Many people pay attention to taking their daily multivitamin, their B complex or maybe even their calcium. However, the role of minerals for our daily nutrition is often overlooked. Luckily mainstream media continues to catch up and magnesium is now getting its chance to shine. This magnificent little mineral is involved in over 300 process in the body and chances are you have experience some of the side effects of having not quite enough. Symptoms you might have experienced include irritability, fatigue, anxiety, difficulty concentrating and stiffness and cramping in muscles. While not all of these may be directly linked to magnesium, you can be that it plays a part. Magnesium deficiency has been linked with a variety neurological, psychological and muscular disorders so we have much more to learn.
Magnesium is not a newly discovered element in our modern day nutrition. The first use of magnesium dates back to 1697 when Dr. Grew identified Epsom salt as magnesium sulfate (MgSO4). Extracted from a well in Epsom, England, this new mineral was used in a variety of ailments to which it is still recognized for today including sprains, muscle sprains, constipation, abdominal pain and cerebral edema. The magnesium ion was not recognized as a mineral into several years later in 1755 when isolated from magnesia and mercury. The importance of this mineral wasn’t truly known until it was officially isolated in from blood plasma in 1920 by Wiley Glover Denis and in 1926 found to be utterly essential. The first reports of magnesium deficiency in humans were reported in 1934 and the growing evidence of our need for this little mineral has grown since. It is often still referred to as the “forgotten mineral.”
Symptoms of deficiency
Constipation, muscle cramps or weakness, fatigue, nausea, irritability, memory problems, lack of appetite, tremors, vertigo, irregular heartbeat, seizures, difficulty swallowing
Cardiovascular disorders including acute myocardial infarction, atherosclerosis, hypertension, and and arrhythmia. Diabetes mellitus, alcoholism, aldosteronism, hyperthyroidism, renal tubular disorders, premenstrual syndrome, depression, fibromyalgia, sleep disorders, ADHD, migraines and chronic fatigue syndrome.
Magnesium and the nervous system
An interested statement was written by Durlach and Bach (1997) in which “the clinical pattern induced through magnesium deficiency was always neurotic (e.g. generalized anxiety disorder, panic attacks and depression) but never psychotic.” There is not a specific set of symptoms with magnesium deficiency based on its involvement in so many enzymatic reactions to pin down its direct link with a disease. However, based on its role in nervous system and our understanding of the system science has found some strong correlations that have made it a great ally in combating a variety of neurosis.
One role in which low magnesium may contribute to nervous system dysfunction is interaction with N-methyl-D-aspartate (NMDA) receptors on the terminal ends of nerve cells. Magnesium prevents the binding of glutamate to the NMDA receptor inhibiting the neuron from firing. Low levels of magnesium allow greater binding of glutamate leading to an influx of calcium and sodium into these nerve cells causing them to fire more often. This can lead to an overactive nerve system eventually causing ischemic or damaged nerve cells while depleting the body’s energy stores. This creates a self-destructive cycle since magnesium is also a require to activate the energy, in the form of ATP, need for the cell.
Magnesium also plays the opposite role of being an agonist of GABA receptors. When magnesium binds to these receptors it actual stimulates the release of GABA, a well studied neurotransmitter that keeps your nervous system in check. It is generally known as a relaxant for the nervous system which is something many of us need. GABA also has an effect on the NMDA receptors we mentioned earlier. GABA makes it harder for neurons to fire by increasing polarization of the neuron, in other words, increasing the amount of glutamate needed to cause the cell to fire. When GABA is lower due to decreased magnesium, not only do the neurons fire easier but it causes magnesium to release from the NMDA receptor sites. Finally, the last way that has been researched for magnesium’s direct effect on nervous function in the brain involves the release of glutamate, a stimulatory neurotransmitter.
The other area of interest when talking about stress and the nervous system is the hypothalamic pituitary axis. Magnesium plays another serious role here as an important cofactor in each step of the process. In the hypothalamus magnesium is responsible for the regulation of corticotropic releasing hormone (CRH). Low magnesium contributed to an increase in production of CRH then triggers release of adrenocorticotropin hormone (ACTH) from the pituitary signalling for the release of cortisol from the adrenal cortex as needed. There were some interesting findings in 2012 using magnesium deficient mice in a variety of stress tests. Some of the noted differences in mice with magnesium deficiency undergoing the stress test in comparison to their well supplemented counterparts included increase in weight, elevated body temperature (elevated basal body temperature is indicator of chronically stressed animals), greater hesitation to eat and increased time in hiding.
These findings have shone a bit of light on the utilization of magnesium as a tool that can be used as a treatment for anxiety either by itself or in conjunction with other nutritional supplementation or pharmaceutical intervention.
Magnesium in depression
Depression is fairly recent phenomenon that has become all to common in our modern day society. Before 1905, less than 1% of the population in the U.S. suffered from depression. By 1955, 6% of Americans had developed depression by the young age of 24 years. The importance of magnesium specific to disorders of the nervous system date back to the 1920s when improvement in mood was documented in individuals being given supplementation of magnesium sulfate after being diagnosed with depression.
A lot has changed since the early 1900s with one of the major contributors here being the source and quality of the foods being produced. There are so many factors that play in here including the increase in refined grains, poor quality soils leading to less nutrient dense vegetables, genetically modified foods having variable nutrient levels, contaminated waters forcing purification and leading to decrease in minerals, increase in processed foods, and overall increased stress levels. It is not uncommon in human populations in which diets were obviously high in processed foods and low in green leafy vegetables leading to overt magnesium deficiency to have higher rates of depression. The correlation here of which came first is unknown but highly processed, refined diets can increase the risk of depression and depression is likely to induce poor nutrition. Poor diet is not the only causative factor since poor absorption and elevated stress levels can also be problematic. It is viscious cycle that can be very difficult to break.
Over the years low magnesium levels have been linked with fatigue, anxiety, agitation, irritability, headaches and a variety of other symptoms that are often associated with depression and other psychological disturbances. In rodents with induced magnesium deficiency there were noted symptoms of depression that were alleviated upon resaturation with the mineral. Postpartum depression has been linked with low magnesium levels due to increased amounts being shuttled off to care for the fetus. Other research concluded that high doses of magnesium glycinate and taurinate postpartum were enough to alleviate these depressive symptoms.
Magnesium has also been found useful in the elderly in which regular administration over a 12 week period resulted in decreased depression in elderly with low magnesium and Type-2 diabetes and was found to be more effective than 50mg imipramine, a tricyclic antidepressant.
Further research has provided a positive correlation between erythrocyte magnesium levels in individuals with diagnosed moderate or severe depression. It was also noted that low erythrocyte magnesium was also correlated with the severity of depression and patients already taking antidepressants had significantly lower levels as well. In a study just prior to this the author also noticed lower plasma levels of magnesium and elevated copper in patients with diagnosed major depression. Despite the research, plasma levels of magnesium themselves are not indicative of the development of depression. There are also several studies that had a positive correlation between magnesium concentration and depression indicating high levels of magnesium were more problematic. Many of these studies predate the former research, however, looking more deeply into methods here may shine a light on the variable information.
Magnesium does not necessarily to work as a standalone treatment here. It has been found to actually aid treatment resistant depression by having patients take magnesium along with their antidepressant medications. The glycinate and taurinate forms have been the most successful here while one case report noted a worsening of symptoms utilizing magnesium aspartate.
Magnesium as the muscle manager
This just touches on the role of magnesium throughout the body. Calcium and magnesium also maintain a delicate balance in muscle contraction which has greater effects than just your standard charlie horse. All your arterial blood vessels that line you body are made of smooth muscle. Magnesium binds to receptors on the muscle allowing the release of calcium which causes the muscle to relax. When there is excess calcium, or just more calcium to magnesium, the cell is more likely to contract and remain so. When this happens in the smooth muscle in your arteries this can contribute to a familiar pathology called high blood pressure or hypertension. Several studies have now been cited showing the 400-600mg of magnesium can help lower blood pressure. Think about his also in regards to the heart itself being one large muscle. The cardiovascular system is one of the most energy draining systems in the body. Your heart beats 24/7 for your entire life. Decrease magnesium intake not only decreases the amount of ATP energy your body produces to feed the muscle and nerve cells of the heart but the muscles and nerves themselves are not able to function optimally.
It was actually found in 2008 that patients with chronic lower back had a 49% reduction in back pain just from taking magnesium. Magnesium can go a long way in helping individuals suffering from muscle and joint pain. This includes those suffering from more debilitating disorders such as fibromyalgia and osteoarthritis through cation balance.
The relaxing of smooth muscle isn’t just important for hardworking athletic muscles or those found in the arterial tree but also in the respiratory tree. Asthma is an extremely common pathology recognized by too many people. Generally this is a response by the system that involves tight muscular constriction and increased nerve stimulation. Sounds familiar right? Just another way that magnesium is an integral part in creating a more regulated, relaxed response to life’s stressors.
Magnesium comes in a variety of forms. Chelated (bound to amino acid) forms of magnesium have shown to have the greatest bioavailability and less likely to cause gastrointestinal distress in therapeutic doses. The most common forms found in supplements include:
The average adult needs around 5mg of magnesium per 1kg of weight meaning the average adult needs between 300-400mg per day. So why are recommendations so high? This is how much magnesium your body needs to absorb. If you take into account: total intake, bioavailability, competition with other nutrients, binding to phytates, increased stress, insulin resistance, kidney dysfunction, and inflammation or damage to the duodenal wall… you have to take a little extra to make up for all that.
Recommended intake: 300-400 of chelated Mg; 600-1000mg for therapeutic dose.
*Magnesium oxide should be avoided as an oral supplement unless the laxative effect is desired.
*Excess calcium can interfere with absorption of magnesium. It is recommended that these supplements should be taken in a 1:2 ratio, particularly for individuals taking these supplements for osteoporosis, cardiovascular disease and depression.
While you can test serum magnesium levels, the results are not the most indicative of total magnesium. A human adult contains around 24mg magnesium with around 60% of that being stored in the bones, 20% in muscle and 20% in soft tissue. The remaining magnesium is distributed in the blood which makes up around 1% of total body magnesium. It is the second most abundant cation in the cell and the fourth most abundant cation in the total body. Basically, it’s a big deal. The probably with testing serum magnesium is that 95% of magnesium is intracellular, or inside the cells leaving a very small portion in the serum. Levels of magnesium in erythrocytes, red blood cells, is around three times higher than the amount found in the serum itself. This amount still only accounts for about 1% of total body magnesium which makes it hard to estimate total body saturation leaving many folks with low or deficient levels to go unnoticed.
Another method of determining magnesium status that is also approved includes measuring erythrocyte magnesium concentration and a 24 hour urine test to measure amount of magnesium being excreted as well as other nutrients in relationship such as calcium and potassium. Compliance with the urinary test gets to be a little more difficult.
Safety and contraindications
Caution should be used in individuals taking digoxin, blood pressure medications, insulin for type-II diabetes, renal disease, quinolone (ciprofloxacin, moxifloxacin) and tetracycline antibiotics (doxycycline, minocycline), levothyroxine, blood thinning medications (warfarin, coumadin), osteoporosis medications (tiludronate, alendronate), and low heart rate. Diuretics can also deplete magnesium and many other minerals in the body quickly.
Magnesium should be taken at least 2 hours from medications to decrease risk of interference. Always check in with your pharmacists if you should have any questions about contraindications of these medicines. It is important to note that using magnesium can decrease your dose needed of some of the above medications so it is important to work with your physician if deciding to start supplementation.
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