Table Of Content

Space Nutrition Nutrient Systems Requirements Bone Energy Muscle CHO (fiber), Fat, Protein Cardio Fat-soluble vitamins Fluid/Electrolyte Water-soluble vitamins Immunology Minerals Hematology Fluid Neuro Endo GI BHP CCoouunntteerrmmeeaassuurreess Energy Bisphosphonates Vehicle/Mission Amino acids KCitrate Protein Medications Duration SFaotdtyiu amcids EOxtheercrise FoRoadd Siaytisotnem Antioxidants EVA Other Schedule Energy Energy and Cardio/Ox. Damage 110 100 8 % WHO predicted% 234567892000000000 # of Finishers02460 HHNNyyoopprrmmooccooaaccllaaoollrrooiiccrrii ccAB BmeAdmebrduebrslueatlstaottroyry 10 0 5 10 15 20 25 0 Time (minutes) of LBNP Florian, 2004 10 ApolloSkylabShuttleMir E1-4 E5-11 E12-21 m Preflight 05 fro -5 %-10 -15 0 20 40 60 80 100 120 140 160 180 200 220 W. Carpentier Stein, 2002 Mission Duration (days) Energy and Muscle/Bone Energy 12 HHNNyyoopprrmmooccooaaccllaaoollrrooiiccrrii ccBA eAmBdembrduebrslueatsltaottroyry Weight (kg)-10 -2 -3 Stabilization Intervention Recovery 0 5 10 15 20 25 30 Time (days) Eucaloric diet Leucine oxidation(mol/kg LBM/min)000...123 Hypocaloric diet Energy Intake(% WHO)110550000 BEnoedryg My ianstsake --05150Body Mass(% from preflight) 0.0 Ambulatory Bed rest 0 50 Day o1f0 0Flight150 200 Heer et al. Biolo, 2007 Ihleand Loucks, 2004 Smith et al., J Nutr, 2005 1 SLAMMD Nutrition SMO Nutrition SMO Protein (and muscle) Countermeasures Dietary Protein akeProtein Intaeight/day)kg Body We22011.....05505 m/ (g0.0 FD 1F5D 2F0D 2F5D 3F0D 3F5D 4F0D 5F0D 5F5D 6F0D 7F0D 8F0D 9F0D F9D 51F0D 01F1D 01F1D 51F2D 01F3D 01F3D 51F4D 01F4D 51F5D 01F6D 01F7D 01F7D 5185 Amino Acids 2 Muscle Protein Amino Acids Amino acid supplementation IIssssuueess:: •Protein synthesis vs. breakdown •Exercise •Catabolic effectors (e.g., stress/cortisol, hypocaloric diet, T3) •Intake (and/or supplement) of control group Protein Synthesis Protein Breakdown Protein Intake(gm/kg Body Weight/day)001122......F050505D 1F5D 2F0D 2F5D 3F0D 3F5D 4F0D 5F0D 5F5D 6F0D 7F0D 8F0D 9F0D F9D 51F0D 01F1D 01F1D 51F2D 01F3D 01F3D 51F4D 01F4D 51F5D 01F6D 01F7D 01F7D 5185 Protein Synthesis Breakdown Inflammation Bed rest Arachidonic acid Unloading-induced atrophy is a relatively uncomplicated Hindlimbunloading PIF LPS RANKL TNF- form of muscle loss…. most of the loss of muscle mass Spaceflight during disuse atrophycan be accounted for by a Ionizing radiation/UVC depression in the rate of protein synthesis. NF-kB whereas in disease statesassociated with inflammation NF-kB (active) (cancer cachexia, AIDS, burns, sepsis, and uremia), there NF-kB is a procatabolichormonal and cytokine environment. …. kB Inhibitor kB Inhibitor Ub-prot activation Muscle proteolysis Phillips, et al, J ApplPhysiol, 2009 …procatabolichormonal and Inflammatory Markers cytokine environment… 20 15 ivationFB p65 acti68240000 * * TNF(pg/mL)22Pr105e0050 MeanL-10FD15FD30FD60FD120FD180 R+0R+30 5CXCL 5)(pg/mL)6824000000000000 N 0 0 L-10 R+0 R+14 AME IL-1(pg/mL)1105 Pre mean L-10FD15FD30FD60FD120FD180 R+0R+30 5 0 Pierson et al., 2009 Pre mean L-10FD15FD30FD60FD120FD180 R+0R+30 3 Inflammation/Muscle Protein/Muscle 600 It is imperative that these studies include examination of dynamic measures of muscle protein turnover and putative Hat)acre440000 Pre mbaestaicb orelics pcoonnstreoslle tros .i.m. umnolebsilsiz watei ohnavpee ra s cel,e tahre iedfefeac otsf othf e Mg Inflight such factors will not be easily teased out and therapeutic 3-ol/ R+0 goals will remain largely unattainable. m200  R+30 ( 0 0 2 4 6 TNFa (pg/mL) Phillips, et al, J ApplPhysiol, 2009 Hypercatabolism Hypercatabolism Hyper-catabolic conditions associated with Hyper-catabolic conditions associated with upregulationof the ubiquitin-proteasome system: proteolysis: Cancer cachexia (Loriteet al. 2001; Tisdale et al. 2009) CCaanncceerr ccaacchheexxiiaa CCaacchheexxiiaa aassssoocciiaatteedd wwiitthh hheeaarrtt ffaaiilluurree((FFiilliippppaattoosseett aall.. 22000055,, Freeman et al. 1998) Cachexia associated with heart failure Sepsis (Voisinet al. 1996; Tiaoet al. 1994) Sepsis Starvation (Whitehouse, 2001) Starvation Metabolic acidosis (Mitch et al. 1994) Stress/trauma associated with excess glucocorticoids Metabolic acidosis (Wing et al. 1993; Biolo et al. 2000) Stress/trauma associated with excess glucocorticoids Space flight (Ikemotoet al. 2001; Riley et al. 1992) Space flight Omega 3 (n3) Fatty Acids n3/EPA and Muscle  Eic2Do0ies-Ctaa,pr yoe msnoetaugreacn-e3os :fi ac ft itasyhc a iodcii ld(, EflaPxAse)ed, walnuts ge in weight (kg/month)Chang------012432165 1 2 3 4 5 6 7 8 9 10111213141516BG1e7LfAo1re8 G1L9A20 Subject  Bmeentaebfiocilaislm e,f faencdts coanr dcihoovlaesscteurlaorl, hliepaidlt h Change in weight (kg/month)--------87654321012 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16BEePf1Ao7re E18PA Subject Muscle… Whitehouse Teits adla. l2e,0 e0t1 al. 4 Omega-3 and Cancer 30 25 20 Change in weight (kg/month)------012654321123456789S1u0bj1ec1t12131415161BGe7LfAo1re8 G1L9A20 110505 CornP OriolportionF oishf Oil Change in weight (kg/month)M--------01287654321123u45s6c78lS9ueb1je0ct11…1213141516BEeP1fAo7re 1E8PA tumor bearing rats Vanamalaet al., CarcinogenTeissdiasle, , 2et0 a0l.8 Vitamin D Vitamin D Vitamin D Intake Guidelines Sources UVB radiation Food RDA (1997 IOM) Seafood,, mushrooms,, egggg yyolk,, 1199--5500 yy:: 220000 IIUU//dd Fortified foods 50-70 y: 400 IU/d Nomenclature The 2005 Dietary Guidelines for Americans Vitamin D (ergocalciferol) recommendation advised older adults, people 2 Vitamin D (cholecalciferol) with dark skin, and people exposed to 3 25-OH vitamin D insufficient sunlight to consume 1000 IU/d. 1,25 (OH) vitamin D 2 Contributing Factors to Vitamin D Vitamin D: Review Vitamin D Status Age Ethnicity VViittamiin DD SSttattus SSallt-sensiitiive hhypertensiion Other metabolites: Increased protein excretion in salt-sensitive 24,25(OH)2D3 individuals and Dahl rats with salt loading 25,26(OH)2D3 35 others… Adiposity/obesity Holick, AJCN, 2004 5 D D Vitamin D is associated with: Vitamin D is associated with: Calcium metabolism Calcium metabolism Fracture Risk/BMD Fracture Risk/BMD Muscle strength/function 110 110 Cancer 110000 110000 Cardiovascular health 25 (OH) Vitamin D(nmol/L) 2345678900000000 25 (OH) Vitamin D(nmol/L) 2345678900000000 InPMcaIiumdrkleTtmDiinnupDeucsblemineoea e nSrbeoc ’ecnsffu ul ttCelDeionar-ssciossitseseioicasntsioen 10 10 The common cold 0 0 SSmmiitthh eett aall..,, JJ NNuuttrr,, 22000065 SN Control Pre flight Post flight SSmmiitthh eett aall..,, JJ NNuuttrr,, 22000065 SN Control Pre flight Post flight Vitamin D and PTH Vitamin D and Disease Vitamin D status has been related to: Fractures, fracture risk, BMD Muscle strength/function, falls Cancer (prostate, breast, colon) Multiple sclerosis Blood pressure/heart disease Diabetes (type 1) Erkal, Osteo Int, 2006 Thomas et al., NEJM, 1998 Bischoff-Ferrari, Am J ClinNutr, 2006 Chapuy et al., Osteo Int, 1997 Recommendations Space Food Vit D (IU) Encourage adequate vitamin D: Flight Requirement (per day) 400 Menu 172 ±44 – Intake Salmon 396 • Fortified milk, orange juice Tuna 152 • Fish (salmon, tilapia, tuna) BBTurreenaaakk Nffaaossott dDDlerrii nnCkkasserole 11911666 • Few other sources… Cornflakes 88 – Sunlight TBuranna CShaelaxd Spread 8648 – Supplements Scrambled Eggs 64 Bread Pudding 56 Granola w/Raisins 44 Tapioca Pudding 44 …the criterion for broad-based supplementation in the Teriyaki Beef 36 general population is not fulfilled, except for in high Pork Chops 32 risk groups, such as the elderly…all other persons with Vegetable Quiche 28 negligible exposure to sunshine. Potato Soup 28 6 Upper Limits Vitamin D Toxicity 2000 IU/day is current defined IOM no observed adverse events limit (NOAEL) Hypercalcemia, hypercalciuria, soft tissue Studies of higher levels have proven safe… calcification, kidney stones Hathcocket al., AJCN, 2007 Sunlight does not result in toxicity Watch multivitamins (vitA and other nutrients may be in excess) Vitamin D Stability Study I-13 I-14 I-15 I-16 I-17 Vitamin D status goes down after long- 13 d 353 d 596 d 880 d duration spaceflight. ULF1.1 Questions: SUTLSF-11.211 CDABB A JuSlyT 1S7-,1 220106 BB JJuunnSeeT 122S322-A1, 1227000077 CFeSbT 2S10E-,1 220208 D NoSvUUT 2SLL9FF-,1 --22220608 July 4, 2006 A A Is the stability of vitamin D in the food system and B B supplement different during spaceflight? C C D D Is the daily dose not high enough to maintain status? Tortillas Almonds Does vitamin D metabolism change during spaceflight? Vitamin D analysis: Salmon Broccoli au Gratin Dried apricots Vitamin D supps Multivitamin supps Stability Study Stability Study V (Sitaamlmino nD) (SVuiptapmleimn eDnt) Stability of vitamin D in food/supplement is 600 600 not altered duringg sppacefligght IU/100 g 240000 IU/tablet 240000 Question: Ba0s1e3l idn eGro1u3n dd3 5Fl3i gd htGr3o5u3n dd5 9Fl6i gd htGr5o9u6n dd8 8Fl0i gd htGr8o8u0n dd Flight Ba0s1e3l idn eGro1u3n dd3 5Fl3i gd htGr3o5u3n dd5 9Fl6i gd htGr5o9u6n dd8 8Fl0i gd htGr8o8u0n dd Flight  Isst athtues dina ialyn d eonsveir soinmmpelyn tn owti thhi gnho esnuonu egxhp toos umraei?n tain (Zwart et al., 2009) 7 Polar Vitamin D Polar Vitamin D 25-OH vitamin D 200 120 2000 IU/d 3 leve411l000s000 0 0oI UIIfUU/ dv// ddi(t n((a nn=m = 1 i811n)99 ))D supplementation: PTH (pg/mL)11055000 nmol/L10468400000 14N00o00 p0 Ii UllIsU/dd 2000 IU/d (n = 18) 00 50 100 150 200 20 25-OH vitamin D (nmol/L) 3 blood collections and diet logs 0 April/March June/July Sept 25D, 1,25D, PTH, Ca, VDBP, NTX 100 Session 80 Double blinded supplementation PTH (pg/mL)246000 C84o%m polnia nacveerage (Smith et al., 2009) 0 April/March June/July Sept (Smith et al., 2009) Polar Vitamin D Polar Vitamin D Vitamin D status is related to body weight… 1000 or 2000 IU/d was enough to reach –what if we exclude subjects with BMI >29 kg/m2? 80 nmol/L and maintain vitamin D status 25-OH vitamin D 25-OH vitamin D 120 (Excluding subjects with BMI >29 kg/m2) 25 D (nmol/L) Session 1112505000000 25D (nmol/L) at Session 3112050500000 nmol/L102468000000 April/March JSuenses/Jiounly Sept nmol/L110224680000000 April/March JSuenses/iJounly Sept 0 Bo1d0y0 weight2 0S0ession 310 (0lb) 400 0 B1o0d0y weig20h0t at se3s00sion 34 (0l0b) (S5m00ith et al., 2009) 21400000000 I UIIUU/d//dd ( n((nn===111889))) 21400000000 I UIIUU/d//dd ( n((nn===1311)10)) Residual Questions… Polar II 2,000 IU/d (n=15) 10,000 IU/wk (n=14) Could compliance be improved with a Vitamin D, Calcium weekly dose instead of a daily dose? Immune Markers Is vitamin D status related to observed changes in immune function during polar winters? 8 Polar II Polar II 120 2000 IU/d 100 10000 IU/wk In addition to BMI, the efficacy of vitamin D % change25 D (nmol/L)2115054682000000000 Feb June Sept 21NPNP00oooo00 l laas00sruru 0 IpIpI U Ip(p(U/2l2ldee/00wmm00ke0e0n n IIttUU//dd)25 D (nmol/L))111C20202468000000000oE0mx0clp FuIeldUibain/ngd c s–eub:9jJe1ucn%tes with BSMeIp t>NN 2==91132 suppChange from baseline (nmol/L)l-e22468000000m0 entati5o0n is af1f0e0cted b15y0 PPboollaaarr s12 e&10 2lKi /2nwKke/ d(P (s<P0<t.0a0.10t)5u)s -50 Baseline 25D (nmol/L) Feb June Sept 10000 IU/wk –97% Vitamin D Dosing Study Residual Questions… 2,000 IU/d 10,000 IU/wk 50,000 IU weekly x4; then 1/mo Is a higher, less frequent dose as VitD (and metabolites) effective as a daily or weekly dose? Ca, etc. DDooeess aa hhiigghh ddoossee rreessuulltt iinn aa hhiigghh sseerruumm Diet, uv concentration of 25-OH vitamin D (or metabolites) or alter serum or urine calcium? Vitamin D Dosing Study Vitamin D Dosing Study 50,000 IU group ONLY uv/diet diet uv/diet diet 2000 IU/d S-uFruianbsejte escdat m bslpcolroeede dnrianwg; 24-h MFu25ra00oiansTBTB0,nd0te0iielltoo0mmm hS sdIoo0 Ua ueei1dd bnmI::p,U: ld i ddo s161epT orrot2 v0rlaarhiesdvi m,awwth0re iasd t r0e imer o 0 a 0d n iw--I n U /-o 2 Dffo4 3r-h bloFoWuadrshik nt& ee1 d2 4-admIUi nvbiiSlstoFatuoWurmapadrshiekt int&inr eoe2v dn2Dis 43oe- dfd 5o0s,e00b0lo FoWuadrshik n&t ee3 d2 4- MFu25raoin00sanet0,de0t 0hsd0mS aI 02Ubuim n:lIp,oU d ipTs1eo oltiev0rdmrsvi, at0ediaest0ri meao00dwn i In /-U2o D4ffo -3rh MFu25raoi00nsTBTBan0,ted0iilletoomm0 h0msdooS Ia0ee Udd3bui m::n I:lp, ddUod61 ipsT1erro 2 oaalthv0ried rmswwvhir,a t0e id rase t0 rime o a00 d--wn iI n U/-o2 D4ffo -3rh FuMraoinsnteet hsd a 4bm:lo pToliedm der a0w /-24-h nmol/L11055000 25 D 15P00la00c00e00b IIoUU//wmko % change from Time 0115050000 25D % ch TBilomoed: d2r4a wh r - F2a4s the dla btleoro:d TBilomoed: d2r4a wh r - 0 0 30 Days 60 90 -50 0 30Days60 90 TBuriloimnoeed: d4r8a wh r& s-pot TBuriloimnoeed: d4r8a wh r& s-pot 9 Vitamin D Dosing Study Vitamin D Dosing Study Urine Ca 2000 IU/d 8 10000 IU/wk 50000 IU/mo Placebo Baseline 60 Days 6 200 200 21000000 0I UIU/d/wk mol/d4 nmol/L111505000 nmol/L111505000 5P0la0c0e0b oIU/mo m02 50 50 0 28Time (d)60 90 0 0 6Hours a1f2ter dose24 48 0 0 6Hours a1f2ter dos2e4 48 15 2000 IU/d 15 10000 IU/wk 15 50000 IU/wk for 1 mo then monthly 1 subject in 2000 IU/d group had 2 values >150 nmol/L mmol/d150 mmol/d105 mmol/d105 2 subjects in 50000 IU group had 3-5 values > 150 nmol/L 0 0 7 14Tim2e1 (d)28 60 90 0 0 7 14Tim2e1 (d)28 60 90 0 0 7 14Tim2e1 (d)28 60 90 Nutrition SMO 150 D 125 n amiL)100 VitH)mol/mn 75 150 O( 50 25(OH) Vitamin D(nmol/L)112570205505 25 ( 250 SNContrPorle fliPgohtst flightPre BPRost BRaRED PPoollaarr (post) 0 Pre L-10FD15FD30FD60FD120FD180 R+0R+30 Calcium Human Body Excretion Diet StIonmteasctihn easnd Feces Absorption SSeeccrreettiioonn Calcium Pools Urine +24% Excretion Deposition Resorption 600 Bone 450 mg/day300 150 0 Preflight Inflight 10