A in rats fed either vitamin A or β-carotene

The objective of this work was to evaluate the effects of ethanol feeding with moderate or high fat diets upon hepatic and nonhepatic tissue contents of vitamin A. In the first experiment male rats were fed control or 30% ethanol liquid diets containing retinul acetate and either moderate fat (17% of total calories) or high fat (35% of total calories) for four weeks. Three days prior to killing the rats on the high fat diets received an intragastric dose of [³H] retinyl acetate. The second experiment was similar to the first except that diets contained β-carotene and all rats received a dose of [³H] β-carotene. In both experiments the amount of vitamin A stored in the liver was lower in ethanol-fed rats, and the amount of liver vitamin A was lower in ethanol-fed rats on the high fat diet compared to those on low fat diet. The vitamin A levels in lungs and adrenals were higher in ethanol-fed rats, whereas the vitamin A levels of kidneys of ethanol-fed groups were either no different or lower than in controls. The results of the recovery of radioactivity in these tissues were similar. This study has demonstrated that chronic ethanol consumption causes increased vitamin A content of nonhepatic tissues, primarily the lung and adrenals, but not of kidneys. Also, the effects of ethanol consumption are more pronounced in combination with a high fat diet.     

Combined effect of sesamin and α-lipoic acid on hepatic fatty acid metabolism in rats

Purpose

Dietary sesamin (1:1 mixture of sesamin and episesamin) decreases fatty acid synthesis but increases fatty acid oxidation in rat liver. Dietary α-lipoic acid lowers hepatic fatty acid synthesis. These changes can account for the serum lipid-lowering effect of sesamin and α-lipoic acid. It is expected that the combination of these compounds in the diet potentially ameliorates lipid metabolism more than the individual compounds. We therefore studied the combined effect of sesamin and α-lipoic acid on lipid metabolism in rats.

Methods

Male Sprague–Dawley rats were fed diets supplemented with 0 or 2 g/kg sesamin and containing 0 or 2.5 g/kg α-lipoic acid for 22 days.

Results and conclusions

Sesamin and α-lipoic acid decreased serum lipid concentrations and the combination of these compounds further decreased the parameters in an additive fashion. These compounds reduced the hepatic concentration of triacylglycerol, the lignan being less effective in decreasing this value. The combination failed to cause a stronger decrease in hepatic triacylglycerol concentration. The combination of sesamin and α-lipoic acid decreased the activity and mRNA levels of hepatic lipogenic enzymes in an additive fashion. Sesamin strongly increased the parameters of hepatic fatty acid oxidation enzymes. α-Lipoic acid antagonized the stimulating effect of sesamin of fatty acid oxidation through reductions in the activity of some fatty acid oxidation enzymes and carnitine concentration in the liver. This may account for the failure to observe strong reductions in hepatic triacylglycerol concentration in rats given a diet containing both sesamin and α-lipoic acid.     

Exercising fasting or fed to enhance fat loss? Influence of food intake on respiratory ratio and excess postexercise oxygen consumption after a bout of endurance training

Exercise and nutrition are often used in combination to lose body fat and reduce weight. In this respect, exercise programs are as important as correct nutrition. Several issues are still controversial in this field, and among them there are contrasting reports on whether training in a fasting condition can enhance weight loss by stimulating lipolytic activity. The authors' purpose was to verify differences in fat metabolism during training in fasting or feeding conditions. They compared the effect on oxygen consumption (VO2) and substrate utilization, estimated by the respiratory-exchange ratio (RER), in 8 healthy young men who performed the same moderate-intensity training session (36 min of cardiovascular training on treadmill at 65% maximum heart rate) in the morning in 2 tests in random sequence: FST test (fasting condition) without any food intake or FED test (feeding condition) after breakfast. In both cases, the same total amount and quality of food was assumed in the 24 hr after the training session. The breakfast, per se, increased both VO2 and RER significantly (4.21 vs. 3.74 and 0.96 vs. 0.84, respectively). Twelve hours after the training session, VO2 was still higher in the FED test, whereas RER was significantly lower in the FED test, indicating greater lipid utilization. The difference was still significant 24 hr after exercise. The authors conclude that when moderate endurance exercise is done to lose body fat, fasting before exercise does not enhance lipid utilization; rather, physical activity after a light meal is advisable.     

Serum and liver lipids in rats fed mixtures of corn and palm oils ± cholesterol

Rats were fed diets containing various mixtures of corn and palm oils ranging from 100% corn (CO) or palm oil (PO) to 90:10, 75:25, or 50:50 CO, and 75:25, 10:90, or 100% PO. One set of diets was augmented with 0.4% cholesterol and 0.1% cholic acid. When the diets were cholesterol-free, there were virtually no differences between groups in serum total or HDL cholesterol. Serum triglyceride levels were lowest in the rats fed 100% PO. Liver cholesterol levels were virtually the same in all groups. As the PO contribution to the dietary fat was increased, liver triglyceride levels fell, being lowest in rats fed 100% PO. Serum total and HDL cholesterol levels in rats fed CO plus cholesterol-cholic acid were the same as those seen in rats on the cholesterol-free diet. Introduction of the lowest level of PO raised serum cholesterol levels significantly and they continued to rise as more palm oil (palmitic acid) was introduced into the diet. Serum triglyceride levels were similar in all groups, but liver triglycerides fell with increasing dietary PO.The data support the assertion of Hayes and Khosla that palmitic acid becomes hypercholesterolemic only in cholesterol-containing diets. The observed effects of palmitic acid on serum and liver triglyceride levels, especially the latter, merit further study.     

The effect of dietary quercetin and rutin on AOM‐induced acute colonic epithelial abnormalities in mice fed a high‐fat diet

Dietary quercetin (QU) and rutin (RU), phenolic flavonoids found in many fruits and vegetables, when fed to mice on a low‐fat diet successfully modified the response to azoxymethanol (AOM) by initially inhibiting hyperproliferation and the formation of foci of dysplasia (FADs) and ultimately reducing tumor incidence (Carcinogenesis 12, 1193–1196, 1991). In this study, we tested the efficacy of QU and RU when a high‐fat diet was presented. An AIN 76A diet made with 20% corn oil (CO) was supplemented with QU (0.5%, 2.0%, or 5.0%) and RU (2.0% or 4.0%). These five diets, as well as a 5.0% and a 20.0% CO diet, were fed to a group of CF1 female mice for nine weeks. Both QU and RU showed nonsignificant dose‐related trends toward normalization of the AOM‐induced upward extension of S phase cells. Examination of 500 μm of serially sectioned distal colon revealed that 29% of mice fed the 20% CO control diet were free of FADs. Among the mice fed QU, regardless of dose, >80% were free of FADs. When the three groups fed QU were pooled and compared with the control 20% CO‐fed mice, the degree of protection was significant (p < 0.01). Mice fed RU expressed a level of protection that bordered on the significant (p < 0.08). These data suggest that, regardless of the fat content of the diet, QU and RU are capable of modifying or inhibiting events in the development of chemically induced colonic neoplasia.     

Single oral dose of micellar β-carotene containing phospholipids improves β-carotene metabolism and plasma lipids in vitamin A-deficient rats

Background  

Vitamin A (VA) deficiency is still a major health problem in the developing world. It affects various cellular functions and causes hypolipidemic effects in the body. β-Carotene (BC)-rich foods are promising sources of VA. Phospholipids are reported to improve BC bioefficacy in normal rats, but whether they show similar effects during VA deficiency is unknown.     

Effect of a dietary fiber (beet fiber) on Dimethylhydrazine‐induced colon cancer in wistar rats

The modifying effect of a dietary fiber, Fibeta (beet fiber), on experimentally induced colorectal cancer was studied in Wistar rats. The rats were fed a powdered semisynthetic casein‐based diet in which the carbohydrate pool was substituted with Fibeta as the sole source of fiber. Dimethylhydrazine dihydrochloride (DMH‐2HCI) was used as initiator in a dose of 20 mg/kg body wt and given by gavage once a week for 10 weeks. Throughout the experiment the rats were offered the diets with different levels of fiber in a preinitiation period of 8 weeks, during the initiation, or in a 30‐week postinitiation period. The study was terminated after one year.

A protective effect of the fiber was not found at any stage of the colorectal carcinogenic process. Even though differences (not statistically significant) in tumor incidences were seen, these did not reflect any effect of the high or low fiber intake during the study.

Analysis for volatile fatty acids in cecal content showed that continuous feeding with a fiber‐rich diet resulted in significant increase in most of the volatile fatty acids. The relative change was highest for butyric acid. These findings do not support the hypothesis that butyric acid has a protective effect on colorectal cancer. The tumor yield in the present study was low compared with that reported in the literature, and possible causes for this are discussed.     

Soy β-conglycinin (7S globulin) reduces plasma and liver cholesterol in rats fed hypercholesterolemic diet

The aim of this study was to examine the comparative hypocholesterolemic effect of soybean 7S fraction in rats fed a high-cholesterol diet. Soybean 7S globulin (β-conglycinin) was administered orally once a day to rats, and the effects were measured after 28 days. Wistar rats were divided into four groups: standard diet (STD) (casein alone), hypercholesterolemic (HC) diet (STD plus 1?g/100?g cholesterol and 0.5?g/100?g cholic acid), HC+7S(1) diet (HC diet plus 200?mg of 7S/kg of body weight/day), and HC+7S(2) diet (HC diet plus 300?mg of 7S/kg of body weight/day). Food intake, weight gain, animals' growth, and feeding efficiency ratio were similar among the STD and three HC groups, indicating that these parameters were not affected by treatments. Animals that had received different doses of soybean 7S globulin had lower total cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL)/high-density lipoprotein (HDL) ratio in serum and lower levels of hepatic TC and TG than those fed only the HC diet. The atherogenic indexes of HC+7S(1) and HC+7S(2) groups were 40% and 55% lower than that of the HC group, respectively. The results showed that the oral daily administration of β-conglycinin in the diet to HC rats, at between 1.85% and 2.75% of total ingested protein, promotes the reduction of TC, LDL-cholesterol, and TG and an increase in HDL-cholesterol in the plasma, besides a small but significant reduction in cholesterol and TG levels in the liver of the animals as well as a reduced atherogenic index.