STU-03 · Landmark study · Research

ISS Long-Duration Cohort Studies

Cardiovascular Musculoskeletal Neuro-ophthalmic Immune & Hematologic Vestibular & Sensorimotor Renal & GU In-flight Postflight Recovery LEO long-duration Clinician Researcher Student

draft AI-assisted Last reviewed: Pending review · Reviewer: Pending review

Bottom line

ISS cohorts consistently show deconditioning, bone loss, eye changes and immune changes on 4- to 6-month missions, despite countermeasures. ◆◆◆◇ Moderate · F
Responses vary widely between individuals, and samples are small. Averages hide important outliers. ◆◆◆◆ High · F

Proposed certainty (◆ High → ◇ Very low) and evidence-type tags: F flight · A analog · M model/animal · C computational · E expert/operational/standards. AI-proposed, pending reviewer confirmation. How to read the grades.

Selected cohort studies

Study	Who	What was measured	Key finding
Scott 2023 [1]	46 astronauts, 178 ± 48 days	Multisystem fitness	About 600 min/week of exercise didn’t fully prevent deconditioning; wide individual variation
Mader 2011 [2]	7 astronauts (plus questionnaires from about 300)	Eyes	First detailed report of optic disc edema, globe flattening, folds and hyperopic shifts, now called SANS
Roberts 2017 [3]	18 long- vs 16 short-duration	Brain MRI	Central sulcus narrowing in 17 of 18 long-duration vs 3 of 16 short-duration
Gabel 2022 [4]	17 astronauts	Tibia and radius HR-pQCT	9 of 17 had not recovered tibia density at 12 months
LeBlanc 2013 [5]	7 on alendronate vs 18 and 11 exercise-only	Bone DXA/QCT	ARED plus alendronate reduced almost all expected bone changes
Moore 2014 [6]	14 astronauts	Peak VO₂	About 17% drop early in flight, partial recovery in flight
Lee 2015 [7]	20 ISS vs 65 Shuttle	Tilt test	Landing-day completion: 2 of 6 ISS vs 52 of 65 Shuttle
Crucian 2015 [8]	23 astronauts	Immune function	Reduced T-cell function persisted through 6-month missions
Mehta 2017 [9]	23 astronauts	Latent viruses	8 of 23 shed EBV, VZV or CMV
Marshall-Goebel 2019 [10]	11 astronauts	Jugular vein ultrasound	Stagnant or reverse flow in 6; 1 occlusive thrombus
Smith 2015 [11]	ISS crews, 4–6 months	Bone markers, stone risk	Stone risk rose regardless of exercise; low urine volume key
Mulavara 2010 [12]	18 crew, about 185 days	Obstacle course	Median 48% slower; about 15 days to 95% recovery
Whitson 2009 [13]	30 Mir/ISS crew	Potassium citrate (randomized, placebo-controlled on ISS)	Lower urinary calcium; stone risk held at preflight levels

What the cohorts show together

Countermeasures help but don’t fully protect. Exercise and nutrition reduce, but don’t eliminate, losses in fitness and bone [1][4][5].
Recovery is often incomplete or slow, especially for bone [4].
Individual variation is large, so averages hide people who are much more affected [1].

Limitations

Most missions were 4–6 months in low Earth orbit. Mars-length exposures are untested.
Few women in most cohorts, and few people over 55.
Countermeasure protocols changed over the ISS era, which makes comparisons across years hard.
Many measures are taken only before and after flight, which misses the in-flight time course.

Evidence profile

Overall certainty: ◆◆◆◇ Moderate (proposed)
Evidence types: F · Flight data
Literature through: 2026-10-14

Requirements referenced 0

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References 13

Scott JM, et al. Effects of exercise countermeasures on multisystem function in long duration spaceflight astronauts. NPJ Microgravity. 2023;9:11. doi:10.1038/s41526-023-00256-5 PMID:36737441 Peer-reviewed F
Mader TH, et al. Optic disc edema, globe flattening, choroidal folds, and hyperopic shifts observed in astronauts after long-duration space flight. Ophthalmology. 2011;118(10):2058–2069. doi:10.1016/j.ophtha.2011.06.021 PMID:21849212 Peer-reviewed F
Roberts DR, et al. Effects of spaceflight on astronaut brain structure as indicated on MRI. N Engl J Med. 2017;377(18):1746–1753. doi:10.1056/NEJMoa1705129 PMID:29091569 Peer-reviewed F
Gabel L, et al. Incomplete recovery of bone strength and trabecular microarchitecture at the distal tibia 1 year after return from long duration spaceflight. Sci Rep. 2022;12:9446. doi:10.1038/s41598-022-13461-1 PMID:35773442 Peer-reviewed F
LeBlanc A, et al. Bisphosphonates as a supplement to exercise to protect bone during long-duration spaceflight. Osteoporos Int. 2013;24(7):2105–2114. doi:10.1007/s00198-012-2243-z PMID:23334732 Peer-reviewed F
Moore AD Jr, et al. Peak exercise oxygen uptake during and following long-duration spaceflight. J Appl Physiol. 2014;117(3):231–238. doi:10.1152/japplphysiol.01251.2013 PMID:24970852 Peer-reviewed F
Lee SMC, et al. Orthostatic intolerance after ISS and Space Shuttle missions. Aerosp Med Hum Perform. 2015;86(12 Suppl):A54–A67. doi:10.3357/AMHP.EC08.2015 PMID:26630196 Peer-reviewed F
Crucian B, et al. Alterations in adaptive immunity persist during long-duration spaceflight. NPJ Microgravity. 2015;1:15013. doi:10.1038/npjmgrav.2015.13 PMID:28725716 Peer-reviewed F
Mehta SK, et al. Latent virus reactivation in astronauts on the International Space Station. NPJ Microgravity. 2017;3:11. doi:10.1038/s41526-017-0015-y PMID:28649633 Peer-reviewed F
Marshall-Goebel K, et al. Assessment of jugular venous blood flow stasis and thrombosis during spaceflight. JAMA Netw Open. 2019;2(11):e1915011. doi:10.1001/jamanetworkopen.2019.15011 PMID:31722025 Peer-reviewed F
Smith SM, et al. Bone metabolism and renal stone risk during International Space Station missions. Bone. 2015;81:712–720. doi:10.1016/j.bone.2015.10.002 PMID:26456109 Peer-reviewed F
Mulavara AP, et al. Locomotor function after long-duration space flight: effects and motor learning during recovery. Exp Brain Res. 2010;202(3):649–659. doi:10.1007/s00221-010-2171-0 PMID:20135100 Peer-reviewed F
Whitson PA, et al. Effect of potassium citrate therapy on the risk of renal stone formation during spaceflight. J Urol. 2009;182(5):2490–2496. doi:10.1016/j.juro.2009.07.010 PMID:19765769 Peer-reviewed F

Machine-checked on 2026-10-14: each URL resolved, each DOI's title/journal/year matched via Crossref, and claims were checked against the source text (abstract or full NASA page). Human verification against full text is still required before review. NASA documents are U.S. Government works (public domain) and are summarized with attribution; journal articles are summarized, not reproduced.

Article info

Authors: Pending (AI-assisted draft)
Reviewer: Pending review
Last reviewed: Pending review
Literature through: 2026-10-14
AI-assisted: Yes (disclosed)
COI: Pending
License: CC BY-SA 4.0
Use: Educational only · Disclaimer
Cite this version: Pending first edition