25(OH)Vitamin D Deficiency and Calcifediol Treatment in Pediatrics

Vitamin D is essential for the normal mineralization of bones during childhood. Although diet and adequate sun exposure should provide enough of this nutrient, there is a high prevalence of vitamin D deficiency rickets worldwide. Children with certain conditions that lead to decreased vitamin D production and/or absorption are at the greatest risk of nutritional rickets. In addition, several rare genetic alterations are also associated with severe forms of vitamin-D-resistant or -dependent rickets. Although vitamin D3 is the threshold nutrient for the vitamin D endocrine system (VDES), direct measurement of circulating vitamin D3 itself is not a good marker of the nutritional status of the system. Calcifediol (or 25(OH)D) serum levels are used to assess VDES status. While there is no clear consensus among the different scientific associations on calcifediol status, many clinical trials have demonstrated the benefit of ensuring normal 25(OH)D serum levels and calcium intake for the prevention or treatment of nutritional rickets in childhood. Therefore, during the first year of life, infants should receive vitamin D treatment with at least 400 IU/day. In addition, a diet should ensure a normal calcium intake. Healthy lifestyle habits to prevent vitamin D deficiency should be encouraged during childhood. In children who develop clinical signs of rickets, adequate treatment with vitamin D and calcium should be guaranteed. Children with additional risk factors for 25(OH)D deficiency and nutritional rickets should be assessed periodically and treated promptly to prevent further bone damage.     

Nutrition Support in Liver Transplantation and Postoperative Recovery: The Effects of Vitamin D Level and Vitamin D Supplementation in Liver Transplantation

Vitamin D plays an important role in the arena of liver transplantation. In addition to affecting skeletal health significantly, it also clinically exerts immune-modulatory properties. Vitamin D deficiency is one of the nutritional issues in the perioperative period of liver transplantation (LT). Although vitamin D deficiency is known to contribute to higher incidences of acute cellular rejection (ACR) and graft failure in other solid organ transplantation, such as kidneys and lungs, its role in LT is not well understood. The aim of this study was to investigate the clinical implication of vitamin D deficiency in LT. LT outcomes were reviewed in a retrospective cohort of 528 recipients during 2014–2019. In the pre-transplant period, 55% of patients were vitamin-D-deficient. The serum vitamin D level was correlated with the model for end-stage liver disease (MELD-Na) score. Vitamin D deficiency in the post-transplant period was associated with lower survival after LT, and the post-transplant supplementation of vitamin D was associated with a lower risk of ACR. The optimal vitamin D status and vitamin D supplementation in the post-transplant period may prolong survival and reduce ACR incidence.     

Vitamin D and COVID-19: Narrative Review after 3 Years of Pandemic

Active vitamin D [1,25(OH)₂D₃—calcitriol] is a secosteroid hormone whose receptor is expressed on all cells of the immune system. Vitamin D has a global anti-inflammatory effect and its role in the management of a SARS-CoV-2 infection has been investigated since the beginning of the COVID-19 pandemic. In this narrative review, the laboratory and clinical results of a vitamin D supplementation have been collected from both open-label and blinded randomized clinical trials. The results are generally in favor of the utility of maintaining the serum concentrations of calcifediol [25(OH)D₃] at around 40 ng/mL and of the absolute usefulness of its supplementation in subjects with deficient serum levels. However, two very recent large-scale studies (one open-label, one placebo-controlled) have called into question the contribution of vitamin D to clinical practice in the era of COVID-19 vaccinations. The precise role of a vitamin D supplementation in the anti-COVID-19 armamentarium requires further investigations in light of the breakthrough which has been achieved with mass vaccinations.     

Effects of vitamin D supplementation on 25-hydroxyvitamin D, high-density lipoprotein cholesterol, and other cardiovascular disease risk markers in subjects with elevated waist circumference

The objective of the present trial was to assess the effects of vitamin D supplementation on serum 25-hydroxyvitamin D [25(OH)D] and high-density lipoprotein cholesterol (HDL-C) in subjects with high waist circumference. Subjects were randomly assigned a daily multivitamin and mineral (MVM) supplement or a MVM supplement plus vitamin D 1,200 IU/day (MVM+D) for 8 weeks. There was a significant difference in mean change for 25(OH)D between the MVM and MVM+D treatment groups ( - 1.2 ± 2.5 nmol/l vs. 11.7 ± 3.0 nmol/l, respectively; P = 0.003). Vitamin D 1,200 IU/day did not increase 25(OH)D to a desirable level ( ≥ 75 nmol/l) in 61% of participants. There were no significant changes in cardiovascular disease risk markers. Thus, vitamin D supplementation with 1,200 IU/day was insufficient to achieve desirable serum 25(OH)D in most participants and did not affect cardiovascular disease risk markers.     

Vitamin D Deficiency in Older Patients—Problems of Sarcopenia,Drug Interactions,Management in Deficiency

Vitamin D deficiency frequently occurs in older people, especially in individuals with comorbidity and polypharmacotherapy. In this group, low vitamin D plasma concentration is related to osteoporosis, osteomalacia, sarcopenia and myalgia. Vitamin D levels in humans is an effect of the joint interaction of all vitamin D metabolic pathways. Therefore, all factors interfering with individual metabolic stages may affect 25-hydroxyvitamin D plasma concentration. The known factors affecting vitamin D metabolism interfere with cytochrome CYP3A4 activity. There is another group of factors that impairs intestinal vitamin D absorption. The phenomenon of drugs and vitamin D interactions is observed first and foremost in patients with comorbidity. This is a typical situation, where the absence of “hard evidence” is not synonymous with the possible lack of adverse effects. Osteoporosis and sarcopenia (generalized and progressive decrease of skeletal muscle mass and strength) are some of the musculoskeletal consequences of hypovitaminosis D. These consequences are related to an increased risk of adverse outcomes, including bone fractures, physical disabilities, and a lower quality of life. This can lead not only to an increased risk of falls and fractures but is also one of the main causes of frailty syndrome in the aging population. Generally, Vitamin D plasma concentration is significantly lower in subjects with osteoporosis and muscle deterioration. In some observational and uncontrolled treatment studies, vitamin D supplementation resulted in a reduction of proximal myopathy and muscle pain. The most conclusive results were found in subjects with severe vitamin D deficiency and in patients avoiding large doses of vitamin D. However, the role of vitamin D in muscle pathologies is not clear and research has provided conflicting results. This is plausibly due to the heterogeneity of the subjects, vitamin D doses and environmental factors. This report presents data on some problems with vitamin D deficiency in the elderly population and the management of vitamin D deficiency D in successful or unsuccessful aging.     

Evaluating the Evidence in Clinical Studies of Vitamin D in COVID-19

Laboratory evidence provides a biological rationale for the benefits of vitamin D in COVID-19, and vitamin D supplementation is associated with reduced risk of respiratory infections. Most of the clinical studies of vitamin D in COVID-19 have been observational, and the most serious problem with observational study design is that of confounding. Observational studies typically assess the relationship of 25(OH)D values with COVID-19 outcomes. Many conditions associated with low vitamin D status are also associated with worse COVID-19 outcomes. Randomized controlled trials (RCTs) overcome the problem of confounding, typically comparing outcomes between groups receiving vitamin D supplementation or placebo. However, any benefit of vitamin D in COVID-19 may be related to the dose, duration, daily vs. bolus administration, interaction with other treatments, and timing of administration prior to or during the illness. Serum 25(OH)D values >50 nmol/L have been associated with reduced infection rates, severity of COVID-19, and mortality in observational studies. Few RCTs of vitamin D supplementation have been completed, and they have shown no benefit of vitamin D in hospitalized patients. Vitamin D may benefit those with mild or asymptomatic COVID-19, and those with greater 25(OH)D values may have lower risk of acquiring infection. Because those at greatest risk of COVID-19 are also at greatest risk of vitamin D deficiency, it is reasonable to recommend vitamin D supplementation 15–20 mcg (600–800 IU) daily for the general population during the COVID-19 pandemic. Vitamin D doses greater than 100 mcg (4000 IU) daily should not be used without monitoring serum 25(OH)D and calcium.     

The Role of Vitamin D in Stroke Prevention and the Effects of Its Supplementation for Post-Stroke Rehabilitation: A Narrative Review

Hypovitaminosis D is a serious public health problem, representing an independent factor in mortality among the general population. Vitamin D deficiency may affect up to one billion people worldwide. Recently, the potential association between vitamin D levels and stroke has gained increasing attention. Many studies suggest that maintaining normal serum vitamin D levels is associated with improvement of the cardiovascular system and a reduction in stroke risk. As a neurosteroid, vitamin D influences brain development and function and immunomodulation and affects brain neuroplasticity. It supports many processes that maintain homeostasis in the body. As stroke is the second most common cause of death worldwide, more studies are needed to confirm the positive effects of vitamin D supplementation, its dosage at different stages of the disease, method of determination, and effect on stroke onset and recovery. Many studies on stroke survivors indicate that serum vitamin D levels only offer insignificant benefits and are not beneficial to recovery. This review article aims to highlight recent publications that have examined the potential of vitamin D supplementation to improve rehabilitation outcomes in stroke survivors. Particular attention has been paid to stroke prevention.     

Vitamin D and cardiovascular disease

Vitamin D participates in numerous physiologic and pathologic processes. Most tissues have vitamin D receptors (VDRs), and vitamin D is an important regulator of gene expression. Approximately 1 billion people worldwide have insufficient levels of vitamin D. Deficiency has been associated with many chronic diseases, including cardiovascular disease (CVD), which is the leading cause of death in both men and women. A relationship between vitamin D and CVD is implicated; however studies show conflicting data. Epidemiologic evidence and observational studies demonstrate an association between vitamin D deficiency and CVD; however, this is not substantiated by randomized controlled trials (RCTs). Many questions remain unanswered, but growing evidence supports a beneficial role of vitamin D on cardiovascular health. Key teaching points: ? Vitamin D influences many cellular functions. ? A global pandemic of vitamin D deficiency exists. ? Epidemiologic data and observational studies suggest that vitamin D deficiency may increase cardiovascular risk. ? RCTs show no significant relationship (however, studies have significant limitations). ? The association between vitamin D status and CVD is uncertain, but low vitamin D levels may be an independent and modifiable CV risk factor.     

Supplementation with vitamin D and calcium in long-term care residents

Vitamin D deficiency is a common finding in institutionalized older persons. Vitamin D-deficient elderly persons are at higher risk of falls and fractures. Long-term care residents should be considered at high risk of vitamin D deficiency and therefore vitamin D supplementation is highly recommended in this population. The minimal effective dose is 800 IU per day. It is recommended that vitamin D supplementation should be implemented in all patients in residential aged care facilities. In addition to vitamin D, calcium supplementation has shown to enhance the effect of vitamin D on bone. Calcium intake should be optimized (1200-1500 mg per day recommended) and supplementation offered to those with inadequate intake. The addition of calcium depends on tolerance, history of kidney stones, and emerging data regarding its cardiovascular safety.     

Vitamine D chez la personne âgée : pourquoi ? Quand ? Comment ?

Vitamin D deficiency is reported in young and older adults. However, elderly persons represent an important target for supplementation. First, aging of the skin reduces vitamin D synthesis. Second, lifestyle or dependency results in low sun exposure. More importantly, the effect of vitamin D deficiency may become more rapidly apparent in aging subjects with poorer bone and muscle reserve. Interventional studies that have shown positive clinical results of vitamin D supplementation have been conducted in aging subjects. Vitamin D supplementation reduces the risk of fracture and falls in the elderly, costs little, and this could have a major impact on public health. It is recommended to systematically supplement all elderly persons with vitamin D, with doses ranging from 800 to 1000 UI/day, either daily or 80,000 to 100,000 UI every 2–3 months.     

Does vitamin D deficiency contribute to increased rates of cardiovascular disease and type 2 diabetes in African Americans?

African Americans have higher rates of type 2 diabetes (T2D) and some forms of cardiovascular disease (CVD) than do European Americans. African Americans also have much higher rates of vitamin D deficiency. There is emerging evidence that vitamin D deficiency may be a risk factor for hypertension, T2D, and CVD, but the extent to which racial disparities in disease rates are explained by racial differences in vitamin D status is uncertain. Despite a large number of observational studies and a limited number of clinical trials that examined 25-hydroxyvitamin D [25(OH)D] concentrations as a potential determinant of CVD and T2D or its precursors, it remains uncertain whether improving vitamin D status would reduce risk of these conditions in the general US population or in African Americans specifically. However, if the associations reported from the observational studies are of the estimated magnitudes and causal, vitamin D supplementation could potentially have a strong preventive effect on some of these conditions and could reduce race-related disparities in their prevalence. Because of the low 25(OH)D concentrations of many, if not most, African Americans, and the low risk associated with vitamin D supplementation, it is important to obtain more definitive answers to these questions.     

Effects of a nutritional supplement fortified with vitamin B-12 on well nourished, free-living elderly subjects

Vitamin B-12 deficiency is prevalent among the elderly population but it is often unrecognized because the clinical manifestations are not present. OBJECTIVE: To evaluate the effects of a nutritional supplement fortified with vitamin B-12 on well nourished, free-living elderly subjects. PATIENTS AND METHODS: Healthy elderly subjects attending two of four clinics were allocated to receive, over six months' duration, a nutritional supplement with 3.8 microg of vitamin B-12. Subjects attending the other two clinics served as controls. Serum vitamin B-12 levels were measured at baseline and 6 months after the supplementation was started. RESULTS: After 6 months of consuming the supplement fortified with vitamin B-12, serum B-12 concentration increased from 350.1 +/- 166.5 pmol/L to 409.0 +/- 166.1 and decreased in the control group from 319.4 +/- 129.1 to 290.1 +/- 135.7 (ANOVA, p < 0.005). CONCLUSION: A supplementation with 3.8 microg /day of vitamin B-12 led to significant improvements in the serum concentrations of vitamin B-12 in older persons.     

Old wine in new bottles: vitamin D in the treatment and prevention of tuberculosis

Tuberculosis (TB) is a major cause of mortality, responsible for 1·68 million deaths worldwide in 2009. The global prevalence of latent Mycobacterium tuberculosis infection is estimated to be 32%, and this carries a 5-20% lifetime risk of reactivation disease. The emergence of drug-resistant organisms necessitates the development of new agents to enhance the response to antimicrobial therapy for active TB. Vitamin D was used to treat TB in the pre-antibiotic era, and its active metabolite, 1,25-dihydoxyvitamin D, has long been known to enhance the immune response to mycobacteria in vitro. Vitamin D deficiency is common in patients with active TB, and several clinical trials have evaluated the role of adjunctive vitamin D supplementation in its treatment. Results of these studies are conflicting, reflecting variation between studies in baseline vitamin D status of participants, dosing regimens and outcome measures. Vitamin D deficiency is also recognised to be highly prevalent among people with latent M. tuberculosis infection in both high- and low-burden settings, and there is a wealth of observational epidemiological evidence linking vitamin D deficiency with increased risk of reactivation disease. Randomised controlled trials of vitamin D supplementation for the prevention of active TB have yet to be performed, however. The conduct of such trials is a research priority, given the safety and low cost of vitamin D supplementation, and the potentially huge public health consequences of positive results.     

Clinical Practice in the Prevention,Diagnosis and Treatment of Vitamin D Deficiency: A Central and Eastern European Expert Consensus Statement

Vitamin D deficiency has a high worldwide prevalence, but actions to improve this public health problem are challenged by the heterogeneity of nutritional and clinical vitamin D guidelines, with respect to the diagnosis and treatment of vitamin D deficiency. We aimed to address this issue by providing respective recommendations for adults, developed by a European expert panel, using the Delphi method to reach consensus. Increasing the awareness of vitamin D deficiency and efforts to harmonize vitamin D guidelines should be pursued. We argue against a general screening for vitamin D deficiency but suggest 25-hydroxyvitamin D (25(OH)D) testing in certain risk groups. We recommend a vitamin D supplementation dose of 800 to 2000 international units (IU) per day for adults who want to ensure a sufficient vitamin D status. These doses are also recommended for the treatment of vitamin D deficiency, but higher vitamin D doses (e.g., 6000 IU per day) may be used for the first 4 to 12 weeks of treatment if a rapid correction of vitamin D deficiency is clinically indicated before continuing, with a maintenance dose of 800 to 2000 IU per day. Treatment success may be evaluated after at least 6 to 12 weeks in certain risk groups (e.g., patients with malabsorption syndromes) by measurement of serum 25(OH)D, with the aim to target concentrations of 30 to 50 ng/mL (75 to 125 nmol/L).     

Update on vitamin D and type 2 diabetes

The prevalence of type 2 diabetes mellitus continues to climb in many parts of the globe in association with the rise in obesity. Although the latter is clearly a predominant factor in the pathogenesis of type 2 diabetes, other modifiable lifestyle factors such as exercise, alcohol consumption, smoking, and certain nutritional factors, such as vitamin D deficiency, are also believed to play a role. In contrast to the findings of observational studies, information pooled from vitamin D intervention trials lack conclusive evidence in support of vitamin D supplementation and changes in diabetes risk or measures of glucose intolerance, although an effect on insulin resistance may exist. Well-designed trials that focus on intermediate biomarkers of diabetes risk in response to increased vitamin D intake are still needed. It will be important to include in the design of these studies selection of insulin-resistant study subjects who have a low (< 50 nmol/L) initial serum vitamin D (25-hydroxyvitamin D) status and administration of sufficient vitamin D to adequately increase their vitamin D status to > 75 nmol/L serum 25-hydroxyvitamin D.     

Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis

The purpose of this review is to put into perspective the many health benefits of vitamin D and the role of vitamin D deficiency in increasing the risk of many common and serious diseases, including some common cancers, type 1 diabetes, cardiovascular disease, and osteoporosis. Numerous epidemiologic studies suggest that exposure to sunlight, which enhances the production of vitamin D(3) in the skin, is important in preventing many chronic diseases. Because very few foods naturally contain vitamin D, sunlight supplies most of our vitamin D requirement. 25-Hydroxyvitamin D [25(OH)D] is the metabolite that should be measured in the blood to determine vitamin D status. Vitamin D deficiency is prevalent in infants who are solely breastfed and who do not receive vitamin D supplementation and in adults of all ages who have increased skin pigmentation or who always wear sun protection or limit their outdoor activities. Vitamin D deficiency is often misdiagnosed as fibromyalgia. A new dietary source of vitamin D is orange juice fortified with vitamin D. Studies in both human and animal models add strength to the hypothesis that the unrecognized epidemic of vitamin D deficiency worldwide is a contributing factor of many chronic debilitating diseases. Greater awareness of the insidious consequences of vitamin D deficiency is needed. Annual measurement of serum 25(OH)D is a reasonable approach to monitoring for vitamin D deficiency. The recommended adequate intakes for vitamin D are inadequate, and, in the absence of exposure to sunlight, a minimum of 1000 IU vitamin D/d is required to maintain a healthy concentration of 25(OH)D in the blood.     

Vitamin D and cardiovascular disease risk

PURPOSE OF REVIEW: Despite our understanding of how to prevent and treat traditional cardiovascular risk factors, cardiovascular disease remains the leading cause of death of both men and women in the US. Thus, there is widespread interest in a number of emerging nontraditional risk factors for the detection of early cardiovascular disease in order to implement aggressive preventive therapies. 25-Hydroxyvitamin D deficiency has been identified as a potential novel cardiovascular disease risk factor. This review outlines what is known about the association of 25-hydroxyvitamin D levels and cardiovascular disease risk. RECENT FINDINGS: Low 25-hydroxyvitamin D levels have been associated with the cardiovascular disease risk factors of hypertension, obesity, diabetes mellitus and the metabolic syndrome, as well as cardiovascular disease events including stroke and congestive heart failure. Studies suggest vitamin D deficiency may be a contributor to the development of cardiovascular disease potentially through associations with diabetes or hypertension. SUMMARY: Vitamin D deficiency is easy to screen for and easy to treat with supplementation. Further larger observational studies and randomized clinical trials are, however, needed to determine whether vitamin D supplementation could have any potential benefit in reducing future cardiovascular disease events and mortality risk.     

Effects of Vitamin D on Fertility,Pregnancy and Polycystic Ovary Syndrome—A Review

Polycystic ovary syndrome (PCOS) is one of the most common endocrine reproductive disorders in women. Vitamin D deficiency is also quite common in this condition. The degree of vitamin D deficiency correlates with the severity of PCOS. Both male and female vitamin D levels play a role in fertility and affect the outcomes of in vitro fertilization (IVF). Moreover, fertility and IVF indicators are improved by vitamin D not only in healthy women but in those diagnosed with PCOS. Both vitamin D deficiency and PCOS increase pregnancy-related complications. Vitamin D supplementation and optimal vitamin D levels decrease both maternal and fetal risk for complications and adverse events. Furthermore, vitamin D supplementation may ameliorate or even prevent pregnancy-related reversible bone loss in mothers. This review emphasizes the roles of vitamin D deficiency and vitamin D supplementation and their correlation with PCOS regarding reproductive health.     

Vitamin D and Cardiovascular Disease

Vitamin D participates in numerous physiologic and pathologic processes. Most tissues have vitamin D receptors (VDRs), and vitamin D is an important regulator of gene expression. Approximately 1 billion people worldwide have insufficient levels of vitamin D. Deficiency has been associated with many chronic diseases, including cardiovascular disease (CVD), which is the leading cause of death in both men and women. A relationship between vitamin D and CVD is implicated; however studies show conflicting data. Epidemiologic evidence and observational studies demonstrate an association between vitamin D deficiency and CVD; however, this is not substantiated by randomized controlled trials (RCTs). Many questions remain unanswered, but growing evidence supports a beneficial role of vitamin D on cardiovascular health.

Key teaching points:

? Vitamin D influences many cellular functions.

? A global pandemic of vitamin D deficiency exists.

? Epidemiologic data and observational studies suggest that vitamin D deficiency may increase cardiovascular risk.

? RCTs show no significant relationship (however, studies have significant limitations).

? The association between vitamin D status and CVD is uncertain, but low vitamin D levels may be an independent and modifiable CV risk factor.