When it comes to high altitude mountaineering, acclimatisation becomes a critical process to optimise. There are some factors that are better studied when it comes to their effect on the acclimatisation and some that are less explored. During my recent expedition to Kilimanjaro, I was surprised to notice a possible significant relationship of vitamin B12 stores to time spent in high altitude conditions. Could the B vitamins be a potentially weak link to be considered when preparing for a high altitude expedition and dealing with altitude sickness?

Concrete observations

Red blood cells and hemoglobin results

In order to quantify some of the metabolic changes occurring in my body during a high altitude adventure, I’ve decided to take as detailed bloodwork as possible shortly before and shortly after the expedition to Mount Kilimanjaro. You may reasonably argue that looking at bloodwork alone is too limiting a perspective when looking at acclimatisation, and one should also evaluate other things, such as mitochondria health. But one step at a time – let’s start basic, evaluate, derive action points and then dive next level deeper during the next expedition (this one likely to Lobuche in Nepal).

When comparing the two snapshots of the labs, most of the values didn’t provide significant deltas that would stir one’s curiosity. One noted development that was expected after an high altitude expedition was an overall increase in the volume of red blood cells (RBC) and their hemoglobin content. This is in line with our understanding that creation of new blood cells (erythropoiesis) is one of major mechanisms of altitude acclimatization and drives greater oxygen carrying capacity^​1,2​.

B12 & B9 Results

Among all the remaining lab results however rested two surprising values. Firstly, it was the level of vitamin B12, which has dropped to a half of its pre-expedition value. The value as measured two days before the start of the expedition has been 154 pmol/l. That is, given its reference frame, low and borderline value and the lab admits it may signal a deficiency. Yet is still considered, in US and in Switzerland, to be in ‘normal’ range^​3​. Not the best starting point, but OK to gather some data against.

After the expedition concluded and I returned to my home country for another test 18 days later, the value of vitamin B12 shows a drop to less than a half of the value to a clear deficiency range. This despite regime of supplementation and diet of eggs and beef – decent sources of the vitamin.

Second surprising value was the amount of B9 (folate) in red blood cells (RBC) – jumped significantly above the normal range in the same observed period. This is slightly confusing but is (among other possibilities) recognised as a signal of deficiency of B12.

Significance of B vitamins in erythropoiesis

In simple terms, vitamins B12 (cobalamin), B9 (folate or folic acid), and B6 (pyridoxine) play essential roles in the formation of new red blood cells through their involvement in various processes within the body. Here’s a brief overview of how each vitamin contributes to red blood cell formation:

• Vitamin B12 (Cobalamin): Vitamin B12 is crucial for DNA synthesis and helps maintain the health of nerve cells. It works closely with vitamin B9 (folate) in the production of red blood cells. B12 is necessary for the proper functioning of an enzyme called methionine synthase, which converts homocysteine to methionine. This conversion is critical for DNA synthesis, which is required for the formation of new red blood cells^​3​.
• Vitamin B9 (Folate or Folic Acid): Folate is vital for the synthesis of DNA, RNA, and proteins, which are essential components of red blood cells. It plays a significant role in the process of cell division, enabling the rapid production of red blood cells in the bone marrow. Like B12, folate is also involved in the conversion of homocysteine to methionine, which is necessary for DNA synthesis. In fact there is an interdependence between folate and B12 and impairment of any of the two leads to the same macrocytic anemia^​4–6​.
• Vitamin B6 (Pyridoxine): Vitamin B6 is involved in the synthesis of heme, a component of hemoglobin, which is the protein in red blood cells responsible for carrying oxygen. B6 also plays a role in the metabolism of amino acids, which are the building blocks of proteins, and supports the immune system. Furthermore, vitamin B6 is required for the conversion of homocysteine to cysteine, which can indirectly affect red blood cell production^​7,8​.

Erythropoiesis, high altitude and B vitamins in scientific literature

The relationship between the cobalamin, folate and pyridoxine and the process of erythropoiesis seems to be well established and documented in the literature^​9,10​. Deficiency in any of the three vitamins impairs either the red blood cells creation itself through diminishing the number of RBCs created or impairs their function through lower hemoglobin content or other structural issues in their synthesis. All these result in worsened oxygen carrying capacity of one’s blood.

When it comes to the literature on effects of intermittent hypoxia (state of not enough oxygen being available for homeostasis) during exposure to high altitude conditions, it is also well documented that these conditions promote erythropoiesis^​1,2​.

Unfortunately, there don’t seem to be studies that directly try to put all three topics together and evaluate the impact of the B12 and B9 on the red blood cells creation within the context of high altitude conditions. One could assume the high altitude which increases the rate of erythropoiesis leads to higher rate of usage of B vitamins required for these metabolic processes. Higher rate of usage then likely leads to the required intake of the two vitamins above the commonly accepted recommended daily values. On one hand, there is the question of how to avoid deficiency that certainly would hamper mountaineer’s acclimatisation progress. On the other, it might be worth investigating if additional care and supplementation of B12 might improve the acclimatisation rate and success on top of healthy baseline values, even when deficiency doesn’t come into play.

If you do encounter such a study or even anecdotal evidence, please share it in the comments below the post.

Conclusion

In conclusion, while there is a lack of direct evidence linking vitamin B12 and high altitude acclimatization or acute mountain sickness, the roles of vitamins B12, B9, and B6 in erythropoiesis are well-established. These vitamins play essential roles in the formation of new red blood cells, and their deficiency may lead to anemia, potentially affecting the body’s ability to adapt to high altitude environments. While further research is needed to explore the direct relationship between these B vitamins and high altitude acclimatization or acute mountain sickness, focusing on B vitamin status and supplementation before and during a mountaineering expedition might be beneficial. I’ll certainly run this experiment a few times this year and compare the lab results.

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Sources

1. Haase VH. Hypoxic regulation of erythropoiesis and iron metabolism. American Journal of Physiology-Renal Physiology. Published online July 2010:F1-F13. doi:10.1152/ajprenal.00174.2010
2. Vizcardo-Galindo G, León-Velarde F, Villafuerte FC. High-Altitude Hypoxia Decreases Plasma Erythropoietin Soluble Receptor Concentration in Lowlanders. High Altitude Medicine & Biology. Published online March 1, 2020:92-98. doi:10.1089/ham.2019.0118
3. Office of dietary supplements – vitamin B12 Fact Sheet for Health Professionals. U.S. Department of Health and Human Services, National Institutes of Health. Published December 22, 2022. Accessed March 20, 2023. https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/
4. The Water-Soluble Vitamins: B Vitamins and Vitamin C – Folate. In: Understanding Normal & Clinical Nutrition. 11th ed. Engage; 2018:315-319.
5. Folic Acid. In: Modern Nutrition in Health and Disease. 10th ed. Lippincott Williams & Wilkins; 2006:470-480.
6. Office of dietary supplements – Folate Fact Sheet for Health Professionals. U.S. Department of Health and Human Services, National Institutes of Health. Published November 30, 2022. Accessed March 18, 2023. https://ods.od.nih.gov/factsheets/Folate-HealthProfessional/
7. Office of dietary supplements – Vitamin B6 Fact Sheet for Health Professionals. U.S. Department of Health and Human Services, National Institutes of Health. Published June 2, 2022. Accessed March 19, 2023. https://ods.od.nih.gov/factsheets/VitaminB6-HealthProfessional/
8. Vitamin B6. In: Modern Nutrition in Health and Disease. 10th ed. Lippincott Williams & Wilkins; 2006:452-459.
9. Koury MJ, Ponka P. NEW INSIGHTS INTO ERYTHROPOIESIS: The Roles of Folate, Vitamin B₁₂, and Iron. Annu Rev Nutr. Published online July 14, 2004:105-131. doi:10.1146/annurev.nutr.24.012003.132306
10. Koury M, Ponka P. New insights into erythropoiesis: the roles of folate, vitamin B12, and iron. Annu Rev Nutr. 2004;24:105-131. doi:10.1146/annurev.nutr.24.012003.132306