Article

Vitamin D 2 Is as Effective as Vitamin D 3 in Maintaining Circulating Concentrations of 25-Hydroxyvitamin D

Department of Medicine, Boston University School of Medicine, 715 Albany Street, M-1013, Boston, Massachusetts 02118, USA.
Journal of Clinical Endocrinology & Metabolism (Impact Factor: 6.21). 04/2008; 93(3):677-81. DOI: 10.1210/jc.2007-2308
Source: PubMed
ABSTRACT
Two reports suggested that vitamin D2 is less effective than vitamin D3 in maintaining vitamin D status.
Our objective was to determine whether vitamin D2 was less effective than vitamin D3 in maintaining serum 25-hydroxyvitamin D levels or increased the catabolism of 25-hydroxyvitamin D3.
This was a randomized, placebo-controlled, double-blinded study of healthy adults ages 18-84 yr who received placebo, 1000 IU vitamin D3, 1000 IU vitamin D2, or 500 IU vitamin D2 plus 500 IU vitamin D3 daily for 11 wk at the end of the winter.
Sixty percent of the healthy adults were vitamin D deficient at the start of the study. The circulating levels of 25-hydroxyvitamin D (mean+/-sd) increased to the same extent in the groups that received 1000 IU daily as vitamin D2 (baseline 16.9+/-10.5 ng/ml; 11 wk 26.8+/-9.6 ng/ml), vitamin D3 (baseline 19.6+/-11.1 ng/ml; 11 wk 28.9+/-11.0 ng/ml), or a combination of 500 IU vitamin D2 and 500 IU vitamin D3 (baseline 20.2+/-10.4 ng/ml; 11 wk 28.4+/-7.7 ng/ml). The 25-hydroxyvitamin D3 levels did not change in the group that received 1000 IU vitamin D2 daily. The 1000 IU dose of vitamin D2 or vitamin D3 did not raise 25-hydroxyvitamin D levels in vitamin D-deficient subjects above 30 ng/ml.
A 1000 IU dose of vitamin D2 daily was as effective as 1000 IU vitamin D3 in maintaining serum 25-hydroxyvitamin D levels and did not negatively influence serum 25-hydroxyvitamin D3 levels. Therefore, vitamin D2 is equally as effective as vitamin D3 in maintaining 25-hydroxyvitamin D status.

Full-text

Available from: Tai C Chen, Jan 25, 2016
Vitamin D
2
Is as Effective as Vitamin D
3
in
Maintaining Circulating Concentrations of
25-Hydroxyvitamin D
Michael F. Holick, Rachael M. Biancuzzo, Tai C. Chen, Ellen K. Klein, Azzie Young, Douglass Bibuld,
Richard Reitz, Wael Salameh, Allen Ameri, and Andrew D. Tannenbaum
Endocrine Section (M.F.H., R.M.B., T.C.C., E.K.K., A.A., A.D.T.), Department of Medicine, Boston University School of Medicine, Boston,
Massachusetts 02118; Mattapan Community Health Center (A.Y., D.B.), Mattapan, Massachusetts 02126; and Quest Diagnostics Nichols
Institute (R.R., W.S.), San Juan Capistrano, California 92675
Context: Two reports suggested that vitamin D
2
is less effective than vitamin D
3
in maintaining
vitamin D status.
Objective: Our objective was to determine whether vitamin D
2
was less effective than vitamin D
3
in
maintaining serum 25-hydroxyvitamin D levels or increased the catabolism of 25-hydroxyvitamin D
3
.
Subjects and Design: This was a randomized, placebo-controlled, double-blinded study of healthy
adults ages 1884 yr who received placebo, 1000 IU vitamin D
3
, 1000 IU vitamin D
2
, or 500 IU
vitamin D
2
plus 500 IU vitamin D
3
daily for 11 wk at the end of the winter.
Results: Sixty percent of the healthy adults were vitamin D deficient at the start of the study. The
circulating levels of 25-hydroxyvitamin D (mean
SD) increased to the same extent in the groups that
received 1000 IU daily as vitamin D
2
(baseline 16.9 10.5 ng/ml; 11 wk 26.8 9.6 ng/ml), vitamin D
3
(baseline 19.6 11.1 ng/ml; 11 wk 28.9 11.0 ng/ml), or a combination of 500 IU vitamin D
2
and 500
IU vitamin D
3
(baseline 20.2 10.4 ng/ml; 11 wk 28.4 7.7 ng/ml). The 25-hydroxyvitamin D
3
levels did
not change in the group that received 1000 IU vitamin D
2
daily. The 1000 IU dose of vitamin D
2
or
vitamin D
3
did not raise 25-hydroxyvitamin D levels in vitamin D-deficient subjects above 30 ng/ml.
Conclusion: A 1000 IU dose of vitamin D
2
daily was as effective as 1000 IU vitamin D
3
in maintaining
serum 25-hydroxyvitamin D levels and did not negatively influence serum 25-hydroxyvitamin D
3
levels. Therefore, vitamin D
2
is equally as effective as vitamin D
3
in maintaining 25-hydroxyvitamin
D status. (J Clin Endocrinol Metab 93: 677– 681, 2008)
V
itamin D
2
, which comes from the UV irradiation of ergos
-
terol obtained from yeast, has been the mainstay for the
prevention and treatment of vitamin D deficiency in children and
adults for more than 80 yr (1, 2). As little as 100 IU vitamin D
2
was found to be effective in the prevention of rickets(2– 4). When
humans are exposed to sunlight, 7-dehydrocholesterol in the skin
absorbs UVB (290 –315 nm) radiation resulting in the produc-
tion of vitamin D
3
(1, 3). Vitamin D
3
is found naturally in cod
liver oil and oily fish such as salmon (1, 3). Vitamin D
3
is also
made by irradiating 7-dehydrocholesterol obtained from lanolin
from sheep’s wool with UVB radiation (1). Both vitamin D
2
and
vitamin D
3
when ingested undergo metabolism in the liver to
form 25-hydroxyvitamin D [25(OH)D; D represents either D
2
or
D
3
] and in the kidneys to 1,25-dihydroxyvitamin D (1, 3, 5, 6).
Both vitamin D
2
and vitamin D
3
are available in supplements,
but only vitamin D
2
is available as a pharmaceutical preparation
because its use predated the Food and Drug Administration and,
thus, was grandfathered as a pharmaceutical drug. Vitamin D
3
was commercially developed in the 1950s and has not been ap-
proved as a pharmaceutical agent in the United States but is used
in food supplementation and vitamin supplements.
Since the 1930s, vitamin D
2
has been considered to be equally
0021-972X/08/$15.00/0
Printed in U.S.A.
Copyright © 2008 by The Endocrine Society
doi: 10.1210/jc.2007-2308 Received October 15, 2007. Accepted December 10, 2007.
First Published Online December 18, 2007
Abbreviation: 25(OH)D, 25-Hydroxyvitamin D.
ORIGINAL ARTICLE
Endocrine Care
J Clin Endocrinol Metab, March 2008, 93(3):677– 681 jcem.endojournals.org 677
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Page 1
as effective as vitamin D
3
for bone health (3, 7). Recently, it was
suggested that vitamin D
2
was less effective than vitamin D
3
in
maintaining serum 25(OH)D levels when given either as 4000
IU/d for 2 wk (8) or as a single dose of 50,000 IU (9). Further-
more, it was observed that when a single dose of 50,000 IU
vitamin D
2
was given to healthy adults that the serum 25(OH)D
levels decreased more rapidly than the placebo group, suggesting
that vitamin D
2
not only was less effective in maintaining serum
25(OH)D levels but also enhanced the degradation of25(OH)D
3
(9).
These two observations have led to the conclusion that vita-
min D
2
is approximately 30 –50% as effective as vitamin D
3
in
maintaining serum 25(OH)D in humans (8, 9). Our purpose was
to evaluate in healthy adults what the effect of ingesting 1000 IU
vitamin D
2
, 1000 IU vitamin D
3
, or a combination of 500 IU
vitamin D
2
and 500 IU vitamin D
3
daily for 11 wk at the end of
the winter had on circulating levels of total 25(OH)D as well as
25(OH)D
2
and 25(OH)D
3
.
Subjects and Methods
Subjects
Healthy, white, African-American, Hispanic, Asian, and Native
American adults between the ages of 18 and 84 yr were enrolled in
February 2007 after signing a consent formapproved by our Institutional
Review Board at Boston University Medical Center. We excluded those
with chronic liver and kidney disease and those taking medications, in-
cluding anticonvulsants, glucocorticoids, and barbiturates, that might
affect vitamin D metabolism as well as subjects who were taking a vi-
tamin D supplement. Subjects were permitted to take their multivitamin,
a majority of which contained 400 IU vitamin D
3
(Table 1
).
Design
Sixty-eight subjects were randomly assigned in a double-blinded
fashion to receive daily in a capsule for 11 wk 1) placebo, 2) 1000 IU (25
g) vitamin D
2
(ergocalciferol), 3) 1000 IU (25
g) vitamin D
3
(chole
-
calciferol), or 4) 500 IU vitamin D
2
plus 500 IU vitamin D
3
. All of the
capsules made by Tishcon Corp. (Salisbury, MD) contained lactose
(98.75%), magnesium stearate (1.0%), and silicon dioxide (1.25%). All
of the products were analyzed in our laboratory by HPLC and found to
contain either no vitamin D (placebo) or concentrations within 10% of
their specified content. All subjects had blood samples collected at base-
line and every week for a total of 11 wk. Each subject was given a dietary
questionnaire at baseline to assess multivitamin and milk consumption.
Pill compliance (Table 1) was determined by a pill count at each visit.
Analytical methods
Serum 25(OH)D
2
and 25(OH)D
3
were determined by liquid chro
-
matography tandem mass spectroscopy at Quest Diagnostics Nichols
Institute, San Juan Capistrano, CA (10). The detection limit for the assay
was 4 ng/ml, and the interassay coefficient of variation was about 10%.
Values for serum 25(OH)D
2
reported as less than 4 ng/ml were obtained
by subtracting 25(OH)D
3
from the total 25(OH)D.
Statistical methods
The results are presented as means SD. Data were analyzed using
mixed-effects regression to perform a repeated-measures analysis of
25(OH)D levels across time and groups. Pairwise comparisons were
TABLE 1. Subject demographics
Characteristics
Placebo group
(n 14)
D
2
D
3
group
(n 18)
D
3
group
(n 20)
D
2
group
(n 16)
Age (yr)
Mean
SD 40.5 11.7 35.5 14.6 40.0 18.0 38.4 12.0
Range 22–59 18–70 2081 18–59
Females, n (%) 11 (78.6) 13 (72.2) 13 (65) 10 (62.5)
Males, n (%) 3 (21.4) 5 (27.8) 7 (35) 6 (37.5)
Body mass index 29.3 31.7 30.0 31.0
Multivitamin, n (%) 6 (42.9) 4 (22.2) 5 (25) 6 (37.5)
Multivitamin-D
3
, n (%)
4 (28.6) 3 (16.7) 5 (25) 6 (37.5)
Vitamin D supplement intake 0 0 0 0
Dropout, n (%) 4 (20) 2 (10) 0 (0) 4 (20)
Menopausal status, n (%) 3 (21.4) 2 (11.1) 5 (25) 3 (18.8)
Oral contraceptive pill use, n (%) 0 (0) 2 (11.1) 1 (5) 0 (0)
Compliance (%) 96.6 95.0 95.3 93.6
Mean initial 25(OH)D
SD (ng/ml) 18.6 8.9 20.2 10.4 19.6 11.1 16.9 10.5
Mean final 25(OH)D
SD (ng/ml) 18.8 7.9 28.4 7.7 28.9 11.0 26.8 9.6
Mean differences SD 0.2 5.3 8.2 7.8
a,d
9.3 7.1
b,d
9.9 3.2
c,d
95% CI 2.6–3.0 4.6–11.8 6.2–12.7 5.2–14.6
Demographics, n (%)
Asian 2 (14.3) 1 (5.6) 4 (20) 1 (6.3)
American Indian 0 (0) 0 (0) 0 (0) 1 (6.3)
Black 6 (42.9) 9 (50) 8 (40) 9 (56.3)
Hispanic 0 (0) 2 (11.1) 2 (10) 1 (6.3)
White 6 (42.9) 6 (33.3) 6 (30) 4 (25)
CI, Confidence interval.
a
P 0.041 for D
3
D
2
vs. placebo.
b
P 0.027 for D
3
vs. placebo.
c
P 0.023 for D
2
vs. placebo.
d
No statistically significant difference between D
3
D
2
,D
3
, and D
2
(P 0.957).
678 Holick et al. Vitamin D
2
in Maintaining 25(OH)D J Clin Endocrinol Metab, March 2008, 93(3):677–681
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Page 2
performed between all treatment groups as well as each treatment group
vs. placebo. Interactions between treatment group and time compared
the linear change in 25(OH)D over time between the groups. A repeated-
measures mixed-effect model also compared the 25(OH)D
2
and
25(OH)D
3
across visits for each of the treatment groups. Statistical anal
-
ysis was performed using SAS (SAS Institute, Inc., Cary, NC).
Results
Sixty percent of our healthy adult subjects were vitamin D
deficient [25(OH)D 20 ng/ml], and 87% were insufficient
[25(OH)D 30 ng/ml], even though about 29% took a mul-
tivitamin daily that contained 400 IU vitamin D and about
47% drank about 1.2 glasses of milk per day. Adults who
received the placebo capsule daily for 3 months demonstrated
no significant change in their total 25(OH)D levels during the
winter and early spring (Fig. 1). Adults who ingested 1000 IU
vitamin D
2
/d gradually increased their total 25(OH)D levels
from 16.9 10.5 ng/ml to 25.8 6.6 ng/ml during the first
6 wk and then remained stable (Fig. 1). Adults who ingested
1000 IU vitamin D
3
had a baseline 25(OH)D of 19.6 11.1
ng/ml that was statistically no different from the baselines of
either the placebo group or the groups that took 1000 IU
vitamin D
2
/d or 500 IU vitamin D
2
plus 500 IU vitamin D
3
/d
(P 0.79). The vitamin D
3
group increased their serum
25(OH)D levels similar to that of the group that ingested
vitamin D
2.
The 25(OH)D levels in the vitamin D
3
group
began to plateau by wk 6 and was 28.9 11.0 ng/ml at the end
of the study, which was not statistically different from the
vitamin D
2
group (26.8 9.6 ng/ml) (Fig. 1).
To determine whether vitamin D
2
ingestion had any effect
on circulating levels of 25(OH)D
3
, we determined 25(OH)D
2
and 25(OH)D
3
in the samples. The 25(OH)D
2
levels increased
from undetectable (4 ng/ml) to 14 5.3 ng/ml by wk 6 and
remained at approximately 14 ng/ml for the ensuing 5 wk in
the group that received 1000 IU vitamin D
2
(Fig. 2
A). The
baseline 25(OH)D
3
level in the same subjects was 15.1 9.8
ng/ml and did not significantly change during the entire study
and was 13.6 10.2 ng/ml at the end of the study (P 0.14)
(Fig. 2A). Similarly, the group that received vitamin D
3
showed no significant change in the serum 25(OH)D
2
throughout the study (P 0.33) (Fig. 2B).
To determine further whether vitamin D
2
interfered with
vitamin D
3
metabolism, we gave one group of subjects 500 IU
vitamin D
2
mixed with 500 IU vitamin D
3
. The rise in the total
25(OH)D was identical to that observed for the groups who
received either 1000 IU vitamin D
2
or 1000 IU vitamin D
3
FIG. 1. Mean ( SEM) serum 25(OH)D levels after oral administration of
vitamin D
2
and/or vitamin D
3
. Healthy adults recruited at the end of the
winter received placebo (F;n 14), 1000 IU vitamin D
3
(D
3
, f;n 20), 1000
IU vitamin D
2
(D
2
, Œ;n 16), or 500 IU vitamin D
2
and 500 IU vitamin D
3
[D
2
and D
3
, ;n 18) daily for 11 wk. The total 25(OH)D levels are
demonstrated over time. *, P 0.027 comparing 25(OH)D over time between
vitamin D
3
and placebo; **, P 0.041 comparing 25(OH)D over time
between 500 IU vitamin D
3
plus 500 IU vitamin D
2
and placebo; ***, P
0.023 comparing 25(OH)D over time between vitamin D
2
and placebo.
FIG. 2. Effect of vitamin D
2
or vitamin D
3
on serum 25(OH)D
2
and 25(OH)D
3
levels. Serum levels of 25(OH)D
2
(f) and serum 25(OH)D
3
() were measured in
healthy subjects receiving 1000 IU vitamin D
2
(A), 1000 IU vitamin D
3
(B), or 500
IU vitamin D
2
plus 500 IU vitamin D
3
(C) daily for 11 wk. Results are presented as
means
SEM over time. *, P 0.0001 comparing 25(OH)D
2
between baseline
and 11 wk (A); *, P 0.0001 comparing 25(OH)D
3
between baseline and 11
wk (B); *, P 0.0014 comparing between 25(OH)D
3
and placebo group (C); **,
P 0.0031 comparing 25(OH)D
2
and placebo group (C). Note serum 25(OH)D
2
levels less than 4 ng/ml were obtained by subtracting the total 25(OH)D
3
from
the total 25(OH)D levels.
J Clin Endocrinol Metab, March 2008, 93(3):677– 681 jcem.endojournals.org 679
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Page 3
daily, and the total 25(OH)D levels at the end of the study
were no different in all three groups (P 0.957) (Fig. 1). An
analysis of the 25(OH)D
2
and 25(OH)D
3
also demonstrated
a comparable increase in both levels in the group that received
the combination of 500 IU vitamin D
2
(5.7 4.5 ng/ml) and
500 IU vitamin D
3
(6.1 4.3 ng/ml) (Fig. 2C).
Discussion
Many multivitamin preparations and some foods are fortified
with vitamin D
2
. Two recent observations have raised questions
as to whether vitamin D
2
should be used either as a pharmaceu
-
tical agent or as a supplement because it appeared that vitamin
D
2
not only was less effective than vitamin D
3
in maintaining
25(OH)D levels (8, 9) but that it also had a negative effect on
25(OH)D status (9). There has also been concern that vitamin D
2
may not be bioequivalent to vitamin D
3
in maintaining bone
health (11).
The Food and Nutrition Board has recommended that adults
up to the age of 50 yr require 200 IU vitamin D/d, whereas adults
51–70 yr and 71 yr and older require 400 and 600 IU/d, respec-
tively (12). However, many experts now agree that in the absence
of adequate sun exposure, at least 1000 IU vitamin D/d is re-
quired to maintain 25(OH)D in the sufficient range (1, 13).
Because the placebo group did not demonstrate any change in
their circulating levels of 25(OH)D, there was little influence of
environmental sun exposure or dietary or supplemental vitamin
D intake on their vitamin D status. Subjects who received 1000
IU vitamin D
2
or 1000 IU vitamin D
3
daily gradually increased
blood levels of 25(OH)D to the same levels throughout the study.
The increase from baseline in the total 25(OH)D levels at the end
of the study was 9.3 ng/ml for the vitamin D
3
group, 9.9 ng/ml
for the vitamin D
2
group, and 8.2 ng/ml for the vitamin D
2
plus
vitamin D
3
group, which is consistent with the observation that
serum 25(OH)D levels increased by 1 ng/ml for every 100 IU
vitamin D
3
(14). However, the 25(OH)D levels did not rise above
30 ng/ml, which is now considered to be the vitamin D-sufficient
range, suggesting that more than 1000 IU vitamin D
2
or vitamin
D
3
is necessary to maintain serum 25(OH)D levels above 30
ng/ml when the sun provides no vitamin D
3
.
Armas et al. (9) reported that a single dose of 50,000 IU
vitamin D
2
was less effective than 50,000 IU vitamin D
3
in main
-
taining serum 25(OH)D levels over the ensuing 30 d in the sum-
mer. Furthermore, when compared with the group that received
placebo, the group that received 50,000 IU vitamin D
2
had a
significant reduction in serum 25(OH)D at the end of the study.
We did not observe any negative influence of vitamin D
2
on
either total 25(OH)D or 25(OH)D
3
levels (Figs. 1 and 2). The
maintenance of the serum 25(OH)D
3
levels observed in this re
-
port (Fig. 1) was most likely due to the release of vitamin D
3
stored in the body fat because skin synthesis of vitamin D
3
does
not occur during the winter in Boston (1). It is possible that a
single pharmacological dose of vitamin D
2
enhanced the destruc
-
tion of both vitamin D
2
and vitamin D
3
and their 25-hydroxy
derivatives. However, when 50,000 IU vitamin D
2
was given
weekly for 8 wk (15) or twice a week for 5 wk (16), there was on
average a 100% increase in serum 25(OH)D levels (15) and a
significant increase in bone mineral density in both the hip and
spine (16). Thus, vitamin D
2
when given in pharmacological
doses is effective in maintaining serum 25(OH)D levels and is
beneficial for skeletal health (16). Why Trang et al. (8) observed
that the daily dosing of 4000 IU vitamin D
3
for 2 wk was 1.7
times more effective in raising blood levels of 25(OH)D (in-
creased 9.0 2 ng/ml) than 4000 IU vitamin D
2
/d (increased
4.2 2 ng/ml) is unclear at this time. The rise in serum
25(OH)D
3
was only about 20% of what would have been ex
-
pected for a 4000 IU dose, i.e. 40 ng/ml. This may be due to their
ethanol formulation. This could also be due to the short time
course because we observed that 25(OH)D levels did not begin
to plateau until 6 wk. When vitamin D
2
was combined with
vitamin D
3
, there was no significant difference in the rise in
25(OH)D (Fig. 1). Furthermore, the group that received 1000 IU
vitamin D
2
had no significant change in the level of 25(OH)D
3
,
suggesting that vitamin D
2
at least at 1000 IU/d had no influence
on the catabolism of vitamin D
3
or 25(OH)D
3
. Thus, 1000 IU
vitamin D
2
/d is as effective as vitamin D
3
in maintaining
25(OH)D status. These observations are consistent with those of
Markestad et al. (17) and Rapuri et al. (18) who observed that
vitamin D
2
and vitamin D
3
contributed equally to serum
25(OH)D levels in mothers and their neonates and elderly
women, respectively. Furthermore, the concentrations of 1,25-
dihydroxyvitamin D
2
and 1,25-dihydroxyvitamin D
3
were re
-
ported to be proportional to the distribution of 25(OH)D
2
and
25(OH)D
3
(19, 20), implying that the 25(OH)D-1-hydroxylase
(CYP27B-1) recognized 25(OH)D
2
equally as well as
25(OH)D
3
. Therefore, collectively, these data and our results
suggest that vitamin D
2
is as effective as vitamin D
3
in sustaining
both 25(OH)D and 1,25(OH)
2
D levels (19, 20) and improving
bone health (16). More studies are needed to determine whether
the carrier (i.e. ethanol vs. oil vs. lactose) that vitamin D
2
and
vitamin D
3
are dissolved in influence either their bioavailability
or catabolism. Our observations also suggest that 1000 IU vita-
min D
2
or vitamin D
3
is required to sustain blood levels of
25(OH)D above a mean of 20 ng/ml but was insufficient in rais-
ing the levels above a mean of 30 ng/ml.
Acknowledgments
We thank Lindsey Minion, Bernadette Folly, Thomas Peeples, Sr.,
Horace Shearer, Johanna Gusman, Tarma Johnson, and Deborah Lan-
caster for their help with the study; Tim Heeren for his statistical acumen;
and Donna Gendron and Lorrie MacKay for their secretarial assistance.
Address all correspondence and requests for reprints to: Michael F.
Holick, Boston University School of Medicine, 715 Albany Street,
M-1013, Boston, Massachusetts 02118. E-mail: mfholick@bu.edu.
This work was supported by National Institutes of Health Grant
M01RR00533 and The Beverage Institute for Health and Wellness, a
Division of The Coca-Cola Co., Atlanta, GA.
Disclosure Statement: M.F.H. is on the Speaker’s Bureau for Merck,
Proctor and Gamble, and Eli Lilly and a consultant for Amgen, Novartis,
Quest Diagnostics, Proctor and Gamble, and Merck. R.M.B., T.C.C.,
E.K.K., A.Y., D.B., W.S., A.A., and A.D.T. have nothing to declare. R.R.
is Medical Director ofQuest Diagnostics/Nichols Institute andhas equity
interests in Quest Diagnostics/Nichols Institute.
680 Holick et al. Vitamin D
2
in Maintaining 25(OH)D J Clin Endocrinol Metab, March 2008, 93(3):677–681
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Page 4
References
1. Holick MF 2007 Vitamin D deficiency. N Engl J Med 357:266 –281
2. Eliot MM, Park EA 1938 Rickets. In: Brennemann’s practice of pediatrics. Vol.
1. Hagerstown, MD: WF Prior; 1–110
3. Holick MF 2006 Resurrection of vitamin D deficiency and rickets. J Clin Invest
116:2062–2072
4. Jeans PC 1950 Vitamin D. JAMA 143:177–181
5. Dusso AS, Brown AJ, Slatopolsky 2005 Vitamin D. Am J Physiol Renal Physiol
289:F8–F28
6. DeLuca H 2004 Overview of general physiologic features and functions of
vitamin D. Am J Clin Nutr 80(Suppl):1689S–1696S
7. Selye, H 1932 On the stimulation of new bone-formation with parathyroid
extract and irradiated ergosterol. Endocrinology 16:547–588
8. Trang HM, Cole DEC, Rubin LA, Pierratos A, Siu S, Vieth R 1998 Evidence
that vitamin D
3
increases serum 25-hydroxyvitamin D more efficiently than
does vitamin D
2
. Am J Clin Nut 68:854 858
9. Armas LAG, Hollis B, Heaney RP 2004 Vitamin D
2
is much less effective than
vitamin D
3
in humans. J Clin Endocrinol Metab 89:5387–5391
10. Holick MF,SirisES, Binkley N, Beard MK, Khan A, Katzer JT, Petruschke RA,
Chen E, de Papp AE 2005 Prevalence of vitamin D inadequacy among post-
menopausal North American women receiving osteoporosis therapy. J Clin
Endocrinol Metab 90:3215–3224
11. Glendenning P 2002 Vitamin D deficiency and multicultural Australia. Med J
Aust 176:242–243
12. Standing Committee on the Scientific Evaluation of Dietary Reference Intakes
Food and Nutrition Board, Institute of Medicine 1999 Dietary reference in-
takes for calcium, phosphorus, magnesium, vitamin D and fluoride. Wash-
ington, DC: National Academy Press
13. Vieth R, Bischoff-Ferrari H, Boucher BJ, Dawson-Hughes B, Garland C,
Heaney RP, Holick MF, Hollis BW, Lamberg-Allardt C, McGrath JJ, Norman
Aw, Scragg R, Whiting SJ, Willett WC, Zittermann A 2007 The urgent need
to recommend an intake of vitamin D that is effective. Am J Clin Nutr 85:
649650
14. Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ 2003 Human
serum 25-hydroxycholecalciferol response to extended oral dosing with chole-
calciferol. Am J Clin Nutr 77:204 –210
15. Malabanan A, Veronikis IE, Holick MF 1998 Redefining vitamin D insuffi-
ciency. Lancet 351:805–806
16. Adams JS, Kantrorovich V, Wu C, Javanbakht M, Hollis BW 1999 Resolution
of vitamin D insufficiency in osteopenic patients results in rapid recovery of
bone mineral density. J Clin Endocrinol Metab 84:2729 –2730
17. Markestad T, Aksnes L, Ulstein M, Aarskog D 1984 25-Hydroxyvitamin D
and 1,25-dihydroxyvitamin D of D
2
and D
3
origin in maternal and umbilical
cord serum after vitamin D
2
supplementation in human pregnancy. Am J Clin
Nutr 40:1057–1063
18. Rapuri PB, Gallagher JC, Haynatzki G 2004 Effect of vitamins D
2
and D
3
supplement use on serum 25(OH)D concentration in elderly women in summer
and winter. Calcif Tissue Int 74:150 –156
19. Clemens TL, Zhou XY, Myles M, Endres D, Lindsay R 1986 Serum vitamin
D
2
and vitamin D
3
metabolite concentrations and absorption of vitamin D
2
in
elderly subjects J Clin Endocrinol Metab 63:656 660
20. Hartwell D, Hassager C, Christiansen C 1987 Effect of vitamin D
2
and vitamin
D
3
on the serum concentrations of 1,25(OH)
2
D
2
in normal subjects. Acta
Endocrinol (Copenh) 115:378–384
J Clin Endocrinol Metab, March 2008, 93(3):677– 681 jcem.endojournals.org 681
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    • "Vitamin D 3 is mainly produced in the skin via photolysis of 7-DHC through a two-step process in which the B-ring is broken in a photolytic process driven by ultraviolet B (UVB) irradiation, giving the previtamin D 3 [4]. Previtamin D 3 very It is well established that vitamin D 2 is as effective as vitamin D 3 in maintaining the proper level of the main circulating vitamin D metabolite, which is 25-hydroxyvitamin D (25(OH)D) [5]. Vitamin D is biologically inert and regardless of the source it requires two subsequent steps of hydroxylations to gain activity. "
    [Show abstract] [Hide abstract] ABSTRACT: Vitamin D is a lipid soluble steroid hormone with pleiotropic biological properties, including regulation of cell proliferation, differentiation and apoptosis. As to these desirable anticancer actions, 1,25-dihydroxyvitamins D and analogs have been reported to inhibit the proliferation and to induce differentiation of a wide variety of cancer cell types, including human malignant melanoma. However, there is a need for novel and more efficacious vitamin D analogs, and how best to design such is still an open issue. A series of double point modified (DPM) analogs of 1,25-dihydroxyvitamin D₂ (1,25(OH)₂D₂) induced differentiation of the vitamin D receptor (VDR) positive A375 and VDR negative SK-MEL 188b human malignant melanoma cell lines. Surprisingly, the dose of 1,25(OH)₂D₂ required to inhibit the proliferation of the A375 melanoma cell line by was several fold lower than that required in the case of 1,25(OH)₂D₃. To evaluate the impact of the modification in the side chain (additional 22-hydroxyl) and in the A-ring (5,6-trans modification), the regular side-chain of vitamin D₂ or D₃ was retained in the structure of our analogs. As expected, 5,6-trans modification was advantageous to enhancing the anti-proliferative activity of analogs, but not as a single point modification (SPM). Very unexpectedly, the additional 22-hydroxyl in the side-chain reduced significantly the anti-proliferative activity of both the natural and 5,6-trans series analogs. Finally, an induction of pigmentation in melanoma SK-MEL 188b cells was observed to sensitized cells to the effect of vitamin D analogs.
    Full-text · Article · Jan 2016 · International Journal of Molecular Sciences
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    • "Vitamin D2 (ergocalciferol), is made by plants and vitamin D3, is made by sunlight exposure on skin. It has been thought that vitamins D2 and D3 are equivalent as increases in circulating 25(OH)D levels were found to be similar in subjects after an 11-week supplementation of 1000 IU/day of vitamin D2 or D3 [11]. In contrast, differences in 25(OH)D concentrations are seen following a one-time oral 50,000 IU bolus of D2 or D3 [12]. "
    Full-text · Article · Nov 2015
    • "A recent, randomized controlled trial showed that ingested vitamin D 3 was almost twice as potent in increasing and maintaining 25(OH)D serum levels as vitamin D 2 . However, discordance about the superiority of vitamin D 3 exists because different dose regimens have been used in previous studies (Heaney, Recker, Grote, Horst, & Armas, 2011; Holick et al., 2008). "
    [Show abstract] [Hide abstract] ABSTRACT: Vitamin D insufficiency correlates with increased incidence of inflammatory disorders and cancer of the colon, breast, liver, and prostate. Preclinical studies demonstrated that the hormonally active form of vitamin D, 1,25(OH)2D3, has antiproliferative, proapoptotic, anti-inflammatory, and immunomodulatory effects. Tissue levels of 1,25(OH)2D3 are determined by expression and activity of specific vitamin D hydroxylases expressed at renal and extrarenal sites. In order to understand how perturbations in the vitamin D system affect human health, we need to understand the steps involved in the synthesis and catabolism of the active metabolite. This review provides an overview about recent findings on the altered vitamin D metabolism in inflammatory conditions and carcinogenesis. We will summarize existing data on the pathophysiological regulation of vitamin D hydroxylases and outline the role of adequate levels of 1,25(OH)2D3 on tissue homeostasis.
    No preview · Article · Aug 2015 · Advances in pharmacology (San Diego, Calif.)
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