Evaluating a novel method for vitamin A analysis in an observational study of the UAE's obese population.

Vitamin A plays a critical role in various biological functions, including vision, cellular differentiation, and immune regulation. However, accurately assessing its status, particularly in obese individuals, presents challenges due to potential alterations in metabolism and distribution. This study utilized Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) methodology to precisely measure serum vitamin A concentrations in population of UAE. The methodology's reliability and precision, as demonstrated through validation procedures, underscore its potential utility in clinical settings. Employing the Multiple Reaction Monitoring mode of positive ion electrospray ionization, the LC-MS/MS system achieves a limit of detection (LOD) of 0.48 ng/mL in serum, while adhering to FDA-US regulations for accuracy and compliance. A key aspect of this study was the application of LC-MS/MS to assess vitamin A status in an obese population within UAE. By employing a diverse cohort of 452 Emirati participants, including 277 individuals from a randomized controlled trial who were assessed at baseline and at 6th month, and 175 healthy individuals aged 18-82 assessed at baseline, this study explores the relationship between obesity and vitamin A levels, shedding light on potential implications for health and well-being. It was an observational study based on a new vitamin A method and participants were asked to eat vitamin A rich foods. The robust performance of the LC-MS/MS methodology positions it as a valuable tool for clinical research. By accurately quantifying vitamin A levels in human serum, this methodology opens avenues for advancing our understanding of vitamin A physiology and its implications for health, particularly in obese populations. In summary, this LC-MS/MS methodology presents a potent tool for clinical studies, providing reliable, specific, and robust detection of vitamin A in human serum, thus, opening a new frontier for advancing our understanding of vitamin A related physiology and health in the obese population.

Unraveling the complex interplay between obesity and vitamin D metabolism.

Vitamin D deficiency and obesity are a worldwide health issue. Obesity refers to the accumulation of excessive fats in the body which could lead to the development of diseases. Obese people have low vitamin D levels for several reasons including larger volume of distribution, vitamin D tightly bound in fatty tissues, reduced absorption, and diets with low vitamin D. Accurately measuring vitamin D metabolites is challenging. The Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-MS/MS) method was developed and validated for the analysis of vitamin D metabolites in the serum. Blood samples were collected from 452 subjects which consisted of baseline (vitamin D deficient obese subjects), follow-up (supplemented obese subjects), and healthy volunteers. The vitamin D metabolites were separated adequately by the developed UHPLC-MS/MS method. Moreover, the validation criteria for the method were within an acceptable range. The baseline, follow-up and even healthy volunteers were deficient in 25OHD3 and 25OHD2. The baseline and healthy subjects had comparable concentration of vitamin D2 and D3. However, healthy subjects had a higher concentration of 25OHD and its epimer compared to the baseline subjects. The vitamin D3 was increased significantly in the follow- up subjects; therefore, the 25OHD3 was increased significantly compared to the baseline as well; however, the increase was insufficient to achieve the optimal range. The UHPLC-MS/MS method test was applied successfully on estimation of vitamin D metabolites in subjects. This study indicates the significance of taking into account the metabolic and storage effects when evaluating the vitamin D status in obese subjects.

Frequency of Vitamin D Receptor Gene Polymorphisms in a Population with a very High Prevalence of Vitamin D Deficiency, Obesity, Diabetes and Hypertension.

BACKGROUND: Although vitamin D levels and underlying vitamin D receptor (VDR) genetic polymorphisms have been linked to many common diseases including obesity, the association remains unclear. There is also co-existence of pathologically high proportions of obesity and vitamin D deficiency conditions in our UAE society. We therefore aimed to determine the genotypes and allele percentage frequency distribution of four polymorphisms-FokI, BsmI, ApaI and TaqI-in the VDR gene in healthy Emirati individuals and their association with vitamin D levels and chronic conditions including diabetes mellitus, hypertension and obesity. METHODS: 277 participants who were part of a randomized controlled trial had their assessment that included clinical and anthropometric data. Whole blood samples were taken for measurements of vitamin D [25(OH) D], four vitamin D receptor gene polymorphism SNPs, including BsmI, FokI, TaqI and ApaI, metabolic and inflammatory markers and related biochemical variables. Multiple logistic regression analysis was used to assess the influence of vitamin D receptor gene SNPs on vitamin D status after adjusting for clinical parameters known to influence vitamin D status in the study population. RESULTS: Overall, 277 participants with a mean (±SD) age of 41 ± 12, 204 (74%) of them being female, were included in the study. There were statistically significant differences in vitamin D concentrations between different genotypes of the four VDR gene polymorphisms (p < 0.05). There were, however, no statistically significant differences in vitamin D concentrations between subjects with and those without the four VDR gene polymorphisms genotype and alleles except for AA and AG and allele G in Apal SNP (p < 0.05). Multivariate analysis revealed no significant independent associations between vitamin D status and the four VDR gene polymorphisms after adjusting for dietary intake, physical activity, sun exposure, smoking and body mass index. In addition, no significant differences were found in the frequency of the genotypes and alleles of the four VDR genes among patients with obesity, diabetes and hypertension compared to those without these medical conditions. CONCLUSIONS: Although we found statistically significant differences in vitamin concentrations between different genotypes of the four VDR gene polymorphisms, multivariate analysis revealed no association after adjusting for clinical parameters known to influence vitamin D status. Furthermore, no association was found between obesity and related pathologies and the four VDR gene polymorphisms.

Mechanisms and Effect of Increased Physical Activity on General and Abdominal Obesity and Associated Metabolic Risk Factors in a Community with Very High Rates of General and Abdominal Obesity.

BACKGROUND: The growing prevalence of obesity and related type 2 diabetes is reaching epidemic proportions in the UAE. Physical inactivity is one of the possible factors linking obesity to diabetes and other related complications. However, the molecular mechanisms through which physical inactivity is contributing to increased obesity-related pathologies are not clear. AIMS: to measure the effects of increased physical activity on obesity and related metabolic risk factors. MATERIALS AND METHODS: We investigated the effects of physical activity on body weight, waist circumference (WC) and metabolic risk factors in 965 community free-living Emirati subjects. Physical activity, dietary intake, antioxidant enzymes and markers of oxidative damage and inflammation were measured both at baseline and follow up. A validated questionnaire was used to assess occupation and leisure-related physical activity. We compared metabolic risk factors between subjects stratified by physical activity levels. The Cox proportional hazards analysis was used to determine the independent effects of increased physical activity on presence and absence of obesity, body weight and waist circumference (WC) change at follow up. RESULTS: A total of 965 community free-living subjects [801 (83%) females, mean (SD) age 39 ± 12 years] were recruited and followed up with for a period of 427 ± 223 days. Using WHO cut-of-points for body mass index (BMI), 284 (30%) subjects were overweight and 584 (62%) subjects were obese, compared to 69 (8%) at normal body weight. We found men to be more physically active than women at both leisure and work times. BMI, hip circumference, total body fat, HDL and inflammatory markers (us CRP, TNF) were significantly higher in female subjects, whilst fat free-mass, WC, blood pressure and HbA1c were higher in male subjects (p < 0.05). Hypertension and diabetes were more common in male subjects compared to female subjects (p < 0.05). Increased physical activity both at baseline and follow up were associated with decreased BMI, WC and inflammatory markers, including us-CRP and TNF. Increased physical activity was associated with significant decrease in abdominal obesity in female subjects and general obesity in both male and females after adjusting for important prognostic indicators [hazard ratio (95% CI): 0.531 (0.399, 0.707); p < 0.001; 0.475 (0.341, 0.662); p < 0.001 respectively]. CONCLUSION: Our findings suggest that increased physical activity may decrease the risk of obesity and also mitigate the associated oxidative damage and inflammatory responses.

Increased Fruit and Vegetable Consumption Mitigates Oxidative Damage and Associated Inflammatory Response in Obese Subjects Independent of Body Weight Change.

INTRODUCTION: The growing prevalence of obesity and related type 2 diabetes is reaching epidemic proportions in the Gulf countries. Oxidative damage and inflammation are possible mechanisms linking obesity to diabetes and other related complications, including cardiovascular disease (CVD). AIMS: To measure the effects of increased fruit and vegetable consumption on body weight, waist circumference, oxidative damage, and inflammatory markers. MATERIALS AND METHODS: We recruited and followed up with 965 community free-living subjects. All recruited subjects had fruit and vegetable intakes, physical activity, antioxidants, and markers of oxidative damage and inflammation measured at baseline and follow up. A validated, semi-quantitative food-frequency questionnaire was used to assess subjects' fruit and vegetable consumption. We stratified subjects based on their daily fruit and vegetable consumption and compared metabolic risk factors between those with high fruit and vegetable consumption and those with low consumption. A multiple logistic regression analysis was performed to determine the independent effects of fruit and vegetable intake on changes in body weight and waist circumference (WC). RESULTS: A total of 965 community free-living subjects (801 (83%) females, mean (SD) age 39 ± 12 years) were recruited and followed up with for a mean (SD) period of 427 ± 223 days. Using WHO cut-off points for body mass index (BMI), 284 (30%) subjects were overweight and 584 (62%) obese, compared to 69 (8%) at normal body weight. An increased fruit and vegetable consumption was associated with a significant decrease in inflammatory markers (hs CRP, TNF-α) and oxidative damage markers (TBARs) and with increased antioxidant enzymes (catalase, glutathione peroxidase) compared to a low consumption (p < 0.05). The benefits of an increased fruit and vegetable consumption in obese subjects was independent of changes in body weight and WC and was maintained at follow up. CONCLUSION: Our results support the beneficial role of a higher fruit and vegetable intake in obese subjects independent of changes in body weight and WC.

Score Gains on the NBME Subject Examinations in Internal Medicine Among Clerkship Students: a Two-Year Longitudinal Study from the United Arab Emirates.

Background: The impact of clinical proficiency on individual student scores on the National Board of Medical Examiners (NBME) Subject Examinations remains uncertain. We hypothesised that increasing the length of time spent in a clinical environment would augment students' performance. Methods: Performance on the NBME Subject Examination in Internal Medicine (NBME-IM) of three student cohorts was observed longitudinally. Scores at the end of two unique internal medicine clerkships held at the third and fourth years were compared. The score differences between the two administrations were compared using paired t-tests, and the effect size was measured using Cohen's d. Moreover, linear regression was used to assess the correlation between the NBME-IM score gains and performance on a pre-clinical Comprehensive Basic Science Examination (CBSE). A two-tailed p-value <0.05 was considered significant. Results: Of the 236 students enrolled during the third year, age, gender, CBSE, and NBME-IM scores were similar across all cohorts. The normalised score gain on the NBME-IM at the fourth year was 9.5% (range -38 to +45%) with a Cohen's d of 0.47. However, a larger effect size with a Cohen's d value of 0.96 was observed among poorly scoring students. Performance on the CBSE was a significant predictor of score gain on the NBME-IM (R 0.51, R 2 0.26, p-value < 0.001). Conclusions: Despite the increased length of clinical exposure, modest improvement in students' performance on repeated NBME-IM examination was observed. Medical educators need to reconsider how the NBME-IM is used in clerkship assessments.

Urinary Oxidative Damage Markers and Their Association with Obesity-Related Metabolic Risk Factors.

Oxidative damage and inflammation are possible mechanisms linking obesity to diabetes and related complications. This study investigates the levels of oxidative damage markers in the urine of community free-living subjects with increased prevalence of obesity. METHODS: Participants were assessed regarding clinical, anthropometric, and physical activity data at baseline and at 6 months. Blood and urine samples were taken for the measurements of oxidative markers in urine ((glutathione (GSH), thiobarbituric acid reactive substances (TBARS), pteridine, 8-isoprostane and 8-hydroxy-2'-deoxyguanosine (8-OH-dG)), metabolic and inflammatory markers, and related biochemical variables in the blood. Univariate and multiple regression analyses were used to assess the association between oxidative markers and other clinical prognostic indicators. RESULTS: Overall, 168 participants with a complete 6-month follow-up with a mean (±SD) age of 41 ± 12 (119 (71%) females) were included in the study. In multiple regression analysis, log-transformed urinary pteridine levels were significantly correlated with log-transformed urinary GSH, 8-isoprostane, and TBARS after adjusting for urinary creatinine at both baseline and follow-up. Significant correlations were also found between oxidative damage markers and cardiovascular disease risk factors, including systolic blood pressure, HbA1c, plasma glucose, us-C-reactive proteins, total cholesterol, and HDL. Higher TBARS levels were found in males and diabetic subjects, with lower GSH in diabetic hypertensive and obese subjects, but the latter result did not reach statistical significance. We found nonsignificantly higher TBARS, 8-isoprostane, and pteridine levels in smokers compared to those in nonsmokers. All measured urinary oxidative damage markers levels were higher in obese subjects compared with normal-weight subjects, but results did not reach statistical significance. CONCLUSION: we found significant associations between urinary oxidative damage and metabolic risk factors, and higher levels of urinary oxidative damage markers in diabetic, hypertensive, smoker, and male subjects.

A randomized, double-blind, placebo-controlled trial of vitamin D supplementation with or without calcium in community-dwelling vitamin D deficient subjects.

BACKGROUND: Although vitamin D deficiency is highly prevalent in the Middle East, very few studies have attempted to measure its health impact. AIMS: We aimed to assess whether vitamin D3 and calcium, either alone or in combination, have health benefit. METHODS: In a 2 × 2 factorial design double-blind, placebo-controlled trial, Community free living adults living in the city of Al Ain, UAE were randomly assigned to receive daily 2000 IU oral vitamin D3 alone, 600 mg calcium alone, oral vitamin D3 (2000 IU per day) combined with 600 mg calcium, or a placebo for 6 months. Primary outcomes were self-rated health and bone turnover markers. RESULTS: Of the 545 randomized, 277 subjects completed 6 months follow up. 25(OH)D levels marginally increased in the two groups received vitamin D3 alone or combined with calcium compared to the decline seen in those who received calcium supplement alone or a placebo. Sub-group analysis revealed that parathyroid hormone (PTH) concentration decreased and Calcium/creatinine ratio increased significantly in the combined vitamin D and Calcium group compared to the vitamin D alone or Calcium alone in contrast to the increase seen in the placebo group [p < 0.05 for between group difference at 6 months]. There were no statistically significant differences between the supplement and placebo groups at the 6 months follow-up in body weight, body mass index (BMI), blood pressure, body pains and general health. CONCLUSION: PTH concentration decreased and calcium/creatinine ratio increased in subjects who received vitamin D and Calcium together compared to those who received vitamin D alone. TRIAL REGISTRATION: NCT02662491 , First registered on 25 January 2016 ( https://register. CLINICALTRIALS: gov/prs/app/action/SelectProtocol?sid=S00060CE&selectaction=Edit&uid=U0001M6P&ts=3&cx=scu4cb , Last update: 05 August 2019.

Vitamin D deficiency associations with metabolic, bone turnover and adverse general health markers in community free living adults.

BACKGROUND: Although there is some evidence that vitamin D deficiency is highly prevalent in the Middle East, however its health impact is still not clear. The aim of this study was to assess the prevalence, causes and health implications of vitamin D deficiency in local United Arab Emirates (UAE) citizens. METHODS: A cross-sectional study was conducted on community free living adults living in the city of Al Ain, UAE. Following informed written consent eligible subject's blood and urine samples were taken for measurements of vitamin D [25(OH)D], metabolic and bone turnover markers. Clinical assessment that includes general and self-rated health, muscle health, and physical activity were also performed. RESULTS: A total of 648 subjects (491 female) were included in this analysis. Their mean (SD) age was 38 (12) years. Mean 25(OH)D was 24 ng/ml (range: 4-67) with 286 (44%) subjects found to have vitamin D deficiency (< 20 ng/ml), 234 (36%) subjects have insufficiency (20-32 ng/ml) and 128 (20%) subjects have optimal concentrations (> 32 ng/ml). 25(OH)D concentrations were significantly higher in local indigenous UAE subjects compared to other Arab expatriates (p = 0.071). Although there were no statistically significant differences in clinical markers between groups, however, utra-sensitive C-reactive protein (us-CRP), parathyroid hormone (PTH), body mass index (BMI) and the bone markers U-PYD and PYD/CR were higher in vitamin D deficient older subjects aged ≥50 years and female subjects younger than 50 years respectively compared to those with insufficiency or optimal concentrations (p value < 0.05. Multiple logistic regression analysis revealed significant and independent association between 25(OH)D status and age and sex (p < 0.05). CONCLUSION: Older subjects with vitamin D deficiency have increased BMI, inflammation and PTH compared with those with insufficiency or optimal concentrations. Co-existence of obesity and vitamin D deficiency may have increased adverse health effects.

Vitamin D [25(OH)D] metabolites and epimers in obese subject: Interaction and correlations with adverse metabolic health risk factors.

BACKGROUND: Although both vitamin D deficiency and obesity are highly prevalent in the UAE, the role of vitamin D metabolites in mediating obesity-related adverse health effects is not clear. We aimed to assess the role of vitamin D metabolites as potential mediators in the association between obesity, inflammation and metabolic risk factors. METHODS: 277 participants who were part of a randomized controlled trial had their assessment that included clinical, anthropometric and physical activity data at baseline and at 6 months. Blood and urine samples were taken for measurements of serum 25(OH)D, 25(OH)D metabolites including 25(OH)D3), 25(OH)D2), 1,25(OH)2D3, 3-Epi-D3), metabolic and inflammatory markers and related biochemical variables. Multiple regression analysis used to assess the role of 25(OH)D metabolites in mediating the effect of increasing body mass index (BMI) on inflammation and metabolic risk factors. RESULTS: Overall, 277 participants with complete 6 months follow up with a mean (±SD) age of 41 ± 12 and 204 (74%) female were included in the study. Blood pressure, inflammatory, metabolic and lipid profile markers significantly increased in overweight and obese subjects compared to subjects with normal BMI both at baseline and at 6 months (p < 0.05). 25(OH)D revealed significant association with age, gender, HbA1c and type 2 diabetes (p < 0.05). No statistically significant changes in any of 25(OH)D metabolites assessed. Multivariate analysis revealed significant and independent associations between BMI and important inflammatory and metabolic risk factors (p < 0.05). No similar association observed with 25(OH)D metabolites. CONCLUSION: Although we found significant association between 25(OH)D and prevalence of type 2 diabetes, we found no evidence however to support a role of 25(OH)D metabolites in mediating the effect of BMI on inflammatory or metabolic risk factors.

Metabolomic Profiling of Lipids and Fatty Acids: 3 Years Postoperative Laparoscopic Sleeve Gastrectomy.

Visceral obesity is common in the United Arab Emirates and worldwide. Although laparoscopic sleeve gastrectomy (LSG) leads to effective and sustainable weight loss, its long-term beneficial impact on other risk factors, including blood lipid and fatty acid (FA) profiles, remains unknown. These two profiles were assessed in patients 3 years after undergoing LSG and in LSG candidates (controls). Lipid profiles were measured using the Cobas e411 modular analyzer, and 35 FAs were identified. The age and body mass index were 36.55 ± 8.65 years and 31.49 ± 6.43 kg/m2 in the LSG group and 35.44 ± 9.51 years and 32.29 ± 5.38 kg/m2 in the control group, respectively. The overall lipid profile was more favorable in the LSG group than in the control group. Total saturated, monounsaturated, and polyunsaturated FAs were similar between the groups, but total medium-chain FAs were more abundant in the LSG group. In endogenous FA synthesis, the estimated activity of C16Δ9 desaturase and Δ5 desaturase decreased, whereas that of elongase increased in the LSG group compared with that in the control group. The benefits of LSG on blood lipid and FA profiles in patients with 3-year LSG may be limited. Hence, lifestyle interventions combined with a long-term and strict regular follow-up regime may be warranted for patients undergoing LSG.

Significantly Elevated Levels of Plasma Nicotinamide, Pyridoxal, and Pyridoxamine Phosphate Levels in Obese Emirati Population: A Cross-Sectional Study.

Water-soluble vitamins like B3 (nicotinamide), B6 (pyridoxine), and B9 (folic acid) are of utmost importance in human health and disease, as they are involved in numerous critical metabolic reactions. Not surprisingly, deficiencies of these vitamins have been linked to various disease states. Unfortunately, not much is known about the physiological levels of B6 vitamers and vitamin B3 in an ethnically isolated group (such as an Emirati population), as well as their relationship with obesity. The aim of the present study was to quantify various B6 vitamers, as well as B3, in the plasma of obese and healthy Emirati populations and to examine their correlation with obesity. A sensitive and robust HPLC-MS/MS-based method was developed for the simultaneous quantitation of five physiologically relevant forms of vitamin B6, namely pyridoxal, pyridoxine, pyridoxamine, pyridoxamine phosphate, and pyridoxal phosphate, as well as nicotinamide, in human plasma. This method was used to quantify the concentrations of these vitamers in the plasma of 57 healthy and 57 obese Emirati volunteers. Our analysis showed that the plasma concentrations of nicotinamide, pyridoxal, and pyridoxamine phosphate in the obese Emirati population were significantly higher than those in healthy volunteers (p < 0.0001, p = 0.0006, and p = 0.002, respectively). No significant differences were observed for the plasma concentrations of pyridoxine and pyridoxal phosphate. Furthermore, the concentrations of some of these vitamers in healthy Emirati volunteers were significantly different than those published in the literature for Western populations, such as American and European volunteers. This initial study underscores the need to quantify micronutrients in distinct ethnic groups, as well as people suffering from chronic metabolic disorders.

Role of Functional Biomarkers to Identify Early Vitamin B12 Deficiency in Patients with Sleeve Gastrectomy: A Cross-Sectional Study.

Background and objectives: Although laparoscopic sleeve gastrectomy (LSG) is effective for obesity management, postoperative vitamin B12 (B12) deficiency is of major concern. In this cross-sectional study, we assessed the levels of B12 and its related functional biomarkers, namely, total homocysteine (tHcy), methylmalonic acid (MMA), folate, methylcitric acid (MCA), and hemoglobin (Hb), in one-year postoperative LSG patients and matched controls. Materials and Methods: Plasma B12, tHcy, MMA, folate, and MCA were measured in matched controls (n = 66) and patients (n = 71) using validated liquid chromatography-tandem mass spectrometry techniques and protocols in the United Arab Emirates (UAE). Results: The median B12 concentration in patients (177 pmol/L) was significantly lower (p < 0.001) than in the controls (334.7 pmol/L). The tHcy and MMA levels were significantly increased (p < 0.001 and p = 0.011, respectively) and folate levels were significantly decreased (p = 0.001) in the LSG patients compared to the controls. Interestingly, no significant difference in MCA levels were observed between the two groups. The levels of tHcy and MMA were concomitantly increased with the decreased folate levels in postoperative LSG patients when compared with the controls. The Hb levels were significantly lower in males and females in the patient group compared with those in the control group, respectively (p = 0.005 and p = 0.043). Conclusions: This is the first report of serum levels of B12 and its functional biomarkers in postoperative LSG patients among a local population from the UAE. Our findings revealed significant alterations of the B12 biomarkers, total B12, MMA, and tHcy in one-year postoperative LSG patients.

Associations between low muscle mass, blood-borne nutritional status and mental health in older patients.

BACKGROUND: Although low muscle mass is an important predictor of increased physical morbidity in older patients, information on its impact on mental health and well-being is lacking. The first aim of this report is to look for associations if any between low muscle mass and mental health of older people in clinical practice. The second aim is to study underlying mechanisms including nutritional status. METHODS: In this prospective longitudinal study we randomly selected and studied 432 hospitalized older patients' baseline demographic data, clinical characteristics and nutritional status on admission, at 6 weeks and at 6 months. Low muscle mass was diagnosed using anthropometric measures based on the European Working Group criteria. Mental health outcome measures including cognitive state, depression symptoms and quality of life were also measured. RESULTS: Out of 432 patients assessed 44 (10%) were diagnosed with low muscle mass. Patients diagnosed with low muscle mass at admission and over a 6-month follow up period had significantly poor cognitive function, quality of life and increased depression symptoms compared with those with normal muscle mass. After adjustment for poor prognostic indicators, age, disability, severity of acute illness and low muscle mass were associated with poor cognitive function and quality of life and higher depression symptoms in older patients over a 6 months period (p < 0.05). Although patients with low muscle mass had lower micronutrient concentrations compared to those patients with normal muscle mass, only serum albumin showed significant correlations with quality of life at admission and depression symptoms at 6 weeks. CONCLUSION: Low muscle mass is associated with poor blood-borne poor nutritional status and mental health in hospitalized older patients, however, this is partly explained by underlying co morbidity.

Epimers of Vitamin D: A Review.

In this review, we discuss the sources, formation, metabolism, function, biological activity, and potency of C3-epimers (epimers of vitamin D). We also determine the role of epimerase in vitamin D-binding protein (DBP) and vitamin D receptors (VDR) according to different subcellular localizations. The importance of C3 epimerization and the metabolic pathway of vitamin D at the hydroxyl group have recently been recognized. Here, the hydroxyl group at the C3 position is orientated differently from the alpha to beta orientation in space. However, the details of this epimerization pathway are not yet clearly understood. Even the gene encoding for the enzyme involved in epimerization has not yet been identified. Many published research articles have illustrated the biological activity of C3 epimeric metabolites using an in vitro model, but the studies on in vivo models are substantially inadequate. The metabolic stability of 3-epi-1α,25(OH)2D3 has been demonstrated to be higher than its primary metabolites. 3-epi-1 alpha, 25 dihydroxyvitamin D3 (3-epi-1α,25(OH)2D3) is thought to have fewer calcemic effects than non-epimeric forms of vitamin D. Some researchers have observed a larger proportion of total vitamin D as C3-epimers in infants than in adults. Insufficient levels of vitamin D were found in mothers and their newborns when the epimers were not included in the measurement of vitamin D. Oral supplementation of vitamin D has also been found to potentially cause increased production of epimers in mice but not humans. Moreover, routine vitamin D blood tests for healthy adults will not be significantly affected by epimeric interference using LC-MS/MS assays. Recent genetic models also show that the genetic determinants and the potential factors of C3-epimers differ from those of non-C3-epimers.Most commercial immunoassays techniques can lead to inaccurate vitamin D results due to epimeric interference, especially in infants and pregnant women. It is also known that the LC-MS/MS technique can chromatographically separate epimeric and isobaric interference and detect vitamin D metabolites sensitively and accurately. Unfortunately, many labs around the world do not take into account the interference caused by epimers. In this review, various methods and techniques for the analysis of C3-epimers are also discussed. The authors believe that C3-epimers may have an important role to play in clinical research, and further research is warranted.

Total adiponectin in overweight and obese subjects and its response to visceral fat loss.

BACKGROUND: Visceral obesity and related diabetes is reaching epidemic proportions in the United Arab Emirates (UAE). Adiponectin is a hormone that is secreted by adipose tissue and may play an important role in obesity-related morbidity. The aim of this study was to investigate total adiponectin levels in overweight and obese UAE subjects visiting health care facilities for weight management. METHODS: All overweight and obese subjects visiting community health centers were invited to take part in the study. Two hundred and six participants received individualized structured dietary education for weight management. Demographic data, anthropometric measurements and fasting venous blood samples were taken for measurements of total adiponectin and markers of inflammation and nutritional status at baseline and follow up. Multivariate analysis was performed to determine the independent effects of prognostic factors on serum adiponectin levels. RESULTS: A total of 193 (93%) females with a mean age (±SD) 36 ± 11 years were included in the analysis. During a follow up period of 427 ± 223 days, participants received 13 ± 5 structured dietary education sessions. We observed decreased levels of total adiponectin with increasing quartiles of both waist circumference (WC) and body mass index (BMI). Male gender and history of both gestational and type 2 diabetes were associated with significantly lower total adiponectin levels (p < 0.05). After adjusting for age, gender, BMI and hip circumference, multiple regression analysis revealed a significant and independent association between waist circumference and total adiponectin levels. At follow up visceral fat loss was associated with a significant decrease in inflammatory markers and a non-significant increase in total adiponectin levels. CONCLUSION: Increased visceral fat in overweight and obese subjects is associated with decreased total adiponectin levels. The health benefits of increasing adiponectin levels using different dietary intervention strategies need to be explored in larger studies. TRIAL REGISTRATION: NCT01691365 , registered on 11/09/2012.

Association between nutritional blood-based biomarkers and clinical outcome in sarcopenia patients.

BACKGROUND: Although several micronutrients deficiency were reported to be associated with poor muscle function, however information on sarcopenia patients is still lacking. The aim of this report was to measure some micronutrients blood-based status in sarcopenia patients during both acute illness and recovery. DESIGN: We assessed nutritional status of randomly selected hospitalised patients using anthropometric, haematological and biochemical data at baseline, 6 weeks and at 6 months. Sarcopenia was diagnosed from low muscle mass and low muscle strength using anthropometric measures based on the European Working Group criteria. Micronutrient status was compared between sarcopenia patients and those without sarcopenia over a 6 months period. RESULTS: Forty-four out of 432 patients (10%) were diagnosed with sarcopenia on admission. Patients diagnosed with sarcopenia had lower micronutrients concentrations compared to those patients without sarcopenia however, the results were statistically significant only for baseline serum albumin, red cell folate and plasma zinc (p < 0.05). Lycopene, retinol, red cell folate and zinc were also significantly lower in sarcopenia patients at 6 weeks. Sarcopenia patients readmitted to hospital had poor baseline micronutrient status compared with sarcopenia patients stayed in the community during the 6-months follow up period but differences were not statistically significant. Both baseline serum albumin and plasma zinc were significantly higher in sarcopenia patients who were alive compared with those died at 6 months follow up. CONCLUSION: Baseline serum albumin and plasma zinc concentrations were lower in patients diagnosed with sarcopenia compared to those without sarcopenia, and also in sarcopenia patients who died compared with those alive at 6 months follow up.

Application of a new vitamin D blood test on the Emirati population.

Research shows that immunoassay techniques are not the best choice for the estimation of vitamin D in human blood samples. The main reasons are that some immunoassays are not able to distinguish between 25-OHD3 and 25-OHD2 vitamin D metabolites. Furthermore, immunoassays cannot differentiate between 25OHD and inactive epimers of vitamin D. Vitamin D epimers and isobars have been known to overlap with the 25OHD signals and give false positives when tested. Liquid chromatography tandem-mass spectrometry (LC-MS/MS) can differentiate between 25OHD3 and 25OHD2. Separating epimers and isobars (which have the same molecular weight) from vitamin D is achieved through chromatographic separation from actual 25OHD peaks, although this could also cause inaccuracies in vitamin D measurements. The main aim of this study was to develop and validate an improved LC-MS/MS method (using a Shimadzu 8060 system) that could accurately detect and quantitate up to 10 different metabolites of vitamin D, as well as differentiate the epimers and isobars. The secondary aim was to apply the developed LC-MS/MS method for the accurate measurement of blood vitamin D levels in the Emirati population. The Shimadzu 8060 system was run using positive ion electrospray ionization (ESI) in Dynamic Multiple Reaction Monitoring (DMRM) mode for quantification. The method involved blood sample collection from 80 Emirati volunteers, followed by serum extraction and liquid-liquid extraction. The chromatography column used for the analysis was an Ascentis Express F5. Precursor and product ions were detected using a Shimadzu 8060 LC-MS/MS system, and 10 metabolites of vitamin D were detected and quantified, including epimers and isobars. The method validation showed good sensitivity, recovery, linearity, precision, specificity, and accuracy. Furthermore, the data showed that vitamin D epimer 3-epi-25OHD and isobar 7-α-hydroxy-4-cholesten-3-one (7αC4) accounted for a significant portion of vitamin D results in the Emirati population. We report a more reliable, reproducible, and robust LC-MS/MS method for the accurate detection of 25OHD (vitamin D) in the Emirati population. The method has the capacity to detect and separate 10 metabolites of vitamin D as well as separate 25OHD from co-eluting epimers and isobars. The method has also been successfully implemented in gauging vitamin D deficiency in the Emirati population. Thus, this improved LC-MS/MS method could prove very useful in accurately estimating the levels of vitamin D in the Emirati population and in further clinical studies.

Association between muscle function, cognitive state, depression symptoms and quality of life of older people: evidence from clinical practice.

BACKGROUND: Although low muscle function/strength is an important predictor of poor clinical outcome in older patients, information on its impact on mental health in clinical practice is still lacking. AIMS: The aim of this report is to measure the impact of low muscle function measured by handgrip strength on mental health of older people during both acute illness and recovery. METHODS: Four hundred and thirty-two randomly selected hospitalized older patients had their baseline demographic and clinical characteristics assessed within 72 h of admission, at 6 weeks and at 6 months. Low muscle strength-handgrip was defined using the European Working Group criteria. Mental health outcome measures including cognitive state, depression symptoms and quality of life were also measured. RESULTS: Among the 432 patients recruited, 308 (79%) had low muscle strength at baseline. Corresponding figures at 6 weeks and at 6 months were 140 (73%) and 158 (75%). Patients with poor muscle strength were significantly older with increased disability and poor nutritional status compared with those with normal muscle strength. After adjustment for age, gender, disability, comorbidity including severity of acute illness and body mass index patients with low muscle strength had worse cognitive function, quality of life and higher depression symptoms compared with those with normal muscle strength over a 6-month period (p < 0.05). CONCLUSION: Poor muscle strength in older people is associated with poor cognitive state and quality of life and increased depression symptoms during both acute illness and recovery.

Oxidative damage and associated inflammatory risk factors in obese Emirati women. Body mass index versus waist circumference.

OBJECTIVES: To establish whether body mass index (BMI) or waist circumference (WC) is a better predictor of cardio metabolic risk factors that are associated with increased visceral fat among obese women from the United Arab Emirates (UAE). METHODS: In this  cross-sectional study, 333 obese subjects visiting community health centers in Al Ain city, UAE, were recruited between 2012 and 2015. After a written consent subjects had anthropometric, clinical and biochemical measurements.  Fasting serum and plasma samples were collected for the measurement of markers of oxidative damage, antioxidants and inflammation.  Outcome measures were compared between 4 equal BMI and WC quartiles. RESULTS: We observed significantly higher blood pressure, c-reactive protein levels, IL6 levels, and protein carbonyls contents and lower ß-carotene levels in the fourth quartile than in the first quartile for both BMI and WC (p less than 0.01). Glutathione peroxidase and adiponectin both decreased and TNF-α increased with increasing WC quartiles but not BMI quartiles; however, the results were statistically significant only for TNF-α (p=0.032). Conclusion: Both elevated BMI and elevated WC are associated with increased cardio metabolic risk factors in obese Emirati women; however, WC is a stronger predictor than is BMI.