Q&A VITAMIN D: WHAT YOU NEED TO KNOW

For many years, clinicians have been aware of • Infectious diseases3 and asthma in developing fetuses
the link between vitamin D levels and bone and young children.4
health; however, recent studies have shown that • Cardiovascular disease and hypertension.3
vitamin D may play a role in maintaining other
Only a few randomized control trials have a dosing range
aspects of overall health.1-4 The following is a
adequate to provide strong evidence for the benefit of
list of frequently asked questions (FAQ) with
vitamin D in reducing the risk of these chronic diseases.3
answers that further support the clinician’s
understanding of the clinical aspects of Q: How can individuals increase their vitamin D levels?
vitamin D. A: There are two sources of vitamin D: diet and exposure to
sunlight. The normal diet is very low in vitamin D. Most
foods, with the exception of fatty fish oils, contain little
Q: What’s so exciting about vitamin D? vitamin D. Some foods (milk and cereals) are fortified
A: The World Health Organization’s International Agency with vitamin D. Vitamin D levels can be increased by
for Research on Cancer (IARC) has concluded that there spending some time in the sun. Energy from the sun
appears to be a link between an individual’s vitamin D converts a precursor in the skin to vitamin D.3,4
levels and the risk of developing colorectal cancer.2
Studies have also revealed that higher vitamin D levels
Q: Who is at greatest risk of vitamin D deficiency?
are associated with a decreased incidence of other
A: Vitamin D deficiency has been defined by the Institute
malignancies, including breast cancer.5
of Medicine and an Endocrine Society practice guideline
as a level of serum 25-hydroxy vitamin D of less than
Q: What about bone health? 20 ng/mL.3,4 The Endocrine Society went on to define
A: Vitamin D plays an integral role in calcium homeostasis vitamin D insufficiency as levels between 21 ng/mL and
and in the maintenance of healthy bone. Vitamin D 29 ng/mL.3 Because the sun is an important source of
stimulates the absorption of calcium at the level of the vitamin D, serum levels in individuals tend to be lower
intestine and may also serve to increase calcium and in the winter than in the summer. Even at the end of
phosphate resorption at the kidney level. Deficiency summer, in one study that looked at median blood levels
of vitamin D leads to the mobilization of calcium from of vitamin D in a population of healthy men, more than
bone, which can lead to osteoporosis, osteomalacia, half of the studied healthy population had levels below
and rickets.1,3,4 30 ng/mL.6 The elderly, individuals with dark complexion,
people who do not get enough sun exposure, and people
Q: Does vitamin D play a role in any other conditions? with illnesses (including malabsorption syndromes, liver
A: Many tissues and cells in the body have a vitamin D disease, and kidney disease) appear to be at higher risk
receptor. It has been estimated that the expression of as of deficiency.3 As a result, a large percentage of these
much as one third of the human genome is influenced individuals will have low serum vitamin D levels.
by 1,25-(OH)2 vitamin D along with other factors.3 Many
studies have demonstrated an association of vitamin D Q: Do I have to worry about my vitamin D levels if I get a
deficiency with increased risk for:
lot of sun?
• Autoimmune diseases, including both type 1 and A: Exposure to direct sunlight converts a precursor in the
type 2 diabetes, rheumatoid arthritis, Crohn’s disease,
skin to vitamin D.3,4 Vitamin D levels in the fall and winter
and multiple sclerosis.3
tend to be lower because the energy from the sun is not
high enough for optimal vitamin D production.3 It should
also be noted that some people have low vitamin D
levels even with very high sun exposure.7 In a recent
study, Binkley and coworkers tested vitamin D levels of
individuals in Hawaii in late March who were patrons of
Q&A VITAMIN D: WHAT YOU NEED TO KNOW

the A’ala Park Board Shop (a skateboard shop frequented Q: Does it matter what type of vitamin D a person takes?
by young adults) and volunteers from the University of A: Clinical studies have shown that vitamin D
Hawaii at Manoa.7 More than half of these individuals supplementation with D3 may be more effective than
had low vitamin D levels, despite reported sun exposure supplementation with D2.11 Armas and coworkers
of three or more hours per day at least five days a week.7 showed giving the same dose of D3 or D2 produces the
High levels of sun exposure do not necessarily correlate same immediate increase in total vitamin D levels11;
with optimal vitamin D levels. however, the D2 levels fall off precipitously while D3 levels
are maintained for a longer time (Figure 1). This study
Q: How much vitamin D do you need to take each day? suggests that D2 may be cleared faster than D3, reducing
A: The Institute of Medicine has published Recommended the effectiveness of supplementation with D2.
Dietary Allowances (RDA) for daily intake of vitamin D by
various populations.8 Vitamin D3 (cholecalciferol on the label) and vitamin D2
(ergocalciferol on the label) are both available in many
Age Children Men Women Pregnancy Lactation
stores without prescription. According to this study, to
Birth to 1 years 400 IU
optimize the efficiency of vitamin D supplementation, the
1 to 70 years 600 IU 600 IU 600 IU 600 IU
supplement should contain vitamin D3 (cholecalciferol on
71+ years 800 IU 800 IU
the label) and not vitamin D2 (ergocalciferol on the label).
Vitamin D3 supplements in the form of 1000 IU tablets are
available in many stores without prescription.
The daily intake (RDA) of vitamin D recommended by
the Institute of Medicine should be enough to prevent
most people from experiencing vitamin D deficiency
(defined as a serum level of 25-OH vitamin D of less than
20 ng/mL).4,8 Higher levels of intake may be required
to prevent vitamin D insufficiency (defined by the
Endocrine Society as levels of 25-OH vitamin D
between 21-29 ng/mL).3

Heaney and coworkers9 showed that supplementing with

levels as high as 10,000 IU/day did not cause toxicity in
a healthy cohort, and supplementing with 1000 IU/day
caused only a minimal increase in serum vitamin D levels.

The Endocrine Society Clinical Practice Guideline has

indicated that raising serum vitamin D levels consistently Figure 1. Time course of the rise in serum 25OHD after a single oral dose of 50,000 IU of either
cholecalciferol (vitamin D3) or ergocalciferol (vitamin D2) in two groups of 10 normal men
above 30 ng/mL may require at least 1500-2000 IU/day.3 each.11
These levels are significantly higher than the RDA. Note: A serum concentration of 30 ng/mL of vitamin D is equal to 75 nmol/L of vitamin D.
Reprinted from Armas LA, Hollis BW, Heaney RP. Vitamin D2 is much less effective than vitamin D3 in
Q: Are all vitamin D supplements the same? humans. J Clin Endocrinol Metab. 2004 Nov; 89(11):5387-5391, with permission from The Endocrine
Society, copyright 2004.
A: The vitamin D produced in the skin and that found
naturally in animal-based foods are both derived from the
same cholecalciferol (vitamin D3) family.10 An alternate, Q: What is the latest research on vitamin D and disease?
plant-based form of vitamin D can also be manufactured A: A few recent studies are discussed on the following pages.
by irradiation of ergosterol from yeast to produce
ergocalciferol, or vitamin D2. Both the D2 and D3 forms
have similar biologic activity.10

2
Q&A VITAMIN D: WHAT YOU NEED TO KNOW

Vitamin D and Bone Health Fall prevention with supplemental and

active forms of vitamin D: A meta-analysis
of randomised controlled trials.
Positive association between 25-hydroxy vitamin D Bischoff-Ferrari HA, Dawson-Hughes B, Staehelin HB et al. BMJ.
levels and bone mineral density: A population- 2009;339:b3692. doi: 10.1136/bmj.b3692.
based study of younger and older adults. The authors performed a systematic review of articles
Bischoff-Ferrari HA, Dietrich T, Orav EJ, Dawson-Hughes B. Am J Med. 2004
May 1; 116(9):634-639. published between 1960 and 2008 that assessed the
In this study, the authors correlated total hip bone effectiveness of vitamin D supplementation with or
mineral density by dual-energy X-ray absorptiometry without calcium in the prevention of falls among
to measured total vitamin D levels in 13,432 subjects older individuals. Heterogeneity was noted among
enrolled in the NHANES III study. Their statistical analysis the eight randomized controlled trials (n=2426) of
took into account sex, age, estrogen use, and race/ supplemental vitamin D dosage and achieved serum
ethnicity. The figures below show the locally weighted 25-OH D concentration. The authors concluded that
regression (LOWESS) plots of bone density versus serum supplementation of vitamin D of 700-1000 IU a day was
vitamin D levels. The authors observed a significant associated with a 19% reduced risk of falling among
positive association between serum vitamin D levels and older individuals. The risk of falling may not be reduced
measured bone mineral density. in this population if vitamin D supplementation is less
than 700 IU or serum 25-OH D concentrations of less
than 25 ng/mL.

Prevention of nonvertebral fractures with oral

vitamin D and dose dependency: A meta-analysis
of randomized controlled trials
Bischoff-Ferrari HA, Willett WC, Wong JB et al. Arch Intern Med.
2009;169(6):551-561.
The authors performed a systematic review of articles
published between 1960 and 2008 that assessed the
effectiveness of supplemental vitamin D, with or without
calcium, in the prevention of nonvertebral and hip
fractures among individuals 65 years of age or older.
Twelve double-blind randomized controlled trials (RCTs)
Figure 2. Regression plot of bone mineral density by 25-hydroxy vitamin D level in younger for nonvertebral fractures (n = 42,279) and eight RCTs
adults (20 to 49 years). Circles represent whites, squares represent Mexican Americans, and
triangles represent blacks. for hip fractures (n = 40,886) were included. The authors
Reprinted from Bischoff-Ferrari HA, Dietrich T, Orav EJ, Dawson-Hughes B. Am J Med. 2004 May noted a higher dose of vitamin D and higher achieved
1;116(9):634-639, with permission from Elsevier. 25-OH D blood levels were associated with a significant
increase in antifracture efficacy. The higher dose of
vitamin D reduced nonvertebral fractures in individuals
living in community dwellings or in institutionalized older
individuals. The authors concluded that the prevention
of nonvertebral fracture was dependent on the dosage of
vitamin D, and with a higher dose of vitamin D, those 65
years old and older should see a reduction in fractures by
at least 20%.

Figure 3. Regression plot of bone mineral density by 25-hydroxy vitamin D level in older adults
(>50 years). Circles represent whites, squares represent Mexican Americans, and triangles
represent blacks.
Reprinted from Bischoff-Ferrari HA, Dietrich T, Orav EJ, Dawson-Hughes B. Am J Med. 2004
May 1;116(9):634-639, with permission from Elsevier.
3
Q&A VITAMIN D: WHAT YOU NEED TO KNOW

Serum 25-hydroxyvitamin D concentrations and women from the population of healthy postmenopausal
risk for hip fractures. women were randomly assigned to receive 1400 to
Cauley JA, Lacroix AZ, Wu L, et al. Ann Intern Med. 2008 Aug 19; 149(4):
1500 mg of supplemental calcium per day alone
242-250.
(Ca-only), supplemental calcium plus 1100 IU vitamin D3
In this study, the authors performed a nested case-control
per day (Ca+D), or placebo. The unadjusted relative
study of patients from 40 clinical centers in the United
risks of incident cancer in the Ca+D and Ca-only groups
States. The goal was to determine whether low serum
were 0.402 (P=0.01) and 0.532 (P=0.06), respectively.
vitamin D concentrations are associated with hip fractures
When analysis was limited to cancer diagnosed after
in community-dwelling postmenopausal women. Case
the first 12 months, the relative risk for the Ca+D group
patients and matched control patients who were not on
fell to 0.232 (CI: 0.09, 0.60; P<0.005) but did not change
estrogen replacement or other bone-active therapies
significantly for the Ca-only group. The authors found
were followed for incident hip fracture for a median of 7.1
that in multiple logistic regression models both treatment
years. Women with serum vitamin D levels of less than
and serum vitamin D concentrations were “significant,
19 ng/mL had a higher fracture risk than did those with
independent predictors of cancer risk” and improvements
vitamin D levels 28.3 ng/mL (adjusted odds ratio: 1.71
in vitamin D nutritional status in postmenopausal women
[confidence interval: 1.05 to 2.79]). The authors noted
was associated with a reduced all-cancer risk.
the risk increased in a statistically significantly manner
across quartiles of serum vitamin D concentration (P for
Vitamin D and prevention of breast cancer: Pooled
trend = 0.016). Findings suggest an increased risk of hip analysis.
fracture for community-dwelling women with low serum Garland CF, Gorham ED, Mohr SB, et al. J Steroid Biochem Mol Biol. 2007 Mar;
vitamin D concentrations. 103(3-5):708-711.
The authors performed a meta-analysis of pooled
Serum 25-hydroxyvitamin D and hip fracture risk in dose-response data from two studies (The Harvard
older US white adults. Nurses Health and Saint Georges Hospital Studies).
Looker AC, Mussolino ME. J Bone Miner Res. 2008; 23(1):143-150.
This publication reported that individuals with serum
In this study, the authors evaluated the relationship vitamin D of approximately 52 ng/mL had a 50% lower
between serum vitamin D levels and incident hip risk for breast cancer than those with levels measuring
fracture risk in older non-Hispanic white adults. Data less than 13 ng/mL. This group concluded a daily intake
from the NHANES III cohort were mined using linked of 2000 IU/day and an additional 10 to 15 minutes of daily
mortality and Medicare records to identify incident hip sun exposure (an amount estimated to be equivalent
fracture cases for white men and women aged 65 or to an oral intake of 3000 IU of vitamin D3) would be
older. After correcting for age, diet, and several other associated with a 50% lower incidence of breast cancer.
confounders, the analysis showed that serum vitamin D
levels greater than 24 ng/mL were associated with a Circulating levels of vitamin D and colon and rectal
significant decrease in hip fracture risk. The data revealed cancer: the Physicians’ Health Study and a meta-
that higher serum vitamin D levels were associated with analysis of prospective studies.
decreased fracture risk in this cohort. Lee JE, Li H, Chan AT, Hollis BW et al. Cancer Prev Res (Phila). 2011;4(5):735-
743.
The authors performed a systematic review of articles
that evaluated the association between circulating
Vitamin D and Cancer vitamin D levels and colon and rectal cancer. They
conducted a meta-analysis of eight prospective studies
Vitamin D and calcium supplementation reduces of the relationship between circulating levels of 25-OH D
cancer risk: Results of a randomized trial.
Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. Am J Clin and colon and rectal cancers. The combined studies
Nutr. 2007 Jun; 85(6):1586-1591. included a total of 1822 colon and 868 rectal cancers.
Researchers from Creighton University evaluated the Statistical comparison of the top and bottom quantiles
effectiveness of calcium alone and calcium in addition of circulating 25-OH D levels revealed a significant
to vitamin D and its association in the reduction of inverse association for colorectal cancer (OR = 0.66; 95%
all-cancer incidence. One thousand one hundred CI: 0.54-0.81. The inverse association was stronger for
seventy- nine randomly selected community-dwelling rectal cancer with the lowest quantile of serum vitamin D
4
Q&A VITAMIN D: WHAT YOU NEED TO KNOW

levels experiencing double the number of rectal cancer

(OR = 0.50 for top versus bottom quantiles; 95% CI: 0.28- Vitamin D and Cesarean Delivery
0.88). The risk of colon cancer associated with the lower
25-OH D levels was lower than that of rectal cancer (OR = Association between vitamin D deficiency and
0.77; 95% CI: 0.56-1.07). The results of this meta-analysis primary cesarean section.
Merewood A, Mehta SD, Chen TC, Bauchner H, Holick MF. J Clin Endocrinol
of multiple studies suggest that colorectal cancer and Metab. 2009 Mar; 94(3):940-945.
circulating 25-OH D levels show an inverse association. Prior to the discovery of vitamin D and its role in healthy
The results also noted a stronger inverse association bone formation, many women died in childbirth. The
between circulating 25-OH D levels for rectal cancer. “rachitic” pelvises of women with profound vitamin D
deficiency did not allow the child to pass through,
Optimal vitamin D status for colorectal cancer
resulting in mortality. Vitamin D supplementation has
prevention: A quantitative meta analysis.
Gorham ED, Garland CF, Garland FC, et al. Am J Prev Med. 2007 Mar; essentially eliminated rickets and dramatically improved
32(3):210-216. pregnancy outcomes. A number of recent studies,
The authors performed a meta-analysis of data from five however, have indicated that vitamin D deficiency is
studies and reported that raising vitamin D levels may on the rise and, in the US, the cesarean birth rate has
reduce the incidence of colorectal cancer cases in the been climbing. In this study, the authors analyzed the
United States. They found a linear trend toward reduced relationship between maternal serum vitamin D levels
risk for colorectal cancer as the levels of serum vitamin D and the prevalence of primary cesarean section. Two
increased. Compared with a serum vitamin D level of hundred fifty-three women, 43 (17%) of whom had a
≤12 ng/mL, a level of ≥33 ng/mL was associated with primary cesarean section, were enrolled in the study. The
a 50% reduction in the incidence of colorectal cancer. authors found an inverse relationship between maternal
The authors concluded that a vitamin D3 intake of 1000 vitamin D levels and the probability of having a cesarean
to 2000 IU/day would confer an appropriate balance section. Twenty-eight percent of women with vitamin D
between protection against colorectal cancer and levels of less than 15 ng/mL had a cesarean section,
adverse events related to excessive vitamin D intake. while only 14% of women with vitamin D greater than
15 ng/mL had a cesarean section (P = 0.012). Based on
Circulating 25-hydroxyvitamin D levels and the multivariable logistic regression analysis with controls
survival in patients with colorectal cancer. that included race, age, education level, insurance status,
Ng K, Meyerhardt JA, Wu K, et al. J Clin Onc. 2008 Jun 20; 26:2984-2991.
The authors evaluated the association between and alcohol use, lower vitamin D levels in women was
measured vitamin D levels and mortality among 304 associated with four times more likely to have a cesarean
participants in the Nurses’ Health Study (NHS) and the than women with higher values (adjusted odds ratio
Health Professionals Follow-Up Study (HPFS) who were 3.84; 95% confidence interval: 1.71 to 8.62). The authors
subsequently diagnosed with colorectal cancer. Higher concluded that lower vitamin D levels were associated
measured vitamin D levels were associated with a with an increased likelihood of primary cesarean section.
significant reduction in overall mortality. Participants
in the lowest and highest quartiles were compared and
the highest quartile had an increased risk for overall Vitamin D and Heart Disease
mortality; HR=0.52 (95% CI: 0.29–0.94). Authors noted
a trend in improved colorectal cancer-specific mortality; Independent association of low serum
HR=0.61 (95% CI: 0.31–1.19). For overall mortality 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D
levels with all-cause and cardiovascular mortality.
comparing extreme quartiles, the multivariate hazard Dobnig H, Pilz S, Scharnagl H, et al. Arch Intern Med. 2008 Jun 23;
ratio was 0.45 (95% CI: 0.19–1.09). The authors concluded 168(12):1340-1349.
that colorectal cancer patients with higher plasma In this study, vitamin D levels were measured in 3258
vitamin D levels before the diagnosis were associated consecutive male and female patients scheduled for
with a significant improvement in overall survival. coronary angiography at a single tertiary center. The
follow-up period consisted of 7.7 years, and during this
time 737 patients (22.6%) died, 463 from cardiovascular
causes. Patients with vitamin D in the lowest quartile
5
Q&A VITAMIN D: WHAT YOU NEED TO KNOW

(median: 7.6 ng/mL) were at increased risk for all- event during a mean follow up of 5.4 years. Participants
cause mortality compared with patients in the highest with vitamin D levels of less than 15 ng/mL had a
25-OH D quartile (median: 28.4 ng/mL) HR=2.08 (95% CI: multivariable-adjusted hazard ratio (HR)=1.62 (95% CI:
1.60–2.70). Patients with vitamin D in the second highest 1.11–2.36), (P=0.01) for incident cardiovascular events
quartile (median: 13.3 ng/mL) were at increased risk for relative to participants with vitamin D levels in excess
all-cause mortality compared with patients in the highest of 15 ng/mL. Participants with hypertension observed
25-OH D quartile, HR=1.53 (95% CI: 1.17–2.01). Hazard an increased HR; HR=2.13 (95% CI: 1.30–3.48) but not in
ratios for patients in the lower two vitamin D quartiles those without hypertension; HR=1.04 (95% CI: 0.55–1.96).
were also higher for cardiovascular mortality (HR=2.22 The data showed a graded increase in cardiovascular risk
(95% CI: 1.57–3.13) and HR=1.82 (95% CI: 1.29–2.58), with decreased vitamin D levels, HR=1.80 (95% CI: 1.05-
respectively, compared with patients in the highest 3.08) for levels <10 ng/mL (P for linear trend=0.01).
25-hydroxyvitamin D quartile. These associations were
not linked to coronary artery disease, physical activity Low vitamin D levels predict stroke in patients
level, Charlson Comorbidity Index, variables of mineral referred to coronary angiography.
Pilz S, Dobnig H, Fischer JE, et al. Stroke. 2008 Sep; 39(9):2611-2613.
metabolism, and New York Heart Association functional
In this study, vitamin D levels of 25(OH)D were
class. The authors concluded there was an independent
measured in 3299 participants, and levels of
association with low vitamin D levels (25 OH vitamin D
1,25-dihydroxyvitamin D (1,25(OH)2D) were measured
and 1,25 dihydroxyvitamin D) and cardiovascular- and all-
in 3315 patients who were referred for coronary
cause mortality.
angiography. During a median follow- up period of
7.75 years, 769 patients died, including 42 from strokes.
25-Hydroxyvitamin D and risk of myocardial
infarction in men: A prospective study. Using binary logistic-regression analyses against survivor
Giovannucci E, Liu Y, Hollis BW, Rimm EB. Arch Intern Med. 2008 Jun comparison, the authors noted the odds ratios for fatal
9;168(11):1174-1180. stroke was 0.58 (95% CI: 0.43 to 0.78, P<0.001) per z value
The authors conducted a nested case-control study of of 25(OH)D and 0.62 (0.47 to 0.81, P<0.001) per z value of
18,225 men enrolled in the Health Professional Follow- 1,25(OH)2D. Confounders were noted and consideration
up Study who did not have a diagnosis of cardiovascular given, and the odds ratio remained significant for 25(OH)
disease at the time of blood draw. Four hundred fifty-four D at 0.67 (0.46 to 0.97, P=0.032) and 0.72 (0.52 to 0.99,
men developed nonfatal myocardial infarction (MI) or P=0.047) for 1,25(OH)2D. The authors concluded that a
fatal coronary heart disease during 10 years of follow- low level of vitamin D is predictive for fatal strokes and
up. Men with low vitamin D levels (≤15 ng/mL) were suggested that vitamin D supplementation has promise
at increased risk for MI compared with men who had for the prevention of strokes.
vitamin D levels considered to be sufficient (≥30 ng/mL)
(relative risk [RR], 2.42 [95% CI: 1.53–3.84; P <0.001] for
trend). The relationship remained significant even with
additional adjustment for family history and other risk
Vitamin D and Efficacy, Safety, and
factors (RR, 2.09 [95% CI: 1.24–3.54; P=0.02] for trend). It Demographics
was noted that men who had intermediate vitamin D
levels were also at elevated risk compared to those with Demographic differences and trends of vitamin D
higher vitamin D levels (22.6–29.9 ng/mL): RR, 1.60 (95%
insufficiency in the US population, 1988-2004.
Ginde AA, Liu MC, Camargo CA Jr. Arch Intern Med. 2009 Mar 23;169(6):
CI: 1.10–2.32); and 15.0–22.5 ng/mL: RR, 1.43 (95% CI: 626-632.
0.96–2.13), respectively. The goal of this study was to analyze the trends in
vitamin D levels in the US during the last two decades.
Vitamin D deficiency and risk of cardiovascular The authors performed a statistical analysis comparing
disease. the serum vitamin D levels of participants of the Third
Wang TJ, Pencina MJ, Booth SL, et al. Circ. 2008 Jan 29; 117(4):503-511.
National Health and Nutrition Examination Survey
In this study, vitamin D levels were measured in 1739
(NHANES III), collected from 1988 through 1994, with
participants of the Framingham Offspring Study who did
NHANES data collected from 2001 through 2004. The
not have prior cardiovascular disease. One hundred and
data revealed a trend for all populations studied; the
twenty participants experienced a first cardiovascular
6
Q&A VITAMIN D: WHAT YOU NEED TO KNOW

mean values and the entire distributions of vitamin D References

levels had shifted downward in the time between the 1. Souberbielle JC, Body JJ, Lappe JM et al. Vitamin D and musculoskeletal health,
cardiovascular disease, autoimmunity and cancer: Recommendations for clinical
survey collections. Serum vitamin D levels for the entire practice. Autoimmun Rev. 2010 Sep;9(11):709-15.

population studied was 30 ng/mL for the earlier study 2. IARC. Vitamin D and Cancer. IARC Working Group Reports Vol.5, International
Agency for research on Cancer, Lyon, 25 November 2008.
group and had decreased to 24 ng/mL for the later group. 3. Holick MF, Binkley NC, Bischoff-Ferrari HA et al. Evaluation, treatment, and prevention
Authors noted the percentage of the population with of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin
Endocrinol Metab. 2011 Jul;96(7):1-20.
vitamin D levels of 30 ng/mL or more saw a decrease from 4. IOM (Institute of Medicine). Dietary reference intakes for calcium and vitamin D.
45% for the earlier group to 23% for the later group. In Washington DC: The National Academies Press; 2011.

non-Hispanic blacks, vitamin D serum levels of less than 5. Chen P, Hu P, Xie D et al. Meta-analysis of vitamin D, calcium and the prevention of
breast cancer. Breast Cancer Res Treat. 2010 Jun;121(2):469-77.
10 ng/mL rose from 9% for the early group to 29% for 6. Hypponen E, Power C. Hypovitaminosis D in British adults at age 45 y: Nationwide
the later group. A decrease of vitamin D levels was also cohort study of dietary and lifestyle predictors. Am J Clin Nutr. 2007 Mar; 85(3):860-868.
7. Binkley N, Novotny R, Krueger D, et al. Low vitamin D status despite abundant sun
noted in non-Hispanic blacks in the prevalence of levels exposure. J Clin Endocrinol Metab. 2007 Jun; 92(6):2130-2135.
of 30 ng/mL or more from 12% to 3%. In the most recent 8. Institute of Medicine Report Brief: Dietary Reference Intake for Calcium
and Vitamin D. November 2010. Washington, DC: National Academy of Sciences; 2011.
NHANES population studied (2001-2004) more than
9. Heaney RP, Davies KM, Chen TC, et al. Human serum 25-hydroxycholecalciferol
60% of non-Hispanic whites had vitamin D insufficiency response to extended oral dosing with cholecalciforol. Am J Clin Nutr. 2003; 77:204-210.
(defined as serum levels less than 30 ng/mL). Vitamin D 10. Endres DB, Rude RK. Mineral and bone metabolism. In: Burtis CA, Ashwood ER, eds.
Tietz Textbook of Clinical Chemistry. 3rd ed. Philadelphia, Pa: W.B. Saunders; 1999:1395-
insufficiency was shown in 97% of non-Hispanic blacks 1457.
and 90% of Mexican Americans. The authors concluded 11. Armas LA, Hollis BW, Heaney RP. Vitamin D2 is much less effective than vitamin D3 in
humans. J Clin Endocrinol Metab. 2004 Nov; 89(11):5387-5391.
that a marked decrease in serum vitamin D levels
12. Centers for Disease Control and Prevention. National Health and Nutrition
had occurred from the 1988-1994 to the 2001-2004 Examination Survey. 2005 - 2006 Data Documentation, Codebook, and Frequencies.
Available at: http://www.cdc.gov/nchs/nhanes/nhanes2005-2006/VID_D.htm. Accessed
NHANES data collections. The data revealed racial/ethnic December 16, 2011.
differences in vitamin D levels, which may have some 13. Jackson RD, LaCroix AZ, Gass M et al. Calcium plus vitamin D supplementation and
the risk of fractures. NEJM. 2006 Feb 16;354(7):669-683.
role in the etiology of known health disparities between
14. Wu K, Feskanich D, Fuchs CS, Willett WC, Hollis BW, Giovannucci EL. A nested case-
races and ethnic groups. The authors commented there control study of plasma 25-hydroxyvitamin D concentrations and risk of colorectal
is an epidemic of vitamin D insufficiency and current cancer. J Natl Cancer Inst. 2007 July 18;99(14):1120-1128.
15. Eliassen AH, Spiegelman D, Hollis BW et al. Plasma 25-hydroxyvitamin D and risk of
recommendations for vitamin D supplementation were breast cancer in the Nurses’ Health Study II. Breast Cancer Research. 2011. 13:R50.
not adequate to address the epidemic.

Vitamin D: Criteria for safety and efficacy.

Heaney RP. Nutr Rev. 2008; 66(10 Suppl 2):S178-181.
In this comprehensive review of numerous recent
publications, Dr Heaney concluded that serum vitamin D
levels greater than 80 nmol/L may be required to achieve
several health endpoints involving bone, neuromuscular
function, cancer, and immune function. The author
provides support for the contention that a daily intake
of 1000 to 2000 IU of D3 from combined sources (food,
cutaneous production, and supplements) is required
to achieve this level (80 nmol/L). The review also
summarized published findings that vitamin D toxicity
from excessive supplemental intake has only rarely been
shown to occur at serum levels less than 500 nmol/L.
Finally, this review summarizes a number of published
studies that have shown that vitamin D supplementation
with levels as high as 10,000 IU/day has not been
associated with toxicity.

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Q&A VITAMIN D: WHAT YOU NEED TO KNOW

Q: What vitamin D tests does LabCorp offer? LabCorp also offers the following specialized
A: LabCorp offers several vitamin D tests that may be vitamin D tests.
useful in certain clinical applications.
Calcitriol (1,25 di-OH Vitamin D)
Vitamin D, 25-Hydroxy (Total Vitamin D) Measurement of 1,25 dihydroxy vitamin D levels may be
Vitamin D, 25-Hydroxy provides the simplest method useful in the assessment of disorders of calcium metabolism
for the assessment of overall vitamin D status and for and parathyroid disease. This test should not be ordered
the diagnoses of deficiency or toxicity. Low blood levels for assessment of overall vitamin D status. Levels of 1,25-D
of 25-hydroxy vitamin D may mean an individual is not can often be normal in individuals with overall vitamin D
getting enough exposure to sunlight or not enough deficiency. The 1,25 Dihydroxy Vitamin D test uses column
dietary vitamin D to meet the body’s demand, or there
chromatograph, radioimmunassay (RIA) methodology. For
may be an issue with its absorption from the intestines.
ordering information, please consult LabCorp’s Directory of
High levels of 25-hydroxy vitamin D usually reflect excess
Services and Interpretive Guide.
supplementation from vitamin pills or other nutritional
supplements. LabCorp’s Vitamin D, 25-Hydroxy test
Vitamin D, 25-OH, Fractionated (Total, D2, D3), HPLC/MS-MS
employs immunochemiluminometric methodology and
Available through our Endocrine Sciences laboratory in
is performed on the DiaSorin LIAISON® instrument at
Calabasas, Calif, this test provides clinicians with the levels
LabCorp. This highly automated test measures both D2
of D2 and D3 vitamin D as well as the total. D2 levels can
and D3 together and reports a total 25-hydroxy vitamin D.
become measurable when patients are supplemented with
Some major clinical studies, including (but not limited to)
high-dose D2; however, many individuals tested may have
the Centers for Disease Control (CDC) National Health and
no detectable vitamin D2. Only vitamin D3 is produced by
Nutrition Examination Survey (NHANES) data base, the
Women’s Health Initiative (WHI) studies, and the Harvard- the body. The Vitamin D, 25 OH Fractionated Total D2 and
based Health Professionals Studies, have employed D3 assay uses isotope dilution tandem mass spectrometry
DiaSorin reagents.12-15 with HPLC after extraction (HPLC-MS/MS). For ordering
information, please contact your local representative.

Test Name Test No.

Vitamin D, 25-Hydroxy 081950
Visit the online Test Menu at www.LabCorp.com
for full test information, including CPT codes and
specimen collection requirements.

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