Advancing towards practice: A novel LC-MS/MS method for detecting retinol in dried blood spots.

BACKGROUND: To date, clinical laboratories face challenges in quantifying retinol from DBS samples. Disputes arise throughout the whole detection process, encompassing the storage condition, the release strategy as well as the selection of internal standards. METHODS: We incubated DBS with ascorbic acid solution. Then, retinol-d4 in acetonitrile was introduced to incorporate isotopic internal standard and promote protein precipitation. Afterward, sodium carbonate solution was added to ionize cytochromes (such as bilirubin), which amplified the difference of their hydrophobicity to retinol. Subsequently, cold-induced phase separation could be facilitated to separate retinol from the impurities. In the end, the upper layer was injected for LC-MS/MS analysis. RESULTS: By comparing the detected retinol content in whole blood and DBS samples prepared from the same volume, we confirmed the established pretreatment was capable to extract most of retinol from DBS (recovery >90 %). Thereafter, we verified that within DBS, retinol possessed satisfying stability without antioxidation. Indoor-light exposure and storage duration would not cause obvious degradation (<10 %). Following systematic validation, the established method well met the criteria outlined in the relevant guidelines. After comparing with detected DBS results to the paired plasma samples, 54 out of 60 met the acceptance limit for cross-validation of ±20 %. CONCLUSIONS: We realized precise quantification of retinol from one 3.2 mm DBS disc. By circumventing conventional antioxidation, liquid-liquid/solid-phase extraction and organic solvent evaporation, the pretreatment could be completed within 15 min consuming only minimal amounts of low-toxicity chemicals (ascorbic acid, acetonitrile, and sodium carbonate). We expect this contribution holds the potential to significantly facilitate the evaluation of patients' vitamin A status by using DBS samples in the future.

Xeropthalmia and optic neuropathy secondary to ARFID: a case report.

BACKGROUND: Patients with avoidant/restrictive food intake disorder (ARFID) commonly present with loss of weight or faltering growth in the setting of poor nutrition. However, patients with ARFID can present with micronutrient deficiencies without weight loss. In patients with ARFID, clinicians should be vigilant for micronutrient deficiencies and their presentations. CASE PRESENTATION: We report a unique case of ARFID in a twelve-year-old girl, who developed micronutrient deficiencies and presented with acute visual loss with a preceding history of impaired night vision. Ophthalmic examination revealed xerophthalmia and bilateral optic neuropathy. Investigations showed severe Vitamin A and folate deficiencies which accounted for her clinical findings. In addition, she was also found to have low Vitamin B12, copper, and Vitamin D levels. She had a history of selective eating from a young age with a diet consisting largely of carbohydrates, with no regular intake of meat, dairy, fruit and vegetables. This was not driven by weight or body image concerns. The patient's symptoms improved significantly with appropriate vitamin replacement and continued multidisciplinary care. CONCLUSIONS: This report describes a patient with ARFID presenting with visual complaints. In this case, the selective eating behaviours resulted in xeropthalmia and optic neuropathy. Micronutrient deficiencies are uncommon in developed countries. When these deficiencies are suspected, eating disorders, such as ARFID, should be considered. Similarly, clinicians caring for patients with restrictive eating disorders including ARFID should be familiar with the clinical presentations of various micronutrient deficiencies and consider evaluation and treatment for micronutrient deficiencies when clinically indicated.

Therapeutic effects of olfactory training and systemic vitamin A in patients with COVID-19-related olfactory dysfunction: a double-blinded randomized controlled clinical trial.

OBJECTIVES: The new corona virus infection, has a wide range of clinical manifestations. Fever and cough are the most common symptoms. The olfactory function may be also affected with COVID-19. In this randomized clinical trial, we wanted to evaluate the therapeutic effect of olfactory training with and without oral vitamin A for COVID-19-related olfactory dysfunction. METHODS: Patients answered to the standard Persian version of anosmia reporting tool and performed the quick smell test before and after 12 weeks and at the end of the 12 months follow up. The patients were randomly allocated to three groups; Group A treatment with olfactory training, Group B treatment with oral vitamin A and olfactory training, and Group C as control group which only underwent nasal irrigation twice a day. Patients were treated for 3 months and followed up for 12 months. RESULTS: Totally 90 patients were included in three groups. After interventions, 76.9% of patients in Group A, 86.7% of patients in Group B, and 26.7% of patients in Group C completely improved. The average intervention time was statistically significant in relationship with the final olfactory status of the patients in the 12 months follow-up. The olfactory training has significantly improved the smell alteration at the end of 3- and 12- months follow-up in A and B groups. CONCLUSION: A three-months olfactory training is effective for improvement of COVID-19-related olfactory dysfunction. Adding daily oral vitamin A to olfactory training did not lead to better results in improving olfactory dysfunction. LEVEL OF EVIDENCE: Step 2 (Level 2*): Randomized trial.

Establishment of Reference Range for Serum Concentration of Vitamin A and Vitamin E in Southern Sichuan Area of China.

OBJECTIVE: To establish the reference range of serum concentration of vitamin A (VA) and vitamin E (VE) in Southern Sichuan area of China. METHODS: From August 1, 2021, to May 31, 2023, 9482 blood tablets were received for the screening of VA and VE. The information was divided into four different age groups: ≤1 year old, 1< to ≤6 years, 6< to ≤17 years, and 17< to ≤59 years. In each age group, the four seasons were further subdivided into spring, summer, autumn, and winter, as well as male and female genders. The serum concentration of VA and VE was detected by liquid chromatography-tandem mass spectrometry (HPLC-MS), and the reference range was established for verification. RESULTS: The concentration of VA and VE in 9482 cases showed skewed distribution. When comparing between different age groups, the serum concentration of VA and VE was statistically significant (p < 0.05). While comparing different seasons, the serum VA levels in different seasons were significantly different (p < 0.05) except in summer and autumn. There was statistical significance in VE level in different seasons (p < 0.05). And while comparing different genders, there was no statistical significance in VA concentration levels (p > 0.05). The VE concentration levels were statistically significant (p < 0.05). The established reference range was established and verified, and the results were in accordance with the standard. CONCLUSION: The reference range of VA and VE should be set according to different ages, different seasons, and different genders.

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.

Defining a vitamin A5/X specific deficiency - vitamin A5/X as a critical dietary factor for mental health.

A healthy and balanced diet is an important factor to assure a good functioning of the central and peripheral nervous system. Retinoid X receptor (RXR)-mediated signaling was identified as an important mechanism of transmitting major diet-dependent physiological and nutritional signaling such as the control of myelination and dopamine signalling. Recently, vitamin A5/X, mainly present in vegetables as provitamin A5/X, was identified as a new concept of a vitamin which functions as the nutritional precursor for enabling RXR-mediated signaling. The active form of vitamin A5/X, 9-cis-13,14-dehydroretinoic acid (9CDHRA), induces RXR-activation, thereby acting as the central switch for enabling various heterodimer-RXR-signaling cascades involving various partner heterodimers like the fatty acid and eicosanoid receptors/peroxisome proliferator-activated receptors (PPARs), the cholesterol receptors/liver X receptors (LXRs), the vitamin D receptor (VDR), and the vitamin A(1) receptors/retinoic acid receptors (RARs). Thus, nutritional supply of vitamin A5/X might be a general nutritional-dependent switch for enabling this large cascade of hormonal signaling pathways and thus appears important to guarantee an overall organism homeostasis. RXR-mediated signaling was shown to be dependent on vitamin A5/X with direct effects for beneficial physiological and neuro-protective functions mediated systemically or directly in the brain. In summary, through control of dopamine signaling, amyloid ß-clearance, neuro-protection and neuro-inflammation, the vitamin A5/X - RXR - RAR - vitamin A(1)-signaling might be "one of" or even "the" critical factor(s) necessary for good mental health, healthy brain aging, as well as for preventing drug addiction and prevention of a large array of nervous system diseases. Likewise, vitamin A5/X - RXR - non-RAR-dependent signaling relevant for myelination/re-myelination and phagocytosis/brain cleanup will contribute to such regulations too. In this review we discuss the basic scientific background, logical connections and nutritional/pharmacological expert recommendations for the nervous system especially considering the ageing brain.

Efficacy and inflammatory levels (IL-6, IL-10) of adjuvant application of vitamin-A in the treatment of pediatric Mycoplasma pneumoniae pneumonia: a systematic review and meta-analysis.

Objective: The purpose of this study is to evaluate the efficacy of Vitamin A (VitA) as an adjuvant therapy for pediatric Mycoplasma Pneumoniae Pneumonia (MPP) through meta-analysis, and to investigate its impact on inflammation levels (IL-6, IL-10), in order to explore the role of VitA in pediatric MPP. Methods: Using a systematic literature search method, relevant research literature is searched, and RCT studies that meet the requirements are selected based on preset inclusion and exclusion criteria. Then, a quality evaluation was conducted on the included literature, and meta-analysis was used to calculate the combined effect values of mortality rate, hospital stay, lung rale disappearance time, cough duration, fever duration, IL-6 and IL-10 levels, and heterogeneity analysis was conducted. The levels of IL-6 and IL-10 represent the inflammatory levels in pediatric MPP patients, and exploring their changes has significant implications for the anti-inflammatory effect of treatment. Results: A total of 10 RCT studies were included, with a total sample size of 1,485, including 750 cases in the control group and 735 cases in the observation group. The meta-analysis results of this study showed that there was a significant difference in the total clinical efficacy of using VitA adjuvant therapy compared to the control group without VitA [OR = 3.07, 95%CI = (2.81, 4.27)], P < 0.05. However, there was no significant difference in the adverse reaction rate between the use of VitA as an adjuvant therapy and the control without VitA [OR = 1.17, 95%CI = (0.61, 2.27)], P > 0.05. At the same time, the hospitalization time [MSD = -0.86, 95% CI = (-1.61, -0.21)], lung rale disappearance time [MSD = -0.78, 95%CI = (-1.19,-0.51)], cough duration [MSD = -1.07, 95%CI = (-1.41, -0.71)], and fever duration [MSD = -0.47, 95%CI = (-0.72, -0.23)] using VitA as an adjuvant treatment were obviously lower. In addition, the meta-analysis outcomes also showed that the use of VitA adjuvant therapy can significantly reduce IL-6 [MSD = -1.07, 95%CI = (-1.81, -0.27)] and IL-10 [MSD = -0.13, 95%CI = (-0.31, 0.12)] levels. This indicates that the application of VitA in pediatric MPP also has the effect of reducing inflammatory response. Conclusion: Based on the meta-analysis results, VitA adjuvant therapy can significantly improve the clinical symptoms of pediatric MPP patients, shorten hospitalization time, promote the disappearance of lung rales, and alleviate cough and fever symptoms. In addition, VitA adjuvant therapy can effectively reduce inflammation levels, indicating its potential role in inhibiting inflammatory responses. In clinical practice, VitA adjuvant therapy for pediatric MPP can be promoted as a potential treatment option.

Vitamin A deficiency retinopathy in the setting of celiac disease and liver fibrosis.

PURPOSE: Vitamin A is a lipid-soluble compound that is critical in maintaining phototransduction. Ocular manifestations of hypovitaminosis A may present with anterior segment signs of xeropthalmia, with advanced cases also causing classic retinal and electrophysiologic changes of vitamin A deficiency retinopathy. We present a case of vitamin A deficiency retinopathy, with corresponding retinal imaging and electrophysiology, in an adult patient with celiac disease and liver fibrosis. METHODS: A single case report was conducted in Toronto, Canada. RESULTS: A 77-year-old male with known celiac disease and liver fibrosis presented progressively worsening vision noticed primarily when driving. Vision was 20/50 OD and 20/200 OS. Bitot spots were noted on anterior segment examination. Fundus photography demonstrated bilateral peripheral macular hypopigmentation and far-peripheral granular retinal hypopigmentation with focal yellow dots and hyper-pigmented deposits. Optical coherence tomography (OCT) imaging demonstrated indistinct outer retinal banding with mild outer nuclear layer thinning, focal hyper-reflective deposits, and a thin choroid bilaterally. Full-field electroretinography (ERG) testing demonstrated reduced rod-isolated and combined rod-cone response amplitudes, and multifocal ERG testing demonstrated blunted individual responses throughout the field. The patient was treated with pulse vitamin A therapy. After 6 months of therapy, ERG responses were back within reference range, and the outer retinal changes reversed; visual acuity improved to 20/30 OD and 20/40 OS. CONCLUSION: This case represents the classic findings of vitamin A deficiency retinopathy on fundus examination and electrophysiologic testing secondary to gastrointestinal pathology. Prompt treatment of high dose vitamin A supplementation led to improvement of full-field and multifocal ERG results, as well as reconstitution of outer retinal architecture.

Association between Dietary Total Vitamin A, ß-carotene, and Retinol Intake and Risk of cardiometabolic multimorbidity: Results from the China Health and Nutrition Survey, 1997-2015.

Background: The association between vitamin A and single cardiometabolic diseases has been extensively studied, but the relationship between dietary vitamin A intake and the risk of cardiometabolic multimorbidity (CMM) has not been studied. Therefore, the present study was conducted to explore the association with CMM risk by analyzing different sources of vitamin A. Methods: This study utilized 13,603 subjects aged ≥ 18 years from 1997-2015 from the China Health and Nutrition Survey (CHNS). Dietary intake was calculated from 3 consecutive 24-h dietary recalls combined with a house hold food inventory. CMM is defined as the development of at least two cardiometabolic diseases. Results: After a median follow-up of 9.1 years, there were 1050 new cases of CMM. The risk of CMM was significantly lower in those with higher vitamin A intake (Q1 vs Q5 HR 0.66, 95% CI 0.54-0.81). ß-carotene (Q1 vs Q5 HR 0.82, 95% CI 0.66-1.02) and retinol (Q1 vs Q5 HR 0.59, 95%CI 0.48-0.73) intake had a similarly negative correlation. Using restricted cubic spline found an L-shaped relationship between retinol intake and CMM (p non-linear < 0.001). In subgroup analyses, protective effects were stronger for participants aged ≥ 44 years (HR 0.72, 95%CI 0.57-0.92) and for the female group (HR 0.62, 95%CI 0.45-0.84). Conclusion: Dietary vitamin A was a protective factor for CMM, and this effect was stronger in age ≥ 44 years and in the female group. There was a ceiling effect on the protective effect of retinol intake on the risk of CMM.

Association of Vitamin A and D Deficiencies with Infectious Outcomes in Children Undergoing Intensive Induction Therapy for Acute Lymphoblastic Leukemia.

OBJECTIVE: To evaluate the association between deficiency of vitamin A or D at diagnosis of pediatric acute lymphoblastic leukemia (ALL) and subsequent infectious complications during induction therapy. STUDY DESIGN: An IRB-approved, retrospective cohort study of children diagnosed with newly-diagnosed ALL from 2007 to 2017 at St. Jude Children's Research Hospital. We measured vitamin D, vitamin D binding protein, retinol binding protein as a surrogate for vitamin A, and immunoglobulin isotypes in serum obtained at ALL diagnosis, and we assessed the association between vitamin deficiencies or levels and infection-related complications during the 6-week induction phase using Cox regression models. RESULTS: Among 378 evaluable participants, vitamin A and D deficiencies were common (43% and 17% respectively). Vitamin D deficiency was associated with higher risks of febrile neutropenia (adjusted hazard ratio [aHR] 1.7; p=0.0072), clinically-documented infection (aHR 1.73; p=0.025), and likely bacterial infection (aHR 1.86; p=0.008). Conversely, vitamin A deficiency was associated solely with a reduced risk of sepsis (aHR 0.19; p=0.027). CONCLUSIONS: In this retrospective study, vitamin D deficiency was associated with an increased risk of common infection-related complications during induction therapy for ALL. Additional studies are warranted to evaluate whether vitamin D supplementation could mitigate this effect.

Prevalence of micronutrient deficiencies across diverse environments in rural Madagascar.

It is estimated that billions of people around the world are affected by micronutrient deficiencies. Madagascar is considered to be particularly nutritionally vulnerable, with nearly half of the population stunted, and parts of the country facing emergency, near famine-like conditions (IPC4). Although Madagascar is generally considered among the most undernourished of countries, empirical data in the form of biological samples to validate these claims are extremely limited. Our research drew data from three studies conducted between 2013-2020 and provided comprehensive biomarker profile information for 4,710 individuals from 30 communities in five different ecological regions during at least one time-point. Estimated prevalences of nutrient deficiencies and inflammation across various regions of rural Madagascar were of concern for both sexes and across all ages, with 66.5% of the population estimated to be deficient in zinc, 15.6% depleted in vitamin B12 (3.6% deficient), 11.6% deficient in retinol, and lower levels of iron deficiency (as indicated by 11.7% deficient in ferritin and 2.3% deficient assessed by soluble transferrin receptors). Beyond nutrient status biomarkers, nearly one quarter of the population (24.0%) exhibited chronic inflammation based on high values of α-1-acid glycoprotein, and 12.3% exhibited acute inflammation based on high values of C-reactive protein. There is an 8-fold difference between the lowest and highest regional observed prevalence of vitamin B12 deficiency, a 10-fold difference in vitamin A deficiency (based on retinol), and a 2-fold difference in acute inflammation (CRP) and deficiencies of zinc and iron (based on ferritin), highlighting strong geographical variations in micronutrient deficiencies across Madagascar.

Scientific opinion on the tolerable upper intake level for preformed vitamin A and ß-carotene.

Following two requests from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the revision of the tolerable upper intake level (UL) for preformed vitamin A and ß-carotene. Systematic reviews of the literature were conducted for priority adverse health effects of excess vitamin A intake, namely teratogenicity, hepatotoxicity and endpoints related to bone health. Available data did not allow to address whether ß-carotene could potentiate preformed vitamin A toxicity. Teratogenicity was selected as the critical effect on which to base the UL for preformed vitamin A. The Panel proposes to retain the UL for preformed vitamin A of 3000 µg RE/day for adults. This UL applies to men and women, including women of child-bearing age, pregnant and lactating women and post-menopausal women. This value was scaled down to other population groups using allometric scaling (body weight0.75), leading to ULs between 600 µg RE/day (infants 4-11 months) and 2600 µg RE/day (adolescents 15-17 years). Based on available intake data, European populations are unlikely to exceed the UL for preformed vitamin A if consumption of liver, offal and products thereof is limited to once per month or less. Women who are planning to become pregnant or who are pregnant are advised not to consume liver products. Lung cancer risk was selected as the critical effect of excess supplemental ß-carotene. The available data were not sufficient and suitable to characterise a dose-response relationship and identify a reference point; therefore, no UL could be established. There is no indication that ß-carotene intake from the background diet is associated with adverse health effects. Smokers should avoid consuming food supplements containing ß-carotene. The use of supplemental ß-carotene by the general population should be limited to the purpose of meeting vitamin A requirements.

Role of Antioxidant Vitamins in Oral Submucous Fibrosis: A Narrative Review.

Oral submucous fibrosis (OSMF) has a high rate of malignant transformation and is an insidious chronic inflammatory disease. Though this disorder seems to be multifactorial in origin, betel quid chewing appears to be the main etiologic factor. Various treatment strategies have been attempted but none proven to cure the disorder because of its multimodal pathogenesis. Reactive oxygen species (ROS) appear to have a role in cancer formation. As OSMF is an oral premalignant disorder and found to be associated with carcinogens like areca nut and tobacco, it is believed to have some relationship with ROS. Tissue damage due to ROS along with other mechanisms may result in the complex pathophysiology of OSMF. The antioxidant system in the body helps to prevent damage caused by highly reactive ROS and helps in the repair of tissues. To study the levels of oxidative stress and antioxidant vitamins in OSMF condition, the present review was done. We carried out a thorough literature search to identify original reports and studies determining the status of oxidative stress and antioxidant vitamins in OSMF condition using several databases including Google Scholar, PubMed, and Scopus. Our review observed that the oxidative stress increased in the condition of OSMF as shown by an increase in malonaldehyde (MDA) and a decrease in antioxidant vitamins like vitamin A, vitamin C, and vitamin E. Also, after the intake of antioxidant vitamins, there was symptomatic improvement in OSMF patients. With the help of identifying oxidative stress and antioxidant status, we can assess the clinical stage of OSMF and can develop a comprehensive treatment plan.

Vitamin A deficiency in the MENA region: a 30-year analysis (1990-2019).

Background: Vitamin A deficiency (VAD) is a common micronutrient deficiency that imposes a substantial burden worldwide. This study examined the burden of VAD from 1990 to 2019 in the Middle East and North Africa (MENA) region by age, sex and sociodemographic index (SDI). Methods: The data were obtained from the Global Burden of Disease (GBD) 2019 database. We reported the prevalence, incidence, and years lived with disability (YLDs) that were attributable to VAD for the MENA region, along with its constituent countries. Results: In 2019, the MENA region had 30.6 million prevalent cases of VAD, with an age-standardized prevalence rate of 5249.9 per 100,000 population. In addition, VAD was responsible for 62.2 thousand YLDs, with an age-standardized YLD rate of 10.2 per 100,000. The age-standardized prevalence [50.3% (-55.9 to -44.7)] and YLD [-49.3% (-55.3 to -43.1)] rates of VAD have significantly decreased since 1990. In 2019, the MENA region's VAD-attributable YLD rate was below the global average for males and females across all age groups. Additionally, SDI was negatively associated the age-standardized YLD rate of VAD. Conclusion: This study underscores the necessity of frequently updating health data and developing guidelines and regulations to prevent, detect early, and effectively treat VAD in the MENA countries.

Vitamin A-related nutrition knowledge gaps and predictors among caregivers of preschool children in Eastern Uganda: a cross-sectional study.

BACKGROUND: Vitamin A (VA) remains a core micronutrient as VA Deficiency (VAD) in children has persisted as a public health problem in parts of Africa with adverse effects. Caregivers of children are essential in the control of VAD; however, there is a paucity of data on their knowledge of VA, dietary sources, and VAD. This study sought to assess the level of VA-related nutrition knowledge (VANK) and its predictors among caregivers of preschool children in Eastern Uganda. METHODS: A cross-sectional analytical design was used. Both socio-demographic and knowledge and attitude (KA) data were collected using a structured questionnaire partly adapted from the FAO model Knowledge, Attitude and Practice (KAP) questionnaire. A sample size of 256 was used. Caregivers of 24-59 months-old children were selected from Bukwo District in Eastern Uganda using purposive and random sampling methods. Knowledge scores (%) based on responses to ten questions were determined and eventually classified as low (≤ 40%) and moderate or high (˃40%). Descriptive and inferential statistics were computed using SPSS (version 24). Logistic regression was used to identify predictors with p < 0.05 considered significant. RESULTS: The study had 247 caregivers with a mean age of 30.9 ± 7.7 years. The majority were female (90%), married, subsistence crop farmers and had primary-level education or lower. The mean VANK score was 18.9 ± 24.7%. Overall, most of the caregivers had low VANK as only about 20% had moderate or high. The proportions that knew the different aspects of VANK were correspondingly small. About half of the caregivers (46.6%) knew VA itself and only 27% knew any of its sources. Those who knew VAD, its causes, signs/symptoms and prevention measures were 31, 22, 13 and 24% respectively. The caregivers' VANK was significantly associated with their overall VA-related attitude, age and level of education. However, education and age were the significant predictors. CONCLUSION: Caregivers had very low VANK. They barely knew VA and its food sources or VAD. The main predictors of VANK were caregiver age and level of education. The study recommends education of caregivers about VA for effective VAD control which contributes to achievement of the Sustainable Development Goal (SDG) 2.

No Evidence of an Association between Genetic Factors Affecting Response to Vitamin A Supplementation and Myopia: A Mendelian Randomization Study and Meta-Analysis.

The relationship between vitamin A supplementation and myopia has been a topic of debate, with conflicting and inconclusive findings. We aimed to determine whether there is a causal relationship between vitamin A supplementation and the risk of myopia using Mendelian randomization (MR) and meta-analytical methods. Genetic variants from the UK Biobank and FinnGen studies associated with the response to vitamin A supplementation were employed as instrumental variables to evaluate the causal relationship between vitamin A supplementation and myopia. Fixed-effects meta-analysis was then used to combine MR estimates from multiple sources for each outcome. The meta-analysis of MR results found no convincing evidence to support a direct causal relationship between vitamin A supplementation and myopia risk (odds ratio (OR) = 0.99, 95% confidence interval (CI) = 0.82-1.20, I2 = 0%, p = 0.40). The analysis of three out of the four sets of MR analyses indicated no direction of causal effect, whereas the other set of results suggested that higher vitamin A supplementation was associated with a lower risk of myopia (OR = 0.002, 95% CI 1.17 × 10-6-3.099, p = 0.096). This comprehensive MR study and meta-analysis did not find valid evidence of a direct association between vitamin A supplementation and myopia. Vitamin A supplementation may not have an independent effect on myopia, but intraocular processes associated with vitamin A may indirectly contribute to its development.

Calculation of reference intervals for the concentrations of α-tocopherol and retinol in serum using indirect data-mining procedures.

BACKGROUND: Establishing adequate reference intervals (RIs) for vitamins A and E is essential for diagnosing and preventing deficiencies. Due to the current boom in data mining and its easy applicability, more laboratories are establishing RIs using indirect methods. Our study aims to obtain RIs using four indirect data-mining procedures (Bhattacharya, Hoffmann, Kosmic, and RefineR) for vitamins A and E. MATERIAL AND METHODS: 8943 individuals were collected to establish the RIs. After using different data cleaning steps and checking whether these data should be divided according to age and gender based on multiple linear regression and variance component analyses, indirect RIs were calculated using specific Excel spreadsheets or R-packages software. RESULTS: A total of 2004 records were eligible. For vitamin A, the RIs obtained were (1.11 - 2.68) µmol/L, (1.13 - 2.70) µmol/L, (1.13 - 2.71) µmol/L, and (1.17 - 2.66) µmol/L using the Bhattacharya, Hoffmann, Kosmic and RefineR approaches, respectively. For vitamin E, these intervals were (17.3 - 49.9) µmol/L (Bhattacharya), (17.3 - 48.9) µmol/L (Hoffmann), (19.6 - 50.3) µmol/L (Kosmic), and (19.4 - 50.9) µmol/L (RefineR). In all cases, the RIs were comparable. CONCLUSIONS: Suitable RIs for vitamins A and E were calculated using four indirect methods that are suitable and adapted to our population's demographic characteristics.

Early Life Programming of Adipose Tissue Remodeling and Browning Capacity by Micronutrients and Bioactive Compounds as a Potential Anti-Obesity Strategy.

The early stages of life, especially the period from conception to two years, are crucial for shaping metabolic health and the risk of obesity in adulthood. Adipose tissue (AT) plays a crucial role in regulating energy homeostasis and metabolism, and brown AT (BAT) and the browning of white AT (WAT) are promising targets for combating weight gain. Nutritional factors during prenatal and early postnatal stages can influence the development of AT, affecting the likelihood of obesity later on. This narrative review focuses on the nutritional programming of AT features. Research conducted across various animal models with diverse interventions has provided insights into the effects of specific compounds on AT development and function, influencing the development of crucial structures and neuroendocrine circuits responsible for energy balance. The hormone leptin has been identified as an essential nutrient during lactation for healthy metabolic programming against obesity development in adults. Studies have also highlighted that maternal supplementation with polyunsaturated fatty acids (PUFAs), vitamin A, nicotinamide riboside, and polyphenols during pregnancy and lactation, as well as offspring supplementation with myo-inositol, vitamin A, nicotinamide riboside, and resveratrol during the suckling period, can impact AT features and long-term health outcomes and help understand predisposition to obesity later in life.

Retinoic acid signalling inhibits myogenesis by blocking MYOD translation in pig skeletal muscle cells.

Vitamin A is an essential nutrient in animals, playing important roles in animal health. In the pig industry, proper supplementation of vitamin A in the feed can improve pork production performance, while deficiency or excessive intake can lead to growth retardation or disease. However, the specific molecular mechanisms through which vitamin A operates on pig skeletal muscle growth as well as muscle stem cell function remain unexplored. Therefore, in this study, we isolated the pig primary skeletal muscle stem cells (pMuSCs) and treated with retinoic acid (RA), the natural metabolite of vitamin A, and then examined the myogenic capacity of pMuSCs via immunostaining, real-time PCR, CCK8 and western-blot analysis. Unexpectedly, the RA caused a significant decrease in the proliferation and differentiation of pMuSCs. Mechanistically, the RA addition induced the activation of retinoic acid receptor gamma (RARγ), which inhibited the myogenesis through the blockage of protein translation of the master myogenic regulator myogenic differentiation 1 gene (MYOD). Specifically, RARγ inactivate AKT kinase (AKT) signalling and lead to dephosphorylation of eukaryotic translation initiation factor 4E binding protein 1 (eIF4EBP1), which in turn repress the eukaryotic translation initiation factor 4E (eIF4E) complex and block mRNA translation of MYOD. Inhibition of AKT could rescue the myogenic defects of RA-treated pMuSCs. Our findings revealed that retinoid acid signalling inhibits the skeletal muscle stem cell proliferation and differentiation in pigs. Therefore, the vitamin A supplement in the feedstuff should be cautiously optimized to avoid the potential adverse consequences on muscle development associated with the excessive levels of retinoic acid.

Controlled release of vitamin A palmitate from crosslinked cyclodextrin organic framework for dry eye disease therapy.

Controlled release drug delivery systems of eye drops are a promising ophthalmic therapy with advantages of good patient compliance and low irritation. However, the lack of a suitable drug carrier for ophthalmic use limits the development of the aforementioned system. Herein, the crosslinked cyclodextrin organic framework (COF) with a cubic porous structure and a uniform particle size was synthesized and applied to solidify vitamin A palmitate (VAP) by using the solvent-free method. The VAP@COF suspension eye drops were formulated by screening co-solvents, suspending agents, and stabilizing agents to achieve a homogeneous state and improve stability. According to the in vitro release study, the VAP@COF suspension exhibited a controlled release of VAP within 12 h. Both the ex vivo corneal contact angle and in vivo fluorescence tracking indicated that the VAP@COF suspension prolonged the VAP residence time on the ocular surface. This suspension accelerated the recovery of the dry eye disease (DED) model in New Zealand rabbits. Furthermore, the suspension was non-cytotoxic to human corneal epithelial cells and non-irritation to rabbit eyes. In summary, the particulate COF is an eye-acceptable novel carrier that sustains release and prolongs the VAP residence time on the ocular surface for DED treatment.