Protect Your Mitochondria, Protect Your Health
- Mitochondria produce energy, and are vital for health and longevity.
- Mitochondrial damage is implicated in aging, heart disease, dementia, chronic fatigue syndrome, diabetes and many more.
- Common medications damage mitochondria, including drugs for heart disease, diabetes and pain.
- Dr. John Neustadt was recognized by the world’s largest publisher as a Top Ten Cited Author for his research on mitochondrial damage and disease.
- Based on this research, Dr. Neustadt developed MitoForte, that contains the dose and combination of nutrients shown to support mitochondrial health and improve memory, energy and mood.
By Dr. John Neustadt
Mitochondria are the powerhouses of our cells. They create the cellular energy that allows us to think, move, eat, talk, breathe and everything else our bodies do. Along with creating energy as adenosine triphosphate (ATP), they also product heat.
The largest number of mitochondria is found in the most active cells, such as muscles (skeletal and heart), the liver and brain. Mitochondria are found in every human cell except mature red blood cells.
Mitochondria are found in every human cell except mature red blood cells (erythrocytes). Cellular energy requirements control how many mitochondria are in each cell. A single in the body can contain from as little as 16 mitochondria in sperm to as many as 100,000 in a woman’s egg (oocyte). In non-reproductive cells, there are anywhere from 200 to 2000 mitochondria.
DNA provides the biochemical blueprints for our cells to create proteins. While most DNA lives in the cell nucleus, mitochondria have their own DNA. The fact that mitochondria have their own DNA, along with comparative analyses of mitochondria DNA and DNA from other organisms, led scientists to conclude that mitochondria descended from bacteria that colonized an ancient cell between one and three billion years ago. The ability for cells to start producing their own cellular energy allowed for the evolution of multicellular organisms such as humans. The fact that mitochondria contain their own DNA is cited as evidence for the theory that mitochondria evolved from free-living bacteria.
Unlike nuclear DNA, mitochondrial DNA lacks an important protein called histones. Histones protect DNA free radical damage. Since mitochondrial DNA don’t have histones it is more susceptible to attack from free radicals, and it’s this free radical damage that’s is responsible for mitochondria’s role in creating disease.
The first mitochondrial disease was described in 1962, when a thirty-five-year-old woman experienced myopathy (muscle damage), excessive perspiration, heat intolerance (feeling hot when everyone else feels normal or cool), polydipsia (excessive thirst) with polyuria (excessive urination), and a metabolic rate 180% of normal. The patient suffered from mitochondrial damage that resulted in the generation of heat without creating energy, which is why she felt hot. When samples of her muscle were taken and examined under a microscope, numerous enlarged mitochondria were seen. Just like muscles, when mitochondria have to work more, they get bigger. In her case, in order to produce enough energy to simply satisfy the minimum requirements of her body, her mitochondria had to work extremely hard.
Since then, mitochondrial dysfunction has been implicated in nearly all diseases, including:
- Alzheimer’s disease
- Anxiety disorders
- Bipolar disorder
- Cancer, including hepatitis-C virus-associated liver cancer
- Cardiovascular disease, including atherosclerosis (hardening of the arteries)
- Exercise intolerance
- Fatigue, including chronic fatigue syndrome, fibromyalgia, and myofascial pain (pain arising from the connective tissue surrounding muscles)
- Huntington’s disease
- Nonalcoholic steatohepatitis (enlarged, fatty liver not caused by alcoholism)
- Parkinson’s disease
- Sarcopenia (weakness from muscle wasting)
Damage to mitochondrial can create weakness, muscle cramping and pain, atypical migraines, failure to gain weight, respiratory problems, absent or excessive sweating, atypical cerebral palsy, and more. However, since symptoms vary from person to person, mitochondrial dysfunction may not be recognized early on. Symptoms such as fatigue, muscle pain, shortness of breath, and abdominal pain can easily be mistaken for other diseases, such as chronic fatigue syndrome, fibromyalgia, or psychosomatic illness (symptoms caused by psychological conditions). Additionally, most doctors don’t consider mitochondrial damage as a potential underlying cause of these symptoms.
Damage to mitochondria is caused primarily by free radicals, also called reactive oxygen species (ROS), that are generated by the mitochondria themselves during their production of cellular energy. The body maintains sophisticated antioxidant systems that can help neutralize free radicals. However, this system can be overwhelmed when there is an increase in free radical production or a decrease in antioxidants to deal with them.
Within the mitochondria, elements that are particularly vulnerable to free radical damage include fats, proteins, mitochondrial DNA and the enzymes used to create cellular energy. Direct damage can overwhelm their ability to fix the damage and decrease their ability to produce energy. Mitochondrial dysfunction can result in a feedforward process, whereby mitochondrial damage causes additional damage.
Damage to mitochondria explains the side effects and dangers from pharmaceuticals. And when people take drug cocktails (multiple drugs simultaneously), they put themselves at even greater risk for mitochondrial damage. The FDA does not require that drugs be tested for their ability to damage mitochondria, which may occur slowly over time. There is a long list of medications that cause mitochondrial damage.
- Disulfiram (Antabuse)
Pain and anti-inflammatory medications:
- Acetaminophen (Tylenol)
- Diclofenac (Voltaren, Voltarol, Diclon, Dicloflex Difen and Cataflam)
- Fenoprofen (Nalfon)
- Indomethacin (Indocin, Indocid, Indochron E-R, Indocin-SR)
- Naproxen (Aleve, Naprosyn)
Heart Disease Medictations:
- Angina medications: perhexiline, amiodarone (Cordarone), diethylaminoethoxyhexesterol (DEAEH)
- Antiarrhythmic (regulates heartbeat): amiodarone (Cordarone)
- Cholesterol medications:
- Statins: atorvastatin (Lipitor, Torvast), fluvastatin (Lescol), lovastatin (Mevacor, Altocor), pitavastatin (Livalo, Pitava), pravastatin (Pravachol, Selektine, Lipostat), rosuvastatin (Crestor), simvastatin (Zocor, Lipex)
- Bile acidsholestyramine (Questran), clofibrate (Atromid-S), ciprofibrate (Modalim), colestipol (Colestid), colesevelam (Welchol)
Anesthetics: bupivacaine, lidocaine, propofol
Antibiotics: tetracycline, antimycin A
Antidepressants: amitriptyline (Lentizol), amoxapine (Asendis), citalopram (Cipramil), fluoxetine (Prozac, Symbyax, Sarafem, Fontex, Foxetin, Ladose, Fluctin, Prodep, Fludac, Oxetin, Seronil, Lovan)
Antipsychotics: chlorpromazine, fluphenazine, haloperidol, risperidone, quetiapine, clozapine, olanzapine
Anxiety medications: alprazolam (Xanax), diazepam (Valium, Diastat)
Barbiturates: amobarbital (Amytal), aprobarbital, butabarbital, butalbital (Fiorinal), hexobarbital (Sombulex), methylphenobarbital (Mebaral), pentobarbital, methylphenobarbital (Mebaral), pentobarbital (Nembutal), phenobarbital (Luminal), primidone, propofol, secobarbital (Seconal, Talbutal), thiobarbital.
Cancer (chemotherapy) medications: mitomycin C, profiromycin, adriamycin (also called doxorubicin and hydroxydaunorubicin and included in the following chemotherapeutic regimens: ABVD, CHOP and FAC)
Dementia and memory medications: tacrine (Cognex), galantamine (Reminyl)
Diabetes medications: metformin (Fortamet, Glucophage, Glucophage XR, Riomet), troglitazone, rosiglitazone, buformin
HIV/AIDS medications: Atripla, Combivir, Emtriva, Epivir (abacavir sulfate), Epzicom, Hivid (ddc, zalcitabine), Retrovir (AZT, ZDV, zidovudine), Trizivir, Truvada, Videx (ddI, didanosine), Videx EC, Viread, Zerit (d4T, stavudine), Ziagen, Racivir
Epilepsy (seizure) medications: valproic acid (Depacon, Depakene, Depakene syrup, Depakote, Depakote ER, Depakote Sprinkle, Divalproex sodium)
Mood stabilizer: lithium
Parkinson’s disease medications: tolcapone (Tasmar ), entacapone (COMTan, also in the combination drug Stalevo)
Protecting and Repairing Mitochondria
Fortunately, over the last half century since the first mitochondrial disease was identified, researchers have not only better defined the molecular and cellular biology of mitochondria, they have also researched ways to protect and reverse mitochondrial damage.
Since the major reason for mitochondrial dysfunction is free-radical damage, it is not surprising that research has shown that antioxidants may help repair mitochondrial dysfunction. Dietary supplements are not the only potential strategy; diets rich in antioxidants may also help.
Many vitamins and minerals are required to create the mitochondria cellular machinery and energy. These include:
Vitamins: Biotin, CoQ10, Lipoic acid, Vitamin B1, Vitamin B2, Vitamin B3, Vitamin B5, Vitamin B6, Vitamin C, Vitamin E
Minerals: Iron, Magnesium, Manganese, Selenium, Sulfur, Zinc, Copper
Amino Acids: L-Carnitine
Other nutrients: Alpha Lipoic Acid
While these nutrients are available in foods, dietary supplements may be necessary to supply the nutrients in adequate amounts for optimal mitochondrial function.
If you are taking a multiple vitamin and mineral dietary supplement, make sure it has the most-absorbable forms of nutrients. Dr. John Neustadt’s article, When it Comes to Dietary Supplements, it’s Buyer Beware can help you understand how what to look for on a multiple vitamin and mineral product label to make sure you’re getting your money’s worth.
Sone nutrients, like L-Carnitine and Alpha Lipoic Acid (ALA) aren’t typically found in a multiple vitamin and mineral dietary supplement. Research has shown that these two nutrients, when provided in adequate amounts can repair mitochondrial damage and improve energy production. To study whether or not declines in biochemical activity associated with aging are reversible, L-carnitine and Alpha Lipoic Acid—alone and in combination—were administered to rats. L-carnitine was supplemented at dosages of 300 mg to kg of body weight per day (mg/kg bw/day) and Alpha Lipoic Acid at 100 mg/kg bw/day.
At the beginning of the study, the old rats had only approximately one-third of the biochemical function as the young rats. After a month of taking the nutrients, however, biochemical function of the old rats improved about 150%. Only the rats who took both nutrients experienced the improvement. Taking either of the nutrients in isolation didn’t provide the benefit.
Mitochondria are the essential energy-producing part of our cells. Diseases and medications damage mitochondria, which can lead to a reduction in energy and the onset and progression of chronic, degenerative diseases. In essence, what is happening when mitochondria are damaged is that the body then begins to poison itself and cause its own deterioration. Fortunately, research shows that some nutrients can help reverse mitochondrial damage.
Ames BN, Shigenaga MK, Hagen TM. Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci U S A. 1993;90(17):7915-7922. [Article]
Aw TY, Jones DP. Nutrient supply and mitochondrial function. Annu Rev Nutr. 1989;9:229-251. [Article]
Balijepalli S, Boyd MR, Ravindranath V. Inhibition of mitochondrial complex I by haloperidol: the role of thiol oxidation. Neuropharmacology. 1999;38(4):567-577. [Article]
Balijepalli S, Kenchappa RS, Boyd MR, Ravindranath V. Protein thiol oxidation by haloperidol results in inhibition of mitochondrial complex I in brain regions: comparison with atypical antipsychotics. Neurochem Int. 2001;38(5):425-435. [Article]
Beavis AD. On the inhibition of the mitochondrial inner membrane anion uniporter by cationic amphiphiles and other drugs. J Biol Chem. 1989;264(3):1508-1515. [Article]
Berson A, De Beco V, Letteron P, et al. Steatohepatitis-inducing drugs cause mitochondrial dysfunction and lipid peroxidation in rat hepatocytes. Gastroenterology. 1998;114(4):764-774. [Article]
Brown SJ, Desmond PV. Hepatotoxicity of Antimicrobial Agents. Seminars in Liver Disease. 2002(2):157-168. [Article]
Bua EA, McKiernan SH, Wanagat J, McKenzie D, Aiken JM. Mitochondrial abnormalities are more frequent in muscles undergoing sarcopenia. J Appl Physiol. 2002;92(6):2617-2624. [Article]
Buist R. Elevated Xenobiotics, Lactate and Pyruvate in C.F.S. Patients. Journal of Orthomolecular Medicine. 1989;4(3):170-172. [Article]
Chan K, Truong D, Shangari N, O’Brien PJ. Drug-induced mitochondrial toxicity. Expert Opin Drug Metab Toxicol. 2005;1(4):655-669. [Article]
Chitturi SMD, George JPD. Hepatotoxicity of Commonly Used Drugs: Nonsteroidal Anti-Inflammatory Drugs, Antihypertensives, Antidiabetic Agents, Anticonvulsants, Lipid-Lowering Agents, Psychotropic Drugs. Seminars in Liver Disease. 2002(2):169-184. [Article]
Cohen BH, Gold DR. Mitochondrial cytopathy in adults: what we know so far. Cleve Clin J Med. 2001;68(7):625-626, 629-642. [Article]
Conley KE, Esselman PC, Jubrias SA, et al. Ageing, muscle properties and maximal O(2) uptake rate in humans. J Physiol. 2000;526 Pt 1:211-217. [Article]
Corral-Debrinski M, Shoffner JM, Lott MT, Wallace DC. Association of mitochondrial DNA damage with aging and coronary atherosclerotic heart disease. Mutat Res. 1992;275(3-6):169-180. [Article]
Cullen JM. Mechanistic classification of liver injury. Toxicol Pathol. 2005;33(1):6-8. [Article]
DiMauro S, Schon EA. Mitochondrial Respiratory-Chain Diseases. N Engl J Med. 2003;348(26):2656-2668. [Article]
Duchen MR. Mitochondria in health and disease: perspectives on a new mitochondrial biology. Mol Aspects Med. 2004;25(4):365-451. [Article]
Einat H, Yuan P, Manji HK. Increased anxiety-like behaviors and mitochondrial dysfunction in mice with targeted mutation of the Bcl-2 gene: further support for the involvement of mitochondrial function in anxiety disorders. Behav Brain Res. 2005;165(2):172-180. [Article]
Ezoulin MJ, Li J, Wu G, et al. Differential effect of PMS777, a new type of acetylcholinesterase inhibitor, and galanthamine on oxidative injury induced in human neuroblastoma SK-N-SH cells. Neurosci Lett. 2005;389(2):61-65. [Article]
Fattal O, Budur K, Vaughan AJ, Franco K. Review of the literature on major mental disorders in adult patients with mitochondrial diseases. Psychosomatics. 2006;47(1):1-7. [Article]
Fosslien E. Mitochondrial Medicine – Molecular Pathology of Defective Oxidative Phosphorylation. Ann Clin Lab Sci. 2001;31(1):25-67. [Article]
Fromenty B, Pessayre D. Impaired mitochondrial function in microvesicular steatosis effects of drugs, ethanol, hormones and cytokines. Journal of Hepatology. 1997;26(Supplement 2):43-53. [Article]
Gambelli S, Dotti MT, Malandrini A, et al. Mitochondrial alterations in muscle biopsies of patients on statin therapy. J Submicrosc Cytol Pathol. 2004;36(1):85-89. [Article]
Gray MW. Origin and evolution of mitochondrial DNA. Annu Rev Cell Biol. 1989;5:25-50. [Article]
Koike K. Molecular basis of hepatitis C virus-associated hepatocarcinogenesis: lessons from animal model studies. Clin Gastroenterol Hepatol. 2005;3(10 Suppl 2):S132-135. [Article]
Lambert PD, McGirr KM, Ely TD, Kilts CD, Kuhar MJ. Chronic lithium treatment decreases neuronal activity in the nucleus accumbens and cingulate cortex of the rat. Neuropsychopharmacology. 1999;21(2):229-237. [Article]
Levy HB, Kohlhaas HK. Considerations for supplementing with coenzyme Q10 during statin therapy. Ann Pharmacother. 2006;40(2):290-294. [Article]
Lieber CS, Leo MA, Mak KM, et al. Model of nonalcoholic steatohepatitis. Am J Clin Nutr. 2004;79(3):502-509. [Article]
Liu J, Killilea DW, Ames BN. Age-associated mitochondrial oxidative decay: improvement of carnitine acetyltransferase substrate-binding affinity and activity in brain by feeding old rats acetyl-L- carnitine and/or R-alpha -lipoic acid. Proc Natl Acad Sci U S A. 2002;99(4):1876-1881. [Article]
Luft R, Ikkos D, Palmieri G, Ernster L, Afzelius B. A case of severe hypermetabolism of nonthyroid origin with a defect in the maintenance of mitochondrial respiratory control: a correlated clinical, biochemical, and morphological study. J Clin Invest. 1962;41:1776-1804. [Article]
Mansouri A, Haouzi D, Descatoire V, et al. Tacrine inhibits topoisomerases and DNA synthesis to cause mitochondrial DNA depletion and apoptosis in mouse liver. Hepatology. 2003;38(3):715-725. [Article]
Masubuchi Y, Suda C, Horie T. Involvement of mitochondrial permeability transition in acetaminophen-induced liver injury in mice. J Hepatol. 2005;42(1):110-116. [Article]
Maurer I, Moller HJ. Inhibition of complex I by neuroleptics in normal human brain cortex parallels the extrapyramidal toxicity of neuroleptics. Mol Cell Biochem. 1997;174(1-2):255-259. [Article ]
Modica-Napolitano JS, Lagace CJ, Brennan WA, Aprille JR. Differential effects of typical and atypical neuroleptics on mitochondrial function in vitro. Arch Pharm Res. 2003;26(11):951-959. [Article]
Park JH, Niermann KJ, Olsen N. Evidence for metabolic abnormalities in the muscles of patients with fibromyalgia. Curr Rheumatol Rep. 2000;2(2):131-140. [Article]
Puddu P, Puddu GM, Galletti L, Cravero E, Muscari A. Mitochondrial dysfunction as an initiating event in atherogenesis: a plausible hypothesis. Cardiology. 2005;103(3):137-141. [Article]
Reid AB, Kurten RC, McCullough SS, Brock RW, Hinson JA. Mechanisms of acetaminophen-induced hepatotoxicity: role of oxidative stress and mitochondrial permeability transition in freshly isolated mouse hepatocytes. J Pharmacol Exp Ther. 2005;312(2):509-516. [Article]
Roberton AM, Ferguson LR, Cooper GJ. Biochemical evidence that high concentrations of the antidepressant amoxapine may cause inhibition of mitochondrial electron transport. Toxicol Appl Pharmacol. 1988;93(1):118-126. [Article]
Sarah M, Poonam K. Diazepam induced early oxidative changes at the subcellular level in rat brain. Molecular and cellular biochemistry. 1998;V178(1):41-46. [Article]
Savitha S, Sivarajan K, Haripriya D, Kokilavani V, Panneerselvam C. Efficacy of levo carnitine and alpha lipoic acid in ameliorating the decline in mitochondrial enzymes during aging. Clin Nutr. 2005;24(5):794-800. [Article]
Shigenaga M, Hagen T, Ames B. Oxidative Damage and Mitochondrial Decay in Aging. PNAS. 1994;91(23):10771-10778. [Article]
Sirvent P, Bordenave S, Vermaelen M, et al. Simvastatin induces impairment in skeletal muscle while heart is protected. Biochem Biophys Res Commun. 2005;338(3):1426-1434. [Article]
Sirvent P, Mercier J, Vassort G, Lacampagne A. Simvastatin triggers mitochondria-induced Ca2+ signaling alteration in skeletal muscle. Biochem Biophys Res Commun. 2005;329(3):1067-1075. [Article]
Skulachev VP, Longo VD. Aging as a mitochondria-mediated atavistic program: can aging be switched off? Ann N Y Acad Sci. 2005;1057:145-164. [Article]
Spees JL, Olson SD, Whitney MJ, Prockop DJ. Mitochondrial transfer between cells can rescue aerobic respiration. PNAS. 2006;103(5):1283-1288. [Article]
Stavrovskaya IG, Kristal BS. The powerhouse takes control of the cell: Is the mitochondrial permeability transition a viable therapeutic target against neuronal dysfunction and death? Free Radical Biology and Medicine. 2005;38(6):687-697. [Article]
Stork C, Renshaw PF. Mitochondrial dysfunction in bipolar disorder: evidence from magnetic resonance spectroscopy research. Mol Psychiatry. 2005;10(10):900-919. [Article]
Szewczyk A, Wojtczak L. Mitochondria as a pharmacological target. Pharmacol Rev. 2002;54(1):101-127. [Article]
Tanaka M, Kovalenko SA, Gong JS, et al. Accumulation of deletions and point mutations in mitochondrial genome in degenerative diseases. Ann N Y Acad Sci. 1996;786:102-111. [Article]
Velho JA, Okanobo H, Degasperi GR, et al. Statins induce calcium-dependent mitochondrial permeability transition. Toxicology. 2006;219(1-3):124-132. [Article]
Veltri KL, Espiritu M, Singh G. Distinct genomic copy number in mitochondria of different mammalian organs. J Cell Physiol. 1990;143(1):160-164. [Article]
Wallace DC. A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: A dawn for evolutionary medicine. Annual Review of Genetics. 2005;39(1):359-407. [Article]
Wei YH, Lu CY, Lee HC, Pang CY, Ma YS. Oxidative damage and mutation to mitochondrial DNA and age-dependent decline of mitochondrial respiratory function. Ann N Y Acad Sci. 1998;854:155-170. [Article]
West IC. Radicals and oxidative stress in diabetes. Diabet Med. 2000;17(3):171-180.
Westwood FR, Bigley A, Randall K, Marsden AM, Scott RC. Statin-induced muscle necrosis in the rat: distribution, development, and fibre selectivity. Toxicol Pathol. 2005;33(2):246-257. [Article]
Xia Z, Lundgren B, Bergstrand A, DePierre JW, Nassberger L. Changes in the generation of reactive oxygen species and in mitochondrial membrane potential during apoptosis induced by the antidepressants imipramine, clomipramine, and citalopram and the effects on these changes by Bcl-2 and Bcl-X(L). Biochem Pharmacol. 1999;57(10):1199-1208. [Article]
Yousif W. Microscopic studies on the effect of alprazolam (Xanax) on the liver of mice. Pakistan Journal of Biological Sciences. 2002;5(11):1220-1225. [Article]
Yunus MB, Kalyan-Raman UP, Kalyan-Raman K. Primary fibromyalgia syndrome and myofascial pain syndrome: clinical features and muscle pathology. Arch Phys Med Rehabil. 1988;69(6):451-454. [Article]
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