25-Hydroxyvitamin D: functional outcomes in infants and young children

Vitamin D deficiency occurs in the United States in exclusively breastfed infants who have high levels of skin pigmentation, inadequate vitamin D supplementation, and insufficient sunlight exposure. I review serum 25-hydroxyvitamin D [25(OH)D] concentrations and functional outcomes of vitamin deficiency in young children and breastfed and nonbreastfed infants. These outcomes include the presence or absence of vitamin D deficiency rickets, bone mineral content, and serum parathyroid hormone concentration. Daily vitamin D supplements of 400 IU/L keep serum 25(OH)D concentrations higher than 50 nmol/L and prevent rickets in infants and young children. The available evidence is not sufficient to support the use of bone mineral content or parathyroid hormone concentrations in infants and young children as functional outcomes to define deficient or sufficient levels of 25(OH)D. I therefore propose a research agenda to establish the functional definitions of vitamin D sufficiency or deficiency in infants and young children.     

Vitamin D, parathyroid hormone, and bone mass in adolescents

This article provides a review of the evidence identifying the factors related to vitamin D status in adolescents. The prevalence of vitamin D deficiency based on 25-hydroxyvitamin D [25(OH)D] of <25 nmol/L ranges from 0 to 32% depending on the season measured and the latitude of the population assessed. The factors that have been reported to affect serum 25(OH)D in adolescents include ethnicity, gender, puberty stage, parathyroid hormone (PTH), dietary vitamin D intake, and sun exposure. Vitamin D supplementation studies are limited to small populations and with supplementation focused on winter months when sunlight may be inadequate. The effects of vitamin D status and supplementation on bone assessment provide varied results. Differences in study design, modalities of bone assessment, and stage of puberty could contribute to disparate findings. Overall, the results from the available literature provide more questions than answers concerning the role of vitamin D in bone accrual in adolescents.     

Adolescent girls in Maine are at risk for vitamin D insufficiency

The objective was to determine the seasonal fluctuations in serum 25-hydroxyvitamin D (25-OHD) in a group of healthy adolescents living in a northern climate. Twenty-three 9- to 11-year-old girls participated in the study from September 2000 to March 2003. Serum 25-OHD and parathyroid hormone levels were measured each September and March. Dietary intake of vitamin D was assessed each summer and winter. Summer-sun exposure was evaluated using reports of time spent outdoors. The mean decrease in serum 25-OHD from September to March was 28%. Vitamin D insufficiency (at least one serum 25-OHD level <50 nmol/L) was observed in 11 of 23 (48%) subjects. Four of 23 subjects (17%) exhibited vitamin D insufficiency in both September and March. Mean parathyroid hormone levels increased 4 pg/mL (15%) from September to March. Vitamin D intakes need to be increased in winter at northern latitudes.     

Bladder Cancer is Associated with Low Plasma 25-hydroxyvitamin D Concentrations in Tunisian Population

Little evidence suggests an impact of vitamin D on bladder cancer risk in Caucasians. This study aimed to investigate association of plasma 25-hydroxyvitamin D (25-OHD) with urothelial bladder cancer (UBC) risk in Tunisians. A case-control study included 250 patients with UBC and 250 healthy controls. Plasma 25-OHD was assessed by a competitive chemiluminescence immunoassay. Vitamin D deficiency and insufficiency were defined as 25-OHD <30 nmol/L and 30 to 49.99 nmol/L, respectively. Logistic regression models adjusting for gender, age, smoking status, duration of smoking, occupational exposure, and season were applied. Vitamin D deficiency (50.4% vs. 34.8%; P < 0.001) and insufficiency (40.4% vs. 26.8%; P < 0.001) were more frequent in patients than controls. Multivariate analysis showed that UBC is associated with vitamin D deficiency [odd-ratio (95% confidence interval), 3.71 (1.76–7.80); P = 0.001] and vitamin D insufficiency [2.65 (1.40–5.01); P = 0.003]. Other predictors of UBC were female gender, tobacco use, smoking duration, and occupational exposure. Plasma 25-OHD concentrations are low in Tunisian patients with UBC. These findings support experimental and epidemiological evidence of protective role of vitamin D against UBC but could not ascertain causal relationship. Further prospective studies and clinical trials are warranted to check causality.     

Effects of sunlight and diet on vitamin D status of pulmonary tuberculosis patients in Tbilisi, Georgia

ObjectiveVitamin D deficiency is common in tuberculosis (TB) and this may modulate immune responses. This study investigated vitamin D status in patients with TB and examined the sources of vitamin D in Tbilisi, Georgia.MethodsWe measured plasma 25-hydroxyvitamin D (25[OH]D) and dietary vitamin D intake in patients with pulmonary TB (n = 85) in Tbilisi, Georgia. To determine the impact of season on vitamin D status, we tested the in vitro conversion of 7-dehydrocholesterol (7-DHC) to previtamin D₃ after sunlight exposure.ResultsIn subjects with TB, mean plasma 25(OH)D concentrations were 14.4 ± 7.0 ng/mL, and vitamin D insufficiency (25[OH]D <30 ng/mL) occurred in 97% of subjects. The dietary sources of vitamin D were mainly fish, eggs, and butter. The daily intake was well below recommended daily intakes in subjects with TB (172 ± 196 IU). The conversion of 7-DHC to previtamin D₃ was undetectable from October to March and highest in June and July from 11:00 to 14:00 h.ConclusionAn insufficient vitamin D dietary intake and a limited production of vitamin D from sunlight for most of the year may explain the high prevalence of vitamin D insufficiency in patients with TB in Tbilisi.     

Low vitamin D status in preschool children in Greece

Vitamin D status in humans depends on the amount of sun exposure and vitamin D intake. Recent reports suggest that hypovitaminosis D (as defined by serum 25-hydroxyvitamin D [25(OH)D] <10 ng/mL) is reemerging in developed countries and in the Middle East, pointing out the significance of dietary and cultural practices. In the line of prevention, we determined vitamin D status in 393 healthy preschool children randomly selected from 7 day care centers in the Municipality of Athens in October. The data for the analysis were collected from a questionnaire regarding their actual dietary practices, voluntary sun exposure, and lifestyle conditions; clinical investigation for the determination of the skin phototype; and blood sampling for the determination of serum 25(OH)D, parathyroid hormone, and osteocalcin levels. Of the 393 children, 49 were immigrants. According to our results, 6.6% of our population had serum 25(OH)D less than 10 ng/mL. Multilinear analysis showed that the amount of sun exposure and vitamin D intake were the direct determinants of vitamin D status. Immigrant children presented lower serum 25(OH)D levels associated with lower vitamin D intake and lower socioeconomic class when compared with the Greek children. No relationship was found between 25(OH)D concentration and skin phototype, whereas 93.3% of children used topical sunscreen. We suggest that abundant sunlight exposure in Athens is not sufficient to prevent hypovitaminosis D in preschool children. The extensive use of topical sunscreens and environmental factors such as air pollution would account for inadequate sunlight exposure and the need for dietary intake of vitamin D.     

Response to vitamin D supplementation during Antarctic winter is related to BMI, and supplementation can mitigate Epstein-Barr Virus Reactivation

Maintaining vitamin D status without sunlight exposure is difficult without supplementation. This study was designed to better understand interrelationships between periodic vitamin D supplementation and immune function in Antarctic workers. The effect of 2 oral dosing regimens of vitamin D supplementation on vitamin D status and markers of immune function was evaluated in people in Antarctica with no UV light exposure for 6 mo. Participants were given a 2000-IU (50 μg) daily (n = 15) or 10,000-IU (250 μg) weekly (n = 14) vitamin D supplement for 6 mo during a winter in Antarctica. Biological samples were collected at baseline and at 3 and 6 mo. Vitamin D intake, markers of vitamin D and bone metabolism, and latent virus reactivation were determined. After 6 mo, the serum 25-hydroxyvitamin D concentration (mean ± SD) increased from 56 ± 17 to 79 ± 16 nmol/L and from 52 ± 10 to 69 ± 9 nmol/L in the 2000-IU/d and 10,000-IU/wk groups, respectively (main effect over time, P < 0.001). Participants with a greater BMI (participant BMI range = 19–43 g/m2) had a smaller increase in 25-hydroxyvitamin D after 6-mo supplementation (P < 0.05). Participants with high serum cortisol and higher serum 25-hydroxyvitamin D were less likely to shed Epstein-Barr virus in saliva (P < 0.05). The doses given raised vitamin D status in participants not exposed to sunlight for 6 mo, and the efficacy was influenced by baseline vitamin D status and BMI. The data also provide evidence that vitamin D, interacting with stress, can reduce risk of latent virus reactivation during the winter in Antarctica.     

Geographical differences in vitamin D status, with particular reference to European countries

Vitamin D is produced endogenously when the skin is exposed to sunlight and can be obtained exogenously from a few natural food sources, from food fortification and from supplements. Generally, vitamin D intake is low < or = 2-3 microg/d in Europe. Casual exposure to sunlight is thought to provide most of the vitamin D requirement of the human population. However, skin synthesis of vitamin D may not compensate for the low nutritional intake in Europe, even in countries with high supplies from food fortification and supplements. For assessment of vitamin D nutritional status the concentration of 25-hydroxyvitamin D (25(OH)D) in serum is considered to be an accurate integrative measure reflecting an individual's dietary intake and cutaneous production. A substantial percentage of the elderly and adolescents in Europe have a low concentration of 25(OH)D; in the elderly this percentage ranges from approximately 10 in the Nordic countries to approximately 40 in France. Low vitamin D status seems to be aggravated by disease and immobility, and by a low frequency of supplement use.     

Vitamin D insufficiency in North America

Vitamin D insufficiency is a term that has been used to describe the finding of biochemical evidence of deficiency, without obvious clinical signs or symptoms, such as rickets or osteomalacia. The condition is most commonly diagnosed by a serum 25-hydroxyvitamin D below 40 nmol/L (16 microg/L). This paper reviews North American studies addressing the prevalence of the problem, and the growing body of evidence that vitamin D insufficiency predisposes individuals to poor bone and muscle health. The term insufficiency is somewhat misleading, as patients with this condition are really just part of the spectrum of vitamin D deficiency. If the more generous definition of this condition is used (serum 25-hydroxyvitamin D < 80 nmol/L), a much larger proportion of the population has the problem. The response to vitamin D supplementation in clinical trials suggests current recommendations for dietary intake of this vitamin are too low and that a higher adequate intake should be recommended.     

Vitamin D status and its adequacy in healthy Danish perimenopausal women: relationships to dietary intake, sun exposure and serum parathyroid hormone

We conducted this study to assess the prevalence of vitamin D insufficiency in a population of normal perimenopausal women, to examine the influence of sun exposure and vitamin D intake on the concentration of 25-hydroxyvitamin D (25OHD) and to examine the association between parathyroid hormone (PTH) and 25OHD. A total of 2016 healthy women aged 45-58, who had recently undergone a natural menopause, were enrolled over a 2.5-year period in the Danish Osteoporosis Prevention Study. A marked seasonal fluctuation of 25OHD was seen, with an abrupt rise in June and high values until October. The fluctuation could be related to number of hours of sunshine per month with a two months time lag. Dietary vitamin D intake, vitamin supplementation, sunlight exposure, and use of sun-bed were all significantly related to 25OHD concentrations. Sun exposure seemed to contribute the most. The overall prevalence of vitamin D deficiency (defined as serum ) was 7 %. However, in the subgroup avoiding direct sunshine and abstaining from vitamin D supplementation 32.8 % were vitamin D deficient in the winter-spring period. Although mean PTH was increased in the group with low serum 25OHD, PTH was not a sensitive marker of hypovitaminosis D in the individual, as only 16 % of those with vitamin D deficiency had PTH levels above normal range. Thus, we have shown, that healthy middle-aged Danish women are prone to vitamin D insufficiency in the winter-spring period, if they avoid sun exposure in the summer period and abstain from vitamin D supplementation.     

Vitamin D assessment in population-based studies: a review of the issues

In the past decade, research on the relation between vitamin D exposure and disease in population-based studies has increased exponentially. These studies have involved measurement of vitamin D exposure by means of several methods: blood assays, self-reported dietary and supplemental intakes, and sunlight exposure questionnaires or diaries. As with all exposure measurements, researchers must consider the validity of their assessment tools for capturing vitamin D exposure. The purpose of this article is to summarize our current understanding of the various approaches to measuring vitamin D status within populations as reviewed at the 2007 Experimental Biology symposium, "Assessment of Vitamin D in Population-Based Studies." In summary, serum 25-hydroxyvitamin D is the accepted biomarker for short-term vitamin D status, but estimates of long-term dietary and supplemental intakes of vitamin D and long-term sunlight exposure may be the most logistically feasible indicators of lifetime vitamin D exposure in population-based studies. Also discussed are issues investigators should consider when analyzing relations between vitamin D exposure and disease outcomes in population-based studies as well as research avenues that need further exploration. The best method for assessing vitamin D status in population-based studies will depend primarily on the research question asked and the critical window of vitamin D exposure hypothesized to be most important.     

Vitamin d and rehabilitation: improving functional outcomes.

Vitamin D inadequacy is pandemic among rehabilitation patients in both inpatient and outpatient settings. Male and female patients of all ages and ethnic backgrounds are affected. Vitamin D deficiency causes osteopenia, precipitates and exacerbates osteoporosis, causes the painful bone disease osteomalacia, and worsens proximal muscle strength and postural sway. Vitamin D inadequacy can be prevented by sensible sun exposure and adequate dietary intake with supplementation. Vitamin D status is determined by measurement of serum 25-hydroxyvitamin D. The recommended healthful serum level is between 30 and 60 ng/mL. 25-Hydroxyvitamin D levels of >30 ng/mL are sufficient to suppress parathyroid hormone production and to maximize the efficiency of dietary calcium absorption from the small intestine. This can be accomplished by ingesting 1000 IU of vitamin D(3) per day, or by taking 50,000 IU of vitamin D(2) every 2 weeks. Vitamin D toxicity is observed when 25-hydroxyvitamin D levels exceed 150 ng/mL. Identification and treatment of vitamin D deficiency reduces the risk of vertebral and nonvertebral fractures by improving bone health and musculoskeletal function. Vitamin D deficiency and osteomalacia should be considered in the differential diagnosis of patients with musculoskeletal pain, fibromyalgia, chronic fatigue syndrome, or myositis. There is a need for better education of health professionals and the general public regarding the optimization of vitamin D status in the care of rehabilitation patients.     

Very high rates of vitamin D insufficiency in women of child-bearing age living in Beijing and Hong Kong

We aimed to describe the vitamin D status of young women living in two Chinese cities in the spring--Beijing in the north (latitude 39 degrees north) and Hong Kong (latitude 22 degrees north) in the south. We also examined the relationship between serum 25-hydroxyvitamin D and parathyroid hormone (PTH) concentrations to determine a threshold for serum 25-hydroxyvitamin D above which there is no further suppression of PTH. Finally, we examined whether dietary Ca intake influences this relationship. Non-pregnant women aged 18-40 years (n 441) were recruited between February and June. Fasting blood was collected and dietary intakes were assessed using 5 d food records. Mean serum 25-hydroxyvitamin D concentration was lower in Beijing than Hong Kong women (29 v. 34 nmol/l; P < 0.001). Vitamin D deficiency (< or = 25 nmol/l) was indicated in 40% of Beijing and 18% of Hong Kong women, and over 90% of women in both cities were insufficient (< or = 50 nmol/l). Mean Ca and vitamin D intakes were 478 mg/d and 2.0 microg/d, respectively. The relationship between 25-hydroxyvitamin D concentration and PTH was linear throughout the range with a slope of -0.36 (different from 0; P < 0.001; R 0.26), with no apparent threshold. There was no influence of Ca intake on the relationship between 25-hydroxyvitamin D and PTH concentration. Vitamin D deficiency is common and insufficiency is very common in non-pregnant women in Hong Kong and Beijing during spring. Serum 25-hydroxyvitamin D was inversely associated with PTH with no apparent threshold. Strategies such as vitamin D fortification or supplementation may be required.     

Vitamin D deficiency: a worldwide problem with health consequences

Vitamin D deficiency is now recognized as a pandemic. The major cause of vitamin D deficiency is the lack of appreciation that sun exposure in moderation is the major source of vitamin D for most humans. Very few foods naturally contain vitamin D, and foods that are fortified with vitamin D are often inadequate to satisfy either a child's or an adult's vitamin D requirement. Vitamin D deficiency causes rickets in children and will precipitate and exacerbate osteopenia, osteoporosis, and fractures in adults. Vitamin D deficiency has been associated with increased risk of common cancers, autoimmune diseases, hypertension, and infectious diseases. A circulating level of 25-hydroxyvitamin D of >75 nmol/L, or 30 ng/mL, is required to maximize vitamin D's beneficial effects for health. In the absence of adequate sun exposure, at least 800-1000 IU vitamin D3/d may be needed to achieve this in children and adults. Vitamin D2 may be equally effective for maintaining circulating concentrations of 25-hydroxyvitamin D when given in physiologic concentrations.     

Vitamin D and bone health in early life

Prolonged vitamin D deficiency resulting in rickets is seen mainly during rapid growth. A distinct age distribution has been observed in the Copenhagen area where all registered hospital cases of rickets were either infants and toddlers or adolescents from immigrant families. Growth retardation was only present in the infant and toddler group. A state of deficiency occurs months before rickets is obvious on physical examination. Growth failure, lethargy and irritability may be early signs of vitamin D deficiency. Mothers with low vitamin D status give birth to children with low vitamin D status and increased risk of rickets. Reports showing increasing rates of rickets due to insufficient sunlight exposure and inadequate vitamin D intake are cause for serious concern. Many countries (including the USA from 2003) recommend vitamin D supplementation during infancy to avoid rickets resulting from the low vitamin D content of human milk. Without fortification only certain foods such as fatty fish contain more than low amounts of vitamin D, and many children will depend entirely on sun exposure to obtain sufficient vitamin D. The skin has a high capacity to synthesize vitamin D, but if sun exposure is low vitamin D production is insufficient, especially in dark-skinned infants. The use of serum 25-hydroxyvitamin D to evaluate vitamin D status before development of rickets would be helpful; however, there is no agreement on cut-off levels for deficiency and insufficiency. Furthermore, it is not known how marginal vitamin D insufficiency affects children's bones in the long term.     

Vitamin D intake: a global perspective of current status

Global high prevalence of vitamin D insufficiency and re-emergence of rickets and the growing scientific evidence linking low circulating 25-hydroxyvitamin D to increased risk of osteoporosis, diabetes, cancer, and autoimmune disorders have stimulated recommendations to increase sunlight (UVB) exposure as a source of vitamin D. However, concern over increased risk of melanoma with unprotected UVB exposure has led to the alternative recommendation that sufficient vitamin D should be supplied through dietary sources alone. Here, we examine the adequacy of vitamin D intake worldwide and evaluate the ability of current fortification policies and supplement use practices among various countries to meet this recommendation. It is evident from our review that vitamin D intake is often too low to sustain healthy circulating levels of 25-hydroxyvitamin D in countries without mandatory staple food fortification, such as with milk and margarine. Even in countries that do fortify, vitamin D intakes are low in some groups due to their unique dietary patterns, such as low milk consumption, vegetarian diet, limited use of dietary supplements, or loss of traditional high fish intakes. Our global review indicates that dietary supplement use may contribute 6-47% of the average vitamin D intake in some countries. Recent studies demonstrate safety and efficacy of community-based vitamin D supplementation trials and food staple fortification introduced in countries without fortification policies. Reliance on the world food supply as an alternative to UVB exposure will necessitate greater availability of fortified food staples, dietary supplement use, and/or change in dietary patterns to consume more fish.     

Vitamin D Status Of The Elderly: Contributions Of Sunlight Exposure And Diet

Both dietary vitamin D intake and sunlight exposure determined vitamin D status of Finnish elderly with a marked seasonal variation in 25-hydroxyvitamin D levels.     

成都市0～6岁儿童25-羟维生素D水平调查

目的:了解成都市儿童维生素D的营养状况。方法:对来医院儿童保健科门诊进行常规体检的0～6岁701例儿童采用酶联免疫法进行血清25-(OH)D检测。结果:25-(OH)D的平均测定值为(68.60±1.29)nmol/L,25-(OH)D缺乏及严重缺乏的为226例,占32.24%;25-(OH)D水平不足的为237例,占33.811%;水平充足(合适水平)的为238例,占33.95%,前两者占总人数的66.05%。男性和女性血清25-(OH)D水平差异无统计学意义(P>0.05),但25-(OH)D水平随着年龄增高而呈下降(P<0.01)。血清25-(OH)D水平夏秋季显著高于春冬季节(P<0.05)。结论:成都市0～6岁儿童25-(OH)D水平低下,应增加该地区儿童的维生素D摄入量及加强户外活动,尤需重视3～6岁的儿童及冬春季节维生素D的补充。     

The vitamin D epidemic and its health consequences

Vitamin D deficiency is now recognized as an epidemic in the United States. The major source of vitamin D for both children and adults is from sensible sun exposure. In the absence of sun exposure 1000 IU of cholecalciferol is required daily for both children and adults. Vitamin D deficiency causes poor mineralization of the collagen matrix in young children's bones leading to growth retardation and bone deformities known as rickets. In adults, vitamin D deficiency induces secondary hyperparathyroidism, which causes a loss of matrix and minerals, thus increasing the risk of osteoporosis and fractures. In addition, the poor mineralization of newly laid down bone matrix in adult bone results in the painful bone disease of osteomalacia. Vitamin D deficiency causes muscle weakness, increasing the risk of falling and fractures. Vitamin D deficiency also has other serious consequences on overall health and well-being. There is mounting scientific evidence that implicates vitamin D deficiency with an increased risk of type I diabetes, multiple sclerosis, rheumatoid arthritis, hypertension, cardiovascular heart disease, and many common deadly cancers. Vigilance of one's vitamin D status by the yearly measurement of 25-hydroxyvitamin D should be part of an annual physical examination.     

Vitamin D status: effects on quality of life in osteoporosis among Turkish women

Background and objectives Vitamin D deficiency causes muscle weakness, impairs bone formation and neuromuscular coordination thus leading to an increase in fracture risk. It has been found that inadequate levels of vitamin D are present in most of the osteoporosis patients. However, very few studies investigate the association between vitamin D status and quality of life (QOL). The aim of this study is to investigate the effects of vitamin D on QOL among Turkish women with osteoporosis. Methods 259 patients (61.0 ± 8.9 years) with osteoporosis were evaluated by physical activity level, back pain, bone turnover markers, 25-hydroxyvitamin D [25(OH)D], parathyroid hormone levels and bone mineral density. QOL was assessed using QOL Questionnaire of the European Foundation for Osteoporosis (QUALEFFO). 25(OH)D levels below 20 ng/ml was defined as vitamin D insufficiency, below 12 ng/ml as vitamin D deficiency. Results Mean 25(OH)D level was 22.7 ± 12.6 ng/ml and mean total QUALEFFO score was 43.3 ± 14.9. Vitamin D levels were significantly correlated with all subscales and total score of QUALEFFO (r = −0.25, P = 0.0001). Vitamin D insufficiency was determined in 132 patients (51%). In vitamin D deficient (<12 ng/ml) group all subscales and total QOL were found to be poorer when compared with the groups whose vitamin D levels were ≥12 and <20 ng/ml and ≥20 ng/ml (effect sizes 0.41 and 0.62 respectively, P = 0.0001 for total QOL). Vitamin D level, education, concomitant diseases, physical activity level and pain severity were found to be significantly associated with QOL in multiple linear regression analysis model. Conclusions Vitamin D insufficiency affects physical, social and mental functions of osteoporosis patients and impairs QOL. Vitamin D was found to be one of the factors affecting QOL.