Cardiorespiratory fitness and sedentary activities are associated with adiposity in adolescents

Objective: To determine whether physical activity, sedentary activities, and/or cardiorespiratory fitness are related to waist circumference in adolescents, as previously reported in adults. Research Methods and Procedures: The study subjects were a representative sample of Spanish adolescents (N = 2859; 1357 boys, 1502 girls; age, 13 to 18.5 years), all of whom were involved in the AVENA (Food and Assessment of the Nutritional Status of Adolescents) study. BMI, waist circumference, pubertal maturation status, and cardiorespiratory fitness were measured in all. Leisure‐time physical activity, sedentary activities, active commuting to school, and socioeconomic status were assessed by self‐reported questionnaires. Results: No relationship was found between leisure‐time physical activity and BMI or waist circumference. In contrast, and in both boys and girls and after adjustment for confounding variables, cardiorespiratory fitness was found to be inversely associated with waist circumference and BMI, independent of sedentary activities or physical activity (p ≤ 0.001). The maximum oxygen consumption explained 13% of the variance in waist circumference in boys and 16% in girls. Sedentary activities were independently and directly related to waist circumference in both boys and girls (p ≤ 0.05) and to BMI in boys (p ≤ 0.05). Sedentary activities explained 10% of the variance in waist circumference in boys and 18% in girls. The BMI‐adjusted waist circumference was inversely correlated with cardiorespiratory fitness in overweight‐obese boys (p ≤ 0.05) and showed a trend toward significance in girls (p ≤ 0.1). Discussion: Both moderate to high levels of cardiorespiratory fitness and sedentary activities, but not physical activity, are associated with lower abdominal adiposity, as measured by waist circumference.     

Serum 25-Hydroxyvitamin D and Insulin Resistance in Apparently Healthy Adolescents

Purpose

Vitamin D deficiency is a common condition that is associated with diabetes and insulin resistance. However, the association between vitamin D and insulin resistance has not been fully studied, especially in the general adolescent population. Therefore, we assessed the association between serum 25-hydroxyvitamin D [25(OH)D] level and insulin resistance among apparently healthy Korean adolescents.

Methods

A total of 260 (135 male and 125 female) adolescents in a rural high school were assessed for serum 25(OH)D, fasting plasma glucose, and insulin. All of the participants were aged 15 to 16 years old, and without known hypertension or diabetes. Serum 25(OH)D was analyzed both as a continuous and categorical variable in association with insulin resistance. Insulin resistance was estimated by homeostasis model assessment (HOMA-IR). Increased insulin resistance was operationally defined as a HOMA-IR value higher than the sex-specific 75th percentile.

Results

In male adolescents, every 10 ng/ml decrease in 25(OH)D level was associated with a 0.25 unit increase in HOMA-IR (p = 0.003) after adjusting for age and BMI. Compared to those in the highest quartile, male adolescents in the lowest 25(OH)D quartile were at significantly higher risk for insulin resistance: unadjusted odds ratio 4.06 (95% CI, 1.26 to 13.07); age and BMI adjusted odds ratio 3.59 (95% CI, 1.03 to 12.57). However, 25(OH)D level, either in continuous or categorical measure, was not significantly associated with insulin resistance among female adolescents.

Conclusions

This study suggests that serum 25(OH)D level may be inversely associated with insulin resistance in healthy male adolescents.     

25-Hydroxyvitamin D levels of children are inversely related to adiposity assessed by body mass index

Vitamin D deficiency is associated with wide range of pathologies. Some evidences have shown that low vitamin D circulating levels in children and adolescent are related to fat mass and obesity. The objectives of the present study were to characterize vitamin D status in children and adolescents and to determine if serum 25-hydroxyvitamin D (25(OH)D) concentration is related to adiposity assessed by body mass index (BMI). Serum 25(OH)D levels were measured by LIAISON method in 471 children and adolescents (2 to 18 years age) and analyzed according to gender, pubertal period, age, and BMI. An overall prevalence of 25(OH)D insufficiency and deficiency was present in the 67.1%. Lower 25(OH)D levels were found in females (25.56 ± 14.03 vs 29.71 ± 17.10 ng ml^?1; P = 0.004) and pubertal children (25.52 ± 13.97 vs 29.21 ± 16.83 ng ml^?1; P = 0.011). In addition, an inverse relation of BMI and age on 25(OH)D concentrations was observed in children. In conclusion, low vitamin D status was highly prevalent among children and adolescents. Of note, a non-lineal regression model showed that 39.6% of vitamin D levels variability was explained by BMI. These results indicate that adiposity assessed by BMI impacts vitamin D status.     

Rates of insufficiency and deficiency of vitamin D levels in elite professional male and female skiers: A chronobiologic approach

Vitamin D is essential for the maintenance and promotion of musculoskeletal health, for the functioning of the immune, cardiovascular and reproductive systems, and its main action is to keep calcium and phosphate plasmatic physiological concentrations at intestinal, renal and bony level. Vitamin D affects several parameters related to physical performance too and a particularly high percentage of vitamin D insufficiency and deficiency in professional athletes has been observed. Several variables are able to impair the synthesis of 25(OH)D in athletes, specifically both genetic and environmental factors, but the most probable explanation for the deficient/insufficient vitamin D levels is the insufficient ultraviolet B light (UVB) exposure during winter. To confirm this, the existence of a circannual rhythm of vitamin D in professional soccer players, highlighting a peak in summer and lowest values in winter regardless the period of the season, has been documented. Nonetheless, from what we are aware of, no other study adopted a chronobiologic approach to better understand and describe the circannual variations of serum 25(OH)D in other sport disciplines. Therefore, we studied serum vitamin D in a cohort of top-level professional skiers, during a period of three consecutive competitive seasons (2015, 2016 and 2017), in order to evaluate, with a rhythmometric approach, the vitamin D behavior along the year. The study population was composed by 152 professional Italian alpine skiers of FISI (Winter Sport Italian Federation), 63 females and 89 males (mean age: 24.1 ± 3.2 years) and a total of 298 blood drawings were carried out to determine plasma 25(OH)D. Vitamin D data were compared between genders and then processed with the population mean cosinor tests to evaluate the presence of a circannual rhythm, both for female and male athletes. In total, 77 skiers (50.7%) showed, at least once during the three competitive seasons, an insufficient level of 25(OH)D and other 45 subjects (29.6%) showed a deficient status; no differences were observed between genders (mean for females: 26.9 ± 8.1 ng/mL; mean for males: 27.4 ± 7.6 ng/mL). In addition, the rhythmometric analysis highlighted the existence of a significant circannual rhythm for both female and male professional skiers; the acrophases (Φ) occurred in July and both MESOR (M) and amplitude (A) were comparable between the two groups. Our data indicate that, despite the physical effort spent, vitamin D follows a classical season-associated rhythm with a peak in summer and a nadir in winter. Moreover, the percentage of insufficiency and deficiency is in line with that of the general population. In conclusion, our findings reinforce the hypothesis that there is no direct effect of physical activity on vitamin D metabolism and that the factors involved in the determination of vitamin D levels in the general population are valid also for athletes.     

High Prevalence of Vitamin D Insufficiency in China: Relationship with the Levels of Parathyroid Hormone and Markers of Bone Turnover

There is a lack of large-scale studies on vitamin D status and its relationship to parathyroid hormone (PTH) and bone turnover markers in adults living in Shanghai. The objectives were to determine the prevalence of vitamin D insufficiency in Shanghai and to investigate the relationship of 25(OH)D with parathyroid function and bone turnover markers. This cross-sectional study involved 649 men and 1939 women aged 20–89 years who were randomly sampled in Shanghai. Serum concentrations of 25(OH)D, PTH, albumin, and bone turnover markers were measured. During the winter season, the prevalence of vitamin D insufficiency (<30 ng/mL) was 84% in males and 89% in females. The prevalence of vitamin D deficiency (<20 ng/mL) was 30% in males and 46% in females. With increasing serum 25(OH)D concentrations categorized as <10, 10–20, 20–30, and ≥30 ng/mL, the mean PTH and bone turnover markers levels gradually decreasd in both sexes (p<0.001). There was an inverse relationship between the serum 25(OH)D and PTH concentrations in both genders, but no threshold of 25(OH)D at which PTH levels plateaued was observed. There were modest but significantly inverse relationships between the levels of 25(OH)D and bone turnover markers, but no plateau was observed for serum 25(OH)D levels up to 40 ng/mL.     

Targeted delivery of vitamin D to the colon using β-glucuronides of vitamin D: therapeutic effects in a murine model of inflammatory bowel disease

1,25-Dihydroxyvitamin D(3) [1,25(OH)(2)D] has been shown to inhibit development of dextran sodium sulfate (DSS)-induced colitis in mice but can also cause hypercalcemia. The aim of this study was to evaluate whether β-glucuronides of vitamin D could deliver 1,25(OH)(2)D to the colon to ameliorate colitis while reducing the risk of hypercalcemia. Initial studies demonstrated that bacteria residing in the lower intestinal tract were capable of liberating 1,25(OH)(2)D from 1,25-dihydroxyvitamin D(3)-25-β-glucuronide [β-gluc-1,25(OH)(2)D]. We also determined that a much greater upregulation of the vitamin D-dependent 24-hydroxylase gene (Cyp24) was induced in the colon by treatment of mice with an oral dose of β-gluc-1,25(OH)(2)D than 1,25(OH)(2)D, demonstrating targeted delivery of 1,25(OH)(2)D to the colon. We then tested β-glucuronides of vitamin D in the mouse DSS colitis model in two studies. In mice receiving DSS dissolved in distilled water and treated with 1,25(OH)(2)D or β-gluc-1,25(OH)(2)D, severity of colitis was reduced. Combination of β-gluc-1,25(OH)(2)D with 25-hydroxyvitamin D(3)-25-β-glucuronide [β-gluc-25(OH)D] resulted in the greatest reduction of colitis lesions and symptoms in DSS-treated mice. Plasma calcium concentrations were lower in mice treated with β-gluc-1,25(OH)(2)D alone or in combination with β-gluc-25(OH)D than in mice treated with 1,25(OH)(2)D, which were hypercalcemic at the time of death. β-Glucuronides of vitamin D compounds can deliver 1,25(OH)(2)D to the lower intestine and can reduce symptoms and lesions of acute colitis in this model.     

Effectiveness of vitamin D supplementation in Swedish children may be negatively impacted by BMI and serum fructose

In regions where sunlight exposure is limited, dietary vitamin D intake becomes important for maintaining status. However, Swedish children have been shown to have deficient or marginal status during the winter months even if the recommended dietary intake is met. Since low vitamin D status has been associated with several disease states, this study investigated the metabolic changes associated with improved vitamin D status due to supplementation.During the 3 winter months, 5–7-year-old children (n=170) in northern (Umeå, 63° N) and southern (Malmö, 55° N) Sweden were supplemented daily with 2 (placebo), 10 or 25 μg of vitamin D. BMI-for-age z-scores (BAZ), S-25(OH)D concentrations, insulin concentrations and the serum metabolome were assessed at baseline and follow-up.S-25(OH)D concentrations increased significantly in both supplementation groups (P<.001). Only arginine and isopropanol concentrations exhibited significant associations with improvements in S-25(OH)D. Furthermore, the extent to which S-25(OH)D increased was correlated with a combination of baseline BAZ and the change in serum fructose concentrations from baseline to follow up (P=.012). In particular, the change in S-25(OH)D concentrations was negatively correlated (P=.030) with the change in fructose concentrations for subjects with BAZ ≥0 and consuming at least 20 μg vitamin D daily. These results suggest that although the metabolic changes associated with improved vitamin D status are small, the effectiveness of dietary supplementation may be influenced by serum fructose concentrations.     

Retinol assessment among women and children in sahelian mobile pastoralists

Micronutrient deficiencies are widespread in developing countries, particularly in remote communities such as mobile pastoralists. The nutritional and vitamin A status of this population is not well-documented in Chad. This study assessed serum retinol levels among women and children under five-year-old in nomadic and semi-nomadic pastoralist and rural-settled communities, who are similarly exposed to risk factors such as gastrointestinal parasitic infection, anaemia and emaciation. The novel method of portable fluorometry was used for the first time to measure β-carotene and retinol levels in a pastoral nomadic area. Moderate level blood retinol deficiency (<0.7?μmol/L) was observed in 5% (CI 1-11) of nomadic, 29% (CI 13-45) of semi-nomadic and 22% (CI 8-35) of sedentary women. In children, 1% (CI 0.1-4), 17% (CI 9-25) and 28% (CI 18-39), respectively, had moderate level blood retinol deficiency. In nomadic communities, women and children had blood retinol levels close to normal. Deficiency of retinol was strongly linked with lifestyle (nomadic, semi-nomadic and settled) among women and lifestyle and age among children. The results support an ecological linkage between human retinol levels and livestock milk retinol. This study shows the feasibility of portable retinol and β-carotene measurement in human blood as well as human and animal milk under remote field conditions, but the approach requires further validation.     

Serum concentrations of vitamin D metabolites, vitamins A and E, and carotenoids in six canid and four ursid species at four zoos

Nutritional status for six captive canid species (n=34) and four captive ursid species (n=18) were analyzed. The species analyzed included: African wild dog (Lycaon pictus), arctic fox (Alopex lagopus), gray wolf (Canis lupus), maned wolf (Chrysocyon brachyurus), Mexican wolf (Canis lupus baleiyi), red wolf (Canis rufus), brown bear (Ursus arctos), polar bear (Ursus maritimus), spectacled bear (Tremarctos ornatus), and sun bear (Ursus malayanus). Diet information was collected for these animals from each participating zoo (Brookfield Zoo, Fort Worth Zoo, Lincoln Park Zoological Gardens, and North Carolina Zoological Park). The nutritional composition of the diet for each species at each institution met probable dietary requirements. Blood samples were collected from each animal and analyzed for vitamin D metabolites 25(OH)D and 1,25(OH)(2)D, vitamin A (retinol, retinyl stearate, retinyl palmitate), vitamin E (alpha-tocopherol and gamma-tocopherol) and selected carotenoids. Family differences were found for 25(OH)D, retinol, retinyl stearate, retinyl palmitate and gamma-tocopherol. Species differences were found for all detectable measurements. Carotenoids were not detected in any species. The large number of animals contributing to these data, provides a substantial base for comparing the nutritional status of healthy animals and the differences among them.     

Morphological and functional characteristics of 9-to 22-year-old female athletes involved in sports aerobics

Parameters of physical development, the cardiorespiratory system, and physical fitness were studied in female athletes aged 9–22 years. It was found that sports aerobics affects profoundly the functional capacity of the muscular and cardiorespiratory systems and, to a smaller degree, the morphological characteristics of the body.     

Low Vitamin D Status Is Associated with Systemic and Gastrointestinal Inflammation in Dogs with a Chronic Enteropathy

Introduction

Vitamin D deficiency, as assessed by serum concentrations of 25 hydroxyvitamin D (25(OH)D), has been linked to the development of over-zealous and inappropriate inflammation in humans. However, the relationship between vitamin D status and inflammation in dogs is ill-defined. Chronic enteropathies (CE) are frequently diagnosed in client owned dogs, have a wide range of serum 25(OH)D concentrations, and represent a spontaneous model in which to probe the relationship between vitamin D and inflammation. The hypothesis of this study was that vitamin D status would be negatively associated with systemic and gastrointestinal inflammation in dogs with a CE. The aim of this study was to examine the relationship between serum 25(OH)D concentrations and markers of systemic and gastrointestinal inflammation in a cohort of dogs with CE.

Methods and Materials

Serum 25(OH)D concentrations, together with neutrophil, monocyte, eosinophil and lymphocyte counts, duodenal histopathology scores, serum IL-2, IL-6, IL-8 and TNFα concentrations and were measured in 39 dogs with histologically confirmed CE. A linear regression model examined the relationship between serum 25(OH)D status and measures of inflammation.

Results

Serum 25(OH)D concentrations were negatively associated with neutrophil and monocyte counts, duodenal histopathology scores and serum IL-2 and IL-8 concentrations. Dogs with low serum 25(OH)D concentrations typically had an inflammatory signature characterised by high monocyte and neutrophil numbers together with low lymphocyte numbers. There is a need to establish whether low vitamin D status is a cause or consequence of inflammation.     

Non-Linear Relationship between Serum 25-Hydroxyvitamin D and Hemoglobin in Korean Females: The Korean National Health and Nutrition Examination Survey 2010–2011

Background

Anemia and vitamin D deficiency are both important health issues; however, the nature of the association between vitamin D and either hemoglobin or anemia remains unresolved in the general population.

Methods

Data on 11,206 adults were obtained from the fifth Korean National Health and Nutritional Examination Survey. A generalized additive model was used to examine the threshold level for relationship between serum 25-hydroxyvitamin D [25(OH)D] and hemoglobin levels. A multivariate logistic regression for anemia was conducted according to 25(OH)D quintiles. All analyses were stratified according to sex and menstrual status.

Results

The generalized additive model confirmed a threshold 25(OH)D level of 26.4 ng/mL (male, 27.4 ng/mL; premenopausal females, 11.8 ng/mL; postmenopausal females, 13.4 ng/mL). The threshold level affected the pattern of association between 25(OH)D and anemia risk: the odds ratio of the 1^st quintile but not the 2^nd, 3^rd, and 4^th quintiles were significantly different from the 5^th quintile in both premenopausal and postmenopausal females, however there was no obvious trend in males.

Conclusions

This population-based study demonstrated a non-linear relationship with a threshold effect between serum 25(OH)D and hemoglobin levels in females. Further interventional studies are warranted to determine whether the appropriate level of hemoglobin can be achieved by the correction of vitamin D deficiency.     

Investigation of seasonal variations in cow serum retinol and β -carotene by high performance liquid chromatographic method

• 1.1. High performance liquid chromatography (HPLC) was used to determine β-carotene and retinol in cow serum.
• 2.2. Two groups of state and private farm cows (Groups 1 and 2) were used to assess seasonal variation when different food sources were fed to cows on serum β -carotene and retinol concentrations.
• 3.3. Mean serum concentrations of β-carotene and retinol from October to April in both Groups 1 and 2 cows were lower (P < 0.05) than in the other months when the cows were fed various combination of maize silage, alfalfa and carrot residues and grass hay, respectively.
• 4.4. Mean serum β-carotene and retinol concentrations in June and July were higher (P < 0.05) than in other months when the cows were in pasture.
• 5.5. Mean serum β-carotene and retinol concentrations in May, August and September were lower (P < 0.05) than in June and July and higher (P < 0.05) than in other months when a lesser amount of green pasture was available to the cows.
• 6.6. There was a seasonal variation (P < 0.05) in serum β -carotene and retinol concentrations. When the carotene intake is very high, conversion of β -carotene to retinol decreases. Mean monthly serum β -carotene and retinol concentrations showed that combination of alfalfa hay and maize silage, and grass hay and carrot residues can maintain adequate serum β-carotene and retinol concentrations during the dry season.

     

Contribution of adipose tissue to plasma 25-hydroxyvitamin D concentrations during weight loss following gastric bypass surgery

Roux-en-y gastric bypass (RYGB) surgery is associated with dramatic improvements in obesity-related comorbidity, but also with nutritional deficiencies. Vitamin D concentrations are depressed in the severely obese, but the impact of weight loss via RYGB is unknown. We determined associations between adiposity and systemic 25-hydroxyvitamin D (25(OH)D) during weight loss and the immediate and longer-term effects of RYGB. Plasma 25(OH)D concentrations and fat mass (FAT) were determined by immunoassay and air displacement plethysmography, respectively, at 0 (before RYGB surgery), and at 1, 6, and 24 months in severely obese white and African American (AA) women (n = 20). Decreases in adiposity were observed at 1, 6, and 24 months following RYGB (P < 0.05). Plasma 25(OH)D concentrations increased at 1 month (P = 0.004); a decreasing trend occurred over the remainder months after surgery (P = 0.02). Despite temporary improvement in vitamin D status, a high prevalence of vitamin D insufficiency was observed (76, 71, 67, and 82%, at baseline, 1, 6, and 24 months, respectively), and plasma 25(OH)D concentrations were lower in AA compared to white patients (P < 0.05). Strong positive baseline and 1 month cross-sectional correlations between FAT and plasma 25(OH)D were observed, which remained after adjustment for age and race subgroup (β = 0.76 and 0.61, respectively, P = 0.02). In conclusion, 25(OH)D concentrations increased temporarily and then decreased during the 24 months following RYGB. The acute increase and the positive associations observed between adipose tissue mass and systemic 25(OH)D concentrations suggest storage in adipose tissue and release during weight loss.     

Restricted Transport of Vitamin D and A Derivatives Through the Rat Blood-Brain Barrier

The present studies measure the transport of retinol, retinoic acid, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], and 25-hydroxyvitamin D3 [25-(OH)D3] through the rat brain capillary endothelial wall, i.e., the blood-brain barrier (BBB). The vitamin A and D derivatives bind both to albumin and to specific high-affinity binding proteins in plasma. In the presence of physiologic concentrations of plasma proteins, the extraction by brain of all four compounds was 5% or less.     

Independent Association of Circulating Vitamin D Metabolites with Anemia Risk in Patients Scheduled for Cardiac Surgery

Background

Preoperative anemia is considered an independent risk factor of poor clinical outcome in cardiac surgical patients. Low vitamin D status may increase anemia risk.

Methods

We investigated 3,615 consecutive patients scheduled for cardiac surgery to determine the association between preoperative anemia (hemoglobin [Hb] <12.5 g/dL) and circulating levels of the vitamin D metabolites 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D (1,25[OH]₂D).

Results

Of the study cohort, 27.8 % met the criteria for anemia. In patients with deficient 25OHD levels (<30 nmol/l) mean Hb concentrations were 0.5 g/dL lower than in patients with adequate 25OHD levels (50.0–125 nmol/l; P<0.001). Regarding 1,25(OH)₂D, mean Hb concentrations were 1.2 g/dL lower in the lowest 1,25(OH)₂D category (<40 pmol/l) than in the highest 1,25(OH)₂D category (>70 pmol/l; P<0.001). In multivariable–adjusted logistic regression analyses, the odds ratios for anemia of the lowest categories of 25OHD and 1,25(OH)₂D were 1.48 (95%CI:1.19-1.83) and 2.35 (95%CI:1.86-2.97), compared with patients who had adequate 25OHD levels and 1,25(OH)₂D values in the highest category, respectively. Anemia risk was greatest in patients with dual deficiency of 25OHD and 1,25(OH)₂D (multivariable-adjusted OR = 3.60 (95%CI:2.40-5.40). Prevalence of deficient 25OHD levels was highest in anemia of nutrient deficiency, whereas low 1,25(OH)₂D levels were most frequent in anemia of chronic kidney disease.

Conclusion

This cross-sectional study demonstrates an independent inverse association between vitamin D status and anemia risk. If confirmed in clinical trials, preoperative administration of vitamin D or activated vitamin D (in case of chronic kidney disease) would be a promising strategy to prevent anemia in patients scheduled for cardiac surgery.     

Vitamin D and disease prevention with special reference to cardiovascular disease

Circulating 25-hydroxyvitamin D [25(OH)D] is the hallmark for determining vitamin D status. Serum parathyroid hormone [PTH] increases progressively when 25(OH)D falls below 75 nmol/l. Concentrations of 25(OH)D below 50 nmol/l or even below 25 nmol/l are frequently observed in various population groups throughout the world. This paper highlights the relationship of vitamin D insufficiency with cardiovascular disease and non-insulin dependent diabetes mellitus, two diseases that account for up to 50% of all deaths in western countries. There is evidence from patients with end-stage renal disease that high PTH concentrations are causally related to cardiovascular morbidity and mortality. Activated vitamin D is able to increase survival in this patient group significantly. Moreover, already slightly enhanced PTH concentrations are associated with ventricular hypertrophy and coronary heart disease in the general population. Experimental studies have demonstrated that a lack of vitamin D action leads to hypertension in mice. Some intervention trials have also shown that vitamin D can reduce blood pressure in hypertensive patients. In young and elderly adults, serum 25(OH)D is inversely correlated with blood glucose concentrations and insulin resistance. Sun-deprived lifestyle, resulting in low cutaneous vitamin D synthesis, is the major factor for an insufficient vitamin D status. Unfortunately, vitamin D content of most foods is negligible. Moreover, fortified foods and over-the-counter supplements usually contain inadequate amounts of vitamin D to increase serum 25(OH)D to 75 nmol/l. As a consequence, legislation has to be changed to allow higher amounts of vitamin D in fortified foods and supplements.     

Efficient production of retinol in Yarrowia lipolytica by increasing stability using antioxidant and detergent extraction

The demand for bio-based retinol (vitamin A) is currently increasing, however its instability represents a major bottleneck in microbial production. Here, we developed an efficient method to selectively produce retinol in Yarrowia lipolytica. The β-carotene 15,15′-dioxygenase (BCO) cleaves β-carotene into retinal, which is reduced to retinol by retinol dehydrogenase (RDH). Therefore, to produce retinol, we first generated β-carotene-producing strain based on a high-lipid-producer via overexpressing genes including heterologous β-carotene biosynthetic genes, GGS1^F43I mutant of endogenous geranylgeranyl pyrophosphate synthase isolated by directed evolution, and FAD1 encoding flavin adenine dinucleotide synthetase, while deleting several genes previously known to be beneficial for carotenoid production. To produce retinol, 11 copies of BCO gene from marine bacterium 66A03 (Mb.Blh) were integrated into the rDNA sites of the β-carotene overproducer. The resulting strain produced more retinol than retinal, suggesting strong endogenous promiscuous RDH activity in Y. lipolytica. The introduction of Mb.Blh led to a considerable reduction in β-carotene level, but less than 5% of the consumed β-carotene could be detected in the form of retinal or retinol, implying severe degradation of the produced retinoids. However, addition of the antioxidant butylated hydroxytoluene (BHT) led to a >20-fold increase in retinol production, suggesting oxidative damage is the main cause of intracellular retinol degradation. Overexpression of GSH2 encoding glutathione synthetase further improved retinol production. Raman imaging revealed co-localization of retinol with lipid droplets, and extraction of retinol using Tween 80 was effective in improving retinol production. By combining BHT treatment and extraction using Tween 80, the final strain CJ2104 produced 4.86 g/L retinol and 0.26 g/L retinal in fed-batch fermentation in a 5-L bioreactor, which is the highest retinol production titer ever reported. This study demonstrates that Y. lipolytica is a suitable host for the industrial production of bio-based retinol.     

Vitamin D Status among Thai School Children and the Association with 1,25-Dihydroxyvitamin D and Parathyroid Hormone Levels

In several low latitude countries, vitamin D deficiency is emerging as a public health issue. Adequate vitamin D is essential for bone health in rapidly growing children. In the Thai population, little is known about serum 25-hydroxyvitamin D [25(OH)D] status of infants and children. Moreover, the association between 25(OH)D and the biological active form of 1,25-dihydroxyvitamin D [1,25(OH)]₂D is not clear. The specific aims of this study were to characterize circulating serum 25(OH)D, 1,25(OH)₂D and their determinants including parathyroid hormone (PTH), age, sex, height and body mass index (BMI) in 529 school-aged Thai children aged 6–14 y. Adjusted linear regression analysis was performed to examine the impact of age and BMI, and its interaction with sex, on serum 25(OH)D concentrations and 1,25(OH)₂D concentrations. Serum 25(OH)D, 1,25(OH)₂D and PTH concentrations (geometric mean ± geometric SD) were 72.7±1.2 nmol/L, 199.1±1.3 pmol/L and 35.0±1.5 ng/L, respectively. Only 4% (21 of 529) participants had a serum 25(OH)D level below 50 nmol/L. There was statistically significant evidence for an interaction between sex and age with regard to 25(OH)D concentrations. Specifically, 25(OH)D concentrations were 19% higher in males. Moreover, females experienced a statistically significant 4% decline in serum 25(OH)D levels for each increasing year of age (P = 0.001); no decline was seen in male participants with increasing age (P = 0.93). When BMI, age, sex, height and serum 25(OH)D were individually regressed on 1,25(OH)₂D, height and sex were associated with 1,25(OH)₂D with females exhibiting statistically significantly higher serum 1,25(OH)₂D levels compared with males (P<0.001). Serum 1,25(OH)₂D among our sample of children exhibiting fairly sufficient vitamin D status were higher than previous reports suggesting an adaptive mechanism to maximize calcium absorption.     

Vitamin D Status Predicts 30 Day Mortality in Hospitalised Cats

Vitamin D insufficiency, defined as low serum concentrations of the major circulating form of vitamin D, 25 hydroxyvitamin D (25(OH)D), has been associated with the development of numerous infectious, inflammatory, and neoplastic disorders in humans. In addition, vitamin D insufficiency has been found to be predictive of mortality for many disorders. However, interpretation of human studies is difficult since vitamin D status is influenced by many factors, including diet, season, latitude, and exposure to UV radiation. In contrast, domesticated cats do not produce vitamin D cutaneously, and most cats are fed a commercial diet containing a relatively standard amount of vitamin D. Consequently, domesticated cats are an attractive model system in which to examine the relationship between serum 25(OH)D and health outcomes. The hypothesis of this study was that vitamin D status would predict short term, all-cause mortality in domesticated cats. Serum concentrations of 25(OH)D, together with a wide range of other clinical, hematological, and biochemical parameters, were measured in 99 consecutively hospitalised cats. Cats which died within 30 days of initial assessment had significantly lower serum 25(OH)D concentrations than cats which survived. In a linear regression model including 12 clinical variables, serum 25(OH)D concentration in the lower tertile was significantly predictive of mortality. The odds ratio of mortality within 30 days was 8.27 (95% confidence interval 2.54-31.52) for cats with a serum 25(OH)D concentration in the lower tertile. In conclusion, this study demonstrates that low serum 25(OH)D concentration status is an independent predictor of short term mortality in cats.