HQ U.S. Air Force Academy

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Acclimatization to Moderate Altitude: Red Cell

Mass & Performance

Jeff Nelson, Ph.D. USAFA Human Performance

Laboratory

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Outline

Adaptation and acclimatization to moderate altitude via chronic residence at USAFA

Lt Col Michael Brothers, Ph.D. – principal investigator Retrospective study Longitudinal and cross-sectional studies USAFA total hemoglobin mass altitude study

Individual variability, Neocytolysis, Iron supplementation

Summary

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Background

Limited data exists for adaptations occurring at moderate altitude (MA: 1,500-3,000m) despite the fact that ½ billion people reside at MA, & 100 million sojourn to MA annually

Individual variability

Neocytolysis

Iron Supplementation

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USAFA for analysis oflong-term MA adaptation

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USAFA for analysis oflong-term MA adaptation

Elevation = 2210m (7,250 feet) Freshman students from all over the world (SL &

MA) arrive w/in 24-hour period & in-process the same day each summer

Unique, well-controlled military environment: Stringent physiological requirements for appointment Limited travel away from USAFA until Thanksgiving (4-

6 days) or Winter (2-3 week) break (+5.5 month MA exposure)

Rigorous physical training/testing programs all 4 years Nearly identical diet

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Retrospective USAFA data

Examined pre-existing fitness (AFT/PFT) & blood data (H&H) of SL & MA cadets: n = 2,147 male cadets (classes ’03 to ‘09) SL < 153m / 500 ft: DE, FL, LA, MS, RI MA >1500m / 5,000 ft: CO, WY

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Results: 1.5 mile AFT run time

†*†*†*

525

575

625

675

725

1.5 3 7 15 19 27 31

Chronic Alitude Exposure (months)

AF

T R

un T

ime

(sec

s)

MA

SL

C.

Legend: Significant (P < 0.01) main effects of altitude, time, & alt. x time interaction.

*, Significant difference between MA & SL; †, significant differences over time.

MA cadets ran 20-30s (4-5%) faster than SL cohorts

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Retro results: PFT (pull-ups, push-ups, sit-ups,

standing long jump) score

150

250

350

450

1.5 3 7 15 19 27 31

Chronic Altitude Exposure (months)

PF

T S

core

(poi

nts)

MA

SL

B.

Legend: Significant (P < 0.01) main effects of altitude & time; no altitude x time interaction!

MA cadets perform 6-7% better for 2+ yr than SL cohorts

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Results: [Hb]

†‡†‡†‡*†§‡

13

14

15

16

17

18

Pre- USAFA (-6m)

AcuteUSAFA

(4d)

ChronicUSAFA(17m)

ChronicUSAFA(23m)

ChronicUSAFA(30m)

[Hb]

(g ·d

L -1)

MA

SL

Legend: Significant (P < 0.005) main effects of altitude, time, & alt. x time interaction.

Significant difference between MA & SL: § (P< 0.001), * (P < 0.01);

Significant differences over time: Pre, † (P < 0.001); Acute, ‡ (P < 0.01).

MA cadets’ 1.0 g/dL (6%) higher initially;SL cadets’ increased 1.5 g/dL (10%) with long-term MA exposure

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Retrospective Study

MA (USAFA: 2210m) exposure appeared to have an impact on SL cadets’ performance, & significantly increased [Hb]

Based on performance differences, acclimatization to MA appears to require 7+ months

Retrospective analysis prevents us from knowing if changes in performance are related to changes in blood….

While hematological adaptations could account for aerobic differences, anaerobic differences are still evident after hematological acclimatization

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Long-term exposure to MA: Hematological & Physiological

Adaptations Subjects: 116+ male freshman – senior cadets

Freshman: 44+ (29 SL, 15 MA) Sophomore: 30+ (18 SL, 12 MA) Junior & Senior: 42+ (27 SL, 15 MA)

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Longitudinal Design

Time (weeks)Parameters Parameters examined:examined: (SL & MA)(SL & MA)

+.5+.5

(da(day4)y4)

+6+6 +8+8 +12+12 +15+15 +17 +17 to to +20+20

+23+23 +28+28 +30+30 +37+37 +42 +42 to to +45+45

+46+46

Hematological Hematological data:data:(CBC w/ retic. panel, (CBC w/ retic. panel, serum ferritin, sTfR, serum ferritin, sTfR, EPO)EPO)

XX XX XX XX XX XX XX

AFT & PFT:AFT & PFT:(part of USAFA fitness (part of USAFA fitness testing program)testing program)

XX XX XX

GXT:GXT:VOVO2peak2peak, power, sub-, power, sub-

max. economy & max. economy & [BLa], S[BLa], SaaOO22, etc., etc.

XX XX

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Cross-sectional Design

Time (weeks)Parameters Parameters examined:examined: (SL & MA)(SL & MA)

+.5+.5

(da(day4)y4)

+6+6 +8+8 +12+12

(+1(+1-3 -3 yrsyrs))

+15+15 +17 +17 to to +20+20

+23+23 +28+28 +30+30 +37+37

(+1(+1-3 -3 yrsyrs))

+42 +42 to to +45+45

+46+46

Hematological Hematological data:data:(CBC w/ retic. panel, (CBC w/ retic. panel, serum ferritin, sTfR, serum ferritin, sTfR, EPO)EPO)

XX XX XX XX XX XX XX

AFT & PFT:AFT & PFT:(part of USAFA fitness (part of USAFA fitness testing program)testing program)

XX XX XX

GXT:GXT:VOVO2peak2peak, power, sub-, power, sub-

max. economy & max. economy & [BLa], S[BLa], SaaOO22, etc., etc.

XX XX

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Longitudinal/Cross-sectionalResults: AFT/PFT

490

540

590

640

690

6 12 30

Chronic MA Exposure (weeks)

AFT

Tim

e (s

ecs)

MA

SL

Legend: Significant (P < 0.05) main effects of altitude & time with no interaction.

****

500

540

580

620

660

Sem. 1 Sem. 2 Sem. 1 Sem. 2 Sem. 1 Sem. 2

Freshmen Sophomore Jr. & Sr.

USAFA Semester and Class Year

AF

T R

un

Tim

e (s

ecs)

MA

SL

Legend: Significant (P < 0.03) main effects of altitude & time;

*, significant (P < 0.05) differences between MA & SL.

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Results: Cross-sectional hematological differences

†‡

14.5

15

15.5

16

16.5

17

17.5

18

Sem. 1 Sem. 2 Sem. 1 Sem. 2 Sem. 1 Sem. 2

Freshmen Sophomore Jr. & Sr.

[Hb]

(g·d

L-1)

MA

SL

[Hb]: Significant (P < 0.03) main effect of class, & class x time interaction.

†, significant (P < 0.05) between class; ‡, significant (P < 0.05) differences over time.

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Results: VO2peak & economy

***

50

55

60

65

Sem. 1 Sem. 2 Sem. 1 Sem. 2 Sem. 1 Sem. 2

Freshmen Sophomore Jr. & Sr.

VO

2pea

k (m

L·k

g -1

·min

-1)

MA

SL** *

180

200

220

240

260

Sem. 1 Sem. 2 Sem. 1 Sem. 2 Sem. 1 Sem. 2

Freshmen Sophomore Jr. & Sr.

Subm

x. E

con.

(mL

· kg

-1· k

m -1

)MA

SL

Legend: Significant (P < 0.03) main effects of altitude & time, and significant (P < 0.05) alt. x class & alt. x time interactions occurred in sub-maximal running economy. *, Significant (P < 0.05) differences between MA & SL.

7.9% 5.2% 1.8%

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USAFA THM Altitude Study

Consisted of early recruitment & baseline THM assessment (During In-processing)

Double blind, placebo control Fe supplementation w/ nine additional THM assessments (every 4-7 wks)

Additional VO2peak (3) & economy (5) tests at 3-5 velocities, w/ [BLa] & SaO2, plus AFT/PFT dataGenetic testing to assess individual variabilityN = 100 (20 MA, 80 SL; 50% Fe supplementation)

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THM determination via CO re-breathing

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Acute hematological data

Altitude-related differences in erythrocyte (EV), plasma PV), and total blood (BV) volumes among male subjects

#, sig. diff. between MA & SL subjects (p < 0.01)

*, sig. diff. between MA & SL subjects (p < 0.05)

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Acute hematological data

Altitude-related differences in erythrocyte (EV), plasma PV), and total blood (BV) volumes among male subjects

Altitude-related differences in normalized THM among male subjects (no MA females able to be recruited)

#, sig. diff. between MA & SL subjects (p < 0.01)

*, sig. diff. between MA & SL subjects (p < 0.05)

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Chronic hematologicaldata: THM

Male THM longitudinal data

Significant main effect of time (p<0.001), Alt. (p<0.04), no effect of Fe (p=0.173), no interaction (p>0.38)

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THM Peak

Group Week THM % Increase

Fe 2+ 15 +73.7±39.4 g +10.4%

Placebo 28 +68.6±9.4 g +9.4%

Clearly, the iron group had a shorter acclimatization time

Hematological acclimatization is longer in duration than previously thought.

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Indirect evidence of neocytolysis

Group THM loss (g) % of THM gained at MA

Male Iron -33.9±26.8 g -57.8%

Male Placebo -21.2±41.1 g -28.2%

Female Iron -25.7±15.7 g -41.4%

Female Placebo -18.6±20.9 g -33.7%

Winter break at sea level: ~3 weeksRange of total THM: 2.5%-4.0%Does exercise attenuate THM loss?

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Chronic 1.5 mile run (AFT) performance

Male AFT data

Significant main effect of time (p<0.001), no effect of Fe (p = 0.59), Alt. (p=0.36), no interaction (p=0.83)

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Chronic 1.5 mile run (AFT) performance

Female AFT data

Significant main effect of time (p<0.001), no effect of Fe (p=0.422), significant interaction (p=0.049)

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Discussion, conclusions& application

Verified that hematological acclimatization requires longer time on average (~ 3-4 mo if Fe-replete; 4-6 wks possible if ‘fast’ responder, > 6 mo for ‘slow’ responders)

Fe supplement sig. improved female, but not male, adaptations; supplement dose insufficient?

De-acclimatization issues at winter break (neocytolysis)? Ind. variability readily apparent—genetic analysis pending

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Main Points

Hematological acclimatization at MA takes longer than originally thought: 15-28 weeks, depending on genetics and/or iron availability

Performance acclimatization takes ~ 1.5 yrs in our cadet population

Importance in acknowledging neocytolysis in acclimatization time

Iron supplementation – importance to note toxicity potential if unmonitored; individual differences

Application

27/22

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Acknowledgments / Questions

USAFA Human Performance LaboratoryHQ USAFA / ADPH

2169 Field House Drive, Ste 111USAF Academy CO 80840

Jeff Nelson, Ph.D. jeffrey.nelson@usafa.edu

Thanks to: Lt Col Brandon Doan (Ph.D.), Lt Col Michael Zupan (Ph.D.), Mr. Al Wile (M.S.); Dr. Jeff Nelson, Dr. Bill Byrnes & Dr. Randy Wilber; Capt. Jules Macgregor, 2d Lt Andrea Pinchak, TSgt Chris Ruth, Ms. Christina Minares; Cadets Courtney Hemmert, Zach Garrett, Russell Smith, Jane Hwang, Robert Edmonds, Andrew Groberg, Chloe Angello, and Tyner Apt (former USAFA 499 researchers), Ms. Liz Terry, Mr. Ben Ryan, Ms. Darci Thurston, (HPL interns), plus all the USAFA cadet subjects!

Funding: HQ USAF/SGSR, AFRL and USAFA HERC