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