How to Reduce Altitude Sickness, Especially if You Have MTHFR SNP

Heading to the mountains this winter? When we ascend to higher altitudes—typically above 6,000 feet—the air pressure drops, meaning every breath delivers less oxygen to our bodies. This oxygen shortage, or hypoxia, can trigger a cluster of symptoms known as altitude sickness or acute mountain sickness (AMS). People with the MTHFR gene variants struggle more to make the necessary adjustments and are more susceptible to altitude sickness. 

Why Altitude Sickness Happens

At sea level, our lungs and blood efficiently deliver oxygen to every cell. But in thinner air, the body must work harder to adapt. Initially, breathing rate increases, heart rate rises, and more red blood cells are produced to carry oxygen. For some people, though, these adjustments aren’t fast enough. Altitude sickness symptoms, including headache, nausea, fatigue, dizziness, and sleep disturbances, can appear within hours. If ascent continues too rapidly, altitude sickness can escalate into more dangerous conditions such as high-altitude pulmonary edema (HAPE) or high-altitude cerebral edema (HACE)—life-threatening complications caused by fluid buildup in the lungs or brain.

MTHFR Gene Variants and Altitude Intolerance

People with certain MTHFR (methylenetetrahydrofolate reductase) gene variants—especially the C677T or A1298C mutations—may find they struggle to adjust to high altitudes quickly and are more susceptible to altitude sickness. This genetic variant impairs folate metabolism and reduces the body’s ability to recycle homocysteine into methionine, an essential process for blood vessel health and oxygen delivery.  Elevated homocysteine levels are linked with poor endothelial (blood vessel lining) function and reduced nitric oxide availability, both of which can decrease oxygen efficiency and circulation. At high altitude—where oxygen is already scarce—these effects can compound the stress on the cardiovascular and nervous systems.  When headed to high altitudes, individuals with MTHFR gene variants should consider supporting their oxygenation pathways with a strategy to increase nitric oxide (NO). Some studies suggest that individuals with MTHFR variants may experience more pronounced fatigue, headaches, difficulty concentrating, increased oxidative stress, and slower acclimatization.

How to Prevent or Reduce Altitude Sickness

Gradual ascent is the best prevention for altitude sickness. Increasing sleeping elevation by no more than 1,000 feet per night once above 8,000 feet gives the body time to acclimate. Other proven strategies include:

• Hydration: Dehydration can worsen symptoms; drink plenty of water and avoid excess alcohol or caffeine.
• Rest and slow exertion: Overexertion amplifies oxygen demand.
• Three to four weeks prior to departure, meet with your medical provider to put together a good supplementation plan to begin and sustain through the trip. This preparation can be especially important for those who struggle with altitude sickness and/or have MTFHR gene variants.
• Supplementation:  A week before leaving on your trip and during the trip, consider increasing iron, methyl-B12, and methyl-folate to help optimize red blood cell carrying capacity.  Consider supplements that increase nitric oxide production, such as Berkeley Life or QS Cardio Elite.  N-acetylcysteine (NAC), liposomal glutathione, and/or alpha-lipoic acid can help to reduce oxidative stress under hypoxia. CoQ10 can offer mitochondrial support and improve cellular energy under low oxygen.  Magnesium can help relax blood vessels and improve sleep at altitude. These supplements could prove especially helpful for those with the MTFHR gene variant.
• Diet: Before and during your trip, focus on eating dark leafy greens, a wide array of fruits and vegetables, as well as complex carbohydrates such as potatoes, rice, quinoa, and sweet potatoes. Lighter meals with complex carbs can improve oxygen efficiency.
• Train: Several weeks before leaving, increase cardiovascular exercise for peak fitness.
• Oxygen supplementation or descent: If symptoms become severe, descending to a lower altitude and/or using supplemental oxygen is critical.

Enjoy your winter travels. Be well.

References:

1. Basnyat, B., & Murdoch, D. R. (2003). High-altitude illness. The Lancet, 361(9373), 1967–1974.
2. Julian, C. G., Wilson, M. J., & Moore, L. G. (2019). Evolutionary adaptation to high altitude: A view from in utero. American Journal of Human Biology, 31(2).
3. Yi, X., et al. (2010). Sequencing of 50 human exomes reveals adaptation to high altitude. Science, 329(5987), 75–78.
4. Kalhan, S. C., & Marczewski, S. E. (2012). Methylenetetrahydrofolate reductase gene variants and homocysteine metabolism. Nutrition Reviews, 70(2), 80–87.
5. Bailey, D. M., et al. (2013). High-altitude illness: Mechanisms and mitigation. Physiology, 28(2), 87–97.

The Woodlands Institute for Health & Wellness - Mila McManus MD

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