Magnesium and Insulin Resistance

March is here, which means spring delights, including warmer weather, March Madness, gardening, baseball, and spring break, are just around the corner.

Here at InterPlexus, we are dedicating our March blog posts to magnesium – a truly powerful and magical mineral that is rarely consumed in adequate amounts. Magnesium (Mg) is required for many functions in the body because it is a cofactor or activator in hundreds of enzymatic reactions.¹ Mg plays a role in RNA and DNA synthesis; protein, lipid, and carbohydrate metabolism; maintaining the stability of cell membranes; bone strength; vitamin D and calcium metabolism; nervous system function; immune activity; and more.^1,2

Magnesium also plays a predominant role in the production and utilization of energy in the body. Therefore, magnesium deficiency can contribute to the development of an unhealthy metabolism, including abnormal blood glucose and insulin levels.¹

Magnesium and Metabolism

As we learned in a previous blog post, adenosine triphosphate (ATP) is cellular energy. Every molecule of ATP must bind to magnesium to convert into its biologically active form, which is a Magnesium-ATP complex.³ In the mitochondria, where ATP is produced, the Mg-ATP complexes shuttle the ATP outside the mitochondria so the ATP can be used as cellular energy.⁴

Magnesium supports mitochondrial function by increasing ATP production, decreasing the mitochondrial production of reactive oxygen species (ROS), boosting the activity of mitochondrial enzymes, reducing intracellular calcium overload, repolarizing the mitochondrial membranes, and minimizing overall oxidative stress.⁵

Magnesium and ATP are crucial for the optimal function of your metabolism and heart.³ More information about the beneficial effects of Mg on the cardiovascular system will be available in our next blog post, so stay tuned! Continue reading below to learn more about the evidence-based beneficial effects of magnesium on healthy metabolism and insulin sensitivity.*

Magnesium Deficiency

Mg must be consumed in adequate amounts daily to support optimal health. In the United States, the recommended daily allowance (RDA) for Mg is approximately 300-400 mg per day for adults. Ideally, adult females should consume 320 mg, and adult males should consume 420 mg of Mg per day. Unfortunately, epidemiological data show that the majority of those on a standard “Western diet” do not meet their daily Mg needs.¹

This blog post lists several reasons why many people fail to consume enough magnesium. Even though most people in the United States do not consume enough Mg, magnesium deficiency is rarely diagnosed by physicians.^1,2

Magnesium deficiency is difficult to diagnose because less than 1% of total body magnesium is in the blood; therefore, blood levels of Mg are not an ideal test to assess magnesium status.⁶ Diagnosing Mg deficiency is also difficult because the symptoms of Mg deficiency are non-specific and can mimic many other health conditions.⁷

Symptoms and signs of a magnesium deficiency may include:

• Anxiety
• Weakness
• Agitation
• Depression
• Menstrual cramps
• Hyperactivity
• Headache
• Migraine
• Irritability
• Hearing issues
• Low stress tolerance
• Loss of appetite
• Nausea
• Insomnia and other sleep disorders
• Impaired athletic performance
• Muscle spasms
• Aching back pain
• Neck pain
• Urinary spasms
• Magnesium deficiency tetany
• Nervousness
• Increased sensitivity of the N-methyl-D-aspartate receptor (NMDA receptors) to excitatory neurotransmitters
• Nystagmus
• Paresthesia (numbness and tingling)
• Poor memory
• Seizures
• Tremor
• Vertigo
• Constipation
• Cardiac arrhythmias
• Hypertension
• Coronary spasm
• Decreased heart pump function
• Digitalis sensitivity
• Torsade de pointes
• Hypokalemia (low potassium level)
• Hypocalcemia (low calcium level)
• Sodium retention
• Increased blood triglyceride and cholesterol levels (hypertriglyceridemia, hyperlipidemia, or hypercholesterolemia)
• Decreased sugar (glucose) tolerance and altered glucose homeostasis (balance)
• Insulin resistance
• Increased risk of metabolic syndrome
• Suboptimal bone and vitamin D metabolism
• Resistance to parathyroid hormone (PTH)
• Low circulating levels of PTH
• Low circulating levels of 25(OH)D (Vitamin D)
• Recurrence of calcium oxalate calculi (kidney stones)
• Asthma
• Chronic fatigue syndrome
• Osteoporosis
• Pregnancy complications, including miscarriage, premature labor, and eclampsia⁸
• Thyroid dysfunction⁹

So, if you have anxiety, insomnia, insulin resistance, fatigue, thyroid dysfunction, migraines, depression, high blood pressure, asthma, or any of the health concerns mentioned above, a magnesium deficiency might be the underlying cause of or a contributing factor to the health concern.*

As you can see in the list above, adequate Mg intake is important for optimal blood sugar and insulin levels. The metabolic disorder known as insulin resistance is associated with type 2 diabetes and cardiovascular disease, including heart failure and stroke.^10,11,12

Magnesium supplementation in research settings appears to be beneficial for these conditions. A recent meta-analysis that included over one million participants from 40 clinical studies discovered that higher magnesium intake reduced the risk of stroke, heart failure, type 2 diabetes, and all-cause mortality. According to the analysis, increasing the intake of Mg by 100mg per day reduced the risk of all-cause mortality by 10%, stroke by 7%, type 2 diabetes by 19%, and heart failure by 22%.¹³

What is insulin?

Insulin is a polypeptide hormone produced by the pancreas and is primarily known for its ability to lower the blood glucose (blood sugar) level. Insulin was first discovered in 1921 by Frederick G. Banting and Charles H. Best in the laboratory of J.R. Macleod at the University of Toronto in Canada. Insulin is secreted from the β-cells of the pancreatic islets of Langerhans in response to the presence of glucose and amino acids in the blood after consuming food.¹⁴

As you can see in the picture below, insulin “unlocks” the sugar/glucose channel, so blood sugar can enter the cell, where it will either be used as energy or stored as fat. As the blood sugar enters the cells due to the effects of insulin, the blood sugar level decreases.

Insulin not only regulates glucose homeostasis (optimal blood sugar levels) but is also involved in tissue growth and development. Insulin exerts strong control over lipid metabolism (fat metabolism) because it stimulates lipid synthesis in the liver and fat cells. The presence of insulin also blocks the breakdown of fat or adipose tissue, which is known as lipolysis. Because insulin lowers the blood glucose level, it is administered as a medication to those with type 1 diabetes, type 2 diabetes, gestational diabetes, and other health conditions.^14,15

When insulin levels are high (hyperinsulinemia) due to insulin resistance or an underlying genetic predisposition to releasing excessive insulin, it can exacerbate or be an underlying cause of many other health concerns, including obesity, diabetes, and cancer.¹⁶

What is insulin resistance?

When considering the systemic effects of a hormone in the body, one must be mindful of the amount of hormone present AND the number and sensitivity of the hormone receptors. The hormone itself does not have any effect until it binds to a receptor.

Insulin resistance (IR) is a metabolic disorder where there is plenty of the hormone insulin present, but the insulin receptors do not respond optimally. This phenomenon could be caused by either a low number of receptors or receptors that do not respond to or are not sensitive to insulin.^16,17

When the insulin receptors are resistant to the effects of insulin due to genetics or other factors, IR develops. The pancreas must produce extra insulin to force the blood sugar into the cells, resulting in an elevated blood insulin level, which is also known as hyperinsulinemia.¹⁷

There is controversy surrounding the development of IR since there are likely several underlying causes. Some believe IR develops, which then causes elevated insulin levels (hyperinsulinemia), while others suggest the pancreas produces extra insulin to compensate for elevated blood glucose levels, which then leads to IR. Then, some hypothesize both mechanisms occur in parallel to contribute to the development of IR. The relationship between hyperinsulinemia and IR is complicated and still being studied.¹⁸

Magnesium & Insulin Resistance

The relationship between magnesium and insulin resistance is fascinating and multifaceted. Hyperinsulinemia (high insulin levels) will increase the excretion of magnesium via the urine. And low magnesium levels can contribute to the development of both hyperinsulinemia and insulin resistance. So, if your magnesium level is low, your Mg status could rapidly deteriorate due to the presence of excessive insulin.¹⁰

It is a vicious cycle that is similar to the magnesium/stress dynamic. As discussed in Part 2 of our Synergistic Nutrients for Adrenal Support blog post, the presence of stress hormones also increases the amount of magnesium that leaves the body via urination. Then, as magnesium levels decrease, the body’s resistance to stress wanes, which can then increase the secretion of stress hormones, including cortisol, further exacerbating a magnesium deficiency.¹⁹

Normal magnesium levels help protect against the development of insulin resistance via several mechanisms, which include:

• Reducing inflammation
• Normalizing cholesterol levels
• Improving glucose metabolism in the liver
• Optimizing calcium signaling
• Limiting the accumulation of adipose tissue (fat tissue)
• Affecting the amount of insulin released
• Increasing glucose receptor gene expression¹
• Supporting the activity of many Mg-ATP complex-dependent enzymes involved in glucose metabolism²

Regarding glucose receptor gene expression, the skeletal muscles take up approximately 80% of dietary glucose via the glucose receptors known as GLUT4 receptors. Several animal studies have shown that Mg supplementation increases GLUT4 gene expression, and one study was able to quantify the increased expression. Overall, Mg supplementation increases GLUT4 mRNA expression by approximately 23% to improve blood glucose management and reduce the risk of insulin resistance.⁵

Results from the Canadian Health Measures Survey Cycle 3 (2012–2013) showed serum Mg levels in the Canadian population were negatively associated with body mass index (BMI), fasting blood glucose levels, fasting insulin levels, and HOMA-IR scores. The HOMA-IR test is the Homeostatic Model Assessment for Insulin Resistance. HOMA-IR is calculated based on fasting plasma insulin and fasting plasma glucose levels. It is an objective measurement that assesses the severity of insulin resistance and the function of pancreatic β-cells.²⁰

So, the lower the blood magnesium level, the higher the insulin level and the HOMA IR score.²⁰ Therefore, Mg deficiency may directly contribute to pancreatic beta-cell dysfunction.²¹

The results of at least five clinical trials verify that magnesium supplementation significantly reduces the fasting insulin level. When several clinical studies assessing the effect of magnesium supplementation on blood glucose and insulin levels are analyzed together, an increase of 50 mg of dietary magnesium daily leads to a 4.35% decrease in the HOMA-IR score and a 3.05% reduction in the fasting glucose level.²²

You are probably asking questions such as:

• Do we know how to reverse insulin resistance?
• Which magnesium is best for insulin resistance
• Should I take magnesium for insulin resistance?
• How much magnesium should I take for insulin resistance?

We do not yet have answers to these questions, even though the results of many clinical trials and at least two systematic reviews do provide ample evidence of the benefits of magnesium supplementation on insulin levels and glucose management in those who do not consume adequate Mg.^22,23 Further studies will be necessary to determine the optimal dose, type, and timing of Mg supplementation to support healthy blood glucose and insulin levels in the future.²²

Please note too much magnesium can cause side effects, such as diarrhea. If your doctor recommends magnesium supplementation, the best magnesium supplement might be one that offers high bioavailability and a low dose, so it can be taken more than once per day to reduce the risk of side effects. Kindly consult your doctor for further guidance about what supplement, dose, and protocol might be best for you.*

Magnesium fumarate is available in Fura-Mag

Trimagnesium dicitrate (magnesium citrate), magnesium bisglycinate (magnesium glycinate), and magnesium ascorbate are available in Magnesium³

Magnesium citrate and magnesium potassium citrate are available in Potassium+Mag

Magnesium ascorbate is available in Flavo PlexC

* This statement has not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.

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References

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