Magnesium deficiency? Genes that Impact Magnesium Levels

Research shows that about 50% of us don’t get enough magnesium on a daily basis.[ref] Some people genetically are more likely to be deficient than others, based on genetic variants that impact magnesium absorption.

This article goes in-depth into how the body absorbs and uses magnesium. Also included are genetic variants (found in your 23 and Me or AncestryDNA data) that can affect your magnesium levels.

Understanding your genes can help you decide whether you may need more magnesium in your diet or via supplements. Members will see their genotype report below, plus additional solutions in the Lifehacks section. Join today.

Contents

What does magnesium do in the body?

Magnesium is a cofactor for more than 300 different enzymatic reactions. It means that many biochemical reactions in the body need both an enzyme and magnesium for the reaction to occur at the proper rate. Without enough magnesium (or without the required enzymes), some cellular reactions just won’t happen.

One of the reactions that magnesium is crucial for is the synthesis of DNA and RNA, as well as the metabolism of ATP.[ref] As you can imagine, magnesium is essential for life and the proper functioning of the body.

What are the signs of low magnesium?

Low magnesium levels are referred to as hypomagnesemia.

Research shows that common problems associated with hypomagnesemia include:[ref][ref]

migraines
ADHD
strokes
high blood pressure
insulin resistance
neurodegenerative diseases.
muscle weakness
twitches
tremors
heart arrhythmia or palpitations
seizures

In a nutshell, low magnesium shows up in physiological issues with the brain, heart, or skeletal muscles.

One study explains: “magnesium is essential for the regulation of muscular contraction, blood pressure, insulin metabolism, cardiac excitability, vasomotor tone, nerve transmission and neuromuscular conduction. Imbalances in magnesium status…might result in unwanted neuromuscular, cardiac or nervous disorders. Based on magnesium’s many functions within the human body, it plays an important role in prevention and treatment of many diseases.”[ref]

How do we maintain normal magnesium levels?

Your body stores magnesium in the bones (53%), muscles (27%), and soft tissues (19%). That leaves only about 1% of your total magnesium circulating in the blood.[ref]

The body tightly controls serum magnesium levels. While lab ranges can vary a little bit, the normal range for an adult is around 1.3 to 2.1 mEq/L (0.65 to 1.05 mmol/L or 1.5 to 2.6 mg/dL).[ref]

Hypomagnesemia is the term for low magnesium, which is usually defined as under 1.5 mg/dL on a lab test.[ref]

We take in magnesium from food and mineral-rich drinks. Magnesium is absorbed in the intestines. It circulates in the bloodstream and is taken up by cells as needed. The kidneys reabsorb serum magnesium so that only a small percentage is lost in the urine.[ref]

Low magnesium levels can be caused by:[ref]

losing too much magnesium in the urine (e.g., uncontrolled diabetes)
chronic diarrhea
malabsorption disorders (e.g., celiac, IBD)
bones taking up too much magnesium (e.g., following thyroid removal)
alcoholism
chronic pancreatitis

Both diet and genetics play a role in your magnesium levels. Everyone needs to consume enough magnesium, but the exact amount you need depends, in part, on your genes.

Below is a diagram showing some of the factors in magnesium absorption. We’ll first dig into the genetic factors and then return to the ‘exogenous’ factors in detail in the lifehacks section.

diagram showing how magnesium is absorbed in the intestines from PMC5652077 — Absorption of magnesium in the intestines. Creative Commons PMC5652077 (good overview article)

TRPM6 and TRPM7: Magnesium uptake

The TRPM6 and TRPM7 genes encode ion channels that transport magnesium ions across cell membranes. These ion channels can also transport calcium or other ions, but they primarily involve magnesium uptake.

Magnesium absorption occurs in the body in two ways:

Passive absorption in the intestines using an ion gradient to diffuse into intestinal cells
Active transports into intestinal cells using TRPM6 ion channels

The majority of magnesium uptake is via passive absorption in the small intestines. When the body’s magnesium levels aren’t met by passive transport, the TRPM6 ion channel is used to fine-tune the absorption.[ref]

Within the body, magnesium can be taken into cells and utilized as needed. The ion channel TRPM7 regulates the cellular uptake of magnesium. TRPM7 is found in tissues throughout the body and is essential for life. When magnesium levels drop within a cell, it activates the TRPM7 channel to take in more magnesium via this ion channel.[ref][ref][ref]

The TRPM6 ion channel is found in the cells lining the intestines, kidneys, and placenta. This ion channel is thought to dial in the right amount of magnesium absorption in the intestines and may play a role in the reabsorption of magnesium in the kidneys.[ref] Magnesium, via the TRPM6 ion channel, affects blood pressure regulation in the kidneys.[ref]

The TRPM7 ion channel is found in multiple tissues, including the heart and brain. In the heart, TRPM7 is integral in maintaining the heart’s rhythm, along with other ion channels.[ref][ref] Oxidative stress caused by higher intracellular levels of hydrogen peroxide can inhibit the TRPM7 channel.[ref]

CNNM2 and Magnesium Reabsorption:

The body tightly controls magnesium through both the amount absorbed in the intestines and the reabsorption of magnesium in the kidneys. The cyclin M2 (CNNM2) gene encodes a magnesium transporter in the kidneys. When magnesium levels are high in the body, more magnesium is transported out via the urine. Similarly, when magnesium levels are trending lower, more magnesium is reabsorbed. This process is controlled, in part, by the availability of the CNNM2 magnesium transporter.

Rare mutations that cause a deficiency of CNNM2 result in too much magnesium being excreted in the kidneys, which is linked to a loss of circadian rhythm in blood pressure control.[ref] Rare mutations in CNNM2 are also linked to brain development disorders due to the dysregulation of magnesium.[ref]

Magnesium and calcium levels interact through several regulatory mechanisms. Mutations in CNNM2 can show up as calcium dysregulation along with the effect on magnesium.[ref]

Magnesium Genotype Report

Check out the genetic variants below to see how some of your genes may influence your need for magnesium.

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TRPM6 variants:

TRPM6 encodes the ion transporter that regulates magnesium uptake in the intestines and impacts magnesium reabsorption in the kidneys.

Check your genetic data for rs3750425 (23andMe v4, v5; AncestryDNA):

C/C: typical
C/T: lower serum magnesium levels; increased risk of hypomagnesia with proton pump inhibitors; increased risk of type 2 diabetes if magnesium intake is low
T/T: lower serum magnesium levels[ref]; increased risk of hypomagnesia with proton pump inhibitors[ref]; increased risk of type 2 diabetes if magnesium intake is low[ref]

Members: Your genotype for rs3750425 is —

Check your genetic data for rs2274924 (23andMe v4; AncestryDNA):

C/C: lower magnesium levels on average; increased susceptibility to epilepsy post-stroke[ref], increased risk of hypomagnesia with proton pump inhibitors[ref]; increased risk of type 2 diabetes if magnesium intake is low[ref]
C/T: lower magnesium levels, on average; increased risk of hypomagnesia with proton pump inhibitors;
T/T: typical

Members: Your genotype for rs2274924 is —

Check your genetic data for rs121912625 (23andMe v5; AncestryDNA):

A/G: rare mutation linked to hypomagnesia[ref]
G/G: typical

Members: Your genotype for rs121912625 is —

TRPM7 genetic variants:

The TRPM7 gene encodes an ion transporter that moves magnesium into cells throughout the body.

Check your genetic data for rs8042919 T1482I (23andMe v4; AncestryDNA):

A/A: increased sensitivity to low magnesium levels, possibly increased risk of ALS or Parkinson’s with long-term low magnesium and calcium intake[ref]
A/G: increased sensitivity to low magnesium levels, possibly increased risk of ALS or Parkinson’s with long-term low magnesium and calcium intake
G/G: typical

Members: Your genotype for rs8042919 is —

CNNM2 genetic variants:

The CNNM2 gene encodes a transporter in the kidneys that is important in magnesium reabsorption and maintaining normal Mg levels.[ref] Genetic variants in this gene are linked to changes in magnesium levels which influence brain development and blood pressure.

Check your genetic data for rs12413409 (23andMe v4, v5; AncestryDNA):

A/A: decreased risk of hypertension[ref], decreased risk of coronary artery disease[ref], decreased risk of aneurysm[ref]
A/G: decreased risk of hypertension
G/G: typical

Members: Your genotype for rs12413409 is —

Check your genetic data for rs11191548 (23andMe v4, v5; AncestryDNA):

T/T: typical
C/T: decreased risk of hypertension; higher levels of 25(OH)D
C/C: decreased risk of hypertension[ref]; higher levels of 25(OH)D[ref], possibly decreased risk of orthostatic hypertension[ref]

Members: Your genotype for rs11191548 is —

Check your genetic data for rs7914558 (23andMe v5; AncestryDNA)

A/A: decreased gray matter (on average)[ref], possibly altered neural systems relevant to social cognition, increased risk of schizophrenia[ref]
A/G: common genotype
G/G: typical

Members: Your genotype for rs7914558 is —

Lifehacks:

The RDA for magnesium is 320 mg for women and 420 mg for men. Chronometer.com is a free web app to track your daily food intake. Keep track for a few days and see what you average for magnesium as a baseline from foods.

Water accounts for about 10% of magnesium intake in a day. If you are drinking water with the minerals filtered out, you may need to increase the amount of magnesium you get from other sources.

Drinking too much water can lead to low magnesium levels due to excessive urination. Excessive sweating, such as exercising in the heat or using a sauna, can also lead to low magnesium levels, usually temporary.

Drug interactions:

Medications can cause you to have low magnesium levels:[ref]

diuretics
proton pump inhibitors
aminoglycoside antibiotics
digitalis
calcineurin inhibitors
certain chemo drugs

Talk with your doctor or pharmacist if you have questions about whether medications could decrease your magnesium levels.

Food sources of magnesium:

Taken from the NIH Health Information fact sheet:

Food	Mg/serving	% RDA
Pumpkin seeds, roasted, 1 ounce	156	37
Chia seeds, 1 ounce	111	26
Almonds, dry roasted, 1 ounce	80	19
Spinach, boiled, ½ cup	78	19
Cashews, dry roasted, 1 ounce	74	18
Peanuts, oil roasted, ¼ cup	63	15
Cereal, shredded wheat, 2 large biscuits	61	15
Soymilk, plain or vanilla, 1 cup	61	15
Black beans, cooked, ½ cup	60	14
Edamame, shelled, cooked, ½ cup	50	12
Peanut butter, smooth, 2 tablespoons	49	12
Potato, baked with skin, 3.5 ounces	43	10
Rice, brown, cooked, ½ cup	42	10
Yogurt, plain, low fat, 8 ounces	42	10
Breakfast cereals, fortified with 10% of the DV for magnesium, 1 serving	42	10
Oatmeal, instant, 1 packet	36	9
Kidney beans, canned, ½ cup	35	8
Banana, 1 medium	32	8
Salmon, Atlantic, farmed, cooked, 3 ounces	26	6
Milk, 1 cup	24–27	6
Halibut, cooked, 3 ounces	24	6

Do you need a specific type of magnesium for your genes?

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