VITAMIN D: FINDINGS FROM THE
ANTARCTIC, BED REST, HOUSTON,
AND ISS
Sara R. Zwart, Ph.D.
Vitamin D: Review
 Sources
 UVB radiation
 Food
 Seafood, mushrooms, egg yolk, fortified foods
 Nomenclature
 Vitamin D2 (ergocalciferol)
 Vitamin D3 (cholecalciferol)
 25-OH vitamin D
 1,25 (OH)2 vitamin D
Vitamin D: Review
Other metabolites:
24,25(OH)2D3
25,26(OH)2D3
35 others…
Holick, AJCN, 2004
Major Functions
 Maintain normal blood levels of Ca and P
 Evidence-based research shows an increasingly
recognized role in other tissues/organs
 Colon, brain, prostate, lung, muscle (smooth and
cardiac), retina, skin, leukocytes, lymphocytes
 Inhibition of cell proliferation
 Promotion of cell differentiation
 Immune regulation
Vitamin D Status
 Serum 25-OH vitamin D (nmol/L)
 <25 nmol/L – Deficiency
 >80 nmol/L – Optimal
 Based on physiological effects on
bone, Ca absorption, and
serum PTH
(Thomas et al., 1998, Chapuy et al., 1997)
(Bischoff-Ferrari, 2006)
Contributing Factors to
Vitamin D Status
 Age
 Ethnicity
 Salt-sensitive hypertension
 Increased protein excretion in salt-sensitive
individuals and Dahl rats with salt loading
 Increased excretion of vitamin D-VDBP
 Adiposity/obesity
Obesity
 25 (OH) vitamin D is lower in obese subjects
 Lack of sunlight exposure?
 Sequestration of vitamin D in fat stores?
*Deficiency defined as <50 nmol/L
(Cheng et al., 2010)
Obesity
 Measured vitamin D3 before/after whole-body
irradiation (27 mJ/cm2)
 57% less increase in obese subjects
 Peak vitamin D3 was related to body weight
● Control
□ Obese
UV
UV
Body weight (kg)
BMI > 30 kg/m2
(Wortsman et al., 2000)
Vitamin D Intake
 RDA (1997 IOM)
 19-50 y: 200 IU/d
 50-70 y: 400 IU/d
 The 2005 Dietary Guidelines for Americans
recommendation advised older adults, people with
dark skin, and people exposed to insufficient
sunlight to consume 1000 IU/d.
 2005 Standards Panel suggested the flight
recommendation be consistent with the 2005
Dietary Guidelines
Toxicity
 Hypercalcemia, hypercalciuria, soft tissue
calcification, kidney stones
 Current upper limit: 2000 IU/d (1997 IOM)
 Many suggest this is too low
 How much is too much?
Space Flight: Food System
Vit D (IU)
Flight Requirement (per day)
Menu
Salmon
Tuna
Breakfast Drink
Tuna Noodle Casserole
Cornflakes
Tuna Salad Spread
Bran Chex
Scrambled Eggs
Bread Pudding
Granola w/Raisins
Tapioca Pudding
Teriyaki Beef
Pork Chops
Vegetable Quiche
Potato Soup
400
172 ± 44
396
152
116
96
88
84
68
64
56
44
44
36
32
28
28
Russian Winter
25-OH vit D (nmol/L)
Percent change
0
-10
-20
-30
-40
-50
Oct
US
Jan
Feb
Russia
65
60
55
50
45
40
35
30
25
20
15
10
5
0
Oct
US
Feb
Jan
Russia
+
R
0/
1
2
317
+
Fl
ig
ht
1
Fl
ig
ht
Fl
ig
ht
R
La
te
La
te
Ea
rly
25 OH Vitamin D
(% change)
Space Flight: Mir
-10
-20
-30
-40
-50
(Smith et al., 1999, 2005)
Space Flight
25-OH Vitamin D
100
60
40
20
R
+0
0
Pr
e
L10
FD
15
FD
30
FD
60
FD
12
0
FD
18
0
nmol/L
80
(Smith et al., 2005)
Space Flight
 Vitamin D status goes down after long-duration
spaceflight.
 Questions:
 Is the stability of vitamin D in the food system and
supplement different during spaceflight?
 Is the daily dose not high enough to maintain status?
 Does vitamin D metabolism change during spaceflight?
Stability Study
I-13
ULF1.1
STS-121
July 4, 2006
I-14
A
B
C
D
A
A
B
C
D
A
I-15
I-16
ULF1.1
STS-121
July 17, 2006
13 d
I-17
13A
STS-117
June 22, 2007
B
353 d
1E
STS-122
Feb 20, 2008
C
ULF-2
STS-126
Nov 29, 2008
596 d
D
Vitamin D analysis:
B
C
D
Tortillas
Almonds
Salmon
Broccoli au Gratin
Dried apricots
Vitamin D supps
Multivitamin supps
880 d
600
600
400
400
0
IU/tablet
200
B
13 ase
li
d
G ne
r
13 oun
35 d F d
3
l
d igh
G
t
35 rou
3
n
59 d F d
6
l
d igh
G
t
59 rou
6
n
88 d F d
0
l
d igh
G
t
88 rou
0
nd
d
Fl
ig
ht
B
13 ase
li
d
G ne
r
13 oun
35 d F d
3
l
d igh
G
t
35 rou
3
n
59 d F d
6
l
d igh
G
t
59 rou
6
n
88 d F d
0
l
d igh
G
t
88 rou
0
nd
d
Fl
ig
ht
IU/100 g
Stability of Vitamin D
Vitamin D
(Salmon)
Vitamin D
(Supplement)
200
0
(Zwart et al., 2009)
Stability of Vitamin D
 Stability of vitamin D in food/supplement is not
altered during spaceflight
 Question:
 Is the daily dose simply not high
enough to maintain status in an
environment with no sun exposure?
Polar I Study (2007)
 3 levels of vitamin D supplementation:
 400 IU/d (n = 18)
 1000 IU/d (n = 19)
 2000 IU/d (n = 18)
 3 blood collections and diet logs
 25D, 1,25D, PTH, Ca, VDBP, NTX
 Double blinded supplementation
Summary: 3 blood draws (36 ml total), 3 7-d food logs, 3 body
weights, take two pills each day throughout the winter
(Smith et al., 2009)
Results
25-OH vitamin D
120
2000 IU/d
1000 IUd
400 IU/d
No pills
100
150
100
nmol/L
PTH (pg/mL)
200
50
80
60
40
0
0
50
100
150
200
20
25-OH vitamin D (nmol/L)
0
April/March
June/July
Sept
100
Session
PTH (pg/mL)
80
60
Compliance
84% on average
40
20
0
April/March
June/July
Sept
(Smith et al., 2009)
Results
 Vitamin D status is related to body weight
 In this regard, Polar studies were not a good
model for spaceflight – what if we exclude
subjects with BMI >29 kg/m2?
25D (nmol/L) at Session 3
25 D (nmol/L) Session 1
200
150
100
50
0
0
100
200
300
Body weight Session 1 (lb)
400
200
150
100
50
0
0
100
200
300
400
500
Body weight at session 3 (lb)
(Smith et al., 2009)
Results
 1000 or 2000 IU/d was enough to reach 80
nmol/L and maintain vitamin D status
Questions…
 Could compliance be improved with a weekly
dose instead of a daily dose?
 Is vitamin D status related to observed
changes in immune function during polar
winters?
Polar II Study (2009)
 2 levels of vitamin D supplementation:
 2000 IU/d (n = 15)
 10000 IU/wk (n = 14)
 3 blood collections, diet logs, and 10-d saliva
collections
 Vitamin D, Ca, Immune markers
Results
 In addition to BMI, the efficacy of vitamin D
supplementation is affected by baseline status
Questions…
 Is a higher, less frequent dose as effective as a
daily or weekly dose?
 Does a high dose result in a high serum
concentration of 25-OH vitamin D (or
metabolites) or change in serum/urine
calcium after ingestion?
Vitamin D Dosing Study
 4 groups (n=12 per group):
 2,000 IU/d
 10,000 IU/wk
 50,000 IU/wk for 1 month, then per month for the following
2 months
 Placebo (0 IU vitamin D, daily, weekly, or monthly)
 Supplementation period: 3 months
 Blood, urine, diet, and sun exposure
 Liver enzymes, Ca, P, vitamin D, bone markers
 Vitamin D metabolites
 Gene expression (NCI add-on)
gene
Screening
Baseline: Time 0
(blood draw, 24 h urine)
(blood draw, 24 h urine)
Dose
UV/Diet log
50,000 IU group only:
7, 14, 21 d
(blood draw, 24 h urine)
6, 12, 24, 48 h
(blood draw)
Diet log
30 d
(blood draw, 24 h urine)
UV/Diet log
6, 12, 24, 48 h
60 d: Time 0
(blood draw, 24 h urine)
Diet log
90 d
(blood draw, 24 h urine)
Dose
(blood draw)
Results
 3 doses were equally effective at raising
vitamin D status after 60 or 90 d (P<0.001)
Time Course: 25 D
-1 subject in 2000 IU/d group had 2 values >150 nmol/L
-2 subjects in 50000 IU group had 3-5 values > 150 nmol/L
Bed Rest
 No vitamin D supplementation
 Diet provides ~350 IU/d (mean from C1-C3E)
C1-C3D
C5A-C5B
C5C
80
60
40
20
Time
R
+5
B
R
90
B
R
60
B
B
R
28
0
Pr
e
25-OH Vit D, nmol/L
100
Bed Rest
 Started supplementing subjects with vitamin D
before (2000 IU/d if screening 25D < 50 nmol/L)
and during bed rest (800 IU/d for all subjects)
starting in 2009, to model space flight
recommendations
 Collected weekly samples to determine
how/when status changed for first 6 subjects
Bed Rest
 Change over 60 d was related to baseline
vitamin D status
Space Flight
25-OH Vitamin D
150
400 IU/d
100
75
50
25
0
Pr
e
L10
FD
15
FD
30
FD
6
FD 0
12
FD 0
18
0
R
+0
R
+3
0
nmol/L
125
Space Flight
 In 2006, it was recommended that crews take 2 of
the 400 IU supplements/day
Space Flight
 Change in vitamin D status/day was similar for
space flight (0.10 nmol/L/d) and bed rest
(0.14 nmol/L/d) with 800 IU/d
Summary
 Space food system doesn’t contain enough
vitamin D
 Vitamin D is stable in food/supplements on ISS
 Polar studies demonstrate that vitamin D
supplementation at 1000-2000 IU/d or 10000
IU/wk is effective at maintaining status for ~6
mo with no UVB exposure
Summary
 Dosing study demonstrated that a daily,
weekly, or monthly dose was equally effective
at maintaining vitamin D status
 Need to carefully evaluate risks/benefits of 50,000
IU dose
 Convenience of monthly dosing
 Hypercalciuria in some subjects
 Other metabolite data are pending
Summary
 During space flight, preliminary data suggest
that 800 IU/d is sufficient to maintain vitamin
D status
 Important to have a sufficient pre-flight vitamin D
status
 BMI may also be an important factor to consider
 Thanks to the Nutritional Biochemistry
Laboratory who have analyzed over 3500
blood and urine samples, and over 500 weeks
of diet records, to generate over 25,000 data
points between Polar I, D Dosing, and Polar II
studies!