search.jsp?R=20110008495 2018-04-05T20:51:31+00:00Z · 2300 mg/d = US Dietary Reference Intake ......
Transcript of search.jsp?R=20110008495 2018-04-05T20:51:31+00:00Z · 2300 mg/d = US Dietary Reference Intake ......
https://ntrs.nasa.gov/search.jsp?R=20110008495 2018-06-24T09:26:13+00:00Z
OperationsResearch
FlightGround
ServiceEducation/Outreach
Clinical Nutritional Assessment(MedB8.1)
PreflightInflight
Postflight
Nutrition SMOExtend MedB 8.1
Inflight CollectionsCM evaluation
Pre Mea
nL-10
FD15FD30
FD60FD12
0
FD180
R+0R+3
00
20
40
60
80
100
120
25(O
H)v
itam
in D
(nm
ol/L
)
UPA
0 6 12 18 240
15
30
45
60
75
Hour of day
SV u
rine
Ca,
mg/
dL
0 1 2 3 4 5-10
-5
0
5
Mean Fish Servings (#/wk)
Who
le B
ody
BM
D(%
cha
nge
from
pre
-flig
ht)
Omega-3 Fatty Acids
Fish intake may mitigate bone and muscle loss, cardiovascular, and cancer risks.
Vitamin K
Vitamin K status does not appear affected by spaceflight (or bed rest).
4-d High APro:K
4-d High APro:K
4-d Low APro:K
4-d Low APro:K
4-d Low APro:K
4-d High APro:K
4-d Low APro:K4-d Monitored
Preflight InflightL-180 L-45 FD15 FD30 FD120 FD180FD60
4-d Monitored 4-d Monitored
R+30 R+1804-d Monitored
R+365
PostflightNOTE: the low ratio diet is NOT low protein, and NOT vegetarianDiets are designed to maintain: energy, protein, calcium, sodium
0.50 0.55 0.60 0.65 0.70 0.75
0250500750
1000125015001750
Dietary Animal Protein:Potassium Ratio(g/mEq)
Bon
e B
reak
dow
n (N
TX)
Vitamin D
0 20 40 60 80 100 1200.0001
0.01
1 Upper quartile of cortisol
Lower quartile of cortisol
Serum 25-hydroxyvitamin D (nmol/L)
Prob
abili
ty o
f EB
V sh
eddi
ng
800 IU Vitamin D/day maintains vitamin D status during flight.In Antarctic analog: Vitamin D, stress, and viral reactivation are interrelated.
Feb June Sept0
20
40
60
80
100
120 2000 IU/d10000 IU/wk
25(O
H) v
itam
in D
(nm
ol/L
)
April/March June/July Sept0
20
40
60
80
100
120
2000 IU/d1000 IU/d400 IU/d
25(O
H) v
itam
in D
(nm
ol/L
)
Vitamin D2011 Dietary Reference Intakes
0 1000 2000 30000
20
40
60
80
100
120
Total Vitamin D intake (IU/d)
Achi
eved
25O
HD
(nm
ol/L
)Non-obeseObese
0 400 800 1200 1600 2000 2400 2800
20
40
60
80
100
120
Children & AdolescentsYoung & Middle Aged AdultsOlder Adults
Total Vitamin D Intake (IU/day)
Achi
eved
25O
HD
(nm
ol/L
)
Vitamin D Dosing Study
50000 IU/wk for 1 mo then monthly
0 7 14 21 28 60 900
5
10
15
Time (d)
mm
ol/d
2000 IU/d
0 7 14 21 28 60 900
5
10
15
Time (d)
mm
ol/d
10000 IU/wk
0 7 14 21 28 60 900
5
10
15
Time (d)
mm
ol/d
Increased urinary calcium is more often observed at higher vitamin D doses.
0 5 10 15 200
5
10
15
20
Total Body Iron (mg/kg)
Plas
ma
TNF α
(pg/
mL)
0 500 1000 1500 20000
5
10
15
20
SOD (Antioxidant Defense)
Tota
l bod
y iro
n (m
g/kg
)
0 5 10 15 200
5
10
15
20
Oxidative DNA damage (8OHdG, µg/day)
Tota
l bod
y iro
n (m
g/kg
)
IronInflammation/Oxidative Damage
Gaps remain in our understanding the interrelationships of iron, oxidative damage, immune function, and radiation.
Sodium
3500 mg/d = ISS requirement (JSC-28038); and the “old” RDA)2300 mg/d = US Dietary Reference Intake Tolerable Upper Intake Level (UL)**, and NASA exploration requirement (JSC-63555)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 280
2000
4000
6000
8000
10000
ISS Sodium Intake
Week of Spaceflight
mg/
day
* http://www.cdc.gov/media/pressrel/2009/r090326.htm** IOM, Dietary Reference Intakes, 2004
In 2005-2006, the average US intake of Na was estimated at 3,436 mg Na/d*In 1990-1999, the average US intake of Na was estimated at: 3,377 mg for 31-50 yo M**
3,539 mg for 31-50 yo F
0 5 10 15 20 250
100020003000400050006000700080009000
Low NaHigh Na
Study Day
Bon
e B
reak
dow
n(C
TX, µ
g/d)
Biochemistry
Intermediate 1
Enzyme Avitamin
Intermediate 2
Enzyme Bvitamin
XC
XC
Intermediate 3
Intermediate 3
Folic acid
tetrahydrofolate
5,10-methylenetetrahydrofolate
5,10-methylenetetrahydrofolate reductase
(MTHFR)
homocysteine
methionine
Methionine synthase (MS)Vitamin B12
S-adenosylmethionine
(SAM)
S-adenosylhomocysteine
(SAH)
cystathionine
Cystathionine b-synthase
(CBS)Vitamin B6
MethylatedDNA,
proteins, lipids
DNA, proteins,
lipids
5 methyltetrahydrofolate
2MCA
Thymidinesynthesis
MMA
One Carbon Transfer
Proteins• Assembled based on “blueprints”
For many (all?) enzymes, there are small differences in blueprints across the population
• These are known as “polymorphisms” –poly = multiple, “morph” = forms
• Example: blood types
Enzymes/Polymorphisms
• Everybody has 2 copies (one from mom and one from dad), resulting in four possibilities of this MTHFR polymorphism:
C C
C T
T C
T T
C/C (~35% of the population)C/T (or T/C)(~50% of the population)T/T (~15% of the population)
Enzymes/Polymorphisms
Folic acid
tetrahydrofolate
5,10-methylenetetrahydrofolate
5,10-methylenetetrahydrofolate reductase
(MTHFR)
homocysteine
methionine
Methionine synthase (MS)Vitamin B12
S-adenosylmethionine
(SAM)
S-adenosylhomocysteine
(SAH)
cystathionine
Cystathionine β-synthase
(CBS)Vitamin B6
MethylatedDNA,
proteins, lipids
DNA, proteins,
lipids
5 methyltetrahydrofolate
2MCA
Thymidinesynthesis
MMA
tetrahydrofolate
5,10-methylenetetrahydrofolate
5,10-methylenetetrahydrofolate reductase
(MTHFR)
homocysteine
methionine
Methionine synthase (MS)Vitamin B12
S-adenosylmethionine
(SAM)
S-adenosylhomocysteine
(SAH)
cystathionine
Cystathionine β-synthase
(CBS)Vitamin B6
MethylatedDNA,
proteins, lipids
DNA, proteins,
lipids
5 methyltetrahydrofolate
2MCAMMA
2-m
ethy
l citr
ic a
cid
(nm
ol/L
)
Pre Mea
nL-10
FD15FD30
FD60FD12
0FD18
0R+0
R+30
0
100
200
300
MM
A(n
mol
/L)
Pre Mea
nL-10
FD15FD30
FD60FD12
0FD18
0R+0
R+30
0
50
100
150
200
250
300
350C
ysta
thio
nine
(nm
ol/L
)
Pre Mea
nL-10
FD15FD30
FD60FD12
0
FD180
R+0R+3
00
50100150200250300350400700
Hom
ocys
tein
e(u
mol
/L)
Pre Mea
nL-10
FD15FD30
FD60FD12
0
FD180
R+0R+3
00
2
4
6
8
10
12
14
tetrahydrofolate
5,10-methylenetetrahydrofolate
5,10-methylenetetrahydrofolate reductase
(MTHFR)
homocysteine
methionine
Methionine synthase (MS)Vitamin B12
S-adenosylmethionine
(SAM)
S-adenosylhomocysteine
(SAH)
cystathionine
Cystathionine β-synthase
(CBS)Vitamin B6
MethylatedDNA,
proteins, lipids
DNA, proteins,
lipids
5 methyltetrahydrofolate
2MCAMMA
2-m
ethy
l citr
ic a
cid
(nm
ol/L
)
Pre Mea
nL-10
FD15FD30
FD60FD12
0FD18
0R+0
R+30
0
100
200
300
MM
A(n
mol
/L)
Pre Mea
nL-10
FD15FD30
FD60FD12
0FD18
0R+0
R+30
0
50
100
150
200
250
300
350
Cys
tath
ioni
ne(n
mol
/L)
Pre Mea
nL-10
FD15FD30
FD60FD12
0
FD180
R+0R+3
00
50100150200250300350400700
Hom
ocys
tein
e(u
mol
/L)
Pre Mea
nL-10
FD15FD30
FD60FD12
0
FD180
R+0R+3
00
2
4
6
8
10
12
14
Homocysteine misincorporation
into proteinsFe
rriti
n (m
ales
)µg
/L
Pre Mea
nL-10
FD15FD30
FD60FD12
0FD18
0R+0
R+30
0
100
200
300
400
500
Hem
oglo
bin
(g/d
L)
Pre Mea
nR+0
R+30
12
13
14
15
16
tetrahydrofolate
5,10-methylenetetrahydrofolate
5,10-methylenetetrahydrofolate reductase
(MTHFR)
homocysteine
methionine
Methionine synthase (MS)Vitamin B12
S-adenosylmethionine
(SAM)
S-adenosylhomocysteine
(SAH)
cystathionine
Cystathionine β-synthase
(CBS)Vitamin B6
MethylatedDNA,
proteins, lipids
DNA, proteins,
lipids
5 methyltetrahydrofolate
2MCAMMA
2-m
ethy
l citr
ic a
cid
(nm
ol/L
)
Pre Mea
nL-10
FD15FD30
FD60FD12
0FD18
0R+0
R+30
0
100
200
300
MM
A(n
mol
/L)
Pre Mea
nL-10
FD15FD30
FD60FD12
0FD18
0R+0
R+30
0
50
100
150
200
250
300
350
Cys
tath
ioni
ne(n
mol
/L)
Pre Mea
nL-10
FD15FD30
FD60FD12
0
FD180
R+0R+3
00
50100150200250300350400700
Hom
ocys
tein
e(u
mol
/L)
Pre Mea
nL-10
FD15FD30
FD60FD12
0
FD180
R+0R+3
00
2
4
6
8
10
12
14
Homocysteine misincorporation
into proteinsFe
rriti
n (m
ales
)µg
/L
Pre Mea
nL-10
FD15FD30
FD60FD12
0FD18
0R+0
R+30
0
100
200
300
400
500
Hem
oglo
bin
(g/d
L)
Pre Mea
nR+0
R+30
12
13
14
15
16
Seru
m F
olat
e(n
mol
/L)
Pre Mea
nFD15
FD30FD60
FD120
FD180
R+00
20
40
60
Vit B
6 (4
-PA,
µmol
/d)
PreFD15
FD30FD60
FD120
FD180
R+0R+3
00
5
10
15
20
25
30
35
MTHFR polymorphisms associated with: Increased risk of ischemic and hemorrhagic stroke Increased risk of migraine
Increased homocysteine associated with: Increased risk of vascular events Increased risk of stroke Risk factor for retinal venous occlusive disease Risk factor for narrower retinal vasculature in men
Case study(ies?) exists relating folic acid deficiency and optic neuropathy
Polymorphism/Associated Risks
Brain Res Bull 71:45-50, 2006; Annals Neurology 59(2): 372-375; Ophthal 109(2):287-290; Am J Ophthalmol. 2009; 148(6):902-909; J Med Case Reports 2:299, 2008.
We’ve documented 4 intermediates strongly suggesting the existence of polymorphism(s) in the 1-carbon metabolism pathway. Additional evidence: folate/B6; ferritin, hemoglobin
Follow-on proposal submitted to HHC/VIIP Expected results: Inform risks Inform therapeutic options Inform VIIP research
1C/VIIP
Physiological Systems
Countermeasures
Vehicle/Mission
NutrientRequirements
Physiological Systems
Vehicle/Mission
NutrientRequirements
Countermeasures