Osteoporosis: the role of micronutrients

Osteoporosis and low bone mass are currently estimated to be a major public health threat. Adequate nutrition plays a major role in the prevention and treatment of osteoporosis; the micronutrients of greatest importance are calcium and vitamin D. Calcium has been shown to have beneficial effects on bone mass at all ages, although the results are not always consistent. Higher doses than the current US recommendation (600 IU) of vitamin D in the elderly (age > or = 65 y) may actually be required for optimal bone health (800-1000 IU/d). The elderly can clearly benefit from increased vitamin D intakes; however, the potential importance of vitamin D in peak bone mass is just being investigated. Vitamin D has been related to falls, with supplementation reducing the number of falls. There are clear fracture benefits demonstrated in randomized clinical trials of calcium and vitamin D supplementation. The other micronutrient needs for optimizing bone health can be easily met by a healthy diet that is high in fruits and vegetables to ensure adequate intakes for magnesium, potassium, vitamin C, vitamin K, and other potentially important nutrients. Healthcare professionals need to be aware of the importance of adequate calcium and vitamin D intakes (easily monitored by serum 25(OH)D) for optimal bone health, as well as the prevention of falls and fractures. In addition, a healthy diet that includes 5 servings a day of fruits and vegetables should optimize the intake of micronutrients required for bone health.     

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.     

补充钙及维生素D对2～3岁幼儿身长的影响

目的 分析钙与维生素D(VitD)的营养情况与2～3岁幼儿身长发育的相关性,为体格发育偏离干预提供一定理论依据。 方法 回顾性分析在2019年9月—2021年6月西北妇女儿童医院儿童保健科常规体检的204例幼儿(年龄2～3岁)的临床资料。对这些幼儿进行标准体格测量和对其既往钙和维生素D的补充情况以问卷形式进行回顾性调查,同时检测儿童的血清25-(OH)D和骨密度。对体格发育情况与钙和VitD的营养状况采用了Spearman相关及Logistic多因素回归分析等方法进行统计学分析。结果 每日平均补充VitD剂量的中位数为569.5 U,204例幼儿血清25-(OH)D的中位数为35.60 ng/dl。VitD缺乏检出率1.96%、不足检出率0.98%、充足检出率97.06%,无VitD过量;骨密度中位数为P64.0;单因素Spearman秩相关分析显示,每日平均补充VitD的剂量和每日平均补充钙剂量均与身长呈正相关(r=0.172、0.213,P＜0.05);骨密度与身长呈负相关(r=-0.138,P＜0.05);多因素Logistics回归分析显示,每日平均补充钙剂量与身长呈正相关(OR=1.003,95%CI :1.001~1.006,P＜0.05),而每日平均补充VitD剂量及骨密度与身长无显著相关性。结论 持续补充钙剂对2～3岁幼儿的身长发育有良好的促进作用。     

Vitamin D and bone health in postmenopausal women

Osteoporosis, a disease of increased skeletal fragility, is becoming increasingly common as the U.S. population ages. Adequate vitamin D and calcium intake is the cornerstone of osteoporosis prevention and treatment. Age-related changes in vitamin D and calcium metabolism increase the risk of vitamin D insufficiency and secondary hyperparathyroidism. Although longitudinal data have suggested a role of vitamin D intake in modulating bone loss in perimenopausal women, studies of vitamin D and calcium supplementation have failed to support a significant effect of vitamin D and calcium during early menopause. There is a clearer benefit in vitamin D and calcium supplementation in older postmenopausal women. Vitamin D intake between 500 and 800 IU daily, with or without calcium supplementation, has been shown to increase bone mineral density (BMD) in women with a mean age of approximately 63 years. In women older than 65, there is even more benefit with vitamin D intakes of between 800 and 900 IU daily and 1200-1300 mg of calcium daily, with increased bone density, decreased bone turnover, and decreased nonvertebral fractures. The decreases in nonvertebral fractures may also be influenced by vitamin D-mediated decreases in body sway and fall risk. There are insufficient available data supporting a benefit from vitamin D supplementation alone, without calcium, to prevent osteoporotic fracture in postmenopausal women.     

维生素D与儿童感染性疾病相关性及其抗感染机制研究

维生素D是类固醇类激素超家族中的一员,除调节钙磷代谢,维持儿童骨骼健康的经典作用外,维生素D还具有重要的免疫调节作用。近年来多项研究表明,维生素D低水平与儿童多种感染性疾病的发生、进展相关,维生素D增补被用于治疗与预防多种儿童感染性疾病。本文就维生素D营养状况与儿童感染性疾病的相关性及其抗感染机制进行简要综述。     

Effect of vitamin D supplementation on bone and vitamin D status among Pakistani immigrants in Denmark: a randomised double-blinded placebo-controlled intervention study

Severe vitamin D deficiency is common among Muslim immigrants. The dose necessary to correct the deficiency and its consequence for bone health are not known for immigrants. The aim was to assess the effect of relatively low dosages of supplemental vitamin D on vitamin D and bone status in Pakistani immigrants. This 1-year-long randomised double-blinded placebo-controlled intervention with vitamin D3 (10 and 20 microg/d) included girls (10.1-14.7 years), women (18.1-52.7 years) and men (17.9-63.5 years) of Pakistani origin living in Denmark. The main endpoints were serum 25-hydroxyvitamin D (S-25OHD), parathyroid hormone, bone turnover markers and bone mass. The study showed that supplementation with 10 and 20 microg vitamin D3 per d increased S-25OHD concentrations similarly in vitamin D-deficient Pakistani women (4-fold), and that 10 microg increased S-25OHD concentrations 2-fold and 20 microg 3-fold in Pakistani men. S-25OHD concentrations increased at 6 months and were stable thereafter. Baseline S-25OHD concentrations tended to be lower in girls and women than in men; females achieved about 46 nmol/l and men 55 nmol/l after supplementation. Serum intact parathyroid hormone concentrations decreased at 6 months, but there was no significant effect of the intervention on bone turnover markers and dual-energy X-ray absorptiometry measurements of the whole body and lumbar spine.     

Vitamin D in type 1 diabetes prevention

Limited data from human observational studies suggest that early supplementation with 10 microg/d (400 IU/d) or less of vitamin D may not reduce the risk for type 1 diabetes but that doses of 50 microg/d (2000 IU/d) and higher may have a strong protective effect. Current U.S. recommendations (5-25 microg/d, 200-1000 IU/d) fall in the largely unstudied dose range in between. All infants and children should receive between 5 microg/d and 25 microg/d of supplemental vitamin D, particularly if they have limited sun exposure, live in northern areas, are exclusively breastfed, or are dark skinned. Caretakers of infants and children at increased risk of type 1 diabetes might wish to consider supplementation toward the upper end of that range or above. Additional studies are needed that 1) investigate the association between 25-hydroxyvitamin D and autoantibodies predictive of type 1 diabetes in infancy and beyond, 2) test the ability of vitamin D supplement doses between 5 and 50 microg/d to prevent autoantibodies and/or type 1 diabetes in infancy and beyond, and 3) examine the safety of vitamin D intakes of 25 microg/d and higher. Also, we need to consider the possible benefits of vitamin D supplementation when deciding whether or not to screen children for type 1 diabetes risk and to add type 1 diabetes to the growing list of outcomes that are considered when vitamin D recommendations are next revised.     

维生素D与儿童感染性疾病相关性及其抗感染机制研究

维生素D是类固醇类激素超家族中的一员,除调节钙磷代谢,维持儿童骨骼健康的经典作用外,维生素D还具有重要的免疫调节作用。近年来多项研究表明,维生素D低水平与儿童多种感染性疾病的发生、进展相关,维生素D增补被用于治疗与预防多种儿童感染性疾病。本文就维生素D营养状况与儿童感染性疾病的相关性及其抗感染机制进行简要综述。     

Risk assessment for vitamin D

The objective of this review was to apply the risk assessment methodology used by the Food and Nutrition Board (FNB) to derive a revised safe Tolerable Upper Intake Level (UL) for vitamin D. New data continue to emerge regarding the health benefits of vitamin D beyond its role in bone. The intakes associated with those benefits suggest a need for levels of supplementation, food fortification, or both that are higher than current levels. A prevailing concern exists, however, regarding the potential for toxicity related to excessive vitamin D intakes. The UL established by the FNB for vitamin D (50 microg, or 2000 IU) is not based on current evidence and is viewed by many as being too restrictive, thus curtailing research, commercial development, and optimization of nutritional policy. Human clinical trial data published subsequent to the establishment of the FNB vitamin D UL published in 1997 support a significantly higher UL. We present a risk assessment based on relevant, well-designed human clinical trials of vitamin D. Collectively, the absence of toxicity in trials conducted in healthy adults that used vitamin D dose > or = 250 microg/d (10,000 IU vitamin D3) supports the confident selection of this value as the UL.     

Factors Affecting 25-Hydroxyvitamin D Concentration in Response to Vitamin D Supplementation

Sun exposure is the main source of vitamin D. Due to many lifestyle risk factors vitamin D deficiency/insufficiency is becoming a worldwide health problem. Low 25(OH)D concentration is associated with adverse musculoskeletal and non-musculoskeletal health outcomes. Vitamin D supplementation is currently the best approach to treat deficiency and to maintain adequacy. In response to a given dose of vitamin D, the effect on 25(OH)D concentration differs between individuals, and it is imperative that factors affecting this response be identified. For this review, a comprehensive literature search was conducted to identify those factors and to explore their significance in relation to circulating 25(OH)D response to vitamin D supplementation. The effect of several demographic/biological factors such as baseline 25(OH)D, aging, body mass index(BMI)/body fat percentage, ethnicity, calcium intake, genetics, oestrogen use, dietary fat content and composition, and some diseases and medications has been addressed. Furthermore, strategies employed by researchers or health care providers (type, dose and duration of vitamin D supplementation) and environment (season) are other contributing factors. With the exception of baseline 25(OH)D, BMI/body fat percentage, dose and type of vitamin D, the relative importance of other factors and the mechanisms by which these factors may affect the response remains to be determined.     

Vitamin D Deficiency at Birth Among Military Dependants in Hawai‘i

Vitamin D has long been known to be essential in bone mineralization as well as calcium and phosphate regulation. An increasing body of literature suggests that Vitamin D is also key in many other areas to include immune function, brain development, prevention of autoimmune disease, and prevention of certain types of cancers. Studies also suggest that, with decreased sun exposure due to concern for skin cancer risk, much of the world''s population is becoming increasingly deficient in vitamin D. Our hypothesis was that vitamin D deficiency exists, and can be detected, even in sunny climates such as the state of Hawai‘i. To test this hypothesis, eighty-six cord blood samples were collected in the process of routine clinical testing. These samples were tested for 25-hydroxy vitamin D via liquid chromatography mass spectroscopy. Percent deficiency (<20ng/mL) and insufficiency (20–31.9ng/mL) were determined by statistical analysis. Forty-six percent (n=37) of cord blood samples tested were deficient in vitamin D; 47 percent (n=38) of samples had insufficient 25-OH vitamin D. Only 7 percent (n=6) of samples showed vitamin D concentrations at the recommended levels. A vast majority of military dependents in Hawai‘i have less than optimal vitamin D levels at birth. Further investigation of vitamin D supplementation during pregnancy is required to optimize vitamin D status at birth. We conclude that a vast majority of military dependents in Hawai‘i have less than optimal vitamin D levels at birth supporting the recommendation for supplementation in this population.     

The Relationship Between Female Reproductive Functions and Vitamin D

Nonclassical target organs recently defined for vitamin D, a major regulator of calcium phosphorus homeostasis and bone health, include reproductive ones. This compilation study focuses on the potential effects of vitamin D on female reproductive functions. Vitamin D receptor enzymes that metabolize vitamin D are expressed in both central and peripheral reproductive organs. Most studies suggest that vitamin D may be directly or indirectly related to gonadal functions. Vitamin D's effects on reproductive functions may be indirectly related to diseases such as polycystic ovary syndrome (PCOS), uterine leiomyomas, and endometriosis. In case of vitamin D deficiency during infertility treatment, vitamin D supplementation can be recommended especially for women who have PCOS, insulin resistance, or low anti-Mullerian hormone levels. Supplementation, however, should take into account possible toxic effects of high-dose vitamin D. To be able to recommend measuring vitamin D as a routine screening test and to better understand the effects of vitamin D and its supplementation on female reproductive functions, larger randomized controlled prospective studies are needed.     

Vitamin D Supplementation in Patients with Juvenile Idiopathic Arthritis

Vitamin D has been implicated in the pathogenesis of skeletal disorders and various autoimmune disorders. Vitamin D can be consumed from the diet or synthesized in the skin upon ultraviolet exposure and hydroxylation in the liver and kidneys. In its bioactive form, vitamin D exerts a potent immunomodulatory effect and is important for bone health. Juvenile idiopathic arthritis (JIA) is a collection of inflammatory joint diseases in children that share the manifestation of inflamed synovium, which can result in growth arrest, articular deformity, bone density loss, and disability. To evaluate the potential effect of vitamin D on JIA disease manifestations and outcomes, we review the role of vitamin D in bone metabolism, discuss the mechanism of vitamin D in modulating the innate and adaptive immune systems, evaluate the clinical significance of vitamin D in patients with JIA, and summarize the supplementation studies.     

Combined Calcium and Vitamin D Supplementation Reduces Bone Loss and Fracture Incidence in Older Men and Women

A recent supplementation study of 389 men and women over the age of 65 years was conducted to address the impact of combined calcium and vitamin D supplementation on nonvertebral fracture incidence and maintenance of bone mass. Daily supplementation with 500 mg calcium and 700 IU vitamin D for 3 years moderately reduced bone loss at several sites and significantly decreased the rate of nonvertebral fractures, compared with a placebo group. Optimal intake of both calcium and vitamin D may be an easily implemented strategy to maintain existing bone mass and reduce the risk of fracture in older men and women.     

Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety

For adults, the 5-microg (200 IU) vitamin D recommended dietary allowance may prevent osteomalacia in the absence of sunlight, but more is needed to help prevent osteoporosis and secondary hyperparathyroidism. Other benefits of vitamin D supplementation are implicated epidemiologically: prevention of some cancers, osteoarthritis progression, multiple sclerosis, and hypertension. Total-body sun exposure easily provides the equivalent of 250 microg (10000 IU) vitamin D/d, suggesting that this is a physiologic limit. Sailors in US submarines are deprived of environmentally acquired vitamin D equivalent to 20-50 microg (800-2000 IU)/d. The assembled data from many vitamin D supplementation studies reveal a curve for vitamin D dose versus serum 25-hydroxyvitamin D [25(OH)D] response that is surprisingly flat up to 250 microg (10000 IU) vitamin D/d. To ensure that serum 25(OH)D concentrations exceed 100 nmol/L, a total vitamin D supply of 100 microg (4000 IU)/d is required. Except in those with conditions causing hypersensitivity, there is no evidence of adverse effects with serum 25(OH)D concentrations <140 nmol/L, which require a total vitamin D supply of 250 microg (10000 IU)/d to attain. Published cases of vitamin D toxicity with hypercalcemia, for which the 25(OH)D concentration and vitamin D dose are known, all involve intake of > or = 1000 microg (40000 IU)/d. Because vitamin D is potentially toxic, intake of >25 microg (1000 IU)/d has been avoided even though the weight of evidence shows that the currently accepted, no observed adverse effect limit of 50 microg (2000 IU)/d is too low by at least 5-fold.     

High-dose vitamin D supplements are not associated with linear growth in a large Finnish cohort

High vitamin D intake in childhood has been suggested to have an adverse influence on linear growth. In Finland, in the mid-1960s the official recommendation for infant vitamin D supplementation was 2000 IU/d (50 μg/d). We investigated whether high-dose vitamin D supplementation in infancy was associated with subsequent growth in height. We used data from a prospective population-based birth cohort study including all children due to be born in the 2 northernmost provinces in Finland in 1966 (12,058 live-births, coverage 96%). Information on each participant's height was collected at birth and ages 1, 14, and 31 y, as were possible confounding factors (data for analyses available from 10,060 singletons). Information on the frequency and dose of vitamin D supplementation was collected in 1967 when participants were 1 y of age. A weak association was found between frequency of vitamin D supplementation with greater height at age 1 y (P = 0.005), which was explained by birth characteristics and maternal and social factors (adjusted P = 0.34). Neither frequency nor dose of vitamin D supplementation was associated with height at 14 or 31 y (P > 0.13). To conclude, contrary to proposed evidence suggesting that vitamin D has a negative influence on growth rate at a dosage of ~2000 IU/d, supplementation at this level in the Northern Finland Birth Cohort was not associated with reduced height at any age studied.     

维生素D和钙对2型糖尿病的预防作用

越来越多的证据表明维生素D和钙在2型糖尿病的发病过程中发挥重要作用；联合补充维生素D和钙可预防2型糖尿病的发生，且对2型糖尿病高危人群如糖耐量异常者的作用尤为明显。本文综述了维生素D和钙的营养状况与2型糖尿病之间的关系、补充维生素D和钙对糖代谢的影响以及预防作用的可能机制。     

Should we be concerned about the vitamin D status of athletes?

A surprisingly high prevalence of vitamin D insufficiency and deficiency has recently been reported worldwide. Although very little is known about vitamin D status among athletes, a few studies suggest that poor vitamin D status is also a problem in athletic populations. It is well recognized that vitamin D is necessary for optimal bone health, but emerging evidence is finding that vitamin D deficiency increases the risk of autoimmune diseases and nonskeletal chronic diseases and can also have a profound effect on human immunity, inflammation, and muscle function (in the elderly). Thus, it is likely that compromised vitamin D status can affect an athlete's overall health and ability to train (i.e., by affecting bone health, innate immunity, and exercise-related immunity and inflammation). Although further research in this area is needed, it is important that sports nutritionists assess vitamin D (as well as calcium) intake and make appropriate recommendations that will help athletes achieve adequate vitamin D status: serum 25(OH)D of at least 75 or 80 nmol/L. These recommendations can include regular safe sun exposure (twice a week between the hours of 10 a.m. and 3 p.m. on the arms and legs for 5-30 min, depending on season, latitude, and skin pigmentation) or dietary supplementation with 1,000-2,000 IU vitamin D3 per day. Although this is significantly higher than what is currently considered the adequate intake, recent research demonstrates these levels to be safe and possibly necessary to maintain adequate 25(OH)D concentrations.     

Vitamin D in pregnancy and lactation: maternal, fetal, and neonatal outcomes from human and animal studies

During pregnancy and lactation, mothers require significant amounts of calcium to pass on to the developing fetus and suckling neonate, respectively. Given the dependence of adult calcium concentrations and bone metabolism on vitamin D, one might anticipate that vitamin D sufficiency would be even more critical during pregnancy and lactation. However, maternal adaptations during pregnancy and lactation and fetal adaptations provide the necessary calcium relatively independently of vitamin D status. It is the vitamin D-deficient or insufficient neonate who is at risk of problems, including hypocalcemia and rickets. Due to poor penetrance of vitamin D and 25-hydroxyvitamin D [25(OH)D] into milk, exclusively breastfed infants are at higher risk of vitamin D deficiency than are formula-fed infants. Dosing recommendations for women during pregnancy and lactation might be best directed toward ensuring that the neonate is vitamin D-sufficient and that this sufficiency is maintained during infancy and beyond. A dose of vitamin D that provides 25(OH)D sufficiency in the mother during pregnancy should provide normal cord blood concentrations of 25(OH)D. Research has shown that during lactation, supplements administered directly to the infant can easily achieve vitamin D sufficiency; the mother needs much higher doses (100 mug or 4000 IU per day) to achieve adult-normal 25(OH)D concentrations in her exclusively breastfed infant. In addition, the relation (if any) of vitamin D insufficiency in the fetus or neonate to long-term nonskeletal outcomes such as type 1 diabetes and other chronic diseases needs to be investigated.     

Calcium, vitamin D and involutional osteoporosis

PURPOSE OF REVIEW: Previous studies suggest that combined calcium and vitamin D supplementation decreases the risk of fractures in older people, particularly those living in care homes, but trials of vitamin D alone in fracture prevention have generated inconsistent results. This review examines the physiological functions of calcium and vitamin D, and the contrasting views of what constitutes an adequate dietary calcium intake and vitamin D sufficiency in adults, and highlights the results of recent large studies of calcium and vitamin D supplementation. RECENT FINDINGS: The RECORD study shows that calcium (1000 mg/day) and vitamin D (800 IU/day), either alone or in combination, are ineffective in the secondary prevention of osteoporotic fractures in older men and women living in the community. The Northern and Yorkshire Study also suggests that calcium (1000 mg/day) and vitamin D (800 IU/day) are of no benefit in the primary prevention of fractures in community-dwelling older women. Furthermore, the Wessex study demonstrated no reduction in fractures in older people living in the community treated with annual IM injections of vitamin D (300 000 IU). SUMMARY: The latest studies highlight that vitamin D, either alone or in combination with calcium supplementation, is ineffective in the primary or secondary prevention of fractures in community-dwelling older people. In contrast, calcium and vitamin D supplementation prevents fractures in institutionalized elderly people, who commonly have vitamin D deficiency and secondary hyperparathyroidism.