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Associations between Aging and Vitamin D Status with Whole-Body Nitric Oxide Production and Markers of Endothelial Function

Siervo M, Hussin AM, Calella P, Ashor A, Shannon OM, Mendes I, et al.

J Nutr, 2024 Feb;154(2):469-478.
PMID: 38048992 DOI: 10.1016/j.tjnut.2023.12.002

BACKGROUND: Aging and vitamin D deficiency have been associated with reduced nitric oxide (NO) synthesis and impaired endothelial function (EF) but the evidence in humans remains weak.
OBJECTIVES: Two independent cross-sectional studies were designed to evaluate the association between age, sex, and plasma vitamin D concentrations with physiological and biochemical biomarkers of NO synthesis and EF in young and older healthy participants (Study 1) and in overweight and obese postmenopausal females (Study 2).
METHODS: In Study 1, 40 young (20-49 y) and older (50-75 y) males and females (10 participants per age and sex group) were included. Resting blood pressure and ear-to-finger peripheral pulse wave velocity (PWV) were measured. A stable-isotopic method was used to determine whole-body NO production. Plasma 25-hydroxyvitamin D (25(OH)D), nitrate, nitrite, and asymmetric dimethylarginine (ADMA) concentrations were determined. In Study 2, 80 older overweight and obese females (age 61.2 ± 6.2 y, body mass index 29.5 ± 4.4 kg/m2) were recruited. Postocclusion reactive hyperemia (PORH) and peripheral PWV were measured. Plasma concentrations of 25(OH)D, nitrate, cyclic guanosine monophosphate, 3-nitrotyrosine (3-NT), endothelin-1, vascular endothelial growth factor, and ADMA were determined.
RESULTS: In Study 1, whole-body NO production was significantly greater in young compared with older participants (0.61 ± 0.30 μmol·h-1·kg-1 compared with 0.39 ± 0.10 μmol·h-1·kg-1, P = 0.01) but there was no evidence of a sex difference (P = 0.81). Plasma 25(OH)D concentration was not associated with PWV (r = 0.18, P = 0.28) or whole-body NO production (r = -0.20, P = 0.22). Plasma ADMA concentration was associated positively with age (r = 0.35, P = 0.03) and negatively with whole-body NO production (r = -0.33, P = 0.04). In Study 2, age was associated with lower PORH (r = -0.28, P = 0.02) and greater ADMA concentrations (r = 0.22, P = 0.04). Plasma 25(OH)D concentration was inversely associated with 3-NT concentrations (r = -0.31, P = 0.004).
CONCLUSIONS: Older age was associated with lower whole-body NO production. Plasma vitamin D concentrations were not associated with NO production or markers of EF but showed a weak, significant correlation with oxidative stress in postmenopausal overweight females.

Matched MeSH terms: Vitamin D; Vitamin D Deficiency*
Fulltext A Collaborative Analysis of Individual Participant Data from 19 Prospective Studies Assesses Circulating Vitamin D and Prostate Cancer Risk

Travis RC, Perez-Cornago A, Appleby PN, Albanes D, Joshu CE, Lutsey PL, et al.

Cancer Res, 2019 Jan 01;79(1):274-285.
PMID: 30425058 DOI: 10.1158/0008-5472.CAN-18-2318

Previous prospective studies assessing the relationship between circulating concentrations of vitamin D and prostate cancer risk have shown inconclusive results, particularly for risk of aggressive disease. In this study, we examine the association between prediagnostic concentrations of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] and the risk of prostate cancer overall and by tumor characteristics. Principal investigators of 19 prospective studies provided individual participant data on circulating 25(OH)D and 1,25(OH)2D for up to 13,462 men with incident prostate cancer and 20,261 control participants. ORs for prostate cancer by study-specific fifths of season-standardized vitamin D concentration were estimated using multivariable-adjusted conditional logistic regression. 25(OH)D concentration was positively associated with risk for total prostate cancer (multivariable-adjusted OR comparing highest vs. lowest study-specific fifth was 1.22; 95% confidence interval, 1.13-1.31; P trend < 0.001). However, this association varied by disease aggressiveness (P heterogeneity = 0.014); higher circulating 25(OH)D was associated with a higher risk of nonaggressive disease (OR per 80 percentile increase = 1.24, 1.13-1.36) but not with aggressive disease (defined as stage 4, metastases, or prostate cancer death, 0.95, 0.78-1.15). 1,25(OH)2D concentration was not associated with risk for prostate cancer overall or by tumor characteristics. The absence of an association of vitamin D with aggressive disease does not support the hypothesis that vitamin D deficiency increases prostate cancer risk. Rather, the association of high circulating 25(OH)D concentration with a higher risk of nonaggressive prostate cancer may be influenced by detection bias. SIGNIFICANCE: This international collaboration comprises the largest prospective study on blood vitamin D and prostate cancer risk and shows no association with aggressive disease but some evidence of a higher risk of nonaggressive disease.

Matched MeSH terms: Vitamin D/analogs & derivatives*; Vitamin D/blood
Fulltext Maternal Vitamin D Levels during Late Pregnancy and Risk of Allergic Diseases and Sensitization during the First Year of Life-A Birth Cohort Study

Woon FC, Chin YS, Ismail IH, Abdul Latiff AH, Batterham M, Chan YM, et al.

Nutrients, 2020 Aug 12;12(8).
PMID: 32806653 DOI: 10.3390/nu12082418

Allergic diseases are the most common chronic illness in childhood. Findings from developed countries have reported associations between Vitamin D levels during pregnancy and offspring allergy risk. This prospective cohort study aimed to determine the associations between maternal Vitamin D levels during late pregnancy and allergic diseases in Malaysian infants during the first year of life. Serum 25(OH)D concentrations of 380 pregnant women in the third trimester were measured using a chemiluminescent immunoassay. Children's allergic outcomes were assessed at 3, 6, and 12 months based on parental reports. Specific IgE antibodies against food and inhalant allergens were measured in infants at 12 months of age. A total of 43.2% pregnant women were Vitamin D deficient (<30 nmol/L) and 56.8% were nondeficient (≥30 nmol/L). A total of 27.6% of the infants had eczema, 6.1% had wheeze, 27.4% had food sensitization, 10.8% had inhalant allergen sensitization, and 3.8% had IgE-mediated food allergy during the first year of life. Compared with the nondeficient group, maternal Vitamin D deficiency in late pregnancy was not associated with any allergic outcomes after adjustment for potential confounding factors. In conclusion, the present study does not support an association between maternal Vitamin D levels in late pregnancy and allergic outcomes during the first year of life.

Matched MeSH terms: Vitamin D/analogs & derivatives*; Vitamin D/blood; Vitamin D Deficiency/complications*
Effects of 25-hydroxyvitamin D and vitamin D-binding protein on bone mineral density and disease activity in Malaysian patients with rheumatoid arthritis

Wong TH, Das Gupta E, Radhakrishnan AK, Gun SC, Chembalingam G, Yeap SS

Int J Rheum Dis, 2018 May;21(5):992-1000.
PMID: 28217867 DOI: 10.1111/1756-185X.13048

AIM: Vitamin D3 [25(OH)D] has been shown to be important in bone health and can influence rheumatoid arthritis (RA) disease activity. Vitamin D-binding protein (VDBP) levels vary with race and may modulate 'bioavailable' levels of 25(OH)D. The aim of this study was to explore the relationships between 25(OH)D, VDBP and clinical factors on bone mineral density (BMD) in a group of multi-ethnic Malaysian RA patients and healthy controls.

METHODS: A cross-sectional study of 77 female RA patients and 29 controls was performed. Serum 25(OH)D was measured using the Elecsys® Vitamin D total assay. Serum VDBP was measured using a Quantikine® enzyme-linked immunosorbent assay kit. BMD was assessed using dual-energy X-ray absorptiometry (DXA).

RESULTS: Overall, mean 25(OH)D levels were 42.66 ± 21.75 nmol/L with no significant difference between RA patients and controls. 25(OH)D levels were significantly higher in Chinese, compared to Malay/Indian subjects. In RA patients, menopausal status and body mass index (BMI) were significantly associated with BMD but not 25(OH)D or RA Disease Activity Score of 28 joints (DAS28). There was no significant correlation between 25(OH)D and DAS28, even after correction for menopausal status and BMI. VDBP levels were not significantly different between the races and did not significantly correlate with BMD, 25(OH)D overall, or DAS28 in RA patients.

CONCLUSIONS: In Malaysian RA patients, menopausal status and BMI were more important influences on BMD than 25(OH)D or RA disease activity. The utility of measuring VDBP levels in this population remains uncertain.
Study site: Rheumatology clinic, Hospital Tuanku Jaafar, Seremban, Negeri Semblance; Klinik Pakar Puchong, Puchong, Kuala Lumpur, Malaysia

Matched MeSH terms: Vitamin D/analogs & derivatives*; Vitamin D/blood; Vitamin D-Binding Protein/blood*
Milk vitamin D in relation to the 'adequate intake' for 0-6-month-old infants: a study in lactating women with different cultural backgrounds, living at different latitudes

Stoutjesdijk E, Schaafsma A, Nhien NV, Khor GL, Kema IP, Hollis BW, et al.

Br J Nutr, 2017 Nov;118(10):804-812.
PMID: 29103383 DOI: 10.1017/S000711451700277X

Breast-fed infants are susceptible to vitamin D deficiency rickets. The current vitamin D 'adequate intake' (AI) for 0-6-month-old infants is 10 µg/d, corresponding with a human milk antirachitic activity (ARA) of 513 IU/l. We were particularly interested to see whether milk ARA of mothers with lifetime abundant sunlight exposure reaches the AI. We measured milk ARA of lactating mothers with different cultural backgrounds, living at different latitudes. Mature milk was derived from 181 lactating women in the Netherlands, Curaçao, Vietnam, Malaysia and Tanzania. Milk ARA and plasma 25-hydroxyvitamin D (25(OH)D) were analysed by liquid-chromatography-MS/MS; milk fatty acids were analysed by GC-flame ionisation detector (FID). None of the mothers reached the milk vitamin D AI. Milk ARA (n; median; range) were as follows: Netherlands (n 9; 46 IU/l; 3-51), Curaçao (n 10; 31 IU/l; 5-113), Vietnam: Halong Bay (n 20; 58 IU/l; 23-110), Phu Tho (n 22; 28 IU/l; 1-62), Tien Giang (n 20; 63 IU/l; 26-247), Ho-Chi-Minh-City (n 18; 49 IU/l; 24-116), Hanoi (n 21; 37 IU/l; 11-118), Malaysia-Kuala Lumpur (n 20; 14 IU/l; 1-46) and Tanzania-Ukerewe (n 21; 77 IU/l; 12-232) and Maasai (n 20; 88 IU/l; 43-189). We collected blood samples of these lactating women in Curaçao, Vietnam and from Tanzania-Ukerewe, and found that 33·3 % had plasma 25(OH)D levels between 80 and 249·9 nmol/l, 47·3 % between 50 and 79·9 nmol/l and 19·4 % between 25 and 49·9 nmol/l. Milk ARA correlated positively with maternal plasma 25(OH)D (range 27-132 nmol/l, r 0·40) and milk EPA+DHA (0·1-3·1 g%, r 0·20), and negatively with latitude (2°S-53°N, r -0·21). Milk ARA of mothers with lifetime abundant sunlight exposure is not even close to the vitamin D AI for 0-6-month-old infants. Our data may point at the importance of adequate fetal vitamin D stores.

Matched MeSH terms: Vitamin D/administration & dosage*; Vitamin D/analogs & derivatives; Vitamin D/blood; Vitamin D/metabolism
Environmental and genetic determinants of vitamin D insufficiency in 12-month-old infants

Suaini NH, Koplin JJ, Ellis JA, Peters RL, Ponsonby AL, Dharmage SC, et al.

J Steroid Biochem Mol Biol, 2014 Oct;144 Pt B:445-54.
PMID: 25174667 DOI: 10.1016/j.jsbmb.2014.08.018

We aimed to investigate the relationship between genetic and environmental exposure and vitamin D status at age one, stratified by ethnicity. This study included 563 12-month-old infants in the HealthNuts population-based study. DNA from participants' blood samples was genotyped using Sequenom MassARRAY MALDI-TOF system on 28 single nucleotide polymorphisms (SNPs) in six genes. Using logistic regression, we examined associations between environmental exposure and SNPs in vitamin D pathway and filaggrin genes and vitamin D insufficiency (VDI). VDI, defined as serum 25-hydroxyvitamin D3(25(OH)D3) level ≤50nmol/L, was measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Infants were stratified by ethnicity determined by parent's country of birth. Infants formula fed at 12 months were associated with reduced odds of VDI compared to infants with no current formula use at 12 months. This association differed by ethnicity (Pinteraction=0.01). The odds ratio (OR) of VDI was 0.29 for Caucasian infants (95% CI, 0.18-0.47) and 0.04 for Asian infants (95% CI, 0.006-0.23). Maternal vitamin D supplementation during pregnancy and/or breastfeeding were associated with increased odds of infants being VDI (OR, 2.39; 95% CI, 1.11-5.18 and OR, 2.5; 95% CI, 1.20-5.24 respectively). Presence of a minor allele for any GC SNP (rs17467825, rs1155563, rs2282679, rs3755967, rs4588, rs7041) was associated with increased odds of VDI. Caucasian infants homozygous (AA) for rs4588 had an OR of 2.49 of being associated with VDI (95% CI, 1.19-5.18). In a country without routine infant vitamin D supplementation or food chain fortification, formula use is strongly associated with a reduced risk of VDI regardless of ethnicity. There was borderline significance for an association between filaggrin mutations and VDI. However, polymorphisms in vitamin D pathway related genes were associated with increased likelihood of being VDI in infancy.

Matched MeSH terms: Vitamin D/administration & dosage; Vitamin D Deficiency/etiology*; Vitamin D Deficiency/epidemiology*; Vitamin D-Binding Protein/genetics; 25-Hydroxyvitamin D3 1-alpha-Hydroxylase/genetics; Vitamin D3 24-Hydroxylase/genetics
Fulltext Impact of Vitamin D Replacement on Markers of Glucose Metabolism and Cardio-Metabolic Risk in Women with Former Gestational Diabetes--A Double-Blind, Randomized Controlled Trial

Yeow TP, Lim SL, Hor CP, Khir AS, Wan Mohamud WN, Pacini G

PLoS One, 2015;10(6):e0129017.
PMID: 26057782 DOI: 10.1371/journal.pone.0129017

Gestational Diabetes Mellitus (GDM) and vitamin D deficiency are related to insulin resistance and impaired beta cell function, with heightened risk for future development of diabetes. We evaluated the impact of vitamin D supplementation on markers of glucose metabolism and cardio metabolic risk in Asian women with former GDM and hypovitaminosis D. In this double blind, randomized controlled trial, 26 participants were randomized to receive either daily 4000 IU vitamin D3 or placebo capsules. 75 g Oral Glucose Tolerance Test (OGTT) and biochemistry profiles were performed at baseline and 6 month visits. Mathematical models, using serial glucose, insulin and C peptide measurements from OGTT, were employed to calculate insulin sensitivity and beta cell function. Thirty three (76%) women with former GDM screened had vitamin D level of <50 nmol/L at baseline. Supplementation, when compared with placebo, resulted in increased vitamin D level (+51.1 nmol/L vs 0.2 nmol/L, p<0.001) and increased fasting insulin (+20% vs 18%, p = 0.034). The vitamin D group also demonstrated a 30% improvement in disposition index and an absolute 0.2% (2 mmol/mol) reduction in HbA1c. There was no clear change in insulin sensitivity or markers of cardio metabolic risk. This study highlighted high prevalence of vitamin D deficiency among Asian women with former GDM. Six months supplementation with 4000 IU of vitamin D3 safely restored the vitamin D level, improved basal pancreatic beta-cell function and ameliorated the metabolic state. There was no effect on markers of cardio metabolic risk. Further mechanistic studies exploring the role of vitamin D supplementation on glucose homeostasis among different ethnicities may be needed to better inform future recommendations for these women with former GDM at high risk of both hypovitaminosis D and future diabetes.

Matched MeSH terms: Vitamin D/administration & dosage; Vitamin D/therapeutic use*; Vitamin D Deficiency/blood; Vitamin D Deficiency/drug therapy*; Vitamin D Deficiency/ethnology
Fulltext Risk factors for antenatal hypovitaminosis D in an urban district in Malaysia

Bukhary NBI, Isa ZM, Shamsuddin K, Lin KG, Mahdy ZA, Hassan H, et al.

BMC Pregnancy Childbirth, 2016 07 13;16(1):156.
PMID: 27411716 DOI: 10.1186/s12884-016-0939-3

BACKGROUND: Pregnant women form one of the high risk groups facing hypovitaminosis D. Low level of vitamin D will affect directly or indirectly both mother and fetus. Screening vitamin D in the first trimester of pregnancy is important to determine the necessary preventive action. Therefore, this study was aimed to determine the prevalence of hypovitaminosis D and its risk factors among pregnant women in the first trimester.
METHODS: A cross sectional study was carried out among first trimester pregnant women during their first antenatal visit. Samples were taken from different ethnicities in an urban district in Malaysia. A total of 396 respondents (99 % response rate) aged 18-40 years completed self-administered and guided questionnaire (characteristics and risk factors), validated semi-quantitative food frequency questionnaire for vitamin D in Malaysia (FFQ vitamin D/My), anthropometric measures (weight and height), blood test for serum 25(OH)D, skin measurement using Mexameter (MX 18) and Fitzpatrick Skin Type Chart Measurement (FSTCM). Data were analyzed to determine the association between risk factors and hypovitaminosis D.
RESULTS: The prevalence of hypovitaminosis D (serum 25(OH)D vitamin D (especially milk) poorly in order to prevent adverse health outcomes. Further studies need to be conducted among health care workers to determine their level of knowledge related to vitamin D, as they are front liner in detecting the hypovitaminosis D.

Matched MeSH terms: Vitamin D/analogs & derivatives*; Vitamin D/blood; Vitamin D Deficiency/ethnology; Vitamin D Deficiency/etiology*; Vitamin D Deficiency/epidemiology
Impaired microvascular endothelial function in vitamin D-deficient diabetic nephropathy patients

Munisamy S, Kamaliah MD, Suhaidarwani AH, Zahiruddin WM, Rasool AH

J Cardiovasc Med (Hagerstown), 2013 Jun;14(6):466-71.
PMID: 22964652 DOI: 10.2459/JCM.0b013e3283590d3d

AIMS: This study aims to compare microvascular endothelial function between vitamin D-deficient and nondeficient groups of patients with diabetic nephropathy. Serum levels of the inflammatory marker high-sensitivity C-reactive protein (hsCRP) were also measured.
METHODS: This prospective cross-sectional study involved 70 patients with diabetic nephropathy; 40 were categorized into the group with nondeficient serum 25-hydroxyvitamin D levels [25(OH)D >50 nmol/l], whereas 30 patients were categorized to the group with deficient serum 25(OH)D (<50 nmol/l). Microvascular endothelial function was determined using laser Doppler fluximetry and the process of iontophoresis. Acetylcholine and sodium nitroprusside were used to determine endothelium-dependent and independent vasodilatation.
RESULTS: Mean age of patients was 56.7 ± 3.8 years; 50 were men, whereas 20 were women. Mean serum 25(OH)D in the vitamin D-nondeficient group was 69.4 ± 2.9 nmol/l; the level in the vitamin D-deficient group was 42.1 ± 1.3 nmol/l, P < 0.001. Endothelium-dependent vasodilatation was lower in the vitamin D-deficient group compared with the vitamin D-nondeficient group (23.6 ± 2.7 versus 37.3 ± 3.8 arbitrary units, P = 0.004). No significant differences were observed between the two groups in their hsCRP levels, mean age, estimated glomerular filtration rate, systolic blood pressure (SBP) and diastolic blood pressure (DBP) and glycosylated haemoglobin.
CONCLUSION: Microvascular endothelial function was significantly reduced in diabetic nephropathy patients with deficient vitamin D levels compared with those with nondeficient levels.

Matched MeSH terms: Vitamin D/analogs & derivatives; Vitamin D/blood; Vitamin D Deficiency/blood; Vitamin D Deficiency/physiopathology*
Molecular characterization, modeling and docking of CYP107CB2 from Bacillus lehensis G1, an alkaliphile

Ang SS, Salleh AB, Chor AL, Normi YM, Tejo BA, Rahman MB

Comput Biol Chem, 2015 Jun;56:19-29.
PMID: 25766878 DOI: 10.1016/j.compbiolchem.2015.02.015

Cytochrome P450s are a superfamily of heme monooxygenases which catalyze a wide range of biochemical reactions. The reactions involve the introduction of an oxygen atom into an inactivated carbon of a compound which is essential to produce an intermediate of a hydroxylated product. The diversity of chemical reactions catalyzed by cytochrome P450s has led to their increased demand in numerous industrial and biotechnology applications. A recent study showed that a gene sequence encoding a CYP was found in the genome of Bacillus lehensis G1, and this gene shared structural similarity with the bacterial vitamin D hydroxylase (Vdh) from Pseudonocardia autotrophica. The objectives of present study was to mine, for a novel CYP from a new isolate B. lehensis G1 alkaliphile and determine the biological properties and functionalities of CYP in this bacterium. Our study employed the usage of computational methods to search for the novel CYP from CYP structural databases to identify the conserved pattern, functional domain and sequence properties of the uncharacterized CYP from B. lehensis G1. A computational homology model of the protein's structure was generated and a docking analysis was performed to provide useful structural knowledge on the enzyme's possible substrate and their interaction. Sequence analysis indicated that the newly identified CYP, termed CYP107CB2, contained the fingerprint heme binding sequence motif FxxGxxxCxG at position 336-345 as well as other highly conserved motifs characteristic of cytochrome P450 proteins. Using docking studies, we identified Ser-79, Leu-81, Val-231, Val-279, Val-383, Ala-232, Thr-236 and Thr-283 as important active site residues capable of stabilizing interactions with several potential substrates, including vitamin D3, 25-hydroxyvitamin D3 and 1α-hydroxyvitamin D3, in which all substrates docked proximally to the enzyme's heme center. Biochemical analysis indicated that CYP107CB2 is a biologically active protein to produce 1α,25-dihydroxyvitamin D3 from 1α-hydroxyvitamin D3. Based on these results, we conclude that the novel CYP107CB2 identified from B. lehensis G1 is a putative vitamin D hydroxylase which is possibly capable of catalyzing the bioconversion of parental vitamin D3 to calcitriol, or related metabolic products.

Matched MeSH terms: Vitamin D/analogs & derivatives; Vitamin D/metabolism
Pre-diagnostic vitamin D concentrations and cancer risks in older individuals: an analysis of cohorts participating in the CHANCES consortium

Ordóñez-Mena JM, Schöttker B, Fedirko V, Jenab M, Olsen A, Halkjær J, et al.

Eur J Epidemiol, 2016 Mar;31(3):311-23.
PMID: 25977096 DOI: 10.1007/s10654-015-0040-7

The associations of circulating 25-hydroxyvitamin D [25(OH)D] concentrations with total and site-specific cancer incidence have been examined in several epidemiological studies with overall inconclusive findings. Very little is known about the association of vitamin D with cancer incidence in older populations. We assessed the association of pre-diagnostic serum 25(OH)D levels with incidence of all cancers combined and incidence of lung, colorectal, breast, prostate and lymphoid malignancies among older adults. Pre-diagnostic 25(OH)D concentrations and cancer incidence were available in total for 15,486 older adults (mean age 63, range 50-84 years) participating in two cohort studies: ESTHER (Germany) and TROMSØ (Norway); and a subset of previously published nested-case control data from a another cohort study: EPIC-Elderly (Greece, Denmark, Netherlands, Spain and Sweden) from the CHANCES consortium on health and aging. Cox proportional hazards or logistic regression were used to derive multivariable adjusted hazard and odds ratios, respectively, and their 95% confidence intervals across 25(OH)D categories. Meta-analyses with random effects models were used to pool study-specific risk estimates. Overall, lower 25(OH)D concentrations were not significantly associated with increased incidence of most of the cancers assessed. However, there was some evidence of increased breast cancer and decreased lymphoma risk with higher 25(OH)D concentrations. Our meta-analyses with individual participant data from three large European population-based cohort studies provide at best limited support for the hypothesis that vitamin D may have a major role in cancer development and prevention among European older adults.

Matched MeSH terms: Vitamin D/analogs & derivatives; Vitamin D/blood*
Nutritional status and dietary intakes of children aged 6 months to 12 years: findings of the Nutrition Survey of Malaysian Children (SEANUTS Malaysia)

Poh BK, Ng BK, Siti Haslinda MD, Nik Shanita S, Wong JE, Budin SB, et al.

Br J Nutr, 2013 Sep;110 Suppl 3:S21-35.
PMID: 24016764 DOI: 10.1017/S0007114513002092

The dual burden of malnutrition reportedly coexists in Malaysia; however, existing data are scarce and do not adequately represent the nutritional status of Malaysian children. The Nutrition Survey of Malaysian Children was carried out with the aim of assessing the nutritional status in a sample of nationally representative population of children aged 6 months to 12 years. A total of 3542 children were recruited using a stratified random sampling method. Anthropometric measurements included weight, height, mid-upper arm circumference, and waist and hip circumferences. Blood biochemical assessment involved analyses of Hb, serum ferritin, and vitamins A and D. Dietary intake was assessed using semi-quantitative FFQ, and nutrient intakes were compared with the Malaysian Recommended Nutrient Intakes (RNI). The prevalence of overweight (9·8%) and obesity (11·8%) was higher than that of thinness (5·4%) and stunting (8·4%). Only a small proportion of children had low levels of Hb (6·6%), serum ferritin (4·4%) and vitamin A (4·4%), but almost half the children (47·5%) had vitamin D insufficiency. Dietary intake of the children was not compatible with the recommendations, where more than one-third did not achieve the Malaysian RNI for energy, Ca and vitamin D. The present study revealed that overnutrition was more prevalent than undernutrition. The presence of high prevalence of vitamin D insufficiency and the inadequate intake of Ca and vitamin D are of concern. Hence, strategies for improving the nutritional status of Malaysian children need to consider both sides of malnutrition and also put emphasis on approaches for the prevention of overweight and obesity as well as vitamin D insufficiency.

Matched MeSH terms: Vitamin D/blood; Vitamin D Deficiency/epidemiology
Osteoporosis treatment following a low trauma wrist fracture presenting to the accident and emergency department from 2011 to 2015

Yeap SS, Akhir NSM, Thirunavukkarasu V, Thambiah SC, Samsudin IN, Sham SYZ, et al.

Clin Cases Miner Bone Metab, 2018;15:74-78.
DOI: 10.11138/ccmbm/2017.15.1.074

Objective: The aim of this study was to determine the treatment given to patients following a low trauma wrist fracture presenting to an Accident and Emergency (A&E) Department at a tertiary private hospital in Malaysia. Methods: The records of patients over the age of 50 attending A&E Department from 2011-2015 with a diagnosis of Colles Vdistal radius/wrist fracture were obtained. Information was extracted for those with a low trauma fracture. Data was analysed using IBM SPSS Statistics version 22.0 for Windows. Results: 191 patients presented with a wrist fracture for the years 2011-2015. 57 of these were due to accidents which left 134 (70.2%) low trauma wrist fractures for analysis. The mean age of the patients was 61.75 ± 10.23 [standard deviation (SD)] years. There were 87 (64.9%) females, and 90 (67.2%) were of Chinese ethnicity. Following the index low trauma wrist fracture, 16/134 (11.9%) were given anti-osteoporotic medication. Of those given treatment, 11/16 (68.8%) were given calcium/Vitamin D/activated Vitamin D and only 5/16 (31.2%) were given active anti-osteoporotic treatment. The median duration of prescribed treatment was one month. There was no significant difference in demographic factors between patients who were treated and not treated with anti-osteoporosis medication. Conclusions: Currently, treatment for osteoporosis following low trauma wrist fractures in Malaysia is inadequate with only 11.9% receiving treatment, and in those who are treated, the median duration of treatment was only one month. This represents a missed opportunity for the prevention of future fractures. © 2018 CIC Edizioni Internazionali s.r.l. All rights reserved.

Matched MeSH terms: Vitamin D
The influence of omega-3 supplementation on vitamin D levels in humans: a systematic review and dose-response meta-analysis of randomized controlled trials

Alhabeeb H, Kord-Varkaneh H, Tan SC, Găman MA, Otayf BY, Qadri AA, et al.

Crit Rev Food Sci Nutr, 2020 Dec 25.
PMID: 33356450 DOI: 10.1080/10408398.2020.1863905

BACKGROUND: Inconsistencies exist with regard to the influence of omega-3 supplementation on 25-hydroxyvitamin D (25(OH)D) levels, which could be attributed to many factors, such as the duration and dose of omega-3 supplementation, and individuals' baseline 25(OH)D levels. Therefore, to address the inconsistencies, we conducted a systematic review and dose-response meta-analysis to accurately determine the effect of omega-3 supplementation on 25(OH)D levels in humans.
METHODS: We performed a comprehensive literature search in Web of Science, PubMed/Medline, Scopus, and Embase databases from inception up to January 2020. We included only randomized controlled trials (RCTs). We used weighted mean difference (WMD) with 95% confidence interval (CI) to assess the influence of omega-3 supplementation on serum 25(OH)D levels using the random-effects model.
RESULTS: Our pooled results of 10 RCTs demonstrated an overall significant increase in 25(OH)D levels following omega-3 intake (WMD = 3.77 ng/ml, 95% CI: 1.29, 6.25). In addition, 25(OH)D levels were significantly increased when the intervention duration lasted >8 weeks and when the baseline serum 25(OH)D level was ˂20 ng/ml. Moreover, omega-3 intake ≤1000 mg/day resulted in higher 25(OH)D levels compared to omega-3 intake >1000 mg/day.
CONCLUSION: In conclusion, omega-3 supplementation increased 25(OH)D concentrations, particularly with dosages ≤1000 mg/day and intervention durations >8 weeks.

Matched MeSH terms: Vitamin D
Vitamin D deficiency is associated with ethnicity and knee pain in a multi-ethnic South-East Asian nation: Results from Malaysian Elders Longitudinal Research (MELoR)

Mat S, Jaafar MH, Sockalingam S, Raja J, Kamaruzzaman SB, Chin AV, et al.

Int J Rheum Dis, 2018 May;21(5):930-936.
PMID: 29611292 DOI: 10.1111/1756-185X.13279

AIM: To determine the association between vitamin D and knee pain among participants of the Malaysian Elders Longitudinal Research (MELoR) study.

METHOD: This was a cross-sectional study from the MELoR study consisting of a representative group of 1011 community-dwelling older persons (57% female), mean age 86.5 (54-94) years; 313 were Malays, 367 Chinese and 330 Indians. Participants were asked if they had knee pain. Levels of serum 25-hydroxy cholecalciferol (25-[OH]D), an indicator of vitamin D status, were measured using routine laboratory techniques.

RESULTS: In unadjusted analysis, presence of knee pain was significantly associated with vitamin D deficiency (odds ratio [OR] 1.42; 95% confidence interval (CI) 1.08-1.85, P 0.011). Vitamin D levels were significantly associated with ethnicity differences where Malays (OR 7.08; 95% CI 4.94-10.15) and Indians (OR 6.10; 95% CI 4.28-9.71) have lower levels of vitamin D compared to Chinese. Subsequent multivariate analysis revealed that the association between vitamin D deficiency and knee pain was confounded by ethnic differences.

CONCLUSION: A previous study suggested that vitamin D deficiency was associated with knee pain. This relationship was reproduced in our study, but we further established that the association was explained by ethnic variations. As vitamin D status is dependent on skin tone, diet and sunlight exposure, which are all effected by ethnicity, future studies are now required to determine whether a true relationship exists between vitamin D and knee pain.

Matched MeSH terms: Vitamin D Deficiency/blood; Vitamin D Deficiency/diagnosis; Vitamin D Deficiency/ethnology*
Fulltext Antibody dynamics post-Comirnaty and CoronaVac vaccination in Malaysia

Tan CS, Noni V, Melina WUHU, Abdorahman US, Bimbang JN, Malik NMA, et al.

Sci Rep, 2022 09 19;12(1):15665.
PMID: 36123431 DOI: 10.1038/s41598-022-19776-3

Several vaccines have been fast-tracked through clinical trials to mitigate the progression of the SARS‑CoV‑2 pandemic. We analyzed sequential blood samples from 314 recipients of Comirnaty and CoronaVac in East Malaysia for the spike-binding IgG (IgG-S), nucleocapsid-binding IgG (IgG-N), spike-binding IgM (IgM-S) and serum vitamin D (VitD). A subset of samples was analyzed for the neutralizing antibodies (Ig-RBD). Results showed that IgG-S due to Comirnaty was significantly higher than CoronaVac. IgM-S was detected in 80.0% Comirnaty and 69.5% CoronaVac recipients, while IgG-N was detected in 58.1% CoronaVac but not in Comirnaty recipients. All IgG-S-positive vaccines possessed detectable Ig-RBD after the second dose but with a weak to moderate correlation. The serum VitD levels did not influence the antibody magnitude in both vaccines. In essence, SARS-CoV-2 vaccination is an IgG-S-dominant event, Comirnaty was more effective than CoronaVac in mounting IgG-S and Ig-RBD responses, independent of the patient's VitD level.

Matched MeSH terms: Vitamin D
Fulltext Rickets Due to Severe Vitamin D and Calcium Deficiency During the COVID-19 Pandemic in Malaysia

Sodri NI, Mohamed-Yassin MS, Mohd Nor NS, Ismail IA

Am J Case Rep, 2021 Nov 01;22:e934216.
PMID: 34723934 DOI: 10.12659/AJCR.934216

BACKGROUND Rickets is the deficiency in mineralization of the bone associated with lack of sunlight exposure and inadequate dietary calcium and/or vitamin D in children. Important efforts to eradicate rickets include appropriate sunlight exposure advice and fortification of food and milk with vitamin D. However, there is a growing concern that the current Coronavirus Disease 2019 (COVID-19) pandemic will increase the incidence of rickets due to inadequate sunlight exposure resulting from movement restriction measures imposed by governments across the world. CASE REPORT A 22-month-old girl presented to our primary care clinic in Selangor, Malaysia with abnormal gait and bowing of the legs during the COVID-19 pandemic. She had a history of inadequate sun exposure as she lived in an apartment and there was a Movement Control Order in place because of the pandemic. Calcium intake was also poor as she could not tolerate formula milk and did not consume any other dairy products. Investigations revealed severe hypocalcemia and low vitamin D level. She was diagnosed with nutritional rickets and was referred for admission to correct the hypocalcemia. She was subsequently discharged with oral calcium and vitamin D supplementation. Her calcium and vitamin D levels improved and at her 6-month review, her bilateral bowed legs had improved significantly. CONCLUSIONS This case highlights the importance of having a high degree of suspicion for vitamin D deficiency and rickets in young children growing up during the COVID-19 pandemic. Public health messages on preventing the spread of COVID-19 should also be interlaced with messages addressing the possible effects of our new norms such as inadequate sunlight exposure.

Matched MeSH terms: Vitamin D
Fulltext A highly sensitive LC-MS/MS method for quantitative determination of 7 vitamin D metabolites in mouse brain tissue

Stephenson AJ, Hunter B, Shaw PN, Kassim NSA, Trengove R, Takechi R, et al.

Anal Bioanal Chem, 2023 Mar;415(7):1357-1369.
PMID: 36705732 DOI: 10.1007/s00216-023-04527-8

Despite its critical role in neurodevelopment and brain function, vitamin D (vit-D) homeostasis, metabolism, and kinetics within the central nervous system remain largely undetermined. Thus, it is of critical importance to establish an accurate, highly sensitive, and reproducible method to quantitate vit-D in brain tissue. Here, we present a novel liquid chromatography tandem mass spectrometry (LC-MS/MS) method and for the first time, demonstrate detection of seven major vit-D metabolites in brain tissues of C57BL/6J wild-type mice, namely 1,25(OH)2D3, 3-epi-1,25(OH)2D3, 1,25(OH)2D2, 25(OH)D3, 25(OH)D2, 24,25(OH)2D3, and 24,25(OH)2D2. Chromatographic separation was achieved on a pentaflurophenyl column with 3 mM ammonium formate water/methanol [A] and 3 mM ammonium formate methanol/isopropanol [B] mobile phase components. Detection was by positive ion electrospray tandem mass spectrometry with the EVOQ elite triple quadrupole mass spectrometer with an Advance ultra-high-performance liquid chromatograph and online extraction system. Calibration standards of each metabolite prepared in brain matrices were used to validate the detection range, precision, accuracy, and recovery. Isotopically labelled analogues, 1,25(OH)2D3-d3, 25(OH)D3-c5, and 24,25(OH)2D3-d6, served as the internal standards for the closest molecular-related metabolite in all measurements. Standards between 1 fg/mL and 10 ng/mL were injected with a resulting linear range between 0.001 and 1 ng, with an LLOD and LLOQ of 1 pg/mL and 12.5 pg/mL, respectively. The intra-/inter-day precision and accuracy for measuring brain vit-D metabolites ranged between 0.12-11.53% and 0.28-9.11%, respectively. Recovery in acetonitrile ranged between 99.09 and 106.92% for all metabolites. Collectively, the sensitivity and efficiency of our method supersedes previously reported protocols used to measure vit-D and to our knowledge, the first protocol to reveal the abundance of 25(OH)D2, 1,25(OH)D2, and 24,25(OH)2D2, in brain tissue of any species. This technique may be important in supporting the future advancement of pre-clinical research into the function of vit-D in neurophysiological and neuropsychiatric disorders, and neurodegeneration.

Matched MeSH terms: Vitamin D
Serum vitamin D levels among immunoglobulin A nephropathy patients and the associated parameters

Mustafar R, Nesam T, Kamaruzaman L, Mohd R, Sukor N, Safian N, et al.

Med J Malaysia, 2023 Jan;78(1):87-92.
PMID: 36715197

INTRODUCTION: Low serum 25-hydroxyvitamin D is associated with chronic kidney disease progression, and there are limited data on the vitamin D levels in patients with Immunoglobulin A nephropathy. This study was conducted to determine the level of 25-hydroxyvitamin D in a stable immunoglobulin A nephropathy patient and its association with other parameters.
MATERIALS AND METHODS: We performed a cross-sectional study involving 70 patients with biopsy-proven immunoglobulin A nephropathy with a stable estimated glomerular filtration rate and urinary albuminuria. Their demographic profiles were documented, and blood samples were taken for serum 25-hydroxyvitamin D, highly sensitive C-reactive protein, urine albuminuria and other routine blood tests.
RESULTS: We found nine patients (12.9%) had sufficient 25- hydroxyvitamin D [25(OH)D] levels of more than 30ng/mL and the rest of the patients; 61 (87.1%) had serum 25(OH)D levels below 30 ng/ml. Amongst those with low vitamin D, 38 (62.3%) had serum 25(OH)D between 15-30 ng/mL (insufficient), and the remaining 23 (37.7%) had serum 25(OH)D below 15 ng/ml (deficient). Their mean level of serum 25(OH)D was 19.92 ± 9.04 ng/mL with a serum creatinine of 106.23 ± 38.56 μmol/L and mean estimated glomerular filtration rate (eGFR) at 68.11± 27.65 mL/min/1.73 m2. There was no association between urinary albuminuria, highly sensitive C-reactive protein, estimated glomerular filtration rate or systolic blood pressure with serum 25(OH)D level.
CONCLUSION: Low vitamin D (insufficiency and deficiency) are indeed prevalent in stable immunoglobulin A nephropathy patients. We found no correlation between the vitamin D levels with albuminuria, renal function and highly sensitive C-reactive.

Matched MeSH terms: Vitamin D
Fulltext Factors Associated with Low Vitamin D Status among Older Adults in Kuwait

ALbuloshi T, Kamel AM, Spencer JPE

Nutrients, 2022 Aug 15;14(16).
PMID: 36014846 DOI: 10.3390/nu14163342

Low vitamin D levels among older people represent a significant health problem worldwide. This study aimed to examine the factors associated with vitamin D deficiency in older people (aged ≥ 65) in the Kuwaiti population. A cross-sectional study was conducted in seven primary healthcare centers across Kuwait (November 2020 to June 2021). The participants (n = 237) had their serum vitamin D (25(OH)D) concentrations (analyzed using LC-MS) classified as sufficiency 75 nmol/L (30 ng/mL) or deficiency < 75 nmol/L (below 30 ng/mL). The data were collected using self-administered questionnaires and face-to-face interviews with participants in geriatric clinics. Binomial logistic regression analysis was applied to assess factors associated with vitamin D deficiency. Vitamin D deficiency was found to be present in two thirds of the participants (n = 150, 63%), with a higher prevalence of deficiency in participants who did not receive vitamin D supplements, compared to those who did (84% vs. 16%, p = 0.001). The results from the binary logistic regression showed that a low duration of sun exposure (OR = 0.24, 95% C.I. [0.08−0.7], p = 0.011), dark skin pigmentation (OR = 4.46, 95% [1.35−20.49], p = 0.026), and lower caloric intake (OR = 0.9, 95% C.I. [0.85−0.96], p = 0.001) were risk factors for vitamin D deficiency. Furthermore, a significant inverse relationship was found between vitamin D levels and parathyroid hormone (PTH) levels (OR = 1.16, 95% C.I. [1.04−1.31], p = 0.016). These findings support the recommendation that vitamin D supplementation and adequate sunlight exposure are necessary for raising low vitamin D levels in older people in Kuwait.

Matched MeSH terms: Vitamin D

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