Summary

Magnesium is a mineral that must be obtained in the diet in relatively large quantities. Magnesium is required for the function of over 300 enzymatic reactions, including in energy metabolism where it plays a pivoted role. Magnesium is also required for the synthesis of fatty acids and proteins, proper insulin response, and nerve transmission. Magnesium deficiency is not rare, and the majority of Americans ingest sub-optimal amounts. Magnesium deficiency is particularly common in vulnerable populations, including people with gastrointestinal disease. Signs of magnesium deficiency include loss of appetite, nausea, vomiting, fatigue, weakness, anxiety, memory problems, numbness and tingling, tics, cramps, insomnia, seizures, personality changes, and abnormal heart rhythms. The role of magnesium in the treatment of autism has been evaluated in a few studies, some of which have shown benefit in children with ASD, especially when coupled with pyridoxine (which is also in Spectrum Needs). Children with ASD often have diets that are relatively deficient in many nutrients, including magnesium. Magnesium is an agonist for (turns on) GABA receptors, one of the chief inhibitory pathways in the nervous system, and an antagonist for (turns off) NMDA glutamate receptors, one of the chief excitatory pathways in the nervous system, which may play a role in neuroprotection. The combination can lead to abnormal inhibitory–excitatory balance, promoting increased autistic behaviors and possibly regression. The clinical experience of many physicians, and the generally benign nature of magnesium supplementation, have convinced many experts to offer magnesium supplementation to their patients with an ASD. Individuals that are more likely to benefit are those who also suffer with constipation, migraine-like manifestations, other varieties of chronic pain, chronic fatigue, restless leg, signs of insulin resistance, indications of reduced inhibitory–excitatory balance (anxiety, hyperactivity, impulsivity, OCD, etc.), a history of regression, or other conditions among the multitudes of health conditions for which magnesium is frequently employed. Magnesium supplements are available over-the-counter in a variety of forms, and some forms are more bioavailable than others. Side effects are rare at usual doses used in supplementation other than possibly loose stools.

Magnesium in Spectrum Needs

Magnesium is added in order to provide a wide basis of nutrition, especially given the important role of magnesium in energy metabolism, its role in GABA and NMDA glutamate receptor activation, and the preliminary data regarding its use as a food supplement in ASD. In Spectrum Needs, magnesium is provided in equal parts coupled with citrate and malate because both forms have relatively high absorption from the gut, to balance the effects on stooling (magnesium citrate is commonly used for constipation, but not magnesium malate), and because both citrate and malate are Krebs cycle intermediates that might promote energy metabolism. Side effects are unexpected.

The Details

What Is It? Magnesium is a mineral that must be obtained in the diet and is required for life. It is one of the seven essential “macrominerals” that need to be provided by the diet in quantities of at least 100 milligrams per day.

What Does It Do? Magnesium is required for the function of over 300 enzymatic reactions, including in energy metabolism where it plays a pivoted role. Magnesium is also required for the synthesis of fatty acids and proteins, proper insulin response, and the transmission of nerve impulses.

What Does Deficiency Appear as? Magnesium deficiency is not rare. Dietary surveys consistently show that intakes of magnesium are lower than recommended amounts in the majority of Americans. Magnesium deficiency is particularly common in vulnerable populations, including people with gastrointestinal disease, pancreas infections, and liver disease. High doses of supplemented zinc without magnesium supplementation can also provoke a magnesium deficiency. Early signs of magnesium deficiency include loss of appetite, nausea, vomiting, fatigue, weakness, anxiety, and memory problems. Additional findings can include numbness and tingling, tics, cramps, insomnia, seizures, personality changes, and abnormal heart rhythms.

What About Its Use in Autistic Spectrum Disorders (ASD)? The role of magnesium in the treatment of autism has been evaluated in a few studies, especially when combined with pyridoxine (vitamin B6), but results are not definitive. Children with ASD often have diets that are relatively deficient in many nutrients, including magnesium (https://www.ncbi.nlm.nih.gov/pubmed/28074329). While results differ among studies, there is some evidence of lower magnesium levels in the hair and nails of children with ASD (https://www.ncbi.nlm.nih.gov/pubmed/20625937). One review article reported positive results in children with ASD treated with magnesium and pyridoxine (https://www.ncbi.nlm.nih.gov/pubmed/1828703). In another study, 200 mg magnesium supplementation, with pyridoxine and riboflavin, lowered dicarboxylic acid levels in children with ASD, which suggests that the treatment improved fatty acid metabolism (https://www.ncbi.nlm.nih.gov/pubmed/21840465).

Magnesium is an agonist for (turns on) GABA receptors, one of the chief inhibitory pathways in the nervous system, whereas under stimulation in ASD may lead to increased autistic behaviors in some cases. Magnesium is also an antagonist for (turns off) NMDA glutamate receptors, one of the chief excitatory pathways in the nervous system, which may play a role in neuroprotection and thus potentially guard against episodes of autistic regression. There is evidence of abnormal inhibitory–excitatory balance in the brain of individuals with ASD, which may be targeted by therapy via effects on GABA and glutamate neurotransmission (reviewed in https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4910649/pdf/cmped-10-2016-043.pdf).

While more studies are needed, the clinical experience of many expert physicians, and the generally benign nature of magnesium supplementation, have convinced many experts to offer magnesium supplementation to their patients with an ASD. Individuals that are more likely to benefit are those who also suffer with constipation, migraine-like manifestations, other varieties of chronic pain, chronic fatigue, restless leg, signs of insulin resistance, indications of reduced inhibitory–excitatory balance (anxiety, hyperactivity, impulsivity, OCD, etc.), or a history of regression.

What About Its Use in Other Conditions? Magnesium is a very frequent therapy used for constipation. Magnesium is frequently used as a laxative for constipation, where it is often given at very-high dosing. Other gastrointestinal uses include “clean-outs” in preparation of the bowel for surgical or diagnostic procedures, and as an antacid for acid indigestion. Magnesium is also frequently recommended for the prevention of migraine headache. Three of four small, short-term, placebo-controlled trials found modest reductions in the frequency of migraines in patients given up to 600 mg per day of magnesium (https://www.ncbi.nlm.nih.gov/pubmed/19271946?dopt=Abstract). The authors of a review on migraine prophylaxis suggested that taking 300 mg magnesium twice a day, either alone or in combination with medication, can prevent migraines (https://www.ncbi.nlm.nih.gov/pubmed/18325296?dopt=Abstract).

Some people use magnesium for diseases of the heart and blood vessels including chest pain, irregular heartbeat, high blood pressure, high levels of "bad" cholesterol called low-density lipoprotein (LDL) cholesterol, low levels of "good" cholesterol called high-density lipoprotein (HDL) cholesterol, heart valve disease (mitral valve prolapse), metabolic syndrome, clogged arteries (coronary artery disease), stroke, and heart attack. Magnesium is also used for treating seizures, attention deficit-hyperactivity disorder (ADHD), anxiety, chronic fatigue syndrome (CFS), Lyme disease, fibromyalgia, cystic fibrosis, alcoholism, mania, recovery after surgery, leg cramps at night and during pregnancy, diabetes, kidney stones, a long-term pain condition called complex regional pain syndrome, weak bones (osteoporosis), premenstrual syndrome (PMS), altitude sickness, urinary incontinence, a condition that causes burning pain and redness called erythromelalgia, restless leg syndrome, asthma, hay fever, multiple sclerosis, high blood pressure during pregnancy and other pregnancy complications, to induce more rapid wound healing, and for preventing hearing loss and cancer. Athletes sometimes use magnesium to increase energy and endurance.

This is only a partial list, as the use of magnesium is in very wide spread use in medicine.

What Form of Magnesium is Best? Magnesium supplements are available over-the-counter in a variety of forms, including coupled with oxide, sulfate, chloride, carbonate, lactate, orotate, citrate, malate, glycinate, threonate, glutamate, aspartate, arginate, and taurate. The Supplement Facts panel on product labels declares the amount of only the magnesium in the product (elemental magnesium), not the weight of the entire magnesium-containing compound (e.g. magnesium oxide). The absorption of magnesium from different kinds of supplements varies, with magnesium coupled with organic and amino acids being absorbed better than magnesium coupled with oxide or sulfate. The citrate form in particular is frequently used to treat constipation.

What Are the Common and/or Important Side Effects? Very-high doses of magnesium are routinely recommended for bowel conditions, and this mineral is considered to be generally non-toxic. Side effects are rare at usual doses used in supplementation other than possibly loose stools.

Is There Any Laboratory Testing? Laboratory testing can reveal the presence of a magnesium deficiency, and this test is indicated in specific situations where magnesium deficiency is likely or suspected.

How and Why is this Nutrient Used in Spectrum Needs

Magnesium is added to Spectrum Needs in order to provide a wide basis of nutrition, especially given the important role of magnesium in energy metabolism, its role in GABA and NMDA glutamate receptor activation, and because of the available data suggesting a possible role in the dietary supplementation of ASD. While definitive large double-blind studies have not been performed to date, the multiple studies performed to date, the clinical experience of many expert physicians, and the generally benign nature of magnesium supplementation, have convinced many experts to offer magnesium supplementation to their patients with an ASD.

In Spectrum Needs, magnesium is provided in equal parts coupled with citrate and malate, which are both organic acids and thus have relatively high absorption from the gut. The citrate form, but not the malate form, is commonly used for constipation, and thus can make the stool loose. In Spectrum Needs, providing equal amounts of both forms hopes to balance the effect on stooling and prevent diarrhea. In addition, both citrate and malate are Krebs cycle intermediates, so supplementing with these compounds might promote energy metabolism. Side effects of magnesium-containing compounds are unexpected at the doses used in Spectrum Needs.

What About Additional Dosing Beyond Spectrum Needs?

Therapeutic dosages of magnesium in functional bowel obstruction (pseudo-obstruction, severe functional constipation, obstipation) is oftentimes much higher (~900-1,000 mg/day in adults) than the dose provided in Spectrum Needs (adult dose 300 mg). A common dose used for migraine is 400-500 mg/day in adults. Thus, you may wish to speak to your health care provider regarding additional magnesium supplementation beyond Spectrum Needs if your child has or one of the conditions for which higher doses of magnesium supplementation is often recommended.