Fortification of orange juice with vitamin D(2) or vitamin D(3) is as effective as an oral supplement in maintaining vitamin D status in adults.
ABSTRACT Vitamin D has been added to calcium-fortified orange juice. It is unknown whether vitamin D is as bioavailable from orange juice as it is from supplements.
The objective was to compare the bioavailability of vitamin D(2) and vitamin D(3) from orange juice with that from vitamin D(2) and vitamin D(3) supplements. A secondary aim was to determine which form of vitamin D is more bioavailable in orange juice.
A randomized, placebo-controlled, double-blind study was conducted in healthy adults aged 18-84 y (15-20/group) who received 1000 IU vitamin D(3), 1000 IU vitamin D(2), or placebo in orange juice or capsule for 11 wk at the end of winter.
A total of 64% of subjects began the study deficient in vitamin D (ie, 25-hydroxyvitamin D [25(OH)D]) concentrations <20 ng/mL). Analysis of the area under the curve showed no significant difference in serum 25(OH)D between subjects who consumed vitamin D-fortified orange juice and those who consumed vitamin D supplements (P = 0.084). No significant difference in serum 25(OH)D(3) was observed between subjects who consumed vitamin D(3)-fortified orange juice and vitamin D(3) capsules (P > 0.1). Similarly, no significant difference in serum 25(OH)D(2) was observed between subjects who consumed vitamin D(2)-fortified orange juice and vitamin D(2) capsules (P > 0.1). No significant overall difference in parathyroid hormone concentrations was observed between the groups (P = 0.82).
Vitamin D(2) and vitamin D(3) are equally bioavailable in orange juice and capsules.
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ABSTRACT: Vitamin D deficiency is widely prevalent in India, despite abundant sunshine. Fortification of staple foods with vitamin D is a viable strategy to target an entire population. Vitamin D fortification programs implemented in the United States and Canada have improved the vitamin D status in these countries, but a significant proportion of the population is still vitamin D deficient. Before fortification programs are designed and implemented in India, it is necessary to study the efficacy of the American and Canadian vitamin D fortification programs and then improve upon them to suit the Indian scenario. This review explores potential strategies that could be used for the fortification of foods in the Indian context. These strategies have been proposed considering the diverse dietary practices necessitated by social, economic, cultural and religious practices and the diverse climatic conditions in India. Fortification of staple foods, such as chapati flour, maida, rice flour and rice, may be more viable strategies. Targeted fortification strategies to meet the special nutritional needs of children in India are discussed separately in a review entitled, "Fortification of foods with vitamin D in India: Strategies targeted at children".Nutrients 09/2014; 6(9):3601-3623. · 3.15 Impact Factor
- Journal of Medical Biochemistry 01/2013; 32(1):1-58. · 1.08 Impact Factor
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ABSTRACT: Orange juice (OJ) fortified with calcium (Ca) and vitamin D has turned OJ into a readily available source of these nutrients for children and adults. However, the impact of OJ consumption on Ca and vitamin D adequacy and bone health has not been documented. The aim of this study was the evaluation of the contribution of 100% OJ consumption to dietary and serum Ca and vitamin D status, and bone health parameters in the U.S. population aged 4 years and older (n = 13,971) using the National Health and Nutrition Examination Survey (NHANES) 2003–2004 and 2005–2006. Food consumption data were coded to produce micronutrient intake values using the USDA Food and Nutrient Database for Dietary Studies 3.0. Serum concentrations of bone-related micronutrients and biomarkers, bone mineral density (BMD), and bone mineral content (BMC) were measured. Analysis of data was conducted using SAS software 9.2 and SUDAAN. OJ consumers showed higher intakes of bone-related micronutrients, compared with nonconsumers (P < .05). In addition, OJ consumers had higher serum Ca levels in adults (P < .01) and had a lower odds ratio for serum 25-hydroxyvitamin D3 < 20 ng/mL in children (P < .05). OJ consumption was positively associated with femur BMD in children (P < .05) and with femur BMC in both children and adults (P < .05). In conclusion, OJ may be recommended as an effective dietary means of improving the status of Ca and vitamin D, acid-base balance, and of promoting bone health in children and adults.Journal of Medicinal Food 10/2014; · 1.70 Impact Factor
Fortification of orange juice with vitamin D2or vitamin D3is as effective
as an oral supplement in maintaining vitamin D status in adults1–4
Rachael M Biancuzzo, Azzie Young, Douglass Bibuld, Mona H Cai, Michael R Winter, Ellen K Klein, Allen Ameri,
Richard Reitz, Wael Salameh, Tai C Chen, and Michael F Holick
Background: Vitamin D has been added to calcium-fortified orange
juice. It is unknown whether vitamin D is as bioavailable from
orange juice as it is from supplements.
Objectives: The objective was to compare the bioavailability of
vitamin D2and vitamin D3from orange juice with that from vitamin
D2and vitamin D3supplements. A secondary aim was to determine
which form of vitamin D is more bioavailable in orange juice.
Design: A randomized, placebo-controlled, double-blind study was
conducted in healthy adults aged 18–84 y (15–20/group) who
received 1000 IU vitamin D3, 1000 IU vitamin D2, or placebo in
orange juice or capsule for 11 wk at the end of winter.
Results: A total of 64% of subjects began the study deficient in
vitamin D (ie, 25-hydroxyvitamin D [25(OH)D]) concentrations
,20 ng/mL). Analysis of the area under the curve showed no
significant difference in serum 25(OH)D between subjects who
consumed vitamin D–fortified orange juice and those who con-
sumed vitamin D supplements (P = 0.084). No significant difference
in serum 25(OH)D3was observed between subjects who consumed
vitamin D3–fortified orange juice and vitamin D3capsules (P .
0.1). Similarly, no significant difference in serum 25(OH)D2was
observed between subjects who consumed vitamin D2–fortified
orange juice and vitamin D2capsules (P . 0.1). No significant
overall difference in parathyroid hormone concentrations was
observed between the groups (P = 0.82).
Conclusion: Vitamin D2and vitamin D3are equally bioavailable in
orange juice and capsules.Am J Clin Nutr 2010;91:1621–6.
Vitamin D (D2, D3, or both) deficiency is an international
health concern (1–10) that has been associated with rickets,
osteomalacia, muscle weakness, osteoporosis (11–15), and an
increased risk of wheezing diseases, autoimmune diseases (eg,
type 1 diabetes, multiple sclerosis, rheumatoid arthritis, and
Crohns disease), and cancer, such as of the prostate, breast, and
The major source of vitamin D is exposure to sunlight (31, 32).
A secondary yet limited source of vitamin D is through the diet
(33). Oily fish such as salmon, cod liver oil and sun-dried
mushrooms are the only natural food sources of vitamin D (33,
In the 1930s, fortification of dairy products with vitamin D
eradicated rickets (35). Whereas milk is a commonly fortified
food source of vitamin D, many children and adults have lactose
maldigestion and avoid drinking milk (35–37). According to the
US Department of Agriculture, 49% of Americans older than 2 y
drink more than one glass (236.6 mL; 8 fluid oz) of juice every
day. Tangpricha et al (38) reported that orange juice fortified
with 1000 IU vitamin D3/236.6 mL increased the serum 25-
hydroxyvitamin D [25(OH)D] concentrations of adults by
.150% over 12 wk, which indicated that the fortification of
orange juice with vitamin D3is an effective way to increase
vitamin D intake in adults.
Bread has been fortified with vitamin D since the 1930s (1). It
was observed that fortifying wheat and rye bread with 400 IU
vitamin D3/100 g per serving resulted in a significant increase
in serum 25(OH)D concentrations but no significant change in
parathyroid hormone (PTH) concentrations after 3 wk compared
with a control group (39). However fortification of bread with
5000 IU vitamin D3/serving for 1 y not only increased serum
25(OH)D concentrations but also caused significant reductions
in the PTH concentrations (40). A 3-wk bioavailability study
showed comparable elevations in blood 25(OH)D concentrations
between subjects who ingested wild mushrooms and those who
ingested 400 IU vitamin D2(41).
Whether vitamin D2is equally as effective as vitamin D3at
maintaining blood concentrations of 25(OH)D is still under
discussion. A study of the bioavailability of 4000 IU vitamin D2
and vitamin D3ingested in alcohol for 2 wk (42) or as a single
50,000-IU dose (43) suggested that vitamin D2was less effective
than vitamin D3in raising and maintaining blood concentrations
of 25(OH)D. However, elevations in blood 25(OH)D concen-
1From the Endocrine Section, Department of Medicine, Boston Univer-
sity School of Medicine, Boston, MA (RMB, MHC, EKK, AA, TCC, and
MFH); the Data Coordinating Center, Department of Public Health, Boston
University School of Medicine, Boston, MA (MRW); Quest Diagnostics
Nichols Institute, San Juan Capistrano, CA (RR and WS); and Mattapan
Community Health Center, Mattapan, MA (AY and DB).
2The contents are solely the responsibility of the authors and do not
necessarily represent the official view of the NCRR or NIH.
3Supported by grant M01 RR000533 from the National Center for Re-
search Resources, a component of the National Institutes of Health, and the
Beverage Institute for Health & Wellness, a Division of Coca-Cola North
America, Atlanta, GA.
4Address correspondence to MF Holick, Boston University School of
Medicine, 85 East Newton Street, M-1013, Boston, MA 02118. E-mail:
Received April 23, 2009. Accepted for publication March 8, 2010.
First published online April 28, 2010; doi: 10.3945/ajcn.2009.27972.
Am J Clin Nutr 2010;91:1621–6. Printed in USA. ? 2010 American Society for Nutrition
trations were identical between healthy adults given 1000 IU
vitamin D2or 1000 IU vitamin D3in capsule form at the end of
the winter for 3 mo (44). Similarly, children who received 2000
IU daily or 50,000 IU vitamin D2weekly experienced an ele-
vation in blood 25(OH)D concentrations equivalent to concen-
trations observed in children who received 2000 IU vitamin D3
It is unknown whether vitamin D2and vitamin D3are equally
bioavailable from the same fortified food source or whether
vitamin D in orange juice is as bioavailable as it is in a capsule.
The purpose of our study was to compare the bioavailability of
vitamin D2and vitamin D3from orange juice with that from
vitamin D2and vitamin D3supplements.
SUBJECTS AND METHODS
blind study that began on 14 February 2007 (Table 1). The
subjects were randomly assigned into 1 of 5 groups by using
a computer-generated randomization code. Potential subjects
were excluded if they had a history of intestinal malabsorption,
a severe medical illness, allergies, or an intolerance or dislike of
orange juice or were taking a supplement containing .400 IU
vitamin D/d. The subjects signed a consent form approved by
the Institutional Review Board at Boston University Medical
All of the vitamin D and placebo capsules were manufactured
by Tishcon Corp (Salisbury, MD) and contained lactose
(98.75%), magnesium stearate (1.0%), and silicon dioxide
(1.25%). All of the calcium-fortified orange juices were prepared
by Coca-Cola North America (Apoka, FL).
Cold water–soluble vitamin D (1000 IU) was added to every
236.6 mL calcium-fortified orange juice (39). The vitamin D was
each use were placed on each orange juice container to ensure
that the vitamin D was evenly distributed.
Stability of vitamin D in orange juice and capsules
HPLC was used to determine the amount and stability of
vitamin D2and vitamin D3 in the orange juice and capsules. The
orange juice and capsules were found to contain either no vi-
tamin D (placebo) or vitamin D within 10% of their specified
The study began in mid-February 2007. The subjects were
randomly assigned into 1 of 5 groups: 1) placebo capsule +
orange juice without vitamin D (placebo orange juice), 2) pla-
cebo capsule + orange juice containing 1000 IU vitamin D3/
236.6 mL, 3) placebo capsule + orange juice containing 1000 IU
vitamin D2/236.6 mL, 4) 1000 IU vitamin D3capsule + placebo
orange juice, or 5) 1000 IU vitamin D2capsule + placebo orange
juice. All orange juice contained 350 mg Ca/236.6 mL. Subjects
consumed one capsule and one 236.6-mL glass of orange juice
daily. The subjects were instructed to drink the orange juice in
the morning and to ingest the capsule at night. Blood was col-
lected once weekly for a total of 11 wk. Calcium, albumin,
parathyroid hormone (PTH), 25(OH)D2, and 25(OH)D3were
measured (Table 2).
Serum 25(OH)D was ascertained by liquid chromatography
tandem mass spectroscopy at Quest Diagnostic Laboratory (San
Demographic characteristics of the subjects1
(n = 15)
OJ (n = 18)
OJ (n = 17)
capsules (n = 20)
capsules (n = 16)
Mean 6 SD
Sex [n (%)]
Race [n (%)]
Multivitamin use [n (%)]
Vitamin D supplement use (n)
Dropouts [n (%)]
40.8 6 10.8
41.4 6 12.6
40.1 6 15.6
40.1 6 18.0
38.9 6 12.3
1OJ, orange juice.
BIANCUZZO ET AL
intraassay CVof 9% and an interassay CVof 12%. Serum PTH
was assessed by using an Immutopics International PTH (1-84)
enzyme-linked immunosorbent assay (San Clemente, CA). The
assay has an intraassay CV of from 2.2% to 2.3% and an
interassay CV of from 5.6% to 8.6%.
Statistical calculations were performed by using SAS version
9.1 (SAS Institute, Cary, NC). Mean differences and 95% CIs for
calcium, albumin, 25(OH)D, and PTH from baseline to week 11
were calculated for all subjects (Table 2). The mean (6 SD)
areas under the curve (AUCs) for serum 25(OH)D2, 25(OH)D3,
25(OH)Dtotal, PTH, calcium, and albumin concentrations from
baseline to week 11 were calculated for each treatment group.
One-factor analysis of variance was used to detect overall sig-
nificant differences in AUCs between treatment groups. To de-
tect significant differences in AUCs between specific treatment
groups, Tukey’s honestly significant differences test was used.
Tukey’s honestly significant differences test was used regardless
of the outcome of the analysis of variance. All significant dif-
ferences were measured at the P = 0.05 level.
Of the 105 subjects who started the study, 86 subjects com-
pleted the study (18 in the vitamin D3orange juice group, 20 in
the vitamin D3capsule group, 17 in the vitamin D2orange juice
group, 16 in the vitamin D2capsule group, and 15 in the placebo
group). Sixty-four percent of all subjects were vitamin D de-
ficient [25(OH)D , 20 ng/mL] and 21% were insufficient [25
(OH)D 21–30 ng/mL]. No significant changes in serum calcium
and albumin AUCs from baseline to week 11 were observed in
any of the treatment groups.
The AUC of serum concentrations against time is the best
indicator of the total bioavailability of an administered agent. No
significant difference in the AUC for serum 25(OH)Dtotalwas
observed between the subjects who received vitamin D2in or-
ange juice (279.2 6 80.6 ng ? wk/mL) and those who received
vitamin D3in orange juice (307.6 6 82.6 ng ? wk/mL).The
overall difference in the AUC for serum 25(OH)Dtotalbetween
all subjects who received either 1000 IU vitamin D2or vitamin
D3in orange juice or in a capsule was not significant (P = 0.084)
(Figure 1, A and B).
Subjects who received vitamin D3in orange juice had an AUC
for serum 25(OH)D3of 296.4 6 74.4 ng ? wk/mL, which was
not significantly different from the AUC for serum 25(OH)D3in
the group who received vitamin D3in a capsule (302.3 6 120.8
ng ? wk/mL) (Figure 2A). The AUC for serum 25(OH)D3was
not significantly different (P . 0.05) between the group who
received vitamin D3in orange juice and those who received
placebo in orange juice (209.16 104.4 ng ? wk/mL), whereas the
AUC for serum 25(OH)D3 was significantly different (P ,
0.0001) between the group who received vitamin D3in capsules
and those who received placebo in orange juice (Figure 2A).
No significant difference (P . 0.05) in the AUC for serum
25(OH)D2 was observed between the subjects who received
vitamin D2in orange juice (127.3 6 57.9 ng? wk/mL) and the
subjects who received vitamin D2in capsules (118.0 6 38.4 ng ?
wk/mL) (Figure 2B). However, the AUC for serum 25(OH)D2
was significantly different (P , 0.0001) between the subjects
who received vitamin D2in orange juice and those who received
placebo in orange juice (11.4 6 28.7 ng ? wk/mL) (Figure 2B).
No significant overall difference in PTH was observed between
the groups (P = 0.82).
The bioavailability of vitamin D in orange juice and capsules
was determined by analyzing the AUCs of serum 25(OH)D2and
serum 25(OH)D3. It was determined that the bioavailability of
(n = 15)
Vitamin D3in OJ
(n = 18)
Vitamin D2in OJ
(n = 17)
Vitamin D3in capsules
(n = 20)
Vitamin D2in capsules
(n = 16)
19.8 6 9.6
18.1 6 6.4
21.7 6 5.8
17.9 6 11.1
30.7 6 8.5
12.8 6 10.1
15.8 6 10.0
26.4 6 7.4
10.6 6 7.2
19.6 6 11.1
28. 6 11.0
9.3 6 7.1
16.6 6 9.9
27.4 6 10.5
10.8 6 5.9
44.3 6 27.1
41.1 6 19.4
23.2 6 20.3
37.1 6 23.2
25.6 6 14.7
211.5 6 19.9
35.7 6 17.4
25.7 6 14.9
210.0 6 17.5
42.0 6 31.0
34.2 6 24.6
27.8 6 22.9
29.0 6 18.7
36.2 6 22.9
7.2 6 18.7
9.4 6 0.3
9.4 6 0.3
0.0 6 0.3
9.4 6 0.3
9.4 6 0.4
0.0 6 0.4
8.8 6 2.1
9.6 6 0.3
20.8 6 2.3
9.3 6 0.4
9.4 6 0.4
0.1 6 0.3
9.5 6 0.4
9.5 6 0.3
0.0 6 0.3
4.4 6 0.3
4.3 6 0.3
20.1 6 0.3
4.3 6 0.4
4.1 6 0.3
20.2 6 0.2
4.4 6 0.4
4.4 6 0.3
0.0 6 0.2
4.3 6 0.3
4.2 6 0.4
20.1 6 0.3
4.3 6 0.3
4.3 6 0.2
0.0 6 0.2
1All values are means 6 SDs; 95% CIs in parentheses. OJ, orange juice; 25(OH)D, 25-hydroxyvitamin D; PTH, parathyroid hormone.
BIOAVAILABILITY OF VITAMINS D2AND D3IN ORANGE JUICE
vitamin D was equivalent in orange juice and capsules. The
AUC analysis showed that the bioavailability of vitamin D2and
of vitamin D3from orange juice was similar to that from cap-
sules. The results indicate that vitamin D in orange juice is as
bioavailable as is vitamin D in capsules. Furthermore, it was
shown that vitamin D2and vitamin D3in orange juice were
equally effective as vitamin D in capsules at raising serum
The results of the weekly blood analysis indicated that serum
25(OH)D2concentrations were significantly greater in subjects
who consumed orange juice fortified with 1000 IU vitamin D2
than in those who consumed the placebo plus orange juice
without vitamin D. As expected, baseline 25(OH)D2concen-
trations were very low or undetectable in all subjects. Because
vitamin D2can only be obtained through the diet in a limited
amount of fortified foods, most persons who do not eat large
quantities of these foods (eg, sun-dried mushrooms), do not take
vitamin D2supplements, or do not take prescription vitamin D2
do not have measurable concentrations of 25(OH)D2. Whereas
25(OH)D2concentrations seemed to increase more rapidly in
the subjects who consumed orange juice containing vitamin D2
than in the subjects who consumed vitamin D2capsules, the
increase was not statistically significant and peaked at week 5
(13.8 6 4.8 ng/mL) in both groups (Figure 2B).
No changes in serum 25(OH)D2or 25(OH)D3concentrations
were observed in the placebo group, which indicated that sun
exposure and diet had no significant effect on their vitamin D
status. Subjects who consumed orange juice containing 1000 IU
vitamin D3had significantly greater 25(OH)D3concentrations
than the placebo group. Subjects who consumed orange juice
containing vitamin D3and those who consumed vitamin D3
capsules began the study with average 25(OH)D3concentrations
of 17.6 6 6.4 ng/mL. Their serum 25(OH)D3concentrations
steadily increased until week 5, at which time they plateaued.
The increases in 25(OH)D3in these 2 groups were not signifi-
cantly different, which suggests that serum 25(OH)D3concen-
trations will increase similarly when 1000 IU vitamin D3is
consumed in orange juice or in capsule form.
Serum PTH concentrations decreased in subjects who con-
sumed orange juice fortifiedwith vitamin D and calcium, vitamin
FIGURE 1. A: Mean (6SEM) total 25-hydroxyvitamin D [25(OH)D]
concentrations over time after the oral administration of 1000 IU vitamin
D3in orange juice (d; n = 18), 1000 IU vitamin D3in capsules (n; n = 20),
or unfortified orange juice plus placebo capsules (¤; n = 15). No statistically
significant differences were observed between areas under the curve for
serum total 25(OH)D between the vitamin D3in orange juice and vitamin
D3capsule groups (one-factor ANOVA, P = 0.084). B: Mean (6SEM) total
25(OH)D concentrations over time after oral administration of 1000 IU
vitamin D2in orange juice (d; n = 17), 1000 IU vitamin D2in capsules
(n; n = 16), or unfortified orange juice plus placebo capsules (¤; n = 15). No
statistically significant differences were observed between areas under the
curve for serum total 25(OH)D between the vitamin D2in orange juice and
vitamin D2capsule groups (one-factor ANOVA, P = 0.084).
FIGURE 2. A: Mean (6SEM) serum 25-hydroxyvitamin D [25(OH)D3]
concentrations over time after oral administration of 1000 IU vitamin D3in
orange juice (d; n = 18), 1000 IU vitamin D3in capsules (n; n = 20), or
unfortified orange juice plus placebo capsules (¤; n = 15). The area under
the curve for serum 25(OH)D3after consumption of vitamin D3in orange
juice and after vitamin D3in capsules was not significantly different (one-
factor ANOVA, P . 0.05). B: Mean (6SEM) serum 25(OH)D2
concentrations over time after oral administration of 1000 IU vitamin D2
in orange juice (d; n = 17), 1000 IU vitamin D2in capsules (n; n = 16), or
unfortified orange juice plus placebo capsules (¤; n = 15). The area under
the curve for serum 25(OH)D2after consumption of vitamin D2in orange
juice and of the vitamin D2capsules was not significantly different (one-
factor ANOVA, P . 0.05).
BIANCUZZO ET AL
D3capsules, or placebo; however, the results were not statisti-
cally significant. Overall, there was no statistically significant
difference in serum PTH concentrations between any of the
groups (P = 0.82).
Two studies have suggested that vitamin D3is more effective
than vitamin D2at maintaining serum 25(OH)D concentrations
(42, 43). The results of our study indicate that consumption of
1000 IU vitamin D2or vitamin D3in orange juice was equally as
effective as 1000 IU vitamin D2or D3in capsule form in raising
and maintaining circulating concentrations of total 25(OH)D
(Figure 1, A and B). The results are consistent with our previous
observation that the consumption of 1000 IU vitamin D2daily in
capsule form was equally as effective as consuming a 1000-IU
capsule of vitamin D3in raising serum 25(OH)D2and 25(OH)
are at risk of a myriad of diseases ranging from type 1 diabetes to
osteoporosis. Exogenous factors such as time of day, season, and
latitude influence cutaneous production of vitamin D. The vari-
ability inherent in these factors makes relying on sun exposure as
a necessary component of ensuring sufficient 25(OH)D concen-
trations in the blood, especially for those living in the northern
hemisphere during the winter months. However, studies that
milk regularly. Fortification of orange juice with vitamin D is as
effective as oral supplementation in enhancing 25(OH)D con-
centrations in adults. Therefore, fortification of orange juice
with vitamin D2or vitamin D3is a resourceful way of enhancing
vitamin D status in children and adults.
Quest Diagnostics/Nichols Institute is a clinical laboratory that specializes
in liquid chromatography tandem mass spectroscopy and performed the 25
(OH)D assays for this study. We thank Jeff Mathieu for measuring the serum
concentrations of PTH in all of the specimens and the staff at the Mattapan
Community Health Center for their help in recruiting the study subjects.
The authors’ responsibilities were as follows—MFH AY, DB, and RMB:
participated in the study design, statistical analysis, recruitment of subjects,
study visits, data collection, and preparation of the manuscript; MHC and
MRW: helped in the statistical analysis of the study; EKK: participated in
the study oversight and study design; AA: participated in the recruitment
of the subjects, study visits, and data collection; TCC: participated in the de-
sign of the study and the analysis of the blood samples; and RR and WS:
participated in the designof the assay methodology, performance ofthe assay,
and interpretation of the data. MFH is on the Speaker’s Bureau for Merck,
Proctor and Gamble, and Eli Lilly and is a consultant for Amgen, Novartis,
Quest Diagnostics, Bayer, Abbott, Proctor and Gamble, and Merck. RMB,
MHC, MRW, EKK, AA, WS, TCC, AY, and DB had no conflicts of interest
to declare. RR is Medical Director of Quest Diagnostics/Nichols Institute and
has equity interests in Quest Diagnostics/Nichols Institute. The Beverage In-
stitute for Health & Wellness, a Division of Coca-Cola North America,
Atlanta, GA, funded the study but had no role in the design, implementation,
analysis, or interpretation of the research.
1. Holick MF. Vitamin D deficiency. N Engl J Med 2007;357:266–81.
2. Holick MF. High prevalence of vitamin D inadequacy and implications
for health. Mayo Clin Proc 2006;81:353–73.
3. Holick MF, Siris ES, Binkley N, et al. Prevalence of vitamin D in-
adequacy among postmenapausal North American women receiving
osteoporosis therapy. J Clin Endocrinol Metab 2005;90:3215–24.
4. Chapuy MC, Preziosi P, Maamer M, et al. Prevalence of vitamin D
insufficiency in an adult normal population. Osteoporos Int 1997;7:
5. Tangpricha V, Pearce EN, Chen TC, Holick MF. Vitamin D insufficiency
among free-living adults. Am J Med 2002;112:659–62.
6. Datta S, Alfaham M, Davies D, et al. Vitamin D deficiency in pregnant
women from a non-European ethnic minority population: an in-
ternational study. Br J Obstet Gynaecol 2002;109:905–8.
7. Shaw NJ, Pal BR. Vitamin D deficiency in UK Asian families. Arch Dis
8. Waiters B, Godel JC, Basu TK. Perinatal vitamin D and calcium status
of northern Canadian mothers and their newborn infants. JAm Coll Nutr
9. Henriksen C, Brunvard L, Stoltenberg C, et al. Diet and vitamin D status
among pregnant Pakastani women in Oslo. Eur J Clin Nutr 1995;49:
10. Goswami R, Gupta N, Goqwami D, et al. Prevalence and significance of
low 25-hydroxyvitamin D concentrations in healthy subjects in Dehli.
Am J Clin Nutr 2000;72:472–5.
11. Holick MF. Vitamin D: the underappreciated D-lightful hormone that is
important for skeletal and cellular health. Curr Opin Endocrinol Di-
12. Holick MF. Vitamin D: importance in the prevention of cancers, type 1
13. Holick MF. The sunlight “D” ilemma: risk of skin cancer or bone dis-
ease and muscle weakness. Lancet 2001;357:4–5.
14. Holick MF. Resurrection of vitamin D deficiency and rickets. J Clin
15. Rajakumar K. Vitamin D, cod-liver oil, sunlight and rickets: a historical
perspective. Pediatrics 2003;112:e132–5.
16. Holick MF. Sunlight and Vitamin D for bone health and prevention of
autoimmune diseases, cancer and cardiovascular disease. Am J Clin
17. Harries AD, Brown R, Heatley RV, Williams LA, Woodhead S, Rhodes
J. Vitamin D status in Crohn’s disease: association with nutrition and
disease activity. Gut 1985;26:1197–203.
18. Hypponen E, Laara E, Reunanen A, Jarvelin MR, Virtanen SM. Intake
of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet
19. Garland CF, Comstock GW, Garland FC, Helsing KJ, Shaw EK, Gorham
ED. Serum 25-hydroxyvitamin D and colon cancer: eight year pro-
spective study. Lancet 1989;2:1176–8.
20. Martinez ME, Giovannuccci EL, Colditz GA, et al. Calcium, vitamin D
and the occurrence of colorectal cancer among women. J Natl Cancer
21. Gorham ED, Garland CF, Garland FC. Acid haze air pollution and breast
and colon cancer mortality in 20 Canadian cities. Can J Public Health
22. Garland FC, Garland CF, Gorham ED, Young JF. Geographic variation
in breast cancer mortality in the United States: a hypothesis involving
exposure to solar radiation. Prev Med 1990;19:614–22.
23. Schwartz GG, Hulka BS. Is vitamin D deficiency a risk factor for
prostate cancer? Anticancer Res 1990;10:1307–11.
24. Hanchette CL, Schwartz GG. Geographic patterns of prostate cancer
mortality. Cancer 1992;70:2861–9.
25. Ahonen MH, Tenkanen L, Teppo L, Hakama M, Tuohimaa P. Prostate
cancer risk and prediagnostic serum 25-hydroxyvitamin D levels (Fin-
land). Cancer Causes Control 2000;11:847–52.
26. Luscombe CJ, Fryer AA, French ME, et al. Exposure to ultraviolet ra-
diation: association with susceptibility and age at presentation with
prostate cancer. Lancet 2001;358:641–2.
27. Grant WB. An ecologic study of dietary and solar ultraviolet-B links to
breast carcinoma mortality rates. Cancer 2002;94:272–81.
28. Ponsonby A-L, McMichael A, van der Mei I. Ultraviolet radiation and
autoimmune disease: insights from epidemiological research. Toxicol-
29. Merlino LA, Curtis J, Mikuls TR, Cerhan JR, Criswell LA, Saag KG.
Vitamin D intake is inversely associated with rheumatoid arthritis: re-
sults from the Iowa Women’s Health Study. Arthritis Rheum 2004;50:
30. Pittas AG, Dawson-Hughes B, Li T, et al. Vitamin D and calcium intake
in relation to type 2 diabetes in women. Diabetes Care 2006;29:650–6.
31. Webb AR, Kline L, Holick MF. Influence of season and latitude on the
cutaneous synthesis of vitamin D3: exposure to winter sunlight in Boston
BIOAVAILABILITY OF VITAMINS D2AND D3IN ORANGE JUICE
and Edmonton will not promote vitamin D3synthesis in human skin.
J Clin Endocrinol Metab 1988;67:373–8.
32. PoskittEME, Cole TJ,Lawson
25-hydroxyvitamin D in healthy children and adults. BMJ 1979;1:221–3.
33. Moore C, Murphy MM, Keast DR, Holick MF, Vitamin D. Intake in the
United States. J Am Diet Assoc 2004;104:980–3.
34. Lu Z, Chen TC, Zhang A, et al. An evaluation of the vitamin D3
content in fish: is the vitamin D content adequate to satisfy the dietary
requirement for vitamin D? J Steroid Biochem Mol Biol 2007;103:
35. Holick MF, Shao Q, Liu WW, Chen TC. The vitamin D content of
fortified milk and infant formula. N Engl J Med 1992;326:
36. Simoons FJ. The geographic hypothesis and lactose malabsorption. A
weighing of the evidence. Am J Dig Dis 1978;23:963–80.
37. Zeiger RS. Dietary aspects of food allergy prevention in infants and
children. J Pediatr Gastroenterol Nutr 2000;30(suppl):S77–86.
38. Tangpricha V, Koutkia P, Rieke SM, et al. Fortification of orange juice
with vitamin D: a novel approach for enhancing vitamin D nutritional
health. Am J Clin Nutr 2003;77:1478–83.
39. Natri AM, Salo P, Vikstedt T, et al. Bread fortified with cholecalciferol
increases the serum 25-hydroxyvitamin D concentration in women as
effectively as cholecalciferol supplement. J Nutr 2006;136:123–7.
40. Mocanu V, Stitt PA, Costan AR, et al. Long-term effects of giving
nursing home residents bread fortified with 125 lg (5000 IU) vitamin D3
per daily serving. Am J Clin Nutr 2009;89:1132–7.
41. Outila TA, Mattila PH, Piironen VI, Lamberg-Allardt CJE. Bio-
availability of vitamin D from wild edible mushrooms (Cantharellus
tubaeformis) as measured with a human bioassay. Am J Clin Nutr 1999;
42. Trang HM, Cole DEC, Rubin LA, Pierratos A, Siu S, Vieth R. Evidence
that vitamin D3increases serum 25-hydroxyvitamin D more efficiently
than does vitamin D2. Am J Clin Nutr 1998;68:854–8.
43. Armas LAG, Hollis B, Heaney RP. Vitamin D2is much less effective
thanvitamin D3ion humans. J Clin Endocrinol Metab 2004;89:5387–91.
44. Holick MF, Biancuzzo RM, Chen TC, et al. Vitamin D2is as effective as
vitamin D3 in maintaining circulating concentrations of 25-hydrox-
yvitamin D. J Clin Endocrinol Metab 2008;93:677–81.
45. Gordon CM, Williams AL, Feldman HA, et al. Treatment of hypo-
vitaminosis in infants and toddlers. J Clin Endocrinol Metab 2008;93:
46. Tanner JT, Smith J, Defibaugh P, et al. Survey of vitamin content of
fortified milk. J Assoc Off Anal Chem 1988;71:607–10.
47. Chen TC, Shao Q, Heath H, Holick MF. An update on the vitamin D
content of fortified milk from the United States and Canada. N Engl J
BIANCUZZO ET AL