The intake of micronutrients such as vitamins and minerals is vital to human health, influencing various diseases, including cancer and neurological disorders. Numerous studies suggest that micronutrients play an essential role in maintaining genome integrity and establishing correct DNA methylation patterns. When these processes are disrupted due to micronutrient deficiencies, it accelerates aging (senescence) and heightens the risk of developing cancer by promoting chromosome aberrations and disrupting the regulation of oncogenes. Here, Alice Chang, Ph.D. at CMU Institute of Biochemistry, summarizes the role of B vitamins, particularly vitamin B6, in protecting against DNA damage and cancer.
Micronutrients, including B vitamins, serve as cofactors or substrates for enzymes involved in DNA repair and metabolism. A deficiency in these vitamins can damage DNA, similar to the action of carcinogens. However, the precise relationship between micronutrient intake and DNA damage remains complex, as it is influenced by individual genetic variations. Research on the impact of micronutrients on DNA damage, especially the B vitamins B6, B12, B9, and B1, highlights their involvement in one-carbon metabolism. This metabolic pathway is critical for processes like purine and thymidylate synthesis and the remethylation of homocysteine, which are vital for cell growth and DNA replication.
Vitamin B9 (folate) deficiency has been extensively studied due to its role in DNA synthesis. Folate deficiency has been shown to cause chromosome breakage, fragile sites, and aneuploidy, leading to DNA instability. In laboratory studies on human and animal cell cultures, folate deficiency induces significant genome instability, as indicated by the presence of micronuclei, nucleoplasmic bridges, and nuclear buds—markers of DNA misrepair and genetic damage. These findings underscore the importance of folate in maintaining genomic stability and preventing mutations that could lead to cancer.
Vitamin B6, a water-soluble vitamin, plays a crucial role in over 100 enzymatic reactions related to protein, carbohydrate, and lipid metabolism. Its involvement in one-carbon metabolism, which is important for DNA synthesis and methylation, links it to genome integrity and cancer risk. Epidemiological studies on the role of vitamin B6 in cancer prevention, particularly colorectal cancer, have produced mixed results. Some studies report an inverse association between plasma levels of vitamin B6 and colorectal cancer risk, showing a 30% to 50% reduction in cancer risk for individuals with higher plasma pyridoxal 5’-phosphate (PLP) concentrations compared to those with lower levels. However, studies examining dietary intake of vitamin B6 have shown inconsistent results. This discrepancy suggests that factors like genetic variations in one-carbon metabolism or the timing of vitamin B6 intake, such as during early life, might influence the vitamin’s protective effects against cancer.
Colorectal cancer remains a significant global health issue, with environmental factors like diet playing a crucial role in its development. While certain dietary factors like red meat and alcohol have been conclusively linked to colorectal cancer, the role of other nutrients, such as vitamin B6, is still under investigation. Vitamin B6 may influence colorectal carcinogenesis by regulating DNA methylation and synthesis, as well as reducing inflammation, oxidative stress, and cell proliferation—all of which are involved in cancer development. Some animal models have shown that vitamin B6 supplementation can suppress tumor formation and reduce cell proliferation in the colon.
Vitamin B6’s potential to influence inflammation is another key factor in cancer prevention. Chronic inflammation has been implicated in the development of colorectal cancer, and studies have shown that low vitamin B6 levels are associated with higher inflammation markers in diseases such as inflammatory bowel disease and rheumatoid arthritis. This connection suggests that maintaining optimal vitamin B6 levels might help reduce inflammation and, by extension, lower the risk of inflammation-related cancers like colorectal cancer. Moreover, vitamin B6’s ability to modulate oxidative stress and inhibit angiogenesis (the formation of new blood vessels that supply tumors) further highlights its potential as a preventive agent against cancer. Supplementing with vitamin B6 has been shown to reduce nitric oxide levels, which play a role in tumor growth and inflammation, while also reducing oxidative stress, a key factor in DNA damage and cancer development.
Despite the promising evidence linking vitamin B6 to cancer prevention, especially colorectal cancer, there are still unresolved questions. The effects of vitamin B6 intake during childhood or adolescence on cancer risk are not fully understood, nor is it clear how genetic variants in one-carbon metabolism affect the vitamin’s role in preventing cancer. Additionally, determining the optimal intake of vitamin B6 for cancer prevention remains challenging, as individual responses can vary widely.
To better understand these complex relationships, model organisms like Drosophila (fruit flies) can be valuable tools. These models offer a simpler system in which to study the mechanisms through which vitamin B6 and other micronutrients maintain genome integrity, helping to overcome the limitations of studying more complex human systems. By using various animal models, researchers hope to gain a deeper understanding of how micronutrients like vitamin B6 influence DNA damage and cancer risk, ultimately leading to more targeted and effective prevention strategies for human health.
References: doi.org/10.1098/rsob.200034, doi.or/10.3748/wjg.v19.i7.1005