Treatment
     Goals of Treatment
     Effectiveness of Treatment
     Key Points to Treatment

Specific Therapies and Things to Avoid
     Dietary Therapy
     Supportive Therapies
     Avoidance of Toxins
     Vitamins and Cofactors
     Vitamins and Supplements That May Be Helpful
     Medication, Minerals, Vitamins and Substrates That May Be Helpful
     Avoidance of Physiologic "Stress"


Treatment
At this time, there are no cures for these disorders.

Goals of treatment 
note: goals may never be met
  • alleviate symptoms
  • slow down the progression of the disease

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  Effectiveness of treatment
  • varies from patient to patient, depending on the exact disorder and the severity of the disorder
  • as a general rule, those with mild disorders tend to respond to treatment better than those with severe disorders
  • in some circumstances, the treatment can be tailored specifically to the patient, and that treatment is effective, whereas in other circumstance, the treatment is "emperic", meaning that the treatment makes sense, but that the benefit of treatment is not obvious or proven to be effective
  • treatment will not reverse the damage already sustained, such as brain malformations
Benefits of Treatment and Effectiveness of Therapies Vary
  • treatment may be beneficial and noted immediately in some disorders
  • benefit of treatment may take a few months to notice
  • benefit of treatment may never be noticed, but the treatment may be effective in delaying or stopping the progression of the disease
  • some patients may not benefit from therapy

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  Key Points to Treatment
  • Never forget there is standard treatment for some symptoms (anticonvulsant medication for epilepsy, physical therapy for motor problems, etc.)
  • Dietary
  • Vitamins and supplements
  • Avoidance of stressful factors
  • Treatment must be tailored by the patient's physician to meet that patient's need. Many of these therapies are totally ineffective in some mitochondrial disorders and would be a waste of time, money and effort. In some cases, the treatment could be dangerous.

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Specific Therapies & Things to Avoid

Dietary Therapy

Many patients, including young children or mentally impaired persons have already "self-adjusted" their diet, because they know what foods their body seem to tolerate. The points below are not meant to be suggested therapies for all patients with OXPHOS disorders, and some of the points are dangerous for patients with other disorders (4b could be lethal in pyruvate dehydrogenase deficiency for example). Do not make any of these dietary changes without consulting a physician. A dietitian experienced in metabolic disorders may be helpful.

Avoid fasting. This is perhaps the most important part of the treatment for most people with metabolic disorders. Fasting means "not eating" and avoiding fasting means avoid prolonged periods without a meal (even an overnight "fast" from 8 pm to 8 am may be dangerous in some patients). This also means that some patients should not intentionally try to loose weight by decreasing their food intake. In some patients an unintended fast resulting from an illness that causes vomiting or loss of appetite (like the flu) should be hospitalized to ensure continuous nutrition (intraveneous glucose for example). In order to ensure adequate frequent nutrition, sometimes a feeding tube needs to be placed in order for the person to receive feeding at night. In some patients, awakening them in the middle of the night for a snack can also be helpful.

Small frequent meals may be better than a typical 3-meal-a-day routine for some patients.

A snack before bedtime may be helpful in some patients. This snack should not be mainly "sugar" , like a candy bar , jello or sweetened cereal. It is usually best if the snack consists of a complex carbohydrate. Cornstarch is the best complex carbohydrate, but this is not very tasty. Theoretically, the best snack would be a homemade low-sugar rice pudding thickened with a lot of cornstarch. If you come up with a tasty recipe, let the UMDF know. Pasta, a peanut butter sandwich, bread and butter, unsweetened cereal (oatmeal) or a sandwich are acceptable. Many patients benefit by being woken up in the middle of the night for a small meal and others clearly improve when a gastrostomy tube is placed for continuous feeds. These final two suggestions are a small price to pay for health.

a) There are conflicting lines of evidence regarding the use of high fat meals in patients with electron transport chain disorders. In patients that seem to gain weight and thrive on a high-fat diet, it makes sense to continue the treatment. The extra fat can also be in the form of MCT (medium chain triglyceride oil), which is easier to metabolize (4c).

b) In other patients with OXPHOS disorders, reducing fat may be helpful. This includes reducing added oil, butter, & margarine, and cutting down on cheese and fatty meats. This recommendation is not meant to avoid fats altogether. A defect in OXPHOS can create an "energy backup", as the respiratory chain cannot handle the flow of electrons coming into it. This backup may result in the formation of excess free fatty acids (fats waiting to be burned) , which can poison the enzyme (adenosine nucleotide translocase) that exchanges the low-energy ADP located outside the mitochondria for the high-energy ATP formed at complex v. If you take the approach of limiting fats, extra effort needs to be made to increase the total carbohydrate (in the form of complex carbohydrates) in the diet.

c) In some patients (see #4a and #4b above), adding fat in the form of medium chain triglycerides (MCT), may be helpful. Medium chain triglycerides of 8 to 10 carbons long are easier to metabolize (turn into energy) than the longer chain triglycerides (those with 12-18 carbons) because they do not require carnitine to be transported into the mitochondria. MCT Oil@ is mainly made of 8 and 10 carbon triglycerides and this type of oil does not occur in nature, but is made from coconut oil. MCT Oil@ is made by the baby formula company Mead-Johnson. It comes in quart bottles, available by prescription and runs about $70 a quart. It can be added like oil over pasta and rice. You can cook with it, but this is a light oil and burns easily. The special rules are explained in a recipe book that you can request from the pharmacist. Depending on the situation, a patient may benefit from a few teaspoons to a few tablespoons a day. There are oils sold in health food stores called "MCT Oil" or "medium chain triglyceride oil". These are much less expensive ($25 per quart), but make sure there is a certified analysis on the label, stating that the vast majority of the oil is C-8 and C-1 0 (and not C-12 or higher).

Iron generate free radicals under certain conditions, which is especially bad in mitochondrial diseases because the free radicals injure mitochondrial DNA and "poke holes" in the mitochondria, making a bad problem worse. Therefore, excess iron is theoretically harmful. In people with mitochondrial disease, there is no routine need to give supplemental iron, nor is there a reason to eat foods rich in iron, such as extra red meat, for the purpose of eating foods rich in iron. This does not mean that the person should not eat red meat, especially if they enjoy it. There is no reason to take vitamins with added iron. There is the rare instance when iron is needed, but this is not common. In addition, vitamin C enhances the absorption of iron from the intestines, and vitamin C should not be given around a meal rich in iron. This is important to remember because some experts feel that vitamin C is a good antioxidant, and also may be helpful in some disorders of OXPHOS.

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Supportive Therapies

Some mitochondrial disease patients may need additional supportive therapies such as physical therapy, speech therapy or respiratory therapy.  While these therapies will not reverse the disease process, they may preser or even improve the patient's exhising functioning, mobility and strength.  Parts 1 and 2 of an article on these therapies can be found in the Mitochondrial News Volume 10, Issues 2 and 3.  

Avoidance of Toxins

Alcohol has been know to hasten the progression of some mitochondrial disorders.  Cigarette smoke, probably due to the carbon monoxide is known to hasten the progression of some conditions.  Remember that carbon monoxide kills by inhibiting complex IV of OXPHOS, why make it worse?  Cigarette smoke will make it worse.

MSG (monosodium glutamate) has for years been known to cause migraine headaches in otherwise healthy individuals, and my trigger these events in suceptible people with mitochondrial disease.  MSG is frequently added to Chinese (and other Asian) foods, and is also found in high levels of dried and canned soup.  Read the label and avoid MSG if there is any sensitivity.

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Vitamins and Cofactors

Vitamins and cofactors are compounds that are required in order for the chemical reactions, which make energy, to run efficiently. By definition, a  cofactor can be made by the body, whereas a vitamin cannot, and therefore must be eaten. For most people, a regular diet contains all the vitamins one could possibly need and their bodies can make as much of any specific cofactor that it needs. For those with mitochondrial disorders, added vitamins and cofactors may be useful. The use of supplemental vitamins and cofactors is largely unproven and their use is therefore controversial in patients with mitochondrial diseases. For disorders of OXPHOS, coenzyme Q10 is considered as a generally accepted effective therapy, although it may not ultimately be effective for an individual patient. Other treatments may be effective in one disorder but not in others. Because of the varied nature of mitochondrial diseases some therapies may be helpful in many, but not in all patients and therefore cannot be considered as "proven and effective." Some treatments should only be undertaken under the specific guidance of your physician. For specific information about the controversy, as it relates to your or your child's situation, ask your physician. Most of these vitamins can be purchased from many sources, including the drugstore.

These supplemental compounds can serve two functions:

  • possibly enhance enzyme function and result in improved efficiency of energy generation
  • serve as antioxidants, which may slow the progression of the disease

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Vitamins and Supplements That May be Helpful**

**Consult your physician before starting any of the following possible treatments**

First Tier Supplements

Supplement

Dose Range

CoQ10

5 – 15 mg/kg/day

Levo-carnitine
(Carnitor)

Variable, starting dose of 30 mg/kg/day, typical maximum of 100 mg/kg/day

Riboflavin (B2)

100 – 400 mg a day



Second Tier Supplement

Supplement

Dose Range

Acetyl-L-Carnitine

250 – 1000 mg per day

Thiamine (B1)

50 – 100 mg a day

Nicotinamide (B3)

50 – 100 mg a day

Vitamin E

200 – 400 IU; 1 – 3 times a day

Vitamin C

100 – 500 mg; 1 – 3 times a day

Lipoic Acid
(a -lipoate)

60 – 200 mg; 3 times a day

Selenium

25 – 50 micrograms a day

b -carotene

10,000 IU; every other day to daily

Biotin

2.5 – 10 mg a day

Folic Acid

1 – 10 mg a day

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Medication, Minerals, Vitamins and Substrates that May be Helpful**

**Any use of the following medications, minerals, vitamins and substrates MUST be made only under a physician's direction.**

Supplement

Dose Range

Calcium

Variable

Magnesium

Variable

Phosphorus

Variable

Succinate

6 gm per day

Creatine

5 gm bid after initial load (adults)

Uridine

To be determined

Citrates

Variable

Prednisone

Variable

Vitamin K3

5-30 mg per day

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Avoidance of Physiologic "Stress"

Physiologic stress is triggered by external factors that may result in worsening the metabolic situation, which may result in temporary , or in sometimes, permanent worsening of the condition. It is impossible to avoid all physiologic stressful conditions, so one should not attempt to do so. However, recognizing what may be stressful for patients allows one to adjust the lifestyle. Many patients and their parents have already identified these stresses, despite not knowing why the stresses were important, and avoid them.

Cold Stress is extremely important. Thermal regulation (temperature control) is not always normal in people with mitochondrial diseases and exposure to cold can result in severe heat loss and trigger an energy crisis. When going out into the cold, all exposed body parts should be covered, and exposure to extreme cold should be avoided for anything more than a short period. Over bundling can be a problem too (see below).

Heat Stress can be a problem in some people. This is especially true of those with an inability to sweat normally. Heat exhaustion and heat stroke may occur on hot days. It is typical for parents to describe that their child seems to "wilt" in situations like hot classrooms or direct sunlight, whereas the other children function normally. Light clothing is important. Patients should avoid direct sunlight on hot days and stay indoors if it is too warm outside. An air-conditioned environment may be needed.

Starvation — avoid fasting.

Lack of sleep may possibly be harmful.

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Except where noted, the above excerpts were taken, with permission, from Mitochondrial Cytopathies: A Primer written by Dr. Bruce Cohen, MD