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VITAMIN D:
AN OVERVIEW
DANA BARTLETT, RN, BSN, MSN, MA
Dana Bartlett is a professional nurse and author. His clinical experience includes 16 years of ICU
and ER experience and over 20 years of as a poison control center information specialist. Dana
has published numerous CE and journal articles, written NCLEX material, written textbook
chapters, and done editing and reviewing for publishers such as Elsevire, Lippincott, and Thieme.
He has written widely on the subject of toxicology and was recently named a contributing editor,
toxicology section, for Critical Care Nurse journal. He is currently employed at the Connecticut
Poison Control Center and is actively involved in lecturing and mentoring nurses, emergency
medical residents and pharmacy students.
ABSTRACT
Vitamin D deficiency is recognized to be a worldwide pandemic, which has been
associated with increased risk of common cancers, autoimmune disorders,
cardiovascular and other diseases. Low levels of vitamin D are associated with a
worsening of these diseases once they have developed; and, there are welldefined mechanisms that could explain these associations. Currently, there is a
lack of medical consensus on a standard prevention protocol for vitamin D
supplementation. To benefit health, vitamin D must circulate at accepted serum
levels. When an individual has inadequate sun exposure vitamin D is needed to
achieve optimal blood levels. All age groups can suffer from vitamin D deficiency.
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Continuing Nursing Education Course Planners
William A. Cook, PhD, Director, Douglas Lawrence, MA, Webmaster,
Susan DePasquale, MSN, FPMHNP-BC, Lead Nurse Planner
Policy Statement
This activity has been planned and implemented in accordance with the policies of
NurseCe4Less.com and the continuing nursing education requirements of the
American Nurses Credentialing Center's Commission on Accreditation for
registered nurses. It is the policy of NurseCe4Less.com to ensure objectivity,
transparency, and best practice in clinical education for all continuing nursing
education (CNE) activities.
Continuing Education Credit Designation
This educational activity is credited for 2 hours. Nurses may only claim credit
commensurate with the credit awarded for completion of this course activity.
Pharmacology content is 1 hour.
Statement of Learning Need
Nursing knowledge of the physiological functions of vitamin D and the systemic
effects of vitamin D deficiency will help them educate patients on the prevention
and treatment of vitamin D deficiency. Patients treated for vitamin D deficiency
should be aware of the signs of acute and chronic vitamin D intoxication.
Course Purpose
This course will help nurses identify signs and symptoms of vitamin D
deficiency and its treatment.
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Target Audience
Advanced Practice Registered Nurses and Registered Nurses
(Interdisciplinary Health Team Members, including Vocational Nurses and Medical
Assistants may obtain a Certificate of Completion)
Course Author & Planning Team Conflict of Interest Disclosures
Dana Bartlett, RN, BSN, MSN, MA, William S. Cook, PhD, Douglas Lawrence, MA,
Susan DePasquale, MSN, FPMHNP-BC – all have no disclosures
Acknowledgement of Commercial Support
There is no commercial support for this course.
Activity Review Information
Reviewed by Susan DePasquale, MSN, FPMHNP-BC.
Release Date: 1/1/2016
Termination Date: 4/30/2017
Please take time to complete a self-assessment of knowledge, on page 4,
sample questions before reading the article.
Opportunity to complete a self-assessment of knowledge learned will be
provided at the end of the course.
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1. One of the primary functions of vitamin D is:
a. control of muscle contraction
b. control of calcium and phosphorus metabolism
c. control of potassium and sodium metabolism
d. control of renal blood flow
2. Good dietary sources of vitamin D are:
a. whole grains and fruits
b. leafy green vegetables and red meat
c. fortified milk and certain fishes
d. citrus fruits and nuts
3. True or false: Infants who are exclusively breast-fed are at risk for
vitamin D deficiency.
a. True
b. False
4. Which of these drugs may influence vitamin D levels?
a. Statins, anti-epileptic drugs
b. Beta-blockers, opioid analgesics
c. ACE inhibitors, glucocorticoids
d. Calcium channel blockers, non-steroidal anti-inflammatories
5. Vitamin D intoxication is primarily characterized by:
a. hyperkalemia
b. hypercalcemia
c. hypernatremia
d. hypermagnesemia
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Introduction
Vitamin D and the deficiency of vitamin D have been the focus of much attention
from the medical and scientific communities in the past decade. Vitamin D
deficiency has been described as a pandemic. This course discusses the following
key aspects:
 The synthesis and metabolism of vitamin D
 The physiological functions of vitamin D
 Vitamin D deficiency - how it happens and how it is diagnosed
 The systemic effects of vitamin D deficiency
 Treatment of vitamin D deficiency
 The interaction between medications and vitamin D
 Acute and chronic vitamin D intoxication
Although it is true that millions of people in the United States and in the world
have low levels of vitamin D, to describe vitamin D deficiency as a pandemic may
not, in one sense, be completely accurate. Doing so implies that there are
adverse health risks from this phenomenon; however, aside from the well-known
effects of vitamin D deficiency on bone health, the scientific evidence is
inconclusive that a low level of vitamin D causes diseases or affects any other
organ system. There are strong and well-established associations between
vitamin D deficiency and an increased risk of developing autoimmune,
cardiovascular, neurological and many other pathologies. Low levels of vitamin D
are associated with a worsening of these diseases once they have developed. And
there are well-defined mechanisms that could explain these associations.
When the data is examined closely, the final link, a definite cause and effect, for
disease states due to vitamin D deficiency has not yet been found. Some people
who have low levels of vitamin D do not get cancer, heart disease, or multiple
sclerosis. Supplementation does not seem to prevent disease or act as an
effective therapy. Additionally, the mechanisms by which researchers have
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explained the association between vitamin D deficiency and disease have at times
only been studied in cell cultures or in animals. Much has been discovered about
vitamin D and its possible role in health and preventative medicine. However, at
this point, the questions are more numerous than answers.
Vitamin D: Overview
Vitamin D is a fat-soluble vitamin that is needed for control of calcium and
phosphorous metabolism, normal immune function, modulation of cell growth,
and several other body processes. Vitamin D can be obtained by dietary intake of
foods such as the flesh of certain fatty fishes, fish oils, vitamin D fortified milk,
and (to a small degree) egg yolks, some mushrooms, beef liver, and cheese.
Vitamin D is also synthesized in the skin by exposure of the skin to ultraviolet B
(UVB) radiation from sunlight.
Vitamin D is synthesized by the skin or ingested as cholecalciferol, or D3, and
cholecalciferol is a pro-vitamin. In order for vitamin D in the form of
cholecalciferol and ergocalciferol (ergocalciferol will be discussed in the next
paragraph) to be biologically active it must be first hydroxylated in the liver to
become to 25-hydroxyvitamin D, a.k.a 25(OH) D or calcidiol, the major
circulating form of vitamin D. Calcidiol is then hydroxylated by the kidneys to
1,25-dihydroxyvitamin D, or calcitriol, the metabolically active form of vitamin
D.1,2 Tissues and organs have vitamin D receptors, and the physiological actions
of vitamin D are mediated by the binding of vitamin D with these receptors.
There is another form of vitamin D: ergocalciferol, which is also known as vitamin
D2. Ergocalciferol is found in some plants and fungi, but human consumption is
almost exclusively in the form of D2 supplements that are produced by the
irradiation of yeast. Cholecalciferol and ergocalciferol are essentially identical
compounds and they were long considered to be equivalent to use for patients
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who needed supplemental vitamin D. However, there is evidence that this may
not be true, and this issue will be discussed briefly later in this learning module.
Vitamin D is absorbed in the small bowel (jejunum), and dietary fat and bile are
needed for vitamin D to be absorbed; hence, the term fat-soluble vitamin. Excess
vitamin D that is not needed immediately is stored in the liver and in fat tissues.
Learning Break: A vitamin is defined as an essential nutrient that cannot be
synthesized by the body; therefore, vitamin D is not truly a vitamin. Vitamin D
is a hormone. However, the use of the term vitamin D is so common and so well
understood that it is used almost exclusively.
The Physiological Functions Of Vitamin D
The section below will provide some basic information about the benefits of
vitamin D as well as the systemic effects when there is a long-term deficit as
observed in population-based and animal studies.
Calcium and Phosphorus Metabolism
A normal serum calcium level is important for blood clotting, bone growth and
density, and optimal functioning of the cardiac and nervous systems. Normal
serum phosphorus levels are essential for adequate mineralization of the bones.
Calcium and phosphorus metabolism and absorption are regulated in large part
by vitamin D, and low serum vitamin D levels can cause hypocalcemia and
hypophosphatemia.
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The parathyroid gland, in response to low serum calcium levels, will secrete
parathyroid hormone. Parathyroid hormone increases the activity of 25hydroxyvitamin D3 1-hydroxylase, an enzyme in the kidney that stimulates the
production of 1,25-dihydroxvitamin D, calcitrol. Calcitrol increases the serum
calcium level according to the following pathways and processes:
1) Increasing the level of a transport system in the small bowel that
increases the absorption of calcium by the gut
2) Increasing the amount of calcium that is reabsorbed by the kidneys
3) Mobilizing calcium from the bone into the serum
Immune System
Animal studies and some supplementation studies done with humans have shown
that vitamin D increases the activity of the immune system, decreases the
inflammatory response, and inhibits the development of autoimmunity.
Insulin Secretion and Insulin Sensitivity
Low levels of vitamin D3 have been reported to be associated with decreased
insulin production and increased insulin sensitivity in people with type 2 diabetes.
There is also epidemiological evidence suggesting that low levels of vitamin D are
a risk factor for the development of type 2 diabetes.
Renin-Angiotensin System
Animal studies indicate that vitamin D deficiency affects the function of the reninangiotensin system, causing hypertension and cardiac hypertrophy. Observational
studies in humans have found an association between low serum levels of vitamin
D and an increased incidence of hypertension.
Cell Differentiation and Proliferation
Vitamin D is involved in the control of cell differentiation and the inhibition of cell
proliferation. There are cell-specific factors that influence cell responsiveness to
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vitamin D related to cell growth and differentiation, which is outside the scope of this
study.
Vitamin D: Sources And Daily Requirements
There are few foods that are good sources of vitamin D content: most of the
nutritional intake of vitamin D is from fortified foods. The following table is from
the National Institutes of Health website.
Food Sources of Vitamin D
IUs per
Percent
Food
serving*
DV**
Cod liver oil, 1 tablespoon
1,360
340
Swordfish, cooked, 3 ounces
566
142
Salmon (sockeye), cooked, 3 ounces
447
112
Tuna fish, canned in water, drained, 3 ounces
154
39
Orange juice fortified with vitamin D, 1 cup (check product labels, as
137
34
115-124
29-31
80
20
Margarine, fortified, 1 tablespoon
60
15
Sardines, canned in oil, drained, 2 sardines
46
12
Liver, beef, cooked, 3 ounces
42
11
Egg, 1 large (vitamin D is found in yolk)
41
10
Ready-to-eat cereal, fortified with 10% of the DV for vitamin D, 0.75-
40
10
amount of added vitamin D varies)
Milk, nonfat, reduced fat, and whole, vitamin
D-fortified, 1 cup
Yogurt, fortified with 20% of the DV for vitamin D, 6 ounces (more
heavily fortified yogurts provide
more of the DV)
1 cup (more heavily fortified cereals might provide more of the DV)
Cheese, Swiss, 1 ounce
** DV = daily value
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These foods are sources of vitamin D3, cholecalciferol. There are few natural
sources of vitamin D2, ergocalciferol. Wild mushrooms, sun-dried mushrooms,
and commercially grown mushrooms that have been treated with ultra-violet light
are reasonably good sources of vitamin D2.3
Sunlight as a Source of Vitamin D
Foods can be an important source of vitamin D, but approximately 80-90% of our
vitamin D is obtained by exposure to UVB radiation from sunlight.4 Age, altitude,
cloud cover, latitude, season, skin pigmentation, smog layer, time of day, and the
use of sunscreen can all affect the amount of sunlight that is received and the
production of vitamin D; additionally, these variables make it difficult to know
how much exposure to the sun is needed to produce vitamin D. A striking
example is that people living in equatorial areas in which there is a high level of
sunshine have been found to be vitamin D deficient. Whereas, elderly adults in a
temperate climate (a population less exposed to the sun and with less opportunity
to synthesize vitamin D) were able to significantly increase serum levels of
vitamin D by regular participation in certain outdoor activities.5,6
The amount of sunlight that is needed to synthesize an adequate amount of
vitamin D has been estimated to be 5-30 minutes, three times week, with the
arms, back, face, and legs receiving the most exposure.7 Over-exposure to the
sun will not produce an excess amount of vitamin D as too much sunlight
degrades both vitamin D3 and pre-vitamin D.8
Daily Vitamin D Requirement and Serum Levels
The recommended daily dietary intake of vitamin D varies somewhat depending
on age and gender. Not all authoritative sources agree on the optimal daily intake
of vitamin D, but most sources agree on the following.

0-12 months: 10 mcg/400 IU a day

1 year-70 years: 15 mcg/600 IU a day
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
71 years and older: 20 mcg/800 IU a day

Pregnant and lactating females: 15 mcg/600 IU a day
Nutritional supplements of vitamin D usually list the content of D in international
units, which is commonly abbreviated as IU. An international unit (IU) is an
arbitrary amount that reflects the amount of a nutrient that is needed to produce
a biological effect. The microgram amount of an IU varies depending on the
substance. For example, an IU of vitamin D is equal to 0.25 mcg of ergocalciferol
or cholecalciferol.
Vitamin D serum levels measure the amount of 25-hydroxyvitamin D/calcidiol,
the major circulating form of vitamin D. The serum levels of vitamin D that have
traditionally been used to identify normal, deficient and toxic states are listed
below as:
 0-25 nmol/L - Deficiency
 >25-50 nmol/L - Insufficiency
 >50-70 nmol/L - Hypovitaminosis
 >70-250 nmol/L - Adequate
 250nmol/L - Toxic
The serum levels of vitamin D as listed here were derived from population
studies; and, they are thought to represent the levels at which calcium absorption
declines or parathyroid hormone levels increase. It is generally agreed in the
medical/scientific community that very low vitamin D levels of 0-25 represent a
significant risk factor for poor bone health. However, the optimal vitamin D level
that will promote bone health is not clearly known, and is a matter of some
controversy.9
The Institute of Medicine recommends maintaining a serum level >50 nmol/L to
have healthy bones. However, the National Osteoporosis Foundation, the
American Geriatric Society, and other professional organizations recommend a
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level of at least 75 nmol/L,10 and some researchers have suggested that the
optimum level of vitamin D should be even higher. It is also not clear what the
optimal vitamin D level is for maintaining and promoting the health of other organ
systems. Most researchers define vitamin D deficiency as a serum level of < 50
nmol/l, but not all do. At this point there are more questions than answers.
Vitamin D Deficiency
Vitamin D deficiency is very common in the adult and the pediatric population.11
The prevalence of vitamin D deficiency, defined in some population and
epidemiological studies as a serum vitamin D level as < 30 nmol/L, has been
estimated to be 69.5% in the United States and 86.4% in Europe.12 If the serum
level defined as representing deficiency is lowered to 20 nmol/L then 41.6% of
U.S. adults would be found to be vitamin D deficient;13 and, Holick (2007)
estimated that approximately 1 billion people worldwide had vitamin D levels less
than 50 nmol/L; and, that 40-100% of elderly adults in the U.S. living in the
community were vitamin D deficient.14
Regardless of the level that is used to define vitamin D deficiency, it is
characterized by hypocalcemia and hypophosphatemia. The basic causes of
vitamin D deficiency are listed below as:
1) Decreased intake
2) Decreased absorption
3) Decreased synthesis by the kidneys, liver, or skin
4) Increased breakdown by the liver
There are specific risk factors for vitamin D deficiency,1,15,16 which include those
outlined below.
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1. Decreased intake
2. Inadequate sunlight exposure:
The elderly and people who are hospitalized or institutionalized are at risk
for decreased sunlight exposure.
3. Advanced age:
The elderly have a decreased ability to synthesize and store vitamin D. The
elderly are less likely to be exposed to the sun and for unclear reasons the
elderly are less likely to consume foods that have vitamin D.
4. Excessive use of sunscreen and/or covering large areas of the skin with
clothing:
The use of a sunscreen with a sun protection factor of 15 and higher will
decrease skin synthesis of vitamin D3 by 99%.
5. Obesity
6. Dark skin pigmentation
7. Extensive burns:
People who have had extensive burns are likely to be vitamin D deficient.
8. Chronic kidney or liver disease:
Significant liver and/or kidney disease can cause decreased production or
abnormal excretion of calcidiol and calcitriol.
9. Cystic fibrosis:
Vitamin D deficiency is almost universal in people who have cystic fibrosis,
due to inadequate intake, inadequate sunlight exposure, and decreased
absorption through the gut.
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10. Fat malabsorption syndromes:
People who have celiac disease, those who have had gastric bypass surgery
or other types of gastric surgery, and people who have diseases of the
pancreas or small bowel are likely to have vitamin D deficiency.
11. Sedentary life style
12. Infants who are exclusively breast-fed
13. Low level of high-density cholesterol
14. The use of certain medications such as anti-epileptics and glucocorticoids.
(Note: The interaction between medications and vitamin D and the effect of
medications on vitamin D levels will be discussed later in the learning
module).
Many infants are breast-fed, dark skin pigmentation is a risk factor that cannot be
altered, and obesity is very common. Therefore, these risk factors of vitamin D
deficiency will be discussed in more detail in the next sections.
Breastfed Infants
The incidence of vitamin D deficiency in breast-fed infants is quite high and has
been estimated to be between 43-70%, depending on the definition of deficiency
and the latitude.17 The American Academy of Pediatrics (APA) recommends that
children who are less than six months old should not be directly exposed to the
sun, thus removing the most important source of vitamin D. Also, breast milk has
between 20-80 IU/L of vitamin D, while fortified infant formula has between 270677 IU/L of vitamin D.
The lack of infant exposure to sunlight and the low vitamin D content of breast
milk can result in vitamin D deficiency. The APA recommends that infants who are
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exclusively breast-fed should receive 400 IU of vitamin D daily. This form of
supplementation or increasing the mother’s vitamin D intake has been proven to
increase serum vitamin D levels in infants.17,18
Skin Pigmentation
Low levels of serum 25-hydroxyvitamin D/calcidiol and low levels of vitamin Dbinding protein are much more common in black Americans than in white
Americans.19 It has been estimated that less than 10% of black and Latino
Americans are vitamin D sufficient,20,21 and, in particular, the number of American
black mothers that are vitamin D deficient has been found to be very low. This
association with race and vitamin D deficiency is well established and well known,
but what is not clear is why it occurs and how it affects the health status of these
populations.
The decrease in milk consumption, avoiding exposure to the sun to prevent skin
cancer, and the use of sunscreens may explain part of the high incidence of
vitamin D deficiency in black and Latino Americans. However, other factors are
almost certainly involved, such as, melanin content of the skin, lactose maldigestion, and obesity.
Vitamin D synthesis in the skin is dependent on skin exposure to UVB radiation,
but vitamin D synthesis in the skin is also dependent on the melanin content of
the skin. Melanin absorbs UVB and people with high melanin content who live in
temperate latitudes and that practice sun avoidance may not get sufficient UVB to
produce an adequate level of vitamin D.22
There are hereditary and cultural dietary considerations that need to be taken
into account when evaluating a patient for vitamin D deficiency. Approximately
80% of black Americans are lactose mal-digesters and would be likely to avoid
vitamin D fortified milk, a major source of vitamin D.22 Additionally, obesity is
more common in black Americans and obesity is a risk factor for vitamin D
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deficiency; there is an inverse relationship between body mass index (BMI) and
vitamin D levels.23 However, researchers have found that even after controlling
for the factor of body fat, black Americans have lower serum levels of vitamin D
than do white Americans.22
Obesity
Obesity is also associated with vitamin D deficiency.23-25 Body mass index, body
fat, and waist circumference have been found to be inversely related to serum
vitamin D levels less than 50 nmol/L.23 The same study reported that 88% of
obese subjects were vitamin D deficient, but only 31% of the non-obese subjects
were vitamin D deficient.
Bellan, et al., (2014) found that 95% of the severely obese patients studied had
serum vitamin D levels that were defined as deficient or insufficient, or less than
20 or 30 nmol/L, respectively.26 Although many researchers have found an
association between obesity, none as yet have discovered a definitive reason as to
why this association occurs.11,27,28 It is possible that people who are obese receive
less sunlight, do not eat enough vitamin D-fortified foods, and sequester vitamin
D in fat.28 However, it is not known whether obesity is in part caused by vitamin D
deficiency or if vitamin D deficiency is simply an effect of obesity.
The Health Effects Of Vitamin D Deficiency
In recent years there has been a considerable amount of research that has
investigated the health effects of vitamin D deficiency. As mentioned earlier,
vitamin D deficiency has been associated with several disease states, such as
auto-immune disorders, cancer, cardiovascular, diabetes, infectious, kidney,
neurological, and respiratory diseases, in addition to a corresponding increased
risk of death.12,29,30 However, at this point, with the exception of the clear and
well-established link between vitamin D deficiency and bone integrity, the effects
of vitamin D deficiency are unclear.
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Certainly, there are epidemiological and observational studies that show a
consistent association between low levels of vitamin D and systemic diseases.
There are well outlined mechanisms by which vitamin D could influence systemic
inflammation, the immune system, cell growth and differentiation and thus affect
systemic health. However, definitive cause and effect relationships between
vitamin D deficiency and autoimmune diseases, cancer, cardiovascular disease, or
any of the other conditions listed above, have not been found. The possibility
exists that a low level of vitamin D is an effect, and not a cause.
The list of systemic health effects that have been associated with vitamin D
deficiency is exhaustive, and no organ system seems to be exempt. A
comprehensive discussion of all of these would not be feasible in this study
module, however, some basic information is provided here on a selected number
of systemic effects/diseases that may be affected and/or caused by vitamin D
deficiency.
Bone Health: Osteomalacia/Rickets
Vitamin D deficiency is a cause of ostemalacia, a bone disease that is commonly
called rickets when it occurs in children. Osteomalcia/rickets is characterized by
demineralized bone. Patients with this disease typically have bone pain, muscle
weakness, difficulty walking, and several distinctive radiographic findings.31 In the
early stages of the disease the symptoms can be intermittent and non-specific,
and the patient may not have any complaints.32
Osteomalacia/rickets that is caused by nutritional vitamin D deficiency or by lack
of exposure to sunlight is a rare disease, but there is some evidence that the
incidence of rickets is increasing.33 Risk factors for rickets include dark skin
pigmentation, inadequate vitamin D supplementation of the child or the mother,
the exclusive use of breastfeeding, and inadequate exposure of the child or the
nursing mother to sunlight. If the disease is not detected and treatment is
delayed, the patient can have fractures and significant skeletal deformities.
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Autoimmune Diseases
Low serum levels of vitamin D have consistently been associated with type 2
diabetes, type 1 diabetes in children and adolescents, and multiple sclerosis (MS),
all of which are considered to be autoimmune diseases. A low level of vitamin D is
a predictor of an increased risk for developing MS, an increased number of
relapses, and a more rapid progression of the disease,34 and low levels of vitamin
D are common in patients who have MS.34-37 Similar findings have been reported
for type 1 and type 2 diabetes. Researchers have found an inverse relationship
between vitamin D levels and the risk of developing type 2 diabetes, insulin
sensitivity, and glucose tolerance.38-41
In both diseases there are well-outlined mechanisms that could explain the
association between vitamin D deficiency and MS and type 1 and type 2 diabetes.
There are vitamin D receptors on various cells of the immune system; and, in
vitro and animal studies have shown that high levels of vitamin D inhibit activity
of these cells while low levels heighten their activity.41-43
Multiple sclerosis being a chronic inflammatory disease, an increased
inflammatory state induced by low levels of vitamin D could, possibly, increase
the intensity of the disease or accelerate its progression. In type 2 diabetes,
animal studies have shown that vitamin D deficiency decreases insulin secretion
and adversely affects glucose tolerance by binding to the vitamin D receptors on
pancreatic beta cells.39 This effect, plus an initiation of a pro-inflammatory state
and/or an affect on calcium homeostasis44 may explain the association between
vitamin D levels and diabetes, but the results of human studies have been
equivocal.45-47
Cancer
Calcitrol plays a part in cell proliferation, apoptosis, cell differentiation,
angiogenesis, inflammation, and metastasis; and, so it is plausible that low serum
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levels of vitamin D could influence the growth and progression of cancers.48
Vitamin D deficiency has been linked to cancers of the bladder, breast, colon,
esophagus, kidney, lung, pancreas, thyroid and many other organs.49 However,
some research shows a link between vitamin D and total cancer death rates while
other research does not.48,50-52 Cell cultures and animal studies have provided
strong evidence for a link between vitamin D intake, calcitrol levels, and the risk
of cancer development and progression. Whereas, human trials have been
inconclusive and the data they have provided has been inconsistent.48
Cardiovascular Disease
Observational research and longitudinal studies have associated Vitamin D
deficiency with an increased risk for developing angina, congestive heart failure
(CHF), coronary artery disease (CAD), hypertension (HTN), myocardial infarction
(MI), stroke, and transient ischemic attack (TIA).15 Cell studies and some human
studies suggest that a low level of vitamin D can adversely influence the
cardiovascular system by increasing vascular stiffness and vascular function,53
affecting platelet function and the renin-angiotensin-aldosterone system, and
negatively affecting mortality rate in patients who have CHF or have suffered a
MI.4,54 However, despite the evidence provided by this and other research, it is
still not known whether vitamin D deficiency is a cause of cardiovascular disease
or an effect of these pathologies.55
Recent evidence suggests that there is an association between blood pressure
and vitamin D status. More research is needed to determine more specifically
what level of vitamin D and in what sub-populations it has its effect on blood
pressure.56
Strokes are also related to vitamin D levels. Those with the lowest level of vitamin
D are at increased risk for fatal stroke. In addition, vitamin D supplementation
may reduce the risk of a future stroke.57
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Cognitive Impairment, Dementia and Alzheimer’s Disease
Low levels of vitamin D have been associated with an increased risk of developing
cognitive impairment, dementia, and Alzheimer’s disease,58-60 perhaps as a result
of vitamin D deficiency on the cardiovascular supply to the brain. However, these
are associations and many older adults with low levels of vitamin D do not
develop Alzheimer’s disease or another neurological impairment.
Drug Interactions With Vitamin D
Drug interactions with vitamin D could occur when:
1) The drug affects the absorption of the vitamin D, either enhancing or
inhibiting absorption.
2) The drug interferes with the metabolism by way of the cytochrome P450
enzyme system.
3) When calcium-sparing medications are used along with vitamin D.
A recent (2013) review of the literature examined the evidence for interactions of
commonly used medications with vitamin D.61 Many of these interactions are
listed in widely used drug information sources, but it appears that in most cases
the connection is tenuous and unproven. However, it is reasonable to be aware of
these possible interactions, identify patients at risk and, in selected cases, modify
drug therapy and/or monitor patients low of high levels of vitamin D.
Bile Acid Sequestrants
Colestipol and cholestyramine are used to bind to bile acids and lower serum
cholesterol. These drugs could bind fat-soluble vitamins, but the majority of the
clinical data (albeit a small amount) does not support this.
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Lipase Inhibitors
Orlistat is an inhibitor of gastric and pancreatic lipase. Lipase is an enzyme that
catalyzes the hydrolysis of fats, a metabolic step that is needed for their
absorption; and, because of this mechanism of action it has been suggested this
drug could interfere with the absorption of fat-soluble vitamin D. There is
evidence that serum 25(OH) D can be reduced by Orlistat therefore monitoring of
25(OH) D levels in patients taking Orlistat would be prudent.
Statin Drugs
The statin drugs reduce cholesterol synthesis and cholesterol is needed for
vitamin D synthesis. The statin drugs also may compete for CYP3A4, a
cytochrome P450 enzyme that is used by the liver for the conversion of
cholecalciferol and ergocalciferol. The data on the effect of the statin drugs on
vitamin D level does suggest that atorvastatin can increase 25(OH) D levels, but
that pravastatin does not and the authors of this review article found only five
studies and their quality was considered to be either neutral or negative).
Anti-tubercular Drugs
Vitamin D deficiency has been associated with and increased susceptibility to
tuberculosis and with reactivation of latent infections. However, Lexicomp, a
widely used and actively updated source of drug information does not list an
interaction between cholecalciferol, ergocalciferol and isoniazid or rifampin. The
2013 review examined six small studies that addressed this issue; all were
considered to be of negative quality, most (four) found that vitamin D levels
decreased, but there was no control for sun exposure. In addition, the reviewers
noted that patients with tuberculosis had low vitamin D levels before being
treated with these antituberculars.
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Antiepilepetic Drugs
Osteopenia and osteoporosis have long been associated with the use of antiepileptic drugs. It is difficult to draw conclusions from the published studies that
examined the effect these drugs have on vitamin D levels. Most of the literature but not all - did show that patients who were taking an anti-epileptic drug or
drugs did have lower vitamin D levels than patients who were not. However, the
studies that examined the effect of a single antiepileptic did not find lower serum
vitamin D levels when compared to control subjects. The reviewers felt that low
vitamin D levels that were associated with the use of anti-epileptics were most
likely due to lack of sunlight or dietary deficiency.
Glucocorticoids
Osteoporosis has long been known as an adverse effect of drugs such as
prednisone, hydrocortisone, and dexamethasone. Researchers have not found
that the gluocorticoids consistently and significantly affect vitamin D levels.
Immunosuppressive drugs
Cyclosporine and tacrolimus are used for patients who have had an organ
transplant and for the treatment if immunosuppressive diseases such as
rheumatoid arthritis. Osteoporosis is a common long-term side effect of these
drugs, but the few studies that examined the effect cyclosporine and tacrolimus
have on vitamin D have not shown a strong association between the use of these
drugs and low serum vitamin D levels.
Histamine2 – Receptor Antagonists
Animal studies have shown that cimetidine is an inhibitor of enzymes that are
involved in converting cholecalciferol and ergocalciferol to 25 (OH) D, but one
small human study provided only confusing results. Patients taking cimetidine did
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not develop a decrease in their serum vitamin D levels from baseline, but when
the patients stopped taking cimetidine their serum vitamin D levels increased.
Thiazide Diuretics
The thiazide diuretics decrease renal excretion of calcium and it is reasonable to
assume that taking one of these drugs and a vitamin D supplement would elevate
serum calcium levels. Three cases have been reported that supported this - the
patients were taking vitamin D and a thiazide diuretic and developed
hypercalcemia - but the other literature reviewed did not find that the thiazide
diuretics increased serum vitamin D levels. The reviewers concluded that the
concomitant use of a vitamin D supplement and a thiazide diuretic could cause
hypercalcemia and that the elderly and/or people with decreased renal function or
hyperparathyroidism may be especially vulnerable.
Highly-Active Anti-Retroviral Therapy (HAART)
The drugs used for HAART can inhibit or induce CYP3A4. However, at the time of
the review there was no conclusive evidence that HAART negatively affects
vitamin D levels.
Vitamin D Toxicity: Acute And Chronic
Toxicity from vitamin D, either acute toxicity or chronic, is rare. Vitamin D is
lipophilic, rapidly removed from circulation and sequestered in fat, and it has a
long half-life. Because of these properties, toxicity from vitamin D usually results
from chronic over-ingestion of high supplemental doses. Acute toxicity is quite
rare, and the case reports of acute toxicity seem to involve at least several days
of excessive ingestion.62,63
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Chronic vitamin D toxicity, although rare, is well known and well described. The
primary effect of vitamin D intoxication is hypercalcemia. If the serum calcium is
< 12 mg/dL this is considered mild; if it is between 12-14 mg/dL it is considered
moderate; and, if > 14m mg/dL it is considered severe.64 However, the risk of
toxicity and the signs and symptoms associated with each serum calcium level
will also be influenced by the patient’s age, and the duration of the
hypercalcemia. It is common for patients with vitamin D intoxication to be
anorexic, lethargic, fatigued, and dehydrated. Excess calcium acts as a diuretic
and also causes nausea and vomiting, and serious symptoms such as
obtundation, renal impairment and seizures may be seen.64-66
What is not well known is how much vitamin D is required to produce intoxication.
The recommendations for dietary intake of vitamin D and serum vitamin D levels
assumed minimal sun exposure. The upper limit for daily intake has been
estimated to be 4000 IU. Several sources indicate that doses of 10,000 IU daily
may be safely used,49,67,68 and it is quite easy to obtain 10,000 IU of vitamin D
per day by exposure to sunlight. However, doses that are considered normal and
therapeutic have produced toxicity,69 much higher doses (up to 100,000-200,000
IU a day and higher) have been used without producing vitamin D toxicity and
hypercalcemia.70
A 2014 review notes that most cases of pediatric intoxication involve doses of
240,000 IU - 4,500,000 IU per day.70 The serum level that defines vitamin D
intoxication has been estimated to be > 375 nmol/L.67,70 The treatment for
vitamin D intoxication is identified below as:9,64,66
1) Discontinue the vitamin D supplementation.
2) Fluid replacement.
3) Cautious use of loop diuretics to increase calcium excretion.
4) The use of biphosphonates to decrease bone resorption and release of
calcium into the serum.
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5) The use of calcitonin, which decreases bone resorption of calcium, blocks
the release of calcium into the serum, promotes renal excretion of calcium
and antagonizes the physiological effects of parathyroid hormone.
6) In severe cases hemodialysis may be needed.
Prevention And Treatment Of Vitamin D Deficiency:
Therapeutic Use Of Vitamin D Supplementation
In individuals that are not vitamin D deficient the daily requirement for vitamin D
can be obtained by exposure to sunlight and by dietary intake. Direct sunlight
exposure is an easy way to get vitamin D. Individuals who get 10-30 minutes of
sunlight between 10 am and 3 pm, two times a week, will most often have
enough vitamin D. It does not require full body sunbathing to get vitamin D.
Exposing the arms and face allows the body to acquire adequate vitamin D in
most individuals. The recommended dietary intake of vitamin D was discussed
earlier in this learning module. Routine screening of the general population for
vitamin D deficiency by primary care is not recommended;9,71 however, as
ongoing research outcomes on the health benefits of vitamin D evolve the general
guidelines for screening deficiency may change. For now, only individuals
considered at risk, for example, elderly or those with osteoporosis, are
recommended for screening of vitamin D deficiency.
The value of supplemental vitamin D for disease prevention and/or modification of
disease progress are not clear at this time. Although low serum vitamin D levels
may be a risk factor for the development of chronic diseases and influence the
course of those diseases, there is no firm evidence at this time that vitamin D
supplementation is helpful for people with autoimmune diseases, cardiovascular
diseases, cancer, or other pathologies.29,72,74
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Recommending vitamin D supplementation as a standard health prevention
strategy is complicated because there is no absolute consensus on the optimal
vitamin D level, how to measure it, and what doses are effective and safe.75
However, there are guidelines for the treatment of vitamin D deficiency. Either
cholecalciferol or ergocalciferol can be used, but a meta-analysis of seven
randomized trials found that cholecalciferol was more effective at elevating serum
vitamin D levels.76
Learning Break: The vitamin D metabolites calcidiol and calcitrol can be used to
treat vitamin D deficiency, as can artificial UVB. However, these drugs are
typically second-tier choices and using artificial UVB is difficult because there is
no established safe dose. These therapies will not be discussed in detail.
The following dosing regimens are from the Endocrine Society,77 the National
Osteoporosis Foundation,78 the National Kidney Foundation,79 and other
professional resources.80
Endocrine Society Guidelines
1. People who are obese, people who have malabsorption syndrome and are
vitamin d deficient, or people who are taking medications that may affect
vitamin D levels: 6000-10,000 IU a day to attain a serum level of 75
nmol/L, then a maintenance dose of 3000-6000 IU a day.
2. Adults who are vitamin D deficient: 50,000 IU once a week for eight weeks
or 6000 IU a day for eight weeks. This should be followed by a maintenance
dose of 1500-2000 IU a day. The goal is to reach and maintain a serum
level of 75 nmol/L/.
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3. Children 1-18 years who are vitamin D deficient: 50,000 IU a week for at
least six weeks or 2000 IU a day for at least six weeks. This should be
followed by a maintenance dose of 600-1000 IU a day. The goal is to reach
and maintain a serum vitamin D level of 75 nmolL.
4. Children 0-1 years: 2000 IU a day for six weeks or 50,000 IU a week for six
weeks. This should be followed by a maintenance dose of 400-1000 IU a
day. The goal is to reach and maintain a serum level of 75nmol/L.
National Osteoporosis Foundation Guidelines
Osteoporosis prevention, adults ≥ 50 years: Cholecalciferol or ergocalciferol, 8001000 IU a day.
National Kidney Foundation
Vitamin D deficiency/insufficiency in patients with chronic kidney disease stages;
Oral treatment duration should be a total of 6 months:
1. Serum 25 (OH)D < 12.5 nmol/L: Ergocalciferol, 50,000 units/week for 12
weeks, then 50,000 units/month.
2. Serum 25(OH)D 12.5-37.5 nmol/L: Ergocalciferol, 50,000 units/week for 4
weeks, then 50,000 units/month.
3. Serum 25(OH)D 40-80 nmol/L: Ergocalciferol, 50,000 units/month.
Osteomalacia, Familial Hypophosphatemia, and Rickets
1. Hypoparathyroidism: Ergocalciferol, 25,000-200,000 IU a day and calcium
supplements.
2. Nutritional rickets and osteomalacia: Adults with normal absorption,
ergocalciferol, 1000-5000 IU a day.
3. Adults with malabsorption: Ergocalciferol, 10,000-300,000 IU a day.
4. Vitamin D-dependent rickets: Ergocalciferol, 10,000-60,000 IU a day.
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5. Vitamin D-resistant rickets: Ergocalciferol 12,000-500,000 IU a day
6. Familial hypophosphatemia: Ergocalciferol 10,000-60,000 IU a day plus
phosphate supplements.
The contraindications for the use of vitamin D are hypercalcemia, malabsorption
syndrome, and vitamin D toxicity. Adverse effects are related to elevated vitamin
D levels.
Vitamin D does enter breast milk. Caution should be used when prescribing
vitamin D supplementation to breastfeeding mothers, and vitamin D is considered
to be category D for pregnancy.
Summary
Vitamin D is an essential nutrient that is needed for normal calcium and
phosphorus metabolism. It is synthesized in the skin by exposure to sunlight and
it is ingested in the daily diet. The recommended daily allowance for vitamin D is
currently considered to be 600 IU a day, 400 IU a day for children
0-12 months
and 800 IU a day for adults ≥ 71 years. In recent years, vitamin D has been the
subject of intense scrutiny. Researchers have tried to determine: 1) How much
vitamin D is needed for optimal health; 2) How much is needed to treat certain
diseases and certain populations; 3) The health effects of vitamin D deficiency,
and why vitamin D deficiency is so widespread, and; 4) How much vitamin D is
safe and how much is toxic. Despite the attention focused on vitamin D, the
knowledge that has been gained is out-shadowed by questions that remain.
Vitamin D deficiency is widespread (that is not disputed), but it is still not known
precisely why so many people have low serum levels of vitamin D and how
vitamin D deficiency affects health. Epidemiological studies have consistently
shown an association between vitamin D deficiency and the development of many
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chronic diseases and the progress of chronic diseases. However, definitive proof of
a cause and effect relationship has remained elusive. If we accept that vitamin D
deficiency can cause chronic diseases and it is not an effect of chronic diseases
than supplementation would be expected to prevent and/or treat illness. However,
research that has focused on vitamin D supplementation as a preventative
measure or as a treatment has yielded ambiguous results.
Individual risk factors for vitamin D deficiency need to be more clearly defined
and understood. The recommended daily allowance for vitamin D has been set,
but there is still research that needs to be done to determine exactly how much
vitamin D should be used for treating specific diseases and certain patient
populations. The amount of vitamin D that is safe is not entirely clear nor is the
amount that is toxic. Vitamin D intoxication is well known and well described, but
the reported amounts that are safe or toxic vary considerably. There appear to be
genetic variations in vitamin D metabolism that affect individual susceptibility to
intoxication from vitamin D, but they are not completely understood.
Vitamin D deficiency is common. Nurses need to know that this nutritional
deficiency is widespread, understand which patient populations are potentially at
risk, and know the chronic diseases that may be caused and/or influenced by
vitamin D deficiency. Finally, nurses need to know why vitamin D is needed, how
vitamin D is obtained and be able to advise patients about the basics of vitamin D
as it relates to their diet and health.
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nursing knowledge needs met by completing the self-assessment of
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1. Vitamin D is obtained by:
a. exposure to sunlight and dietary intake
b. exposure to sunlight
c. dietary intake
d. ingestion of manufactured supplements
2. One of the primary functions of vitamin D is:
a. control of muscle contraction
b. control of calcium and phosphorus metabolism
c. control of potassium and sodium metabolism
d. control of renal blood flow
3. Good dietary sources of vitamin D are:
a. whole grains and fruits
b. leafy green vegetables and red meat
c. fortified milk and certain fishes
d. citrus fruits and nuts
4. Vitamin D deficiency is characterized by:
a. hypokalemia
b. hyponatremia
c. hypomagnesemia
d. hypocalcemia
5. True or false: Vitamin D excess can be caused by over-exposure to
sunlight.
a. True
b. False
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6. Risk factors for vitamin D deficiency include:
a. excessive exposure to sunlight, malabsorption syndrome, obesity
b. poor dietary intake, cardiac disease, multiple sclerosis
c. lack of exposure to sunlight, use of certain medications, obesity
d. kidney disease, excessive dietary fat, hypertension
7. True or false: Infants who are exclusively breast-fed are at risk for
vitamin D deficiency.
a. True
b. False
8. Vitamin D deficiency has NOT been linked to which disease?
a. Osteoporosis
b. Heart disease
c. Diabetes
d. Pneumonia
9. Which of these drugs may influence vitamin D levels?
a. Statins, anti-epileptic drugs
b. Beta-blockers, opioid analgesics
c. ACE inhibitors, glucocorticoids
d. Calcium channel blockers, non-steroidal anti-inflammatories
10. Vitamin D intoxication is primarily characterized by:
a. hyperkalemia
b. hypercalcemia
c. hypernatremia
d. hypermagnesemia
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Correct Answers:
1. A
2. B
3. C
4. D
5. B
6. C
7. A
8. D
9. A
10. B
References Section
The reference section of in-text citations include published works intended as
helpful material for further reading. Unpublished works and personal
communications are not included in this section, although may appear within the
study text.
1. Higdon J, Drake VJ. Evidence-based approach to vitamins and minerals: health
benefits and intake recommendations. 2nd ed. New York, New York: Thieme;
2012.
2. Friedman, PA. Agents affecting mineral ion homeostasis and bone turnover. In:
Brunton LL, Chabner BA, Knollman BC, eds. Goodman & Gilman’s The
Pharmacological Basis of Therapeutics. 12th ed. New York, NY: McGraw-Hill; 2011:
Chapter 44. On-line edition. Retrieved April 11, 2014 from: www.UCHC.edu.
3. Stephenson CB, Zerofsky M, Burnett DJ, et al. Ergocalciferol from mushrooms
or supplements consumed with a standard meal increases 25nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com
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hydroxyergocalciferol but decreases 25-hydroxycholecalciferol in the serum of
healthy adults. Journal of Nutrition. 2012; 142;1246-1252.
4. Pourdjabbr A, Dwivedi, G. Haddad H. The role of vitamin D in chronic heart
failure. Current Opinion in Cardiology. 2013;28:216-222.
5. Gebreegziabher T, Stoecker BJ. Vitamin D insufficiency in a sunshine-sufficient
area: southern Ethiopia. Food and Nutrition Bulletin. 2013;34:429-433.
6. De Rui M, Toffanello ED, Veronese N, et al. Vitamin d deficiency and leisure
time activities in the elderly: are all pastimes the same? PLoS One.
2014;10:e94805.
7. National Institutes of Health: Office of Dietary Supplements. Vitamin D: Fact
Sheet for Health Professionals. June 24, 2011. Retrieved April 13, 2014 from:
http://ods.od.nih.gov/factsheets/VitaminD-HealthProfessional/
8. Gröber U, Spitz J, Reichrath J, Kisters K, Holick MF. Vitamin D: Update 2013.
From rickets prophylaxis to general preventative healthcare. DermatoEndocrinology. 2013;5:331-347.
9. Dawson-Hughes B. Vitamin D deficiency in adults: Definition, clinical
manifestations, and treatment. UpToDate. March 13, 2014. Retrieved April 13,
2014 from: www.UCHC.edu
10. National Osteoporosis Foundation. Osteoporosis Clinical Updates. Vitamin D
and Health. February, 2014. Retrieved April 24, 2014 from: www.nof.org.
11. Walker GE, Ricotti R, Roccio M, et al. Pediatric obesity and vitamin D
deficiency: A proteomic approach identifies multimeric adiponection as a key link
between these conditions. PLoS One. 2014;9:383865.
12. Chowdhury R, Kunutsor S, Vitezova A, et al. Vitamin D and risk of cause of
specific death: systematic review and meta-analysis of observational cohort and
randomized intervention studies. BMJ. 2014; April1, 2014.
13. Forrest KY, Stuhldreher WL. Prevalence and correlates of vitamin D deficiency
in US adults. Nutrition Research. 2011;31:48-54.
14. Holick MF. Vitamin D deficiency. New England Journal of Medicine.
2007;357:266-281.
nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com
33
15.Kunadian V, Ford GA, Bawamia B, Qiu W, Manson JE. Vitamin D deficiency and
coronary artery disease: A review of the evidence. American Heart Journal.
2014;167:283-291.
16. Agus ZS, Drezner MK. Causes of vitamin D deficiency and resistance.
UpToDate. March 14, 2014. Retrieved April14, 2014 from: www.uchc.edu.
17. Oberhelman SS, Meekins ME, Fischer PR, et al. Maternal vitamin D
supplementation to improve the vitamin D status of breast-fed infants: A
randomized controlled trial. Mayo Clinic Proceedings. 2013;88:1378-1387.
18. Gallo S, Corneau K, Vanstone C, et al. Effect of different dosages of oral
vitamin D supplementation on vitamin D status in healthy breast-fed infants: A
randomized trial. Journal of the American Medical Association. 2013;309:17851972.
19. Powe CE, Evans MK, Wenger J, et al. Vitamin D binding protein and vitamin D
status of black Americans and white Americans. New England Journal of Medicine.
2012;369:1991-2000.
20. Adams JS, Hewison M. Update in vitamin D. Journal of Clinical Endocrinology
& Metabolism. 2010;95:471-478.
21. Ginde AA. Liu MC, Camargo Jr CA. 2009 Demographic differences and trends
in vitamin D insufficiency in the US population, 1988-2004. Archives of Internal
Medicine. 2004;169:626-632.
22. O’ Connor MY, Thoreson CK, Ramsey NLM, Ricks M, Sumner AF. The uncertain
significance of low vitamin D levels in African descent populations: A review of the
bone and cardio-metabolic literature. Progress in Cardiovascular Diseases.
2013;56:261-269.
23. Coney P, Demers LM, Dodson WC, Kunselman AR, Ladson G, Legro RS.
Determination of vitamin D in relation to body mass index and race in a defined
population of black and white women. International Journal of Gynecology &
Obstetrics. 2012;119:21-25.
24. Stokić E, Kupusinac A, Tomić-Naglić D, et al. Obesity and vitamin D. Trends to
promote a more pro-atherogenic cardio-metabolic risk profile. Angiology. 2014;
March 21[Epub ahead of print].
nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com
34
25. Soskić S Stokić E, Isenović ER. The relationship between vitamin D and
obesity. Current Medical Research and Opinion. 2014; March 18 [Epub ahead of
print].
26. Bellan M, Guzzaloni G, Rinaldim, et al. Altered glucose metabolism rather
than naïve type 2 diabetes (T2DM) is related to vitamin D deficiency is severe
obesity. Cardiovascular Diabetology. 2014;13:57.
27. Vimaleswaran KS, Cavadino A, Berry DJ, et al. Genetic association analysis of
vitamin D pathway with obesity traits. International Journal of Obesity.
2013;37:1399-1406.
28. Pathak K, Soares MJ, Calton EK, Zhao Y, Hallett J. Vitamin D supplementation
and body weight status: a systematic review and meta-analysis of randomized
controlled trials. Obesity Reviews. 2014; Feb. 14: [Epub ahead of print].
29. Autier P, Boniol M, Pizot C, Mullie P. Vitamin D status and ill health: a
systematic review. Lancet Diabetes & Endocrinology. 2014;2:76-89.
30. Theodoratou E, Tzoulaki I, Zgaga L. Vitamin D and multiple health outcomes:
umbrella review of systematic reviews and meta-analyses of observational studies
and randomized trials. BMJ. 2014; April 1: 348:g2035. doi: 10.1136/bmj.g2035.
31. Bhan A, Rao AD, Rao S. Osteomalacia as a result of vitamin D deficiency.
Endocrinology & Metabolism Clinics of North America. 2010;39:321-331.
32. Hazzazi MA, Alzeer I, Tamimi W, Al Atawi M, Al Awan I. Clinical presentation
and etiology of osteomalcia/rickets in adolescents. Saudi Journal of Kidney
Diseases and Transplantation. 2013;24:938-941.
33. Thacher TD, Fischer PR, Tebben PJ, et al. Increased incidence of nutritional
rickets: A population-based study in Olmstead County, Minnesota. Mayo Clinic
Proceedings. 2013;88:176-183.
34. Ascherio A, Munger KL, White R. Vitamin D as an early predictor of multiple
sclerosis activity and progression. JAMA Neurology. 2014;71:306:306-314.
35. Smolders J, Peelen E, Thewissen M, Menheere D, Damoiseaux J, Hupperts R.
Circulating vitamin D binding levels are not associated with relapses or vitamin D
status in multiple sclerosis. Multiple Sclerosis Journal. 2014;20;433-437.
nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com
35
36. Salzer J, Hallmans G, Nyström M, Stenlund H, Waddell G, Sundström P.
Vitamin D as a protective factor in multiple sclerosis. Neurology. 2012;79:21402145.
37. Summerday NM, Brown SJ, Allington DR, Rivey MP. Vitamin D and multiple
sclerosis: Review of a possible association. Journal of Pharmacy Practice.
2012;25:75-84
38. Lazear J, Kasputin J. Vitamin D deficiency and type 2 diabetes: A
retrospective review. The Journal for Nurse Practitioners. 2014;3:175-182.
39. Griz LHM, Bandeira F, Andrade M, Gabbay L, Dib SA, de Cavalho EF. Vitamin
D and diabetes: an update - 2013. Arquivos Brasileiros de Endocrinologia e
Metabologia. 2013; 58:1-8.
40. Jehle S, Lardi A, Felix B, Hulter HN, Stettler L, Krapf R. Effect of large doses
of parenteral vitamin D on glycaemic control and calcium/phosphate metabolism
in patients with stable type 2 diabetes mellitus. A randomised, placebo-controlled,
prospective pilot study. Swiss Medicine Weekly. 2014;144:w13942.
41. Wolden-Kirk H, Overbergh L, Christesen HT, Brusgaard K, Chantal M. Vitamin
D and diabetes: its importance for beta cell and immune function. Molecular and
Cellular Endocrinology.2011;347:106-120.
42. Smolders J, Damoiseaux J, Menheere, P, Hupperts R. Vitamin D as an immune
modulator in multiple sclerosis: A review. Journal of Neuroimmunology.
2008;194:7-17.
43. Smolders J, Damoiseaux J. Vitamin D as a T-cell modulator in multiple
sclerosis. Vitamins & Hormones. 2011;86:401-428.
44. Eduardo C, Chagas A, Borges MC, Martini LA, Rogero MM. Focus on vitamin D,
inflammation, and type 2 diabetes. Nutrients. 2012;4:52-67.
45. Gulseth HL, Gjelstad IM, Tierney AC, et al. Serum vitamin D concentration
does not predict insulin action or secretion in European subjects with metabolic
syndrome. Diabetes Care. 2010;33:923-925.
46. Kayaniyil S, Vieth R, Retnakaran, et al. Prospective associations of vitamin D
with β-cell function and glycemia: the PROspective Metabolism and Islet cell
Evaluation (PROMISE) cohort study. Diabetes. 2011;60:2947-2953.
nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com
36
47. Veronese N, Sergi G, De Rui M, et al. Serum 25-hydroxyvitamin D and the
incidence of diabetes in elderly people: the PRO V.A. Study Journal of Clinical
Endocrinology & Metabolism. 2014; April 14. [Epub ahead of print.]
48. Feldman D, Krishnan AV, Swami S, Giovanucci E, Feldman BJ. The role of
vitamin D in reducing cancer risk and progression. Nature Reviews Cancer. 2014;
April 4: [Epub ahead of print].
49. Glade MJ. Vitamin D: Health panacea or false prophet? Nutrition. 2013;29:3741.
50. Pittas AG, Lau J, Hu FB, Dawson-Hughes B. The role of vitamin D and calcium
in type 2 diabetes. A systematic review and meta-analysis. Journal of Clinical
Endocrinology Metabolism 2007; 92: 2017-2029.
51. Giovannucci E, Liu Y, Rimm EB, et al. Prospective study of predictors of
vitamin D status and cancer incidence and mortality in men. National Cancer
Institute 2006; 98:451–459.
52. Freedman DM, Looker AC, Chang SC, Graubard BI. Prospective study of
serum vitamin D and cancer mortality in the United States. Journal of the
National Cancer Institute 2007; 99: 1594-602.
53. Al Mheid I, Patel R, Murrow J, et al. Vitamin D status is associated with
arterial stiffness and vascular dysfunction in healthy humans. Journal of the
American College of Cardiology. 2011;58:186-192.
54. Khalili H, Talasaz AH, Salarifar M. Serum vitamin D concentration and its
correlation with early biomarkers of remodeling following acute myocardial
infarction. Clinical Research in Cardiology. 2012;101:321-327.
55. Schneider ALC. Michos AD. Invited commentary: The association of low
vitamin D with cardiovascular disease – getting at the “heart and soul” of the
relationship. American Journal of Epidemiology. 2014;April 3:[Epub ahead of
print].
56. Martini LA, Wook RJ. Vitamin D and blood pressure connection: update on
epidemiological, clinic, and mechanistic evidence. Nutrition Reviews.
2008;66:291-297.
nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com
37
57. Pilz S, Dobning H, Fischer JE, et al. Low vitamin D levels predict stroke in
patients referred to coronary angiography. Stroke. 2008;39:2611-2613.
58. Schlogl M., Holick MF. Vitamin D and neurocognitive function. Clinical
Interventions in Aging. 2014; 9:559-568.
59. Annweiler C, Karras SN, Anagnostis P, Beauchet O. Vitamin D supplements: a
novel therapeutic approach for Alzheimer’s patients. Frontiers in Pharmacology.
2014; Jan 28. doi: 10.3389/fphar.2014.00006.
60. Zhao Y, Sun Y, Ji HF, Shen L. Vitamin D levels in Alzheimer’s and Parkinson’s
disease: a meta-analysis. Nutrition. 2013;29:828-832.
61. Roven K, Oppeneer SJ, Kelly JA, Hamilton-Reeves JM. Drug-vitamin D
interactions: A systematic review of the literature. Nutrition in Clinical Practice.
2013;28:194-208.
62. Thomson RB, Johnson JK. Another family with acute vitamin D intoxication:
another case of familial hypercalcemia. Postgraduate Medical Journal.
1986;62:1025-1028.
63. Down PF, Polak A, Regan RJ. A family with massive acute vitamin D
intoxication. Postgraduate Medical Journal. 1979;55:897.
64. Özkan B, Hatun S, Bereket A. Vitamin D intoxication. The Turkish Journal of
Pediatrics. 2012;54:93-98.
65. Bell DA, Crooke MJ, Hay N. Glendenning P. Prolonged vitamin D intoxication:
presentation, pathogenesis, and progress. Internal Medicine Journal.
2013;43:1148-1150.
66. Nordt SP, Williams SR, Clark RF. Pharmacologic misadventure resulting in
hypercalcemia from vitamin D intoxication. The Journal of Emergency Medicine.
2002;22:302-303.
67. Kaptein S, Risselada AJ, Boerma C, Egbers PHM, Niebor P. Life-threatening
complications of vitamin D intoxication due to over-the-counter supplements.
Clinical Toxicology. 2010;48:460-462.
68. Veith R. Vitamin D toxicity, policy, and science. Journal of Bone & Mineral
Research. 2007;22(S2):V64-V68.
nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com
38
69. Vanstone MB, Olberfield SE, Shader L, Ardeshirpour L, Carpenter TO.
Hypercalcemia in children receiving pharmacologic doses of vitamin D. Pediatrics.
2012;129:e1060-e1063.
70. Vogiatzi MG, Jacobson-Dickman E, DeBoer MD. Vitamin D toxicity and the risk
of supplementation in pediatrics: A review of the current literature. Journal of
Clinical Endocrinology & Metabolism. 2014;99:1132-1141.
71. Holik MF, Binkley NC, Heike A, et al. Evaluation, prevention, and treatment of
vitamin D deficiency: an Endocrine Society clinical practice guideline. Journal of
Clinical Endocrinology & Metabolism. 2011;96:1911-1930.
72. Cree BAC. 2014 multiple sclerosis therapeutic update. The Neurohospitalist.
2014;4:63-65.
73. Brum DG, Comini-Frota ER, Vasconcelos CCF, Dias-Tosta E. Supplementation
and therapeutic use of vitamin D in patients with multiple sclerosis: Consensus of
the Scientific Department of Neuroimmunology of the Brazilian Academy of
Neurology. Arquivos de Neuro-Psiquiatria. 2014;72:152-156.
74. Bolland MJ, Grey A, Gamble GD, Reid IR. The effect of vitamin D
supplementation on skeletal, vascular, or cancer outcomes: a trial sequential
meta-analysis. Lancet Diabetes & Endocrinology. 2014;2:307-320.
75. Romganoli E, Carnevale V, Biondi P, Minisola S. Vitamin D supplementation:
when and how? Journal of Endocrinological Investigation. 2014. April 3 [Epub
ahead of print].
76. Tripkovic L, Lambert H, Hart K, et al. Comparison of vitamin D2 and vitamin
D3 supplementation in raising serum 25-hydroxyvitamin D status: a systematic
review and meta-analysis. American Journal of Clinical Nutrition. 2012;95:13571364.
77. Holik MF, Binkley NC, Heike A, et al. Evaluation, prevention, and treatment of
vitamin D deficiency: an Endocrine Society clinical practice guideline. Journal of
Clinical Endocrinology & Metabolism. 2011;96:1911-1930.
78. National Osteoporosis Foundation (NOF), Clinician’s Guide to Prevention and
Treatment of Osteoporosis,” Washington, DC, 2013. Retrieved April 22, 2014
from: http://www.nof.org/files/nof/public/content/resource/913/files/580.pdf.
nursece4less.com nursece4less.com nursece4less.com nursece4less.com nursece4less.com
39
79. K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in
Chronic Kidney Disease. Guideline 7. Prevention and Treatment of Vitamin D
Insufficiency and Vitamin D Deficiency in CKD Patients. Retrieved April 24, 2014
from: http://www.kidney.org/professionals/KDOQI/guidelines_bone/Guide7.htm.
80. Cholecalciferol and ergocalciferol. Lexicomp®. Retrieved April 25, 2014 from:
www.UCHC.edu.
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