Loss Of Retinol Research Articles

Immunodeficiency Accelerates Vitamin A Deficiency.

ABSTRACTBackgroundVitamin A deficiency increases susceptibility to infection caused by impaired immune function.ObjectivesWe investigated whether immunodeficiency could facilitate the development of vitamin A deficiency.MethodsVitamin A deficiency was followed in 2 mouse models of immunodeficiency: the athymic nude mouse (nu/nu) and the humoral immunodeficient SENCAR (SENsitive to CARcinogenesis) mouse. Vitamin A deficiency was also monitored in outbred Balb/c and in NIH mice. The monitoring of vitamin A deficiency was done after feeding the mice and their mothers a semisynthetic, vitamin A–deficient diet from birth of the experimental mice. These mice were weaned onto the same deficient diet at 3–4 wk of age, while control groups were fed the same diet containing 3 μg retinoic acid per gram of diet.ResultsThe immunodeficient nu/nu and SENCAR mice developed vitamin A deficiency earlier than either the heterozygous nu/+ controls or the Balb/c and NIH strains. In female mice, symptoms included depletion of liver retinol and retinyl palmitate, squamous metaplasia of the uterus, and death. Male mice lost weight more frequently and sooner than female mice, in which mortality generally occurred in the absence of loss of body weight. Pairwise comparisons using Tukey's honest significant difference test of the nu/nu and SENCAR mice versus the Balb/c and NIH mice showed a faster loss of retinol and retinyl palmitate in all pairs (P ≤ 0.0001) except for retinol when comparing nu/nu and NIH strains (P = 0.3383).ConclusionsOur findings are consistent with an increased usage of liver retinol and retinyl palmitate in the immunocompromised nu/nu and in the immunodeficient SENCAR mice and suggest that compensatory mechanisms dependent on vitamin A utilization are called upon to rescue immunodeficiency both in the T-cell–deficient phenotype of the nu/nu mice and in the humoral immunodeficient SENCAR mice.

Retention of Ascorbic Acid, Retinol, β-Carotene, and α-Tocopherol in Milk Subjected to Pressure-Assisted Thermal Processing (PATP)

Thermal treatments can cause undesirable sensory quality and nutritional changes in food, whereas high-quality retention has been widely reported for high-pressure processing (HPP). The aim of this study was to assess the retention of whole-fat milk vitamins after pressure-assisted thermal processing (PATP). The retention of ascorbic acid (AA), retinol, β-carotene, and α-tocopherol was determined by HPLC after 0.5 to 10 min treatments at 46 to 75 °C and 95 to 705 MPa. AA content was particularly sensitive to PATP treatments, particularly at 705 MPa and 75 °C for 5 min, reaching a loss of 55.1 ± 0.9%. Liposoluble vitamin losses were much lower than those observed for AA. For all treatments, retinol loss remained below 10.2 ± 1.7% and it was independent of the processing times tested (0.5, 5, and 10 min) for treatments at 400 MPa and 75 °C with losses of 6.3 ± 1.3, 6.1 ± 1.5, and 8.1 ± 3.2%, respectively. For PATP treatments at 75 °C, 5 min, and 95–705 MPa, α-tocopherol losses were minor and ranging from 5.0 ± 2.1 to 6.4 ± 0.6%. These values were similar to those observed after conventional thermal pasteurization. Low β-carotene losses were also observed at 75 °C for all PATP treatments with losses of −0.6 ± 2.9 to 4.4 ± 0.5% for 95–705 MPa/5 min and 2.4 ± 0.3 to 4.9 ± 2.1% for 400 MPa/0.5–10 min treatments. This study showed that in whole-fat milk subjected to PATP treatments, AA is significantly more sensitive than retinol, β-carotene, and α-tocopherol.

Improving long-term stability of retinol in dried blood spots and quantification of its levels via a novel LC-MS/MS method.

Vitamin A deficiency (VAD) is a major micronutrient deficiency in children. Although plasma and serum retinol levels are proposed as the key indicators of VAD, collecting and transporting plasma and serum are difficult and inconvenient in field studies. Dried blood spot (DBS) retinol has been used as an alternative to plasma retinol in several epidemiological and clinical studies. A limitation of methods that use DBS retinol is the instability and apparent loss of retinol in DBSs. Therefore, an accurate, reliable method for stabilizing retinol in DBSs and quantifying and comparing DBS retinol concentrations with equivalent plasma retinol levels is required. In this study, antioxidants on paper combined with vacuum treatment were found to greatly increase the stability of DBS retinol during 120min of air drying and 30days of room-temperature storage. A surrogate matrix of whole blood prepared using a mixture of human erythrocytes and 2% BSA in PBS was firstly used in DBS retinol determination based on the fact that retinol is excluded from erythrocytes. The method was linear in the concentration range of 0.04-300μg/mL. Both the between-run (n = 5) and within-run (n = 6) precision (relative standard deviations, RSD%) were below 8.42%. The spiked recoveries at 3 concentrations ranged from 86.48 to 98.13%. The internal standard (IS)-normalized matrix factor (MF) was 99.72% with a RSD% of 10.50% (n = 3). The accuracy was calibrated using two National Institute of Standards and Technology (NIST) serum-generated calibrants at concentrations of 0.1962 and 0.3948g/mL, and relative errors (RE% values) of 0.07% and 4.95% were found, respectively. A simple calibration model was first developed to convert DBS retinol concentration to the equivalent plasma retinol concentration, thereby enabling comparisons with clinical reference ranges and with studies using serum or plasma samples. Graphical abstract.

Household Processing Practices of Milk and Cottage Cheese: Implications for Vitamin A Retention

<p><span style="font-size: medium;"><span style="font-family: Times New Roman;">Milk and milk products are excellent sources of several important nutrients including retinol in the diets of young children. Household processing practices followed by the mothers (n=400) of young children (1-9 yrs) of Delhi was assessed using an interview schedule. The effect of boiling on the retinol content in milk and frying on cottage cheese was assessed using HPLC. All households were boiling milk before consumption. Increasing the time period of boiling from 2 to 10 minutes did not lead to any significant losses (5 to 9 %) of retinol in milk. About 10.32 % of reduction in retinol content was observed in the milk which was boiled, cooled in refrigerator and cream was removed before consumption. However, children preferred removing the creamy layer formed on boiled, cooled milk before consumption which led to significant loss of 28.43% retinol especially if milk was stored overnight in refrigerator (p<0.05). In cottage cheese, sautéing led to insignificant loss of 5.80 % in the retinol content while deep frying led to 15.78 % of significant reduction in retinol (p<.05). Consuming milk immediately with cream after boiling or homogenising milk with cream after storage will retain most of the vitamin A. Sautéing is preferred over deep fat frying cottage cheese for different preparations for better retention. </span></span></p>

Effects of Cooking and Defrost Methods on Retinol Concentration of Chicken Liver

This study aimed to analyze the retinol concentration of chicken livers in various brands, batches and types of both organic and free range by HPLC. In addition, the effects of different cooking and defrosting methods on the retinol levels of chicken livers were also determined. Chicken livers samples were roasted for 35 minutes at 200°C, cooked for 40 minutes at (26 to 100)°C, fried for 5 minutes at 180°C. Other samples were frozen for 72 hours and divided to be defrosted by fridge for 8 hours at 3°C, at ambient temperature for 2 hours at 23°C, submersed in water for 35 minutes at 25°C, and microwaved on defrost function for 1 minute, where all methods were compared to its natural state (3°C). The mean retinol concentrations in brands A, B, C and organic and free-ranged were 9152, 4673, 5943, 3401, 30094 µg/100 g (P < 0.001). Significant losses of 39.9 % (P < 0.05), and 26.2 % (P < 0.01) were found when compared to natural state (raw) to roasting and microwave, respectively. This study showed a significant difference between brands and types of chicken livers, and a significant loss of retinol in chicken liver, in food processes commonly used. Otherwise, vitamin A values in chicken liver suggest that consumption could be recommended to prevent vitamin A deficiency.

Using front-face fluorescence spectroscopy for prediction of retinol loss in milk during thermal processing

The objectives of the present study were to model the kinetics of retinol loss and assess the potential of predicting retinol loss during thermal processing using front-face fluorescence spectroscopy (FFFS). A factorial design with three different temperatures (70, 80 and 90 °C) and five heating times (0, 5, 10, 15 and 30 min) was used in this study. The kinetics of the retinol degradation process fitted well a first-order reaction. Further, several milk native fluorophores were selected as fluorescent markers for development of retinol prediction models such as tryptophan, dityrosine, Maillard intermediate compounds and riboflavin. The maximum emission intensities of the markers were used to evaluate the correlation of retinol concentration with fluorescent markers and to establish the corresponding prediction models of retinol concentration. Retinol concentration was significantly correlated (P < 0.05) with all the fluorescent markers. The optimum prediction model was obtained from 45 samples using three fluorescent predictors, with an R2 of 0.87. The results obtained are encouraging and suggest that FFFS, as a low-cost, rapid, direct and non-destructive technique, has the potential to replace existing conventional analytical techniques practiced for retinol evaluation in heat treated milk and be adopted by dairy industry.

СТВОРЕННЯ ФОРМУЛИ СКРИНІНГУ ГІПОВІТАМІНОЗУ РЕТИНОЛУ ПРИ ХРОНІЧНОМУ ПАНКРЕАТИТІ В АМБУЛАТОРНИХ УМОВАХ

У хворих на хронічний панкреатит часто розвивається гіповітаміноз ретинолу, який бере участь в окисно-відновних процесах, регуляції синтезу білків, сприяє нормальному обміну речовин, функції клітинних і субклітинних мембран, відіграє важливу роль у формуванні кісток і зубів, а також жирових відкладень. Метою роботи було створення формулу прогнозування дефіциту ретинолу на основі встановленими нами предикторних факторів: рівень холестерину, об’єм м’язів плеча, УЗ-критерії та критерії копрограми. Для персоніфікованого прогнозування дефіциту ретинолу в хворих на хронічний панкреатит застосували встановлені попередніми дослідженнями фактори формування і глибини дефіциту ретинолу як показового прояву полінутрієнтної недостатності. Ці показники є доступними для визначення у практиці лікарів первинної медичної допомоги. Запропонована математична модель прогнозування дефіциту ретинолу в хворих на хронічний панкреатит створена на основі доступних для визначення характеристик хронічний панкреатит. Формулу можна використовувати для виділення груп ризику за виникненням зниження рівня вітаміну А серед хворих на ХП для своєчасного проведення профілактичних і лікувальних заходів по корекції втрати ретинолу, що особливо актуально для рівня первинної медичної допомоги.

High-Performance Liquid Chromatography with Fluorescence Detection for Simultaneous Analysis of Retinoids (Retinyl Palmitate, Retinyl Acetate, and Free Retinol) and α-, β-, γ-, and δ-Tocopherols in Foods

A method based on high-performance liquid chromatography with fluorescence detection for the simultaneous analysis of retinoids (vitamin A) and tocopherols (vitamin E) was developed. This method consists of an isocratic solution using hexane/ethyl acetate (85:15, v/v) as the mobile phase and fluorescence detection using a time program that sets the excitation (Ex) and emission (Em) wavelengths at adequate elution times for retinoids (Ex 342 nm, Em 476 nm) and tocopherols (Ex 298 nm, Em 325 nm), respectively. The separation of three retinoids (retinyl palmitate, retinyl acetate, and free retinol) and four tocopherol homologs was achieved with sufficient reproducibility and quantitative ability. Additionally, the necessity of saponification was considered. As a result, saponification was not used in this method because of the complexity of the procedure and the loss of free retinol. The retinoid and tocopherol contents of various foods were evaluated using the developed method. Our method could evaluate the retinoid and tocopherol contents of fish (eel, Anguilla japonica, and amberjack, Seriola dumerili) muscle and liver, roasted soybean (Glycine max) flour, and Japanese torreya seed (Torreya nucifera). Additionally, our method could be applied to the determination of retinoids and tocopherols not only in foods but also in supplements and cosmetics.

Spaceflight Activates Lipotoxic Pathways in Mouse Liver

Spaceflight affects numerous organ systems in the body, leading to metabolic dysfunction that may have long-term consequences. Microgravity-induced alterations in liver metabolism, particularly with respect to lipids, remain largely unexplored. Here we utilize a novel systems biology approach, combining metabolomics and transcriptomics with advanced Raman microscopy, to investigate altered hepatic lipid metabolism in mice following short duration spaceflight. Mice flown aboard Space Transportation System -135, the last Shuttle mission, lose weight but redistribute lipids, particularly to the liver. Intriguingly, spaceflight mice lose retinol from lipid droplets. Both mRNA and metabolite changes suggest the retinol loss is linked to activation of PPARα-mediated pathways and potentially to hepatic stellate cell activation, both of which may be coincident with increased bile acids and early signs of liver injury. Although the 13-day flight duration is too short for frank fibrosis to develop, the retinol loss plus changes in markers of extracellular matrix remodeling raise the concern that longer duration exposure to the space environment may result in progressive liver damage, increasing the risk for nonalcoholic fatty liver disease.

Simultaneous HPLC–DAD quantification of vitamins A and E content in raw, pasteurized, and UHT cow’s milk and their changes during storage

An improved extraction and HPLC method for the simultaneous extraction and quantitation of retinol, α-tocopherol, α-tocotrienol, and β-carotene was developed to analyze commercial whole/semi-skim/skim samples of raw/pasteurized/UHT milk in transparent plastic/glass bottles and Tetra Brik™ containers. The sample preparation method required prior saponification at 40 °C for 15 min followed by n-hexane extraction. An isocratic acetonitrile/methanol (65:35 v/v) mobile phase, C18 analytical column, and UV detector were chosen for HPLC quantification. The liposoluble vitamin content in raw, pasteurized conventional/organic, and UHT milk ranged 0.055–5.540 (retinol), 0.135–1.410 (α-tocopherol), and 0.040–0.850 mg/L (β-carotene). No significant differences (p > 0.05) were observed on losses of retinol, α-tocopherol, and β-carotene content in UHT whole milk after 5 days at 4 °C in the dark. After 14 days at 4 °C in the dark, the contents of retinol, α-tocopherol, and β-carotene remained higher in milk with higher fat content and were higher in unopened containers. In UHT whole milk, samples containing 0.02 % NaN3, retinol (33 %), and α-tocopherol (11 %) but not β-carotene (2 %) decreased significantly (p < 0.05).

Urinary retinol excretion in children with acute watery diarrhoea.

Children with diarrhoea due to rotavirus infection excrete retinol in urine. This study aimed at demonstrating the extent and mechanism of urinary retinol excretion in children with acute watery diarrhoea caused by pathogens other than rotavirus. Thirty-two children, aged five months to five years, hospitalized with watery diarrhoea predominantly due to enterotoxigenic Escherichia coli in Bangladesh, were studied. Their serum retinol and retinol-binding protein (RBP) were low at admission and increased significantly after recovery from illness. The mean hospital stay of these patients was four days. Forty-seven percent of the children excreted retinol in urine on day 1, and about 38% continued excreting retinol on day 3. The estimated urinary retinol loss of 3.44 micromol for the illness episode represented more than 40% of liver retinol reserve (8.25 micromol) in malnourished children. A conservative estimate of the loss would represent at least 20% of the liver reserve in relatively better-nourished children. Kidney tubular dysfunctions of increased RBP excretion significantly predicted urinary retinol excretion in children with watery diarrhoea.

Effects of green tea catechin on the lipid oxidation, volatile compound formation, and losses of retinol and α-tocopherol in whole milk during light illumination as compared with ascorbic acid

Effects of green tea catechin (GTC, catechin content 61.4%) on the formations of hydroperoxide, malonaldehyde, and volatile compounds, and losses of retinol and tocopherol in milk during light illumination were studied. GTC showed surprisingly high protective activity of milk photooxidation, in a dose dependent manner. GTC at 25 ppm exerted 82.1 and 75.0% inhibitions of hydroperoxide and malonaldehyde formation during 30 h light illumination, respectively. GTC at 25 ppm exerted 88.7 and 94.3% inhibition of hexanal and heptanal formation in milk during 30 h light illumination, respectively. The 25 ppm GTC greatly suppressed the losses of retinol and α-tocopherol, showing 53.6 and 58.7% protections of their losses in milk after 12 h light illumination, respectively. The protective activity of GTC was at least 4 times higher than ascorbic acid. The inhibitory activities of GTC and ascorbic acid against the photooxidation of milk were in consistent with their singlet oxygen quenching abilities.

Effect of metal specific amino acid complexes and inorganic trace minerals on vitamin stability in premixes

Stability of vitamin activity in a swine premix containing metal specific amino acid complexes, inorganic trace minerals, or no trace minerals was evaluated over a 120-day storage period. Two vitamin-trace mineral premixes containing either metal specific amino acid complexes or inorganic trace mineral sources were formulated to contain 200% of NRC (1988) sow requirements for I, Cu, Zn, Mn, Fe, and Se based on a 5g/kg dietary inclusion rate. A separate vitamin premix containing no trace minerals served as the control. The vitamin premix and the two vitamin-trace mineral premixes were formulated to contain the same level of vitamins. Vitamin levels exceeded NRC (1988) and were chosen to represent “typical” industry levels based on an informal survey of vitamin levels in commercial premixes in the U.S.A. Premixes were stored in an environmentally controlled feed storage room and samples were collected every month to determine vitamin activity. Minimal monthly vitamin stock losses in activity (0–1%) were observed for all vitamins except cyanocobalamin (2.8%) and choline (1.3%). Pantothenate, vitamin E, riboflavin, biotin and niacin were most resistant to destruction, while menadione, retinol, vitamin B-6, and thiamine were subject to the greatest loss of activity during the 120-day storage period. Use of metal specific amino acid complexes in vitamin-trace mineral premixes significantly reduced the loss of retinol, menadione, cyanocobalamin, thiamine, folates, vitamin B-6, and choline activity (P<0.05) compared to losses of vitamin activity in premixes containing inorganic trace minerals. Activity losses in retinol, cyanocobalamin, thiamine, and choline were similar between the vitamin premix and the vitamin-complexed trace mineral premix. Biotin activity was undetectable in the vitamin-complexed trace mineral premix due to unexplained analytical interference. Each vitamin was ranked according to relative vitamin assay cost, loss in vitamin activity per month, and susceptibility to multiple stress factors. This ranking was used to identify vitamins that could represent overall vitamin activity in a premix and could be assayed at a reasonable cost for a feed manufacturing quality control program. Retinol was identified as the best indicator vitamin, followed by thiamine, menadione, and cyanocobalamin. These results suggest that vitamin stability in swine vitamin-trace mineral premixes is improved when using metal specific amino acid complexes compared to inorganic trace mineral sources. More liberal safety margins for vitamins may be needed when formulating vitamin-trace mineral premixes using inorganic sources of trace minerals.

Post-Therapy Profile of Serum Total Cholesterol, Retinol and Zinc in Pediatric Acute Lymphoblastic Leukemia and Non-Hodgkin's Lymphoma

Objective: To assess serum albumin, total cholesterol, retinol, zinc and hemoglobin in children who had completed treatment for acute lymphoblastic leukemia (ALL) and Non-Hodgkin's lymphoma (NHL).Methods: The above parameters were analyzed in 105 ALL and NHL and 108 age and sex-matched controls. Serum albumin, serum cholesterol and hemoglobin were estimated by colorimetric methods. Serum retinol was estimated by HPLC and serum zinc was estimated by atomic emission spectrophotometer (ICP-AES). Comparisons were made to stage of treatment (maintenance 6 with post-therapy), type of treatment (chemotherapy and radiation with only chemotherapy) and type of malignancy (ALL with NHL).Results: Only serum albumin in patients included at Maintenance6 was significantly higher (t = 2.31, p = 0.05) than post-therapy patients. No significant difference in serum values was observed by type of treatment. Only total cholesterol was significantly higher in NHL patients than in ALL patients (t = 1.954, p = 0.05). Patients had comparable serum levels to that of controls. However, in patients and controls more than 75% children had deficient serum retinol levels, (< than 0.6989 μmol/l, or 20 μg/dl). Further, 75% patients and 54.7% controls had serum retinol levels less than 0.3439 μmol/l or 10 μg/dl.Conclusion: The results of the present study indicate that cancer and its treatment did not have any long-lasting effect on serum albumin, total cholesterol, retinol, zinc and hemoglobin. Majority of subjects had low serum retinol suggestive of depleted liver reserves. The deficient serum retinol levels (< than 0.6989 μmol/l, or 20 μg/dl) in at least 75% of the patients and controls probably reflect poor dietary intake. A higher percentage of patients with low serum retinol levels may also be attributed to the possibility of urinary losses of retinol that occur during episodes of infection while on immunosuppressive anti-cancer drug therapy.

Recommended dose for repair of serum vitamin A levels in patients with HIV infection/AIDS may be insufficient because of high urinary losses

Objective Retinol deficiency is quite frequent in the population of human immunodeficiency virus (HIV)-infected individuals. Serum retinol levels of less than 1.05 μmol/L determine a 3.5 to five times higher death risk. However, studies evaluating the efficacy of retinol supplementation in HIV-seropositive individuals have reported conflicting results. The World Health Organization recommends the treatment of vitamin A deficiency in seropositive individuals in the same manner as for seronegative individuals, but clinical studies proving the efficacy of this scheme are lacking. The proposal of the present study was to assess the efficacy of supplementation with high retinol doses in HIV-infected patients with vitamin A deficiency. Methods Twenty-five adult HIV-seropositive individuals were monitored over a period of 9 months, with determination of serum and urinary retinol every 3 months. The subjects received retinol palmitate doses ranging from 300,000 IU to 600,000 IU. Patients whose retinol levels were higher than 1.60 μmol/L were only observed. Results Eighteen patients received supplementation during clinical monitoring. The dose of 600,000 IU induced a significant mean increase in serum levels of 0.47 μmol/L ( P = 0.049) within a period of three months. Those who received 300,000 IU presented a mean increase of 0.29 μmol/L. In contrast, the patients who did not receive replacement therapy presented a significant decrease ( P = 0.017) in serum retinol levels, with initial and final values of 1.77 μmol/L and 1.55 μmol/L. The individuals with the worst response to supplementation presented a higher urinary loss of retinol at the beginning of the study. Even with a mean retinol supplementation of 771,428 IU during the study period, six patients had marginal serum retinol levels at the end of the study. Conclusion We conclude that, in view of the high urinary loss of this nutrient, there is the need to redefine the ideal dose for the treatment of HIV-infected individuals.

The effect of processing on the Vitamin A content of human milk

To analyze the effect of processing on the Vitamin A levels of milk that is donated to the Human Milk Bank at the University Maternity Hospital, and to evaluate whether this milk supplies the infants' Vitamin A requirement. Sixty milk samples from the Human Milk Bank were divided into two equal portions. One milk portion was extracted prior to processing, while another fraction was subjected to pasteurization and later extracted. The samples were analyzed using high performance liquid chromatography. Analysis with Student's t test indicated that the difference between mean retinol levels was statistically significant at the p < 0.05 level. The retinol content found in the milk prior to processing was 55.4+/-34.0 microg/100 ml, whereas for the processed milk this level was 36.6+/-26.1 microg/100 ml (p < 0.001). It was found that retinol loss occurs during milk processing and that the milk from the Human Milk Bank does not meet infants' Vitamin A requirement.

Diets supplemented with fiber do not increase accumulation of 1-naphthol

The influence of fiber on the absorption, accumulation and elimination of environmental contaminants varies among amounts and types of fiber and contaminants. We performed a study in mice to examine how different fibers (cellulose, rice bran, chitosan, lactosucrose, polydextrose, indigestible dextrin, and soy polysaccharides) influence accumulation and elimination of 1-naphthol and retinol. Urine and feces were collected daily during a 2-week exposure period, and blood samples were collected on days 1, 3, 7, and 14. Accumulation at day 14 was measured in the small and large intestine, liver, gallbladder, mesentery, kidney, and brain. Urinary excretion was the principal route of 1-naphthol elimination but was not responsive to fiber type. The colon contents of mice fed poorly fermented fibers had higher 1-naphthol concentrations, but this did not increase 2-week fecal elimination. Accumulation of 1-naphthol varied among tissues and fiber types except in the brain and kidney. Fecal retinol loss varied among fiber types, but not tissue accumulation except in the mesentery.

Characterization of the effect of retinol on Plasmodium falciparum in vitro

A preliminary study from our laboratory found retinol (vitamin A alcohol) to have in vitro activity against Plasmodium falciparum at concentrations close to those in normal human serum (1–3 μM). To characterize the antimalarial potential of retinol in more detail, the 3D7 and K1 laboratory strains of P. falciparum were maintained in continuous culture and [ 3H]hypoxanthine incorporation and microscopy were used to assess the effect of retinol against asexual stages of the parasite life-cycle. Losses of retinol and retinol-associated hemolysis were also quantified in the in vitro culture system. There were retinol losses of >50% but no hemolysis was observed with added retinol concentrations up to 100 μM. All stages of parasite development showed comparable sensitivity to retinol including merozoite invasion (range of mean IC 50 values 10.1–21.4 μM after adjustment for losses). Retinol pre-treatment of uninfected RBC did not inhibit merozoite invasion. Retinol treatment was associated with increased vacuolization within the parasite food vacuole and evidence of parasite membrane rupture. These appearances were similar to those seen with quinoline and artemisinin compounds. Although these data do not support a role for acute retinol supplementation in the treatment of falciparum malaria, they add to knowledge regarding potential antimalarial therapies and justify assessment of more potent synthetic retinoids and their metabolites.

Impaired bioavailability of vitamin A in adults and children with persistent diarrhoea in Zambia.

We have previously demonstrated a strong relationship between low serum retinol concentration and mortality in Zambian AIDS patients with diarrhoea, but were unable to detect any benefit from oral micronutrient supplementation. To test the hypothesis that this is related to impaired availability of vitamin A, we analysed serum retinol concentration changes over 6 h following oral mega-dose therapy (60, 120 or 180 mg retinol). Twenty-four men without diarrhoea, 15 adults with persistent diarrhoea and 11 children (six girls, five boys) with persistent diarrhoea were studied. Men with persistent diarrhoea had lower baseline serum retinol concentrations (median 0.39 micromol/L, interquartile range 0.21-0.56) than controls (median 1.16 micromol/L, interquartile range 0.84-1.47; P=0.0003). After 60 mg retinol, the rise in serum retinol in HIV seropositive controls (median 0.63 micromol/L, interquartile range 0.35-0.77) did not differ significantly from that observed in HIV seronegative controls (median 0.35 micromol/L, interquartile range - 0.04-0.56; P=0.20). Increasing the dose to 120 mg or 180 mg retinol did not enhance the increase in serum retinol concentration. The increase in serum retinol was less in adults with persistent diarrhoea (median 0.25 micromol/L, interquartile range 0.04-0.35) and in children (median 0.11 micromol/L, interquartile range 0.04-0.46) than in men without diarrhoea (median 0.44 micromol/L, interquartile range 0.26-0.74; P=0.03). Adults and children with diarrhoea had greater losses of retinol in urine over a 24-h period than controls, but less than 1% of the ingested dose was excreted. These results suggest that persistent diarrhoea in this population is associated with reduced bioavailability of retinol. Further work is required to determine the metabolic fate of therapeutic doses of retinol and to determine appropriate replacement strategies for HIV infected individuals.

Comparison of the Rates of Vitamin Degradation when Mixed with Metal Sulphates or Metal Amino Acid Chelates

Mixes containing retinol, cholecalciferol, tocopherol, menadione, thiamin, riboflavin, pyridoxine, cyanocobalamin, ascorbic acid, nicotinamide, pantothenic acid, folic acid, and biotin were blended with either metal sulphates or metal amino acid chelates of Cu, Zn, Fe, Mn, and Co. Half of the mixes were stored at 37°C and the other half at 20°C. Vitamin potencies were determined at 0, 90, and 180 days. The percentages of losses of retinol, menadione, pyridoxine, and ascorbic acid were significantly less when these vitamins were stored with metal amino acid chelates compared to storage with metal sulphates at either temperature. There was significant degradation of pyridoxine and riboflavin at 37°C and of ascorbic acid, retinol, and menadione at 20°C in the presence of the metal sulphates, but not in the presence of the amino acid chelates. It was concluded that in stored foods containing vitamins and minerals, there would be significantly less degradation of the vitamins prone to oxidation if the sources of the added minerals were amino acid chelates.