BACKGROUND/AIM: Low levels of vitamin D are a widespread global issue. This study aimed to determine the optimal vitamin D3 supplementation dose for healthy young adults by comparing the effectiveness of gradually increasing cholecalciferol doses over two years. PATIENTS AND METHODS: Thirty-five volunteers participated in a two-season pilot study conducted from October to April to avoid sunlight-induced vitamin D3 synthesis. The participants used oil-based drops of cholecalciferol, increasing their dose from 1,000 to 2,000, 4,000, and then 8,000 IU daily for 60 days with a 30-day break. RESULTS: Supplementing with 1,000 IU/day raised vitamin D levels to the recommended range (above 75 nmol/l), but levels dropped below this range after a 30-day break. A dose of 2,000 IU/day maintained vitamin D levels within the recommended range, even after the break. Increasing the dose to 4,000 IU/day produced a rapid rise, though levels dropped more significantly after stopping supplementation. With 8,000 IU/day, both the rise and subsequent decline in vitamin D levels were more pronounced. CONCLUSION: Effective vitamin D supplementation in healthy young adults can be achieved with a daily dose of 2,000 IU during winter. However, 4,000 IU/day was more effective for maintaining levels above 100 nmol/l, supporting broader health benefits. Regular monitoring of [25(OH)D], calcium, and phosphorus levels is essential.
- MeSH
- Cholecalciferol * administration & dosage MeSH
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Vitamin D Deficiency drug therapy blood MeSH
- Pilot Projects MeSH
- Dietary Supplements * MeSH
- Seasons MeSH
- Vitamin D * administration & dosage blood MeSH
- Dose-Response Relationship, Drug MeSH
- Healthy Volunteers * MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Comparative Study MeSH
V článku je uveden přehled současných poznatků o vitaminu D z klinického hlediska. Jsou shrnuta základní fakta o jeho formách, fyziologických účincích a metabolismu. Z klinického hlediska se článek věnuje stavu zásobení vitaminem D, defi- citu vitaminu D a jeho klinickým projevům a léčbě. V části věnované léčbě jsou shrnuty současné poznatky o používaných formách vitaminu D, jejich indikacích, strategiích léčby a doporučeném dávkování.
The article reviews current knowledge about vitamin D from the clinical point of view. The basic facts about its forms, physiological effects and metabolism are summarized. From clinical point of view the article deals with the state of supply of vitamin D, vitamin D deficiency and its clinical signs, symptoms and therapy. In paragraphs devoted to the treatment the current knowledge about forms of vitamin D, their indication, doses and dosage regimens are summarized.
Aterosklerotická kardiovaskulární onemocnění (ASKVO) jsou i přes možnosti kardiovaskulární (KV) prevence a snahu ji implementovat nejčastější příčinou morbidity a mortality v rozvinutých zemích. Dyslipidemie, resp. hypercholesterolemie, patří spolu s arteriální hypertenzí, diabetem a nikotinismem k hlavním ovlivnitelným rizikovým faktorům v rámci primární a sekundární prevence ASKVO. I přes významný pokrok ve farmakoterapii těchto chorob, včetně hypercholesterolemie, není dosaženo doporučovaných cílových hladin sérových lipidů až u dvou třetin pacientů. Relativní novinkou mezi hy- polipidemiky je kyselina bempedoová, inhibitor ATP-citrát lyázy. Omezuje endogenní syntézu cholesterolu, a tím snižuje hladinu LDL-cholesterolu, a následně incidenci KV příhod. Tato nová léčba získala příznivé výsledky v klinických studiích, zejm. ve studii CLEAR Outcomes. Kyselina bempedoová má perspektivu zejm. v kombinaci s ezetimibem u statinových intolerantů. Na závěr článku je uveden praktický návod současné možnosti indikace a kritérií úhrady.
Atherosclerotic cardiovascular diseases (ASCVD) remain the most common cause of morbidity and mortality in developed countries, despite the availability of cardiovascular (CV) prevention strategies and efforts to implement them. Dyslipidemia, particularly hypercholesterolemia, along with arterial hypertension, diabetes, and nicotine dependence, are among the main modifiable risk factors in both primary and secondary prevention of ASCVD. Despite significant progress in the pharmacotherapy of these conditions, including hypercholesterolemia, the recommended target serum lipid levels are not achieved in up to two-thirds of patients. A relatively new addition to the lipid-lowering medications is bempedoic acid, an ATP-citrate lyase inhibitor. It limits the endogenous synthesis of cholesterol, thereby reducing LDL-cholesterol levels and subsequently the incidence of CV events. This new treatment has shown favorable results in clinical trials, particularly in the CLEAR Outcomes study. Bempedoic acid holds promise, especially in combination with ezetimibe in statin-intolerant patients. The article concludes with a practical guide on current indications and reimbursement criteria.
- Keywords
- kyselina bempedoová,
- MeSH
- Atherosclerosis prevention & control MeSH
- Dyslipidemias drug therapy MeSH
- Hypolipidemic Agents * administration & dosage pharmacology therapeutic use MeSH
- Cardiovascular Diseases prevention & control MeSH
- Drug Therapy, Combination MeSH
- Cholesterol, LDL drug effects MeSH
- Humans MeSH
- Check Tag
- Humans MeSH
The study focused on the changes in C-peptide, glycemia, insulin concentration, and insulin resistance according to LDL-cholesterol concentration ranges. The metabolic profile of individuals in the Czech Republic (n = 1840) was classified by quartiles of LDL-cholesterol into four groups with the following ranges: 0.46-2.45 (n = 445), 2.46-3.00 (n = 474), 3.01-3.59 (n = 459), and 3.60-7.18 mmol/l (n = 462). The level of glucose, C-peptide, insulin, and area of parameters during OGTT and HOMA IR were compared with a relevant LDL-cholesterol range. The evaluation involved correlations between LDL-cholesterol and the above parameters, F-test and t-test. Generally, mean values of glucose homeostasis-related parameters were higher with increasing LDL-cholesterol levels, except for mean HOMA IR values which rapidly increased (2.7-3.4) between LDL-cholesterol ranges of 3.00-3.59 and 3.60-7.18 mmol/l. Glucose, C-peptide, insulin concentrations, and the area of parameters reached greater changes especially after glucose load during OGTT (p ≤ 0.001). Considerable changes were already observed for the above parameters between groups with LDL-cholesterol ranges of 2.46-3.00 and 3.01-3.59 mmol/l. HOMA IR increased with higher LDL-cholesterol concentrations, but the differences in mean values were not statistically significant. Most important differences appeared in glucose metabolism at LDL-cholesterol concentrations of 3.60-7.18 mmol/l in comparison to LDL-cholesterol lower ranges. In particular, the areas of C-peptide, glucose, and insulin ranges showed statistically significant differences between all groups with growing LDL-cholesterol ranges. The variances of HOMA IR statistically differed between groups created according to LDL-cholesterol concentrations ranges.
- MeSH
- C-Peptide * blood MeSH
- Adult MeSH
- Glucose Tolerance Test MeSH
- Insulin * blood MeSH
- Insulin Resistance * MeSH
- Blood Glucose * analysis metabolism MeSH
- Cholesterol, LDL * blood MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
BACKGROUND AND AIMS: Overweight and obesity are modifiable risk factors for atherosclerotic cardiovascular disease (ASCVD) in the general population, but their prevalence in individuals with heterozygous familial hypercholesterolaemia (HeFH) and whether they confer additional risk of ASCVD independent of LDL cholesterol (LDL-C) remains unclear. METHODS: Cross-sectional analysis was conducted in 35 540 patients with HeFH across 50 countries, in the EAS FH Studies Collaboration registry. Prevalence of World Health Organization-defined body mass index categories was investigated in adults (n = 29 265) and children/adolescents (n = 6275); and their association with prevalent ASCVD. RESULTS: Globally, 52% of adults and 27% of children with HeFH were overweight or obese, with the highest prevalence noted in Northern Africa/Western Asia. A higher overweight/obesity prevalence was found in non-high-income vs. high-income countries. Median age at familial hypercholesterolaemia diagnosis in adults with obesity was 9 years older than in normal weight adults. Obesity was associated with a more atherogenic lipid profile independent of lipid-lowering medication. Prevalence of coronary artery disease increased progressively across body mass index categories in both children and adults. Compared with normal weight, obesity was associated with higher odds of coronary artery disease in children (odds ratio 9.28, 95% confidence interval 1.77-48.77, adjusted for age, sex, lipids, and lipid-lowering medication) and coronary artery disease and stroke in adults (odds ratio 2.35, 95% confidence interval 2.10-2.63 and odds ratio 1.65, 95% confidence interval 1.27-2.14, respectively), but less consistently with peripheral artery disease. Adjusting for diabetes, hypertension and smoking modestly attenuated the associations. CONCLUSIONS: Overweight and obesity are common in patients with HeFH and contribute to ASCVD risk from childhood, independent of LDL-C and lipid-lowering medication. Sustained body weight management is needed to reduce the risk of ASCVD in HeFH.
- MeSH
- Child MeSH
- Adult MeSH
- Heterozygote MeSH
- Hyperlipoproteinemia Type II * epidemiology complications MeSH
- Body Mass Index MeSH
- Cardiovascular Diseases epidemiology etiology MeSH
- Cholesterol, LDL blood metabolism MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Overweight * epidemiology complications MeSH
- Obesity * complications epidemiology MeSH
- Prevalence MeSH
- Cross-Sectional Studies MeSH
- Registries * MeSH
- Risk Factors MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
Statínová intolerancia predstavuje významnú výzvu v liečbe dyslipidémie, najmä u pacientov s vysokým kardiovaskulárnym rizikom. Tento problém, definovaný ako neschopnosť pacienta tolerovať dávku statínu potrebnú na efektívne zníženie hladín LDL-cholesterolu (LDL-C), môže byť asociovaný so svalovými symptómami, zvýšením pečeňových enzýmov alebo inými nežiaducimi účinkami. Prevalencia statínovej intolerancie sa pohybuje od 7 % do 29 % v klinickej praxi, pričom úplná intolerancia sa vyskytuje iba u 3–6 % pacientov. Mierne formy svalových symptómov, ako sú myalgie, sú najčastejšie, zatiaľ čo závažné komplikácie, ako je rabdomyolýza, sú veľmi zriedkavé. Diagnóza statínovej intolerancie zahŕňa hodnotenie časovej súvislosti medzi začiatkom liečby a symptómami, vylúčenie alternatívnych príčin a potvrdenie kauzality pomocou opätovného nasadenia lieku. Zaujímavým fenoménom je nocebo efekt, ktorý môže zodpovedať za väčšinu subjektívnych sťažností na svalové symptómy bez priameho súvisu so statínmi. Manažment pacientov so statínovou intoleranciou zahŕňa nefarmakologické prístupy, ako je zmena životného štýlu, a farmakologické alternatívy, vrátane podávania ezetimibu, kyseliny bempedoovej a inhibítorov PCSK9. Väčšina pacientov aj napriek určitému stupňu statínovej intolerancie toleruje malú dávku statínu a ezetimibu, prípadne novú inovatívnu terapiu (ak je indikovaná) a u týchto pacientov vieme efektívne dosiahnuť cieľové hladiny LDL-C. Jedinou limitáciou pri využití alternatívnych liekov na dosiahnutie cieľového zníženia hladiny LDL-C je hradenie týchto postupov zo zdrojov verejného zdravotného poistenia.
Statin intolerance represents a significant challenge in the treatment of dyslipidemia, particularly in patients with high cardiovascular risk. This condition, defined as the inability of a patient to tolerate a statin dose required for effective LDL cholesterol reduction, can result from muscle symptoms, elevated liver enzymes, or other adverse effects. The prevalence of statin intolerance ranges from 7 % to 29 % in clinical practice, with complete intolerance observed in only 3–6 % of patients. Mild forms of muscle symptoms, such as myalgia, are the most common, while severe complications like rhabdomyolysis are very rare. The diagnosis of statin intolerance involves evaluating the temporal relationship between the onset of therapy and symptoms, excluding alternative causes, and confirming causality through rechallenge with the drug. An interesting phenomenon is the nocebo effect, which may account for the majority of subjective complaints of muscle symptoms without a direct link to statins. The management of patients with statin intolerance includes non-pharmacological approaches, such as lifestyle modifications, and pharmacological alternatives, including ezetimibe, PCSK9 inhibitors, and novel drugs like inklisiran. Inklisiran, an RNA interference-based drug, offers a significant reduction in LDL cholesterol of over 50 % with only biannual dosing and minimal side effects.
- MeSH
- Dyslipidemias drug therapy therapy MeSH
- Hypolipidemic Agents pharmacology classification therapeutic use MeSH
- Cholesterol, LDL blood drug effects MeSH
- Humans MeSH
- Muscular Diseases chemically induced diagnosis physiopathology pathology MeSH
- Drug-Related Side Effects and Adverse Reactions diagnosis epidemiology pathology MeSH
- Hydroxymethylglutaryl-CoA Reductase Inhibitors * adverse effects MeSH
- Drug Tolerance * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Lipoproteín(a) [Lp(a)] má štrukturálnu podobnosť s LDL-cholesterolom, ale líši sa od neho tým, že obsahuje glykoproteín apolipoproteín(a) [apo(a)]. Vďaka svojim protrombotickým a prozápalovým vlastnostiam je Lp(a) nezávislým rizikovým faktorom pre aterosklerózou podmienených kardiovaskulárnych ochorení (ASKVO) a aortálnu stenózu. Hladiny Lp(a) sú prevažne geneticky podmienené, pričom približne 20–25 % svetovej populácie má hladiny ≥ 50 mg/dl (alebo ≥ 125 nmol/l). Zmena životného štýlu a diétne opatrenia majú na hladiny Lp(a) len minimálny alebo žiadny vplyv. V súčasnosti je lipoproteínová aferéza jedinou schválenou liečbou zvýšených hladín Lp(a). Táto metóda je však pre pacienta časovo náročná a jej účinnosť je len mierna. Napriek veľkej snahe vyvinúť optimálnu farmakologickú intervenciu za účelom zníženia hladín Lp(a) a s tým súvisiaceho kardiovaskulárneho (KV) rizika, majú existujúce liečivá len obmedzenú účinnosť pri redukcii Lp(a). Hoci statíny zostávajú na účely zníženia hladín LDL-cholesterolu metódou prvej voľby, nepreukázali zníženie rizika ASKVO spojeného s Lp(a). Lieky ako alirokumab, evolokumab a inklisiran dokážu znížiť hladiny Lp(a) o 20–25 %, ale nie je jasné, ako sa tento pokles premieta do zníženia rizika ASKVO sprostredkovaného Lp(a). Niacín taktiež znižuje hladiny Lp(a), avšak jeho účinnosť v redukcii súvisiacich rizík je nejasná a jeho vedľajšie účinky obmedzujú jeho široké používanie. Odporúčania na skríning a manažment vysokých hladín Lp(a) sa značne líšia naprieč národnými a medzinárodnými odporúčaniami. Medzi nové liečby zamerané na Lp(a) patria 3 skúmané zlúčeniny: malé interferujúce RNA agens (olpasiran a SLN360) a antisense oligonukleotid (pelacarsen/pelakarsen). Tieto lieky fungujú tak, že blokujú transláciu mediátorovej RNA pre apo(a), ktorý je kľúčovou súčasťou Lp(a), a tým výrazne znižujú jeho produkciu v pečeni. Táto prehľadová práca si kladie za cieľ opísať súčasné odporúčania pre skríning a manažment zvýšenej hladiny Lp(a), zhodnotiť účinky dostupných liekov na zníženie jeho hladín a preskúmať potenciál nových liečebných postupov zameraných na Lp(a).
Lipoprotein(a), or Lp(a), shares structural similarities with low-density lipoprotein (LDL) but is distinct because it includes the glycoprotein apolipoprotein(a) [apo(a)]. Due to its roles in promoting thrombosis and inflammation, Lp(a) is recognized as an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis. Lp(a) levels are predominantly determined by genetics, with approximately 20%–25% of the global population having levels ≥ 50 mg/dL (or ≥ 125 nmol/L). Lifestyle and dietary changes have minimal or no impact on Lp(a) levels. Currently, lipoprotein apheresis is the only approved treatment for elevated Lp(a). However, this approach is time-consuming for patients and provides only moderate efficacy. While there is considerable interest in pharmacological strategies to lower Lp(a) levels and mitigate associated risks, existing lipid-lowering treatments show limited success in reducing Lp(a). Although statins remain the first-line therapy for lowering LDL cholesterol, they have not demonstrated a reduction in Lp(a)-related ASCVD risk. Medications like alirocumab, evolocumab, and inclisiran can reduce Lp(a) levels by 20–25%, but it is unclear how these reductions translate into lower Lp(a)-mediated ASCVD risk. Niacin also lowers Lp(a) levels, though its role in reducing associated risks is uncertain, and side effects limit its widespread use. Guidelines for screening and managing high Lp(a) levels vary significantly across national and international recommendations. Emerging therapies targeting Lp(a) include three investigational compounds: small interfering RNA (siRNA) agents (olpasiran, SLN360) and an antisense oligonucleotide (pelacarsen). These treatments work by blocking the translation of messenger RNA (mRNA) for apo(a), a critical component of Lp(a), thus significantly reducing its production in the liver. This review aims to outline current screening and management recommendations for elevated Lp(a), evaluate the impact of existing lipid-lowering therapies on Lp(a), and explore the potential of new treatments targeting Lp(a).
- MeSH
- Hypolipidemic Agents administration & dosage pharmacology classification MeSH
- Cardiovascular Diseases * drug therapy prevention & control MeSH
- Cholesterol, LDL blood drug effects MeSH
- Humans MeSH
- Lipoprotein(a) * pharmacology blood drug effects MeSH
- Heart Disease Risk Factors MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Background/Objectives: Given the crucial health benefits of vitamin D, addressing severe deficiencies is a pressing medical concern. This study aimed to evaluate the effectiveness and safety of two new weekly doses of calcifediol (100 μg and 125 μg) for long-term management in patients with severe vitamin D deficiency, defined as plasma 25(OH)D levels ≤10 ng/mL. Methods: This study was a randomized, two-cohort, controlled, double-blind, multicentre phase II-III trial. Subjects were randomized 2:2:1 to weekly calcifediol 100 μg, 125 μg or a placebo. The primary endpoint was the proportion of patients achieving plasma 25(OH)D levels of ≥20 ng/mL and/or ≥30 ng/mL by week 16. Results: A total of 276 patients (mean age: 55.2 years, SD 15.42) were randomized. By week 16, 92.3% and 91.8% of patients in the calcifediol 100 μg and 125 μg groups, respectively, reached ≥20 ng/mL, compared to 7.3% in the placebo group. Levels of ≥30 ng/mL were achieved by 49% (100 μg) and 76.4% (125 μg) of participants, with none in the placebo group. Calcifediol demonstrated superior efficacy at all response levels and time points (p < 0.0001). Plasma 25(OH)D concentrations increased by week 24 and remained stable. The incidence of adverse events was comparable across groups. Conclusions: A weekly calcifediol dose of 100 μg demonstrates the best profile of efficacy and tolerability, providing a reliable solution for achieving and maintaining adequate vitamin D levels in patients with severe deficiency.
- MeSH
- Adult MeSH
- Double-Blind Method MeSH
- Calcifediol * blood administration & dosage MeSH
- Middle Aged MeSH
- Humans MeSH
- Vitamin D Deficiency * drug therapy blood MeSH
- Dietary Supplements MeSH
- Drug Administration Schedule MeSH
- Aged MeSH
- Vitamin D blood analogs & derivatives administration & dosage MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase II MeSH
- Clinical Trial, Phase III MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
Constitutive androstane receptor (CAR) and pregnane X receptor (PXR) are closely related nuclear receptors with overlapping regulatory functions in xenobiotic clearance but distinct roles in endobiotic metabolism. Car activation has been demonstrated to ameliorate hypercholesterolemia by regulating cholesterol metabolism and bile acid elimination, whereas PXR activation is associated with hypercholesterolemia and liver steatosis. Here we show a human CAR agonist/PXR antagonist, MI-883, which effectively regulates genes related to xenobiotic metabolism and cholesterol/bile acid homeostasis by leveraging CAR and PXR interactions in gene regulation. Through comprehensive analyses utilizing lipidomics, bile acid metabolomics, and transcriptomics in humanized PXR-CAR-CYP3A4/3A7 mice fed high-fat and high-cholesterol diets, we demonstrate that MI-883 significantly reduces plasma cholesterol levels and enhances fecal bile acid excretion. This work paves the way for the development of ligands targeting multiple xenobiotic nuclear receptors. Such ligands hold the potential for precise modulation of liver metabolism, offering new therapeutic strategies for metabolic disorders.
- MeSH
- Cholesterol * metabolism blood MeSH
- Cytochrome P-450 CYP3A metabolism genetics MeSH
- Diet, High-Fat * adverse effects MeSH
- Hypercholesterolemia * drug therapy metabolism MeSH
- Hypolipidemic Agents pharmacology therapeutic use MeSH
- Liver metabolism drug effects MeSH
- Constitutive Androstane Receptor * MeSH
- Humans MeSH
- Lipid Metabolism drug effects MeSH
- Disease Models, Animal MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Pregnane X Receptor * metabolism genetics MeSH
- Pyridines MeSH
- Receptors, Cytoplasmic and Nuclear * metabolism agonists genetics MeSH
- Gene Expression Regulation drug effects MeSH
- Bile Acids and Salts * metabolism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
To evaluate vitamin D levels in children treated with fractures during the healing period. A four-year prospective study, including healthy children treated with diaphyseal fracture of femur or forearm bones. Vitamin D levels were examined four times: at the time of the injury and then one, three, and five months after the injury, together with P1NP, ALP, GGT, and parathormone. In the beginning, patients were blindly divided into two groups, one supplemented with vitamin D3 for the entire follow-up period, the other non-supplemented. Altogether, 107 children underwent examination at the time of their injuries. Of these, 63 were included in the study and examined for the entire follow-up period - 36 supplemented, 27 non-supplemented. At the time of injury, 42 % had a deficit of vitamin D, 36.5 % had insufficiency, only 21.5 % had normal levels. In the children supplemented with cholecalciferol, vitamin D levels increased statistically significantly during the follow-up period (already after 1 month), in contrast with non-supplemented patients, where they did not. When we divided patients according to the initial vitamin D levels (deficit/insufficiency/normal levels) or fracture type (femur/forearm), we also observed significantly better results in supplemented groups. We observed a high prevalence of vitamin D deficit or insufficiency in healthy children at the time of their injuries. Patients supplemented with vitamin D3 had normal levels already after one month and this persisted throughout the follow-up period, in contrast with non-supplemented patients. Therefore, we recommend vitamin D testing and administration for children treated for fractures. Keywords: Vitamin D, Pediatric fracture, Children, Vitamin D supplementation.
- MeSH
- Cholecalciferol blood therapeutic use MeSH
- Child MeSH
- Femoral Fractures blood epidemiology MeSH
- Fracture Healing * drug effects MeSH
- Humans MeSH
- Adolescent MeSH
- Follow-Up Studies MeSH
- Vitamin D Deficiency * blood epidemiology drug therapy MeSH
- Dietary Supplements MeSH
- Child, Preschool MeSH
- Prospective Studies MeSH
- Vitamin D * blood therapeutic use MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH