Related Terms

  • Adrenoleukodystrophy, ALD, alkaptonuria, biotin-responsive inborn errors of metabolism, coronary artery disease, cystinosis, DIDMOAD syndrome, Folling’s disease, G6PD deficiency, GAMT deficiency, hyperalaninemia, hyperornithinemia, Kearns-Sayre syndrome, Leigh’s disease, maple syrup urine disease, McArdle’s disease, MELAS syndrome, metabolic syndrome, ornithine, PDH, phenylketonuria, PKU, pyruvate carboxylase deficiency, pyruvate dehydrogenase deficiency, subacute necrotizing encephalopathy, Tay-Sachs disease, trimethylaminuria, urea synthesis, wolfram syndrome.

Background

  • Metabolic disorders are illnesses that occur when the body is unable to process fats (lipids), proteins, sugars (carbohydrates), or nucleic acids properly. Most metabolic disorders are caused by genetic mutations that result in missing or dysfunctional enzymes that are needed for the cell to perform metabolic processes.
  • Most metabolic disorders are inherited, which means they are passed down through families. Examples of metabolic disorders include adrenoleukodystrophy (ALD), alkaptonuria, cystinosis, DIDMOAD syndrome (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness syndrome), glucose 6-phosphage dehydrogenase
    (G6PD) deficiency, hyperornithinemia-hyperammonemia-homocitrullinuria (HHH), inborn errors of urea synthesis, Kearns-Sayre, maple syrup urine disease, McArdle’s disease, MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes) syndrome, metabolic syndrome, phenylketonuria (PKU), pyruvate carboxylase deficiency, subacute necrotizing encephalopathy, Tay-Sachs disease, and trimethylaminuria.
  • Prognosis and treatment varies, depending on the type and severity of the disorder.

Integrative Therapies

Note
: The integrative therapies listed below are indicated for a variety of metabolic disorders. It is recommended to consult with a healthcare provider to select the appropriate therapy for the patient’s specific metabolic disorder.

A

Strong scientific evidence

  • L-arginine
    : L-arginine helps maintain the body’s fluid balance (urea, creatinine). It also helps fight against infection and aids in wound healing, hair growth, sperm production (spermatogenesis), blood vessel relaxation (vasodilation), and fights infection. In patients with inborn errors of urea synthesis, high blood ammonia levels and metabolic alkalosis may occur, particularly in patients with ornithine carbamoyl transferase (OCT) deficiency or carbomoyl phosphate synthetase (CPS) deficiency. Arginine can be a helpful treatment by shifting the way the body processes nitrogen. However, it should be avoided in patients with hyperargininemia (high arginine levels). Other drugs may have similar benefits, such as citrulline, sodium benzoate, or sodium phenylbutyrate, although dialysis may be necessary initially. This use of arginine should be supervised by a qualified healthcare professional.

  • Avoid if allergic to arginine. Avoid with a history of stroke, liver disease, or kidney disease. Use cautiously if taking blood-thinning drugs (such as warfarin), blood pressure drugs, or herbs or supplements with similar effects. Check blood potassium levels while taking L-arginine. Avoid if pregnant or breastfeeding.
  • Biotin
    : Biotin is a vitamin that is produced by bacteria in the gut. Disorders such as multiple carboxylase deficiency can cause inborn errors of metabolism that cause a “functional” biotin deficiency. High-dose biotin is used to treat these disorders. Management should be under strict medical supervision.

  • Avoid if allergic or hypersensitive to constituents of biotin supplements.
  • Thiamin
    : Thiamin (also spelled thiamine) is a water-soluble B-complex vitamin. It is also known as vitamin B1 or aneurine. Thiamin is involved in nervous system and muscle functioning, enzyme processes, breakdown of carbohydrates, and production of hydrochloric acid (which is needed for digestion).
    Taking thiamin by mouth helps to temporarily correct some complications of metabolic disorders associated with genetic diseases, including subacute necrotizing encephalopathy (SNE, Leigh’s disease), maple syrup urine disease (branched-chain aminoacidopathy), and lactic acidosis associated with pyruvate carboxylase deficiency and hyperalaninemia. Long-term management should be under strict medical supervision.

  • Thiamin is generally considered safe and relatively nontoxic, even at high doses. Avoid if allergic or hypersensitive to thiamin.
    Thiamin appears safe if pregnant or breastfeeding. The Recommended Dietary Allowance (RDA) for pregnant or breastfeeding women is 1.4 milligrams taken by mouth.

C

Unclear or conflicting scientific evidence

  • L-arginine
    : L-arginine is an amino acid that helps maintain the body’s fluid balance. Injections of arginine have been proposed to help manage adrenoleukodystrophy (ALD), although most study results are inconclusive. Further research is needed to evaluate the use of arginine in ALD. Limited available study found that two years of supplementation with oral L-arginine significantly improved endothelial function in patients with MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke). Further research is warranted in this area.

  • Avoid if allergic to arginine. Avoid with a history of stroke, liver disease, or kidney disease. Use cautiously if taking blood-thinning drugs (such as warfarin), blood pressure drugs, or herbs or supplements with similar effects. Check blood potassium levels while taking L-arginine. Avoid if pregnant or breastfeeding.
  • Black tea
    : Black tea has been suggested as a possible agent for metabolic enhancement.
    Additional research is needed to understand exactly how black tea may affect human metabolism.

  • Avoid if allergic or hypersensitive to caffeine or tannins. Skin rash and hives have been reported with caffeine ingestion. Use caution with diabetes. Use caution if pregnant. Heavy caffeine intake during pregnancy may increase the risk of SIDS (sudden infant death syndrome). Very high doses of caffeine have been linked with birth defects. Caffeine is transferred into breast milk. Caffeine ingestion by infants can lead to sleep disturbances/insomnia. Infants nursing from mothers consuming greater than 500 milligrams of caffeine daily have been reported to experience tremors and heart rhythm abnormalities. Tea consumption by infants has been linked to anemia, decreased iron metabolism and irritability.
  • Coenzyme Q10
    : Coenzyme Q10 (CoQ10) is produced by the human body, and it is necessary for basic functioning of cells. CoQ10 levels decrease with age. CoQ10 is often recommended for patients with mitochondrial diseases, including myopathies, encephalomyopathies, and Kearns-Sayre syndrome. Better studies are needed before a conclusion can be made.

  • No reported allergies have been associated with Coenzyme Q10 supplements, although rash and itching have been reported rarely. Stop use two weeks before and immediately after surgery/dental/diagnostic procedures with bleeding risks. Use cautiously with a history of blood clots, diabetes, high blood pressure, heart attack, or stroke. Use cautiously if taking anticoagulants (blood thinners) or anti-platelet drugs, blood pressure, blood sugar, cholesterol, or thyroid drugs. Avoid if pregnant or breastfeeding.
  • Copper
    : Copper is a mineral that occurs naturally in many foods, including vegetables, legumes, nuts, grains, fruits, shellfish, avocado, beef, and animal organs, (e.g. liver and kidneys). Preliminary evidence suggests that the use of copper chlorophyllin results in a reduced urinary free trimethylamine (TMA) concentration and normalization of trimethylamine N-oxide (TMAO). Further research is required before recommendations can be made for the use of copper for trimethylaminuria.

  • Avoid if allergic/hypersensitive to copper. Avoid use of copper supplements during the early phase of recovery from diarrhea. Avoid with hypercupremia or genetic disorders affecting copper metabolism (e.g. Wilson’s disease, Indian childhood cirrhosis, or idiopathic copper toxicosis). Avoid with HIV/AIDS. Use cautiously with water containing copper concentrations greater than six milligrams per liter. Use cautiously with anemia, arthralgias, or myalgias. Use cautiously if taking oral contraceptives. Use cautiously if at risk for selenium deficiency. The Recommended Dietary Allowance (RDA) is 1,000 micrograms for pregnant women. The Recommended Dietary Allowance (RDA) is 1,300 micrograms for nursing women.
  • Creatine
    : Creatine is an amino acid that is found in the muscles. Some individuals are born with a genetic disorder in which there is a deficiency of the enzyme guanidinoacetate methyltransferase (GAMT). A lack of this enzyme causes severe developmental delays and abnormal movement disorders. The condition is diagnosed by a lack of creatine in the brain. There is currently only limited research on the use of creatine supplementation for GMAT deficiency. Additional study is needed to reach a conclusion in this area.

  • Ornithine is a byproduct formed in the liver. Some individuals are born with a genetic disorder that prevents them from appropriately breaking down ornithine, and blood levels of ornithine become too high. High amounts of ornithine can lead to blindness, muscle weakness, and reduced storage of creatine in muscles and the brain. Although there is only limited research in this area, early evidence suggests that long-term, daily creatine supplements may help replace missing creatine and may slow vision loss in patients with hyperornithinemia.
  • In McArdle’s disease, there is a deficiency of energy compounds stored in muscle. This leads to muscle fatigue, exercise intolerance, and pain when exercising. Creatine has been proposed as a possible therapy for this condition. However, research is limited, and the results of existing studies disagree with each other. Therefore, it remains unclear if creatine offers any benefits to patients with McArdle’s disease.
  • Avoid if allergic to creatine or if taking diuretics (such as hydrochlorothiazide or furosemide). Use cautiously with asthma, diabetes, gout (foot inflammation), kidney, liver, or muscle problems, stroke, or with a history of these conditions. Avoid dehydration. Avoid if pregnant or breastfeeding.
  • Grapefruit
    : Early studies suggest grapefruit may have some benefit in the management of metabolic syndrome. More studies are needed to understand this relationship.

  • Avoid
    if allergic to grapefruit. Grapefruit may interact with prescription drugs, herbs, or supplements. Use cautiously if taking anticoagulants, anti-platelet drugs, antiarrhythmics, anticonvulsants, antidepressants, antihistamines, antihypertensives, benzodiazepines, calcium channel blockers, caffeine, corticosteroids, erectile dysfunction medications, estrogens, immune modulators, HMG-CoA reductase inhibitors, macrolide antibiotics, protease inhibitors, or drugs that are broken down by the liver. Use cautiously if drinking red wine or tonic water. Use cautiously when smoking or with liver cirrhosis or if at risk for kidney stones. Use cautiously in patients that have undergone gastric bypass surgery. Use cautiously if pregnant or breastfeeding.
  • Soy
    : Soy nuts may help reduce inflammation, improve blood sugar control, and improve lipid profiles in postmenopausal women with metabolic syndrome. More research is needed in this area.

  • Avoid if allergic to soy. Breathing problems and rash may occur in sensitive people. Soy, as a part of the regular diet, is traditionally considered to be safe during pregnancy and breastfeeding, but there is limited scientific data available. The effects of high doses of soy or soy isoflavones in humans are not clear, and therefore are not recommended. People who experience intestinal irritation (colitis) from cow’s milk may experience intestinal damage or diarrhea from soy. It is not known if soy or soy isoflavones share the same side effects as estrogens, like increased risk of blood clots. The use of soy is often discouraged in patients with hormone-sensitive cancers, such as breast, ovarian or uterine cancer. Other hormone-sensitive conditions such as endometriosis may also be worsened. Patients taking blood-thinning drugs like warfarin should check with a doctor and pharmacist before taking soy supplementation.
  • Thiamin
    : DIDMOAD (Wolfram) syndrome is believed to cause a decrease in the enzyme that converts thiamin to its active form. Management, including thiamin supplementation, should be under strict medical supervision. There is preliminary evidence of clinical improvements in children with pyruvate dehydrogenase deficiency (PDH) following thiamin administration. Further evidence is necessary before a firm conclusion can be reached.

  • Thiamin is generally considered safe and relatively nontoxic, even at high doses. Avoid if allergic or hypersensitive to thiamin.
    Thiamin appears safe if pregnant or breastfeeding. The U.S. Recommended Daily Allowance (RDA) for pregnant or breastfeeding women is 1.4 milligrams taken by mouth.
  • Vitamin C (ascorbic acid)
    : Vitamin C (ascorbic acid) is a vitamin that the body needs to form collagen in bones, cartilage, muscle, and blood vessels. It also helps the body absorb iron. Vitamin C is found in foods, such as fruits and vegetables (especially citrus fruits like oranges). Alkaptonuria is a disorder characterized by the absence of the enzyme homogentisic acid oxidase, with a resulting accumulation of homogentisic acid in the blood and urine. Limited research reports that daily high-dose vitamin C may provide symptomatic relief and slow progression of complications in patients with alkaptonuria. Additional evidence is merited in this area.

  • Vitamin C is generally considered safe in amounts found in foods. Vitamin C supplements are also generally considered safe in most individuals if taken in recommended doses. Avoid high doses of vitamin C with glucose 6-phosphate dehydrogenase deficiency, kidney disorders or stones, cirrhosis (inflammation of the liver), gout (foot inflammation), or paroxysmal nocturnal hemoglobinuria (bleeding disorder). Vitamin C intake from food is generally considered safe if pregnant or breastfeeding. It is unclear if vitamin C supplements in doses higher than dietary reference intake recommendations are safe for pregnant or breastfeeding women. Vitamin C is naturally found in breast milk.
  • Vitamin E
    : Vitamin E exists in eight different forms (“isomers”): alpha, beta, gamma and delta tocopherol; and alpha, beta, gamma, and delta tocotrienol. Alpha-tocopherol is the most active form in humans. Vitamin E supplementation has been studied for the inherited disorder G6PD deficiency with conflicting evidence. Additional research is necessary before a clear conclusion can be drawn.

  • Avoid if allergic or hypersensitive to vitamin E. For short periods of time, vitamin E supplementation is generally considered safe in the recommended doses. Use cautiously with bleeding disorders.

D

Fair negative scientific evidence

  • Pantethine
    : Pantethine is the active form of pantothenic acid. Research suggests that pantethine, when taken by mouth, can lower cholesterol. It is also used for lowering the risk of heart disease, increasing energy, improving adrenal function, and preventing allergy symptoms in people allergic to formaldehyde. Preliminary research does not show any benefit for oral pantethine in the treatment of cystinosis.

  • Avoid if allergic or hypersensitive to pantethine or any component of the formulation. Use cautiously with bleeding disorders. Avoid if pregnant or breastfeeding.

Prevention

  • Individuals can take steps to reduce their risk of developing metabolic syndrome by eating healthy foods and exercising regularly. Patients should also visit their doctors regularly to determine if they are at risk of developing metabolic syndrome.
  • There are currently no known methods of prevention for metabolic disorders that are inherited. However, individuals can be tested to determine if they are carriers of the disease. Although carriers do not experience symptoms of the disease, they may pass them on to their children.
  • Patients who have genetically inherited metabolic disorders or are carriers of certain disorders may wish to receive genetic counseling. A counselor will provide information and answer questions about the risk of passing the disorders on to their children.
  • Patients with metabolic disorders should take their medications exactly as prescribed and/or strictly follow their diets in order to help prevent complications.

Author Information

  • This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

References

Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

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    View Abstract
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    View Abstract
  4. Endocrine and Metabolic Diseases Information Service. . Accessed April 16, 2009.
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    View Abstract
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    View Abstract
  7. Natural Standard: The Authority on Integrative Medicine. . Copyright © 2009. Accessed April 16, 2009.
  8. Oka Y. Wolfram syndrome. Article in Japanese. Nippon Rinsho. 2006 Sep 28;Suppl 3:138-42.
    View Abstract
  9. Olsson GM, Montgomery SM, Alm J. Family conditions and dietary control in phenylketonuria. J Inherit Metab Dis. 2007 Jun 14; Epub ahead of print.
    View Abstract
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    View Abstract
  11. Zachwieja J. Cystinosis–an orphan disease. Pathogenesis and current treatment. Article in Polish. Przegl Lek. 2006;63 Suppl 3:29-31.
    View Abstract