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Project Title:  B Complex: A Nutraceutical SANS Countermeasure Reduce
Images: icon  Fiscal Year: FY 2022 
Division: Human Research 
Research Discipline/Element:
HRP HHC:Human Health Countermeasures
Start Date: 01/03/2022  
End Date: 01/02/2028  
Task Last Updated: 03/25/2022 
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Principal Investigator/Affiliation:   Zwart, Sara  Ph.D. / NASA Johnson Space Center 
Address:  Department of Preventive Medicine and Community Health 
2101 Nasa Pkwy, Mail Stop SK3 
Houston , TX 77058-3607 
Email: sara.zwart-1@nasa.gov 
Phone: 281-483-3753  
Congressional District: 36 
Web:  
Organization Type: NASA CENTER 
Organization Name: NASA Johnson Space Center 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Smith, Scott  Ph.D. NASA Johnson Space Center 
Chen, John  M.D., Ph.D. Mayo Clinic 
Heer, Martina  Ph.D. University of Bonn, Germany 
Laurie, Steven  Ph.D. KBR/NASA Johnson Space Center 
Macias, Brandon  Ph.D. NASA Johnson Space Center 
Pardon, Laura  O.D., Ph.D. NASA Johnson Space Center 
Young, Millennia  Ph.D. NASA Johnson Space Center 
Project Information: Grant/Contract No. Directed Research 
Responsible Center: NASA JSC 
Grant Monitor: Stenger, Michael  
Center Contact: 281-483-1311 
michael.b.stenger@nasa.gov 
Solicitation / Funding Source: Directed Research 
Grant/Contract No.: Directed Research 
Project Type: FLIGHT 
Flight Program:  
TechPort: No 
No. of Post Docs:  
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:  
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No. of Bachelor's Degrees:  
Human Research Program Elements: (1) HHC:Human Health Countermeasures
Human Research Program Risks: (1) HHC Food:Risk of Performance Decrement and Crew Illness Due to an Inadequate Food System (IRP Rev J)
(2) SANS:Risk of Spaceflight Associated Neuro-ocular Syndrome (IRP Rev I)
Human Research Program Gaps: (1) FN-401:Food as a Physiological CM - Understand and develop strategies for use of food as a physiological countermeasure (for aspects such as radiation/oxidative stress, cardiovascular health, bone, SANS, exercise, immune, MicroHost) (IRP Rev M)
(2) SANS-202:Determine if genetic/metabolic/anatomic dispositions and biomarkers, and sex differences have a contributing role in the development of ocular manifestations (IRP Rev L)
Task Description: Some astronauts on International Space Station (ISS) missions have experienced ophthalmic pathologies including optic disc edema, part of what is characterized as Spaceflight Associated Neuro-ocular Syndrome (SANS). While the precise cause for the optic disc edema is not known, it is likely that there are multiple contributing factors, including genetic and environmental factors that may affect the response to headward fluid shifts. Biochemical evidence reveals that crewmembers with optic disc edema have higher circulating concentrations of at least 4 metabolites from the one-carbon metabolic pathway before, during, and after flight compared to astronauts that did not develop optic disc edema. B-vitamin status at landing and the presence of specific one-carbon pathway single nucleotide polymorphism (SNP) alleles were significant predictors for the incidence of astronaut ophthalmic pathologies, including optic disc edema, choroidal folds, and cotton wool spots. When looking at the individual SNPs, the G allele of methionine synthase reductase (MTRR, rs1801394) A66G, and the C allele of serine hydroxymethyltransferase-1 (SHMT1, rs1979277) C1420T, were associated with higher incidence of ophthalmic findings after flight compared to those with the A or T alleles.

In ground analog studies, end-tidal CO2, a reflection of arterial CO2, response to acute head-down tilt (HDT) bed rest and CO2 exposure was related to G and C alleles of MTRR A66G and SHMT1 C1420T and B-vitamin status. Supportive of this, these same alleles were related to the presence of optic disc edema in different bed rest subjects. Subjects were exposed to strict 6°-HDT bed rest and 0.5% CO2 for 30 days and 5 out of 11 subjects developed optic disc edema. The number of G and C alleles were found to be associated with the change in total retina thickness (ΔTRT), a quantitative measure of optic disc edema. Based on our data, differences in genetics and altered one-carbon biochemistry before flight support that one-carbon metabolism may be involved.

We hypothesize that genetics and B-vitamin status are indispensable elements of this phenomenon, along with other potential factors. Dietary B-vitamin insufficiencies and variants in genes involved in the one-carbon metabolic pathway can contribute to lower B-vitamin status and pathway inefficiency, which can affect numerous outcomes, including nitric oxide (NO) production and endothelial function.

To that end, we propose a nutraceutical containing bioactive B-vitamins as a countermeasure to optimize function of the one-carbon pathway and prevent or mitigate optic disc edema during spaceflight.

This proposal aims to test the hypotheses that one-carbon pathway genetics can predispose an individual to SANS pathologies during flight, and that this effect may be prevented or mitigated through supplementation of vitamins that can affect one-carbon pathway function.

The hypothesis will be tested in the following specific aims:

1. Determine whether provision of a daily nutraceutical containing 5-methyltetrahydrofolate (5-MTHF), pyridoxine, methylcobalamin (vitamin B12), and riboflavin prevents or mitigates SANS pathology (significant ΔTRT) compared to astronauts who did not take the supplement in previously flown astronauts with available TRT data.

2. Determine one-carbon pathway SNP profiles in all participating astronauts being supplemented, and assess whether individuals with 3-4 risk alleles for MTRR A66G and SHMT1 C1420T polymorphisms have greater mitigation of ΔTRT during and after spaceflight.

3. Determine whether subjects with 3-4 risk alleles exhibit differences in biomarkers of endothelial function, compared to subjects with 0-2 risk alleles.

We propose to provide the nutraceutical countermeasure to all participating crewmembers before and during flight, and we will assess whether the supplement provides greater mitigation of changes in TRT in individuals with 3-4 risk alleles. We will include assessments of ocular health, along with determinants of vascular endothelial function, advanced glycation end products, and nutritional status and one carbon biochemistry. These additional measures will be critical for the further definition of the causes of SANS, and in understanding the effect of the countermeasure. Finally, the supplemented subjects in this study will be compared against TRT data from previously flown astronauts known to have not taken supplements during their missions.

Rationale for HRP Directed Research: This research is directed because it contains highly constrained research. This project originated as an update to a proposal originally titled “B Complex: 5- Methyltetrahydrofolate, Riboflavin, Pyridoxine, and Methylcobalamin Supplementation as a Non-Mechanical Countermeasure to Mitigate Optic Disc Edema Changes During Strict 6º Head-Down Tilt Bed Rest”, which was reviewed and selected from the 80JSC018N0001-SANS NASA Research Announcement. The implementation of this countermeasure during bed rest was not possible given constraints around this type of countermeasure study at the German Aerospace Center's (DLR) :envihab facility. Therefore, this bed rest study was converted to a flight study in order to test this countermeasure in an actual spaceflight environment.

Research Impact/Earth Benefits:

Task Progress & Bibliography Information FY2022 
Task Progress: New project for FY2022.

Bibliography Type: Description: (Last Updated: ) 

Show Cumulative Bibliography Listing
 
 None in FY 2022