There is truth in the old proverb about apple consumption and medical appointments. Insufficient vitamin C can contribute to leukemia. This observed relationship has now been shown to operate through the regulatory role the vitamin plays in the operation of bone marrow stem cells.
These days messages touting a single ingredient as being capable of curing all ills are more likely to peddle turmeric or cannabis, but a few decades ago it was vitamin C that was hailed as preventing everything from the flu to cancer if you took enough. As exaggerated as most of these claims were, it's certainly true that ascorbate, as it is also known, is vital to our health, sometimes in ways that are still unexplained.
“We have known for a while that people with lower levels of ascorbate (vitamin C) are at increased cancer risk, but we haven’t fully understood why,” said Dr Sean Morrison of Children’s Medical Center Research Institute UT Southwestern. Stem cells clearly played a part, but are so rare in any individual tissue that it is impossible to collect the millions usually used for metabolic analysis. Moreover, most mammals make their own ascorbate, but humans cannot, impeding the use of animal models.
Morrison and his co-authors of a paper published in Nature had to develop new techniques to measure metabolite usage in populations as small as 10,000 stem cells to address the first problem. On applying these techniques the authors discovered each type of blood-forming cell has a distinctive signature to its metabolite consumption. They tackled the second problem using mice that lack ascorbate-producing enzymes.
When given a low vitamin C diet these mice had more, and more active, bone marrow stem cells, increasing blood cell production at the price of higher rates of leukemia. The vitamin C concentration was related to levels of the enzyme Tet2, which regulates blood production. Without enough Tet2, the stem cells behaved like an overheating engine, turning out blood cells at a great rate until they turned cancerous. Something similar is observed when mutations reduce Tet2 production.
The first clinical application of the discovery is for patients with clonal hematopoiesis, a condition that often involves reduced Tet2 production and leukemia. “Our results suggest patients with clonal hematopoiesis and a Tet2 mutation should be particularly careful to get 100 percent of their daily vitamin C requirement,” Morrison said. “These patients... need to maximize the residual Tet2 tumor-suppressor activity to protect themselves from cancer.”
Since stem cells are much sparser in the rest of the body than in bone marrow it will be even more challenging to extend the research to other cancers.
The ideal dose of vitamin C remains to be established, although a paper, coincidentally published last week, may indicate benefits beyond current recommendations.