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Vitamin D status and nutrition in Europe and Asia

Lips P

J Steroid Biochem Mol Biol, 2007 Mar;103(3-5):620-5.
PMID: 17287117

Vitamin D status is highly different in various countries of Europe, the Middle East and Asia. For this review, vitamin D deficiency is defined as serum 25-hydroxyvitamin D (25(OH)D) <25 nmol/l. Within European countries, serum 25(OH)D is <25 nmol/l in 2-30% of adults, increasing in the elderly and institutionalized to more than 80% in some studies. A north-south gradient was observed for serum 25(OH)D in the Euronut and MORE studies with higher levels in Scandinavia and lower levels in Italy and Spain and some Eastern European countries. This points to other determinants than sunshine, e.g. nutrition, food fortification and supplement use. Mean vitamin D intake in Scandinavia is 200-400IU/d, twice that in other European countries. Very low serum 25(OH)D levels have been reported in the Middle East, e.g. Turkey, Lebanon, Jordan and Iran. In these countries serum 25(OH)D was lower in women than in men and associated with clothing habits. In a Lebanese survey, vitamin D deficiency was observed in the majority and occurred mainly in veiled women. In India, vitamin D deficiency was observed in more than 30%, vitamin D status being poor in school children, pregnant women and large cities. Vitamin D status was much better in Malaysia and Singapore, but lower serum 25(OH)D was observed in Japan and China. Rickets and osteomalacia appear quite common in India, but precise data are lacking. Immigrants in Europe from the Middle East and Asia carry a high risk for vitamin D deficiency, pregnant women being especially at risk. Comparison of vitamin D status between countries is hampered by interlaboratory variation of serum 25(OH)D measurement. In addition, there is a need of population-based data. In conclusion, vitamin D deficiency is common in Southern Europe, the Middle East, India, China and Japan. It is less common in Northern Europe and Southeast Asia. Risk groups are young children, the elderly, pregnant women and non-western immigrants in Europe. Important determinants are skin type, sex, clothing, nutrition, food fortification, supplement use, BMI and degree of urbanization.

Matched MeSH terms: Vitamin D/metabolism*
Differences in vitamin D status and calcium intake: possible explanations for the regional variations in the prevalence of hypercalcemia in tuberculosis

Chan TY

Calcif. Tissue Int., 1997 Jan;60(1):91-3.
PMID: 9030487

The prevalence of hypercalcemia in patients with untreated tuberculosis (TB) varies widely between countries. Since the vitamin D status and calcium intake are important determinants of hypercalcemia in TB, these two factors were compared among four populations (U.K., Hong Kong, Malaysia, Thailand) with a low prevalence (<3%) and two populations (Sweden, Australia) with a high prevalence (>25%). In the three Asian countries, the circulating vitamin D levels are abundant, but the calcium intakes are low. Subjects from the U.K. have the lowest circulating vitamin D level of all, although their calcium intake is high. In Sweden and Australia, both the circulating vitamin D levels and calcium intakes are high. Since serum 1,25(OH)2D concentration will only be raised if its substance for extrarenal conversion, 25(OH)D, is plentiful and the effect of a given serum 1,25 (OH)2D concentration on serum calcium is determined by the calcium intake, it is postulated that the regional variation in the prevalence of hypercalcemia in TB may be due to differences in the circulating vitamin D levels and calcium intakes in these populations.

Matched MeSH terms: Vitamin D/metabolism*
Fulltext The clinical significance of vitamin D in systemic lupus erythematosus: a systematic review

Sakthiswary R, Raymond AA

PLoS One, 2013;8(1):e55275.
PMID: 23383135 DOI: 10.1371/journal.pone.0055275

BACKGROUND: Vitamin D deficiency is more prevalent among SLE patients than the general population. Over the past decade, many studies across the globe have been carried out to investigate the role of vitamin D in SLE from various clinical angles. Therefore, the aim of this systematic review is to summarise and evaluate the evidence from the published literature; focusing on the clinical significance of vitamin D in SLE.
METHODS: THE FOLLOWING DATABASES WERE SEARCHED: MEDLINE, Scopus, Web of Knowledge and CINAHL, using the terms "lupus", "systemic lupus erythematosus", "SLE and "vitamin D". We included only adult human studies published in the English language between 2000 and 2012.The reference lists of included studies were thoroughly reviewed in search for other relevant studies.
RESULTS: A total of 22 studies met the selection criteria. The majority of the studies were observational (95.5%) and cross sectional (90.9%). Out of the 15 studies which looked into the association between vitamin D and SLE disease activity, 10 studies (including the 3 largest studies in this series) revealed a statistically significant inverse relationship. For disease damage, on the other hand, 5 out of 6 studies failed to demonstrate any association with vitamin D levels. Cardiovascular risk factors such as insulin resistance, hypertension and hypercholesterolaemia were related to vitamin D deficiency, according to 3 of the studies.
CONCLUSION: There is convincing evidence to support the association between vitamin D levels and SLE disease activity. There is paucity of data in other clinical aspects to make firm conclusions.

Matched MeSH terms: Vitamin D/metabolism*
Vitamin D is a potential inhibitor of COVID-19: In silico molecular docking to the binding site of SARS-CoV-2 endoribonuclease Nsp15

Shalayel MH, Al-Mazaideh GM, Aladaileh SH, Al-Swailmi FK, Al-Thiabat MG

Pak J Pharm Sci, 2020 Sep;33(5):2179-2186.
PMID: 33824127

Novel coronavirus disease (COVID-19) has become a pandemic threat to public health. Vaccines and targeted therapeutics to prevent infections and stop virus proliferation are currently lacking. Endoribonuclease Nsp15 plays a vital role in the life cycle, including replication and transcription as well as virulence of the virus. Here, we investigated Vitamin D for its in silico potential inhibition of the binding sites of SARS-CoV-2 endoribonuclease Nsp15. In this study, we selected Remdesivir, Chloroquine, Hydroxychloroquine and Vitamin D to study the potential binding affinity with the putative binding sites of endoribonuclease Nsp15 of COVID-19. The docking study was applied to rationalize the possible interactions of the target compounds with the active site of endoribonuclease Nsp 15. Among the results, Vitamin D was found to have the highest potency with strongest interaction in terms of LBE, lowest RMSD, and lowest inhibition intensity Ki than the other standard compounds. The investigation results of endoribonuclease Nsp15 on the PrankWeb server showed that there are three prospective binding sites with the ligands. The singularity of Vitamin D interaction with the three pockets, particularly in the second pocket, may write down Vitamin D as a potential inhibitor of COVID-19 Nsp15 endoribonuclease binding sites and favour addition of Vitamin D in the treatment plan for COVID-19 alone or in combination with the other used drugs in this purpose, which deserves exploration in further in vitro and in vivo studies.

Matched MeSH terms: Vitamin D/metabolism
The Physiological/Pathophysiological Significance of Vitamin D in Cancer, Cardiovascular Disorders and Beyond

AlMatar M, AlMandeal H, Makky EA, Kayar B, Yarar E, Var I, et al.

Curr Drug Metab, 2017;18(3):207-224.
PMID: 27928943 DOI: 10.2174/1389200217666161207161212

BACKGROUND: Vitamin D, a molecular precursor of the potent steroid hormone calcitriol, has crucial functions and roles in physiology and pathophysiology. Tellingly, calcitriol has been shown to regulate various cellular signalling networks and cascades that have crucial role in cancer biology and diagnostics. Mounting lines of evidences from previous clinical and preclinical investigations indicate that the deficiency of vitamin D may contribute to the carcinogenesis risk. Concomitantly, recent reports suggested that significant reduction in the cancer occurrence and progression is more likely to appear after vitamin D supplementation. Furthermore, a pivotal role functioned by vitamin D in cardiovascular physiology indicates that the deficiency of vitamin D is significantly correlated with enhanced prevalence of stroke, hypertension and myocardial infarction. Notably, vitamin D status is more likely to be used as a lifestyle biomarker, since poor and unhealthy lifestyles are correlated with the deficiency of vitamin D, a feature which may result in cardiovascular complications. Moreover, recent reports revealed that the effect of vitamin D is to cover not only cardiovascular system but also skeletal system.
OBJECTIVE: Herein, we are highlighting the recent knowledge of vitamin D roles and functions with respect to pathophysiological disorders such as cancer, cardiovascular diseases, rheumatoid arthritis (RA) and debate the potential avails of vitamin D on slowing cancer, cardiovascular disease and RA progression.
CONCLUSION: The findings of this review confirm that the importance of vitamin D metabolites or analogues which can provide a helpful platform to target some kinds of cancer, particularly when used in combination with existing therapies. Moreover, the correlation between vitamin D deficiencies with cardiovascular diseases and rheumatoid arthritis (RA) progression might suggest a pivotal role of vitamin D in either initiation or progression of these diseases.

Matched MeSH terms: Vitamin D/metabolism
Fulltext Cohort profile: Japanese human milk study, a prospective birth cohort: baseline data for lactating women, infants and human milk macronutrients

Nojiri K, Higurashi S, Takahashi T, Tsujimori Y, Kobayashi S, Toba Y, et al.

BMJ Open, 2021 Dec 30;11(12):e055028.
PMID: 36282635 DOI: 10.1136/bmjopen-2021-055028

PURPOSE: The Japanese Human Milk Study, a longitudinal prospective cohort study, was set up to clarify how maternal health, nutritional status, lifestyle and sociodemographic and economic factors affect breastfeeding practices and human milk composition. This would eventually determine factors affecting the growth and development of infants and children.
PARTICIPANTS: A total of 1210 Japanese lactating women who satisfied the inclusion criteria, were invited across the country at various participating sites, between 2014 and 2019. Finally a total of 1122 women were enrolled in this study.
FINDINGS TO DATE: Among 1122 eligible participants, mean age at delivery was 31.2 (SD 4.4) years and mean prepregnancy BMI was 20.8 (SD 2.7). Among these women, 35% were previously nulliparous and 77.7% had college, university or higher education. The mean gestational period was 39.0 (SD 1.3) weeks. Caesarean section was reported among 11.9%; mean infant birth weight was 3082 (SD 360) g. Of the infants, 53.7% were male. Overall, our participants appeared to be healthier than the general population in Japan. Analyses of the 1079 eligible human milk samples obtained at the first and second months postpartum showed the following composition: carbohydrate, 8.13 (SD 0.32) g/100 mL; fat, 3.77 (SD 1.29) g/100 mL; and crude protein, 1.20 (SD 0.23) g/100 mL. We also analysed osteopontin, fatty acid, vitamin D and phospholipid levels in limited subcohorts of the samples.
FUTURE PLANS: Follow-up surveys will be conducted to obtain milk samples every 2 months for 12 months and to investigate mother and child health until the children reach 5 years of age. These will be completed in 2024. We plan to longitudinally analyse the composition of macronutrients and various bioactive factors in human milk and investigate the lifestyle and environmental factors that influence breastfeeding practices, maternal and child health, and child development.
TRIAL REGISTRATION NUMBER: UMIN000015494; pre-results.

Matched MeSH terms: Vitamin D/metabolism
Fulltext Potential treatment of squamous cell carcinoma by targeting heparin-binding protein 17/fibroblast growth factor-binding protein 1 with vitamin D3 or eldecalcitol

Shintani T, Higaki M, Rosli SNZ, Okamoto T

In Vitro Cell Dev Biol Anim, 2024 Jun;60(6):583-589.
PMID: 38713345 DOI: 10.1007/s11626-024-00913-3

Heparin-binding protein 17 (HBp17), first purified in 1991 from the conditioned medium of the human A431 squamous cell carcinoma (SCC) cell line, was later renamed fibroblast growth factor-binding protein 1 (FGFBP-1). HBp17/FGFBP-1 is specifically expressed and secreted by epithelial cells, and it reversibly binds to fibroblast growth factor (FGF)-1 and FGF-2, as well as FGFs-7, -10, and -22, indicating a crucial involvement in the transportation and function of these FGFs. Our laboratory has investigated and reported several studies to elucidate the function of HBp17/FGFBP-1 in SCC cells and its potential as a molecular therapeutic target. HBp17/FGFBP-1 transgene exoression in A431-4 cells, a clonal subline of A431 that lacks tumorigenicity and does not express HBp17/FGFBP-1, demonstrated a significantly enhanced proliferation in vitro compared with A431-4 cells, and it acquired tumorigenicity in the subcutis of nude mice. Knockout (KO) of the HBp17/FGFBP-1 by genome editing significantly suppressed tumor growth, cell motility, and tumorigenicity compared with control cells. A comprehensive analysis of expressed molecules in both cell types revealed that molecules that promote epithelial cell differentiation were highly expressed in HBp17/FGFBP-1 KO cells. Additionally, we reported that 1α,25(OH)2D3 or eldecalcitol (ED-71), which is an analog of 1α,25(OH)2D3, suppresses HBp17/FGFBP-1 expression and tumor growth in vitro and in vivo by inhibiting the nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway. Here, we discuss the prospects of molecular targeted therapy targeting HBp17/FGFBP-1 with 1α,25(OH)2D3 or ED71 in SCC and oral SCC.

Matched MeSH terms: Vitamin D/metabolism
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/metabolism
Biochemical Characterization of the Cytochrome P450 CYP107CB2 from Bacillus lehensis G1

Ang SS, Salleh AB, Chor LT, Normi YM, Tejo BA, Rahman MBA, et al.

Protein J, 2018 04;37(2):180-193.
PMID: 29508210 DOI: 10.1007/s10930-018-9764-z

The bioconversion of vitamin D3 catalyzed by cytochrome P450 (CYP) requires 25-hydroxylation and subsequent 1α-hydroxylation to produce the hormonal activated 1α,25-dihydroxyvitamin D3. Vitamin D3 25-hydroxylase catalyses the first step in the vitamin D3 biosynthetic pathway, essential in the de novo activation of vitamin D3. A CYP known as CYP107CB2 has been identified as a novel vitamin D hydroxylase in Bacillus lehensis G1. In order to deepen the understanding of this bacterial origin CYP107CB2, its detailed biological functions as well as biochemical characteristics were defined. CYP107CB2 was characterized through the absorption spectral analysis and accordingly, the enzyme was assayed for vitamin D3 hydroxylation activity. CYP-ligand characterization and catalysis optimization were conducted to increase the turnover of hydroxylated products in an NADPH-regenerating system. Results revealed that the over-expressed CYP107CB2 protein was dominantly cytosolic and the purified fraction showed a protein band at approximately 62 kDa on SDS-PAGE, indicative of CYP107CB2. Spectral analysis indicated that CYP107CB2 protein was properly folded and it was in the active form to catalyze vitamin D3 reaction at C25. HPLC and MS analysis from a reconstituted enzymatic reaction confirmed the hydroxylated products were 25-hydroxyitamin D3 and 1α,25-dihydroxyvitamin D3 when the substrates vitamin D3 and 1α-hydroxyvitamin D3 were used. Biochemical characterization shows that CYP107CB2 performed hydroxylation activity at 25 °C in pH 8 and successfully increased the production of 1α,25-dihydroxyvitamin D3 up to four fold. These findings show that CYP107CB2 has a biologically relevant vitamin D3 25-hydroxylase activity and further suggest the contribution of CYP family to the metabolism of vitamin D3.

Matched MeSH terms: Vitamin D/metabolism
Vitamin D status and oxidative stress in diabetes mellitus

Lee WC, Mokhtar SS, Munisamy S, Yahaya S, Rasool AHG

Cell Mol Biol (Noisy-le-grand), 2018 May 30;64(7):60-69.
PMID: 29974854

Diabetes mellitus is an epidemic that is gaining global concern. Chronic hyperglycemia in diabetes induces the excess production of free radicals. The deleterious effects of excess free radicals are encountered by endogenous antioxidant defense system. Imbalance between free radicals production and antioxidants defense mechanisms leads to a condition known as "oxidative stress". Diabetes mellitus is associated with augmented oxidative stress that induced micro- and macrovascular complications, which presents a significant risk for cardiovascular events. Low vitamin D levels in the body have also been reported to be associated with the pathogenesis of diabetes and enhanced oxidative stress. The article is to review available literature and summarize the relationship between oxidative stress and vitamin D levels in diabetes. We also review the effects of vitamin D analogs supplementation in improving oxidative stress in diabetics.

Matched MeSH terms: Vitamin D/metabolism*
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/metabolism
Determinants of low bone mineral density in children with epilepsy

Fong CY, Kong AN, Noordin M, Poh BK, Ong LC, Ng CC

Eur. J. Paediatr. Neurol., 2018 Jan;22(1):155-163.
PMID: 29122496 DOI: 10.1016/j.ejpn.2017.10.007

INTRODUCTION: Children with epilepsy on long-term antiepileptic drugs (AEDs) are at risk of low bone mineral density (BMD). The aims of our study were to evaluate the prevalence and determinants of low BMD among Malaysian children with epilepsy.
METHOD: Cross-sectional study of ambulant children with epilepsy on long-term AEDs for >1 year seen in a tertiary hospital in Malaysia from 2014 to 2015. Detailed assessment of anthropometric measurements; environmental lifestyle risk factors; serum vitamin D, calcium and parathyroid hormone levels; genotyping of single nucleotide polymorphisms of genes in vitamin D and calcium metabolism; and lumbar spine BMD were obtained. Low BMD was defined as BMD Z-score ≤ -2.0 SD.
RESULTS: Eighty-seven children with mean age of 11.9 years (56 males) participated in the study. The prevalence of low lumbar BMD was 21.8% (19 patients). Multivariate logistic regression analysis identified polytherapy >2 AEDs (OR: 7.86; 95% CI 1.03-59.96), small frame size with wrist breadth of <15th centile (OR 14.73; 95% CI 2.21-98.40), and body mass index Z-score 2 AEDs, underweight or with small frame size as they are at higher risk of having low BMD.

Matched MeSH terms: Vitamin D/metabolism

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