Indrop d references

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Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease

American Journal of Clinical Nutrition.

2004 Dec;80(6 Suppl):1678S-88S. Abstract

Most humans depend on sun exposure to satisfy their requirements for vitamin D. Solar

ultraviolet B photons are absorbed by 7-dehydrocholesterol in the skin, leading to its

transformation to previtamin D3, which is rapidly converted to vitamin D3. Season,

latitude, time of day, skin pigmentation, aging, sunscreen use, and glass all influence

the cutaneous production of vitamin D3. Once formed, vitamin D3 is metabolized in the

liver to 25-hydroxyvitamin D3 and then in the kidney to its biologically active form,

1,25-dihydroxyvitamin D3. Vitamin D deficiency is an unrecognized epidemic among

both children and adults in the United States. Vitamin D deficiency not only causes

rickets among children but also precipitates and exacerbates osteoporosis among adults

and causes the painful bone disease osteomalacia. Vitamin D deficiency has been

associated with increased risks of deadly cancers, cardiovascular disease, multiple

sclerosis, rheumatoid arthritis, and type 1 diabetes mellitus. Maintaining blood

concentrations of 25-hydroxyvitamin D above 80 nmol/L (approximately 30 ng/mL)

not only is important for maximizing intestinal calcium absorption but also may be

important for providing the extrarenal 1alpha-hydroxylase that is present in most

tissues to produce 1,25-dihydroxyvitamin D3. Although chronic excessive exposure to

sunlight increases the risk of nonmelanoma skin cancer, the avoidance of all direct sun

exposure increases the risk of vitamin D deficiency, which can have serious


consequences. Monitoring serum 25-hydroxyvitamin D concentrations yearly should

help reveal vitamin D deficiencies. Sensible sun exposure (usually 5-10 min of exposure

of the arms and legs or the hands, arms, and face, 2 or 3 times per week) and increased

dietary and supplemental vitamin D intakes are reasonable approaches to guarantee

vitamin D sufficiency.

Vitamin D deficiency: a worldwide problem with health consequences

American Journal of Clinical Nutrition,

Vol. 87, No. 4, 1080S-1086S, April 2008

Abstract 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.


Sunlight, UV-radiation, vitamin D and skin cancer: how much sunlight do we need?

Advances in Experimental Medicine and Biology 2008 ;624:1-15.

Abstract Vtamin D is the sunshine vitamin for good reason. During exposure to sunlight, the

utraviolet B photons enter the skin and photolyze 7-dehydrocholesterol to previtamin D3

which in turn is isomerized by the body's temperature to vitamin D3. Most humans have

depended on sun for their vitamin D requirement. Skin pigment, sunscreen use, aging, time

of day, season and latitude dramatically affect previtamin D3 synthesis. Vitamin D

deficiency was thought to have been conquered, but it is now recognized that more than 50%

of the world's population is at risk for vitamin D deficiency. This deficiency is in part due to

the inadequate fortification of foods with vitamin D and the misconception that a healthy

diet contains an adequate amount of vitamin D. Vitamin D deficiency causes growth

retardation and rickets in children and will precipitate and exacerbate osteopenia,

osteoporosis and increase risk of fracture in adults. The vitamin D deficiency has been

associated pandemic with other serious consequences including increased risk of common

cancers, autoimmune diseases, infectious diseases and cardiovascular disease. There needs

to be a renewed appreciation of the beneficial effect of moderate sunlight for providing all

humans with their vitamin D requirement for health.


Serum 25-hydroxyvitamin D status of the US population: 1988–1994 compared with 2000–2004

American Journal of Clinical Nutrition,

Vol. 88, No. 6, 1519-1527, December 2008

Conclusions:

Overall, mean serum 25(OH)D was lower in 2000–2004 than 1988–1994. Assay changes

unrelated to changes in vitamin D status accounted for much of the difference in most

population groups. In an adult subgroup, combined changes in BMI, milk intake, and

sun protection appeared to contribute to a real decline in vitamin D status.

Presentation and Predisposing Factors of Nutritional Rickets in Children of Hazara Division

Journal of Ayub Medical College, Abbottabad : 2005;17(3)

Conclusion:

Rickets is common in Hazara Division presenting with variable signs and symptoms, predisposing the childhood population to different illnesses and skeletal deformities. In the presence of abundant sunshine lack of awareness of exposure to sun, malnutrition and antenatal factors may be the important predisposing factors for development of nutritional rickets.Non-infectious rickets remains an important preventable illness, which predisposes to infectious diseases like bacterial pneumonias, recurrent diarrheas and bone deformities in cases of late presentation. Nutritional rickets in sunny clime of Hazara Division presenting with multiple clinical presentation is predisposing factor for different childhood illnesses. Lack of awareness of importance of sun exposure, malnutrition and antenatal factors were found to be the predisposing factors for nutritional rickets.


Persisting vitamin D deficiency in the Asian adolescent

Archives of Disease in Childhood59 (8): 766–770.

Conclusion:

We conclude with other workers that until there is an improvement in the vitamin D status of the Asian population in Britain, adolescents should receive supplements. This is of particular importance to the adolescent girl who may soon be embarking on child bearing. Cholcalciferol given by the oral route in the autumn to produce a sustained rise in plasma 25-hydroxyvitamin D until the springtime would seem appropriate. It concluded that fortifying foods with vitamin D would lead to some people ingesting unacceptably high amounts of the vitamin, but recommended that health authorities should consider the provision of free vitamin D supplements to high risk Asian adolescents. Two years after publication subclinical rickets remains a problem in this group against a background of vitamin D deficiency.

Vitamin D deficiency linked to asthmatic severity in kids

Am J ResP and Critical Care Medicine. 23 April 2009

They study led by Dr Juan Celedon, Dr. P.H. and Dr Augusto Litonjua, of Harvard Medical School has shown that children with lower vitamin D levels were significantly more likely to have been hospitalized for asthma, tended to have airways with increased hyper reactivity and were likely to have used more inhaled corticosteroids, all signifying higher asthma severity. These children were also significantly more likely to have several markers of allergy, including dust-mite sensitivity."To our knowledge this is the first study to demonstrate an inverse association between circulating levels of vitamin D and markers of asthma severity and allergy," said researchers."While it is difficult to establish causation in a cross-sectional study such as this, the results were robust even after controlling for markers of baseline asthma severity," they added."This study suggests that there may be added health benefits to vitamin D supplementation,” said Dr. Celedon. The study showed that serum levels of vitamin D in more than 600 Costa Rican children were inversely linked to several indicators of allergy and asthma severity,Current recommendations for optimal vitamin D levels geared toward preserving bone health, such as preventing rickets in children and osteoporosis in adults."This study also provides epidemiological support for a growing body of in vitro evidence that vitamin D insufficiency may worsen asthma severity, and we suspect that giving vitamin D supplements to asthma patients who are deficient may help with their asthma control" wrote the researchers. However, whether vitamin D supplementation can prevent the development of asthma in very young children is a separate question and requires further investigation, they said.


Vitamin D deficiency in exclusively breast-fed infants

Indian Journal of Medical Research. 2008 Mar; 127(3):250-5

Conclusion

With the renewed worldwide emphasis on exclusive breast-feeding of infants for the first 6 months of life, infants even in developing countries are at risk of developing vitamin D deficiency unless adequate preventive measures are taken. Predisposing factors include reduced exposure to sunlight in spite of this being available in plenty in a country like India, due to various social and cultural reasons. There is a need to consider implementation of a vitamin D Supplementation Programme in infancy at the community level. Nutritional rickets in early infancy may become a more widespread problem in the near future unless strategies to ensure optimal vitamin D status for pregnant women and newborns are developed.

Vitamin-D status in a Population of healthy adults in Pakistan

Pak J Med Sci 2009;25(4):545-550

ABSTRACT

Objective: To determine the prevalence of hypovitaminosis D and its predictors in healthy adult Pakistanis. This study was conducted at various hospitals in Karachi from April 2007 to September 2007. Methodology: In this study 244 healthy adults 16-62 years of age, visited hospital as an attendant of the patients and fulfilled the inclusion and exclusion criteria has been enrolled. After taking written consent a questionnaire regarding age, gender, occupation, duration of sun exposure, area of skin exposed, type of residence used, clothing and dietary habits were recorded. Serum 25-OH Vitamin D3 levels were determined by electrochemiluminescence method and Vitamin D deficiency was defined as a level <20µg/ml. serum calcium. Phosphorus and Alkaline Phosphatase were also measured in all of these subjects. Results: Among 244 subjects ranging from 16-62 years, 193(79%) were female. Subjects were predominantly married (72%), mostly residing in apartments (47.5%) and most of them (41.8%) only exposed their face and hands while outdoor. Duration of sun exposure in majority was 1-2 hour /day (42%). Majority used clothes of variable colour (72%) and fabric (41%). One hundred and eighty six (76.2%) subjects had deficiency of Vitamin D and significantly correlated with duration of sunlight exposure, large area of skin exposed, vitamin D in diet consumed and colour of clothes worn. Vitamin D was


significantly correlated negatively with serum Phosphorus and Alkaline Phosphatase whereas serum calcium correlated positively. Conclusion: Prevalence of hypovitaminosis D among healthy Pakistanis is high and duration of sun exposure is the most common predictor of hypovitaminosis D.

Vitamin D and bone health in early life Proceedings of the Nutrition Society. 2003 Nov; 62(4):823-8

Abstract 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 deficiency: a worldwide problem with health consequences.

American Journal of Clinical Nutrition. 2008 Apr; 87(4):1080S-6S.

Abstract 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.


Low vitamin D during pregnancy linked to

pre-eclampsia Journal of Clinical Endocrinology and Metabolism. September 7, 2007

“Vitamin D deficiency early in pregnancy is associated with a five-fold increased risk of preeclampsia”.

“Our results showed that maternal vitamin D deficiency early in pregnancy is a strong, independent risk factor for preeclampsia,” said Lisa M. Bodnar, Ph.D., M.P.H., R.D., assistant professor of epidemiology at the University of Pittsburgh Graduate School of Public Health (GSPH) and lead author of the study. “Women who developed preeclampsia had vitamin D concentrations that were significantly lower early in pregnancy compared to women whose pregnancies were normal. And even though vitamin D deficiency was common in both groups, the deficiency was more prevalent among those who went on to develop preeclampsia.”

“Even a small decline in vitamin D concentration more than doubled the risk of preeclampsia,” noted James M. Roberts, M.D., senior author of the study and MWRI founding director. “And since newborn’s vitamin D stores are completely reliant on vitamin D from the mother, low vitamin levels also were observed in the umbilical cord blood of newborns from mothers with preeclampsia.”

Low vitamin D during pregnancy linked to pre-eclampsia

American Journal of Obstetrics & Gynecology Volume 203, Issue 4 , Pages 366.e1-366.e6, October 2010

Objective: Vitamin D deficiency has been linked to adverse pregnancy outcomes. The purpose of this investigation was to assess total 25-hydroxyvitamin D (25-OH-D) levels at diagnosis of early-onset severe preeclampsia (EOSPE). Study Design: After institutional review board approval, we enrolled subjects with EOSPE (<34 weeks' gestation with severe preeclampsia) in this case-control investigation in a 1:2 ratio with gestation-matched, contemporaneous control subjects. Demographic and outcome information was collected for each subject. Plasma total 25-OH-D levels were determined by radioimmunoassay and reported in nanograms per milliliter. Results were analyzed by Mann-Whitney U and multivariable regression.


Results: Subjects with EOSPE (n = 50) were noted to have decreased total 25-OH-D levels relative to healthy control subjects (n = 100; P < .001). This difference in total 25-OH-D remained significant after control for potential confounders. Conclusion: Total 25-OH-D is decreased at diagnosis of EOSPE. Further study is needed to understand the impact of vitamin D deficiency on pregnancy outcomes.

Maternal vitamin-D deficiency in Pakistan.

Scandinavian Association of Obstetricians and Gynecologists 1998 Nov;77(10):970-3.

Abstract OBJECTIVE OF THE STUDY: This study was performed to assess the vitamin D status of

healthy Pakistani nursing mothers and their breastfed infants.

METHODS: Seventy-one nursing mothers and their breastfed infants belonging to upper

and lower socio-economic class were examined 6 weeks to 11 months after delivery. Serum

25-hydroxy vitamin D [25(OH)D], serum calcium, phosphorus and alkaline phosphatase

were measured.

RESULTS: The mean serum 25(OH)D in mothers was 36.7+/-32.4 nmol/L and 41.25+/-35.4

nmol/ L in infants. Thirty-four (48%) mothers and 37 (52%) infants had levels less than 25

nmol/ L. Significantly higher levels were found in uneducated mothers (p=0.01), mothers

of lower socio-economic class (p<0.001) and in those living in mud houses (p<0.001). A

significant correlation was found between serum 25(OH)D levels of infants under three

months of age and their mothers (p<0.01).

CONCLUSIONS: High prevalence of vitamin D deficiency was found in nursing mothers

and their infants predominantly in the upper socioeconomic class.


Vitamin D and cardiovascular disease risk Current Opinion in Clinical Nutrition & Metabolic Care: January 2008 - Volume 11 - Issue 1 - p 7-12

Abstract

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.

Vitamin D for the Prevention of Preeclampsia?

Nutrition Reviews Volume 63, Issue 7, pages 225–232, July 2005

Abstract:Preeclampsia has been suggested to result from a partial breakdown of tolerance to the developing fetus after maternal immune maladaptation. Several of the proposed immunomodulatory properties of the hormonal vitamin D system could potentially have beneficial effects for successful maintenance of pregnancy. Preeclampsia is characterized by marked changes in vitamin D metabolism. This paper reviews the evidence suggesting that the immunomodulatory properties of 1,25(OH)2D may play a key role in maintaining immunological tolerance in pregnancy, and proposes that ensuring adequate vitamin D status/intake may help in the prevention and management of preeclampsia


Vitamin D supplementation and reduced risk of preeclampsia in nulliparous women.

Epidemiology. 2009 Sep;20(5):720-6.

Abstract

Background: A recent study showed that nulliparous women who develop preeclampsia had low concentrations of vitamin D in serum sampled in midpregnancy. The aim of the present study was to estimate the association between intake of vitamin D during pregnancy and the risk of preeclampsia in 23,423 nulliparous pregnant women taking part in the Norwegian Mother and Child Cohort Study.

Methods: Participating women answered questionnaires at gestational week 15 (general health questionnaire), at week 22 (food frequency questionnaire), and at week 30 (general health questionnaire). Pregnancy outcomes were obtained from the Medical Birth Registry. Nutrient intake was calculated from foods and dietary supplements. We estimated relative risks as odds ratios, and controlled for confounding with multiple logistic regression.

Results: The odds ratio of preeclampsia for women with a total vitamin D intake of 15-20 microg/d compared with less than 5 microg/d was 0.76 (95% confidence interval = 0.60-0.95). Considering only the intake of vitamin D from supplements, we found a 27% reduction in risk of preeclampsia (OR = 0.73 [0.58-0.92]) for women taking 10-15 microg/d as compared with no supplements. No association was found between intake of vitamin D from the diet alone and the occurrence of preeclampsia.

Conclusions: These findings are consistent with other reports of a protective effect of vitamin D on preeclampsia development. However, because vitamin D intake is highly correlated with the intake of long chain n-3 fatty acids in the Norwegian diet, further research is needed to disentangle the separate effects of these nutrients.


Vitamin D deficiency widespread across India Pakistan News.Net

Tuesday 14th December, 2010 (ANI)

The results of various studies show severe Vitamin D deficiency across India and Pakistan in all age groups,as well as insufficiency in populations of South-East and East Asia.Bone health experts attending the 1st Asia-Pacific Osteoporosis Meeting in Singapore this week have flagged vitamin D deficiency as a major concern in the region, particularly in South Asia. Nikhil Tandon, Professor of Endocrinology and Metabolism at the All India Institute of Medical Sciences of New Delhi, said, "A lack of exposure to sunshine, genetic traits and dietary habits are all factors which influence vitamin D levels. In certain regions, vitamin D deficiency can also be attributed to skin pigmentation and traditional clothing, as well as air pollution and limited outdoor activity in urban populations."Vitamin D is primarily made in the skin when it is exposed to sunlight, with limited amounts obtained from food sources.At a Vitamin D Roundtable held in conjunction with the meeting, nutrition and bone health experts discussed the importance of encouraging further studies on vitamin D status and risk factors in countries where data are scarce. The group is developing interactive vitamin D maps based on published data of 25(OH)D serum levels, the biomarker used to measure vitamin D status in the blood. Chair of the Roundtable, Professor Robert Josse, Professor in the Departments of Medicine and Nutritional Sciences at the University of Toronto, Canada commented, "The maps will track vitamin D levels by region and different population groups, giving a valuable overview of the prevalence of vitamin D deficiency around the world." "The global maps are innovative tools that will help identify problem areas, encourage awareness and stimulate research studies. By facilitating global comparisons, the maps should provide an incentive for health authorities to implement strategies to improve vitamin D status in the population," he concluded.

Low vitamin D levels tied to pregnancy complication By Amy Norton

NEW YORK | Wed Aug 18, 2010 12:20pm EDT

(Reuters Health) - A new study finds that women who develop a severe form of pregnancy-related high blood pressure tend to have lower blood levels of vitamin D than healthy pregnant women -- raising the possibility that the vitamin plays a role in the complication.The condition is known as early-onset severe preeclampsia, and while it arises in about 2 to 3 percent of pregnancies, it contributes to about 15 percent of


preterm births in the U.S. each year.Preeclampsia is a syndrome marked by a sudden increase in blood pressure and a buildup of protein in the urine due to stress on the kidneys. Early-onset severe preeclampsia is a particularly serious form that arises before the 34th week of pregnancy.

In the current study, researchers found that vitamin D levels were generally lower among 50 women with early severe preeclampsia compared with those of 100 healthy pregnant women. The average vitamin D level in the former group was 18 nanograms per milliliter (ng/mL), versus 32 ng/mL in the latter group.There is debate over what constitutes an adequate level of vitamin D in the blood. But many experts say that at least 32 ng/mL is needed for overall health.The findings, reported in the American Journal of Obstetrics & Gynecology, do not prove that lower vitamin D levels contribute to early-onset severe preeclampsia.They do, however, add to a spate of recent research finding connections between vitamin D levels in the blood, or vitamin D intake, and the risks of a host of health problems.Studies have, for example, linked relatively low vitamin D levels to higher risks of type 1 diabetes and severe asthma attacks in children and, in adults, heart disease, certain cancers and depression.But whether vitamin D is the reason for the excess risks -- and whether taking supplements can curb those risks -- has yet to be shown.A few past studies have found an association between vitamin D and preeclampsia in general. Now more work is needed to see whether pregnant women's vitamin D levels predict the odds of preeclampsia developing -- and whether raising those levels with vitamin D supplements lowers women's risk of the complication, according to Dr. Christopher J. Robinson, of the Medical University of South Carolina in Charleston.If vitamin D is involved in preeclampsia risk, Robinson told Reuters Health, then it might help explain why African American women are at greater risk of the complication than other racial groups -- even when factors like income and healthcare access are taken into account.

Vitamin D is naturally synthesized in the skin when it is exposed to sunlight. This process is less efficient in people with darker skin, and studies have found that African Americans commonly have low levels of vitamin D in their blood; a recent study of U.S. teenagers, for example, found that while 14 percent overall had vitamin D deficiency -- defined as less than 20 ng/mL -- the same was true of half of black teens.The current findings are based on 50 pregnant women with early-onset preeclampsia seen at the Medical University of South Carolina, along with 100 women with healthy pregnancies.Of the preeclampsia group, 54 percent were deemed to have vitamin D deficiency (less than 20 ng/mL), versus 27 percent of the healthy group. Only 24 percent of women with preeclampsia had vitamin D levels greater than 32 ng/mL, compared with 47 percent of their healthy counterparts.When Robinson and his colleagues accounted for a number of factors in preeclampsia risk -- including older age, heavier body weight and African American race -- vitamin D levels were independently related to the odds of early preeclampsia.


Severe proximal myopathy with remarkable recovery after vitamin D treatment.

The Canadian Journal Neurological Sciences. 2009 May;36(3):336-9.

CONCLUSIONS: Vitamin D deficiency is an important treatable cause of osteomalacic myopathy in Saudi Arabia. The diagnosis is frequently delayed or missed. Screening for Vitamin D deficiency in patients with acquired myopathy is needed to identify this treatable disorder.

A phase 2 trial exploring the effects of high-dose (10,000 IU/day) vitamin D(3) in breast cancer patients with bone metastases.

Cancer. 2010 Jan 15;116(2):284-91.

Conclusions: Daily doses of 10,000 IU vitamin D(3) for 4 months appear safe in patients without comorbid conditions causing hypersensitivity to vitamin D. Treatment reduced inappropriately elevated parathyroid hormone levels, presumably caused by long-term bisphosphonate use. There did not appear to be a significant palliative benefit nor any significant change in bone resorption.

Vitamin D and chronic widespread pain in a white middle-aged British population: evidence from a cross-sectional

population survey.

Annals of the rheumatic diseases2009 Jun;68(6):817-22. Epub 2008 Aug 12.

CONCLUSION: Current vitamin D status was associated with CWP in women but not in men. Follow-up studies are needed to evaluate whether higher vitamin D intake might have beneficial effects on the risk of CWP.


Post herpetic neuralgia, schwann cell activation and vitamin D.

The Medical Hypotheses. 2009 Dec;73(6):927-9. Epub 2009 Jul 26.

Abstract While the underlying pathophysiology of herpes zoster infection has been well

characterised, many of the mechanisms relating to the subsequent development of post

herpetic neuralgia (PHN) remain uncertain. The dorsal horn atrophy and reduction in skin

innervation seen in PHN patients does not adequately explain many clinical features or the

efficacy of a number of topical treatments. In the central nervous system the glia, their

receptors and their secreted signalling factors are now known to have a major influence on

neural function. In the peripheral nervous system, schwann cell activation in response to

infection and trauma releases a number of neuroexcitatory substances. Activation of the

nervi nervorum in the peripheral nervous system also leads to the release of calcitonin gene

related peptide, substance P and nitric oxide. Schwann cell and/or nervi nervorum

activation could be an additional mechanism of pain generation in PHN. Such a paradigm

shift would mean that drugs useful in the treatment of glial cell activation such as naloxone,

naltrexone, minocycline, pentoxifyllline, propentofylline, AV411 (ibudilast) and interleukin

10 could be useful in PHN. These drugs could be used systemically or even topically. High

dose topical vitamin D would appear to offer particular promise because vitamin D has the

ability to both reduce glial inflammation and reduce nitric oxide production.

Vitamin D status and its associations with disease activity and severity in African Americans with

recent-onset rheumatoid arthritis The Journal of Rheumatology. 2010 Feb;37(2):275-81. Epub 2009 Dec 23

Conclusion: Vitamin D insufficiency is common in African Americans with recent-onset RA. Unadjusted associations of circulating vitamin D with baseline pain, swollen joints, and DAS28 were explained by differences in season, age, and gender and were not significant in multivariate analyses. In contrast to reports of Northern Europeans with


early inflammatory arthritis, there are not strong associations of 25(OH)-D concentration with symptoms or disease severity in African Americans with RA.

Demographic differences and trends of vitamin D insufficiency in the US population, 1988-2004.

Archives of Internal Medicines. 2009 Mar 23;169(6):626-32.

Conclusions: National data demonstrate a marked decrease in serum 25(OH)D levels from the 1988-1994 to the 2001-2004 NHANES data collections. Racial/ethnic differences have persisted and may have important implications for known health disparities. Current recommendations for vitamin D supplementation are inadequate to address the growing epidemic of vitamin D insufficiency.

Effect of vitamin D supplementation on serum 25-hydroxy vitamin D levels, joint pain, and fatigue in women starting

adjuvant letrozole treatment for breast cancer.

Breast Cancer Research Treatment. 2010 Jan;119(1):111-8. Epub 2009 Aug 5.

Abstract Vitamin D deficiency and insufficiency may contribute to musculoskeletal symptoms and

bone loss observed in women taking aromatase inhibitors (AIs). This study was conducted

to determine the prevalence of suboptimal vitamin D levels in women initiating adjuvant

letrozole for breast cancer and to determine whether supplementation with 50,000 IU of

vitamin D3 weekly could reduce musculoskeletal symptoms and fatigue in women who

have suboptimal vitamin D levels. Sixty women about to begin an adjuvant AI were

enrolled. Baseline 25OHD levels were obtained, and women completed symptom

questionnaires. They were then started on letrozole, along with standard dose calcium and

vitamin D. Four weeks later, women with baseline 25OHD levels </=40 ng/ml started

additional vitamin D3 supplementation at 50,000 IU per week for 12 weeks. 25OHD levels

were re-assessed at 4, 10, and 16 weeks; the questionnaires were repeated at weeks 4 and 16.

At baseline, 63% of women exhibited vitamin D deficiency (<20 ng/ml) or insufficiency (20-


31 ng/ml). 25OHD levels >40 ng/ml were achieved in all 42 subjects who received 12 weeks

of supplementation with 50,000 IU vitamin D3 weekly, with no adverse effects. After 16

weeks of letrozole, more women with 25OHD levels >66 ng/ml (median level) reported no

disability from joint pain than did women with levels <66 ng/ml (52 vs. 19%; P = 0.026).

Vitamin D deficiency and insufficiency are prevalent in post-menopausal women initiating

adjuvant AI. Vitamin D3 supplementation with 50,000 IU per week is safe, significantly

increases 25OHD levels, and may reduce disability from AI-induced arthralgias.

The same annual dose of 292000 IU of vitamin D (cholecalciferol) on either daily or four monthly basis for

elderly women Clinical Endocrinology (Oxf). 2010 Apr;72(4):455-61. Epub 2009 May 25.

Conclusions: In terms of serum 25(OH)D(3) concentrations, 800 IU daily was more efficient

than a 97333 IU every 4 months. However, to increase adherence, the latter is still worth

developing. Both treatments increased urinary excretion of calcium, but did not worsen

renal function.

Vitamin D: Bone and Beyond, Rationale and

Recommendations for Supplementation The American Journal of Medicine Volume 122, Issue 9

Pages 793-802 (September 2009)

Conclusions:Vitamin D deficiency remains an evolving, worldwide health concern contributing to a multitude of disease entities, whereas vitamin D sufficiency is proving to be essential for overall health and well-being. Although ultraviolet radiation serves as an option to assist in increasing serum vitamin D levels, less harmful and more reliable alternatives exist. Because ultraviolet radiation-induced skin cancer and photoaging are an increasing problem, we recommend vitamin D supplementation over deliberate sun


exposure to ensure adequate vitamin D levels, especially in fair-skinned individuals. Mounting evidence has shown that it remains vital for physicians and health professionals to counsel their patients and ensure adequate intake to avoid the harmful effects of vitamin D deficiency.

Vitamin d and chronic pain in immigrant and ethnic minority patients-investigation of the relationship and

comparison with native Western populations.

International Journal of Endocrinology. 2010; 2010:753075. Epub 2009 Oct 19.

Abstract

Vitamin D deficiency has been implicated in chronic pain. Immigrant and ethnic minority populations have been shown to have lower vitamin D levels than native Western populations and often to be vitamin D deficient. This systematic review investigates the relationship between vitamin D and chronic pain in immigrant and ethnic minority populations. Included were studies reporting on 25-OH vitamin D levels in immigrant/ethnic minority populations affected by chronic pain, and/or reporting on the treatment of chronic pain with vitamin D preparations in such populations. We found that 25-OH vitamin D levels were low and often deficient in immigrant/ethnic minority populations. Vitamin D levels depended on the latitude of the study location and hence sunlight exposure. There was insufficient evidence to reach a verdict on the value of treating chronic pain in immigrant/ethnic minority patients with vitamin D preparations because the studies were few, small, and of low quality.

Vitamin D insufficiency and musculoskeletal symptoms in breast cancer survivors on aromatase inhibitor therapy

Cancer Nursing. 2009 Mar-Apr;32(2):143-50.

Abstract:Breast cancer survivors (BCSs) on aromatase inhibitor (AI) therapy often experience musculoskeletal symptoms (joint pain and stiffness, bone and muscle pain, and muscle weakness), and these musculoskeletal symptoms may be related to low serum levels of vitamin D. The primary purpose of this pilot exploratory study was to determine whether serum levels of 25-hydroxyvitamin D (25[OH]D) concentration were below normal (<30 ng/mL) in 29 BCSs on AI therapy and if musculoskeletal symptoms were related to these low vitamin D levels. The mean (SD) serum 25(OH)D level was 25.62 (4.93) ng/mL; 86% (n = 25) had levels below 30 ng/mL. Patients reported muscle pain in the neck and back, and there was a significant inverse correlation between


pain intensity and serum 25(OH)D levels (r = -0.422; P < .05 [2 tailed]). This sample of BCSs taking AIs had below normal levels of serum 25(OH)D despite vitamin D supplements. This is one of the few studies to document a significant relationship between vitamin D levels and muscle pain in BCSs on AI therapy. Findings from this pilot study can be used to inform future studies examining musculoskeletal symptoms in BCSs on AI therapy and relationships with low serum levels of vitamin D.

Vitamin D and Bone Health

Current Sports Medicine Reports

July/August 2010 - Volume 9 - Issue 4 - pp 220-226

Abstract While it is well recognized that vitamin D is necessary for optimal bone health, emerging evidence is finding that adequate vitamin D intake reduces risk for conditions such as stress fracture, total body inflammation, infectious illness, and impaired muscle function. Studies in athletes have found that vitamin D status is variable and is dependent on outdoor training time (during peak sunlight), skin color, and geographic location. Although research has found that athletes generally do not meet the U.S. dietary reference intake for vitamin D, inadequate endogenous synthesis is the most probable reason for insufficient/deficient status. Given the recent findings, it is imperative that sports dietitians and physicians routinely assess vitamin D status and make recommendations to help athletes achieve a serum 25(OH)D concentration of ≥32 and preferably ≥40 ng·mL−1. Further research is needed to determine the effect of vitamin D status on injury, training, and performance in athletes.

Athletic Performance and Vitamin D.

Medicine and Science in Sports and Exercise 2009 May;41(5):1102-10

ABSTRACT PURPOSE: Activated vitamin D (calcitriol) is a pluripotent pleiotropic secosteroid hormone. As a steroid hormone, which regulates more than 1000 vitamin D-responsive human genes, calcitriol may influence athletic performance. Recent research indicates that intracellular calcitriol levels in numerous human tissues, including nerve and muscle tissue, are increased when inputs of its substrate, the prehormone vitamin D, are increased. METHODS: We reviewed the world's literature for evidence that vitamin D affects physical and athletic performance. RESULTS: Numerous studies, particularly in the German literature in the 1950s, show vitamin D-producing ultraviolet light improves athletic performance. Furthermore, a consistent literature indicates physical and athletic performance is seasonal; it peaks when


25-hydroxy-vitamin D [25(OH)D] levels peak, declines as they decline, and reaches its nadir when 25(OH)D levels are at their lowest. Vitamin D also increases the size and number of Type II (fast twitch) muscle fibers. Most cross-sectional studies show that 25(OH)D levels are directly associated with musculoskeletal performance in older individuals. Most randomized controlled trials, again mostly in older individuals, show that vitamin D improves physical performance. CONCLUSIONS: Vitamin D may improve athletic performance in vitamin D-deficient athletes. Peak athletic performance may occur when 25(OH)D levels approach those obtained by natural, full-body, summer sun exposure, which is at least 50 ng x mL(-1). Such 25(OH)D levels may also protect the athlete from several acute and chronic medical conditions.

Vitamin D and Human Skeletal Muscle Scandinavian Journal of Medicine & Science in Sports

2010 Apr;20(2):182-90. Epub 2009 Oct

Abstract Vitamin D deficiency is an increasingly described phenomenon worldwide, with well-known impacts on calcium metabolism and bone health. Vitamin D has also been associated with chronic health problems such as bowel and colonic cancer, arthritis, diabetes and cardiovascular disease. In recent decades, there has been increased awareness of the impact of vitamin D on muscle morphology and function, but this is not well recognized in the Sports Medicine literature. In the early 20th century, athletes and coaches felt that ultraviolet rays had a positive impact on athletic performance, and increasingly, evidence is accumulating to support this view. Both cross-sectional and longitudinal studies allude to a functional role for vitamin D in muscle and more recently the discovery of the vitamin D receptor in muscle tissue provides a mechanistic understanding of the function of vitamin D within muscle. The identification of broad genomic and non-genomic roles for vitamin D within skeletal muscle has highlighted the potential impact vitamin D deficiency may have on both under-performance and the risk of injury in athletes. This review describes the current understanding of the role vitamin D plays within skeletal muscle tissue.

Vitamin D - Muscle Function and Exercise Performance

Pediatric clinics of North America 2010 Jun;57(3):849-61

Abstract Vitamin D has an important role in skeletal muscles. Previously recognized for its effects on bone, it is now known that vitamin D has a much wider spectrum of usefulness for muscle.


Studies indicate that vitamin D deficiency is pandemic. Those affected include the young and otherwise healthy members of the population, including athletes. Controversy exists regarding the amount of supplementation required to reverse deficiency and the relative effect of such a reversal on overall health. This article reviews current data on the role of vitamin D on muscle function, and explores the potential implications of its deficiency and supplementation on physical fitness and athletic performance. Vitamin D Status and Muscle Function in Post-Menarchal

Adolescent Girls

The Journal of Clinical Endocrinology and Metabolism

2009 Feb;94(2):559-63. Epub 2008 Nov 25

ABSTRACT Context: There has been a resurgence of vitamin D deficiency among infants, toddlers, and adolescents in the United Kingdom. Myopathy is an important clinical symptom of vitamin D deficiency, yet it has not been widely studied. Objective: Our objective was to investigate the relationship of baseline serum 25 hydroxyvitamin D [25(OH)D] concentration and PTH with muscle power and force. Design: This was a cross-sectional study. Setting: The study was community based in a secondary school. Participants: A total of 99 post-menarchal 12- to 14-yr-old females was included in the study. Main Outcome Measures: Jumping mechanography to measure muscle power, velocity, jump height, and Esslinger Fitness Index from a two-legged counter movement jump and force from multiple one-legged hops was performed. Body height, weight, and serum concentrations of 25(OH)D, PTH, and calcium were measured. Results: Median serum 25(OH)D concentration was 21.3 nmol/liter (range 2.5-88.5) and PTH 3.7 pmol/liter (range 0.47-26.2). After correction for weight using a quadratic function, there was a positive relationship between 25(OH)D and jump velocity (P = 0.002), jump height (P = 0.005), power (P = 0.003), Esslinger Fitness Index (P = 0.003), and force (P = 0.05). There was a negative effect of PTH upon jump velocity (P = 0.04). Conclusion: From these data we conclude that vitamin D was significantly associated with muscle power and force in adolescent girls.

Vitamin D and Calcium Supplementation Reduces

Cancer Risk American Journal of Clinical Nutrition 2007; 85(6):1586–1591.


Randomized clinical trials designed to investigate the effects of vitamin D intake on bone health have suggested that higher vitamin D intakes may reduce the risk of cancer. One study involved nearly 1,200 healthy postmenopausal women who took daily supplements of calcium (1,400 mg or 1,500 mg) and vitamin D (25 μg vitamin D, or 1,100 IU-a relatively large dose) or a placebo for 4 years. The women who took the supplements had a 60 percent lower overall incidence of cancer.

Vitamin D and Colorectal Cancer American Journal of Clinical Nutrition 1999; 69(6):1330S–1338S.

A number of observational studies have investigated whether people with higher vitamin D levels or intake have lower risks of specific cancers, particularly colorectal cancer and breast cancer. Associations of vitamin D with risks of prostate, pancreatic, and other, rarer cancers have also been examined. These studies have yielded inconsistent results, most likely because of the challenges of conducting observational studies of diet.

Prospective Study of Serum Vitamin D and Cancer Mortality in the United States

Journal of the National Cancer Institute 2007; 99(21):1594–1602. At least one epidemiologic study has reported an association between vitamin D and reduced mortality from colorectal cancer. Among the 16,818 participants in the Third National Health and Nutrition Examination Survey, those with higher vitamin D blood levels (≥80 nmol/L) had a 72 percent lower risk of colorectal cancer death than those with lower vitamin D blood levels (< 50 nmol/L).

Vitamin D and Neoplasia Journal of the American Medical Association 2003; 290(22):2959–2967

The vitamin D intakes of 3,000 people from several Veterans Affairs medical centers were examined to determine whether there was an association between intake and advanced colorectal neoplasia (an outcome that included high-risk adenomas as well as colon cancer). Individuals with the highest vitamin D intakes (more than 16 μg, or 645 IU, per day) had a lower risk of developing advanced neoplasia than those with lower intakes.

Vitamin D and Colorectal Adenoma Cancer Epidemiology, Biomarkers, and Prevention 2008; 17(11):2958–2969

A pooled analysis of data from these and a number of other observational studies found that higher circulating levels of vitamin D and higher vitamin D intakes were associated with lower risks of colorectal adenoma.

Vitamin D and Breast Cancer Journal of Steroid Biochemistry and Molecular Biology 2008; 111(3–5):195–199

Most women in these studies had relatively low vitamin D intakes, and, when the analysis was


restricted to women with the highest vitamin D intakes (>10 μg, or 400 IU, per day), their breast cancer risks were lower than those of women with the lowest intakes (typically <1.25 μg, or 50 IU, per day).

Vitamin D and Pancreatic Cancer Cancer Epidemiology, Biomarkers, and Prevention 2006; 15(9):1688–1695

There is conflicting evidence about vitamin D’s relationship to risk of pancreatic cancer. A study of more than 120,000 men and women from the Health Professionals Follow-Up Study and the Nurses’ Health Study showed that participants with higher dietary intake of vitamin D had progressively lower risk of pancreatic cancer, compared with those who had the lowest intake.

Vitamin D deficiency with cognitive impairment in older women

Neurology. 2010. 74(1), 27-32.

Low vitamin D levels are associated with cognitive impairment, specifically in individuals over age 75. A 2010 study of 752 women found that women with vitamin D deficiency had

increased rates of significant cognitive impairment. Low levels of vitamin D have previously been associated with neurological concerns and disorders, but this new research

indicates the importance of ample vitamin D for optimal brain health.

Cancer Prevention Clinical Cancer Research. 2011. 17(4), 817-26.

Vitamin D has been linked with fighting numerous cancers including lung, breast, colon, and prostate. In the case of lung cancer, supplementing with Vitamin D may help offset elevated levels of an enzyme that is associated with the development of aggressive lung

cancer tumors. In a 2011 study, lung cancer patients with high vitamin D levels had an 81 percent survival rate after five years compared to those with low levels (41percent survival

rate). Scientists are investigating other anti-cancer benefits of taking vitamin D supplementation.


Vitamin D and the postmenopausal population

Menopause Int 2011 17: 102-107 Abstract

Vitamin D, a hormone critical to the body's maintenance of serum calcium and phosphorus concentrations, is currently the subject of much scientific interest. Low levels of vitamin D have been observed in many populations and epidemiological studies have suggested a link between this biochemical state and a range of diseases, such as cancer, diabetes and multiple sclerosis. While the consequence of vitamin D deficiency is well documented for bone (rickets and osteomalacia), with mixed findings relating to falls and fractures, a causal link between vitamin D deficiency and these wider health outcomes has not been established. If these relationships were found to be causal, the morbidity and mortality resulting from low levels of vitamin D could be substantial; the current evidence base, however, most robustly supports the assessment of serum 25(OH)-vitamin D in the context of specific symptoms, low bone mineral density or biochemical abnormalities, rather than as an entity to treat in its own right or as the basis for a population-wide screening programme.

Prevalence of Vitamin D Deficiency in Healthy Adults in Scotland, and Supplementation Reduces the Proportion That

Are Severely Deficient

J. Nutr. 2011 141: 1535-1542

Abstract

Vitamin D deficiency has recently been implicated as a possible risk factor in the etiology of numerous diseases, including nonskeletal conditions. In humans, skin synthesis following exposure to UVB is a potent source of vitamin D, but in regions with low UVB, individuals are at risk of vitamin D deficiency. Our objectives were to describe the prevalence of vitamin D deficiency and to investigate determinants of plasma 25-hydroxyvitamin D (25-OHD) concentrations in a high northern latitude country. Detailed dietary, lifestyle, and demographic data were collected for 2235 healthy adults (21–82 y) from Scotland. Plasma 25-OHD was measured by liquid chromatography-tandem MS. Among study participants, 34.5% were severely deficient (25-OHD <25 nmol/L) and 28.9% were at high risk of deficiency (25–40 nmol/L). Only 36.6% of participants were at low risk of vitamin D deficiency or had adequate levels


(>40 nmol/L). Among participants who were taking supplements, 21.3% had a May-standardized 25-OHD concentration >50 nmol/L, 54.2% had 25–50 nmol/L, and 24.5% had <25 nmol/L, whereas this was 15.6, 43.3, and 41%, respectively, among those who did not take supplements (P < 0.0001). The most important sources of vitamin D were supplements and fish consumption. Vitamin D deficiency in Scotland is highly prevalent due to a combination of insufficient exposure to UVB and insufficient dietary intake. Higher dietary vitamin D intake modestly improved the plasma 25-OHD concentration (P = 0.02) and reduced the proportion of severely deficient individuals (P < 0.0001). In regions with low UVB exposure, dietary and supplement intake may be much more important than previously thought and consideration should be given to increasing the current recommended dietary allowance of 0–10 μg/d for adults in Scotland.

A cross-sectional study of vitamin D and insulin resistance in children

Arch. Dis. Child. 2011 96: 447-452 Abstract

Objective Vitamin D deficiency is common and has been associated with several non-bone/calcium related outcomes. The objective was to determine the association between serum 25-hydroxyvitamin D (25-OH-D) and fasting glucose, insulin and insulin sensitivity in obese and non-obese children. Patients/setting/design Cross-sectional study of 85 children aged 4–18 years recruited from the local Philadelphia community and Sleep Center. Main outcomes measures Fasting blood glucose, insulin and 25-OH-D were measured. Insulin resistance was calculated using homeostasis model assessment (HOMA). Body mass index standard deviation scores (BMI-Z) and pubertal stage were determined. Multivariable linear regression was used to determine factors associated with decreased 25-OH-D and to determine the association of vitamin D with HOMA. Results Median 25-OH-D was 52 nmol/l (IQR 34–76). 26% of subjects were vitamin D sufficient (25-OH-D ≥75 nmol/l), 27% had intermediate values (50–75 nmol/l) and 47% were insufficient (25–50 nmol/l) or frankly deficient (<25 nmol/l). In the multivariable model, older age, higher BMI-Z and African–American race were all negatively associated with 25-OH-D; summer was positively associated with 25-OH-D. Lower 25-OH-D was associated with higher fasting blood glucose, insulin and HOMA after adjustment for puberty and BMI-Z. Conclusion Low 25-OH-D, common in the paediatric population at risk for diabetes (older children, African–Americans, children with increasing BMI-Z) is associated with worse insulin resistance.


Vitamin D Insufficiency in Korea—A Greater Threat to Younger Generation

J. Clin. Endocrinol. Metab. 2011 96: 643-651

Abstract

Context:Vitamin D status in the Korean population has not been adequately determined. Objective:To investigate the vitamin D status and the prevalence of vitamin D insufficiency in the Korean population, and also identify the predictors for vitamin D insufficiency in Korea. Design and Setting:The Fourth Korea National Health and Nutrition Examination Surveys (KNHANES IV) in the Korean population conducted in 2008. Participants:3,047 males and 3,878 females aged 10 years and older selected in all the 16 administrative districts of South Korea. Main Outcome Measures:Serum 25-hydroxyvitamin D [25(OH)D] levels and the prevalence of vitamin D insufficiency defined as serum 25(OH)D level of less than 20 ng/ml. Results:Vitamin D insufficiency was found in 47.3% of males and 64.5% of females, whereas only 13.2% of male and 6.7% of female population had a serum 25(OH)D level of greater than 30 ng/ml. Vitamin D insufficiency was most prevalent in the age of 20–29, with a rate of 65.0% in males and 79.9% in females, and least prevalent in the age of 60–69 in males and 50–59 in females. Those who work usually indoors were more predisposed to vitamin D insufficiency. In the adult population, predictors for vitamin D insufficiency included young age groups, spring and winter seasons, living in an urban area, and indoor occupations. Conclusions:Vitamin D insufficiency is very common, and it is now a greater threat to the younger generation in Korea. Current recommendations for vitamin D intakes for Koreans are inadequate, especially for the youth.


Vitamin D insufficiency and prognosis in chronic lymphocytic leukemia

Blood 2011 117: 1492-1498

Abstract

Vitamin D insufficiency is common globally and low levels are linked to higher cancer incidence. Although vitamin D insufficiency is related to inferior prognosis in some cancers, no data exist for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). We evaluated the relationship of 25(OH)D serum levels with time-to-treatment (TTT) and overall survival (OS) in newly diagnosed CLL patients participating in a prospective cohort study (discovery cohort) and a separate cohort of previously untreated patients participating in an observational study (confirmation cohort). Of 390 CLL patients in the discovery cohort, 119 (30.5%) were 25(OH)D insufficient. After a median follow-up of 3 years, TTT (hazard ratio[HR] = 1.66; P = .005) and OS (HR = 2.39; P = .01) were shorter for 25(OH)D-insufficient patients. In the validation cohort, 61 of 153 patients (39.9%) were 25(OH)D insufficient. After a median follow-up of 9.9 years, TTT (HR = 1.59; P = .05) and OS (HR 1.63; P = .06) were again shorter for 25(OH)D-insufficient patients. On pooled multivariable analysis of patients in both cohorts adjusting for age, sex, Rai stage, CD38 status, ZAP-70 status, immunoglobulin heavy chain variable (IGHV) gene mutation status, CD49d status, and cytogenetic abnormalities assessed by interphase fluorescent in situ hybridization testing, 25(OH)D insufficiency remained an independent predictor of TTT (HR = 1.47; P = .008), although the association with OS was not significant (HR = 1.47; P = .07). Vitamin D insufficiency is associated with inferior TTT and OS in CLL patients. Whether normalizing vitamin D levels in deficient CLL patients would improve outcome merits clinical testing.

Clinical Response in Patients with Dengue Fever to Oral Calcium plus Vitamin D Administration

Proc. West. Pharmacol. Soc. 52: 14-17 (2009)

Abstract A dengue epidemic is one of the most important public health problems in the tropical and subtropical areas of the World. In 2005, 7,062 dengue cases were reported in Tamaulipas on Mexico's eastern coast, including 1,832 (26%) cases classified as Dengue


Hemorrhagic Fever (DHF). Dengue fever (DF) is characterized by fever, intense headache, myalgias, arthralgias, rash, nausea and vomiting. A proportion of infected persons may develop DHF characterized by prominent hemorrhagic manifestations associated with thrombocytopenia. An immune mechanism of thrombocytopenia due to increased platelet destruction appears to be operative in patients with DHF. Excessive capillary permeability may lead to Dengue Shock Syndrome (DSS). Patients with DHF/DSS who also have prolonged fever (> 5 days) are at high risk for concurrent bacteremia. Standard treatment is limited to electrolytic solutions, rest, measurements of body temperature, blood pressure, hematocrit, platelet count, and administration of antipyretics like paracetamol when fever is too high. Extracellular calcium plays a key role in platelet aggregation and for the regulation of the immune response in persons infected with Dengue Virus (DV), and dihydroxy-vitamin D has recently been found to alter IL-12 expression and dendritic cell maturation. We report the cases of five patients who received oral calcium carbonate plus Vitamin D3, who improved overall clinical condition and reduced the duration of signs and symptoms of DF.

Vitamin D and the anti-viral state Journal of clinical Virology vol 150 issue 3, March 2011

Vitamin D has long been recognized as essential to the skeletal system. Newer evidence suggests that it also plays a major role regulating the immune system, perhaps including immune responses to viral infection. Interventional and observational epidemiological studies provide evidence that vitamin deficiency may confer increased risk of influenza and respiratory tract infection. Vitamin D deficiency is also prevalent among patients with HIV infection. Cell culture experiments support the thesis that vitamin D has direct anti-viral effects particularly against enveloped viruses. Though vitamin D’s anti-viral mechanism has not been fully established, it may be linked to vitamin D’s ability to up-regulate the anti-microbial peptides LL-37 and human beta defensin 2. Additional studies are necessary to fully elucidate the efficacy and mechanism of vitamin D as an anti-viral agent.

Genetic Influences on Dengue Virus Infections J.F.P. Wagenaar#, A.T.A. Mairuhu and E.C.M. van Gorp

Department of Internal Medicine, Slotervaart Hospital, Louwesweg 6, 1066 EC Amsterdam,The Netherlands

Abstract Dengue virus infections are an important cause of morbidity and mortality in the tropics, with 100 million people infected annually and an estimated 2.5 billion people at risk. Human infections can be asymptomatic or can manifest as the self-limited febrile dengue fever, or the more severe and lifethreatening dengue haemorrhagic fever (DHF). There are several possible reasons why some infected individuals might develop a more


severe form of the disease than others. Antibody enhancement and viral virulence have been implicated in the pathogenesis of DHF but host genetic factors may also be relevant and predispose some individuals to DHF. This review discusses the possible involvement of a variety of genetic polymorphisms on the course of dengue virus infections. It has been shown that several common genetic polymorphisms can influence the susceptibility to dengue hemorrhagic fever. Gene polymorphisms concerning human leucocyte antigens, antibody receptors, inflammatory mediators and other factors with immunoregulatory effects are described. The study of genetic polymorphisms might provide important insights into the pathogenesis of a more severe disease and could have an impact on the design of future vaccines.

Reducing fracture risk with calcium and vitamin D

Clinical Endocrinology. 2010. 73( 3), 277–285.

Low levels of vitamin D contribute to osteopenia, osteoporosis, and bone fractures. It is not news that low calcium intake and poor vitamin D status are key determinants of osteoporosis and fracture risk, but a 2010 study suggests that calcium and vitamin D supplementation is an essential component in maintaining bone health. Together these minerals can improve bone mineralization, and correct secondary hyperparathyroidism , thereby preventing falls.

The role of vitamin D in skeletal muscle function

Endocrine Reviews. 1986. 7(4), 434-448

New England Journal of Medicine. 2007. 357(3), 266-281

Researchers have known for years that skeletal muscle is a target organ for vitamin D and that deficiencies lead to muscle weakness. Specifically, a lack of vitamin D leads to abnormalities in muscle contraction and relaxation, affecting muscle force production.

There is also evidence that adequate levels of vitamin D reduce the degradation of protein in muscle.

Vitamin D status and muscle function in post-menarchal

adolescent girls The Journal of Clinical Endocrinology and Metabolism.

2009. 94(2), 559-563 Optimal levels of vitamin D have been shown to improve muscle power development and jump height. Researchers found that the ability of the muscles to contract and produce force is affected by vitamin D status. Participants in a 2008 study with low


concentrations of vitamin D generated less power than those with higher concentrations, leading to the conclusion that vitamin D is significantly associated with power and force Further, researchers suggest that sub-optimal force development has negative implications for long-term bone development.

Vitamin D status and its relation to muscle mass and muscle fat in young women

Journal of Clinical Endocrinology and Metabolism.

2010. (95)4. 1595-1601. Vitamin D is essential for the maintenance of muscle, lean body mass, and for avoiding the development of fat in muscle. A vitamin D deficiency can cause both muscle weakness and an increase in fat mass. A 2010 study found that vitamin D shortage is associated with increased fat infiltration in muscle. Vitamin D deficiency was identified as a serum concentration less than 29 ng/ml, a level that 59 percent of the subjects were below. The vitamin D-insufficient subjects had approximately 24 percent greater muscle fat infiltration than those with vitamin D levels above 29 ng/ml, leading researchers to conclude that vitamin D levels are significantly associated with the degree of fat in skeletal muscle. Vitamin D importance in the prevention of cancers, type

1 diabetes, heart disease, and osteoporosis

American Journal of Clinical Nutrition. 2004. 29 (3), 362-371 Skin disorders such as psoriasis can be responsive to treatment with vitamin D because it lessens inflammation. Recent studies have shown that patients suffering from a variety of inflammatory conditions including psoriasis, dermatitis, dandruff, eczema, rosacea, and severe acne were often vitamin D-deficient. Vitamin D may actually help retard the abnormal growth and shedding rate of skin cells in conditions like psoriasis.


Blood sugar regulation and insulin resistance British Journal of Nutrition. 2009. 4(103), 549 – 555.

Journal of Clinical Endocrinology and Metabolism. 2007. 92, 2017-2029. New England Journal of Medicine. 2007. 357(3), 266-81.

Supplementing with vitamin D has been shown to increase insulin sensitivity and decrease insulin resistance, indicating that it may be an effective way to offset the

symptoms of diabetes. A 2010 study of South Asian women with insulin sensitivity (in a pre-diabetes state) found that taking 4,000 IUs of vitamin D a day resulted in significant decreases in insulin sensitivity, adding to data from a 2009 study that found that higher

vitamin D levels lowered diabetes risk.

Vitamin D intake and incidence of multiple sclerosis

Neurology. 2004. 62(1), 60-65.

Neurology. 2011. (76)21, 1824-1830.

Vitamin D deficiency is known to contribute to bone mineral loss and osteoporosis, but the good news is that adequate vitamin D levels have a protective effect on the risk of multiple sclerosis (MS). Researchers studied over 190,000 women in two studies called the Nurses’ Study I and II and found that women who used supplemental vitamin D, largely from multivitamins, had a 40 percent lower risk of MS than women who did not supplement. Findings from a second study of African Americans with MS published in 2011 supported the link between vitamin D deficiency and MS. Researchers reported that low vitamin D is a major risk factor for MS susceptibility and severity. Interestingly, in national surveys, African Americans have a lower vitamin D status than non-Hispanic whites and Mexican Americans. The most likely explanation for this disparity is that melanin, the primary determinant of skin pigmentation, functions as an optical filter of ultraviolet (UV) light, limiting vitamin D synthesis. Darker pigmented individuals require longer UV exposure times than lighter pigmented individuals to synthesize equivalent amounts of vitamin D.


Vitamin D levels, lung function, and steroid response in adult asthma

American Journal of Respiratory Critical Care Medicine. 2010. 181(7), 699-704. Journal of Clinical Endocrinology and Metabolism. 2003. 88(1), 157-161 Journal of Clinical Endocrinology and Metabolism. 2010. 89(3), 1196-9.

A study at the University of Colorado-Denver found that higher vitamin D levels are associated with improved lung function, reduced airway hyper-responsiveness, and improved in vitro glucocorticoids. The findings suggest that supplementation of vitamin D in patients with asthma may result in decreasing asthma severity and improved treatment response. This study also found that participants with lower vitamin D levels had more inflammation. Also, there was an inverse relationship between the participants’ Body Mass Index and their vitamin D levels, meaning that the fattest participants had the lowest vitamin D levels—more data to support what we already know about vitamin D supporting weight loss and an ideal lean body mass.

Vitamin D is positively associated with sperm motility and increases intracellular calcium in human spermatozoa

European Journal of Human Reproduction and Embryology. 2011. 26(6), 1307-1317.

New research from the University of Copenhagen found that vitamin D is associated with male reproductive health, specifically in regards to normal sperm count and sperm motility. Men with vitamin D deficiency had a lower proportion of mobile and morphologically normal sperm compared with men with high vitamin D levels. For maximal reproductive health and optimal sperm function, vitamin D supplementation is crucial in light of studies indicating that 51percent of men have low D levels. Vitamin D deficiency and risk of cardiovascular disease

Journal of the American Heart Association. 2008. 117, 503-511.

Vitamin D deficiency is linked with cardiovascular disease and high levels of vitamin D are associated with heart health. The Framingham Heart Study followed 1739 Caucasian individuals with a mean age of 59 years without prior cardiovascular disease. Participants’ vitamin D levels and cardiovascular health was assessed at the beginning of the study and 5 years later. The follow up study identified 120 individuals who had developed a first cardiovascular event. Additionally, for individuals with high blood pressure and low vitamin D levels there was a two-fold risk of cardiovascular


incidence. The study indicates that maintaining optimal vitamin D levels is crucial in avoiding cardiovascular disease and that vitamin D supplementation could contribute to the prevention of cardiovascular disease.

Maternal vitamin D depletion alters neurogenesis in the developing rat brain

International Journal of Developmental Neuroscience. 2007. 25, 227–232.

Federation of American Societies of Experimental Biology Journal. 2008. 22, 982–1001.

Journal of Tropical Pediatrics. 2004. 50, 364–368. In light of the role of vitamin D on brain health, it is not surprising that it plays a role in fetal brain development. Scientists have concluded that pregnant mothers who are deficient in vitamin D have fetuses with developmental impairment in brain cells. Additionally, there is evidence that the offspring of vitamin D-deficient mothers are more susceptible to schizophrenia, bone disorders such as rickets, and the development of diabetes.

Vitamin D inadequacy in pregnancy Fertility and Sterility. E-Pub: July 8, 2009.

Journal of Clinical Endocrinology and Metabolism. 2009. 94(3), 940–945. Nutrition Reviews. 2010. 68(8), 465-477.

Vitamin D plays a role in female fertility and rates of fetal implantation in the uterus. Additionally, vitamin D-deficient women are at risk for pre-eclampsia and gestational diabetes. Interestingly, due to the effect of vitamin D on muscle strength and function,

women with low vitamin D levels appear to have a higher rate of cesarean sections due to sub-optimal muscle performance and strength during pregnancy.

Serum vitamin D concentrations are related to depression in

young adult US population International Archives of Medicine. 3(1), 29.

Likelihood of having depression and other brain disorders is significantly higher in vitamin D-deficient persons compared to those with adequate levels. Scientists are not entirely clear how vitamin D plays a role in mental health but they do know that vitamin D enhances the metabolic processes in brain neurons, promoting antioxidant activities that protect from oxidative degenerative processes. Additionally, vitamin D promotes nerve growth, and is an essential enzyme involved in the production of


neurotransmitters that play a paramount role in mood regulation. Low levels are also linked to incidences of bipolar and schizophrenia. Vitamin D controls T cell antigen receptor signaling and

activation of human T cells.

Nature Immunology. 2010. 11, 344–349. New England Journal of Medicine. 2007. 357(3), 266-281.

Vitamin D is crucial to activating immune defenses and low serum levels inhibit the body’s T-cells ability to fight off serious infections. Specifically, inactive T-cells rely on vitamin D to activate them so that they can effectively fight off harmful pathogens that enter the body. Along with helping immune cells fight viruses such as the H1N1 flu, vitamin D helps increase the immune response by limiting inflammation, a major obstacle to healing and health.

Vitamin D and Chronic Kidney Disease

Ethnicity and Disease. 2009. 19(4 Suppl 5), 8-11. Vitamin D is vital for kidney health. Vitamin D is a key compound in treating chronic kidney disease and decreasing subsequent death rates. Understandably, individuals who are vitamin D deficient are at risk to develop kidney disease.

The association of serum vitamin D level with presence of

metabolic syndrome and hypertension in middle-aged

Clinical Endocrinology. 73(3), 330–338.

Vitamin D deficiency is strongly associated with high blood pressure and associated metabolic diseases such as diabetes and obesity. Vitamin D supplementation is most

effective at significantly reducing blood pressure when it is paired with taking calcium.


Relationship of vitamin D and parathyroid hormone with obesity and body composition in

African Americans

Clinical Endocrinology. 72(5), 595–603. Low vitamin D levels may make you fat. Research shows that body fat mass is higher in individuals with vitamin D deficiency and that this shortage correlates with elevated levels of parathyroid hormone and intracellular calcium, considered to be major factors in determining obesity. The increased calcium levels trigger metabolic pathways that promote the accumulation of fat tissue and suppress fat burning. Previously it was thought that low vitamin D levels were consequences of obesity but a 2010 study suggests that reduced levels actually play a role in the development of obesity.

High prevalence of hypovitaminosis D status in patients with early Parkinson Disease

Archives of Neurology. 2011. 68, 314-319. Researchers have found a relationship between low Vitamin D levels and the early onset of Parkinson’s disease. Parkinson’s disease is an incurable disorder of the nervous system, with symptoms that include trembling hands, stiff muscles, digestive and urinary problems, and a decrease in dexterity and coordination. The average age of onset of the disease is 60, and when the disease appears before the age of 40 it is referred to as early-onset Parkinson’s disease. It is estimated that Parkinson’s affects approximately 5 million people worldwide, with 50,000 new Americans being diagnosed each year. Muhammad Ali, Michael J. Fox, and the Reverend Billy Graham are among the most famous people who have this disease.

Prevention of Rickets and Vitamin D Deficiency in Infants, Children, and Adolescents

Pediatrics. 2008. 122(5), 1142-1152. The development of rickets and osteomalacia is directly related to vitamin D deficiency. Rickets is a childhood disease that is characterized by the softening of bone, leading to bone fractures and skeletal deformities. For adults, osteomalacia is associated with osteoporosis but is a separate disease that starts with aches in the lumbar region and spreads to the arms and ribs. Bones become deformed, often fracturing, and sufferers typically complain of chronic fatigue.


Chronic Obstructive Pulmonary Disease Prevention and

Treatment American Journal of Respiratory Critical Care Medicine. 183, A2533.

Chronic Obstructive Pulmonary Disease, also known as COPD, is characterized by respiratory weakness and the obstruction of the air pathways in the lungs. It typically manifests as emphysema and chronic bronchitis and can be treated by vitamin D supplementation. Considering the effect of vitamin D on increasing muscle strength and diminishing the symptoms of asthma, it is logical that it has positive effects on COPD. A 2011 study found that individuals supplementing with a monthly dose of 100,000 IU of vitamin D had significant improvements in all measures of COPD including oxygen consumption.

Vitamin D and clinical disease progression in HIV infection

Official Journal of the International AIDS Society. 2010 Vitamin D deficiency affects immune function and is associated with an increased risk of AIDS progression and death from the disease. Conversely, in recent studies individuals with the highest levels of vitamin D have been seen to have a significantly lower risk of death than those with low levels. Vitamin D deficiency is seen as an important co-factor in HIV progression and supplementing with the vitamin may be an effective anti-viral therapy.

Low vitamin D levels linked to anemia in children. Annual Meeting of the Pediatric Academic Societies 2011.

Low vitamin D levels in children can cause anemia, a severe condition that leads to the damage of vital organs by depriving them of oxygen. Anemia occurs when the body has too few oxygen-carrying red blood cells and is diagnosed by measuring hemoglobin levels. Symptoms of mild anemia include fatigue, lightheadedness, and low energy.


A review of the critical role of vitamin D in the functioning of the immune system and the clinical implications of vitamin D

deficiency.

Molecular Nutrition and Food Research. 2011 55(1), 96–108.

Adequate vitamin D plays a role in the prevention of infections and it may be used as a primary treatment for viral, bacterial, and fungal infections. In a recent review of the benefits of vitamin D on immune health and avoiding infections, researchers found that treatments of all of the following conditions benefit from optimal vitamin D levels: tuberculosis, psoriasis, eczema, Crohn's disease, chest infections, wound infections, influenza, urinary tract infections, eye infections, and wound healing.

Relationship between Serum Vitamin D, Disease Severity and Airway Remodeling in Children with Asthma

Am. J. Respir. Crit. Care Med..2011

Abstract

Objective:Rationale little is known about vitamin D status and its effect on asthma pathophysiology in children with severe, therapy resistant asthma (STRA). Relationships between serum vitamin D, lung function, and pathology were investigated in pediatric STRA. Methods: Serum 25-hydroxyvitamin D (25[OH]D3) was measured in 86 children (mean age 11.7 years), 36 STRA, 26 moderate asthmatics (MA) and 24 non-asthmatic controls. Relationships between 25[OH]D3, the asthma control test (ACT), spirometry, corticosteroid usage, and exacerbations were assessed. 22/36 children with STRA underwent fibreoptic bronchoscopy, bronchoalveolar lavage and endobronchial biopsy with assessment of airway inflammation and remodeling. Results 25[OH]D3 levels (median [IQR]) were significantly lower in STRA (28[22-38])nmol/L than MA (42.5[29-63])nmol/L and controls (56.5[45-67])nmol/L (p<0.001). There was a positive

relationship between 25[OH]D3 levels and %predicted forced expired volume (FEV1) (r=0.4, p<0.001) and forced vital capacity (FVC) (r=0.3, p=0.002) in all subjects. 25[OH]D3 levels were positively associated with ACT (r=0.6, p<0.001), and inversely

associated with exacerbations (r=-0.6, p<0.001) and inhaled steroid dose (r=-0.39, p=0.001) in MA & STRA. Airway smooth muscle (ASM) mass, but not epithelial shedding or reticular basement membrane thickness, was inversely related to 25[OH]D3


levels (r=-0.6, p=0.008). There was a positive correlation between ASM mass and bronchodilator reversibility (r=0.6, p=0.009) and an inverse correlation between ASM mass and ACT (r=-0.7, p<0.001)

Conclusions: Lower vitamin D levels in children with STRA were associated with

increased ASM mass, worse asthma control and lung function. The link between vitamin D, airway structure and function suggests vitamin D supplementation may be useful in pediatric STRA.

Vitamin D supplementation during pregnancy: double-blind, randomized clinical trial of safety and effectiveness.

J Bone Miner Res. 2011 Dec; 26(12):3001.

Abstract

The need, safety, and effectiveness of vitamin D supplementation during pregnancy remain controversial. In this randomized, controlled trial, women with a singleton pregnancy at 12 to 16 weeks' gestation received 400, 2000, or 4000 IU of vitamin D(3) per day until delivery. The primary outcome was maternal/neonatal circulating 25-hydroxyvitamin D [25(OH)D] concentration at delivery, with secondary outcomes of a 25(OH)D concentration of 80 nmol/L or greater achieved and the 25(OH)D concentration required to achieve maximal 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] production. Of the 494 women enrolled, 350 women continued until delivery: Mean 25(OH)D concentrations by group at delivery and 1 month before delivery were significantly different (p < 0.0001), and the percent who achieved sufficiency was significantly different by group, greatest in 4000-IU group (p < 0.0001). The relative risk (RR) for achieving a concentration of 80 nmol/L or greater within 1 month of delivery was significantly different between the 2000- and the 400-IU groups (RR = 1.52, 95% CI 1.24-1.86), the 4000- and the 400-IU groups (RR = 1.60, 95% CI 1.32-1.95) but not between the 4000- and. 2000-IU groups (RR = 1.06, 95% CI 0.93-1.19). Circulating 25(OH)D had a direct influence on circulating 1,25(OH)(2)D(3) concentrations throughout pregnancy (p < 0.0001), with maximal production of 1,25(OH)(2)D(3) in all strata in the 4000-IU group. There were no differences between groups on any safety measure. Not a single adverse event was attributed to vitamin D supplementation or circulating 25(OH)D levels. It is concluded that vitamin D supplementation of 4000 IU/d for pregnant women is safe and most effective in achieving sufficiency in all women and their neonates regardless of race, whereas the current estimated average requirement is comparatively ineffective at achieving adequate circulating 25(OH)D concentrations, especially in African Americans.


Vitamin D and calcium supplementation reduces cancer risk:

Results of a randomized trial

Am J ClinNutr 2007;85:1586–91. ABSTRACT Background: Numerous observational studies have found supplemental calcium and vitamin D to be associated with reduced risk of common cancers. However, interventional studies to test this effect are lacking. Objective: The purpose of this analysis was to determine the efficacyof calcium alone and calcium plus vitamin D in reducing incidentcancer risk of all types. Design: This was a 4-y, population-based, double-blind, randomized placebo-controlled trial. The primary outcome was fracture incidence, and the principal secondary outcome was cancer incidence. The subjects were 1179 community-dwelling women randomly selected from the population of healthy postmenopausal women aged_55 y in a 9-county rural area of Nebraska centered at latitude 41.4°N. Subjects were randomly assigned to receive 1400– 1500 mg supplemental calcium/d alone (Ca-only), supplemental calcium plus 1100 IU vitamin D3/d (Ca _ D), or placebo. Results: When analyzed by intention to treat, cancer incidence was lower in the Ca_Dwomen than in the placebo control subjects (P_ 0.03). With the use of logistic regression, the unadjusted relative risks (RR) of incident cancer in the Ca_Dand Ca-only groups were 0.402 (P_0.01) and 0.532 (P_0.06), respectively. When analysis was confined to cancers diagnosed after the first 12 mo, RR for the Ca _ D group fell to 0.232 (CI: 0.09, 0.60; P _ 0.005) but did not change significantly for the Ca-only group. In multiple logistic regression models, both treatment and serum 25-hydroxyvitamin D concentrations were significant, independent predictors of cancer risk. Conclusions: Improving calcium and vitamin D nutritional status substantially reduces all-cancer risk in postmenopausal women. This trial


Vitamin D supplementation to improve treatment outcomes among children diagnosed with

respiratory infections

Biological, behavioral and contextual rationale

April 2011

Acute lower respiratory infections, predominantly pneumonia, kill more children under the age of five in every region of the world1 than any other cause. In 2007, of the estimated nine million child deaths that occurred globally, close to 20% or 1.8 million were attributable to pneumonia. Under nutrition has been shown to both increase the severity and overall prevalence of acute lower respiratory infections and is an important factor in determining the mortality rates from severe forms of respiratory infections1–4.

Poor nutritional status is a well-recognized cause of early childhood susceptibility to acute lower respiratory infections, along with lower socioeconomic status, ethnicity, suboptimal immunization, tobacco exposure, air pollution and other underlying chronic diseases or infant prematurity5–7. Several micro nutrient interventions have been proposed to both protect and prevent children from developing acute lower respiratory infections. Vitamin D deficiency in children has been strongly associated with risk of acute lower respiratory infections in a number of settings8–13. In Ethiopia, for example, researchers found that 42% of children in hospital with pneumonia had rickets, or severe vitamin D deficiency14.

Vitamin D is a group of fat-soluble molecules that are important micro nutrients for health. Both vitamin D2 and vitamin D3 can be obtained from the diet15, 16 but in relatively low quantity. Only fatty fish such as salmon, tuna, sardines or cod liver oil contain significant amounts of vitamin D3. Most vitamin D3 is synthesized in the skin after exposure to UVB light from the sun. For children, fortified foods such as cereals, cheese and milk represent an important source of vitamin D in some countries, although these items contain low and often fluctuating amounts of vitamin D15, 16, 17. Diet contributes to only 10–20% of vitamin D stores in adults, with this percentage most likely even smaller in children 18.

During the winter months, when vitamin D synthesis is naturally diminished because of the decreasing hours of sunlight, angle of solar radiation and skin exposed, acute lower respiratory infections are more frequent in adults and children19, 20. Vitamin D is thought to play an important role in immune system regulation, and can potentially protect against infections21, 22, in addition to cancer, cardiovascular disease and autoimmune disorders such as type 1 diabetes23–26. Vitamin D supplementation appears to reduce the incidence of and adverse outcomes from these conditions and others such as acute lower respiratory infections, as well as reducing all-cause mortality27, 28.


Nutritional interventions aimed at the treatment or prevention of forms of acute lower respiratory infections have thus far been very few in the published literature. A randomized control trial in Afghanistan showed that one high dose of vitamin D3, combined with antibiotic treatment, given to children aged 1–36 months who were hospitalized for pneumonia, did reduce the re-occurrence of pneumonia among children living in an area of high vitamin D deficiency28.

Future studies, however, need to be undertaken in different settings to confirm these results, especially among populations of children who are not classified as vitamin D deficient living in high-resource settings. Children in more northern latitudes lacking sun exposure, and dark-skinned children, are most at risk of vitamin D deficiency and of developing more severe forms of acute lower respiratory infections29, 30. However, cut-off values for vitamin D sufficiency and recommended daily intake in children are still under debate13, 31, 32. The American Academy of Pediatrics currently recommends supplementation with 400 IU (international units) daily of vitamin D from shortly after birth and continued throughout childhood and adolescence22. Recommendations for increased sun exposure to increase vitamin D3 synthesis in areas where supplementation does not occur must be balanced with concerns over excess exposure to UV radiation33. More data on the role of vitamin D in pediatric infection and immune function are required34.

References 1 . Geneva, World Health Organization, 2009.

2 Bulletin of the World Health Organization, 2008, 86:356–364.

3 Turkish Journal of Pediatrics, 2009, 51(2):110–115.

4 Pediatric Pulmonology, 2009, 44(12):1207–1215.

5 Journal of Pediatrics, 2003, 143:S112–S117.

6 Pediatric Pulmonology, 2009, 44(10):981–988.

7 The Lancet, 2010, 375(9725):1545–1555.

8 Acta Paediatrica, 2010, 99(3):389–393.

9 European Journal of Clinical Nutrition, 2004, 58(4):563–567.

10Journal of Tropical Pediatrics, 1994, 40:58.

11 Journal of Infectious Diseases, 2008, 197(5):676–680.

12 . European Journal of Clinical Nutrition, 2009, 63(4):473–477.


13 Tropical Medicine and International Health, 2010, 15:1148–1155.

14 The Lancet, 1997, 349:1801–1804.

15 Pediatric Research, 2009, 65:106R–113R.

16 Institute of Medicine. Dietary reference intakes for calcium and vitamin D. 2011.

17 Journal of Pediatrics, 2010, 156(5):698–703.

18 Journal of Nutrition, 2006, 136:1329–1333.

19 Annals of Otology, Rhinology and Laryngology, 2010, 119(1):64–70.

20 Journal of Nutrition, 2005, 135(11):2602–2608.

21 Maternal and Child Nutrition, 2008, 4(2):83–85.

22 Breastfeed Medicine, 2008, 3(4):239–250.

23 American Journal of Clinical Nutrition, 2003, 78(6):1128–34.

24 Nutrition and Clinical Practice, 2007, 22(3):305–22.

25 Journal of Allergy and Clinical Immunology, 2008, 121(2):533–534.

26 American Journal of Clinical Nutrition, 2010, 91(5):1255–1260.

27 Archives of Internal Medicine, 2007, 167:1730–1737.

28 Tropical Medicines and International Health, 2010, 15(10):1148–1155.

29 Journals of Pediatrics and Child Health, 2010.

30 Pediatric Infectious Diseases Journal, 2008, 27(9):853.

31 Journal of Human Nutrition and Dietetics, 2006, 19(3):203–8.

32 Archives of Internal Medicine, 2009, 169(4):384–390.

33 I Geneva, World Health Organization, 2003.

34 Cochrane Database of Systematic Reviews, 2010, Issue 11. Art no: CD008824.


Vitamin D (New Literature)

Jan 2013

Vitamin D Deficiency

J Am Coll Cardiol 2008;52:1949–56) Vitamin D deficiency is a highly prevalent condition; present in approximately 30% to 50% of the general population.A growing body of data suggests that low 25-hydroxyvitamin D levels may adversely affect cardiovascular health. Vitamin D deficiency activates the renin-angiotensin-aldosterone system and can predispose to hypertension and left ventricular hypertrophy. Additionally, vitamin D deficiency causes an increase in parathyroid hormone, which increases insulin resistance and is associated with diabetes, hypertension, inflammation, and increased Cardio vascular risk. Epidemiologic studies have associated low 25-hydroxyvitamin D levels with coronary risk factors and adverse cardiovascular outcomes. Vitamin D supplementation is simple, safe, and inexpensive .Large randomized controlled trials are needed to firmly establish the relevance of vitamin D status to cardiovascular health. In the meanwhile, monitoring serum 25-hydroxyvitamin D levels and correction of vitamin D deficiency is indicated for optimization of musculoskeletal and general health.


Longitudinal vitamin D status in pregnancy and

the risk of pre-eclampsia BJOG 2012;119:832–839.

Objective Whether vitamin D deficiency in pregnancy is a cause of pre-eclampsia remains controversial. Most previous studies to date have assessed exposure at only one time-point in pregnancy. We assessed longitudinal vitamin D status during pregnancy and the risk of pre-eclampsia. Design: Prospective cohort study. Setting: Seventeen urban obstetric hospitals, Canada. Population :Pregnant women who were participants in a trial of vitamin C and E supplementation for the prevention of preeclampsia.Canadian participants who consented to participate in a biobank with plasma specimens available at the baseline visit were included (n = 697). Methods Maternal plasma 25-hydroxyvitamin D (25(OH)D) concentrations were measured at 12–18 and 24–26 weeks of gestation using chemiluminescence immunoassay. Main outcome measures Pre-eclampsia. Results: Of the women, 39% were vitamin D deficient (25(OH)D <50 nmol/l). A strong positive correlation was observed in maternal 25(OH)D concentrations between the two gestational age windows (r = 0.69, P < 0.0001). Mean maternal 25(OH)D concentrations at 24–26 weeks of gestation were significantly lower in women who subsequently developed pre-eclampsia compared with those who did not (mean ± SD: 48.9 ± 16.8 versus 57.0 ± 19.1 nmol/l, P = 0.03). Women with 25(OH)D < 50 nmol/l at 24–26 weeks gestation experienced an increased risk of pre-eclampsia (adjusted odds ratio 3.24, 95% confidence interval 1.37–7.69), whereas the association was not statistically significant for maternal 25(OH)D level at 12–18 weeks of gestation. Conclusions: Lower maternal 25(OH)D levels at late mid-trimester were associated with an increased risk of pre-eclampsia.


The relationship between vitamin D and cancer.

Clin J Oncol Nurs. 2011 Oct;15(5):557-60.

Abstract

Vitamin D, a fat-soluble vitamin naturally present in very few foods, is synthesized when ultraviolet rays from sunlight contact the skin. Research suggests that vitamin D insufficiency may result from lack of exposure to sunlight and ultraviolet-B radiation. Individuals from geographic areas of high latitude and low sunlight exposure may be at increased risk for vitamin D deficiency. Emerging evidence supports the protective role of vitamin D in the prevention of several cancers, including breast, colon, and prostate..


Vitamin D deficiency and supplementation and relation to cardiovascular health

Am J Cardiol. 2012 Feb 1;109(3):359-63 Abstract

Recent evidence supports an association between vitamin D deficiency and hypertension, peripheral vascular disease, diabetes mellitus, metabolic syndrome, coronary artery disease, and heart failure. The effect of vitamin D supplementation, however, has not been well studied. We examined the associations between vitamin D deficiency, vitamin D supplementation, and patient outcomes in a large cohort. Serum vitamin D measurements for 5 years and 8 months from a large academic institution were matched to patient demographic, physiologic, and disease variables. The vitamin D levels were analyzed as a continuous variable and as normal (≥30 ng/ml) or deficient (<30 ng/ml). Descriptive statistics, univariate analysis, multivariate analysis, survival analysis, and Cox proportional hazard modeling were performed. Of 10,899 patients, the mean age was 58 ± 15 years, 71% were women (n = 7,758), and the average body mass index was 30 ± 8 kg/m(2). The mean serum vitamin D level was 24.1 ± 13.6 ng/ml. Of the 10,899 patients, 3,294 (29.7%) were in the normal vitamin D range and 7,665 (70.3%) were deficient. Vitamin D deficiency was associated with several cardiovascular-related diseases, including hypertension, coronary artery disease, cardiomyopathy, and diabetes (all p <0.05). Vitamin D deficiency was a strong independent predictor of all-cause death (odds ratios 2.64, 95% confidence interval 1.901 to 3.662, p <0.0001) after adjusting for multiple clinical variables. Vitamin D supplementation conferred substantial survival benefit (odds ratio for death 0.39, 95% confidence interval 0.277 to 0.534, p <0.0001). In conclusion, vitamin D deficiency was associated with a significant risk of cardiovascular disease and reduced survival. Vitamin D supplementation was significantly associated with better survival, specifically in patients with documented deficiency.



Pediatrics 2008;122:1142–1152

ABSTRACT Rickets in infants attributable to inadequate vitamin D intake and decreased exposure to sunlight continues to be reported in the United States. There are also concerns for vitamin D deficiency in older children and adolescents. Because there are limited natural dietary sources of vitamin D and adequate sunshine exposure for the cutaneous synthesis of vitamin D is not easily determined for a given individual and may increase the risk of skin cancer, the recommendations to ensure adequate vitamin D status have been revised to include all infants, including those who are exclusively breastfed and older children and adolescents. It is now recommended that all infants and children, including adolescents, have a minimum daily intake of 400 IU of vitamin D beginning soon after birth. The current recommendation replaces the previous recommendation of a minimum daily intake of 200 IU/day of vitamin D supplementation beginning in the first 2 months after birth and continuing through adolescence. These revised guidelines for vitamin D intake for healthy infants, children, and adolescents are based on evidence from new clinical trials and the historical precedence of safely giving 400 IU of vitamin D per day in the pediatric and adolescent population. New evidence supports a potential role for vitamin D in maintaining innate immunity and preventing diseases such as diabetes and cancer. The new data may eventually refine what constitutes vitamin D sufficiency or deficiency.


Vitamin D supplementation in infants, children, and adolescents.

Am Fam Physician. 2010 Mar 15;81(6):745-8.

Abstract

Vitamin D deficiency in children can have adverse health consequences, such as growth failure and rickets. In 2008,the American Academy of Pediatrics increased its recommended daily intake of vitamin D in infants, children, and adolescents to 400 IU. Infants who are breastfed and children and adolescents who consume less than 1 L of vitamin D-fortified milk per day will likely need supplementation to reach 400 IU of vitamin D per day. This recommendation is based on expert opinion and recent clinical trials measuring biomarkers of vitamin D status. It is also based on the precedent of preventing and treating rickets with 400 IU of vitamin D. In addition to dietary sources, exposure to ultraviolet B sunlight provides children and adults with additional vitamin D. Although the American Academy of Pediatrics recommends keeping infants out of direct sunlight, decreased sunlight exposure may increase children's risk of vitamin D deficiency. No randomized controlled trials assessing patient-oriented outcomes have been performed on universal vitamin D supplementation. However, vitamin D may reduce the risk of certain infections and chronic diseases. Physicians should help parents choose the appropriate vitamin D supplement for their child.

Vitamin D and Fracture Prevention Endocrinol Metab Clin N Am 39 (2010) 347–353

Vitamin D modulates fracture risk in 2 ways: by decreasing falls and increasing bone density. Two most recent meta-analyses of double-blind randomized controlled trials (RCTs) came to the conclusion that vitamin D reduces the risk of falls by 19%, the risk of hip fracture by 18%, and the risk of any non vertebral fracture by 20%. However, this benefit was dose-dependent. Fall prevention was only observed in trials of at least 700 IU vitamin D per day, and fracture prevention required a received dose (treatment dose multiplied by adherence) of more than 400 IU vitamin D per day. Antifall efficacy started with achieved 25-hydroxyvitamin D levels of at least 60 nmol/L (24 ng/mL) and antifracture efficacy started with achieved 25-hydroxyvitamin D levels of at least 75 nmol/L (30 ng/mL). Both end points improved further with higher achieved 25- hydroxyvitamin D levels. Based on these evidence-based data derived from the general older population, vitamin D supplementation should be at least 700 to 1000 IU per day and taken with good adherence to cover the needs for fall and fracture prevention. Desirable 25-hydroxyvitamin D for optimal fracture prevention may be atleast 75 nmol/L for both end points. Further work is needed to better define the doses that will achieve optimal blood levels in most of the population. \


Vitamin D deficiency and pregnancy:from preconception to birth.

Mol Nutr Food Res. 2010 Aug;54(8):1092-102.

Abstract Vitamin D is important for bone health, as well as an increasing number of other health outcomes. Here we discuss the evidence relating to vitamin D in pregnancy, from preconception to the perinatal period. During pregnancy extra calcium required for fetal skeletal growth is attained by both maternal bone resorption and increased absorption from dietary sources, necessitating increased maternal vitamin D. Many women have low vitamin D status during pregnancy and may require supplementation, although optimal serum levels and intake required to achieve those levels is not yet well defined. Evidence from animal studies, with some supportive human evidence, suggests that fertility may be impaired in mothers with low vitamin D. During pregnancy, maintaining vitamin D and calcium levels may decrease the risks of pre-eclampsia, while gestational diabetes mellitus appears to be more common in those with low vitamin D status, although there is insufficient evidence of causality. The evidence in relation to increased risks of bacterial vaginosis and caesarean section similarly requires confirmation in carefully designed observational and experimental studies. This review outlines the emerging evidence that maternal vitamin D status during pregnancy is important for the health of the mother and offspring across a range of possible health outcomes.


Vitamin D in pregnancy: current concepts.

Curr Opin Obstet Gynecol. 2012 Mar;24(2):57-64.

PURPOSE OF REVIEW:

Vitamin D is part of a complex steroid hormone system long known to be involved in bone metabolism. Recently, vitamin D has been implicated in physiologic processes as diverse as vascular health, immune function, metabolism and placental function. This review summarizes the current evidence for the role of vitamin D in pregnancy and perinatal outcomes A systematic review of articles published in PubMed between May 2010 and October 2011 was undertaken using key words for vitamin D and pregnancy. Seventy-eight studies were reviewed.

RECENT FINDINGS:

The biologic evidence regarding a role for vitamin D in reproductive outcomes is strong, and rates of vitamin D deficiency may be high among pregnant women. However, no consensus exists regarding optimum vitamin D levels in pregnancy or standard measurement of vitamin D deficiency. Clinical studies establishing an association between vitamin D levels and adverse pregnancy outcomes such as preeclampsia, gestational diabetes, low birthweight, preterm labor, cesarean delivery and infectious diseases have conflicting results. This is likely due to a paucity of randomized trials, heterogeneity of populations studied and low sample size with poor adjustment for confounding among observational studies.

SUMMARY:

Further research should focus on defining optimum 25-hydroxy vitamin D levels in pregnancy as well as among various subgroups of the population. Randomized trials are needed to determine whether vitamin D supplementation can improve pregnancy outcomes. Currently, the American College of Obstetrics and Gynecology and the Institute of Medicine recommend 600 IU of daily vitamin D supplementation during pregnancy to support maternal and fetal bone metabolism.



Pediatrics 2008;122:1142–1152

ABSTRACT Rickets in infants attributable to inadequate vitamin D intake and decreased exposure to sunlight continues to be reported in the United States. There are also concerns for vitamin D deficiency in older children and adolescents. Because there are limited natural dietary sources of vitamin D and adequate sunshine exposure for the cutaneous synthesis of vitamin D is not easily determined for a given individual and may increase the risk of skin cancer, the recommendations to ensure adequate vitamin D status have been revised to include all infants, including those who are exclusively breastfed and older children and adolescents. It is now recommended that all infants and children, including adolescents, have a minimum daily intake of 400 IU of vitamin D beginning soon after birth. The current recommendation replaces the previous recommendation of a minimum daily intake of 200 IU/day of vitamin D supplementation beginning in the first 2 months after birth and continuing through adolescence. These revised guidelines for vitamin D intake for healthy infants, children, and adolescents are based on evidence from new clinical trials and the historical precedence of safely giving 400 IU of vitamin D per day in the pediatric and adolescent population. New evidence supports a potential role for vitamin D in maintaining innate immunity and preventing diseases such asdiabetes and cancer. The new data may eventually refine what constitutes

.


Vitamin D deficiency and supplementation and relation to cardiovascular health.

Am J Cardiol. 2012 Feb 1;109(3):359-63. Abstract

Recent evidence supports an association between vitamin D deficiency and hypertension, peripheral vascular disease, diabetes mellitus, metabolic syndrome, coronary artery disease, and heart failure. The effect of vitamin D supplementation, however, has not been well studied. We examined the associations between vitamin D deficiency, vitamin D supplementation, and patient outcomes in a large cohort. Serum vitamin D measurements for 5 years and 8 months from a large academic institution were matched to patient demographic, physiologic, and disease variables. The vitamin D levels were analyzed as a continuous variable and as normal (≥30 ng/ml) or deficient (<30 ng/ml). Descriptive statistics, univariate analysis, multivariate analysis, survival analysis, and Cox proportional hazard modeling were performed. Of 10,899 patients, the mean age was 58 ± 15 years, 71% were women (n = 7,758), and the average body mass index was 30 ± 8 kg/m(2). The mean serum vitamin D level was 24.1 ± 13.6 ng/ml. Of the 10,899 patients, 3,294 (29.7%) were in the normal vitamin D range and 7,665 (70.3%) were deficient. Vitamin D deficiency was associated with several cardiovascular-related diseases, including hypertension, coronary artery disease, cardiomyopathy, and diabetes (all p <0.05). Vitamin D deficiency was a strong independent predictor of all-cause death (odds ratios 2.64, 95% confidence interval 1.901 to 3.662, p <0.0001) after adjusting for multiple clinical variables. Vitamin D supplementation conferred substantial survival benefit (odds ratio for death 0.39, 95% confidence interval 0.277 to 0.534, p <0.0001). In conclusion, vitamin D deficiency was associated with a significant risk of cardiovascular disease and reduced survival. Vitamin D supplementation was significantly associated with better survival, specifically in patients with documented deficiency.


Vitamin D Supplementation: What's Known, What to Do, and What's Needed

Pharmacotherapy. 2012 Apr;32(4):354-82

Abstract

The use of vitamin D supplements to prevent and treat a wide range of illnesses has increased substantially over the last decade. Epidemiologic evidence links vitamin D deficiency to autoimmune disease, cancer, cardiovascular disease, depression, dementia, infectious diseases, musculoskeletal decline, and more. The Institute of Medicine published an exhaustive report in 2010 that concluded that vitamin D supplementation for indications other than musculoskeletal health was not adequately supported by evidence and that most North Americans receive sufficient vitamin D from their diet and sun exposure. These conclusions are at odds with some clinical practice guidelines; thus, we sought to summarize the best available evidence regarding the benefits of vitamin D supplementation, to examine the potential risks, and to provide practical dosing advice. The adequacy of vitamin D stores is determined by measuring the 25-hydroxyvitamin D serum concentrations. The demarcations between deficiency (< 20 ng/ml), insufficiency (20-30 ng/ml), and optimal (30-80 ng/ml) serum concentrations are controversial. Vitamin D in doses of 800-5000 IU/day improve musculoskeletal health (e.g., reduces the rate of fractures and falls in older adults (aged ≥ 65 yrs). In patients with documented vitamin D deficiency, a cumulative dose of at least 600,000 IU administered over several weeks appears to be necessary to replenish vitamin D stores. Single large doses of 300,000-500,000 IU should be avoided. Vitamin D supplementation should not be offered routinely to other patient populations. Although results from some prospective clinical trials are promising, most have not been robustly designed and executed. The decision by young, otherwise healthy adults to take vitamin D in doses of 2000 IU/day or lower is unlikely to cause harm. For patients who are not at risk for developing vitamin D deficiency, sensible sun exposure is an inexpensive and enjoyable way to maintain vitamin D stores.


Vitamin D deficiency in exclusively breast-fed infants

Indian Journal of Medical Research. 2008 Mar;127(3):250-5

Abstract

With the renewed worldwide emphasis on exclusive breast-feeding of infants for the first 6 months of life,infants even in developing countries are at risk of developing vitamin D deficiency unless adequate preventive measures are taken. Predisposing factors include reduced exposure to sunlight in spite of this being available in plenty in a country like India, due to various social and cultural reasons. There is a need to consider implementation of a vitamin D Supplementation Programmed in infancy at the community level. Nutritional rickets in early infancy may become a more widespread problem in the near future unless strategies to ensure optimal vitamin D status for pregnant women and newborns are developed.

Vitamin D status and longitudinal lung function decline in the Lung Health Study

Eur. Respir. J., February 1, 2011; 37(2): 238 - 243

Abstract

Low blood vitamin D levels have been postulated to be a risk factor for worse lung function, based largely on cross-sectional data. We sought to use longitudinal data to test the hypothesis that baseline plasma 25-hydroxyvitamin D (25(OH)D) is lower in subjects with more rapid lung function decline, compared to those with slow lung function decline. We conducted a nested, matched case-control study in the Lung Health Study 3 cohort. Cases and controls were continuous smokers with rapid and slow lung function decline, respectively, over ~6 yrs of follow-up. We compared baseline 25(OH)D levels between cases and controls, matching date of phlebotomy and clinical centre. Among 196 subjects, despite rapid and slow decliners experiencing strikingly and significantly different rates of decline of forced expiratory volume in 1 s (-152 versus -0.3 mLyr; p < 0.001), there was no significant difference in baseline 25(OH)D levels (25.0 versus 25.9 ngmL; p = 0.54). There was a high prevalence of vitamin D insufficiency (35%) and deficiency (31%); only 4% had a normal 25(OH)D level in the winter. Although vitamin D insufficiency and deficiency are common among continuous smokers with established mild-to-moderate chronic obstructive pulmonary disease, baseline 25(OH)D levels are not predictive of subsequent lung function decline.


Vitamin D for Cancer Prevention: Global Perspective Ann Epidemiol 2009;19:468–483.

Abstract Purpose: Higher serum levels of the main circulating form of vitamin D, 25-hydroxyvitamin D(25(OH)D), are associated with substantially lower incidence rates of colon, breast, ovarian, renal, pancreatic, aggressive prostate and other cancers. Methods: Epidemiological findings combined with newly discovered mechanisms suggest a new model of cancer etiology that accounts for these actions of 25(OH)D and calcium. Its seven phases are disjunction, initiation, natural selection, overgrowth, metastasis, involution, and transition (abbreviated DINOMIT). Vitamin D metabolites prevent disjunction of cells and are beneficial in other phases Conclusions: It is projected that raising the minimum year-around serum 25(OH)D level to 40 to 60 ng/mL (100–150 nmol/L) would prevent approximately 58,000 new cases of breast cancer and 49,000 new cases of colorectal cancer each year, and three fourths of deaths from these diseases in the United States and Canada, based on observational studies combined with a randomized trial. Such intakes also are expected to reduce case-fatality rates of patients who have breast, colorectal, or prostate cancer by half. There are no unreasonable risks from intake of 2000 IU per day of vitamin D3, or from a population serum 25(OH)D level of 40 to 60 ng/mL. The time has arrived for nationally coordinated action to substantially increase intake of vitamin D and calcium.

Role of vitamin D in the pathogenesis of type 2 diabetes mellitus

Diabetes Obes Metab. 2008 Mar;10(3):185-97.

Abstract

Vitamin D deficiency has been shown to alter insulin synthesis and secretion in both humans and animal models. It has been reported that vitamin D deficiency may predispose to glucose intolerance, altered insulin secretion and type 2 diabetes mellitus. Vitamin D replenishment improves glycaemia and insulin secretion in patients with type 2 diabetes with established hypovitaminosis D, thereby suggesting a role for vitamin D in the pathogenesis of type 2 diabetes mellitus. The presence of vitamin D receptors (VDR) and vitamin D-binding proteins (DBP) in pancreatic tissue and the relationship between certain allelic variations in the VDR and DBP genes with glucose tolerance and insulin secretion have further supported this hypothesis. The mechanism of action of vitamin D in type 2 diabetes is thought to be mediated not only through


regulation of plasma calcium levels, which regulate insulin synthesis and secretion, but also through a direct action on pancreatic beta-cell function. Therefore, owing to its increasing relevance, this review focuses on the role of vitamin D in the pathogenesis of type 2 diabetes mellitus

Vitamin D in diabetes mellitus—a new field of knowledge poised for Development

Diabetes/Metabolism Research and Reviews

Volume 25, Issue 5, pages 417–419, July 2009

Abstract

This commentary reviews the current state of knowledge regarding the role of vitamin D in the pathogenesis of diabetes mellitus. In type 1 diabetes mellitus or in adult onset latent autoimmune diabetes (LADA), vitamin D exhibits immunomodulatory actions, influencing the activity of lymphocytes and interleukins. In type 2 diabetes mellitus vitamin D appears to act through different mechanisms, affecting insulin secretion and insulin sensitivity through its effects on the β cells, mediators of inflammation and parathyroid hormone. Much work remains to be done in this new field of knowledge before the role of vitamin D in the pathogenesis of diabetes mellitus is completely understood.


Effects of vitamin D and calcium supplementation on pancreatic β cell function, insulin sensitivity, and glycemia in adults at high risk of diabetes: the Calcium and

Vitamin D for Diabetes Mellitus randomized controlled trial

Am J Clin Nutr August 2011

Abstract

Background: A suboptimal vitamin D and calcium status has been associated with higher risk of type 2 diabetes in observational studies, but evidence from trials is lacking.

Objective: We determined whether vitamin D supplementation, with or without calcium, improved glucose homeostasis in adults at high risk of diabetes.

Design: Ninety-two adults were randomly assigned in a 2-by-2 factorial design, double-masked, placebo-controlled trial to receive either cholecalciferol (2000 IU once daily) or calcium carbonate (400 mg twice daily) for 16 wk. The primary outcome was the change in pancreatic β cell function as measured by the disposition index after an intravenous-glucose-tolerance test. Other outcomes were acute insulin response, insulin sensitivity, and measures of glycemia.

Results: Participants had a mean age of 57 y, a body mass index (BMI; in kg/m2) of 32, and glycated hemoglobin (Hb A1c) of 5.9%. There was no significant vitamin D × calcium interaction on any outcomes. The disposition index increased in the vitamin D group and decreased in the no–vitamin D group (adjusted mean change ± SE: 300 ± 130 compared with −126 ± 127, respectively; P = 0.011), which was explained by an improvement in insulin secretion (62 ± 39 compared with −36 ± 37 mU · L−1 · min, respectively; P = 0.046). Hb A1c increased less, but nonsignificantly, in the vitamin D group than in the no–vitamin D group (0.06 ± 0.03% compared with 0.14 ± 0.03%, respectively; P = 0.081). There was no significant difference in any outcomes with calcium compared with no calcium. Conclusion: In adults at risk of type 2 diabetes, short-term supplementation with cholecalciferol improved β cell function and had a marginal effect on attenuating the rise in Hb A1c.


Vitamin D and respiratory infection in adults.

Proc Nutr Soc. 2012 Feb;71(1):90-7. Epub 2011 Nov 25.

Abstract

Vitamin D insufficiency is a global issue that has significant implications for health. The classical role of vitamin D in bone mineralisation is well known; vitamin D deficiency leads to rickets, osteomalacia or osteoporosis. The role of vitamin D in an immune system is less known. Vitamin D is not an actual vitamin but a secosteroid hormone produced in the skin from 7-dehydrocholesterol after exposure to sunlight UVB radiation. Nutrition and supplements are main sources of vitamin D in wintertime in northern countries as sunlight exposure is inadequate for the production. For activation vitamin D needs to be hydroxylated in liver to form 25-hydroxyvitamin D and in kidney to 1,25-dihydroxyvitamin D, the most active hormone in Ca absorption in the gut. For determination of vitamin D status serum 25-hydroxyvitamin D level, the major circulating form of the hormone is to be measured. Vitamin D regulates gene expression through binding with vitamin D receptors, which dimerises with retinoid X receptor. This complex binds to vitamin D-responsive elements inside the promoter regions of vitamin D-responsive genes. Vitamin D has a key role in innate immunity activation; the production of antimicrobial peptides (cathelicidin and defensins) following Toll-like receptor stimulation by pathogen lipopeptides is dependent on sufficient level of 25-hydroxyvitamin D. Clinically, there is evidence of the association of vitamin D insufficiency and respiratory tract infections. There is also some evidence of the prevention of infections by vitamin D supplementation. Randomized controlled trials are warranted to explore this preventive effect

Vitamin D status: a review with implications for the pelvic floor.

Int Urogynecol J. 2012 Mar 14.]

Abstract

Vitamin D is a micronutrient vital in calcium homeostasis and musculoskeletal function. Vitamin D insufficiency is a common variant of vitamin D deficiency that shows clinical signs of rickets and osteomalacia. The clinical significance of vitamin D insufficiency is being explored in several medical conditions. However, the most robust work suggests a role in musculoskeletal disease. The pelvic floor is a unique part of the body and the function of which is dependent on interrelationships between muscle, nerve, connective


tissue, and bone. Pelvic floor disorders result when these relationships are disrupted. This paper reviews current knowledge regarding vitamin D nutritional status, the importance of vitamin D in muscle function, and how insufficient or deficient vitamin D levels may play a role in the function of the female pelvic floor.

Vitamin D and bone health: potential mechanisms.

Nutrients. 2010 Jul;2(7):693-724.

Abstract

Osteoporosis is associated with increased morbidity, mortality and significant economic and health costs. Vitamin D is a secosteriod hormone essential for calcium absorption and bone mineralization which is positively associated with bone mineral density [BMD]. It is well-established that prolonged and severe vitamin D deficiency leads to rickets in children and osteomalacia in adults. Sub-optimal vitamin D status has been reported in many populations but it is a particular concern in older people; thus there is clearly a need for effective strategies to optimise bone health. A number of recent studies have suggested that the role of vitamin D in preventing fractures may be via its mediating effects on muscle function (a defect in muscle function is one of the classical signs of rickets) and inflammation. Studies have demonstrated that vitamin D supplementation can improve muscle strength which in turn contributes to a decrease in incidence of falls, one of the largest contributors to fracture incidence. Osteoporosis is often considered to be an inflammatory condition and pro-inflammatory cytokines have been associated with increased bone metabolism. The immunoregulatory mechanisms of vitamin D may thus modulate the effect of these cytokines on bone health and subsequent fracture risk. Vitamin D, therefore, may influence fracture risk via a number of different mechanisms


Estimated equivalency of vitamin D production from natural sun exposure versus oral vitamin D supplementation across seasons at two US latitudes.

J Am Acad Dermatol. 2010 Jun;62(6):929.e1-9

Abstract

BACKGROUND: The relationship between oral vitamin D supplementation and cutaneous photosynthesis is not well understood. OBJECTIVE: We sought to provide estimates of the equivalency of vitamin D production from natural sun exposure versus oral supplementation. METHODS: Using the FastRT simulation tool, we determined sun exposure times needed to achieve serum vitamin D(3) concentrations equivalent to 400 or 1000 IU vitamin D for individuals of various Fitzpatrick skin types living in Miami, FL, and Boston, MA, during the months of January, April, July, and October. RESULTS: Peak ultraviolet B irradiation for vitamin D synthesis occurs around 12 pm Eastern Standard Time (EST). In Boston, MA, from April to October at 12 pm EST an individual with type III skin, with 25.5% of the body surface area exposed, would need to spend 3 to 8 minutes in the sun to synthesize 400 IU of vitamin D. It is difficult to synthesize vitamin D during the winter in Boston, MA. For all study months in Miami, FL, an individual with type III skin would need to spend 3 to 6 minutes at 12 pm EST to synthesize 400 IU. Vitamin D synthesis occurs faster in individuals with lighter Fitzpatrick skin types. The duration to attain 1000 IU of vitamin D is longer in all scenarios.

LIMITATIONS: Results of the computer model are only approximations. In addition, calculations were made based on the assumption that (1/4) of 1 minimal erythema dose directed at (1/4) body surface area is equal to 1000 IU of oral vitamin D.

CONCLUSIONS: Although it may be tempting to recommend intentional sun exposure based on our findings, it is difficult, if not impossible to titrate one's exposure. There are well-known detrimental side effects of ultraviolet irradiation. Therefore, oral supplementation remains the safest way for increasing vitamin D status.


Bone Health Journal of the American Medical Association. 2005;293:225

Annals of Internal Medicine. 2008;149:242-250.

Federal Register. 2008;73:56477-56487.

It's probably vitamin D's most established role in health - keeping your bones healthy and strong. Vitamin D helps your body absorb calcium, and after reviewing years of research, the government recently concluded that adequate calcium and vitamin D throughout life, as part of a well-balanced diet, may reduce the risk of osteoporosis - the debilitating disease that's a major public health threat for more than 44 million Americans.

Too little vitamin D has been linked to an increased risk of bone fractures. One University of Pittsburgh study found that women ages 50 to 79 with the lowest levels of vitamin D had a 71 percent increased risk for hip fractures compared with women with the highest levels of vitamin D. The case-control study compared 400 women with hip fractures to 400 women without who were matched for age, race or ethnicity and date of blood draw, measuring the vitamin D levels in the body and finding a significant difference between the two groups.

One analysis that reviewed 12 clinical trials evaluating vitamin D supplements and fracture prevention found that higher daily doses of vitamin D - in the range of 700-800 IU - reduced the risk of fractures in older adults by 23 to 26 percent. The Harvard researchers concluded that this higher supplement dose appeared to reduce the risk of hip and any nonvertebral fractures in older adults, however there was no significant benefit when a 400 IU daily supplement was tested.


Journal of Geriatric Psychology and Neurology. 2008;Dec 10

Nutrition Journal. 2004;3:8.

Scientists have identified an important role for vitamin D in normal brain development and function. While more research is needed, experts suggest this "smart" vitamin could affect healthy mood and even cognition (our ability to think), especially for older Americans at risk for cognitive decline. The early research suggests vitamin D could affect proteins in our brain directly related to memory and learning.

One study suggests that for the estimated 11 million Americans who feel down during the winter (technically referred to as Seasonal Affect Disorder), low levels of vitamin D in the body may be at least one factor involved in the condition. In fact, a study found that boosting vitamin D levels (600 IU to 4,000 IU daily) improved winter well-being scores for older adults. In a two-part study of 37 and 66 men and women (average age about 50 years old), Canadian researchers compared the effects of different doses of vitamin D supplements on wellbeing response (as measured by a wellbeing questionnaire) finding benefits for what they term "low" (600 IU) and "high" (4,000IU) dose supplementation.

Another recent cross-sectional study published in the Journal of Geriatric Psychiatry and Neurology investigated the effects of vitamin D on cognition in older adults. The British researchers studied nearly 2,000 adults over age 65 and found that the adults with the lowest vitamin D levels in the bloodstream were more than twice as likely to be cognitively impaired (lower levels of attention, orientation in time, space and memory) as those with optimum levels.

Healthy Smile American Journal of Clinical Nutrition. 2004;80:108-113.

Some research suggests vitamin D may support healthy gums and strong teeth.

One clinical study of 145 adults (originally designed to determine risk of hip bone loss) found that supplementation with vitamin D and calcium was linked to reduced tooth loss in men and women ages 65 and older over a 3-year period. The elderly adults were given a supplement of 1,000mg of calcium with 400 to 600 IU of vitamin D daily and during the 3-year period, 27 percent subjects taking a placebo lost one or more teeth compared to just 13 percent of those taking supplements.


Another study from the American Journal of Clinical Nutrition looked at data from more than 11,000 adults and found that among women and men aged 50 and older, those with the lowest vitamin D levels had 23 to 27 percent more tooth loss than had those in the highest range. The researchers suggest vitamin D may affect inflammation and gum health, which could lead to tooth loss - independent of bone density.

Ongoing research is investigating the link between vitamin D and type 1 and type 2 diabetes. In fact, some scientists hypothesize that America's shortfall in vitamin D may be one of the reasons behind the current epidemic of type 2 diabetes - the more common form of diabetes.

One large, 20-year study published in Diabetes Care found that a high intake of supplemental vitamin D (more than 800 IU daily) along with more than 1,200mg of calcium daily, compared to a low intake (less than 400 IU of vitamin D and 600mg of calcium daily) reduced the risk of type 2 diabetes by one-third for otherwise healthy women. As a part of the Nurses' Health Study, researchers identified nearly 5,000 cases of type 2 diabetes over a 20-year period and concluded that their research suggests "a potential beneficial role for both vitamin D and calcium intake in reducing the risk of type 2 diabetes."

Additionally, in a thorough analysis of more than 50 previously published studies, Tufts University researchers found chronically low levels of vitamin D were linked to as high as 46 percent greater risk of type 2 diabetes, compared to higher vitamin D levels. Yet boosting vitamin D alone would likely have little effect in healthy adults. Instead, the researchers suggested that a combination of vitamin D and calcium, like that found in milk, would have the greatest potential to help prevent diabetes, especially among those at highest risk for the disease.

Examining the intake of milk and milk products specifically, the researchers found there was nearly a 15 percent lower risk for type 2 diabetes among individuals with the highest dairy intake (3-5 servings per day) compared to those getting less than 1 1/2 servings each day. Most of the studies assessed were observational and the limited number of intervention trials makes definitive conclusions difficult, yet the Tufts researchers suggest calcium and vitamin D may affect the body's ability to produce or utilize insulin, the hormone the body makes to process sugar that is impaired in those with diabetes and pre-diabetes.

Research suggests vitamin D may also affect type 1 diabetes risk. In a long-term study including all pregnant women, due to give birth in select Finnish cities, more than 10,000 children were given 2,000 IU of vitamin D daily and were followed for the next 31 years. After controlling for other factors affecting child health, researchers found that children who regularly took their vitamin D supplements were 78 percent less likely to


develop type 1 diabetes, compared to children who did not get enough vitamin D, according to the 2001 study published in the Lance

Heart Health

Archives of Internal Medicine. 2008;168:1174-1180.

Circulation. 2008;117:503-511

Some research suggests low vitamin D levels could impact your heart health - an important finding since heart disease remains the leading cause of death for both men and women in this country.

One recent study found that men with low blood levels of vitamin D had nearly two and a half times the risk of a heart attack when compared to men with adequate levels of vitamin D. The Harvard case-control study included more than 450 men, ages 40 to 75 who suffered from heart disease and 900 men without the disease (with similar age, smoking status and timing of vitamin D measures). The researchers followed the men for 10 years, and compared those who were deficient in vitamin D to men who were in at least the low end of the "normal" range - finding significant differences between the two groups.

Another study published in the American Heart Association journal, Circulation, found that low levels of vitamin D could increase the risk heart attack, heart failure or stroke by 62 percent for men and women. A team of Boston researchers studied 1739 men and women, with an average age of 59, tracking their vitamin D status and heart health over approximately five years. One hundred and twenty adults had a heart attack or stroke during that time period - and those falling in the lowest category of vitamin D levels, were at significantly higher risk for disease, even after the researchers considered other factors such as vitamin use and physical activity. The researchers noted that the effect was magnified in those participants with hypertension, finding that their ris k for a cardiovascular event was more than twice those without hypertension and further noted that cardiovascular risk increased as vitamin D levels decreased.

Blood Pressure

American Journal of Clinical Nutrition. 2008;87:136-141.

Journal of Clinical Endocrinology and Metabolism. 2001;86:1633-1637.

Hypertension. 2008;51:1-7.


Nearly one-third of American adults suffer from high blood pressure - a condition that puts them at serious risk for cardiovascular disease, stroke and even kidney failure. Some research suggests milk and vitamin D could help support healthy blood pressure levels.

A recent cross-sectional study published in the American Journal of Clinical Nutrition investigated the relationship between vitamin D levels and systolic blood pressure. The researchers found that adults with optimal vitamin D levels in the body had a 20 percent lower chance of typical age-related increases in systolic blood pressure, compared to those with lower vitamin D levels. The researchers noted that very few (8 percent) African-Americans achieved optimal vitamin D levels, supporting the need for further investigation in the African-American populations.

A study in The Journal of Clinical Endocrinology and Metabolism evaluated the short-term effect of vitamin D and calcium supplementation compared to calcium supplementation alone on blood pressure. One hundred forty eight older women (70 and older) received either 1200 mg calcium and 800 IU of vitamin D or 1200 mg of calcium per day for eight weeks. The researchers found that only the participants who received the calcium and vitamin D supplementation had a significant reduction, reducing systolic blood pressure by nine percent.

Plus, vitamin D-rich low fat milk is an important part of the clinically-proven healthy eating plan known as DASH (Dietary Approaches to Stop Hypertension). Some research suggests milk's vitamin D contribution may be at least partly responsible for the blood pressure benefit.

In one study, women who drank more fat free milk and had higher intakes of calcium and vitamin D from foods, and not supplements, tended to have a lower risk for developing hypertension or high blood pressure. Harvard researchers investigated the association of milk and milk products, vitamin D and calcium intake with the incidence of hypertension - considering the diets of nearly 30,000 middle-aged and older women. They found that women who consumed more low-fat milk and milk products and had diets higher in calcium and vitamin D from foods were better protected against high blood pressure. When examining the benefits of milk specifically, women who drank two or more servings of fat free milk each day reduced their risk for high blood pressure by up to 10 percent compared to those who drank fat free milk less than once a month. The same was not found for higher fat milk and milk products or calcium and vitamin D supplements.


Children's Health

American Journal of Clinical Nutrition. 2004;80:1697S-1705S.

American Journal of Clinical Nutrition. 2007;86:150-158

Experts have long known that vitamin D deficiency can lead to rickets in growing children - a softening of growing bones, which can lead to stunted growth, and potentially fractures and deformity.

A recent resurgence of this debilitating disease, along with new information on the potential health benefits of vitamin D, prompted the American Academy of Pediatrics to double its recommendations and reaffirm the importance of this bone-building vitamin for children of all ages. The Academy now recommends children and adolescents aim for 400 IU of vitamin D each day to prevent rickets and reap the potential preventive health benefits.

Some researchers estimate that up to 55 percent of adolescents may be deficient putting them at increased risk for osteoporosis and debilitating bone diseases, according to one recent analysis of children living in the northeastern United States.

Wagner CL, Greer FR; American Academy of Pediatrics Section on Breastfeeding; American Academy of Pediatrics Committee on Nutrition. Prevention of rickets and vitamin D deficiency in infants, children, and adolescents. Pediatrics. 2008;122:1142-1152.

Muscles Archives of Physical Medicine and Rehabilitation. 1999;80:54-58.

Pain Medicine 2008;9:979-984.

Journal of Clinical Endocrinology and Metabolism. 2009; 94:559-563.

Annals of Rheumatic Disease. 2008 Aug 12.

Researchers have known for decades that vitamin D plays a role in normal muscle function. Now, there's new evidence to suggest vitamin D deficiency could negatively affect performance, muscle power and pain.

Not only does vitamin D work with calcium to keep bones strong and help teens perform their best, one recent study published in the Journal of Clinical Endocrinology and


Metabolism found that teenage girls (ages 12 to 14) with higher vitamin D levels may be able to jump higher and faster than their peers with lower levels, after considering differences in body weights.

The UK researchers collected vitamin D levels for 99 girls, ages 12 to 14. To test the girls' muscle function, the girls were instructed to jump as high as possible while researchers used a device designed to measure power and performance called jumping mechanography. After controlling for differences in the girls' body weight, the girls with the highest vitamin D levels had the highest jump speeds, jump height, power and force.

Muscle weakness is also a recognized symptom of vitamin D deficiency in children and a number of studies have also suggested a link between low levels of vitamin D and reduced muscle strength in adults. One study of nearly 300 patients in Switzerland linked reduced muscle strength in older men and women to lower vitamin D levels. Twelve percent of the women and 18 percent of the men studies had low vitamin D values - and by measuring leg extension power, they concluded that muscle strength was modestly, but significantly linked to vitamin D levels in the body. The researchers suggest that increasing vitamin D may help improve muscle strength, thereby also reducing fracture risk through fall prevention.

Additionally, vitamin D inadequacy has been linked to higher incidence of chronic pain - possibly linked to impaired neuromuscular function. In a recent retrospective Mayo Clinic study of 267 patients with chronic pain, those with the highest vitamin D levels reported the lowest use of pain-controlling drugs, compared to the lowest vitamin D levels. The researchers suggest this may be a sign that vitamin D deficiency may be an under-recognized source of pain and muscle weakness. More than one quarter of the adults had inadequate vitamin D levels and the pain-controlling drug users with inadequate vitamin D levels reported worse physical functioning and health perception compared to those with adequate vitamin D levels.

Another British study linked low vitamin D levels to chronic widespread pain for women, after investigating the connection for nearly 10,000 British adults with data collected from the 45-year British survey. Compared to the women with the lowest levels of vitamin D, women with the highest vitamin D levels were the least likely to experience ongoing pain symptoms (as measured by questionnaire), though more research is needed to fully understand the link - the same findings were not replicated for the men in the study.


Cancer Cancer Epidemiology Biomarkers and Prevention. 2007;16:422-429.

American Journal of Clinical Nutrition. 2007;85:1586-1591

With an estimated 10.5 million Americans living with cancer, researchers are on a quest for new means to prevent or delay the occurrence of this deadly disease. While the research is still preliminary, ongoing research is investigating a potential link between vitamin D and certain cancers, including colon and breast cancer. Preliminary mechanism studies suggest vitamin D may play a role in blocking certain cancer cells from multiplying and dividing in the body.

One recent study published in the American Journal of Clinical Nutrition found that increasing intake of vitamin D, along with calcium, may reduce the risk for cancer in women by 60 percent. The four-year clinical trial included more than one thousand women over the age of 55 in one of three supplement groups: 1) calcium (1400-1500mg) plus vitamin D (1100 IU vitamin D) 2) calcium only (1400-1500 mg) or 3) a placebo. The researchers found that the risk of developing cancer was 60 percent lower for those who took calcium and vitamin D and 47 percent lower for those taking calcium alone, compared to the placebo.

Fifty women developed nonskin cancer through the course of the four-year study, including breast, colon, lung and other cancers. When researchers excluded the 13 cancers diagnosed during first year of the study, determining these cancers were likely present at the study onset, the protective effect of calcium and vitamin D was even greater, with a 77 percent lower risk for cancer for those taking calcium plus vitamin D compared to the placebo.

Another study published in the journal Cancer Epidemiology Biomarkers and Prevention found that boosting vitamin D levels early in life (ages 10 to 19) through sun exposure, milk intake and cod liver oil consumption was associated with protection against breast cancer later in life. In the study, drinking at least 10 glasses of milk each week was linked to a reduced risk for breast cancer later in life, which the researchers attributed to the importance of vitamin D. In the case-control study, the scientists identified 972 women with newly diagnosed invasive breast cancer and compared their habits to 1,135 women without cancer diagnoses.


Immune System Epidemiology and Infection. 2006;134:1129-1140.

Archives of Internal Medicine. 2009;169:384-390.

Vitamin D plays an important role in regulating the immune system, helping the body's normal process of fighting illness and infection. There's even some evidence that vitamin D insufficiency may be linked to the seasonal flu and respiratory infections - the "common cold."

One recent cross-sectional study published in the Archives of Internal Medicine examined the association between vitamin D levels and recent upper respiratory tract infection in more than 18,000 Americans ages 12 and older. The researchers found that those with the lowest vitamin D levels in the body were 36 percent more likely to have had a respiratory infection compared to those with the highest levels.

Some researchers suggest the lack of vitamin D may be at least one reason for the seasonal flu - since exposure to sunlight and therefore vitamin D levels in the body tend to go down in the winter. Vitamin D helps support a healthy immune system through its involvement in your body's innate immunity - the general ability to fight off and prevent germs from gaining entry into the body and causing infection.

Autoimmune Diseases

Arthritis and Rheumatism. 2004;50:72-77.

Journal of the American Medical Association. 2006;296:2832-2838.

Neurology. 2004;62:60-65.

There are more than 80 different types of autoimmune diseases - conditions where the body's immune system mistakenly attacks the body instead of protecting it against disease and infection - and some ongoing investigations are suggesting vitamin D could affect certain conditions, specifically, multiple sclerosis and rheumatoid arthritis.

One recent study published in the Journal of the American Medical Association found that higher levels of vitamin D in the body were associated with a lower risk of multiple sclerosis (MS) - one of the most common neurological diseases affecting two million people worldwide. Using data from more than 7 million military personnel, the


researchers identified 257 cases of MS from 1992 through 2004 and then matched the cases to 514 people without the disease with similar age, sex, ethnicity and timing of vitamin D measures, finding the risk of MS significantly decreased with increasing vitamin D levels for Caucasians, though the same could not be seen for the black and Hispanic adults, who generally had lower vitamin D levels. The researchers concluded that high levels of vitamin D in the body "are associated with lower risk of multiple sclerosis."

Another study published in the journal Neurology found that women who met the 400 IU daily recommendation for vitamin D through foods and supplements had a 33 percent lower chance of developing MS, compared to those falling short on vitamin D. Using large sets of data (more than 180,000 women from the Nurses' Health Study I and II), the researchers assessed the diets of the 173 women who developed MS linking total vitamin D intake to lower risk.

Assessing data from nearly 30,000 middle-aged women (ages 55-69) followed over an 11-year period, researchers also found a 33 percent lower likelihood of rheumatoid arthritis for women with the highest vitamin D levels from food and supplements (more than 220 IU per day), compared to those missing the mark on vitamin D intake, according to the study published in the journal Arthritis and Rheumatism.

Brain Health

Journal of Geriatric Psychology and Neurology. 2008;Dec

Nutrition Journal. 2004;3:8

Scientists have identified an important role for vitamin D in normal brain development and function. While more research is needed, experts suggest this "smart" vitamin could affect healthy mood and even cognition (our ability to think), especially for older Americans at risk for cognitive decline. The early research suggests vitamin D could affect proteins in our brain directly related to memory and learning.

One study suggests that for the estimated 11 million Americans who feel down during the winter (technically referred to as Seasonal Affect Disorder), low levels of vitamin D in the body may be at least one factor involved in the condition. In fact, a study found that boosting vitamin D levels (600 IU to 4,000 IU daily) improved winter well-being scores for older adults. In a two-part study of 37 and 66 men and women (average age about 50 years old), Canadian researchers compared the effects of different doses of vitamin D supplements on wellbeing response (as measured by a wellbeing


questionnaire) finding benefits for what they term "low" (600 IU) and "high" (4,000IU) dose supplementation.

Another recent cross-sectional study published in the Journal of Geriatric Psychiatry and Neurology investigated the effects of vitamin D on cognition in older adults. The British researchers studied nearly 2,000 adults over age 65 and found that the adults with the lowest vitamin D levels in the bloodstream were more than twice as likely to be cognitively impaired (lower levels of attention, orientation in time, space and memory) as those with optimum levels.

Journal of the American College of Cardiology Vol. 52, No. 24, 2008


Vitamin D and Cardiovascular Disease Nutrients 2010, 2, 426-437

Abstract: Vitamin D insufficiency/deficiency has been observed worldwide at all stages of life. It has been characterized as a public health problem, since low concentrations of this vitamin have been linked to the pathogenesis of several chronic diseases. Several studies have suggested that vitamin D is involved in cardiovascular diseases and have provided evidence that it has a role in reducing cardiovascular disease risk. It may be involved in regulation of gene expression through the presence of vitamin D receptors in various cells, regulation of blood pressure (through renin-angiotensin system), and modulation of cell growth and proliferation including vascular smooth muscle cells and cardiomyocytes. Identifying correct mechanisms and relationships between vitamin D and such diseases could be important in relation to patient care and healthcare policies.

Rickets–vitamin D deficiency and dependency Indian J Endocrinol Metab. 2012 Mar-Apr; 16(2): 164–176.

Abstract

Rickets is an important problem even in countries with adequate sun exposure. The causes of rickets/osteomalacia are varied and include nutritional deficiency, especially poor dietary intake of vitamin D and calcium. Non-nutritional causes include hypophosphatemic rickets primarily due to renal phosphate losses and rickets due to renal tubular acidosis. In addition, some varieties are due to inherited defects in vitamin D metabolism and are called vitamin D dependent rickets. This chapter highlights rickets/osteomalacia related to vitamin D deficiency or to inherited defects in vitamin D metabolism. Hypophosphatemic rickets and rickets due to renal tubular acidosis are discussed in other sections of the journal.


A Randomised, Double-Blinded, Placebo-Controlled, Parallel Study of Vitamin D3 Supplementation with Different Schemes

Based on Multiples of 25,000 IU Doses Hindawi Publishing Corporation

International Journal of Endocrinology Volume 2013, Article ID 327265, 8 pages http://dx.doi.org/10.1155/2013/327265

Vitamin D (VTD) treatment is recommended in patients presenting different causes of diseases. To treat these patients, physicians rely on the different available pharmaceutical forms present in their country. Unfortunately, even in a given country, there is no consensus on the best way to treat the patients. In Belgium, VTD is mostly prescribed as ampoules containing 25,000 IU of VTD. In this randomised controlled study, we evaluated whether four therapeutic schemes using multiples of 25,000 IU of VTD according to basal vitamin D concentration were able to increase or maintain the 25(OH)D serum level above 30 ng/mL. We randomized 175 subjects who received the drug (n = 140) or placebo (n = 35). Total duration of the study was 12 weeks. Doses ranged from 4167 to 1667 IU/day. Blood sampling was performed at baseline and each 4 visits. In the treated (placebo) subjects, mean 25(OH)D serum concentration was 18.7 (19.1) ng/mL at baseline and 31.5 (20.7) ng/mL at w-12. At the end of the study, 57.1% of the subjects treated with VTD presented 25(OH)D serum concentration ≥30 ng/mL, whereas 94.3% were ≥20 ng/mL. In conclusion, the doses administered were safe and increased or maintained the 25(OH)D concentration ≥20 ng/mL. However, concentrations ≥30 ng/mL were only achieved in 57.1% of the subjects.


Diagnostic and therapeutical role of vitamin D in chronic hepatitis C virus infection.

Front Biosci (Elite Ed). 2012 Jan 1;4:1276-86.

Abstract

Although initially identified as a calcium homeostatic hormone, vitamin D is now known to have pleiotropic functions, dealing with both innate and adaptative immunity. Calcitriol mediates its biological effects by binding to the vitamin D receptor (VDR), which is expressed not only by intestine, bone and kidney but also on cell membranes of T lymphocytes, B lymphocytes, dendritic cells and macrophages. Vitamin D plays a role on the degree of liver damage in patients with chronic hepatitis C (CHC): low vitamin D levels have been associated with high hepatic necroinflammatory activity and progression of liver fibrosis. Vitamin D, in CHC patients, could also affect the response to antiviral therapy: in fact, recent studies have shown a relationship between low responsiveness to IFN-based therapy and low vitamin D serum levels. Further studies are required to better assess if vitamin D could work as a reliable noninvasive marker of liver fibrosis and whether vitamin D supplementation could be given to all CHC patients together with standard antiviral treatment, in order to improve the rate of sustained virological response (SVR).

Short- and Long-Term Safety of Weekly High-Dose Vitamin D3 Supplementation in School Children

(J Clin Endocrinol Metab 93: 2693–2701, 2008) Background: Hypovitaminosis D is prevalent in youth worldwide, but the safety of vitamin D at doses exceeding 200 IU/d is unknown in this age group. We assessed the safety of high doses of vitamin D3 administered to apparently healthy schoolchildren. Methods: To assess short-term safety, 25 subjects randomly received placebo or vitaminD3 at doses of 14,000 IU/wk for 8 wk. To assess long-term safety, 340 subjects randomly received placebo, vitamin D3 as 1,400 IU/wk or 14,000 IU/wk for 1 yr. Biochemical variables were monitored at 0, 2, 4, 6, and 8wk and 8 wk off therapy in the short-term study and at 0, 6, and 12 months in the long-term study. Results: In both the short- and long-term studies, mean serum calcium and 1,25-hydroxyvitamin levels did not change in any group. In the short-term study, mean 25-hydroxyvitamin concentrations increased from 44 (_11) to 54 (_19) ng/ml in the treated groups (P_0.033). In the long-term study, mean 25-hydroxyvitamin D levels increased from 15 _ 8 to 19 _ 7 ng/ml (P _ 0.0001) in subjects receiving 1,400 IU/wk and from 15_7 to36_22 ng/ml (P_0.0001) in the group receiving14,000 IU/wk. No subject developed vitamin D intoxication.


Conclusion: Vitamin D3 at doses equivalent to 2000 IU/d for 1 yr is safe in adolescents and results in desirable vitamin D levels

Low vitamin D serum concentration is associated with high levels of hepatitis B virus (HBV) replication in chronically infected patients

(HEPATOLOGY 2013.)

Vitamin D is an important immune modulator which plays an emerging role in inflammatory and metabolic liver diseases, including infection with hepatitis C virus (HCV). In contrast, the relationship between vitamin D metabolism and chronic hepatitis B is less well characterized. Therefore, we quantified 25-hydroxyvitamin D [25(OH)D3] serum levels in a cohort of 203 treatment-naïve patients with chronic hepatitis B virus (HBV) infection and tested for their association with clinical parameters of chronic hepatitis B. 69 (34%), 95 (47%), and 39 (19%) out of 203 patients had severe vitamin D deficiency [25(OH)D3 <10ng/mL], vitamin D insufficiency [25(OH)D3 ≥10ng/mL and <20ng/mL], or adequate vitamin D serum levels [25(OH)D3 ≥20ng/mL], respectively. In both uni- and multivariate analyses, HBV DNA viral load (log10 IU/mL) was a strong predictor of low 25(OH)D3 serum levels (p=0.0007 and p=0.000048, respectively), and vice versa. Mean 25(OH)D3 serum concentrations in patients with HBV DNA <2000 IU/mL vs. ≥2000 IU/mL were 17 vs. 11 ng/mL, respectively (p<0.00001). In addition, hepatitis B early antigen (HBeAg) positive patients had lower 25(OH)D3 serum levels than HBeAg negative patients (p=0.0013). Finally, 25(OH)D3 and HBV DNA serum levels showed inverse seasonal fluctuations.

Conclusions: Low 25(OH)D3 serum levels are associated with high levels of HBV replication in patients with chronic hepatitis B. This represents a major difference to chronic hepatitis C, were numerous previous studies have shown a lacking correlation between HCV viral load vitamin D serum levels. Inverse seasonal fluctuations of 25(OH)D3 and HBV DNA serum levels are suggestive for a functional relationship between both variables.


Decreased bioavailability of vitamin D in obesity

Am J Clin Nutr 2000;72:690–3.

ABSTRACT Background: Obesity is associated with vitamin D insufficiency and secondary hyperparathyroidism. Objective: This study assessed whether obesity alters the cutaneous production of vitamin D3 (cholecalciferol) or the intestinal absorption of vitamin D2 (ergocalciferol). Design: Healthy, white, obese [body mass index (BMI; in kg/m2) 30] and matched lean control subjects (BMI 25) received either whole-body ultraviolet radiation or a pharmacologic dose of vitamin D2 orally. Results: Obese subjects had significantly lower basal 25- hydroxyvitamin D concentrations and higher parathyroid hormone concentrations than did age-matched control subjects. Evaluation of blood vitamin D3 concentrations 24 h after whole-body irradiation showed that the incremental increase\ in vitamin D3 was 57% lower in obese than in nonobese subjects. The content of the vitamin D3 precursor 7-dehydrocholesterol in the skin of obese and nonobese subjects did not differ significantly between groups nor did its conversion to previtamin D3 after irradiation in vitro. The obese and nonobese subjects received an oral dose of 50 000 IU (1.25 mg) vitamin D2. BMI was inversely correlated with serum vitamin D3 concentrations after irradiation (r = _0.55, P = 0.003) and with peak serum vitamin D2 concentrations after vitamin D2 intake (r = _0.56, P = 0.007). Conclusions: Obesity-associated vitamin D insufficiency is likely due to the decreased bioavailability of vitamin D3 from cutaneous and dietary sources because of its deposition in body fat compartments.


VItamin D supplementation in infants, children, and adolescents.

Am Fam Physician. 2010 Mar 15;81(6):745-8.

Abstract

Vitamin D deficiency in children can have adverse health consequences, such as growth failure and rickets. In 2008,the American Academy of Pediatrics increased its recommended daily intake of vitamin D in infants, children, and adolescents to 400 IU. Infants who are breastfed and children and adolescents who consume less than 1 L of vitamin D-fortified milk per day will likely need supplementation to reach 400 IU of vitamin D per day. This recommendation is based on expert opinion and recent clinical trials measuring biomarkers of vitamin D status. It is also based on the precedent of preventing and treating rickets with 400 IU of vitamin D. In addition to dietary sources, exposure to ultraviolet B sunlight provides children and adults with additional vitamin D. Although the American Academy of Pediatrics recommends keeping infants out of direct sunlight, decreased sunlight exposure may increase children's risk of vitamin D deficiency. No randomized controlled trials assessing patient-oriented outcomes have been performed on universal vitamin D supplementation. However, vitamin D may reduce the risk of certain infections and chronic diseases. Physicians should help parents choose the appropriate vitamin D supplement for their child.


Rickets: concerns over the worldwide increase.

J Fam Health Care. 2011 Mar-Apr;21(2):25-9.

Abstract

Rickets is a childhood disease that causes a softening of the bones, potentially leading to fractures and deformity. Eighty years ago it was thought to have largely been eradicated from the U.K. However a recent increase in cases of rickets, not just in Britain but around the world, has proven this isn't the case. Today the disease affects children from all types of socio-economic backgrounds, not just the poorer ones, and it is primarily caused by low levels of vitamin D and certain foods. In January 2011 the government's chief medical officer Dame Sally Davies recommended all children aged six months to five should be given vitamin D supplements, particularly during winter months when natural sunshine is limited. The irony is that the advice in recent years for children to wear a high factor sunscreen and remain covered up while playing outdoors are partly felt to be behind the reason for its re-emergence. Parents and health professionals alike were shocked when it was revealed that a school girl living on the Isle of Wight developed rickets precisely because of her mother's vigilance at following sun safety rules. NICE, in their latest report (Jan 2011) stated that: "Exposure to the sun has a number of benefits. For example, it increases people's sense of wellbeing, allows them to synthesise vitamin D and provides opportunities for physical activity". A tendency for children to stay indoors and watch TV or play on computer games, rather than play outside when the sun is shining, is arguably also another contributing factor.

Indrop d references

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