Vitamin D for Cancer Prevention and Survival

Higher levels of the principal circulating form of vitamin D, 25-hydroxyvitamin D (25(OH)D), are associated with substantially lower incidence and death rates from colon, breast, and ovarian cancer, with a linear dose–response gradient. The accumulated evidence from observational studies and a randomized trial reveal that population serum levels of 25(OH)D in the range of 40 to 50 ng/ml will markedly reduce incidence and mortality rates of several cancers including those of the breast, colon, and ovary. There is an immediate clinical need for cancer care providers worldwide to assure that a serum 25(OH)D level >40 ng/ml is achieved as soon as feasible after diagnosis of patients with breast and colon cancer, unless specifically contraindicated by pre-existing hypercalcemia. This serum target could be revisited after further rigorous studies are performed, but the evidence that has accumulated during the past 29 years is sufficiently strong now to adopt the above dosages and serum targets for professional and public health action. Such prompt action is likely to cut mortality from these cancers by half within approximately 5 years. Research on a wider range of cancer types with higher serum 25(OH)D levels (≥50 ng/ml or 125 nmol/l) is needed. In the meantime, vitamin D₃ intake by everyone in the continental US and Canada aged 1 year and older should not be less than 2000 IU/day of vitamin D₃, and 1000 IU/day for infants. The views expressed in this report are those of the authors and do not represent an official position of the Department of the Navy, Department of Defense, or the US Government.     

Vitamin D: extraskeletal health

Vitamin D deficiency is the most common nutritional deficiency and likely the most common medical condition in the world. There is a multitude of causes of vitamin D deficiency, but the major cause has been the lack of appreciation that the body requires 5- to 10-fold higher intakes than is currently recommended by the Institute of Medicine and other health agencies. It is likely that our hunter gatherer fore-fathers being exposed to sunlight on a daily basis were making several thousand IU of vitamin D a day. The fact that 100 IU of vitamin D prevented overt signs of rickets led to the false security that ingesting twice this amount was more than adequate to satisfy the body’s vitamin D requirement. Although this may be true for preventing overt skeletal deformities associated with rickets, there is now overwhelming and compelling scientific and epidemiologic data suggesting that the human body requires a blood level of 25(OH)D above 30 ng/mL for maximum health. The likely reason is that essentially every tissue and cell in the body has a VDR and thus, to have enough vitamin D to satisfy all of these cellular requirements, the blood level of 25(OH)D needs to be above 30 ng/mL. It has been estimated that for every 100 IU of vitamin D ingested that the blood level of 25(OH)D increases by 1 ng/mL. Thus to theoretically achieve a blood level above 30 ng/mL requires the ingestion of 3000 IU of vitamin D a day. There is evidence, however, that when the blood levels of 25(OH)D are less than 15 ng/mL, the body is able to more efficiently use vitamin D to raise the blood level to about 20 ng/mL. To raise the blood level of 25(OH)D above 20 ng/mL requires the ingestion of 100 IU of vitamin D for every 1-ng increase; therefore to increase the blood level to the minimum 30 ng/mL requires the ingestion of at least 1000 IU of vitamin D a day for adults. There is a great need to significantly increase the recommended adequate intakes of vitamin D. All neonates during the first year of life should take at least 400 IU/d of vitamin D, and increasing it to 1000 IU/d may provide additional health benefits. Children 1 year and older should take at least 400 IU/d of vitamin D as recently recommended by the American Academy of Pediatrics, but they should consider increasing intake up to 2000 IU/d derive maximum health benefits from vitamin D. Prepubertal and teenage girls who received 2000 IU of vitamin D per day for a year showed improvement in their musculoskeletal health with no untoward toxicity. All adults should be taking 2000 IU of vitamin D per day. A recent study reported that adults who took 50,000 IU of vitamin D once every 2 weeks, which is equivalent to taking 3000 IU of vitamin D a day, for up to 6 years was effective in maintaining blood levels of 25(OH)D of between 40 and 60 ng/mL without any toxicity. There is no downside to increasing either a child’s or adult’s vitamin D intake, with the exception of acquired disorders such as granulomatous diseases including sarcoidosis and tuberculosis, as well as some lymphomas with activated macrophages that produce 1,25(OH)2D3 in an unregulated fashion.     

Vitamin D, sunlight and longevity

Humans acquire vitamin D through skin photosynthesis and digestive intake. Two hydroxylations are needed to obtain the bioactive compound, the first produces 25-hydroxyvitamin D [25(OH)D], and the second 1,25-dihydroxyvitamin D [1,25(OH)2D]. There is no consensus regarding the appropriate cut-off level to define the normal serum 25(OH)D range. Experimental, epidemiological and clinical studies have related low vitamin D status with longevity. Although some results are controversial, low serum 25(OH)D levels have been linked to all-cause, cardiovascular, cancer and infectious related mortality. Throughout life span a significant proportion of human beings display insufficient (20-30 ng/mL) or deficient (<20 ng/mL) serum 25(OH)D levels. Appropriate lifestyle changes, such as regular short exposures to sunlight (15 min a day), and an adequate diet that includes vitamin D rich components, are not always easily accomplished. Studies relating to vitamin D supplementation have methodological limitations or are based on relatively low doses. Therefore, dosages used for vitamin D supplementation should be higher than those traditionally suggested. In this sense, there is an urgent need for prospective controlled studies using high daily vitamin D doses (2,000 IU or higher) including cardiovascular, cancer, infectious and other endpoints. Relationship between vitamin D and health outcomes is not linear, and there are probably various optimal vitamin D levels influencing different endpoints.     

Prevalence of Vitamin D Deficiency in Uninsured Women

Background Vitamin D deficiency, an important risk factor for osteoporosis and other chronic medical conditions, is epidemic in the United States. Uninsured women may be at an even higher risk for vitamin D deficiency than others owing to low intake of dietary and supplemental vitamin D and limited sun exposure. Objective Our goal was to determine the prevalence of vitamin D deficiency in this vulnerable population. Setting and Participants We enrolled 145 uninsured women at a County Free Medical Clinic in urban Michigan. Questionnaires were used to obtain information about demographics, medical history, vitamin supplementation, sunlight exposure, and dietary vitamin D intake. Results The 96 women who were tested for vitamin D status ranged in age from 21 to 65 years (mean 48 ± 11), and 67% were vitamin D deficient as indicated by a 25-hydroxyvitamin D [25(OH)D)] level <50 nmol/L (20 ng/mL). Non-Caucasians were 3 times more likely than Caucasians to be vitamin D deficient (P = .049). Mean dietary vitamin D intake was low (125 ± 109 IU/d) and only 24% of the participants used any supplemental vitamin D. Participants with total vitamin D intake <400 IU/day from diet and supplements were 10 times more likely to be vitamin D deficient than others (P < .001). Conclusions These results demonstrate a high prevalence of vitamin D deficiency in an uninsured, medically underserved female population. Uninsured women should be strongly encouraged to increase their vitamin D intake.     

Chronic Kidney Disease and Diabetes Mellitus Predict Resistance to Vitamin D Replacement Therapy

Background25-Hydroxyvitamin D [25(OH)D] is a marker of nutritional status; however, chronic kidney disease (CKD) results in alterations in vitamin D metabolism, including the loss of vitamin D-binding proteins and alterations in CYP27B1 and CYP24 enzymes that metabolize 25(OH)D. This study was designed to determine the predictors of responsiveness to correction of vitamin D deficiency with oral vitamin D₂ (ergocalciferol) in adults.MethodsA retrospective study of 183 veterans with 25(OH)D level <30 ng/mL, who were treated with 50,000 IU per week of vitamin D₂, was performed. Logistic regression models were developed to determine the factors predicting the response to treatment, defined as either the change in serum 25(OH)D level/1000 IU of vitamin D₂ or the number of vitamin D₂ doses (50,000 IU per dose) administered.ResultsThe mean age of the patients was 63 ± 12 years. About 87% were men and 51% diabetic, and 29% had an estimated glomerular filtration rate of <60 mL/min/1.73 m². The average number of vitamin D₂ doses was 10.91 ± 5.95; the average increase in 25(OH)D level was 18 ± 10.80 ng/mL. 25(OH)D levels remained <30 ng/mL in 61 patients after treatment. A low estimated glomerular filtration rate and the presence of diabetes mellitus were significant independent predictors for inadequate response to vitamin D₂ treatment in logistic regression models. Patients with CKD required greater amounts of vitamin D₂ to achieve similar increases in 25(OH)D levels, versus non-CKD patients.ConclusionsThe presence of CKD and diabetes mellitus is associated with resistance to correction of 25(OH)D deficiency with vitamin D₂ therapy. The underlying mechanism needs to be evaluated in prospective studies.     

Vitamin D and musculoskeletal health

Vitamin D is critical for calcium homeostasis. Following cutaneous synthesis or ingestion, vitamin D is metabolized to 25(OH)D and then to the active form 1,25(OH)2D. Low serum vitamin D levels are common in the general population and cause a decline in calcium absorption, leading to low serum levels of ionized calcium, which in turn trigger the release of parathyroid hormone, promoting skeletal resorption and, eventually, bone loss or osteomalacia. Vitamin D deficiency is generally defined as a serum 25(OH)D concentration <25-37 nmol/l (<10-15 ng/ml), but the definition of the milder state of vitamin D insufficiency is controversial. Three recent meta-analyses concluded that vitamin D must be administered in combination with calcium in order to substantially reduce the risk of nonvertebral fracture in adults over the age of 50 years. Fracture protection is optimal when patient adherence to medication exceeds 80% and vitamin D doses exceed 700 IU/day. In addition to disordered calcium homeostasis, low vitamin D levels might have effects on cell proliferation and differentiation and immune function. Randomized, double-blind, placebo-controlled trials are needed to clarify whether vitamin D supplementation is beneficial in cancer, autoimmune disease and infection. This Review focuses on the pathophysiology, clinical correlates, evaluation and treatment of hypovitaminosis D.     

Heterogeneity in Serum 25‐Hydroxy‐Vitamin D Response to Cholecalciferol in Elderly Women with Secondary Hyperparathyroidism and Vitamin D Deficiency

OBJECTIVES: To compare the effects on parathyroid hormone (PTH) and 25‐hydroxy‐vitamin D (25(OH)D) of two dosing regimens of cholecalciferol in women with secondary hyperparathyroidism (sHPTH) and hypovitaminosis D and to investigate variables affecting 25(OH)D response to cholecalciferol. DESIGN: Randomized‐controlled trial with 6‐month follow‐up. SETTING: Two osteoporosis centers in northern Italy. PARTICIPANTS: Sixty community‐dwelling women aged 65 and older with sHPTH and hypovitaminosis D, creatinine clearance greater than 65 mL/min and without diseases or drugs known to influence bone and vitamin D metabolism. INTERVENTION: Cholecalciferol 300,000 IU every 3 months, once at baseline and once at 3 months (intermittent D₃ group) or cholecalciferol 1,000 IU/day (daily D₃ group). MEASUREMENTS: Serum PTH, 25(OH)D, calcium, bone‐specific alkaline phosphatase, β‐C‐terminal telopeptide of type I collagen, phosphate, 24‐hour urinary calcium excretion. RESULTS: The two groups had similar baseline characteristics. All participants had vitamin D deficiency [25(OH)D<20 ng/mL)], and 36 subjects (60%) had severe deficiency (<10 ng/mL), with no difference between the groups (severe deficiency: intermittent D₃ group, n=18; daily D₃ group, n=18). After 3 and 6 months, both groups had a significant increase in 25(OH)D and a reduction in PTH. Mean absolute increase±standard deviation of 25(OH)D at 6 months was higher in the intermittent D₃ group (22.7±11.8 ng/mL) than in the daily D₃ group (13.7±6.7 ng/mL, P<.001), with a higher proportion of participants in the intermittent D₃ group reaching desirable serum concentration of 25(OH)D ≥ 30 ng/mL (55% in the intermittent D₃ group vs 20% in the daily D₃ group, P<.001). Mean percentage decrease of PTH in the two groups was comparable, and at 6 months, a similar proportion of participants reached normal PTH values. 25(OH)D response to cholecalciferol showed a wide variability. In a logistic regression analysis, body mass index and type of treatment appeared to be significantly associated with normalization of 25(OH)D values. CONCLUSION: Cholecalciferol 300,000 IU every 3 months was more effective than 1,000 IU daily in correcting vitamin D deficiency, although the two groups achieved similar effects on PTH at 6 months. Only 55% of the higher‐dose intermittent group reached desirable concentrations of 25(OH)D, suggesting that yet‐higher doses will be required for adequate vitamin D repletion.     

Vitamin D replacement in children,adolescents and pregnant women in the Middle East and North Africa: A systematic review and meta-analysis of randomized controlled trials

IntroductionHypovitaminosis D affects one-third to two-thirds of children and pregnant women from the Middle East and North Africa (MENA) region.ObjectiveTo evaluate in infants, children, adolescents and pregnant women, from the MENA region, the effect of supplementation with different vitamin D doses on the change in 25-hydroxyvitamin D [25(OH)D] level reached, and other skeletal and non-skeletal outcomes.MethodsThis is a systematic review of randomized controlled trials of vitamin D supplementation conducted in the MENA region. We conducted a comprehensive literature search in 7 databases, without language or time restriction, until November 2016. Two reviewers abstracted data from the included studies, independently and in duplicate. We calculated the mean difference (MD) and 95% CI of 25(OH)D level reached when at least 2 studies were eligible in each comparison (low (< 800 IU), intermediate (800–2000 IU) or high (> 2000 IU) daily dose of vitamin D, or placebo). We pooled data using RevMan version 5.3.ResultsWe identified a total of 15 eligible trials: one in infants, 4 in children and adolescents and 10 in pregnant women.In children and adolescents, an intermediate vitamin D dose (1901 IU/d), resulted in a mean difference in 25(OH)D level of 13.5 (95% confidence interval (CI) 8.1–18.8) ng/ml, compared to placebo, favoring the intermediate dose (p < 0.001). The proportion of children and adolescents reaching a 25(OH)D level ≥ 20 ng/ml was 74% in the intermediate dose group.In pregnant women, four trials started supplementation at 12–16 weeks of gestation and continued until delivery, and six trials started supplementation at 20–28 weeks' gestation and stopped it at delivery. The MD in 25(OH)D level reached was 8.6 (95% CI 5.3–11.9) ng/ml (p < 0.001) comparing the high dose (3662 IU/d) to the intermediate dose (1836 IU/d), and 12.3 (95% CI 6.4–18.2) ng/ml (p < 0.001), comparing the high dose (3399 IU/d) to the low dose (375 IU/d). Comparing the intermediate (1832 IU/d) to the low dose (301 IU/d), the MD in 25(OH)D level achieved was 7.8 (95% CI 4.5–10.8) ng/ml (p < 0.001). The proportion of pregnant women reaching a 25(OH)D level ≥ 20 ng/ml was 80%–90%, 73% and 27%–43% in the high, intermediate, and low dose groups, respectively.The risk of bias in the included studies, for children, adolescents and pregnant women, ranged from low to high across all doamins.ConclusionIn children, adolescents and pregnant women from the MENA, an intermediate vitamin D dose of 1000–2000 IU daily may be necessary to allow for the majority of the population to reach a desirable 25(OH)D level of 20 ng/ml. Further high quality RCTs are required to confirm/refute the beneficial impact of vitamin D supplementation on various clinically important outcomes.     

Vitamin D deficiency,osteomalacia, and primary biliary cirrhosis

Five patients with primary biliary cirrhosis and vitamin D deficiency (serum 25-hydroxyvitamin D less than 6 ng/ml) are presented. All patients had low serum 24, 25-dihydroxyvitamin D₃ concentrations. Three patients had histological osteomalacia, negative calcium balance, and subnormal serum 1,25-dihydroxyvitamin D₃. Malabsorption of a standard dose of [³H]vitamin D₃ was found in three of four patients with steatorrhea, enabling the effective dose of vitamin D₃ given to be calculated. Oral vitamin D₃ 400–4000 IU/day (effectively 400–1860 IU/day) resulted in a return to normal of the serum vitamin D metabolites, correction of the impaired intestinal calcium absorption and healing of the osteomalacia. Increases in serum calcium, phosphate, and the renal tubular reabsorption of phosphate occurred with a concomitant decrease in serum parathyroid hormone. It is suggested that osteomalacia in primary biliary cirrhosis is the end result of vitamin D deficiency; the hepatic and renal hydroxylations of vitamin D are normal and target tissues are responsive to endogenously produced metabolites of vitamin D.     

Vitamin D deficiency among pregnant women and their newborns in Isfahan, Iran

BACKGROUND AND AIMS: Vitamin D deficiency is one of the major health problems and unexpectedly has a high prevalence in sunny countries (e.g. Middle East). In this study we determined the prevalence of vitamin D deficiency in pregnant women and their newborns in Isfahan, a sunny city in Iran. METHODS: In a cross-sectional study, 88 newborns born in Beheshty hospital, affiliated to Isfahan University of Medical Sciences (August-September, 2005) and their mothers were studied. Their data were collected by questionnaires and blood sampling was done to measure serum alkaline phosphatase (ALP), calcium, phosphorus, 25 (OH) vitamin D and parathormone (PTH). Vitamin D deficiency defined as levels of 25 (OH) D < 20 and < 12.5 ng/ml for mothers and newborns, respectively and local cut-offs defined as levels in which mean serum PTH started to increase. RESULTS: The prevalence of vitamin D deficiency according to 25 (OH) D < 20 ng/ml in mothers and < 12.5 ng/ml in newborns was 5.7% and 4.5%, respectively. According to local cut-offs (35 ng/ml for mothers and 26 ng/ml for newborns) 26.1% of mothers and 53.4% of newborns were vitamin D deficient. CONCLUSION: According to local definition, vitamin D deficiency is a health problem in pregnant women and their newborns in this sunny city.     

Low patient compliance—A major negative factor in achieving vitamin D adequacy in elderly hip fracture patients supplemented with 800 IU of vitamin D3 daily

Achievement of adequate vitamin D₃ level is crucial for the treatment of hip fracture patients. Currently used vitamin D₃ supplementation in Israel ranges between 200 and 800 IU/day. The study objectives were to evaluate the effects of 800 IU/day vitamin D₃ and 1.200 mg of calcium carbonate supplementation to achieve adequate vitamin D₃ level of 30 ng/ml in elderly hip fracture patients. One hundred and twenty-two elderly patients after surgical hip fracture correction aged 73.0 ± 9.5, who were enrolled in a post-surgical treatment program (PSTP). The patients received 800 IU of vitamin D₃ and 1.200 mg of calcium carbonate daily. Serum 25(OH)D and plasma PTH levels were assessed during initial hospital stay and at quarterly follow-up visits for 2 years. At baseline, 120 patients (98.4%) had 25(OH)D serum level <30 ng/ml. Forty-two patients (34.4%) had 25(OH)D serum level <10 ng/ml and these were considered as vitamin D₃ deficient. After 3 months, 29 patients (23.8%) were fully adherent to the supplement, 32 were (26.2%) partially adherent. The dropout rate at 1 year was 55.7%. The major reason for the discontinuation of participation was non-compliance. We conclude that the majority of elderly hip fracture patients had inadequate 25(OH)D serum levels. Compliance with calcium and vitamin D₃ supplements was extremely low. An adequate vitamin D status was not achieved with daily vitamin D₃ supplementation of 800 IU. Supplementation strategies using a periodic single high dose of vitamin D₃ might be more appropriate and should be considered in these patients.     

Investigating the Efficiency of Vitamin D Administration with Buccal Spray in the Treatment of Vitamin D Deficiency in Children and Adolescents

Objective:The aim of this study was to evaluate the efficiency of a buccal spray form of vitamin D compared to single oral dose (stoss therapy) and oral drops therapy in the treatment of vitamin D deficiency.Methods:Ninety healthy children and adolescents (3-18 years) with vitamin D deficiency [serum level of 25-hydroxyvitamin D (25(OH) D) <12 ng/mL] were randomized to receive vitamin D3 buccal spray (2000 U, n=30, group 1) for six weeks, oral drops (2000 U, n=30, group 2) for six weeks and a single oral dose (300 000 U) vitamin D3 (n=30, group 3). Serum calcium, phosphorus, alkaline phosphatase, parathyroid hormone and 25(OH)D levels of the patients were measured at baseline and after the treatment on the 42^nd day.Results:All three groups had a significant increase in serum 25(OH)D concentrations (p<0.001). In group 1, baseline mean 25(OH)D was 8.0±0.41 ng/mL, which rose to 22.1 (17.8-28.2) ng/mL after treatment with a mean increase of 15.6±1.3 ng/mL. Similarly in group 2, baseline, post-treatment and mean increase in 25(OH)D concentrations were 7.9±0.45 ng/mL, 24.4 (20.6-29.6) ng/mL and 17.3±1.1 ng/mL while for group 3 these values were 7.6±0.47 ng/mL, 40.3 (29.4-58.4) ng/mL and 34.3±3.2 ng/mL, respectively.Conclusion:We conclude that vitamin D3 supplementation with buccal spray and oral drops is equally effective in terms of raising vitamin D concentrations in short-term treatment of vitamin D deficiency.     

Treatment of hypovitaminosis D in infants and toddlers

CONTEXT: Hypovitaminosis D appears to be on the rise in young children, with implications for skeletal and overall health. OBJECTIVE: The objective of the study was to compare the safety and efficacy of vitamin D2 daily, vitamin D2 weekly, and vitamin D3 daily, combined with supplemental calcium, in raising serum 25-hydroxyvitamin D [25(OH)D] and lowering PTH concentrations. DESIGN: This was a 6-wk randomized controlled trial. SETTING: The study was conducted at an urban pediatric clinic in Boston. SUBJECTS: Forty otherwise healthy infants and toddlers with hypovitaminosis D [25(OH)D < 20 ng/ml] participated in the study. INTERVENTIONS: Participants were assigned to one of three regimens: 2,000 IU oral vitamin D2 daily, 50,000 IU vitamin D2 weekly, or 2,000 IU vitamin D3 daily. Each was also prescribed elemental calcium (50 mg/kg.d). Infants received treatment for 6 wk. MAIN OUTCOME MEASURES: Before and after treatment, serum measurements of 25(OH)D, PTH, calcium, and alkaline phosphatase were taken. RESULTS: All treatments approximately tripled the 25(OH)D concentration. Preplanned comparisons were nonsignificant: daily vitamin D2 vs. weekly vitamin D2 (12% difference in effect, P = 0.66) and daily D2 vs. daily D3 (7%, P = 0.82). The mean serum calcium change was small and similar in the three groups. There was no significant difference in PTH suppression. CONCLUSIONS: Short-term vitamin D2 2,000 IU daily, vitamin D2 50,000 IU weekly, or vitamin D3 2,000 IU daily yield equivalent outcomes in the treatment of hypovitaminosis D among young children. Therefore, pediatric providers can individualize the treatment regimen for a given patient to ensure compliance, given that no difference in efficacy or safety was noted among these three common treatment regimens.     

Nutritional Vitamin D Supplementation in Dialysis: A Randomized Trial

Background and objectives

Vitamin D (25-hydroxyvitamin D; 25[OH]D) deficiency is common in patients initiating long-term hemodialysis, but the safety and efficacy of nutritional vitamin D supplementation in this population remain uncertain.

Design, setting, participants, & measurements

This randomized, placebo-controlled, parallel-group multicenter trial compared two doses of ergocalciferol with placebo between October 2009 and March 2013. Hemodialysis patients (n=105) with 25(OH)D levels ≤32 ng/ml from 32 centers in the Northeast United States were randomly assigned to oral ergocalciferol, 50,000 IU weekly (n=36) or monthly (n=33), or placebo (n=36) for a 12-week treatment period. The primary endpoint was the achievement of vitamin D sufficiency (25[OH]D >32 ng/ml) at the end of the 12-week treatment period. Survival was assessed through 1 year.

Results

Baseline characteristics were similar across all arms, with overall mean±SD 25(OH)D levels of 21.9±6.9 ng/ml. At 12 weeks, vitamin D sufficiency (25[OH]D >32 ng/ml) was achieved in 91% (weekly), 66% (monthly), and 35% (placebo) (P<0.001). Mean 25(OH)D was significantly higher in both the weekly (49.8±2.3 ng/ml; P<0.001) and monthly (38.3±2.4 ng/ml; P=0.001) arms compared with placebo (27.4±2.3 ng/ml). Calcium, phosphate, parathyroid hormone levels, and active vitamin D treatment did not differ between groups. All-cause and cause-specific hospitalizations and adverse events were similar between groups during the intervention period. Lower all-cause mortality among ergocalciferol-treated participants was not statistically significant (hazard ratio, 0.28; 95% confidence interval, 0.07 to 1.19).

Conclusions

Oral ergocalciferol can increase 25(OH)D levels in incident hemodialysis patients without significant alterations in blood calcium, phosphate, or parathyroid hormone during a 12-week period.     

Vitamin D supplementation in older women

BACKGROUND: The purpose of this study was to determine if vitamin D supplementation, 400-800 IU daily, could effectively treat vitamin D deficiency and insufficiency over 3 months. METHODS: To test this hypothesis, we conducted a cross-sectional survey followed by a 3-month, open-label run-in phase prior to a randomized clinical trial. We enrolled 573 community-dwelling women age 65 or older, 373 of whom completed the run-in phase. All women received a daily multivitamin containing 400 IU of vitamin D and one to two calcium supplements containing 200 IU of vitamin D. We assessed bone mineral metabolism (including 25-hydroxyvitamin D and parathyroid hormone), markers of bone turnover, and bone mineral density. RESULTS: Of the 553 screened participants who had baseline vitamin D levels available, 16% had vitamin D deficiency (serum vitamin D < 10 ng/ml) and 48% had vitamin D insufficiency (serum vitamin D between 10 and 20 ng/ml). Only 36% of participants had normal vitamin D levels (serum vitamin D > or = 20 ng/ml). Baseline vitamin D intake was negatively associated with serum parathyroid hormone (r = -0.29, p <.0001), and not associated with bone mineral density or bone resorption. Vitamin D deficiency was associated with decreased physical activity and slower gait. Of the 373 women who completed the run-in phase and received treatment with a multivitamin and vitamin D-containing calcium supplement, vitamin D deficiency decreased from 16% at baseline to 0% at 3 months, and vitamin D insufficiency decreased from 48% at baseline to 20% at 3 months (p <.001). CONCLUSIONS: We conclude that vitamin D deficiency and insufficiency, which are common among ambulatory, community-dwelling elderly women, can be normalized in 80% of patients over 3 months with vitamin D supplementation of 400-800 IU/d.     

Vitamin D and Sunlight: Strategies for Cancer Prevention and Other Health Benefits

Vitamin D deficiency is a worldwide health problem. The major source of vitamin D for most humans is sensible sun exposure. Factors that influence cutaneous vitamin D production include sunscreen use, skin pigmentation, time of day, season of the year, latitude, and aging. Serum 25-hydroxyvitamin D [25(OH)D] is the measure for vitamin D status. A total of 100 IU of vitamin D raises blood level of 25(OH)D by 1 ng/ml. Thus, children and adults who do not receive adequate vitamin D from sun exposure need at least 1000 IU/d vitamin D. Lack of sun exposure and vitamin D deficiency have been linked to many serious chronic diseases, including autoimmune diseases, infectious diseases, cardiovascular disease, and deadly cancers. It is estimated that there is a 30 to 50% reduction in risk for developing colorectal, breast, and prostate cancer by either increasing vitamin D intake to least 1000 IU/d vitamin D or increasing sun exposure to raise blood levels of 25(OH)D >30 ng/ml. Most tissues in the body have a vitamin D receptor. The active form of vitamin D, 1,25-dihydroxyvitamin D, is made in many different tissues, including colon, prostate, and breast. It is believed that the local production of 1,25(OH)₂D may be responsible for the anticancer benefit of vitamin D. Recent studies suggested that women who are vitamin D deficient have a 253% increased risk for developing colorectal cancer, and women who ingested 1500 mg/d calcium and 1100 IU/d vitamin D₃ for 4 yr reduced risk for developing cancer by >60%.Vitamin D is likely to be one of the oldest hormones. It has existed for at least 750 million years, when phytoplankton synthesized it in response to sunlight (1). Throughout evolution, vitamin D played a critical role in the evolution of vertebrates as they left their high-calcium ocean environment for the calcium-deficient terra firma. Nocturnal rodents and other rodent-like species that lived underground needed little, if any, vitamin D to survive. It has been speculated that when the asteroid hit the earth 65 million yr ago, one of the survival characteristics for nocturnal mammals was that they did not require sunlight-mediated vitamin D synthesis to survive, unlike the dinosaurs. Dinosaurs likely depended on the sun to satisfy their vitamin D requirement to utilize dietary calcium efficiently for the maintenance of their massive skeletons (1). Thus, the lack of sunlight-mediated vitamin D synthesis after the asteroid impact may have been related to the demise of the dinosaurs.The industrialization of Europe and the United States in the 17th through the 19th centuries gave birth to the devastating bone-deforming and growth-retarding disease rickets. Although Sniadecki in 1822 suggested that children who were living in the industrialized cities in Poland were at a higher risk for rickets than children who were living in rural areas as a result of lack of sun exposure, it would take 100 yr before it was reported that exposure to ultraviolet radiation from a mercury arc lamp or sun exposure prevented and cured rickets (2,3).     

Bone disease in chronic childhood cholestasis. I. Vitamin D absorption and metabolism

Metabolic bone disease is common in children and adults with chronic cholestasis. We evaluated baseline vitamin D (vitamin D2 and D3), 25-OH vitamin D2 and D3, 1,25(OH)2 vitamin D, vitamin D-binding protein, bone mineral content and dietary mineral content in six children (mean age: 12.1 years) with cholestasis since infancy. Absorption of 25-OH vitamin D3 and vitamin D2 was evaluated by measuring serial serum concentrations after a test dose. Bone mineral content was reduced by greater than 2 S.D. in five of six subjects compared to age-specific controls; none had radiographic evidence of rickets but all had osteopenia. Dietary Ca and P content in the subjects was comparable to the recommended daily allowance for age-specific children. Baseline serum vitamin D2 concentrations were undetectable in all but one cholestatic subject despite oral supplementation with 2,500 to 50,000 IU per day vitamin D2. Baseline serum 25-OH vitamin D was 33.2 +/- 6.0 ng per ml (mean +/- S.E.) and comparable to our laboratory norms (15 to 50 ng per ml). Serum 1,25(OH)2 vitamin D and "free" 1,25(OH)2 vitamin D were both significantly (p less than 0.05) reduced compared to controls. A significantly blunted rise and reduced area under the absorption curve (both p less than 0.001) after 1,000 IU per kg vitamin D2 was found in cholestatic children (0.8 ng +/- 0.5 ng per ml and 18.0 +/- 14.3 ng hr per ml, respectively) compared to controls (59.5 +/- 10.0 ng per ml and 1,780 +/- 253 ng hr per ml, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Prevalence of Vitamin D inadequacy among postmenopausal North American women receiving osteoporosis therapy

PURPOSE: To evaluate serum 25-hydroxyvitamin D [25(OH)D] concentrations and factors related to vitamin D inadequacy in postmenopausal North American women receiving therapy to treat or prevent osteoporosis. METHODS: Serum 25(OH)D and PTH were obtained in 1536 community-dwelling women between November 2003 and March 2004. Multivariate logistic regression was used to assess risk factors for suboptimal (<30 ng/ml) 25(OH)D. RESULTS: Ninety-two percent of study subjects were Caucasian, with a mean age of 71 yr. Thirty-five percent resided at or above latitude 42 degrees north, and 24% resided less than 35 degrees north. Mean (sd) serum 25(OH)D was 30.4 (13.2) ng/ml: serum 25(OH)D was less than 20 ng/ml in 18%; less than 25 ng/ml in 36%; and less than 30 ng/ml in 52%. Prevalence of suboptimal 25(OH)D was significantly higher in subjects who took less than 400 vs. 400 IU/d or more vitamin D. There was a significant negative correlation between serum PTH concentrations and 25(OH)D. Risk factors related to vitamin D inadequacy included age, race, body mass index, medications known to affect vitamin D metabolism, vitamin D supplementation, exercise, education, and physician counseling regarding vitamin D. CONCLUSIONS: More than half of North American women receiving therapy to treat or prevent osteoporosis have vitamin D inadequacy, underscoring the need for improved physician and public education regarding optimization of vitamin D status in this population.     

Vitamin D2 is as effective as vitamin D3 in maintaining circulating concentrations of 25-hydroxyvitamin D

CONTEXT: Two reports suggested that vitamin D2 is less effective than vitamin D3 in maintaining vitamin D status. OBJECTIVE: Our objective was to determine whether vitamin D2 was less effective than vitamin D3 in maintaining serum 25-hydroxyvitamin D levels or increased the catabolism of 25-hydroxyvitamin D3. SUBJECTS AND DESIGN: This was a randomized, placebo-controlled, double-blinded study of healthy adults ages 18-84 yr who received placebo, 1000 IU vitamin D3, 1000 IU vitamin D2, or 500 IU vitamin D2 plus 500 IU vitamin D3 daily for 11 wk at the end of the winter. RESULTS: Sixty percent of the healthy adults were vitamin D deficient at the start of the study. The circulating levels of 25-hydroxyvitamin D (mean+/-sd) increased to the same extent in the groups that received 1000 IU daily as vitamin D2 (baseline 16.9+/-10.5 ng/ml; 11 wk 26.8+/-9.6 ng/ml), vitamin D3 (baseline 19.6+/-11.1 ng/ml; 11 wk 28.9+/-11.0 ng/ml), or a combination of 500 IU vitamin D2 and 500 IU vitamin D3 (baseline 20.2+/-10.4 ng/ml; 11 wk 28.4+/-7.7 ng/ml). The 25-hydroxyvitamin D3 levels did not change in the group that received 1000 IU vitamin D2 daily. The 1000 IU dose of vitamin D2 or vitamin D3 did not raise 25-hydroxyvitamin D levels in vitamin D-deficient subjects above 30 ng/ml. CONCLUSION: A 1000 IU dose of vitamin D2 daily was as effective as 1000 IU vitamin D3 in maintaining serum 25-hydroxyvitamin D levels and did not negatively influence serum 25-hydroxyvitamin D3 levels. Therefore, vitamin D2 is equally as effective as vitamin D3 in maintaining 25-hydroxyvitamin D status.     

Vitamin D levels in patients with small and medium vessel vasculitis

ObjectivesTo determine the prevalence of vitamin D deficiency in patients with small and medium vessel systemic vasculitis.MethodsIn this cross-sectional study, 25-hydroxy (OH) vitamin D3 levels were measured in adult patients with systemic small and medium vessel vasculitis including antineutrophil cytoplasmic antibody-associated vasculitis (AAV), cryoglobulinaemic vasculitis (CryV), IgA vasculitis (IgAV) and polyarteritis nodosa (PAN), and age- and sex-matched healthy subjects (HS) and patients with rheumatoid arthritis (RA) as control groups. 25OH vitamin D3 levels < 30 ng/ml and <20 ng/ml were regarded as insufficiency and deficiency, respectively.ResultsFifty-seven patients (42 AAV, 2 CryV, 8 IgA vasculitis, 5 PAN) with systemic vasculitis, 101 HS, and 111 RA patients were included. The mean 25OH vitamin D3 level was 21.8 ± 14.2 ng/mL in patients with vasculitis, 42.7 ± 27.6 ng/mL in HS (p < .001) and 20.1 ± 18.47 ng/mL in patients with RA (p = .54). Vitamin D insufficiency and deficiency were significantly higher in patients with systemic vasculitis compared to HS (75.4% vs 33.7%, p < .001; %50 vs 21.8%, p < .001, respectively). Vitamin D status was not different in patients with systemic vasculitis compared to RA. There was a negative correlation between vitamin D status and CRP levels (=?.364, p = .007). The multivariate logistic regression analysis showed that renal involvement was significantly associated with vitamin D deficiency/insufficiency in patients with vasculitis (OR 22.5 [95% CI 1.6–128.9].ConclusionVitamin D deficiency and insufficiency are more frequent in patients with systemic small and medium vessel vasculitis and RA than HS. Renal involvement is one of the factors associated with vitamin D deficiency/insufficiency in patients with vasculitis.