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Cited by 139Spaceflight effects on biologyFolate and B Vitamins ResearchEffects of Radiation Exposure

Vision Changes after Spaceflight Are Related to Alterations in Folate- and Vitamin B-12-Dependent One-Carbon Metabolism,

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Zwart, Sara R., Gibson, C. Robert, Mader, Thomas H., Ericson, Karen, Ploutz-Snyder, Robert, Heer, Martina, Smith, Scott M.·2012·The Journal of Nutrition
DOI 10.3945/jn.111.154245
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Abstract

Approximately 20% (7 of 38) of astronauts on International Space Station (ISS) missions have developed measurable ophthalmic changes after flight. This study was conducted to determine if the folate- and vitamin B-12-dependent 1-carbon metabolic pathway is altered in these individuals. Since 2006, we have conducted experiments on the ISS to evaluate nutritional status and related biochemical indices of astronauts before, during, and after flight. Data were modeled to evaluate differences between individuals with ophthalmic changes (n = 5) and those without them (n = 15), all of whom were on ISS missions of 48-215 d. We also determined whether mean preflight serum concentrations of the 1-carbon metabolites and changes in measured cycloplegic refraction after flight were associated. Serum homocysteine (Hcy), cystathionine, 2-methylcitric acid (2MCA), and methylmalonic acid concentrations were 25-45% higher (P < 0.001) in astronauts with ophthalmic changes than in those without them. These differences existed before, during, and after flight. Preflight serum concentrations of Hcy and cystathionine, and mean in-flight serum folate, were correlated with change (postflight relative to preflight) values in refraction (P < 0.05), and preflight serum concentrations of 2MCA tended to be associated (P = 0.06) with ophthalmic changes. The biochemical differences observed in crewmembers with vision issues strongly suggest that their folate- and vitamin B-12-dependent 1-carbon transfer metabolism was affected before and during flight. The consistent differences in markers of 1-carbon metabolism between those who did and those who did not develop changes in vision suggest that polymorphisms in enzymes of this pathway may interact with microgravity to cause these pathophysiologic changes.

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  • Many potential confounding factors were ruled out, including sex, kidney function, vitamin status, and coffee consumption.

    “Many potential confounding factors were ruled out, including: sex, kidney function, vitamin status, and coffee consumption, among others.”

    From Red risks for a journey to the red planet: The highest priority human health risks for a mission to Mars (2020) · cites this paper as [53]

    The Discussion (page not provided) argues that nutritional deficits are unlikely, which partly supports the claim about vitamin status. It lists coffee consumption as a proposed cause but does not rule it out; the Participants and Methods section reports that all affected crewmembers were men, and the passages found do not show kidney function being ruled out. The claim therefore overstates how many factors the paper excluded. (LLM, conf=0.86)

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  • Affected crewmembers had significantly higher circulating concentrations of homocysteine and other one-carbon pathway metabolites compared to non-cases, and differences existed before flight.

    “This analysis revealed that affected crewmembers had significantly higher circulating concentrations of homocysteine and other one-carbon pathway metabolites when compared to non-cases and that these differences existed before flight53.”

    From Red risks for a journey to the red planet: The highest priority human health risks for a mission to Mars (2020) · cites this paper as [53]

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Research works printed but not linked: 3

  1. [18]18. Candito M, Candito E, Chatel M, van Obberghen E, Dunac A. Homocysteinemia and thrombophilic factors in unexplained decom- pression sickness. Rev Neurol (Paris). 2006;162:840-4.
  2. [19]19. Brown BA, Marx JL, Ward TP, Hollifield RD, Dick JS, Brozetti JJ, Howard RS, Thach AB. Homocysteine: a risk factor for retinal venous occlusive disease. Ophthalmology. 2002;109:287-90.
  3. [23]23. Kowa H, Yasui K, Takeshima T, Urakami K, Sakai F, Nakashima K. The homozygous C677T mutation in the methylenetetrahydrofolate reduc- tase gene is a genetic risk factor for migraine. Am J Med Genet. 2000;96:762-4.

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Authors
Zwart, S. R., Gibson, C. R., Mader, T. H., Ericson, K., Ploutz-Snyder, R., Heer, M., & Smith, S. M.
Affiliations
  • Universities Space Research Association (US)
  • Wyle (United States) (US)
  • Alaska Native Medical Center (US)
  • Indiana University – Purdue University Fort Wayne (US)
  • University of Bonn (DE)
  • National Aeronautics and Space Administration (US)
Corresponding author
Smith, Scott M.
ORCID
Venue
The Journal of Nutrition
Publisher
Elsevier BV
Published
2012-03
Volume
142
Issue
3
Pages
427-431
ISSN
0022-3166 (ISSN-L)
DOI
10.3945/jn.111.154245
OpenAlex
W2112439068
Cited by
139
References
26
Citations by year
2026: 7 · 2025: 15 · 2024: 9 · 2023: 11 · 2022: 7 · 2021: 14 · 2020: 15 · 2019: 13 · 2018: 9 · 2017: 13 · 2016: 7 · 2015: 6 · 2014: 4 · 2013: 8 · 2012: 1
FWCI
4.07
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Nutrition (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Aeronautics and Space Administration
  • Purdue University
  • Johnson Space Center
Topics
  • Health Sciences › Medicine › Physiology › Spaceflight effects on biology
  • Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
Keywords
spaceflight, vision changes, one-carbon metabolism, folic acid, vitamin B12, homocysteine, cystathionine, methylmalonic acid, microgravity, astronauts, International Space Station, cycloplegic refraction, nutritional status, genetic polymorphism
MeSH terms
Adult, Carbon Dioxide, Citrates, Cystathionine, Female, Folic Acid, Homocysteine, Humans, Male, Methylmalonic Acid, Middle Aged, Models, Biological, Refraction, Ocular, Space Flight, Vision Disorders, Vitamin B 12, Astronauts, Metabolic Networks and Pathways

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