Genotype Effects on β-Carotene Conversion to Vitamin A: Implications on Reducing Vitamin A Deficiency in the Philippines

Background: The study aimed to identify two beta-carotene 15,15′-monooxygenase (BCMO1) mutations, namely R267S and A379V, and determine their association with vitamin A status among Filipinos 6 to 19 years old respondents of the 2013 Philippine National Nutrition Survey living in the National Capital Region. Materials and Methods: This study followed cross-sectional design. Whole blood specimen was collected in the morning and was used as source of genomic DNA and serum for retinol concentration determination. Fisher exact test was performed to determine whether genotype frequencies were associated to retinol concentrations/vitamin A deficiency status. A level of P < .05 was identified as significant. Results: A total of 693 Filipino children and adolescents were included. Of the 693, there were at least 7.6% who bears the combined mutations for R267S + A379V. Association analysis showed that an inverse relationship exists between the A379V TT variant and vitamin A status. Although the exact role of these identified polymorphisms on retinol/carotenoid metabolism need to be confirmed in dedicated functional studies. Conclusion: This study has identified for the first time the presence of 2 nonsynonymous genetic variants/mutations in the coding region of BCMO1 gene. Interestingly, one of these two variants, the A379V T, was found to be associated with vitamin A status. It is, therefore, warranted to investigate the role of BCMO1 variants for the success of supplementation programs and fortification efforts among vulnerable populations in this region. Genetic variability should be considered for future provitamin A supplementation recommendations among children and adolescents in the Philippines.

Association between serum retinol and overall and cause-specific mortality in a 30-year prospective cohort study

How retinol as a clinical indicator of vitamin A status is related to long-term mortality is unknown. Here we report the results of a prospective analysis examining associations between serum retinol and risk of overall and cause-specific mortality. During a 30-year cohort follow-up, 23,797 deaths were identified among 29,104 men. Participants with higher serum retinol experienced significantly lower overall, CVD, heart disease, and respiratory disease mortality compared to men with the lowest retinol concentrations, reflecting 17–32% lower mortality risk (Ptrend < 0.0001). The retinol-overall mortality association is similar across subgroups of smoking intensity, alcohol consumption, body mass index, trial supplementation, serum alpha-tocopherol and beta-carotene concentrations, and follow-up time. Mediation analysis indicated that <3% of the effects of smoking duration and diabetes mellitus on mortality were mediated through retinol concentration. These findings indicate higher serum retinol is associated with lower overall mortality, including death from cardiovascular, heart, and respiratory diseases.

Influence of Vitamin A Status on the Choice of Sampling Time for Application of the Retinol Isotope Dilution Method in Theoretical Children

ABSTRACT Background Vitamin A status may influence the choice of a blood sampling time for applying the retinol isotope dilution (RID) equation to predict vitamin A total body stores (TBS) in children. Objectives We aimed to identify time(s) after administration of labeled vitamin A that provide accurate estimates of TBS in theoretical children with low or high TBS. Methods We postulated 2- to 5-y-old children (12/group) with low (&lt;200 μmol) or high TBS (≥700 μmol) and used compartmental analysis to simulate individual subject values for the RID equation TBS = FaS/SAp (Fa, fraction of dose in stores; S, retinol specific activity in plasma/in stores; SAp, retinol specific activity in plasma). Using individual SAp and group geometric mean FaS values from 1–28 d, we calculated individual and group mean TBS and compared them to assigned values. Results Mean TBS was accurately predicted for both groups at all times. For individuals, predicted and assigned TBS were closest when the CV% for FaS was low [12–14%; 4–13 d (low), 12–28 d (high)]. The mean percentage error for TBS was &lt;10% from 2–19 d (low) and 7–28 d (high). Predicted TBS was within 25% of assigned TBS for ≥80% of children from 3–23 d (low) and 9–28 d (high). Within groups, RID tended to overestimate lower TBS and underestimate higher TBS. Conclusions Using a good estimate for FaS, accurate RID predictions of TBS for individuals will be obtained at many times. If vitamin A status is low, results indicate that early sampling (e.g., 4–13 d) is optimal; if vitamin A status is high, sampling at 12–28 d is indicated. When vitamin A status is unknown, sampling at 14 d is recommended, or a super-subject design can be used to obtain the group mean FaS at various times for RID prediction of TBS in individuals.

An Updated Comprehensive Review on Vitamin A and Carotenoids in Breast Cancer: Mechanisms, Genetics, Assessment, Current Evidence, and Future Clinical Implications

Vitamin A and carotenoids are fat-soluble micronutrients that play important role as powerful antioxidants modulating oxidative stress and cancer development. Breast cancer is the most common malignancy in women. As the risk of breast cancer is dependent on various lifestyle factors such as dietary modifications, there is increasing interest surrounding the anti-cancerous properties of vitamin A and carotenoids. Despite the suggested protective roles of vitamin A and carotenoids in breast cancer development, their clinical application for the prevention and treatment of breast cancer is limited. In this narrative review, we discuss the roles of vitamin A and carotenoids along with the evaluation method of vitamin A status. We also exhibit the association of genetic variations involved in metabolism of vitamin A and carotenoids with cancers and other diseases. We demonstrate the epidemiological evidence for the relationship of vitamin A and carotenoids with breast cancer risk, their effects on cancer mechanism, and the recent updates in clinical practice of vitamin A or carotenoids as a potential therapeutic agent against breast cancer. This review provides insight into the preventive and therapeutic roles of vitamin A and carotenoids in breast cancer development and progression.

Radiographic analysis of the thickness of the cranial bones in captive compared to wild-living cheetahs and in cheetahs with hypovitaminosis A

Captive cheetahs often demonstrate a high incidence of diseases in which vitamin A imbalances are implicated. These can occur even under controlled and optimised feeding regimens, which is why surveillance of vitamin A status is mandatory in the successful health management of cheetahs. Serum levels of the vitamin do not reflect the true vitamin A status and liver tissue analysis is rather impractical for routine application in large felids. A biomarker for evaluating overt and subclinical vitamin A deficiency in cheetahs is needed. This study evaluates whether increased calvarial bone thickness can be detected on routine skull radiographs of vitamin A deficient cheetahs compared to unaffected animals, and secondly, evaluates whether there is increased bone thickness in clinically sound captive cheetahs in general compared to wild-living controls. Bone thickness in the neuro- and splanchnocranium was measured in 138 skull radiographs. Significant thickening of the parietal bones was found in latero-lateral radiographs of immature cheetahs (< 12 months) with vitamin A deficiency. This finding may allow a presumptive diagnosis of hypovitaminosis A in immature cheetahs. A general difference in skull thickness between free-living and captive cheetahs was not found.

Impact of Maternal Daily Oral Low-Dose Vitamin A Supplementation on the Mother–Infant Pair: A Randomised Placebo-Controlled Trial in China

Background: The nutritional status of vitamin A in lactating mothers and infants is still not optimistic. Due to the dietary habits and dietary restrictions of postpartum customs in China, vitamin A supplementation has been advocated as a potential strategy to improve vitamin A status of lactating mothers with inadequate dietary vitamin A intake. Existing clinical trials are limited to single or double high-dose maternal administrations. However, in China, vitamin A supplements are readily available in the form of daily oral low-dose supplements, and the effect of these is unknown. This study aimed to evaluate the effects of daily oral low-dose vitamin A supplementation on the retinol levels in the serum and breast milk of lactating mothers and the health status of infants in China. Methods: Lactating mothers who met the inclusion criteria and planned to continue exclusive breastfeeding were randomly assigned to receive either daily oral vitamin A and D drops (one soft capsule of 1800 IU vitamin A and 600 IU vitamin D2), or a matching placebo for 2 months. Before and after the intervention, dietary intake was investigated by instant photography, and the retinol concentration in maternal serum and breast milk was determined by ultra-high performance liquid chromatography-tandem mass spectrometry. During the trial, the health status of infants was diagnosed by a paediatrician or reported by lactating mothers. A total of 245 participants completed the study, with 117 in the supplementation group and 128 in the control group. Results: After the 2-month intervention, maternal serum retinol concentrations increased in the supplementation group with no change in the control group. Although breast milk retinol concentrations decreased significantly in both groups, the decrease in the supplementation group was significantly lower than that in the control group. However, maternal vitamin A supplementation was not associated with a lower risk of infant febrile illness, respiratory tract infection, diarrhoea, and eczema. Conclusions: Daily oral low-dose vitamin A supplementation is helpful in improving maternal vitamin A status, despite having no effect on infant health status through breast milk.

Vitamin A Status Improvement in Obesity: Findings and Perspectives Using Encapsulation Techniques

The association between obesity and vitamin A has been studied. Some studies point to the anti-obesity activity related to this vitamin, carotenoids with provitamin A activity, and carotenoid conversion products. This performance has been evaluated in respect of adipogenesis, metabolic activity, oxidation processes, secretory function, and oxidative stress modulation, showing a new property attributed to vitamin A in preventing and treating obesity. However, vitamin A and its precursors are highly sensitive and easily degraded when subjected to heat, the presence of light, and oxygen, in addition to losses related to the processes of digestion and absorption. In this context, encapsulation presents itself as an alternative capable of increasing vitamin A’s stability in the face of unfavorable conditions in the environment, which can reduce its functionality. Considering that vitamin A’s status shows a strong correlation with obesity and is an innovative theme, this article addresses the associations between vitamin A’s consumption and its precursors, encapsulated or not, and its physiological effects on obesity. The present narrative review points out those recent studies that demonstrate that vitamin A and its encapsulated precursors have the most preserved functionality, which guarantees better effects on obesity therapy.

Low maternal vitamin A intake increases the incidence of teratogen induced congenital diaphragmatic hernia in mice

Background Congenital diaphragmatic hernia (CDH) is a severe birth defect associated with high perinatal mortality and long-term morbidity. The etiology of CDH is poorly understood although abnormal retinoid signaling has been proposed to contribute to abnormal diaphragm development. Existing epidemiological data suggest that inadequate dietary vitamin A intake is a risk factor for developing CDH. Methods Using a mouse model of teratogen-induced CDH, the objective of this study was to test the hypothesis that low maternal vitamin A intake contributes to abnormal diaphragm development. To test this hypothesis, we optimized a model of altered maternal dietary vitamin A intake and a teratogenic model of CDH in mice that recapitulates the hallmark features of posterolateral diaphragmatic hernia in humans. Results Our data uniquely show that low maternal dietary vitamin A intake and marginal vitamin A status increases the incidence of teratogen-induced CDH in mice. Conclusion Low dietary vitamin A intake and marginal vitamin A status lead to an increased incidence of teratogen-induced CDH in mice, highlighting the importance of adequate dietary vitamin A intake and CDH risk. Impact This study describes and validates a mouse model of altered maternal and fetal vitamin A status. This study links existing epidemiological data with a mouse model of teratogen-induced congenital diaphragmatic hernia, highlighting the importance of low maternal vitamin A intake as a risk factor for the development of congenital diaphragmatic hernia. This study supports the Retinoid Hypothesis, which posits that the etiology of congenital diaphragmatic hernia is linked to abnormal retinoid signaling in the developing diaphragm.