Vitamin D deficiency and its health consequences

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

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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 25hydroxyvitamin 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 25hydroxyvitamin 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 25OH-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 25OH-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 1520 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 middleaged 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 25hydroxyvitamin 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 wellknown 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 Maystandardized 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 nonbone/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 25OH-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-totreatment (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[2963])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 25hydroxyvitamin 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 1.321.95) 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 placebocontrolled 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 darkskinned 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 reninangiotensin-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 25hydroxyvitamin 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 preeclampsia 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 preeclampsia.
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.


Prevention of Rickets and Vitamin D Deficiency in
Infants, Children, and Adolescents
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 deficiency and its health consequences

Vitamin D deficiency and its health consequences

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