Plasma Retinol Concentrations Research Articles

Chylomicron margination, lipolysis, and vitamin a uptake in the lactating rat mammary gland: implications for milk retinoid content.

We have reported previously that the concentration of vitamin A (VA) in the milk of lactating rats varies with dietary VA intake, even when plasma retinol concentration is unaffected. In the current study, we investigated the role of lipolysis in the uptake of chylomicron (CM) VA into mammary tissue of lactating rats and estimated the proportion of CM-VA that is associated with the mammary gland during CM clearance. Chylomicrons containing [(3)H]VA, mainly as retinyl esters, were prepared in donor rats and administered intravenously to lactating recipient rats. Chylomicron VA rapidly disappeared from plasma and appeared in mammary tissue (maximum within 2-3 mins), followed by a decline. Concomitantly, uptake by liver increased continuously, reaching a plateau within 20-30 mins. Active lipolysis in mammary tissue was necessary for rapid VA uptake, as significantly less CM-VA was recovered in mammary tissue of postlactating rats than of lactating rats, after heparin treatment in lactating rats, or after injection of preformed CM remnants in lactating rats. [(3)H]Vitamin A uptake by mammary tissue increased linearly with CM-VA dose over a 150-fold dose range (R(2) = 0.972, P = 0.0001), suggesting a high capacity for uptake and apparent first-order assimilation of CM-VA during CM remnant formation in situ. Model-based compartmental analysis using WinSAAM predicted that approximately 42% of CM-VA marginated, that is, were temporarily removed, from plasma to the mammary glands during lipolysis and that a total of 3.8% of CM-VA was transferred to mammary tissue. The model-predicted t(1/2) for CM remnants was 3.04 mins. The metabolism of CM-VA in the lactating mammary gland, in proportion to VA absorption and CM-VA contents, may explain how milk VA concentration varies even when plasma retinol levels are unchanged. The mechanism of CM margination and mammary gland uptake described here for VA may be similar for other lipophilic substances.

Effects of subclinical infection on plasma retinol concentrations and assessment of prevalence of vitamin A deficiency: meta-analysis.

Vitamin A deficiency adversely affects child morbidity and survival. This deficiency is estimated by measurement of plasma retinol concentrations, but because plasma retinol is reduced by clinical and subclinical infection, this proxy measure can lead to overestimation. Infection and trauma are accompanied by rises in concentrations of acute-phase proteins in plasma. We aimed to estimate vitamin A deficiency more accurately by measuring changes in plasma retinol and acute-phase proteins associated with subclinical infection or convalescence. We analysed data for concentrations of plasma retinol and one or more acute-phase proteins (alpha1-acid-glycoprotein, alpha1-antichymotrypsin, C-reactive protein, or serum amyloid A) from 15 studies of apparently healthy individuals. We generated summary estimates of differences in retinol concentrations for incubation, early, and late convalescent phases of infection between people with none and those with one or more raised acute-phase proteins. We compared these groups in two, three, and four group analyses. We also compared a subgroup of apparently healthy preschool (1-5 years) children with results from all other studies. For all four proteins, retinol values were much higher in people with normal concentrations of protein, than in individuals with raised concentrations (16% higher for alpha1-antichymotrypsin, 18% for alpha1-acid-glycoprotein, 25% for C-reactive protein, and 32% for serum amyloid A). Estimates of the reduction in plasma retinol for individuals with infection compared with healthy individuals, were 13% (incubation), 24% (early convalescent), and 11% (late convalescent). Estimates of vitamin A deficiency in individuals with no raised acute-phase proteins (healthy group) were much the same as those obtained by adjustment of plasma retinol concentrations in the whole group using acute-phase proteins. We recommend that surveys to estimate vitamin A deficiency should include measurements of serum C-reactive protein and alpha1-acid-glycoprotein concentrations. Information about acute-phase proteins will enable plasma retinol concentrations to be corrected where sub-clinical infection exists, and the healthy sub-group to be identified.

Levels of retinol and retinyl esters in plasma and urine of dogs with urolithiasis.

Vitamin A (VA) deficiency and Tamm-Horsfall glycoprotein (THP), a protein that binds retinol and retinyl esters in canine urine, might be involved in the pathogenesis of urolithiasis in dogs. In the present study, we assessed levels of retinol, retinyl esters, retinol-binding protein (RBP) and THP in plasma and urine of dogs with a history of urolithiasis (n = 25) compared with clinically healthy controls (n = 18). Plasma retinol concentrations were higher in dogs with uroliths of struvit (P < 0.01), calcium oxalate (P < 0.05), urate (P < 0.01) and cysteine, but there were no differences in the concentrations of plasma RBP and retinyl esters. Excretion of urinary retinol and retinyl esters were tentatively, but not significantly higher in the stone-forming groups, which was accompanied by increased levels of urinary RBP (P < 0.01) and lower excretions in THP (P < 0.01). The results show that VA deficiency may be excluded as a potential cause for canine urolithiasis. However, the occurrence of RBP and a concomitant reduction of THP in urine indicates a disturbed kidney function as cause or consequence of stone formation in dogs.

Use of biomarkers of sub-clinical infection, nutrition and neonatal maturity to interpret plasma retinol in Nigerian neonates.

Using the World Health Organization criterion, the prevalence of sub-clinical vitamin A deficiency can be assessed using plasma retinol concentrations <0.7 micromol/l. However, plasma retinol can be depressed by infection; thus, the use of this criterion alone may overestimate deficiency. In the present study, we investigated the usefulness of the acute-phase proteins (APP) alpha1-antichymotrypsin (ACT) and alpha1-acid glycoprotein (AGP), plasma carotenoids and anthropometric and gestational indices to interpret plasma retinol in the blood of 192 apparently healthy Nigerian neonates collected randomly during days 1-20 postpartum. The mean weight (2.64 kg) and length (0.458 m) of the neonates and plasma concentrations (geometric mean, micromol/l) of retinol (0.54), alpha-carotene (0.072), ss-carotene (0.076) and lutein (0.080) were low. The prevalence of vitamin A deficiency was 72 %, indicating a severe public health problem. Babies who were of low birth weight (P<0.003) or premature and low birth weight (P<0.023) had significantly lower retinol concentrations than full-term normal weight babies. Thirty-two neonates had abnormal ACT and forty-four abnormal AGP concentrations. Positive correlations between retinol and ACT (r 0.186, P=0.05) and AGP (r 0.31, P=0.0001) during days 1-5 may be due to the increasing plasma retinol from maternal milk and a coincidental increasing capacity to synthesise APP. Subsequently, negative correlations between retinol and ACT (r -0.28, P=0.02) and AGP (r -0.29, P=0.018) from day 6 onwards reflected the continuing increase in plasma retinol, but no further increase in the APP. Overall, weight, ACT, lutein and age explained 30 % of the variance in retinol, but lutein was the most significant (r(2) 0.18, P<0.0001). Hence, the distribution of plasma retinol concentrations in this group of neonates was more strongly linked with nutrition (via the surrogate marker lutein) than infection.

Effects of chronic renal disease on the transport of vitamin A in plasma and urine of dogs.

To determine plasma and urine concentrations of retinol, retinyl esters, retinol-binding protein (RBP), and Tamm-Horsfall protein (THP) in dogs with chronic renal disease (CRD). 17 dogs with naturally developing CRD and 21 healthy control dogs. A diagnosis of CRD was established on the basis of clinical signs, plasma concentrations of creatinine and urea, and results of urinalysis. Concentrations of retinol and retinyl esters were measured by use of reverse-phase high-performance liquid chromatography. Concentrations of RBP and THP were measured by use of sensitive ELISA systems. Dogs with CRD had higher plasma concentrations of retinol, which were not paralleled by differences in plasma concentrations of RBP. Calculated ratio of urinary total vitamin A (sum of concentrations of retinol and retinyl esters to creatinine concentration) and ratio of the concentration of urinary retinyl esters to creatinine concentration did not differ between groups. However, we detected a significantly higher retinol-to-creatinine ratio in the urine of dogs with CRD, which was paralleled by a higher urinary RBP-to-creatinine ratio. Thus, in dogs with CRD, the estimated fractional clearance of total vitamin A, retinol, and RBP was increased. Furthermore, dogs with CRD had a reduced urinary THP-to-creatinine ratio. Results of this study documented that CRD affects the concentrations of retinol in plasma and urine of dogs. Analysis of the data indicates that measurement of urinary RBP and urinary THP concentrations provides valuable information that can be helpful in follow-up monitoring of dogs with CRD.

A Mixed Fruit and Vegetable Concentrate Increases Plasma Antioxidant Vitamins and Folate and Lowers Plasma Homocysteine in Men

Fruit and vegetable consumption is inversely associated with coronary heart disease (CHD) risk. The aim of the present study was to determine the effect of supplementation with dehydrated juice concentrates from mixed fruit and vegetables on selected plasma vitamins and antioxidant status. We assessed CHD risk by measuring the concentrations of homocysteine, lipids, lipoproteins, glucose and insulin. Men were recruited to participate in a randomized double-blind, crossover trial with 2 periods of 6 wk, separated by a 3-wk wash-out period. Supplementation with the encapsulated mixed extract (Juice Plus) was compared with physically similar placebo capsules. Thirty-two men (13 smokers, 19 nonsmokers) completed the study with a mean compliance of 88%. Compared with placebo, supplementation increased the concentrations of plasma beta-carotene (0.24 +/- 0.15 vs. 1.12 +/- 0.70 micro mol/L; mean +/- SD; P < 0.0001), retinol (1.87 +/- 0.33 vs. 2.00 +/- 0.43 micro mol/L; P < 0.05), alpha-tocopherol (16.8 +/- 7.3 vs. 19.3 +/- 6.8 micro mol/L; P < 0.01), ascorbic acid (72.1 +/- 19.4 vs. 84.1 +/- 13.5 micro mol/L; P < 0.002) and folic acid (24.5 +/- 10.0 vs. 44.9 +/- 16.9 nmol/L; P < 0.0001). Plasma homocysteine was reduced (8.2 +/- 1.5 vs. 7.6 +/- 1.1; P < 0.05) and inversely related (r = -0.40, P < 0.001) with serum folate concentrations. Plasma vitamin C was positively correlated with the resistance of LDL to oxidation (r = 0.26, P < 0.05) and the plasma ferric reducing/antioxidant power (FRAP) tended to be greater after supplementation than after the placebo period (1125.5 +/- 144.1 vs. 1180.3 +/- 158.1 micro mol/L; P < 0.065). Plasma glucose, insulin and lipid concentrations were unaffected. Responses of smokers and nonsmokers did not differ. In the absence of dietary modification, supplementation with a fruit and vegetable concentrate produced responses consistent with a reduction in CHD risk.

Uptake of vitamin A in buccal mucosal cells after topical application of retinyl palmitate: a randomised, placebo-controlled and double-blind trial

Retinoids have been reported to produce regressions in metaplastic changes of the mucosal epithelium. In order to define the role of these micronutrients in the prevention of squamous metaplasia of the oral cavity, it is necessary to measure their uptake in target tissues such as the buccal mucosal epithelium. We demonstrated in a trial that retinyl palmitate applied topically via a toothpaste is taken up by buccal mucosal cells in young healthy volunteers. In the randomised, parallel-designed, placebo-controlled and double-blind trial, forty volunteers divided in two groups cleaned their teeth either with a placebo toothpaste or a retinyl palmitate-containing toothpaste (1 mg/g) for 56 d. Buccal mucosal cells samples were taken from the healthy volunteers during the retinyl palmitate application and the following wash-out phase to determine the concentration of retinyl palmitate and retinol by HPLC. Supplementary blood samples were taken from the volunteers on days 0 and 56 to investigate changes in plasma retinyl palmitate and retinol concentrations. Results from only thirty participants (sixteen placebo and fourteen treated subjects) were used in the statistical evaluation as the remaining sample results were spoiled by a technical defect during the HPLC analysis. A significant (P<0.05) uptake of retinyl palmitate in buccal mucosal cells after 7 d and a significant (P<0.05) increase of plasma retinol after 17 d was demonstrated in our present study. The uptake of retinyl palmitate and the following hydrolysis to retinol led to an enrichment of vitamin A in buccal mucosal cells.

Concentrations of carotenoids, retinol and alpha-tocopherol in plasma and follicular fluid of women undergoing IVF.

Carotenoids are transferred into follicular fluid where they might serve as antioxidants and/or as precursors of retinoids which might modulate follicular or oocyte functions. In 77 women undergoing IVF differences between plasma and follicular fluid in the levels of carotenoids, retinol and alpha-tocopherol were evaluated especially with regard to fertilization success. Concentration of total carotenoids, retinol and alpha-tocopherol determined by HPLC in follicular fluid and plasma were 0.06 +/- 0.02 versus 0.56 +/- 0.23 micro mol/l, 1.26 +/- 0.52 versus 1.66 +/- 0.37 micro mol/l and 4.89 +/- 2.13 versus 21.0 +/- 5.7 micro mol/l (mean +/- SD) respectively (P < 0.001 for all). Differences between plasma and follicular fluid were greater for beta-carotene and lycopene (<20% of plasma concentration) than for lutein and zeaxanthin (>40%). Intrafollicular retinol and retinol-binding protein (RBP) levels represented 58 +/- 23% and 60 +/- 19% of plasma level. Similar molar ratios of retinol/RBP were observed. While no differences in the mean values of all components investigated were observed in plasma and follicular fluid between women with and without reproductive success, the variability in the concentration was much greater in follicular fluid obtained from women without reproductive success. It remains to be elucidated, if this is indicative of a disturbed sieving effect of the blood-follicle barrier with possibly negative consequences for oocyte maturation.

A Multinutrient-Fortified Beverage Enhances the Nutritional Status of Children in Botswana

Due to their widespread acceptability, multinutrient-fortified foods and beverages may be useful in reducing micronutrient deficiencies, especially in developing countries. We studied the efficacy of a new fortified beverage in improving the nutritional status of children in Botswana. We screened 311 lower income urban school children, ages 6-11 y, in two primary schools near Gaborone. Children were given seven 240-mL servings weekly of either an experimental beverage (EXP) fortified with 12 micronutrients or an isoenergetic placebo drink (CON) for 8 wk. Weight, mid-upper arm circumference, hemoglobin, retinol, ferritin, vitamin B-12, folate and riboflavin status were measured at baseline and at the end of the study. Plasma zinc and serum transferrin receptors also were measured at study end. A total of 145 children in the EXP group and 118 in the CON group completed the trial. Using multivariate analysis, the changes in mid-upper arm circumference, weight for age and total weight were significantly better in the EXP group than in the CON group (P < 0.01). Ferritin, riboflavin and folate status were significantly better in the EXP group than in the CON group at study end (P < 0.01), but serum vitamin B-12 was not. Zinc was significantly higher and transferrin receptors were significantly lower at the conclusion of the study in the EXP group than in the CON group (P < 0.001). Mean plasma retinol concentrations, which were low (<0.7 micro mol/L) in both groups, did not change. We conclude that a micronutrient-fortified beverage may be beneficial as part of a comprehensive nutritional supplementation program in populations at risk for micronutrient deficiencies.

Micronutrient intake and status in rural Democratic Republic of Congo

Vitamin, mineral and trace element intakes were assessed in a rural African population using a novel dietary survey method, and compared with status measurements. In addition to the previously described protein deficiency, multiple micronutrient deficiencies were observed. Although vitamin A intakes were generally satisfactory, some low plasma retinol concentrations were observed in adults, due perhaps to the very low protein intakes or infectious diseases. Vitamin B1, B2 and niacin intakes were clearly inadequate, and for the two former were confirmed by status measurements. Whilst B6 intake was low, B6 status was adequate, probably resulting from lower requirements because of low protein intakes. B12 intake was low in some age groups, whereas that of folate was satisfactory. Fe, Cu and Mg intakes appeared to be adequate. Intakes of phosphorus and iodine were low for children and adolescents; those of Zn and Ca were clearly inadequate, except for Zn in women. Dietary interventions to prevent or treat malnutrition in this region should address several micronutrients in addition to protein.

Redistribution of vitamin A after iron supplementation in Indonesian infants

Deficiencies of iron and vitamin A are prevalent worldwide. Single-micronutrient supplementation is widely used to combat these deficiencies. However, micronutrient deficiencies often occur concurrently, and there are many interactions between micronutrients. This study investigated interactions among 3 important micronutrients--iron, vitamin A, and zinc--when they are given as supplements. In a randomized, double-blind, placebo-controlled supplementation trial, 387 Indonesian infants aged 4 mo were supplemented 5 d/wk for 6 mo with 10 mg Fe, 10 mg Zn, 2.4 mg beta-carotene, 10 mg each of Fe and Zn, 10 mg Zn + 2.4 mg beta-carotene, or placebo. Complete data on micronutrient status, including hemoglobin, ferritin, retinol, zinc, and the modified relative dose response (a measure of liver retinol stores), were available from 256 infants at the end of the study. Iron-supplemented infants had significantly lower plasma retinol concentrations and a significantly higher prevalence of vitamin A deficiency, as defined by a plasma retinol concentration <0.70 micromol/L, than did the non-supplemented infants. In contrast, the modified relative dose response of the iron-supplemented infants indicated greater liver stores of vitamin A. Iron supplementation improved iron status, and zinc supplementation improved zinc status, but beta-carotene supplementation did not significantly improve vitamin A status. In this study, iron supplementation in infants with marginal vitamin A status led to lower plasma vitamin A concentrations and simultaneously to greater vitamin A liver stores. This implies a redistribution of retinol after iron supplementation, which might induce vitamin A deficiency. Therefore, iron supplementation in infants should be accompanied by measures to improve vitamin A status.

Effect of Vitamin E Supplementation on Plasma Antioxidant Vitamins and Immunity Status of Crossbred Cows

Twenty crossbred (HF×Tharparkar) dry pregnant cows were divided into four equal groups. They were supplemented with 1,000 I.U. α-tocopheryl acetate from 0 (group I), 15 (group II), 30 (group III) and 60 (group IV) days before parturition to 1month of lactation. All the cows were kept under similar feeding and management conditions. Blood plasma samples collected on specific days were analyzed for α-tocopherol, retinol, total antioxidant activity (FRAP), immunoglobulin and calcium. Plasma α-tocopherol concentration at 30 days prepartum averaged 3.5, 4.1, 4.4 and 3.9 µg/ml and decreased by 50.0, 41.4, 34.1 and 33.3 percent on the day of parturition in the four respective groups. After calving, plasma vitamin E started to recover earlier in groups II, III and IV as compared to group I. Mean plasma α-tocopherol concentration at 21 days postpartum was significantly higher in groups II, III and IV (2.9, 3.5 and 3.1 µg/ml) compared to group I (1.9 µg/ml) cows. Plasma retinol concentration also showed a substantial decrease in all the groups on the day of calving but recovered to its normal value at 3 weeks postpartum. Plasma total antioxidant activity averaged 901, 895, 859 and 875 µmol/l in the four respective groups on 30 days prepartum and decreased on the day of calving in all the groups, but the decrease was less in groups III and IV. Plasma immunoglobulin concentration was higher in group IV, followed by groups III, II and I, respectively, showing better immune status of vitamin E supplemented cows due to less oxidative stress. Supplementation of vitamin E resulted in higher plasma calcium concentration. The data showed that vitamin E supplementation should be started at least 30 days prepartum to reduce oxidative stress in periparturient cows. (Asian-Aust. J. Anim. Sci. 2003. Vol 16, No. 11 : 1614-1618)

Analysis of oxidative DNA damage after human dietary supplementation with linoleic acid

It has been hypothesized that oxygen radicals generated by peroxidation of dietary linoleic acid may induce genetic damage and thereby increase cancer risk. We examined the effect of dietary supplementation with linoleic acid on the levels of oxidative DNA damage in peripheral lymphocytes and on the blood plasma antioxidant potential. Thirty volunteers received during 6 weeks either a high dose of linoleic acid (15 g/day), an intermediate dose of linoleic acid (7.5 g/day) or an isocaloric supplement without linoleic acid (15 g palmitic acid/day). After the intervention, no significant increase in oxidative DNA damage, measured as relative amounts of 7,8-dihydro-8-oxo-2′-deoxyguanosine (8-oxodG) in DNA from peripheral lymphocytes, was observed in both high and intermediate linoleic acid-supplemented groups (increase of respectively 13 and 21%; P>0.05). Also, the differences between levels of oxidative DNA damage in the high or intermediate linoleic acid-supplemented group and the control group receiving palmitic acid (23% decrease) were not significant. Furthermore, no statistically significant differences were found between the total antioxidant capacities of blood plasma from the different experimental groups. Plasma levels of malondialdehyde, an important end-product of lipid peroxidation, were not increased after supplementation, nor were effects found on the plasma concentrations of retinol, α-tocopherol and β-carotene. Despite the experimental design that excludes several forms of bias introduced in studies based on modulation of dietary composition, our results provide no indication of increased oxidative stress or genetic damage as a result of increased dietary intake of linoleic acid. Therefore, we see no scientific basis to reconsider the public health policy to stimulate the intake of polyunsaturated fatty acids aimed at the reduction of coronary heart diseases.

Low plasma concentrations of retinol and α-tocopherol in hematopoietic stem cell transplant recipients: the effect of mucositis and the risk of infection

Although vitamin deficiencies are rare in the United States, acute reductions in concentrations of plasma retinol (vitamin A) or alpha-tocopherol (vitamin E) have been associated with impaired immune responses in some clinical settings. The objectives were to determine the plasma concentrations of retinol and alpha-tocopherol in patients undergoing dose-intensive therapy and hematopoietic stem cell transplant and to examine the association of plasma concentrations with clinical outcomes reflecting immunity. This was an observational trial of 120 consecutive recipients of hematopoietic stem cell transplant and a multivariate analysis of plasma vitamin concentrations, mucositis, infections in the first 30 d, and herpes zoster infections in the first year after hematopoietic stem cell transplant. Plasma retinol and alpha-tocopherol concentrations declined from baseline to day 7, typically recovering without specific replacement toward baseline by day 14. The severity of mucositis was a strong predictor of low plasma retinol on day 7 (P = 0.001). Eighty-two patients (68%) had at least one plasma retinol concentration < or = 1.05 micro mol/L, a concentration previously determined to be of immunologic significance, during the peritransplant period (day -8 to day 14). Men more frequently acquired herpes zoster than women, and men who developed hyporetinolemia (< or = 1.05 micro mol/L) had a significantly higher risk of herpes zoster (OR: 6.6; 95% CI: 1.5, 29.6). Plasma alpha-tocopherol was not associated with any clinical event measured in this study. Hyporetinolemia is common, particularly in subjects with severe mucositis, and is associated with an increased risk of herpes zoster infection in recipients of hematopoietic stem cell transplant. Additional investigations are required to determine whether these findings indicate a causal relation.

A Randomized, 4-Month Mango and Fat Supplementation Trial Improved Vitamin A Status among Young Gambian Children

Supplementation with carotene-rich fruits may be an effective and sustainable approach to prevent vitamin A deficiency. To test the effectiveness of mango supplementation, 176 Gambian children, aged 2 to 7 y, were randomly assigned to one of four treatments: 75 g of dried mango containing approximately 150 micro g retinol activity equivalents with (MF) or without (M) 5 g of fat, 5 d/wk for 4 mo or 60,000 micro g of vitamin A (A) or placebo (P) capsule at baseline. After 4 mo, plasma beta-carotene was greater in both the M (P < 0.05) and MF (P = 0.07) groups compared with the P group. After controlling for baseline plasma retinol, elevated acute phase proteins and age, plasma retinol concentrations in the A and MF, but not M, groups were higher than in the P group at the end of the study (P < 0.01). Increases in retinol concentrations, however, were small in both groups. These results support the use of dietary supplementation with dried mangoes and a source of fat as one of several concurrent strategies that can be used to help maintain vitamin A status of children in developing countries where there is a severe seasonal shortage of carotenoid-rich foods.

Iron Deficiency and Marginal Vitamin A Deficiency Affect Growth, Hematological Indices and the Regulation of Iron Metabolism Genes in Rats

Iron deficiency and marginal vitamin A (VA) deficiency frequently coexist and affect billions of people, mostly children and women, worldwide. The effects of these micronutrient deficiencies alone and in combination on hematologic, biochemical and molecular indices of iron and VA status were investigated in a 2 x 2 randomized blocked study conducted in growing male Sprague-Dawley rats. From 3-8 wk of age, rats were fed one of four purified diets that were either adequate or restricted in iron (Fe) and adequate or marginal in VA: (+)Fe(+)VA, 20.3 and 0.367 micro g/g, respectively, denoted control diet; (-)Fe(+)VA, 3.34 and 0.405 micro g/g; (+)FeVA(m), 22.2 and 0.051 micro g/g; or (-)FeVA(m), 3.03 and 0.055 micro g/g. Weight-matched rats fed adequate micronutrients were included to control for possible confounding effects of Fe deficiency on growth and feed efficiency. Iron restriction reduced (P < 0.05) weight gain, feed efficiency, blood hemoglobin and hematocrit. Plasma and liver iron and plasma transferrin saturation were reduced by approximately 50%, whereas liver transferrin mRNA and protein and transferrin receptor mRNA were elevated, as was liver ferritin light-chain protein and light-chain mRNA. Liver heavy-chain ferritin mRNA, hemopexin, ceruloplasmin and cellular retinol-binding protein mRNA were not affected by iron or VA restriction. Although marginal VA deficiency did not exacerbate indices of poor iron status during iron deficiency, iron deficiency was associated with lower plasma retinol and elevated liver VA concentrations. These results are consistent with an impaired mobilization of liver retinol during iron deficiency as well as multiple alterations in iron metabolism.

Estimation of the Effect of the Acute Phase Response on Indicators of Micronutrient Status in Indonesian Infants

Many indicators of micronutrient status change during infection because of the acute phase response. In this study, relationships between the acute phase response, assessed by measuring concentrations of C-reactive protein (CRP), alpha(1)-antichymotrypsin (ACT) and alpha(1)-acid glycoprotein (AGP), and indicators of micronutrient status were analyzed in 418 infants who completed a 6-mo randomized, double-blind, placebo-controlled, supplementation trial with iron, zinc and/or beta-carotene. The acute phase response, defined by raised CRP (plasma concentration >10 mg/L), raised AGP (>1.2 g/L), or both raised CRP and AGP, significantly affected indicators of iron, vitamin A and zinc status, independently of the effects of supplementation. Plasma ferritin concentrations were higher by 15.7 (raised AGP) to 21.2 (raised CRP and AGP) micro g/L in infants with elevated acute phase proteins compared with infants without acute phase response (P < 0.001). In contrast, plasma concentrations of retinol were lower by 0.07 (P < 0.05, raised AGP) to 0.12 (P < 0.01, raised CRP) micro mol/L, and of zinc lower by 1.49 (P < 0.01, raised AGP) to 1.89 (P < 0.05, raised CRP and AGP) micro mol/L. Hemoglobin concentrations and the modified relative dose response were not affected. Consequently, the prevalence of iron deficiency anemia was underestimated in infants with raised acute phase proteins by >15%, whereas the prevalence of vitamin A deficiency was overestimated by >16% compared with infants without acute phase response. Hence, using indicators of micronutrient status without considering the effects of the acute phase response results in a distorted estimate of micronutrient deficiencies, whose extent depends on the prevalence of infection in the population.

Dose-responsive alteration in hepatic lipid peroxidation and retinol metabolism with increasing dietary beta-carotene in iron deficient rats.

Phosphatidylcholine hydroperoxide (PCOOH) levels are increased in the iron-deficient rat liver. We investigated the antioxidative effect of dietary beta-carotene and altered retinol metabolism in iron-deficient rats. Experiment 1: Male Wistar-strain rats were divided into six groups and fed a control diet, an iron-deficient diet, and iron-deficient diets with four different levels of dietary beta-carotene. The PCOOH concentration in the iron-deficient rat liver was decreased by supplementation with dietary beta-carotene. However, the beta-carotene dose response was not related to antioxidative potency. Hepatic and plasma beta-carotene concentrations were increased by iron deficiency. The hepatic retinol concentration was increased while the plasma retinol concentration was decreased in iron-deficient rats. Experiment 2: Male Wistar-strain rats were divided into two groups, with one group receiving a control diet with beta-carotene and the other an iron-deficient diet with beta-carotene. Intestinal iron was decreased and intestinal beta-carotene was unchanged in iron-deficient rats. The intestinal beta-carotene conversion ratio and beta-carotene cleavage enzyme activity were decreased in iron-deficient rats. Dietary beta-carotene played the role of an antioxidant in hepatic lipid peroxidation in the iron-deficient state, but there was no dose dependency. Moreover, intestinal beta-carotene cleavage and hepatic retinol release appear to be altered in iron-deficient rats.

Alterations in lipid metabolism induced by recombinant bovine tumor necrosis factor-alpha administration to dairy heifers1,2

Endotoxin induces marked changes in lipid metabolism via its effects on cytokines. To evaluate the role of tumor necrosis factor-alpha (TNF) in mediating changes of lipid metabolism in ruminants, we performed a crossover saline-controlled study in Holstein heifers (n = 8; 394.0 kg average BW), investigating the metabolic effects of a single intravenous administration of recombinant bovine TNF (rbTNF, 5.0 μg/kg). Blood samples were taken from a jugular vein at 0 (1100, just before injection), 0.5, 6, 12, and 24 h after each treatment. Dry matter intake in the heifers was not affected by single administration of the rbTNF. The rbTNF produced early as well as later hypertriglyceridemia (P < 0.05) in dairy heifers. The rbTNF also induced an early and sustained rise (P < 0.05) in the plasma NEFA concentration. Plasma retinol concentration was decreased (P < 0.05) at 24 h after rbTNF injection, whereas the α-tocopherol concentration was not significantly affected by rbTNF treatment. At 0.5 and 24 h, there was an increase (P < 0.05) in the plasma concentration of the very-low-density lipoprotein (VLDL) fraction in rbTNF-treated heifers. Between 6 and 24 h after rbTNF treatment, concentration of the low-density lipoprotein fraction declined (P < 0.05) but the high-density lipoprotein fraction was not altered in the rbTNF-treated heifers. These results indicate that TNF produces a hypertriglyceridemic response associated with an increase of the VLDL fraction and a disturbance of retinol metabolism in dairy heifers.

Effect of citric pectin on beta-carotene bioavailability in rats.

The effect of citric pectin on the bioavailability of synthetic beta-carotene was studied. Thirty Wistar rats were used, ten animals were sacrificed at the beginning of the experiment and remaining animals were divided into two groups and received the following diets for 30 days: control group (CG)--24 micrograms beta-carotene/g diet + 0% citric pectin; experimental group (EG)--24 micrograms beta-carotene/g diet + 7% citric pectin. Plasma and liver beta-carotene, vitamin A, and retinyl palmitate concentrations were determined by high-performance liquid chromatography (HPLC). Plasma retinol concentration was 1.42 +/- 0.36 mumol/L for CG and 1.10 +/- 0.24 mumol/L for EG (p = 0.1), and plasma beta-carotene concentration was 0.20 +/- 2.51 mumol/L for CG and 0.07 +/- 0.04 mumol/L for EG (p = 0.01). Only traces of retinyl palmitate were detected in CG and none in EG. Retinol did not differ significantly between groups CG and EG, while a significantly higher beta-carotene concentration was observed for CG. Liver concentrations of retinol (CG: 4.90 +/- 2.51 micrograms/g; EG: 2.68 +/- 1.12 micrograms/g), beta-carotene (CG: 0.98 +/- 0.28 microgram/g; EG: 0.11 +/- 0.06 microgram/g), and retinyl palmitate (CG: 95.47 +/- 45.13 micrograms/g, EG: 37.01 +/- 17.20 micrograms/g) differed significantly between groups (p < 0.05), with a lower concentration being observed for EG. We conclude that 7% citric pectin in the rat diet decreases the bioavailability of synthetic beta-carotene, reducing the liver reserves of vitamin A and beta-carotene.