Vitamin A deficiency (VAD) is common among pregnant women (PW) and has been associated with anaemia and adverse birth outcomes. However, in the Free State Province of South Africa, evidence regarding this is limited. Hence, this cross-sectional study investigated the vitA intake and status of PW in Bloemfontein and its association with anaemia, iron status and birth outcomes. Blood was taken from 427 PW to assess status of vitA (retinol-binding protein 4 (RBP4)), iron (ferritin, soluble transferrin receptor), and anaemia (haemoglobin (Hb)). Sociodemographic, HIV, birth outcomes (birth weight and gestational age), and dietary vitA intake data were obtained using a questionnaire in an interview and medical records. Descriptive statistics and linear regression were used to describe variables and association between vitA and iron status and birth outcomes. Median vitA intake was 1007µgRAE/d, with 19% of participants’ intake below the EAR of 550µg/d. Median (IQR) RBP4 concentration was 1.51 (0.78) µmol/L. Insufficient vitA and VAD prevalence was 12.2% and 1.2%, respectively. VitA intake was positively associated with RBP4 (β=0.068; 95%CI: 0.020, 0.116; p=0.006). RBP4 was positively associated with Hb (β=0.363; 95%CI: 0.186, 0.539; p <0.001) and ferritin (β=0.359; 95%CI: 0.139, 0.579; p=0.001) but negatively with sTfR (β=-0.125; 95%CI: -0.246, -0.005, p=0.041). No significant association between plasma RBP4 and birth weight, as well as preterm birth was observed. There was a low prevalence of VAD in the study population. Nonetheless, the positive association between RBP4 and Hb, and ferritin highlights the importance of optimal vitA status in preventing maternal anaemia in pregnancy.

Retinol binding protein (RBP) is used as a proxy for retinol in population-based assessments of vitamin A deficiency (VAD) for cost-effectiveness and feasibility. When the cut-off of < 0·7 μmol/l for retinol is applied to RBP to define VAD, an equivalence of the two biomarkers is assumed. Evidence suggests that the relationship between retinol and RBP is not 1:1, particularly in populations with a high burden of infection or inflammation. The goal of this analysis was to longitudinally evaluate the retinol:RBP ratio over 1 month of follow-up among fifty-two individuals exposed to norovirus (n 26 infected, n 26 uninfected), test whether inflammation (measured as α-1-acid glycoprotein (AGP) and C-reactive protein (CRP)) affects retinol, RBP and the ratio between the two and assess whether adjusting vitamin A biomarkers for AGP or CRP improves the equivalence of retinol and RBP. We found that the median molar ratio between retinol and RBP was the same among infected (0·68) and uninfected (0·68) individuals. AGP was associated with the ratio and RBP individually, controlling for CRP, and CRP was associated with both retinol and RBP individually, controlling for AGP over 1 month of follow-up. Adjusting for inflammation led to a slight increase in the ratio among infected individuals (0·71) but remained significantly different from the expected value of one. These findings highlight the need for updated recommendations from the WHO on a cut-off value for RBP and an appropriate method for measuring and adjusting for inflammation when using RBP in population assessments of VAD.

Inflammation and infections such as malaria affect estimates of micronutrient status. Medline, Embase, Web of Science, Scopus and the Cochrane library were searched to identify studies reporting mean concentrations of ferritin, hepcidin, retinol or retinol binding protein in individuals with asymptomatic or clinical malaria and healthy controls. Study quality was assessed using the US National Institute of Health tool. Random effects meta-analyses were used to generate summary mean differences. In total, forty-four studies were included. Mean ferritin concentrations were elevated by: 28·2 µg/l (95 % CI 15·6, 40·9) in children with asymptomatic malaria; 28·5 µg/l (95 % CI 8·1, 48·8) in adults with asymptomatic malaria; and 366 µg/l (95 % CI 162, 570) in children with clinical malaria compared with individuals without malaria infection. Mean hepcidin concentrations were elevated by 1·52 nmol/l (95 % CI 0·92, 2·11) in children with asymptomatic malaria. Mean retinol concentrations were reduced by: 0·11 µmol/l (95 % CI −0·22, −0·01) in children with asymptomatic malaria; 0·43 µmol/l (95 % CI −0·71, −0·16) in children with clinical malaria and 0·73 µmol/l (95 % CI −1·11, −0·36) in adults with clinical malaria. Most of these results were stable in sensitivity analyses. In children with clinical malaria and pregnant women, difference in ferritin concentrations were greater in areas with higher transmission intensity. We conclude that biomarkers of iron and vitamin A status should be statistically adjusted for malaria and the severity of infection. Several studies analysing asymptomatic infections reported elevated ferritin concentrations without noticeable elevation of inflammation markers, indicating a need to adjust for malaria status in addition to inflammation adjustments.

This study aimed to document the method standardisation and assessment of micronutrient and inflammatory markers in women from indigenous tribal communities of Jharkhand using a low-volume, high-throughput assay. This cross-sectional study was done among women of the reproductive age group from Sauria Paharia and Santhal tribal households (HH) in selected villages. Capillary blood samples were collected from the women during a HH survey to estimate ferritin, soluble transferrin receptor, retinol binding protein 4 and inflammatory biomarkers, C-reactive protein (CRP) and α-1-acid glycoprotein (AGP) using a multiplex assay. Vitamin D and Hb were estimated using an LC-MS technique and cyanmethaemoglobin method, respectively. A multiplex Luminex-based method was developed and standardised. The assay was used to estimate biomarkers in samples from 413 women (178 and 235 from Sauria Paharia and Santhal tribes, respectively). Over 51 % of women had raised CRP or AGP levels. Fe status was significantly better in Sauria Paharia compared with the Santhal women. Anaemia prevalence was 72 % among Santhal women. The proportion of women with Fe deficiency increased after adjusting for inflammation. The overall prevalence of vitamin A deficiency and insufficiency was 25 and 34 %, respectively, with similar prevalence in both tribes. All Santhal women had sufficient vitamin D levels, while 25 and 20 % of Sauria Paharia women had insufficient and deficient vitamin D levels, respectively. Our low-volume, high-throughput multiplex assays may provide a feasible approach for assessing nutritional biomarkers in nutritionally vulnerable hard-to-reach communities.

Vitamin A is an essential micronutrient for life and the phytochemical β-carotene, also known as pro-vitamin A, is an important dietary source of this vitamin. Vitamin A (retinol) is the parent compound of all bioactive retinoids but it is retinoic acid (RA) that is the active metabolite of vitamin A. The plasma concentration of retinol is maintained in a narrow range and its normal biological activities strictly regulated since excessive intake can lead to toxicity and thus also be detrimental to life. The present review will give an overview of how vitamin A homeostasis is maintained and move on to focus on the link between circulating vitamin A and metabolic disease states. Finally, we will examine how pharmacological or genetic alterations in vitamin A homeostasis and RA-signalling can influence body fat and blood glucose levels including a novel link to the liver secreted hormone fibroblast growth factor 21, an important metabolic regulator.

Vitamin A, retinol, circulates in blood bound to retinol-binding protein (RBP4) which, in turn, associates with another serum protein, transthyretin (TTR), to form a ternary retinol-RBP4-TTR complex. At some tissues, retinol-bound (holo-) RBP4 is recognised by a receptor termed stimulated by retinoic acid 6 (STRA6) which transports retinol into cells. This mini-review summarises evidence demonstrating that, in addition to functioning as a retinol transporter, STRA6 is also a signalling receptor which is activated by holo-RBP4. The data show that STRA6-mediated retinol transport induces receptor phosphorylation, in turn activating a Janus kinases2/signal transducers and activators of transcription (STAT)3/5 cascade that culminates in induction of STAT target genes. STRA6-mediated retinol transport and cell signalling are inter-dependent, and both functions critically rely on intracellular retinol trafficking and metabolism. Hence, STRA6 couples ‘sensing’ of vitamin A homeostasis and metabolism to cell signalling, allowing it to control important biological functions. For example, by inducing the expression of the STAT target gene suppressor of cytokine signalling 3, STRA6 potently suppresses insulin responses. These observations provide a rationale for understanding the reports that elevation in serum levels of RBP4, often observed in obese mice and human subjects, causes insulin resistance. The observations indicate that the holo-RBP4 /STRA6 signalling cascade may comprise an important link through which obesity leads to insulin resistance and suggest that the pathway may be a novel target for treatment of metabolic diseases.

Using the INRA – University of Minnesota porcine 7000 Rad Radiation Hybrid panel (IMpRH) containing 118 clones, porcine cellular retinol binding protein gene 1 (RBP1) and plasma retinol binding protein gene 4 (RBP4) were assigned to porcine chromosomes 13 and 14, respectively. The mRNA distributions of the two genes in adult Wuzhishan pig tissues (lung, skeletal muscle, spleen, heart, stomach, large intestine, lymph node, small intestine, liver, brain, kidney and fat) were examined. One single nucleotide polymorphism (SNP) was identified in Laiwu, Wuzhishan, Guizhou, Bama pig breeds and a Tongcheng experimental population and analysed using a polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) method. Significant associations were found between different genotypes of A/G156 and maximum carcass length (LM), minimum carcass length (LN), haemoglobin (HGB), mean corpuscular volume haemoglobin (MCH), and day to slaughter weight (age) traits in the Tongcheng experimental population. This SNP locus might be used as a genetic marker in pig breeding and production.