Magnesium levels (MUC1)
Monday, August 22, 2022. Author FitnessGenes
Monday, August 22, 2022. Author FitnessGenes
Magnesium is an essential mineral that is required by our body for nerve and muscle function, bone health, control of blood sugar levels, and regulation of blood pressure.
The average adult body contains roughly 25-28 grams of magnesium, about 60% of which is stored in bones. Most of the remaining 40% of the body’s magnesium is stored inside cells of various other tissues, with less than 1% circulating in the bloodstream.
Magnesium is important because it acts as a cofactor for over 300 different enzymes in the body. Cofactors are “helper” molecules and ions that are required by enzymes to carry out chemical reactions effectively.
In this respect, magnesium is a cofactor for enzymes involved in:
Magnesium is also involved in the movement of other ions, such as potassium and calcium, across cell membranes. This process is central to how nerves conduct electrical impulses and how muscles contract in response to these electrical impulses.
Magnesium also plays a structural role in bones and therefore is important for bone health.
Good sources of magnesium include green leafy vegetables (e.g. spinach), as magnesium is a part of chlorophyll, the green pigment found in plants. Half a cup of boiled spinach, for example, contains 78 mg of magnesium.
Other good sources include nuts, legumes, seeds, and whole grains.
According to the Institute of Medicine, the recommended dietary allowance (RDA) for magnesium is:
RDAs refer to the average intake needed to meet the nutrient needs of 97-98% of healthy individuals. Health conditions that affect the absorption, metabolism and excretion of magnesium may cause some individuals to have higher magnesium requirements.
People with gastrointestinal diseases, including inflammatory bowel disease such as Crohn’s disease, coeliac disease, and enteritis, may all need higher magnesium intakes due to poorer mineral ion absorption in the gut.
Type II diabetics and people with insulin resistance may also have higher magnesium requirements. This is because high blood glucose levels can enhance the excretion of magnesium ions into urine by the kidneys.
A healthy blood magnesium level is considered to be: 0.65 - 1.05 mmol/L.
Given that less than 1% of the body’s magnesium stores are circulating in the bloodstream, however, blood magnesium levels are likely to be a poor indicator of the body’s overall magnesium levels.
Furthermore, the body tightly regulates blood magnesium levels within a narrow range, meaning that blood magnesium levels are not necessarily an accurate reflection of a person’s magnesium intake.
A blood magnesium level below 0.7 mmol/L is considered low (known technically as hypomagnesaemia).
Magnesium deficiency that is severe enough to cause symptoms is very rare. This is partly because the kidneys can compensate for low magnesium intakes by reducing its excretion into the urine and reabsorbing more magnesium into the bloodstream.
Chronically low magnesium intakes over time, however, can cause changes in the cell signalling pathways that control blood pressure, glucose metabolism and bone metabolism. This can then increase the risk of various health conditions, including:
For example, a 2020 meta-analysis which compiled the results of 43 prospective cohort studies found that there was an inverse relationship between magnesium intake and risk of Type II diabetes and stroke. This is illustrated in the graphs below.
Source: Zhao, B., Zeng, L., Zhao, J., Wu, Q., Dong, Y., Zou, F., ... & Zhang, W. (2020). Association of magnesium intake with type 2 diabetes and total stroke: an updated systematic review and meta-analysis. BMJ open, 10(3), e032240.
In simple terms, those with lower magnesium intakes were found to have higher risks of developing Type II diabetes and having a stroke. Conversely, increasing magnesium intake was associated with a reduced risk of these conditions. As can be seen in the graphs above, a 100 mg per day increase in magnesium intake was linked to a 6% lower risk of Type II diabetes and a 2% lower risk of stroke.
For more in-depth discussion of the health risks associated with low magnesium intakes, readers are encouraged to read the articles from the National Institutes of Health, Office of Dietary Supplements and the Linus Pauling Institute.
Mucin 1 is a substance that belongs to a family of proteins known as mucins, which make up the layer of mucus that lines our gastrointestinal tract. This layer of mucus that lines our intestine (known as the intestinal mucosal barrier) plays various roles in the body, including:
Mucin 1 in particular is a cell-surface mucin that is present on the surface of epithelial cells in various tissues, including the stomach, small intestine, colon and kidneys. It plays a key role in protecting the gastrointestinal tract from infection and orchestrating an inflammatory response to invading pathogens.
Source: Linden, S. K., Sutton, P., Karlsson, N. G., Korolik, V., & McGuckin, M. A. (2008). Mucins in the mucosal barrier to infection. Mucosal immunology, 1(3), 183-197.
The specific role of mucin 1 in the absorption of magnesium and other mineral ions is not known. Speaking speculatively, it may play a role in the formation of a mucus diffusion barrier in the gut, which allows the passage of mineral ions into the bloodstream. Given that mucin 1 is also expressed in the kidney, it is also possible that it facilitates the excretion and reabsorption of magnesium ions into and from urine.
The mucin 1 protein is encoded by your MUC1 gene.
Variants of the MUC1 gene have been linked to differences in blood magnesium levels.
MUC1 gene variants
A SNP (single nucleotide polymorphism), designated rs4072037, causes an A→ G change in the DNA code of the MUC1 gene. This generates two different MUC1 gene variants or alleles:
Studies suggest that the ‘A’ allele causes reduced production of the mucin 1 protein. By contrast, the ‘G’ allele causes relatively higher production of the mucin 1 protein.
The ‘G’ variant (rs4072037) of the MUC1 gene is associated with slightly lower blood magnesium levels.
Analysis of subjects enrolled in large studies such as the ARIC (Atherosclerosis Risk in Communities) and Cohorts for Aging Research in Genomic Epidemiology (CHARGE) studies have linked the ‘G’ allele to 0.01 to 0.02 mmol/L reductions in serum magnesium levels.
For example, an analysis of subjects in the ARIC study found that each copy of the ‘G’ allele was linked to a 0.014 mmol/L lower blood magnesium level. Another analysis of subjects in CHARGE and other replication cohorts found that each copy of the ‘G’ allele was associated with a 0.01 mmol/L reduction in blood magnesium level.
The same CHARGE study also grouped people into those with and without hypomagnesaemia (defined as a blood magnesium level below 0.7mmol/L) and then compared MUC1 genotypes between the groups. The researchers found that carriers of the ‘G’ allele had a 1.27 greater odds of having hypomagnesaemia compared to non-carriers.
Source: Meyer, T. E., Verwoert, G. C., Hwang, S. J., Glazer, N. L., Smith, A. V., Van Rooij, F. J., ... & Meta Analysis of Glucose and Insulin Related Traits Consortium (MAGIC). (2010). Genome-wide association studies of serum magnesium, potassium, and sodium concentrations identify six Loci influencing serum magnesium levels. PLoS genetics, 6(8), e1001045.
It is important to put these figures in context, however. Firstly, given that a healthy blood magnesium level is 0.65 - 1.05 mmol/L, a 0.01 to 0.02 mmol/L reduction in blood magnesium is fairly small. Secondly, blood magnesium levels are affected by lots of different lifestyle (e.g. diet, blood sugar levels) and genetic factors, so we would not expect a single gene variant alone to have much of an effect on serum magnesium levels. In line with this, the CHARGE analysis found that the MUC1 genome explained 0.57% of the variance in blood magnesium levels.
MUC1 genotype and progestin use
Progestin is a form of the female sex hormone progesterone, and can be used a hormone replacement therapy (HRT) for the treatment of symptoms of menopause.
The ARIC study found that the ‘G’ allele was linked to much (approximately twice) greater reduction in blood magnesium levels in post-menopausal women taking progestin. Each copy of the ‘G’ allele was associated with a 0.028 mmol/L decrease in blood magnesium level in women taking progestin, with this interaction between MUC1 genotype and progestin use accounting for 6.5% of the variance in blood magnesium levels.
It isn’t entirely clear why MUC1 gene variants affect blood magnesium levels.
Recall that the ‘G’ allele (rs4072037) is linked to greater expression of the mucin 1 protein, which helps form the mucus layer that lines our gastrointestinal tract (intestinal mucosal barrier). It is possible that increased mucin 1 expression in the intestinal mucosal barrier negatively impacts the absorption of magnesium ions into the bloodstream.
This mechanism may also explain why progestin use further lowers magnesium levels in ‘G’ allele carriers. Progesterone is also shown to increase production of mucin 1. The combined effects of progestin use and the ‘G’ allele on mucin 1 production may therefore lead to greater impairments of magnesium absorption and lower blood magnesium levels.
Another possibility is that MUC1 gene variants alter the excretion and reabsorption of magnesium ions in the kidney. These are only hypothetical explanations, however, and further research is needed to assess the mechanistic link between MUC1 gene variants and blood magnesium levels.
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