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Improve energy, strength and/or mitochondrial function


The advantages of calcium are many, such as maintaining healthy bones and teeth, healthy muscle tone and function, cardiac function, and nerve transmission. Calcium should not be taken in greater amounts than 500 mg at a time in order to maximize absorption, and it should be taken with meals. Too much calcium could lead to kidney stones. The average daily dose of calcium is 1000-1200 mg daily. Since magnesium works closely with calcium, the suggested ratio is 2:1, calcium to magnesium. Recent research has shown that calcium works best when Vitamin D levels in the blood are adequate.


This mineral is of particular importance in ME/CFS and FM because of its involvement in numerous biological and metabolic functions. Magnesium affects the production of cellu­lar energy, stability of cells, nerve conduction and muscle contraction. It helps transport oxygen to muscles, which in turn, strengthens but also relaxes muscles. Furthermore, there is a link between magnesium and functioning of the immune system. An activated immune system uses magnesium and zinc at rapid rates.

Studies have shown that ME/CFS patients in particular have lower levels of intracellular magnesium than healthy controls. The typical magnesium test only measures serum levels of magnesium and while serum levels can be normal, intracellular levels can be low at the same time. Magnesium deficiency can cause low potassium. Other signs of magnesium deficiency are fatigue and muscle cramps. There is some evidence that magnesium has anti­osteoporotic activity. It definitely has anti­arrhythmic activity. Magnesium may have anti­hypertensive, glucose-regulatory and bron­chodilatory activity and possible anti-migraine activity. Since magnesium is an electrolyte which influences heartbeat and potassium levels (which also affect heartbeat), it is wise to only supplement with magnesium or potassium with regular checks by a doctor of serum blood levels of both minerals.

Magnesium is contraindicated in those with kidney failure and certain types of heart problems. It should not be taken two-to-four hours before or after certain medications such as bisphospho­nate, a quinolone or a tetracycline, as magnesium can interfere with their absorption. The standard recommended dose for healthy people is 100-300 mg per day. But it is often used in higher amounts of 500-750 mg for ME/CFS and FM while frequently combined with malic acid. In view of magnesium's effect on so many functions and other medical conditions, it would be advisable for one's doctor to determine the appropriate dose for each individual.

Malic acid

Malic acid is a natural compound found in fruits, sometimes called fruit acid, which is involved in the Krebs cycle and mitochondrial creation of energy. The Krebs cycle (citric acid cycle) is part of a metabolic pathway involved in the chemical conversion of carbohydrates, fats and proteins into carbon dioxide and water to generate a form of usable energy. Other relevant reactions in the pathway include those in glycolysis and pyruvate oxidation before the citric acid cycle, and oxidative phosphorylation after it. Malic acid has been found to improve energy in ME/CFS as well as reduce pain and stiffness in FM. There are no known contraindications or precautions. A typical dose would be 1200-2400 mg daily with 300 to 600 mg daily magnesium.

Since magnesium is an electrolyte which influences heartbeat and potassium levels (which also affect heartbeat), it is wise to only supplement with magnesium or potassium with regular checks by a doctor of serum blood levels of both minerals.

Vitamin B-12

Vitamin B-12 is a water-soluble vitamin found naturally in animal foods, fish, and dairy products. It is vital to red blood cell formation, absorption of foods, metabolic regulation, growth, and protection of nerve cells and function. Deficiency often presents as chronic fatigue, digestive disorders, pernicious anemia, various memory, mood or neurologic problems. B-12 deficiency may also be present in some individuals who consume a very limited vegan-type diet. Long-term use of proton pump inhibitor medications which reduce stomach acid (like those controlling GERD) may also interfere with the absorption of B-12.

Therapeutic treatment with this vitamin is often delivered as hydroxocobalamin injections and for ME/CFS and FM, at higher and more frequent doses than usual because of the amount needed to notice improvement. Not only does B-12 help to promote energy and overall better function, but also it works at a deeper level to reduce nitric oxide and peroxynitrite levels regarded by some researchers to be the main culprit in causing the ME/CFS process.

It is generally not found to be toxic or problematic in the majority of people, unless they are sensitive to the compounds that make up the vitamin, an ingredient in the injection material and/or have an unusual optic neuropathy. Vitamin B-12 injections, when used for ME/CFS, are often started at a high-dose of approximately 3000 mcg, several times per week, for 15 doses and then it is tapered down. Sublingual B-12 is the preferred oral form, from 1000 up to 5000 mcg day.

Vitamin D

This vitamin has received a lot of attention over recent years because low levels have been detected in many people, but this can be a fairly tricky vitamin to use. Vitamin D deficiency, in particular, is often associated with bone loss and multiple sclerosis, but also with persistent musculoskeletal pain.

There are two types of Vitamin DD-2 is derived from plant sources, and D-3 from animal sources and through the skin when exposed to ultraviolet-B (UVB) rays from the sun. Obtaining adequate Vitamin D from sunlight on a regular basis depends on geographic location, weather, and pollution and is adversely influenced by the current common use of sunscreen. It has been shown that the bodies of people in New England make inadequate amounts of Vitamin D most of the year. Those on certain medications or with autoimmune-driven conditions usually need to avoid direct sunlight, and their levels of Vitamin D can be low as a result.

Vitamin D helps to increase calcium and phosphorous absorption which, in turn, helps to strengthen bones and muscles. It is also commonly thought this vitamin helps to protect people against certain diseases while more recent research (on autoimmunity) has found routine supplementation might actually make some diseases worse by how it affects gene expression at the microbiologic level. It has definitely been established that Vitamin D helps the immune system fight certain viral and bacterial infections. Therefore, there is conflicting data on whether Vitamin D is beneficial or more harmful in certain situations.

Vitamin D-3 has become the preferred type because it is found to work better. Some doctors recommend Vitamin D-3 at about 1000 IU daily, but only for a set period of time, just to build up reserve levels. (It is important to remember this is a fat-soluble vitamin and stored in fatty tissues, so it has the potential of becoming toxic if levels get too high.) The daily dose would then be reduced to about 800 IU/ day and increased again only when patients are found to be deficient. It should be taken with calcium. In view of the emerging controversy on Vitamin D supplementation, patients should get their levels checked and then be advised and monitored by their own physicians regarding the best dose for their needs.

Coenzyme Q-10

Usually referred to as simply CoQ-10 (also called ubiquinone), it is a vitamin-like substance which has notable cardioprotective, cytoprotective and neuroprotective activities. It is vital for the energy generating process at the cellular level in the mitochondrial electron transport chain. CoQ-10 is well regarded and used by physicians to treat various metabolic and neurologic diseases, cardiovascular conditions and diabetes. There are no contraindications, but general side effects may include stomach upset, nausea and headaches.

Individuals with certain illnesses may need to have their medications adjusted or be more closely monitored such as those with type-2 diabetes (CoQ-10 lowers blood sugar levels), those on anticoagulant drugs, and those using statin drugs (which decrease CoQ-10 serum levels). Some beta-blockersmay block CoQ-10 dependent enzymes. The average daily dose recommended by ME/CFS and FM clinicians is 100-200 mg. However, mitochondrial specialists who see ME/CFS patients recommend the same dosage as used for mitochondrial disease patients—300-400 mg twice a day. 


Acetyl-L-carnitine is one of several forms of carnitine. Carnitine has the chemical structure similar to an amino acid and is involved in fatty acid transport across mitochondrial membranes, which increases the use of fat as an energy source. Acetyl-L-carnitine may have neuroprotective, cytoprotective, antioxidant and anti-apoptotic activity. (Anti-apoptotic activity means it inter­feres with abnormal cellular suicide, which is a documented problem in ME/CFS). Mitochondrial membrane potential improves with acetyl-L-carnitine, which improves the functioning of mitochondria. People with seizure disorders should only use it under medical supervision. Adverse reactions are infrequent and are mild gastrointesti­nal symptoms such as nausea, vomiting, abdom­inal cramps and diarrhea. Antiseizure medications (valproic acid), nucleoside analogues, a type of antiviral treatment (didanosine, zalcitabine and stavudine), and pivalic acid-con­taining antibiotics may lead to secondary L-car­nitine deficiency and the need for acetyl-L-carnitine. Dosage may be 500-2000 mg daily in divided doses.

Nicotinamide adenine dinucleotide (NADH)

This is an active coenzyme form of Vitamin B-3 and necessary for energy production. NADH is located both in the mitochondria and cytosol of cells. (The cytosol is the cytoplasm or interior of the cell omitting the mitochondria.) It depends on the essential nutrient nicotinamide (a form of niacin) for its synthesis. The Physician's Desk Reference for Nutritional Supplements notes that mitochondrial membranes are impervious to NADH. However, NADH in the cytosol can still be used in cellular energy production in certain cells—mainly heart and liver cells. A small study was done on its benefits for ME/CFS and the dosage used in the trial was 10 mg daily, taken in the morning, about 45 minutes before eating. Clinicians who have used it since then find that if it is going to work, then about 30% will notice an improvement in 3 months, while 50% will show improvement in 6-12 months.

Dehydroepiandrosterone (DHEA)

DHEA is a steroid hormone produced by the adrenal glands and is converted to other hormones such as estrogen and testosterone. DHEA levels start to decrease with age and are found to be prematurely lower in people with ME/CFS and FM. A few specialists do prescribe this supplement to their patients; however, more are opposed to its use because of a strong potential to cause breast and ovarian cancer as well as prostate cancer.

The Physicians' Desk Reference (PDR) emphasizes that DHEA and its metabolite DHEA-S should not be used unless ordered by a doctor for documented abnormally low levels of DHEA. Canada and the UK have banned its sale over-the-counter.