Use of Theoretical Women and Model-Based Compartmental Analysis to Evaluate the Impact of Vitamin A Intake with or without a Daily Vitamin A Supplement on Vitamin A Total Body Stores and Balance During Lactation.

BACKGROUND: Inadequate vitamin A (VA) intake is common among lactating women in many communities worldwide, but high-dose VA supplementation for postpartum women is not recommended by the World Health Organization as an effective intervention. OBJECTIVES: To simulate the impact of VA intake via diet and daily VA supplements on VA total body stores (TBS) and balance in theoretical lactating women with low/moderate TBS. METHODS: We studied 6 theoretical subjects with assigned values for TBS from 219-624 µmol. Using Simulation, Analysis, and Modeling software and a previously published compartmental model for whole-body VA metabolism, we simulated TBS over 6 mo of established lactation for each subject under 4 conditions: 1) prelactation VA intake was increased to maintain VA balance (LSS); 2) prelactation VA intake was maintained (NLSS); 3) VA intake was the same as 2) but a daily VA supplement (2.8 µmol/d) was added (NLSS+S); and 4) VA intake was as 1) and the daily VA supplement was included (LSS+S). RESULTS: To compensate for the loss of VA via milk while VA balance was maintained (LSS) over 6 mo of lactation, VA intake had to increase by 0.8-1.87 µmol/d (n = 6) compared with NLSS. Over 6 mo of NLSS treatment, VA balance was negative (geometric mean, -0.77 µmol/d) compared with LSS, whereas balance was positive under NLSS+S and LSS+S conditions (0.75 and 1.5 µmol/d, respectively). For LSS, the proportion of total VA disposal was 37% via breastmilk, 32% from VA stores, and 32% from nonstorage tissues. CONCLUSIONS: Adding a daily VA supplement (2.8 µmol/d) to the diet of lactating women with suboptimal VA intake may effectively counterbalance the negative VA balance resulting from the output of VA via breastmilk and thus benefit both mother and infant by maintaining or increasing VA stores and breastmilk VA concentration.

Vitamin A-containing dietary supplements from German and US online pharmacies: market and risk assessment.

Vitamin A supplements are used by many people, and the number of newly registered dietary supplements is continuously increasing. The preparations fall under food law and are not subject to the strict controls of pharmaceuticals. Risk indications and maximum quantity recommendations, e.g., from the Bundesinstitut für Risikobewertung (BfR) and the U.S. Food and Drug Administration (FDA) are not binding, which means that overdoses and potentially serious health problems can easily occur. The hepatotoxicity and teratogenicity of vitamin A are well documented, and other negative effects of high doses of vitamin A are also being discussed. Nevertheless, preparations with exorbitantly high doses are freely available for sale and unrestricted. In this study, 75 supplements containing vitamin A available in Germany and 26 available in the USA were critically examined on the basis of various parameters such as the recommended daily dose according to the manufacturer, daily therapy costs (DTC), the presence of warnings about overdose, use during pregnancy and breastfeeding, and information on adverse effects/interactions. The aim was to gain insights into their risk potential and to examine the need for closer monitoring and stricter guidelines for these preparations. The results show some considerable country-specific differences. Overall, there are serious deficiencies in compliance with the labeling requirements for both the German and the US preparations, and the dosages are often far too high in view of the applicable expert recommendations. Overall, these deficits can pose a risk for consumers that is difficult to assess in its entirety, especially for vulnerable consumer groups. It should be noted that the US preparations perform better overall than the German preparations. This suggests better regulation of dietary supplements in the US market. Based on the available data and literature research, it is doubtful whether the intake of vitamin A-containing preparations, without a diagnosed vitamin A deficiency, has a positive health benefit. Furthermore, it should be examined whether vitamin A should continue to be offered over-the-counter as a food supplement.

Characterization of Nutrient Intake in Biopsy-Confirmed NAFLD Patients.

Objectives: Weight loss improves the liver pathophysiological status of nonalcoholic fatty liver disease (NAFLD) patients. However, there are few studies that investigate the accurate relationships between nutritional intake and disease progression in NAFLD patients. Methods: A total of 37 biopsy-confirmed NAFLD patients were enrolled in this study. Clinical and nutritional control data of 5074 persons were obtained from the National Institute of Health and Nutrition. Each NAFLD subject recorded dietary intake for seven consecutive days using a dietary questionnaire and photographs of each meal. A dietitian analyzed and quantified the nutritional data in each patient. We further analyzed the nutritional intake of NAFLD patients in three groups according to the following criteria: (1) liver fibrosis degree (advanced, early), (2) gender (male, female), and (3) body mass index (BMI) (high, low). Results: Excesses or deficiencies of multiple nutrients were found in NAFLD patients compared with control subjects. In addition, there were variations in nutritional intake. (1) The intake of vitamins A, B6, and E, pantothenic acid, soluble dietary fiber, and salt was lower in the advanced fibrosis group than in the early fibrosis group. (2) Fat intake was higher in male patients, and dietary fiber intake was lower in both male and female patients compared with control subjects. (3) Saturated fatty acid intake was higher, and copper and vitamin E intakes were lower in patients with high BMI than with low BMI. Conclusions: Our study demonstrates that differences were found in some nutrient intake of NAFLD patients and controls and according to the severity of the conditions (liver fibrosis degree, BMI).

Associations of Dietary Vitamin A and Beta-Carotene Intake With Depression. A Meta-Analysis of Observational Studies.

Objective: To clarify the associations of dietary vitamin A and beta-carotene intake with depression based on a meta-analysis of observational studies. Methods: An extensive literature search on February 2022 (PubMed, Web of Science and Embase) was employed to identify observational studies on the associations of dietary vitamin A and beta-carotene intake with depression. The pooled relative risk (RR) of depression for the highest vs. lowest dietary vitamin A and beta-carotene intake category, and the standard mean difference (SMD) of dietary vitamin A and beta-carotene intake for depression vs. control subjects, were calculated. Results: A total of 25 observational studies (100,955 participants), which included 24 cross-sectional/case-control and 1 prospective cohort study, were included in this study. The overall multi-variable adjusted RR demonstrated that dietary vitamin A intake was inversely associated with depression (RR = 0.83, 95%CI: 0.70-1.00; P = 0.05). In addition, the combined SMD showed that the dietary vitamin A intake in depression was also lower than that in control subjects (SMD = -0.13, 95%CI: -0.18 to -0.07; P < 0.001). On the other hand, the overall multi-variable adjusted RR indicated that dietary beta-carotene intake was negatively associated with depression (RR = 0.63, 95%CI: 0.55-0.72; P < 0.001). The combined SMD showed that the dietary beta-carotene intake in depression was also lower than that in control subjects (SMD = -0.34, 95%CI: -0.48 to -0.20; P < 0.001). Conclusion: Our results suggest that both dietary vitamin A and beta-carotene intake is inversely associated with depression. However, due to the limited evidence, further prospective cohort studies are still needed.

Inverse association between dietary vitamin A intake and new-onset hypertension.

BACKGROUND & AIMS: The prospective relation of dietary vitamin A intake with hypertension remains uncertain. We aimed to investigate the relationship of dietary vitamin A intake with new-onset hypertension and examine possible effect modifiers in general population. METHODS: This prospective cohort study included 12,245 participants who were free of hypertension at baseline from China Health and Nutrition Survey (CHNS). Dietary intake was measured by 3 consecutive 24-h dietary recalls combined with a household food inventory. The study outcome was new-onset hypertension, defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg or diagnosed by physician or under antihypertensive treatment during the follow-up. RESULTS: During a median follow-up duration of 6.1 years, a total of 4,304 (35.1%) participants developed new-onset hypertension. Overall, there was an L-shaped relation of total dietary vitamin A intake with new-onset hypertension (P for nonlinearity <0.001). Accordingly, compared with participants with lower vitamin A intake (quartile 1, <227.3 µg RE/day), those with higher vitamin A intake (quartile 2-4, ≥227.3 µg RE/day) had a significantly lower risk of new-onset hypertension (adjusted HR, 0.73; 95%CI: 0.63, 0.78). Similar results were found for plant-derived vitamin A intake (adjusted HR, 0.65; 95% CI, 0.61, 0.70) or animal-derived vitamin A intake (adjusted HR, 0.76; 95% CI, 0.70, 0.82). CONCLUSIONS: There was a L-shaped relation of dietary vitamin A intake with new-onset hypertension in general Chinese adults. Our results emphasized the importance of maintaining relatively higher vitamin A intake levels for the prevention of hypertension.

Prediction of Vitamin A Stores in Young Children Provides Insights into the Adequacy of Current Dietary Reference Intakes.

BACKGROUND: Limited data were available in infants and children when vitamin A (VA) DRIs were established; recommendations were developed based on average breast milk VA intake and extrapolation of data from adults. OBJECTIVES: Our objective was to evaluate whether DRIs and reported intakes, with and without VA from intervention programs, would be sufficient to develop adequate VA stores from birth to age 5 y in Bangladeshi, Filipino, Guatemalan, and Mexican children. METHODS: A mathematical relationship was established, defined by a series of equations, to predict VA total body stores (TBS) as a function of age based on VA intake and utilization. TBS calculated using reported VA intakes, with and without additional VA from intervention programs, were compared to those predicted using DRIs (specifically, Adequate Intake and RDA). Liver VA concentrations were also estimated. RESULTS: Our predictions showed that for these 4 groups, DRIs were sufficient to attain liver VA concentrations >0.07 µmol/g by 1 wk of age and sustain positive VA balance for 5 y. Using reported intakes, which were lowest in Bangladeshis from 1 y on and highest in Guatemalans, predicted VA stores in Bangladeshi and Filipino children increased until ∼2-3 y, then TBS stabilized and liver VA concentrations decreased with age. When VA interventions were included, stores exceeded those predicted using DRIs by 12-18 mo. In contrast, reported intakes alone in Guatemalan and Mexican children resulted in VA stores that surpassed those calculated using DRIs. For all populations, reported intakes were sufficient to build liver concentrations >0.07 µmol/g by 3 mo. CONCLUSIONS: Although more information is needed to better define dietary VA requirements in children, our results suggest that for an average, generally healthy child in a low- or middle-income country, current DRIs are sufficient to maintain positive VA balance during the first 5 y of life.

Addition of Vitamin A Intake Data during Compartmental Modeling of Retinol Kinetics in Theoretical Humans Leads to Accurate Prediction of Vitamin A Total Body Stores and Kinetic Parameters in Studies of Reasonable Duration.

BACKGROUND: Mathematical modeling of theoretical data has been used to validate experimental protocols and methods in several fields. OBJECTIVES: We hypothesized that adding dietary vitamin A intake data as an input during compartmental modeling of retinol kinetics would lead to accurate prediction of vitamin A total body stores (TBS) at 2 specified study lengths and would reduce study duration required to accurately define the system. METHODS: We generated reference values for state variables (including TBS and intake) and kinetic parameters for 12 theoretical individuals (4 each of children, younger adults, and older adults) based on modeling plasma retinol tracer data for 365 d. We compared TBS predictions using data to 28 d (children) or 56 d (adults) without and with intake included in the model to reference values for each subject. Then, by truncating data sets from 365 d, we determined the shortest study duration required to accurately define the system without and with inclusion of vitamin A intake. RESULTS: Reference values for TBS ranged from 30 to 3023 µmol. Study durations of 28 and 56 d were sufficient to accurately predict TBS for 6 of the 12 subjects without intake; adding intake resulted in accurate predictions of TBS for all individuals. When intake was not included as a modeling input, durations of 35-310 d were required to define the system; inclusion of intake data substantially reduced the time required to 10-42 d. CONCLUSIONS: Inclusion of vitamin A intake as additional data input when modeling vitamin A kinetics allows investigators to accurately predict TBS and define the vitamin A system in studies of reasonable length (4 wk in children and 8 wk in adults). Because it is generally possible to obtain estimates/measures of intake, including such data increases confidence in model predictions while also making studies more feasible.

Retention of Pro-Vitamin A Content in Products from New Biofortified Cassava Varieties.

Plant breeding efforts in sub-Saharan Africa (SSA) have produced biofortified cassava with high carotenoid content to address vitamin A deficiencies (VAD). Since carotenoids in foods are easily depleted during processing, the retention of ß-carotene in some newly released cassava varieties is under query. From four of these new varieties, two commonly consumed products (gari and its dough) were processed according to standard methods. Retention of ß-carotene was then probed after applying fermentation periods of a day and three days. The possible contribution of the products to Vitamin A intake in children, adolescents, and women was also assessed. The concentration of ß-carotene in fresh Cassava roots ranged from 5.32 to 7.81 µg/g. The percentage retention ranged from 14.4 to 29.3% and 10 to 21.7% in gari fermented for one and three days respectively. The impact of varietal difference and length of fermentation was significant on retention in the intermediate and final products (p < 0.001). When compared with dietary intake data, cooking biofortified gari into its dough reduced Vitamin A intake in most varieties. We conclude that processing Cassava into gari (especially its dough) could hinder the retention of ß-carotene however some varieties have retention advantage over others irrespective of the initial concentration in their fresh roots.

Overlapping vitamin A interventions in the United States, Guatemala, Zambia, and South Africa: case studies.

Vitamin A (VA) deficiency is a serious public health problem, especially in preschool children who are at risk of increased mortality. In order to address this problem, the World Health Organization recommends periodic high-dose supplementation to children 6-59 months of age in areas of highest risk. Originally, supplementation was meant as a short-term solution until more sustainable interventions could be adopted. Currently, many countries are fortifying commercialized common staple and snack foods with retinyl palmitate. However, in some countries, overlapping programs may lead to excessive intakes. Our review uses case studies in the United States, Guatemala, Zambia, and South Africa to illustrate the potential for excessive intakes in some groups. For example, direct liver analysis from 27 U.S. adult cadavers revealed 33% prevalence of hypervitaminosis A (defined as ≥1 µmol/g liver). In 133 Zambian children, 59% were diagnosed with hypervitaminosis A using a retinol isotope dilution, and 16% had ≥5% total serum VA as retinyl esters, a measure of intoxication. In 40 South African children who frequently consumed liver, 72.5% had ≥5% total serum VA as retinyl esters. All four countries have mandatory fortified foods and a high percentage of supplement users or targeted supplementation to preschool children.

A Population-Based (Super-Child) Approach for Predicting Vitamin A Total Body Stores and Retinol Kinetics in Children Is Validated by the Application of Model-Based Compartmental Analysis to Theoretical Data.

BACKGROUND: Public health nutritionists need accurate and feasible methods to assess vitamin A status and to evaluate efficacy of interventions, especially in children. The application of population-based designs to tracer kinetic data is an effective approach that reduces sample burden for each child. OBJECTIVES: Objectives of the study were to use theoretical data to validate a population-based (super-child) approach for estimating group mean vitamin A total body stores (TBS) and retinol kinetics in children and to use population-based data to improve individual TBS predictions using retinol isotope dilution (RID). METHODS: We generated plasma retinol kinetic data from 6 h to 56 d for 50 theoretical children with high vitamin A intakes, assigning values within physiologically reasonable ranges for state variables and kinetic parameters ("known values"). Mean data sets for all subjects at extensive (n = 36) and reduced (n = 11) sampling times, plus 5 data sets for reduced numbers (5/time, except all at 4 d) and times, were analyzed using Simulation, Analysis and Modeling software. Results were compared with known values; population RID coefficients were used to calculate TBS for individuals. RESULTS: For extensive and reduced data sets including all subjects, population TBS predictions were within 1% of the known value. For 5 data sets reflecting numbers and times being used in ongoing super-child studies, predictions were within 1-17% of the known group value. Using RID equation coefficients from population modeling, TBS predictions at 4 d were within 25% of the known value for 66-80% of subjects and reflected the range of assigned values; when ranked, predicted and assigned values were significantly correlated (Rs  = 0.93, P < 0.0001). Results indicate that 7 d may be better than 4 d for applying RID in children. For all data sets, predictions for kinetic parameters reflected the range of known values. CONCLUSION: The population-based (super-child) approach provides a feasible experimental design for quantifying retinol kinetics, accurately estimating group mean TBS, and predicting TBS for individuals reasonably well.

Effects of total vitamin A, vitamin C, and fruit intake on risk for metabolic syndrome in Korean women and men.

OBJECTIVES: The question of whether the consumption of antioxidants prevents and alleviates metabolic syndrome (MetS) by reducing insulin resistance remains controversial. The aim of this study was to assess whether the intake of vitamin A (including ß-carotene), vitamin C, fruits, or vegetables was negatively associated with MetS in Korean adults aged ≥ 20 y. METHODS: We conducted a cross-sectional study of 27,656 adults ≥ 20 y of age who participated in the 2007-2012 Korean National Health and Nutrition Examination Survey. Daily intake of vitamin A and vitamin C was assessed by 24-h recall, and the consumption of fruits and vegetables was determined using a food frequency questionnaire. Odds ratios (ORs) for MetS were calculated for log2-transformed vitamin A and C intake values and for the interaction of sex with vitamin A and C intake, after covariate adjustment. RESULTS: Interactions were seen between total vitamin A and C intake and sex for MetS. With a twofold increase in total vitamin A and C intake in women, the ORs (95% confidence intervals) for metabolic syndrome were 0.942 (0.901-0.985) and 0.933 (0.883-0.987), indicating decreases of 5.8% and 6.7% in MetS, respectively. There were no equivalent decreases in men. Women in the second and highest tertiles of fruit intake exhibited 17.5% and 21.8% lower incidences of MetS, respectively, compared with women in the lowest tertile. CONCLUSIONS: The intake of total vitamin A and C, as well as moderate and high fruit intake, may have alleviated MetS in women, but not in men, in a representative sample of the general South Korean population.

Vitamin A Intakes and Food Sources of Vitamin A in Female University Students / 대한지역사회영양학회지

The purpose of this study was to estimate the daily intake of vitamin A in Korean female university students. Vitamin A intake was estimated using an inconsecutive 3-day dietary intake survey from 481 young women. Vitamin A intake values were calculated based on the data in USDA database. Average age, height, and weight of the subjects were 20.05 years, 162.13 cm and 54.38 kg, respectively. The subject's average intake of energy was 1645.67 kcal. The mean vitamin A, retinol and beta carotene intakes were 908.35 +/- 863.18 ug retinol equivalent/day, 199.19 +/- 166.00 ug/day and 3872.59 +/- 4972.17 ug/day, respectively. The 21.83% of the subjects consumed less than the Estimated Average Requirement (EAR) for vitamin A. And subjects consumed 141.69% of the Recommended Nutrient Intake (RNI) for vitamin A. Food groups consumed with high vitamin A content in our subjects included vegetables (423.96 ug RE/day), potato and starches (213.64 ug RE/day), cereals (62.60 ug RE/day), eggs (55.17 ug RE/day) and milks (53.45 ug RE/day). The major food sources of vitamin A were sweet potato, carrot, spinach, egg, and cereal, and the top 30 foods provided 89.57% of total vitamin A. Also animal-derived food provided 9.65% of the vitamin A intake from the top 30 foods. In conclusion, judging from RNI, the vitamin A intake of the Korean female university students in this study was generally adequate. The result of our study may be used as a basis for follow-up studies of vitamin A intake like assessment of vitamin A nutritional status or evaluation of carotenoid food sources in Korean young women.

Intakes and Major Food Sources of Vitamins A and E of Korean Adults Living in Seoul and Gyeonggi Province

To determine vitamin A and E intakes and their food sources, dietary intakes were collected by three consecutive 24-hour recalls from 192 adults living in Seoul and Gyeonggi Province, Korea. The mean vitamin A, retinol and beta-carotene intakes were 1240.1 +/- 1101.1 microg retinol equivalent/day (693.3 +/- 563.2 microg retinol activity equivalent/day), 182.6 +/- 149.5 microg/day and 5443.3 +/- 6365.5 microg/day, respectively. Only 9.4% of the subjects consumed less than the Korean Estimated Average Requirement for vitamin A. The mean vitamin E intake was 6.03 +/- 2.54 mg alpha-tocopherol equivalent/day. The alpha-tocopherol and gamma-tocopherol intakes were 4.83 +/- 2.03 and 5.57 +/- 3.41 mg/day, respectively. Most of the subjects (93.8%) consumed less than the Korean Adequate Intake for vitamin E. The major food sources of vitamin A were sweet potato, carrot, red pepper powder, spinach, and citrus fruit, and the top 30 foods provided 91.5% of total Plant foods provided 81.0% and animalderived foods 10.5% of the vitamin A intake from the top 30 foods. The major food sources of vitamin E were soybean oil, red pepper powder, Ramyeon (cup noodles), spinach, and egg. The top 30 foods provided 78.0% of total vitamin E intake. Plant foods provided 61.3% and animal-derived foods 15.9% of the vitamin E intake from the top 30 foods. In conclusion, the vitamin A intake of the Korean adults in this study was ge-nerally adequate, but the vitamin E intake of many subjects was inadequate. Therefore, nutritional education may be of benefit to Korean adults to increase their vitamin E intake.

Vitamin A and Vitamin E Status of Diabetic Patients and Normal Adults in Korea

We evaluated the vitamin A and E status of type 2 diabetic patients and normal adults living in Daegu area. Dietary intakes for two non-consecutive days were measured by 24-hour recall method for 76 diabetic patients and 72 normal adults. Plasma levels of retinol and alpha-tocopherol were measured using HPLC method. Dietary intakes of vitamin A were not significantly different between the diabetic and the normal adults. However, the diabetic patients had significantly lower vitamin E intakes than the normal adults. Major food sources for vitamin A intake were red pepper powder and carrot. Half of the subjects from diabetic as well as normal adults consumed less than estimated average requirement of vitamin A. Plasma levels of retinol and tocopherol were maintained within normal ranges for most of the subjects regardless of diabetic status. Dietary intake of vitamin A was associated with vitamin E intake, however, there was no significant correlations between vitamin E intake and plasma alpha-tocopherol levels. It seems that diabetic patients should try to increase dietary intake of vitamin E, as prolonged lower-level intake of vitamin E could eventually lead to vitamin E depletion. Further studies are needed to identify the magnitude of dietary variance at individual and seasonal levels, and to understand the discrepancies in dietary intake and plasma levels before establishing the dietary reference intake based on Korean dietary pattern.

Vitamin A Intake of Exclusively Breast-Fed Infants in Cheongju and Anseong areas

This study was longitudinally conducted to evaluate vitamin A intake of exclusively breast-fed infants compared with the Recommended Dietary Allowances (RDA) for Korean infants. Twenty-seven Korean lactating women and their infants during the first 6 months of lactation in Cheongju and Anseong areas were participated. Retinol and beta-carotene contents in the milk were determined using HPLC and also the milk consumption of the infants was measured by the test-weighing methods. Vitamin A (retinol and beta-carotene) contents of the milk were 65.7, 57.2, 48.1, 43.9, 38.2, 38.7 and 44.0 R.E./100 ml, and vitamin A intakes of the breast-fed infants were 361, 402, 348, 331, 304, 305 and 322 R.E./day at 0.5, 1, 2, 3, 4, 5 and 6 month of lactation, respectively. The average intake of vitamin A was 339.1 R.E./day and the percentage to RDA was 96.9% during 6 months. Vitamin A intakes per body weight of the breast-fed infants were 96.7, 88.3, 62.1, 50.0, 41.8, 39.3 and 39.6 R.E./kg/day at 0.5, 1, 2, 3, 4, 5 and 6 month. The body weight increased normally from 3.4 +/- 0.5 kg at birth during lactation. It is suggested that the breast-fed infants in Cheongju and Anseong areas consumed adequately vitamin A from the milk compared with RDA for Korean infants.