Assessment of Skin Carotenoid Measurement as a Means to Detect Vitamin A Deficiency in Children and Pregnant Women of Nepal.

BACKGROUND: Vitamin A deficiency (VAD) is an ongoing public health concern among children and pregnant women in Nepal despite robust national efforts to screen and treat this vision- and life-threatening condition. OBJECTIVES: This study aimed to evaluate skin carotenoid scores measured using the Veggie Meter as a rapid, noninvasive screening tool for VAD in Nepali children and pregnant women. METHODS: This comparative cross-sectional study enrolled 164 pregnant women and 168 children (aged 8 to 12 y) from public hospitals in three distinct outlying ecological regions of Nepal (Terai, Hill, and Mountain). The primary outcome assessed whether skin carotenoid status could be a biomarker for VAD. We determined skin carotenoid scores using the Veggie Meter and compared them with serum retinol and total carotenoid concentrations assessed by HPLC. Correlation analysis was used to determine bivariate associations between serum retinol and total carotenoid concentrations, and the Veggie Meter assessed skin carotenoid status. Receiver operating characteristics curves were determined, and a P value <0.05 was considered statistically significant. RESULTS: We found that 8.5% of pregnant women and 13.0% of children in this study had severe VAD (serum retinol < 200 ng/mL). There were significant correlations between skin carotenoid scores with serum retinol and total carotenoid concentrations among pregnant women and children (r = 0.253-0.530, P ≤ 0.001). The Veggie Meter detected severe VAD with 57.1% sensitivity and 82.7% specificity in pregnant women and 61.9% sensitivity and 75.9% specificity in children. CONCLUSIONS: Although sensitivity and specificity were moderate for detecting VAD with the Veggie Meter, skin carotenoid assessment using this rapid, noninvasive portable device could still be valuable for high-risk VAD screening in Nepal and similar developing countries with limited access to laboratory measurement of serum vitamin A concentrations.

Analysis of the association between serum levels of 25(OH)D, retinol binding protein, and Cyclooxygenase-2 and the disease severity in patients with diabetic foot ulcers.

Diabetic foot ulcers (DFUs) pose significant clinical challenges, representing severe complications in diabetes mellitus patients and contributing to non-traumatic amputations. Identifying reliable biomarkers can optimize early diagnosis and improve therapeutic outcomes. This study focused on evaluating the association between serum levels of 25-hydroxyvitamin D [25-(OH)D], Serum Retinol Binding Protein (RBP), and Cyclooxygenase-2 (COX-2) in elderly DFU patients. A retrospective study involving 240 participants, from March 2020 to March 2023. The participants were segmented into three cohorts: 80 with DFUs, 80 diabetic patients without DFUs, and 80 healthy controls. Serum concentrations of the three biomarkers were assayed using methods like enzyme-linked immunosorbent assay (ELISA), chemiluminescence immunoassay, and an automated biochemistry analyser. Comparisons were made both between groups and within the DFU group based on disease severity. Statistical analysis revealed significant differences in biomarker levels across the groups (p < 0.05). COX-2 and RBP concentrations were highest in the DFU group, followed by the non-DFU diabetic group, and lowest in the control group. Conversely, 25(OH)D levels were highest in the control group, followed by the non-DFU diabetic group, and lowest in the DFU group. Within the DFU group, RBP and COX-2 levels increased with disease severity, while 25(OH)D levels decreased. These variations were especially pronounced in patients with the most severe Wagner grading. A significant positive correlation was observed between disease severity and levels of RBP (r = 0.651, p < 0.05) and COX-2 (r = 0.356, p < 0.05). Conversely, a significant negative correlation was identified between disease severity and 25(OH)D levels (r = -0.658, p < 0.05). Assessing 25(OH)D, RBP, and COX-2 serum levels offers a promising tool for evaluating the severity and progression of DFUs. Monitoring these biomarkers can enrich our understanding of the metabolic and inflammatory pathways of the disease and potentially refine therapeutic strategies.

Serum retinol levels are associated with cognitive function among community-dwelling older Mexican adults.

BACKGROUND: Vitamin A (VA) provides neuroprotection against oxidative stress and brain inflammation. VA deficiency (VAD) increases the risk of neurodegeneration in animal models, but results are inconclusive in humans: particularly in the older adult (OA) population which is at higher risk for micronutrient deficiencies and cognitive impairment. OBJECTIVE: To estimate the association between serum retinol levels and cognitive function (CF) in older Mexican adults. METHODS: Cross-sectional study with 803 adults aged ≥60 years with fasting blood sample from the southern region of Mexico, collected in summer of 2015. Low serum retinol (LSR) was defined if serum retinol ≤20 µg/dl. CF was evaluated using Semantic Verbal Fluency Test (SVFT). Mild cognitive impairment (MCI) was defined using normative values for SVFT. Linear and logistic regression models were used to estimate the association of LSR with CF and MCI, respectively. RESULTS: Prevalence of MCI was 9.35% and LSR 3.36%. OA with LSR evoked less words in the SVFT (ß = -2.8, CI95% -4.6, -0.9) and had higher probability of MCI (OR = 2.7, CI95% 0.9, 7.7). Associations remained significant when considered IL-6. CONCLUSION: Frequency of LSR in older Mexican adults was low, but strongly associated with MCI. This result suggests that VA plays a role in maintaining CF in the elderly population. Since VAD is a reversible condition, further studies are needed in order to identify the main causes of LSR and prevent MCI in populations which are at higher risk for malnutrition.Trial registration: ClinicalTrials.gov identifier: NCT04820465.

Reproducibility and Validity of Capillary Dried Blood Spot for Diagnosis of Vitamin A Deficiency and Anemia in Children <5 Years Old.

BACKGROUND: Vitamin A deficiency (VAD) and anemia are the most prevalent nutritional deficiency in children globally. The dried blood spot (DBS) method has been used in prevalence studies of VAD and anemia in different age groups. However, it has not yet been validated for children. OBJECTIVES: This study aimed to assess the reproducibility and validity of DBS in the diagnosis of VAD and anemia in preschoolers. METHODS: Venous and capillary blood samples were collected from a representative sample of children <5 y old who attended the public health system in Rio de Janeiro. Serum retinol and hemoglobin were measured in 235 and 182 children, respectively. Serum retinol was measured with HPLC and hemoglobin was measured with spectrophotometry in samples of venous (gold standard) and capillary blood (test method, DBS). DBS reproducibility was assessed with the intraclass correlation coefficient (ICC), κ, and prevalence-adjusted and bias-adjusted κ (PABAK). DBS validity was assessed with sensitivity, specificity, accuracy index (AI), positive predictive value (PPV), and negative predictive value (NPV). RESULTS: DBS showed very good reproducibility for serum retinol (ICC = 0.94, κ = 0.83, PABAK = 0.76) and very good/good reproducibility for hemoglobin (ICC = 0.86, κ = 0.69, PABAK = 0.69). Prevalence rates for VAD by the reference and test methods were 11.5% and 11.9%, respectively, whereas the anemia rates were 19.2% and 46.2%. The test method showed low sensitivity (33%) and PPV (32%) and high specificity (91%) and NPV (92%) for serum retinol. For hemoglobin, the test method showed fair sensitivity (71%), low PPV (30%), fair specificity (60%), and high NPV (90%). AI was 83% for VAD and 62% for anemia. CONCLUSIONS: The results suggest that DBS is adequate for the diagnosis of VAD in preschool children, but not for anemia.

Breast Milk-Derived Retinol Is a Potential Surrogate for Serum in the 13C-Retinol Isotope Dilution Test in Zambian Lactating Women with Vitamin A Deficient and Adequate Status.

BACKGROUND: Vitamin A (VA) deficiency (VAD) affects ∼19 million pregnant women worldwide. The extent of VAD in Zambian women of reproductive age is unknown owing to lack of survey inclusion or the use of static serum retinol concentrations, a low-sensitivity biomarker. OBJECTIVES: This cross-sectional study employed isotopic techniques to determine VA status with serum and milk among women aged 18-49 y (n = 197) either lactating with infants aged 0-24 mo or nonlactating with or without infants. METHODS: Assistants were trained and piloted data collection. Demographic data, anthropometry, and relevant histories were obtained including malaria and anemia. For retinol isotope dilution (RID), baseline fasting blood and casual breast milk samples were collected before administration of 2.0 µmol 13C2-retinyl acetate and 24-h dietary recalls. On day 14, blood (n = 144) and milk (n = 66) were collected. Prevalence of total liver VA reserves (TLR) ≤0.10 µmol/g was defined as VAD with comparison to the DRI assumption of 0.07 µmol/g as minimally acceptable for North Americans. RESULTS: When a 20% adjustment for dose lost to milk was made in the RID equation for lactation, mean total body VA stores (TBS) for lactating women were 25% lower than for nonlactating women (P < 0.01), which was not the case without adjustment (P = 0.3). Mean ± SD TLR for all women were 0.15 ± 0.11 µmol/g liver. Using retinol purified from breast milk instead of serum for RID analysis yielded similar TBS and TLR, which were highly correlated between methods (P < 0.0001). Serum retinol ≤0.70 µmol/L had 0% sensitivity using either VAD liver cutoff and milk retinol ≤1.0 µmol/L had 42% sensitivity for VAD at 0.10 µmol/g. CONCLUSIONS: Determining accurate VA status among women of reproductive age, especially lactating women, forms a basis for extrapolation to the general population and informing policy development and program implementation.

Serum Retinol and Risk of Overall and Site-Specific Cancer in the ATBC Study.

Retinol, the most biologically active form of vitamin A, might influence cancer-related biological pathways. However, results from observational studies of serum retinol and cancer risk have been mixed. We prospectively examined serum retinol and risk of overall and site-specific cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (n = 29,104 men), conducted in 1985-1993, with follow-up through 2012. Serum retinol concentration was measured using reverse-phase high-performance liquid chromatography. Cox proportional hazards models estimated the association between baseline serum retinol quintile and overall and site-specific cancer risk in 10,789 cases. After multivariable adjustment, higher serum retinol was not associated with overall cancer risk (highest vs. lowest quintile: hazard ratio (HR) = 0.97, 95% confidence interval (CI): 0.91, 1.03; P for trend = 0.43). Higher retinol concentrations were, however, associated with increased risk of prostate cancer (highest vs. lowest quintile: HR = 1.28, 95% CI: 1.13, 1.45; P for trend < 0.0001) and lower risk of both liver and lung cancers (highest vs. lowest quintile: for liver, HR = 0.62, 95% CI: 0.42, 0.91; P for trend = 0.004; and for lung, HR = 0.80, 95% CI: 0.72, 0.88; P for trend < 0.0001). No associations with other cancers were observed. Understanding the mechanisms that underlie these associations might provide insight into the role of vitamin A in cancer etiology.

Functions of Intracellular Retinoid Binding-Proteins.

Multiple binding and transport proteins facilitate many aspects of retinoid biology through effects on retinoid transport, cellular uptake, metabolism, and nuclear delivery. These include the serum retinol binding protein sRBP (aka Rbp4), the plasma membrane sRBP receptor Stra6, and the intracellular retinoid binding-proteins such as cellular retinol-binding proteins (CRBP) and cellular retinoic acid binding-proteins (CRABP). sRBP transports the highly lipophilic retinol through an aqueous medium. The major intracellular retinol-binding protein, CRBP1, likely enhances efficient retinoid use by providing a sink to facilitate retinol uptake from sRBP through the plasma membrane or via Stra6, delivering retinol or retinal to select enzymes that generate retinyl esters or retinoic acid, and protecting retinol/retinal from excess catabolism or opportunistic metabolism. Intracellular retinoic acid binding-proteins (CRABP1 and 2, and FABP5) seem to have more diverse functions distinctive to each, such as directing retinoic acid to catabolism, delivering retinoic acid to specific nuclear receptors, and generating non-canonical actions. Gene ablation of intracellular retinoid binding-proteins does not cause embryonic lethality or gross morphological defects. Metabolic and functional defects manifested in knockouts of CRBP1, CRBP2 and CRBP3, however, illustrate their essentiality to health, and in the case of CRBP2, to survival during limited dietary vitamin A. Future studies should continue to address the specific molecular interactions that occur between retinoid binding-proteins and their targets and their precise physiologic contributions to retinoid homeostasis and function.

Serum retinol in post-partum mothers and newborns from an impoverished South African community where liver is frequently eaten and vitamin A deficiency is absent.

Serum retinol was assessed in mothers and newborns from an impoverished South African community where liver is frequently eaten and vitamin A deficiency known to be absent. Paired cord and maternal blood (n = 201) were collected after delivery and analysed for serum retinol and C-reactive protein (CRP). Liver intake during pregnancy and intention to breastfeed were also assessed. Mean serum retinol was 1.03 µmol/L ± 0.40 in mothers and 0.73 ± 0.24 µmol/L in newborns, with 21.4% and 49.3% having serum retinol <0.70 µmol/L (<20 µg/dL), respectively. Raised CRP was found in 59.9% of mothers, with a significant negative correlation between serum retinol and CRP (r = -0.273; p < 0.0001). Liver was eaten by 87.6% of mothers, and 99% indicated their intention to breastfeed. Despite consumption of liver, serum retinol was low in both the mother and the newborn. The conventional cut-off for serum retinol, i.e. <0.70 µmol/L may therefore not apply for the mother and newborn in the period immediately after delivery. Serum retinol may be influenced by factors other than vitamin A status, e.g. the haemodilution of pregnancy, as well as the acute phase response induced by the birth process, as suggested by raised CRP in 60% of mothers. In the newborns, the low serum retinol is likely to increase rapidly, as liver is frequently eaten by mothers and practically all of them intended to breastfeed. Our results confirm the need for better indicators of vitamin A status or alternative cut-off values during this period.

[Vitamin A nutritional status of Chinese rural children and adolescents in 2010-2012].

OBJECTIVE: To analysis the vitamin A nutritional status of 6-to 17-year-old children and adolescents between 2010-2012 in rural China. METHODS: Based on the China Health and Nutrition Survey 2010-2012 project, the serum vitamin A samples of children and adolescents from survey sites of rural area were selected by random sampling method, and 5888 cases of samples were detected using the high performance liquid chromatography method to evaluate their vitamin A nutritional status. RESULTS: The serum retinol concentration of children and adolescents in rural area was( 1. 44 ± 0. 58) µmol/L, and were( 1. 40 ± 0. 56) µmol/L in general rural areas and( 1. 46 ± 0. 60) µmol/L in poverty rural areas respectively( t = 1. 88, P < 0. 05). The serum retinol concentration of6-to 11-year-old were( 1. 31 ± 0. 53) µmol/L and( 1. 37 ± 0. 60) µmol/L, and serumretinol concentration of 12-to 17-year-old were( 1. 52 ± 0. 57) µmol/L and( 1. 52 ±0. 60) µmol/L( t = 11. 90 and t = 5. 54, P < 0. 05). The prevalence of vitamin A deficiency was 5. 53%, and were 6. 14% in general rural areas and 4. 55% in poverty rural areas, respectively( P > 0. 05). The prevalence of marginal vitamin A deficiency were 18. 75%, and were 19. 17% in general rural areas and 18. 07% in poverty rural areas, respectively( P > 0. 05). CONCLUSION: The situation of vitamin A deficiency in rural China are still widespread, the high prevalence of marginal vitamin A deficiency is more prominent.

Biomarkers of Nutrition for Development (BOND)-Vitamin A Review.

The Biomarkers of Nutrition for Development (BOND) project is designed to provide evidence-informed advice to anyone with an interest in the role of nutrition in health. The BOND program provides information with regard to selection, use, and interpretation of biomarkers of nutrient exposure, status, function, and effect, which will be especially useful for readers who want to assess nutrient status. To accomplish this objective, expert panels are recruited to evaluate the literature and to draft comprehensive reports on the current state of the art with regard to specific nutrient biology and available biomarkers for assessing nutritional status at the individual and population levels. Phase I of the BOND project includes the evaluation of biomarkers for 6 nutrients: iodine, folate, zinc, iron, vitamin A, and vitamin B-12. This review of vitamin A is the current article in this series. Although the vitamin was discovered >100 y ago, vitamin A status assessment is not trivial. Serum retinol concentrations are under homeostatic control due in part to vitamin A's use in the body for growth and cellular differentiation and because of its toxic properties at high concentrations. Furthermore, serum retinol concentrations are depressed during infection and inflammation because retinol-binding protein (RBP) is a negative acute-phase reactant, which makes status assessment challenging. Thus, this review describes the clinical and functional indicators related to eye health and biochemical biomarkers of vitamin A status (i.e., serum retinol, RBP, breast-milk retinol, dose-response tests, isotope dilution methodology, and serum retinyl esters). These biomarkers are then related to liver vitamin A concentrations, which are usually considered the gold standard for vitamin A status. With regard to biomarkers, future research questions and gaps in our current understanding as well as limitations of the methods are described.

Association of nonalcoholic fatty liver disease and liver fibrosis detected by transient elastography with serum retinol in American adults.

Background and objective: Retinol is a precursor of vitamin A, which is metabolized and maintained in the liver and is involved in the pathogenesis of the nonalcoholic fatty liver disease (NAFLD) and liver fibrosis. The relationship between NAFLD and liver fibrosis with serum retinol levels remains insufficient and inconclusive. Our study aimed to investigate the correlation between NAFLD, fibrosis, and serum retinol levels in American adults. Methods: A cross-sectional analysis was conducted using information from the 2017-2018 cycle of the National Health and Nutrition Examination Survey (NHANES). The exposure factors were NAFLD and liver fibrosis status detected using transient elastography (TE), and the outcome was serum retinol levels. Weighted multivariate regressions were established to assess the correlation between NAFLD and liver fibrosis and serum retinol levels. Subgroup analyses were also performed. Results: This study included 3,537 participants. Compared to the group without NAFLD, NAFLD was positively correlated with serum retinol levels (ß = 1.28, 95% CI: 0.19, 2.37). In the subgroup analysis, a positive correlation between NAFLD and serum retinol levels was found in people aged < 60 years, Mexican Americans, and those with a body mass index (BMI) < 25. On the contrary, compared to the group without liver fibrosis, there was a significant negative association between liver fibrosis and serum retinol (ß = -3.46, 95% CI: -5.16, -1.75), especially in people aged < 60 years, non-Hispanic white/black individuals, and people with a BMI ≥ 25. Conclusion: Our study suggests that NAFLD status may be positively associated with serum retinol levels in adult patients, and liver fibrosis may be negatively associated with serum retinol levels. Further studies are required to examine the associations found in our study.

A comparative study on indicators of vitamin A status and risk factors for sensitivity and specificity of the methods to detect vitamin A deficiency.

BACKGROUND: Serum retinol (SR) and retinol-binding protein (RBP) are commonly used indicators, but they are affected by infections and inflammation. This study aimed to assess the sensitivity and specificity of VA indicators to detect vitamin A deficiency (VAD) in 36-59-month-old children living in a rural area in Burkina Faso. METHODS: In a community-based study, two cross-sectional surveys were carried out from November 2016 to September 2017 in the health district of Dandé in Burkina Faso. The surveys included 115 children 36-59 months old. Indicators of VA and inflammation assessed in all children included SR, RBP and total liver VA reserves (TLR) estimated by retinol isotope dilution, and inflammation markers (C-reactive protein (CRP) and alpha 1-acid glycoprotein (AGP)). We calculated the sensitivity, specificity, positive and negative predictive values. In addition, the effects of inflammation, helminth infection, and season on sensitivity and specificity were assessed. RESULTS: The prevalence of VAD assessed by SR (< 0.7 µmol/L), RBP (< 0.7 µmol/L), and TLR (< 0.1 µmol/g liver) were, respectively, 30.9%, 33.3%, and 0%. Compared to TLR, the specificity, positive predictive value, and negative predictive value of SR were 71.1%, 0%, and 100%, and of RBP, were 68.9%, 0%, and 100%, respectively. The sensitivity was indeterminable for SR and RBP. The specificity of SR and RBP was lower during the dry season. Elevated CRP (> 5.0 mg/L) and AGP (> 1.0 g/L) were detected in 1.9% and 28.6% of children, respectively. The adjustment of VA indicators for inflammation improved SR's specificity to 75.9% and decreased RBP's specificity to 67.8%. CONCLUSION: No cases of VAD were identified by TLR. However, (inflammation-adjusted) SR and RBP had varying accuracy in the estimation of VAD. TRIAL REGISTRATION: The study was registered, retrospectively, on 22 March 2018 as a clinical trial with the Pan African Clinical Trials Registry under the number Cochrane South Africa; PACTR201803002999356.

Application of urinary N-acetyl-ß-D-glucosaminidase combined with serum retinol-binding protein in early detection of diabetic nephropathy.

BACKGROUND: Diabetic nephropathy (DN) is a microangiopathy of type 2 diabetes mellitus (T2DM), which can damage the kidney through various ways and mechanisms due to the nature of the disease, involving the renal interstitium and glomeruli. However, in the early stage of the disease, patients only showed kidney volume increase and glomerular hyperthyroidism, and typical symptoms that are difficult to arouse individual attention were noticed. AIM: To observe the expression of serum retinol-binding protein (RBP) and urinary N-acetyl-ß-D-glucosaminidase (NAG) in patients with DN, and to analyze their value in disease prediction, so as to provide new targets for early diagnosis and treatment of DN. METHODS: The baseline data of 50 T2DM patients treated in our hospital between January 2021 and December 2022 were retrospectively reviewed and included in group A. The baseline data of 50 patients with type 2 DN admitted to our hospital during the same period were collected and included in group B. The baseline data and serum RBP and urine NAG expression were compared between the two groups to analyze their value in the early prediction of DN. RESULTS: There was no significant difference in age, gender, duration of diabetes, combined hyperlipidemia and combined hypertension between the two groups (P > 0.05); the expression of urinary NAG and serum RBP in group B was higher than that in group A, and the difference was statistically significant (P < 0.05); a multiple logistic regression model was established, and the results showed that urinary NAG and serum RBP were related to the presence or absence of injury in diabetic patients, and overexpression of urinary NAG and serum RBP may be risk factors for renal injury in T2DM patients (OR > 1, P < 0.05); receiver operating curve curve was plotted, and the results showed that the area under the curve of urinary NAG and serum RBP expression alone and in combination for predicting DN was > 0.80, and the predictive value was satisfactory; bivariate Spearman linear correlation analysis showed that there was a positive correlation between urinary NAG and serum RBP expression in patients with DN (r = 0.566, P = 0.000). CONCLUSION: The increased expression of urinary NAG and serum RBP may be the risk factors leading to the progression of T2DM to DN. The possibility of DN can be considered in patients with urinary NAG and serum RBP overexpression by examining the expression of urinary NAG and serum RBP in patients with T2DM in clinical practice.

Benefits and Harms of Edible Vegetable Oils and Fats Fortified with Vitamins A and D as a Public Health Intervention in the General Population: A Systematic Review of Interventions.

This systematic review aims to assess whether edible vegetable oils and fats fortified with vitamin A and/or D are effective and safe in improving vitamin intake and ameliorating deficiency states in the general population. In November 2022, we systematically searched MEDLINE, Cochrane CENTRAL, Scopus, Global Index Medicus, ClinicalTrials.gov, and WHO ICTRP (International Clinical Trials Registry Platform) for randomized controlled trials (RCT) and non-randomized studies of interventions (NRSI) investigating the fortification of edible vegetable oils and fats with either vitamin A or vitamin D or both as compared to the same vegetable oils and/or fats without vitamin A and D fortification or no interventions, in the general population, without age restriction. We assessed the methodological quality of included RCTs using Cochrane's risk of bias tool 2.0 and of NRSIs using ROBINS-I tool. We performed random-effects meta-analysis and assessed certainty of evidence using GRADE. We included eight studies. Available evidence showed no significant effect of fortification with vitamin A on serum retinol levels (RCTs: MD 0.35 µmol/L, 95% CI -0.43 to 1.12; two trials; 514 participants; low-certainty evidence; CCTs: MD 0.31 µmol/L, 95% CI -0.18 to 0.80; two trials; 205 participants; very low-certainty evidence) and on subclinical vitamin A deficiency. Low-certainty evidence showed no effect of vitamin D fortification on serum 25-hydroxy vitamin D concentration (MD 6.59 nmol/L, 95% CI -6.89 to 20.07; one trial; 62 participants). In conclusion, vitamin A-fortified vegetable oils and fats may result in little to no difference in serum retinol levels in general populations. The dose of vitamin A used in the trials may be safe but may not be sufficient to reduce subclinical vitamin A deficiency. Further, the evidence suggests that vitamin D fortification results in little to no difference in serum 25-hydroxy vitamin D concentration. Several aspects of providing fortified oils and fats to the general population as a public health intervention should be further investigated, including optimal fortification dose, effects on vitamin D deficiency and its clinical symptoms and potential adverse effects.

The Association and Mediating Biomarkers of Serum Retinol in Influencing the Development of Type 2 Diabetes: A Prospective Cohort Study in Middle-Aged and Elderly Population.

The aims of this research are to elucidate whether serum retinol is associated with type 2 diabetes and to explore the underlying mechanisms of the association in a prospective cohort study. A total of 3,526 diabetes-free participants aged 40 years or older were enrolled at baseline in 2010-2012. Multivariable logistic regression was adopted to evaluate the associations of serum retinol and dietary vitamin A (VA) intake with type 2 diabetes. Mediation analyses were used to reveal potential mediators in their associations. After a mean follow-up of 5.3 years, 280 incident cases of type 2 diabetes occurred. Serum retinol was positively associated with the incidence of type 2 diabetes. The multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for type 2 diabetes from the bottom to the top quintile of serum retinol were 1, 1.878 (1.202, 2.936), 2.110 (1.364, 3.263), 1.614 (1.027, 2.538), and 2.134 (1.377, 3.306) (p-trend = 0.009), respectively. Mediation analysis showed that increased homeostasis model assessment - insulin resistance HOMA-IR, triglycerides (TG), and serum xanthine oxidase (XO) activity could account for 8.5, 14.7, and 12.1% of the total effects of serum retinol on type 2 diabetes, respectively. Serum retinol concentration was not significantly associated with dietary VA intake (r = -0.010, p = 0.570). In addition, no significant relationship was observed between dietary VA intake and the risk of type 2 diabetes. Overall, elevated serum retinol might increase the risk of type 2 diabetes which is mainly mediated by increased insulin resistance, TG, or serum XO activity.

Re-Defining the Population-Specific Cut-Off Mark for Vitamin A Deficiency in Pre-School Children of Malawi.

Retinol Binding Protein (RBP) is responsible for the transport of serum retinol (SR) to target tissue in the body. Since RBP is relatively easy and cheap to measure, it is widely used in national Micronutrient Surveys (MNS) as a proxy for SR to determine vitamin A status. By regressing RBP concentration against SR concentration measured in a subset of the survey population, one can define a population-specific threshold concentration of RBP that indicates vitamin A deficiency (VAD). However, the relationship between RBP and SR concentrations is affected by various factors including inflammation. This study, therefore, aimed to re-define the population-specific cut-off for VAD by examining the influence of inflammation on RBP and SR, among pre-school children (PSC) from the 2015-16 Malawi MNS. The initial association between RBP and SR concentrations was poor, and this remained the case despite applying various methods to correct for inflammation. The World Health Organization (WHO) recommends the threshold of 0.7 µmol/L to define VAD for SR concentrations. Applying this threshold to the RBP concentrations gave a VAD prevalence of 24%, which reduced to 10% after inflammation adjustments following methods developed by the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA). Further research is required to identify why SR and RBP were poorly associated in this population. Future MNS will need to account for the effect of inflammation on RBP to measure the prevalence of VAD in Malawi.

Inflammation Adjustments to Serum Retinol and Retinol-Binding Protein Improve Specificity but Reduce Sensitivity when Estimating Vitamin A Deficiency Compared with the Modified Relative Dose-Response Test in Ghanaian Children.

BACKGROUND: Serum retinol and retinol-binding protein (RBP) concentrations are commonly used biomarkers of vitamin A deficiency (VAD); however, evidence indicates that they are not always accurate, especially in populations with high exposure to inflammation. OBJECTIVE: The aim was to assess sensitivity and specificity of serum retinol and RBP concentrations to predict VAD, with and without adjustment for inflammation (using categorical and regression-adjusted approaches), using the modified relative dose-response (MRDR) as the reference standard for liver reserves. METHODS: This secondary analysis of diagnostic accuracy used inflammation and RBP data and analyzed serum retinol and MRDR from a subsample of women of reproductive age (n = 178) and preschool children (n = 166) in the cross-sectional 2017 Ghana Micronutrient Survey. RESULTS: Inflammation (elevated C-reactive protein and/or α1-acid glycoprotein) was present in 41% of children and 16% of women. Among children, estimates of VAD prevalence were as follows: 7% (MRDR), 40% (serum retinol), 29% (categorical-adjusted serum retinol), 24% (RBP), 13% (categorical-adjusted RBP), and 7% (regression-adjusted RBP). Sensitivity (95% CI) ranged from 22.2% (2.81%, 60.0%; both adjusted RBPs) to 80.0% (44.4%, 97.5%; serum retinol), whereas specificity ranged from 63.3% (54.7%, 71.3%; serum retinol) to 93.5% (88.0%, 97.0%; regression-adjusted RBP). Among women, VAD prevalence ranged from 1% (RBP) to 4% (all others); sensitivity was 0% and specificity was >96% for all indicators. CONCLUSIONS: Serum retinol and RBP had varying accuracy in estimating VAD, especially in children; adjustment for inflammation increased accuracy by increasing specificity at the expense of sensitivity. Effects of inflammation adjustment in the context of high inflammation and VAD prevalence need to be further explored. Especially in populations with high inflammation, the MRDR test should accompany serum retinol or RBP measurements in a subsample of subjects in population-based surveys. This trial was registered with the Open Science Framework registry (doi: 10.17605/OSF.IO/J7BP9).

Prevalence and Risk Factors of Vitamin A Deficiency in Children and Women of Childbearing Age in a Southern Indian Tribal Population: A Cross-Sectional Study.

BACKGROUND: Night blindness and keratomalacia continue to be a problem among the tribal children and pregnant women residing in Jawadhi hills. OBJECTIVES: The objective of the study is to determine the prevalence and risk factors of Vitamin A deficiency (VAD) among children aged 1-8 years and women of reproductive age in a southern Indian tribal population. MATERIALS AND METHODS: A cross-sectional study was done among children aged 1-8 years and women aged 15-45 years residing in Jawadhi hills. Participants were randomly selected by cluster sampling. Their sociodemographic characteristics and frequency of consumption of Vitamin A rich food were collected through a structured questionnaire. Anthropometric measures and serum retinol levels, using high-performance liquid chromatography, were estimated for all participants. RESULTS: A total of 166 children and 211 women participated in this study. The prevalence of VAD among the children (1-8 years) was 10.2% (95% confidence interval [CI] 5.5%-14.9%) and among women of the reproductive age group was 3.8% (95% CI: 1.2%-6.4%). Dietary intake was not associated with serum retinol levels. Low educational status of the head of the household (adjusted odds ratio [aOR] = 8.9) and pregnancy (aOR = 11.6) was significantly associated with an increased risk of VAD among children and women, respectively. CONCLUSIONS: The prevalence of VAD among children is a moderate public health problem. Strategies must focus on pregnant women and children from families with more than four children.

Serum retinol binding protein 4 and galectin-3 binding protein as novel markers for postmenopausal nonalcoholic fatty liver disease.

OBJECTIVE: To investigate the differential protein expression before and after menopause in women with nonalcoholic fatty liver disease (NAFLD) and to explore novel markers for menopausal NAFLD. METHODS: Eight serum samples collected from pre- or post-menopausal women with NAFLD were analysed by iTRAQ 2D-LC-MS/MS. Two protein candidates were selected and verified by enzyme-linked immunosorbent assay (ELISA) in serum samples collected from a one hundred and fifty-three female population subsequently, including 51 in post-menopausal status with NAFLD, 41 in pre-menopausal with NAFLD, 19 healthy individuals in post-menopausal status and 42 healthy pre-menopausal women. RESULTS: A total of one hundred and sixty-seven proteins exhibiting significant changes were characterized, among which sixty-five were up-regulated and one hundred and two were down-regulated. Of those altered proteins, the expression of serum retinol binding protein 4 (RBP4) and galectin-3 binding protein (LGALS3BP) was obviously increased in the post-menopausal patient group compared to the other. ELISA validations for the two proteins were consistent with the proteomic profiling. CONCLUSIONS: Serum RBP4 and LGAL3BP were up-regulated after menopause under NAFLD conditions, which suggested the two proteins may be potential markers as NAFLD in postmenopausal population.

The impact of sociodemography, diet, and body size on serum retinol in women 16-35 years of age: SANHANES-1.

To determine the current vitamin A status of a nationally representative sample of women aged 16-35 years, compare it with previous national data, and determine the impact of sociodemography, diet, and body size on vitamin A status, we performed secondary analysis of data on South African women who participated in the first South African National Health and Nutrition Examination Survey (SANHANES-1). Vitamin A status was assessed by serum retinol, and the findings are reported as means and prevalences with corresponding 95% confidence intervals. Overall, the age-standardized vitamin A deficiency prevalence was 11.7%, a decrease from previous national data, but serum retinol levels remained lower than in other developing countries. Overall, unweighted, multilevel, multivariate logistic regression showed that vitamin A deficiency was influenced by race only (odds ratio (OR) = 1.89, P = 0.031), while weighted multiple logistic regression for 16- to 18-year-olds showed that vitamin A deficiency was influenced by locality (OR = 9.83, P = 0.005) and household income (intermediate (OR = 0.2, P = 0.022) and upper (OR = 0.25, P = 0.049)). Despite the decreased prevalence, vitamin A deficiency remains a moderate public health problem in the country. Opportunities for targeted interventions have been identified.