Mighty Mitochondria… and Cardiolipin, Too

mitochondrion-cross-sectionMitochondria Are…

Suppose you were asked to name the most important part of your car?  Of course, without an engine you’re not going anywhere.  Without a transmission you’re not going anywhere, either.  So, which is it, the engine or the transmission?  Then, once you get moving, it’s nice to be able to stop.  Brakes, right?  Or perhaps you choose to steer around an obstacle.  Maybe there isn’t a most important part.  Ditto the cell, the unit of structure and function of living things, the smallest unit that can perform an essential life process.  Like your car, the cell has parts.  Considering that you have more than fifty trillion cells, the parts have to be tiny, really tiny.

Each cell is enclosed by a membrane that is made from proteins and a double layer of lipids.  The membrane is vital to the existence and function of the cell because it controls the flow of materials into and out of it, and it keeps the cell’s contents from spilling all over the place.  Not only does the cell have a membrane, but also do its components.  If we were to open and stretch out all the membranes of your body, they’d cover more than forty square miles.  But that’s nothing.  If we uncoiled all your strands of DNA and laid them end to end, they’d reach the sun and back more than once.  When the Psalmist said he was fearfully and wonderfully made, he didn’t realize how right he was.

A component of the cell that shares its architecture is the mitochondrion, sometimes referred to as the power plant of the cell because it makes most of the cell’s supply of adenosine triphosphate (ATP), used as a source of chemical energy.  Like the cell itself, the mitochondrion has an inner and an outer leaf to the membrane.  Mitochondria have other tasks besides making energy, including signaling, cell death, and control of the cell cycle. You already know that different cells have different jobs, each determined by what the nucleus says. Some cells do more work than others and require more energy.  Therefore, some have more mitochondria than others.  You would expect to find more mitochondria in a bicep than in the muscle that blinks an eye.  Each mitochondrion has an intermembrane space—found between the outer and inner membrane leaflets—that controls the movement of proteins. Small molecules have no problem crossing the outer membrane, but larger proteins need to be escorted by a specialized signaling sequence. (sorry about the alliteration)  A noted protein that is localized to the intermembrane area is called cytochrome c, the most abundant and stable cytochrome, principally involved in energy transfer.  Mitochondrial proteins vary depending on the tissue.  More than six hundred types have been identified in the human cardiac mitochondria, for example.  And, even though most of a cell’s DNA is in the nucleus, mitochondria have their own supply.

If there were no mitochondria, the higher animals could not exist.  Mitochondria perform aerobic respiration, requiring oxygen, which is the reason we breathe.  Without them we would have to rely on anaerobic respiration, without oxygen.  That process is too inefficient to support us.  Besides, the lack of mitochondria would reduce energy production by fifteen times, which is far too low to allow survival. A mitochondrion’s DNA reproduces independently of the cell in which it is found.  In humans, this DNA covers more than sixteen thousand base pairs, not very many compared to the whole organism.  Mitochondrial DNA holds thirty-seven genes, all of which are needed for normal function.  Thirteen of these supply information for making enzymes involved in oxidative phosphorylation, which is how ATP is made by using oxygen and simple sugars.  The other twenty-four genes help to make transfer RNA (tRNA) and ribosomal RNA (rRNA), which are chemically related to DNA.  These kinds of RNA are responsible for assembling amino acids into functioning proteins.

Mitochondria are passed on through maternal lineage.  Just as a car’s energy supply from gasoline is in the rear, so is a sperm’s mitochondrial energy—in the tail, which falls off after the sperm attaches to the egg.  This means that any problems, like mitochondrial diseases, necessarily come from the female.  Mitochondrial DNA (mtDNA) does not get shifted from generation to generation, while nuclear DNA does.  It is mtDNA that sends some diseases down the line.  mtDNA, though, is also subject to non-inherited mutations that cause diseases.  Fortunately, these are not passed on, but are accountable for various cancers, such as breast, colon, stomach and liver, diseases that have been attributed to reactive oxygen species.  mtDNA has limited capability to repair itself, so the inherited changes may cause problems with the body’s systems, where the mitochondria are unable to provide sufficient energy for cells to do their work.  The inherited consequences may present as muscle wasting, movement problems, diabetes, dementia, hearing loss, or a host of other maladies.

Some mitochondrial functions are performed only in specific cells.  In the liver, for example, they are able to detoxify ammonia, a job that need not be accomplished anywhere else in the body.  Other metabolic tasks of mitochondria include regulation of membrane potential, apoptosis, calcium signaling, steroid synthesis, and control of cellular metabolism.  You can see that mitochondria are vital to life, and their malfunction can change the rules.  In some mitochondrial dysfunctions there is an interaction of environmental and hereditary factors that causes disease.  Such may be the case with pesticides and the onset of Parkinson’s disease—cellular damage related to oxidative stress.  In other dysfunctions, there may be mutations of certain enzymes, such as coenzyme Q10 deficiency, or aberrations in the cardiolipin molecules that are found inside mitochondria, causative of Barth syndrome, which is often associated with cardiomyopathy.  Mitochondria-mediated oxidative stress may also play a role in Type 2 diabetes.  In cases where misconstrued fatty acid uptake by heart cells occurs, there is increased fatty acid oxidation, which upsets the electron transport chain, resulting in increased reactive oxygen species.  This deranges the mitochondria and elevates their oxygen consumption, resulting in augmentation of fatty acid oxidation.  Merely because oxygen consumption increases does not necessarily mean that more ATP will be manufactured, mostly because the mitochondria are uncoupled.  Less ATP ultimately causes energy deficit, accompanied by reduced cardiac efficiency.

Mitochondria can become involved in a vicious cycle of oxidative stress leading to mitochondrial DNA mutations, which leads to enzyme irregularities and more oxidative stress.  This may be a major factor in the aging process.

Rescue My Mitochondria, Please

The neurodegeneration of Parkinson’s disease is characterized by a loss of dopaminergic neurons and a deficit in mitochondrial respiration.  Exposure to some neurotoxins can present with both characteristics.  In a Parkinson’s model provoked by a drug that was produced to mimic the effects of morphine or meperidine (Demerol), but which interferes with oxidative phosphorylation in mitochondria instead, causing depletion of ATP and cell death, scientists at Columbia University’s Center for Neurobiology and Behavior found that the administration of ketone bodies akin to those used in the treatment of epilepsy were able to attenuate the dopaminergic neurodegeneration and motor deficits induced by the drug (Tieu, 2003).  From this and other studies it has been determined that ketones may play a therapeutic role in several forms of neurodegeneration related to mitochondrial dysfunction (Kashiwaya, 2000).

Moving across the mitochondrial membrane, phosphatidylcholine (PC) limits the phospholipid turnover in both the inner and outer leaflets that epitomizes the membrane defect identified in neurological diseases (Dolis, 1996), including Alzheimer’s, a disease in which impairment of mitochondrial function is part of the pathophysiology.  Substances that inhibit mitochondrial function also activate an enzyme called phospholipase A2 (PLA2) that degrades PC in the membrane (Farber, 2000), but reparation to mitochondria may be realized by administering PC liposomes, as evidenced by Russian studies performed in the early 1990s (Dobrynina, 1991).

Cardiolipin is an important component of the inner mitochondrial membrane, where it makes up about 20% of the lipid composition.  Its operational character is critical to the optimal function of numerous enzymes essential to mitochondrial energy metabolism.  Mitochondrial cardiolipin is distinguished from other phospholipids by the presence of linoleic acid derivatives (Schlame, 1990).  The formation of cardiolipin is dependent upon molecules donated by PC, but because it contains 18-carbon fatty alkyl chains with two unsaturated bonds, it bespeaks a linoleic acid heritage.   The need for linoleic acid, an omega-6 fat, was announced by the American Heart Association several years ago (Harris, 2009).

In the aforementioned Barth syndrome there exist cardiolipin abnormalities and resultant defects in the electron transport chain proteins and the architecture of the mitochondrion.   The electron transport chain (ETC) moves electrons from one cytochrome to another during the production of ATP, terminating at oxygen through a series of increasingly strong oxidative activities.  Those few electrons that fail to make it through the entire process leak and form superoxide, a substantially reactive molecule that contributes greatly to oxidative stress and aging.

Since the heart is rich in cardiolipin, it is more than appropriate to maintain its stores.  And linoleic acid is just the thing to do that.  Dutch researchers found that linoleic acid, readily available from sunflower, hemp, grape seed and other oils, restores and even increases cardiolipin levels (Valianpour, 2003).   Chronic over-consumption of omega-3 fats, such as those from fish oils, creates a deficit of omega-6 fats that interferes with the rate of oxygen use by mitochondria, with consequent decrease of cardiolipin (Yamaoka, 1999) (Hauff, 2006).

Coronary heart disease is a major health issue that may be addressed by supporting cardiolipin integrity, but other conditions likewise respond to such support.  Besides maintaining membrane potential and architecture, cardiolipin provides sustainment to several proteins involved in mitochondrial energy production.  If cardiolipin activity is interrupted or deranged, either through oxidative stress or alterations in acyl chain composition, we may anticipate contending with other pathological conditions, such as ischemia and hypothyroidism, and accelerated aging (Chicco, 2007).  These concerns can be allayed by attending to the status of the tafazzin protein that partly underlies cardiolipin metabolism (Xu, 2006).  Superheroes have long been associated with a sidekick, occasionally with role reversal for the nonce.  Working with linoleic acid to bolster cardiolipin is phosphatidylcholine (PC), which assists protein reconstitution by its ability to transfer acyl groups (Xu, 2003) (Schlame, 1991) and enhance protein signaling.  PC exists in every cell of the body, occupying the outer leaflet of the membrane.  Throughout the course of life, PC levels become depleted and may drop as low as 10% of the membrane in elderly people.  Being so, supplementation is warranted, not only to maintain cardiolipin levels and mitochondrial stability body-wide, but also to retard senescence and to improve brain function and memory capacity.


Ardail D, Privat JP, Egret-Charlier M, Levrat C, Lerme F, Louisot P.
Mitochondrial contact sites. Lipid composition and dynamics.
J Biol Chem. 1990 Nov 5;265(31):18797-802.

Chicco AJ, Sparagna GC.
Role of cardiolipin alterations in mitochondrial dysfunction and disease.
Am J Physiol Cell Physiol. 2007 Jan;292(1):C33-44. Epub 2006 Aug 9.

Chung SY, Moriyama T, Uezu E, Uezu K, Hirata R, Yohena N, Masuda Y, Kokubu T, Yamamoto S.
Administration of phosphatidylcholine increases brain acetylcholine concentration and improves memory in mice with dementia.
J Nutr. 1995 Jun;125(6):1484-9.

Dobrynina OV, Migushina VL, Shatinina SZ, Kapitanov AB.
 [Reparation of hepatocyte mitochondrial membranes using phosphatidylcholine liposomes].
Biull Eksp Biol Med. 1991 Aug;112(8):135-6.

Danièle Dolis, Anton I. P. M. de Kroon and Ben de Kruijff
Transmembrane Movement of Phosphatidylcholine in Mitochondrial Outer Membrane Vesicles
The Journal of Biological Chemistry. May 17, 1996; 271: 11879-11883.

John R. Dyer, Carol E. Greenwood
The level of linoleic acid in neural cardiolipin is linearly correlated to the amount of essential fatty acids in the diet of the weanling rat
The Journal of Nutritional Biochemistry. Vol 2, Iss 9, Sept 1991, Pages 477–483

Acceleration of phosphatidylcholine synthesis and breakdown by inhibitors of mitochondrial function in neuronal cells: a model of the membrane defect of Alzheimer’s disease
The FASEB Journal. November 1, 2000; vol. 14 no. 14: 2198-2206

Haines, Thomas H.
A New Look at Cardiolipin (Editorial)
Biochimica et Biophysica Acta 1788 (2009): 1997-2001

Hauff KD, Hatch GM.
Cardiolipin metabolism and Barth Syndrome.
Prog Lipid Res. 2006 Mar;45(2):91-101. Epub 2006 Jan 18.

Houtkooper RH, Vaz FM.
Cardiolipin, the heart of mitochondrial metabolism.
Cell Mol Life Sci. 2008 Aug;65(16):2493-506.

Hovius R, Thijssen J, van der Linden P, Nicolay K, de Kruijff B.
Phospholipid asymmetry of the outer membrane of rat liver mitochondria. Evidence for the presence of cardiolipin on the outside of the outer membrane.
FEBS Lett. 1993 Sep 6;330(1):71-6.

Hung MC, Shibasaki K, Yoshida R, Sato M, Imaizumi K.
Learning behaviour and cerebral protein kinase C, antioxidant status, lipid composition in senescence-accelerated mouse: influence of a phosphatidylcholine-vitamin B12 diet.
Br J Nutr. 2001 Aug;86(2):163-71.

Kulik W, van Lenthe H, Stet FS, Houtkooper RH, Kemp H, Stone JE, Steward CG, Wanders RJ, Vaz FM.
Bloodspot assay using HPLC-tandem mass spectrometry for detection of Barth syndrome.
Clin Chem. 2008 Feb;54(2):371-8. Epub 2007 Dec 10.

Ho-Joo Lee, Jana Mayette, Stanley I Rapoport and Richard P Bazinet
Selective remodeling of cardiolipin fatty acids in the aged rat heart
Lipids in Health and Disease. 23 January 2006; 5:2

F. B. Jungalwala, R. M. C. Dawson
The Origin of Mitochondrial Phosphatidylcholine within the Liver Cell
European Journal of Biochemistry. Volume 12, Issue 2, pages 399–402, February 1970

Kashiwaya Y, Takeshima T, Mori N, Nakashima K, Clarke K, Veech RL.
D-beta-hydroxybutyrate protects neurons in models of Alzheimer’s and Parkinson’s disease.
Proc Natl Acad Sci U S A. 2000 May 9;97(10):5440-4.

Nicolay K, Hovius R, Bron R, Wirtz K, de Kruijff B.
The phosphatidylcholine-transfer protein catalyzed import of phosphatidylcholine into isolated rat liver mitochondria.
Biochim Biophys Acta. 1990 Jun 11;1025(1):49-59.

Paradies G, Petrosillo G, Paradies V, Ruggiero FM.
Role of cardiolipin peroxidation and Ca2+ in mitochondrial dysfunction and disease.
Cell Calcium. 2009 Jun;45(6):643-50. Epub 2009 Apr 15.

José L. Quiles, Estrella Martínez, Susana Ibáñez, Julio J. Ochoa, Yolanda Martín, Magdalena López-Frías, Jesús R. Huertas and José Mataix
Ageing-Related Tissue-Specific Alterations in Mitochondrial Composition and Function Are Modulated by Dietary Fat Type in the Rat
Journal of Bioenergetics and Biomembranes . Volume 34, Number 6 (2002), 517-524

Schlame M, Rüstow B.
Lysocardiolipin formation and reacylation in isolated rat liver mitochondria.
Biochem J. 1990 Dec 15;272(3):589-95

Schlame M, Beyer K, Hayer-Hartl M, Klingenberg M.
Molecular species of cardiolipin in relation to other mitochondrial phospholipids. Is there an acyl specificity of the interaction between cardiolipin and the ADP/ATP carrier?
Eur J Biochem. 1991 Jul 15;199(2):459-66.

Sparagna GC, Lesnefsky EJ.
Cardiolipin remodeling in the heart.
J Cardiovasc Pharmacol. 2009 Apr;53(4):290-301

Nicole Testerink , Michiel H. M. van der Sanden , Martin Houweling , J. Bernd Helms, and
Arie B. Vaandrager
Depletion of phosphatidylcholine affects endoplasmic reticulum morphology and protein traffi c at the Golgi complex
J. Lipid Res. 2009. 50: 2182–2192.

Kim Tieu, Celine Perier, Casper Caspersen, Peter Teismann, Du-Chu Wu, Shi-Du Yan, Ali Naini, Miquel Vil, Vernice Jackson-Lewis, Ravichandran Ramasamy and Serge Przedborski
D-β-Hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease

J Clin Invest. Sept 15, 2003; 112(6):892–901.

Trivedi A, Fantin DJ, Tustanoff ER.
Role of phospholipid fatty acids on the kinetics of high and low affinity sites of cytochrome c oxidase.
Biochem Cell Biol. 1986 Nov;64(11):1195-210.

Valianpour F, Wanders RJ, Overmars H, Vaz FM, Barth PG, van Gennip AH.
Linoleic acid supplementation of Barth syndrome fibroblasts restores cardiolipin levels: implications for treatment.
J Lipid Res. 2003 Mar;44(3):560-6. Epub 2002 Dec 16.

Vance JE.
Phospholipid synthesis in a membrane fraction associated with mitochondria.
J Biol Chem. 1990 May 5;265(13):7248-56.

Wright MM, Howe AG, Zaremberg V
Cell membranes and apoptosis: role of cardiolipin, phosphatidylcholine, and anticancer lipid analogues.
Biochem Cell Biol. 2004 Feb;82(1):18-26.

Xu Y, Kelley RI, Blanck TJ, Schlame M.
Remodeling of cardiolipin by phospholipid transacylation.
J Biol Chem. 2003 Dec 19;278(51):51380-5. Epub 2003 Oct 9.

Xu Y, Malhotra A, Ren M, Schlame M.
The enzymatic function of tafazzin.
J Biol Chem. 2006 Dec 22;281(51):39217-24. Epub 2006 Nov 2.

Yamaoka S, Urade R, Kito M.
Cardiolipin molecular species in rat heart mitochondria are sensitive to essential fatty acid-deficient dietary lipids.
J Nutr. 1990 May;120(5):415-21.

Zeisel SH.
Dietary choline deficiency causes DNA strand breaks and alters epigenetic marks on DNA and histones.
Mutat Res. 2011 Oct 20. [Epub ahead of print]

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Statins And Diabetes: Why Didn’t They Tell Me?

heart-measureCan you tell when you’ve eaten too much ice cream? Does the eructation shake your table lamps after too many sodas? Sometimes we learn what enough is by having too much. Too bad it isn’t the same with drugs. A hundred-pound lady doesn’t need as many aspirins to get rid of a headache as a two-hundred-pound guy. And for those who take a statin because the doctor said so, why does everybody start with the same doses? With Zocor, everybody starts with 40 mg. Doesn’t anybody think that maybe 5 mg could do the trick? Hey, if one quart of white semi-gloss will cover the bathroom walls adequately, why buy a gallon unless you have a use for it elsewhere? You gonna paint those walls until the gallon is empty?

Over the last few years, the cholesterol model of cardiovascular disease is steadily being replaced by the inflammation model of CVD, putting statin drugs on the back burner because cholesterol, it is realized, has never caused a heart attack. In fact, half the scary cardiac events happen to people who have what are deemed ideal cholesterol numbers (Sachdeva, 2009). Yes, it is true that statins interfere with cholesterol manufacture by the body, not only in the liver, but also in the brain, where cholesterol is vital to the machinery of thought and function. Low cholesterol can lead to serious health issues when that machinery is interrupted.  Low cholesterol levels are associated with high total mortality, even in patients with coronary heart disease (Behar, 1997) (Krumholz, 1994).

Differences between young and old, and between male and female, are recognized in the cholesterol arena, too. The impact of total cholesterol as a risk factor for heart disease decreases with age (Waverling-Rijnsburger, 1997) and for women, whose moderately elevated cholesterol may actually be beneficial (Petursson, 2012). The age cutoff for both genders is fifty (Anderson, 1987). If this information regarding age was known ten years ago, why are TV ads so adamant about getting cholesterol values below a hundred?

The personal experiences of at least one NASA astronaut have attested to the nasty effects of statins, including transient global amnesia, impaired cognition, personality changes, myopathy, neuropathy and neuromuscular degeneration. The root of all these maladies is the inhibition of Co-enzyme Q 10, a physiologically necessary substance that is blocked by Lipitor, Zocor, Crestor and the rest of the gang. Without CoQ10, mitochondria don’t work their magic at cell metabolism, where they get to burn food for energy, oxidize fatty acids, and use the electrons supplied by CoQ10 for a host of other essential activities. The pathway that makes cholesterol also makes CoQ10 in the body. Stopping one stops the other. This is so well known that statin prescriptions in Canada—for Mevachor®, Pravachol® and Lipitor®— contain a warning about CoQ 10 depletion. Merck even filed two patents for a statin-CoQ 10 combination, no. 4,933,165 and no. 4,929,437, which expired in May and June of 2007 (Koon, 2013). And you thought the drug companies had your best interest at heart, eh? The cholesterol issue is a complicated one and now, to add to the quagmire of hits and misses, is the notice that statins are implicated in the risk of developing diabetes. The endearing stars in this drama are atorvastatin (Lipitor), rosuvastatin (Crestor) and simvastatin (Zocor), brought to you by Pfizer, AstraZeneca and Merck. Atorvastatin was found to be the most influential of the three at elevating blood glucose, followed by rosuvastatin and simvastatin, in a recent Canadian study carried out at the Toronto General Hospital (Carter, 2013). From this work it may be drawn that pravastatin (Pravachol) is the safest drug related to diabetes onset. Regardless of drug of choice, or rather the physician’s choice, dose intensity also seems to make a difference in diabetes risk. Intense doses, especially at 80 mg of Zocor, increase the odds of all statin-induced adverse events (Silva, 2007), extending diabetes risk to almost ten percent of the medicated population (Preiss, 2011).

For all the hoopla that accompanied statins’ debut forty years ago into the pharmaceutical world, recounting their anti-cholesterol beneficence, it’s been discovered that their real claim to fame is being anti-inflammatory. That characteristic, it’s claimed, is more important to their raison d’etre than disrupting the cholesterol (and CoQ 10) pathway (Antonopoulos, 2012) (Mora, 2006) (Weitz-Schmidt, 2002). If so, then anti-inflammatory substances that have zero side effects might be considered. In this list will be simple things with complex mechanisms, like ginger, curcumin (from turmeric), capsaicin (from hot peppers), garlic, fish oil, bromelain (from pineapples), flaxseed oil, and zinc, among others. Aside from an allergic reaction which you already would know about, the only side effects of these ingredients are possibly foul breath (that would be the anti-vampire action) and stomach upset from too much of a good thing.

The mention of CoQ10 needs at least a little thought. Natural stores of this enzyme diminish with age. The fact that it donates electrons to multiple body processes bespeaks its importance to full function. It’s comparable to using the correct gauge extension cord with an electric weed trimmer. If the cord can’t carry the voltage, the trimmer will not work to its potential. Adding CoQ 10 to the daily regimen is a prudent decision whether taking a statin or not. Why?  It helps to control blood glucose (Kolahdouz, 2013) (Mezawa, 2012).


Anderson KM, Castelli WP, Levy D.
Cholesterol and mortality. 30 years of follow-up from the Framingham study.
JAMA. 1987 Apr 24;257(16):2176-80.

Antonopoulos AS, Margaritis M, Lee R, Channon K, Antoniades C.
Statins as anti-inflammatory agents in atherogenesis: molecular mechanisms and lessons from the recent clinical trials.
Curr Pharm Des. 2012;18(11):1519-30.

Behar S, Graff E, Reicher-Reiss H, Boyko V, Benderly M, Shotan A, Brunner D.
Low total cholesterol is associated with high total mortality in patients with coronary heart disease. The Bezafibrate Infarction Prevention (BIP) Study Group.
Eur Heart J. 1997 Jan;18(1):52-9.

Carter AA, Gomes T, Camacho X, Juurlink DN, Shah BR, Mamdani MM.
Risk of incident diabetes among patients treated with statins: population based study.
BMJ. 2013 May 23;346:f2610. doi: 10.1136/bmj.f2610.

Richard Deichmann, MD, Carl Lavie, MD, and Samuel Andrews, MD
Coenzyme Q10 and Statin-Induced Mitochondrial Dysfunction
Ochsner J. 2010 Spring; 10(1): 16–21.

Forette B, Tortrat D, Wolmark Y.
Cholesterol as risk factor for mortality in elderly women.
Lancet. 1989 Apr 22;1(8643):868-70.

Halfdan Petursson MD, Johann A. Sigurdsson MD Dr med, Calle Bengtsson MD Dr med,
Tom I. L. Nilsen Dr Philos and Linn Getz MD PhD
Is the use of cholesterol in mortality risk algorithms in clinical guidelines valid? Ten years prospective data from the Norwegian HUNT 2 study
Journal of Evaluation in Clinical Practice 18 (2012) 159–168

Risto Huupponen, Jorma Viikari
Statins and the risk of developing diabetes
BMJ. 23 MAY 2013;346:f3156

Kolahdouz Mohammadi R, Hosseinzadeh-Attar MJ, Eshraghian MR, Nakhjavani M, Khorami E, Esteghamati A.
The effect of coenzyme Q10 supplementation on metabolic status of type 2 diabetic patients.
Minerva Gastroenterol Dietol. 2013 Jun;59(2):231-6.

Koon, Robin
CoQ 10 Supplementation with Statins
Natural Products Insider. Feb 26, 2013

Kozarevic D, McGee D, Vojvodic N, Gordon T, Racic Z, Zukel W, Dawber T.
Serum cholesterol and mortality: the Yugoslavia Cardiovascular Disease Study.
Am J Epidemiol. 1981 Jul;114(1):21-8.

Krumholz HM, Seeman TE, Merrill SS, Mendes de Leon CF, Vaccarino V, Silverman DI, Tsukahara R, Ostfeld AM, Berkman LF.
Lack of association between cholesterol and coronary heart disease mortality and morbidity and all-cause mortality in persons older than 70 years.
JAMA. 1994 Nov 2;272(17):1335-40.

Mezawa M, Takemoto M, Onishi S, Ishibashi R, Ishikawa T, Yamaga M, Fujimoto M, Okabe E, He P, Kobayashi K, Yokote K.
The reduced form of coenzyme Q10 improves glycemic control in patients with type 2 diabetes: an open label pilot study.
Biofactors. 2012 Nov-Dec;38(6):416-21.

Mora S, Ridker PM.
Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER)–can C-reactive protein be used to target statin therapy in primary prevention?
Am J Cardiol. 2006 Jan 16;97(2A):33A-41A.

Steven E. Nissen, M.D., E. Murat Tuzcu, M.D., Paul Schoenhagen, M.D., Tim Crowe, B.S., et al
Statin Therapy, LDL Cholesterol, C-Reactive Protein, and Coronary Artery Disease
N Engl J Med. January 6, 2005; 352:29-38

Preiss D, Seshasai SR, Welsh P, Murphy SA, Ho JE, Waters DD, DeMicco DA, Barter P, et al
Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis.
JAMA. 2011 Jun 22;305(24):2556-64.

Paul M Ridker, M.D., Christopher P. Cannon, M.D., David Morrow, M.D., Nader Rifai, Ph.D, et al
C-Reactive Protein Levels and Outcomes after Statin Therapy
N Engl J Med. Jan 6, 2005; 352:20-28

Rudman D, Mattson DE, Nagraj HS, Caindec N, Rudman IW, Jackson DL.
Antecedents of death in the men of a Veterans Administration nursing home.
J Am Geriatr Soc. 1987 Jun;35(6):496-502.

Sachdeva A, Cannon CP, Deedwania PC, Labresh KA, Smith SC Jr, Dai D, Hernandez A, Fonarow GC.
Lipid levels in patients hospitalized with coronary artery disease: an analysis of 136,905 hospitalizations in Get With The Guidelines.
Am Heart J. 2009 Jan;157(1):111-117.e2.

Sattar N, Preiss D, Murray HM, Welsh P, Buckley BM, de Craen AJ, Seshasai SR et al
Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials.
Lancet. 2010 Feb 27;375(9716):735-42.

Sattar N, Taskinen MR.
Statins are diabetogenic–myth or reality?
Atheroscler Suppl. 2012 Aug;13(1):1-10.

Shah RV, Goldfine AB.
Statins and risk of new-onset diabetes mellitus.
Circulation. 2012 Oct 30;126(18):e282-4. doi: 10.1161/CIRCULATIONAHA.112.122135.

Silva M, Matthews ML, Jarvis C, Nolan NM, Belliveau P, Malloy M, Gandhi P.
Meta-analysis of drug-induced adverse events associated with intensive-dose statin therapy.
Clin Ther. 2007 Feb;29(2):253-60.

Simsek S, Schalkwijk CG, Wolffenbuttel BH.
Effects of rosuvastatin and atorvastatin on glycaemic control in Type 2 diabetes—the CORALL study.
Diabet Med. 2012 May;29(5):628-31.

Sukhija R, Prayaga S, Marashdeh M, Bursac Z, Kakar P, Bansal D, Sachdeva R, Kesan SH, Mehta JL.
Effect of statins on fasting plasma glucose in diabetic and nondiabetic patients.
J Investig Med. 2009 Mar;57(3):495-9.

Gabriele Weitz-Schmidt
Statins as anti-inflammatory agents
Trends in Pharmacological Sciences, 1 Oct 2002; Vol 23, Iss 10: 482-487,

Weverling-Rijnsburger AW, Blauw GJ, Lagaay AM, Knook DL, Meinders AE, Westendorp RG.
Total cholesterol and risk of mortality in the oldest old.
Lancet. 1997 Oct 18;350(9085):1119-23.

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

You Gotta Have Heart

healthy-heart-smIf you attended high school most days, you might have learned that atoms are made of protons, electrons and neutrons, having charges that are positive, negative or neutral, in that order. If the charges get out of balance, the atom is either negatively or positively charged. The switch between one type of charge and the other allows electrons to move from one atom to the next. It’s this flow of electrons that we call electricity and is the energy that controls everything about the body. This is the source of the signals that allow us to grab the doorknob or turn the ignition switch, or even to think about what to have for dinner. Instead of flowing along a continuous wire, as happens in the house, these signals jump from one cell to the next—and they do it fast.

The potassium inside a cell and the sodium outside have a lot to do with our electrical capacity. At rest, a cell has more negatively charged potassium inside than positively charged sodium. As the negatives and positives are attracted to each other, they cross the barrier between them—the cell membrane—through a gate, and create electricity in order to initiate a movement, thought or biological function. This impulse triggers the gate on the neighboring cell, then on the next one, the next one. This is how the sinoatrial (SA) node of the heart (its pacemaker) tells it to contract and how your eye tells your brain what you just saw. One of the interesting, though admittedly still painful, facets of life happens when you hit a finger with a hammer. The pain message travels through a sensory nerve to the brain in a fraction of a second, and then the brain associates the assault with discomfort before it tells you to move your finger away from the site of injury. Even though you realize what just happened, it takes a brief moment before the throbbing starts. All this is based on electrical activity. This might happen at 250 miles an hour, much slower than the 180,000 miles per second speed of electricity along a wire.

Our cells—more than 60 trillion—work hard every day to multiply themselves, digest nutrients, remove wastes and make energy from something called ATP. Inside each cell are little power plants called mitochondria, the number depending on the job of the cell. An eyelid will not have as many mitochondria as a bicep. ATP is made inside a mitochondrion, where Co-Enzyme Q 10 directs the function of the electron transport chain by collecting and transferring electrons along the chain. In its reduced form, where it gains an electron, CoQ10 acts as an antioxidant, effectively recycling vitamin E and possibly having an anti-atherogenic effect (Turunen, 2002).

Although often ignored by conventional medicine, it is important to note that CoQ10 shares a metabolic pathway with cholesterol and that stores diminish with age, whether by decreased synthesis or by increased requirements, or even by the elevated lipid peroxidation that accompanies aging. If we regulate cholesterol with a statin drug, we also regulate the manufacture of CoQ10; hence the need for supplementation to maintain the electrical grid. In the first double-blinded study ever that examined CoQ10 in cardiac interventions, it was discovered that enzyme supplementation in heart failure patients reduced hospital admissions and death by improving cardiac function through enhancement of the respiratory chain at doses of 100 mg three times a day (Mortensen, 2013).

Allopathic medicine rarely looks into the micronutrient deficiencies that either foretell or cause impaired function of the heart’s electrical circuits. Its therapeutic options are confined to treating symptoms. Cellular—or membrane—medicine recognizes the important components of the energy formation cycle. Patients who suffered congestive heart myopathies had shown remarkable responses to CoQ10 therapy when assiduously administered in a faithful regimen (Langsjoen, 1985). If such was the case decades ago, why has there been so little publicity?  New York Heart Association (NYHA) class IV heart failure defines almost complete cardiac insufficiency. Patients who were expected to die within two years under conventional therapy did not because it was recognized that CoQ10 is indispensable in mitochondrial bioenergetics (Langsjoen, 1988).

Absorption of supplemental CoQ10 on an empty stomach is poor, with more than sixty percent excreted in feces. It improves when taken with foods having a considerable lipid profile. In the presence of bile detergents lipids are broken into very small particles, thus increasing their surface area and subsequent susceptibility to the lipase enzymes that digest fats. Now, especially in the company of phosphatidylcholine, these particles are absorbed by intestinal mucosa and passed into the bloodstream. It takes about three weeks of faithful supplementation to attain maximum serum concentrations.

As with most integrative modalities, ongoing studies are welcome, but suffer lack of funding because they interfere with the profits garnered by pharmaceuticals. The number of eligible heart transplant patients surpasses the available number of donors. On the bright side, CoQ10 has a beneficial effect on these persons by virtue of providing a pharmacological bridge that offers an improvement in functional status and quality of life (Berman, 2004), including ejection fraction (Fotino, 2013).

For a long time, medicine has sought a means to return flexibility to the cardiovascular system that has succumbed to the ravages of time and insult, such as smoking, excessive sugar intake, and diets that promote advanced glycation endproducts. Patients suffering NYHA class III CHF who received supplemental CoQ10 at 100 mg tid, experienced improvement in left ventricular contractility and ejection fraction after only four weeks (Belardinelli, 2005), indicating the plausibility of such a protocol.

Studies may be clouded by anticipated outcomes, the bias of which may be directedby expectations of funding bodies. In too may instances, Eurasian investigatorsfind more successes than North Americans. The bottom line appears that low CoQ10concentrations are predictive of adverse CHF events, leaving one to understandthe rationale for intervention with the supplement. Endogenous manufacture ofCoQ10 requires sufficient vitamin B6 for biosynthesis. Most of us consume lessthan 10 mg of CoQ10 a day from dietary sources, leaving plenty of room for supplementation,even if we lack a pathology. The last thing we need is a power failure.


Abe, K., Matsuo, Y., Kadekawa, J., Inoue, S., and Yanagihara, T.
Effect of coenzyme Q10 in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS): evaluation by noninvasive tissue oximetry.
J Neurol.Sci. 1-1-1999;162(1):65-68.

Baggio, E., Gandini, R., Plancher, A. C., Passeri, M., and Carmosino, G.
Italian multicenter study on the safety and efficacy of coenzyme Q10 as adjunctive therapy in heart failure (interim analysis). The CoQ10 Drug Surveillance Investigators.
Clin Investig. 1993;71(8 Suppl):S145-S149.

Bargossi, A. M., Grossi, G., Fiorella, P. L., Gaddi, A., Di Giulio, R., and Battino, M.
Exogenous CoQ10 supplementation prevents plasma ubiquinone reduction induced by HMG-CoA reductase inhibitors.
Mol.Aspects Med 1994;15 Suppl:s187-s193.

Belaia, O. L., Kalmykova, V. I., Ivanova, L. A., and Kochergina, L. G.
[Experience in coenzyme Q10 application in complex therapy of coronary heart disease with dyslipidemia].
Klin Med (Mosk) 2006;84(5):59-62.

Belardinelli R, Muçaj A, Lacalaprice F, Solenghi M, Principi F, Tiano L, Littarru GP.
Coenzyme Q10 improves contractility of dysfunctional myocardium in chronic heart failure.
Biofactors. 2005;25(1-4):137-45.

Belardinelli R, Muçaj A, Lacalaprice F, Solenghi M, Seddaiu G, Principi F, Tiano L, Littarru GP.
Coenzyme Q10 and exercise training in chronic heart failure.
Eur Heart J. 2006 Nov;27(22):2675-81.

Berman M, Erman A, Ben-Gal T, Dvir D, Georghiou GP, Stamler A, Vered Y, Vidne BA, Aravot D.
Coenzyme Q10 in patients with end-stage heart failure awaiting cardiac transplantation: a randomized, placebo-controlled study.
Clin Cardiol. 2004 May;27(5):295-9.

Chen, R. S., Huang, C. C., and Chu, N. S.
Coenzyme Q10 treatment in mitochondrial encephalomyopathies. Short-term double-blind, crossover study.
Eur.Neurol. 1997;37(4):212-218.

Choe, J. Y., Combs, A. B., and Folkers, K.
Prevention by coenzyme Q10 of the electrocardiographic changes induced by adriamycin in rats.
Res Commun Chem Pathol Pharmacol 1979;23(1):199-202.

Crane FL.
Biochemical functions of coenzyme Q10.
J Am Coll Nutr. 2001 Dec;20(6):591-8.

Folkers K, Vadhanavikit S, Mortensen SA.
Biochemical rationale and myocardial tissue data on the effective therapy of cardiomyopathy with coenzyme Q10.
Proc Natl Acad Sci U S A. 1985 Feb;82(3):901-4.

Folkers, K., Morita, M., and McRee, J., Jr.
The activities of coenzyme Q10 and vitamin B6 for immune responses.
Biochem Biophys.Res Commun. 5-28-1993;193(1):88-92.

Folkers, K.
Heart failure is a dominant deficiency of coenzyme Q10 and challenges for future clinical research on CoQ10.
Clin Investig 1993;71(8 Suppl):S51-S54

Fotino AD, Thompson-Paul AM, Bazzano LA.
Effect of coenzyme Q₁₀ supplementation on heart failure: a meta-analysis.
Am J Clin Nutr. 2013 Feb;97(2):268-75.

Gottlieb, S. S., Khatta, M., and Fisher, M. L.
Coenzyme Q10 and Congestive Heart Failure.
Ann.Intern.Med 11-7-2000;133(9):745-746.

Hofman-Bang, C., Rehnqvist, N., Swedberg, K., Wiklund, I., and Astrom, H.
Coenzyme Q10 as an adjunctive in the treatment of chronic congestive heart failure. The Q10 Study Group.
J Card Fail. 1995;1(2):101-107.

Keogh A, Fenton S, Leslie C, Aboyoun C, Macdonald P, Zhao YC, Bailey M, Rosenfeldt F.
Randomised double-blind, placebo-controlled trial of coenzyme Q, therapy in class II and III systolic heart failure.
Heart Lung Circ. 2003;12(3):135-41.

Laaksonen, R., Ojala, J. P., Tikkanen, M. J., and Himberg, J. J.
Serum ubiquinone concentrations after short- and long-term treatment with HMG-CoA reductase inhibitors.
Eur.J Clin Pharmacol. 1994;46(4):313-317.

Langsjoen PH, Vadhanavikit S, Folkers K.
Response of patients in classes III and IV of cardiomyopathy to therapy in a blind and crossover trial with coenzyme Q10.
Proc Natl Acad Sci U S A. 1985 Jun;82(12):4240-4.

Langsjoen PH, Folkers K, Lyson K, Muratsu K, Lyson T, Langsjoen P.
Effective and safe therapy with coenzyme Q10 for cardiomyopathy.
Klin Wochenschr. 1988 Jul 1;66(13):583-90.

Langsjoen PH, Langsjoen AM.
Supplemental ubiquinol in patients with advanced congestive heart failure.
Biofactors. 2008;32(1-4):119-28.

Molyneux SL, Florkowski CM, George PM, Pilbrow AP, Frampton CM, Lever M, Richards AM.
Coenzyme Q10: an independent predictor of mortality in chronic heart failure.
J Am Coll Cardiol. 2008 Oct 28;52(18):1435-41

Mortensen SA.
Overview on coenzyme Q10 as adjunctive therapy in chronic heart failure. Rationale, design and end-points of “Q-symbio”–a multinational trial.
Biofactors. 2003;18(1-4):79-89.

SA Mortensen, A Kumar, P Dolliner, KJ Filipiak, D Pella, U Alehagen, G Steurer, GP Littarru, F Rosenfeldt
The effect of coenzyme Q10 on morbidity and mortality in chronic heart failure. Results from the Q-SYMBIO study
European Journal of Heart Failure ( 2013 ) 15 ( S1 ), S20

Sander S, Coleman CI, Patel AA, Kluger J, White CM.
The impact of coenzyme Q10 on systolic function in patients with chronic heart failure.
J Card Fail. 2006 Aug;12(6):464-72.

Sinatra ST.
Refractory congestive heart failure successfully managed with high dose coenzyme Q10 administration.
Mol Aspects Med. 1997;18 Suppl:S299-305.

Turunen M, Wehlin L, Sjöberg M, Lundahl J, Dallner G, Brismar K, Sindelar PJ.
beta2-Integrin and lipid modifications indicate a non-antioxidant mechanism for the anti-atherogenic effect of dietary coenzyme Q10.
Biochem Biophys Res Commun. 2002 Aug 16;296(2):255-60.

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.