From a recent study published in the European Journal of NutritionAustralian researchers investigated whether magnesium deficiency in the healthy middle-aged Australian population was independently or in combination with elevated homocysteine levels associated with in vivo deoxyribonucleic acid (DNA) damage.
Background
Magnesium is one of the four most abundant minerals in the human body and plays an integral role in DNA repair and replication. It functions as a cofactor for several enzymes involved in the repair and replication of nucleic acids, as well as in bone development, neuronal function, protein metabolism, cell proliferation, and the regulation of blood pressure and blood sugar levels.
Nearly 200 enzymes require magnesium to activate, and magnesium is also the cofactor for more than 600 enzymes. Enzymes involved in nucleic acid metabolism, such as DNA ligases, endonucleases and polymerase beta, depend on magnesium to function, making magnesium an essential element for maintaining genomic stability.
A magnesium deficiency can increase the risk of several diseases, including chronic degenerative diseases. On the other hand, the level of homocysteine, a product of methionine metabolism, in the blood is an indicator of neurodegenerative diseases such as Parkinson’s and Alzheimer’s diseases. High levels of homocysteine are believed to prevent DNA repair mechanisms and increase DNA damage.
About the study
In the current study, the researchers examined whether low levels of magnesium, independently or in combination with an increase in homocysteine levels, played a role in causing DNA damage.
The study recruited participants between the ages of 35 and 65 who were healthy, did not smoke, and had not been diagnosed with Alzheimer’s disease or mild cognitive impairment. Medications for serious illnesses such as cancer and use of daily mineral, vitamin or fish oil supplements beyond Australian daily allowance recommendations were exclusion criteria.
Blood samples were collected from all participants after an overnight fast for six months and used to measure the levels of numerous biomarkers of DNA damage. The cytokinesis block micronucleus assay was used to assess the levels of micronuclei, nuclear knobs, and nucleoplasmic bridges in the blood.
The blood samples were also analyzed for micronutrients such as folate and vitamin B12and homocysteine. Plasma isolated from the blood samples was also used to determine magnesium levels. Several statistical analyzes have been performed to understand the distribution of biomarkers and determine the correlations between magnesium and homocysteine levels and the concentration of DNA damage biomarkers in the blood.
Results
The study found that levels of magnesium and homocysteine had significant inverse correlations with each other, but magnesium levels had positive correlations with folic acid levels. Furthermore, magnesium levels showed significant inverse correlations with the biomarkers of DNA damage, nucleoplasmic bridges and micronuclei. These correlations remained significant even after the analyzes were adjusted for covariates such as age and gender.
Individuals with a combination of high homocysteine levels and magnesium deficiency had higher levels of nucleoplasmic bridges and micronuclei in their blood than those with high magnesium levels and low homocysteine levels.
These results indicated that magnesium is essential for protecting nucleic acids from endogenous genotoxicity. Other studies have also shown that culturing fibroblasts in magnesium-deficient media results in numerous genomic changes, such as accelerated telomere shortening and an increase in the expression of senescence biomarkers.
Furthermore, the researchers hypothesized that a chronic magnesium deficiency could also increase oxidative stress, possibly by interfering with antioxidant function or DNA synthesis in mitochondria. The increase in reactive oxygen species due to increased oxidative stress could cause breaks in the DNA strands or cause the oxidation of the nucleotides in DNA, increasing the level of DNA damage biomarkers.
Homocysteine is formed when methionine is metabolically converted into cysteine. Decreased levels of vitamin cofactors such as vitamins B6 and B12 and folic acid, which are essential for the folic acid-methionine metabolic pathway, can also increase homocysteine levels. Considering that low magnesium levels in turn result in a decrease in folic acid levels, this could potentially explain the negative correlation between magnesium and homocysteine levels.
Although high levels of homocysteine have been linked to neurodegenerative disorders such as Alzheimer’s disease and cardiovascular disease, studies have also suggested that homocysteine’s ability to act as a pro-oxidant may contribute to DNA damage due to oxidative stress, which may explain the mechanisms by which homocysteine fights chronic degenerative diseases.
Conclusions
Overall, the study found that low magnesium levels independently and together with high homocysteine levels cause increased DNA damage. The increase in DNA damage biomarkers associated with low magnesium levels indicated an increased risk of age-related diseases such as cancer and neurodegenerative disorders.
Furthermore, the results suggested that optimal intake of vitamin B12 and magnesium may help maintain genome integrity and reduce homocysteine levels, contributing to healthy aging.