alleviating congestive heart failure with coenzyme q10

BY PETER H. LANCSjOEN, MD, FACC

Alleviating CongestiveHeart Failure with

Coenzyme QIOOne of the most frequent causes of hospital admissions in older

adults is the devastating condition known as congestive heart failure.

Characterized by disabling symptoms of difficulty breathing, fatigue,

and swelling ofthe extremities, congestive heart failure also increases

the risk of early demise.

Fortunately, scientists have discovered that the mitochondrial

energizer coenzyme QIO (CoQIO) can offer powerful assistance to

those challenged with congestive heart failure, improving the heart's

pumping ability and even reducing the need for medications.

Since CoQIO levels are depleted by aging and statin medications and

tend to be low in those with congestive heart failure, achieving optimal

blood levels of CoQIO may be an important strategy for safeguarding

cardiac health. > >

FEBRUARY 2008 | LIFE EXTENSION | 49

ALLEVIATING CONGESTIVE HEART FAILURE WITH COQIO

WhatisCoQlO?

It has been 50 years since Fred Crane discoveredCoQIO in 1957.' Since that time, scientists havediscovered what this extraordinai^ molecule is andwhat it does in settings of both health and disease. Itis important to clarify that a coenzyme should not beconfused with an enzyme (a protein that acceleratesa biochemical reaction). A coenzyme is a simplemolecule (many vitamins are coenzymes) that isessential tor the nonnal function of specific enzymesystems in our cells. Coenzyme QIO is the cofactoror coenzyme for three large enzyme systems thatare essential for 90% of cellular energy production.Because the heart muscle uses more energy than anyother tissue and normally has the highest concentra-tion of CoQ 10, it is very sensitive to CoQ 10 deficiency.

Coenzyme QIO is well established to be a clinicallyrelevant first-line antioxidant in our defense systemagainst excess oxidative stress. It is the only fat-soluble antioxidant that is synthesized by our body andis capable of regeneration back to its reduced or anti-oxidant form through normal cellular enzyme systems.Its location in the lipid mitochondrial membranesis particularly important, as mitochondria are themajor site of free-radical production, and CoQIO is anexcellent free-radical scavenger.

Coenzyme QIO and Congestive Heart Failure

In the late 1960s and early 1970s, it became clearthat patients suffering from congestive heart failm-ehad measurable deficiency of CoQIO in both bloodand heart muscle, and that the degree of deficiencycon elated with the severity of heart failure. Much of thiswork was performed as a collaborative effort betweenProfessor Karl Folkers, PhD, Gian Paolo Littarru, MD,and Denton Cooley, MD.- In 1980, my father, cardio-logist Per H. Langsjoen, MD, met with Karl Folkere, andtogether they performed the first human trial of CoQIOin the treatment of congestive heart failure in the UnitedStates.^ I joined my father as a cardiology fellow in 1983and after this favorable controlled study was publishedin 1985, we went on to evaluate the long-teiTn efficacyof CoQIO therapy in 126 patients with congestive heartfailure.''

Congestive heart failure is a condition in which thereis weakening of heart muscle function so that fluid orcongestion backs up and causes swelling or edema inthe liver, lungs, the lining of the intestine, and the lowerlegs and feet. It was our initial concern that CoQIO mayhave been acting as a stimulant that could bring aboutshort-term improvement in heart muscle function but

actually increase mortality over time. This is similar toflogging an e.xhaustcd horse, making him ain faster fora few hundred yatds only to promptly drop dead. Byfollowing these 126 heart failure patients for six years,it became clear that the improvement in heart functionwas sustained and that overall mortality was one thii-d ofexpected.-'It was at this time that we realized CoQIO rep-resented a major advance in the treatment of a diseasethat previously could be only palliated and never cured.

In the course of this six-year study, the 126 patientswere followed veiy closely with measurement of bloodCoQIO levels and heart function every three months/We unexpectedly came across the detrimental effectof the cholesterol-lowering drugs known as HMG-CoAreductase inhibitors, or more simply as statins. The firststatin drug, lovastatin (Mevacor*) came on the market in1987, and five of our heart failure patients were startedon this dmg by their primary care physicians. All five ofthese stabilized patients had a significant decline in theirblood CoQ 10 levels and a decline in their heart functionand clinical status. Their heart failure worsened to such adegree that two patients became critically ill and one wenton to require a heart transplant. This clinical deteriorationin our patients was particularly frightening at the timebecause we had no idea of the dramatic CoQ 10-depletingeffects of the newly released statin drugs. One patient inparticular showed a simultaneous drop in plasmaCoQIO level and ejection fraction when started onstatin therapy, wilh improvement after the statin wasdiscontinued (see figure 1). My father first presented

FICUREl. STATIN THERAPY, PLASMA COQIO,AND CONGESTIVE HEART FAILURE

70-Year-Old Female with Congestive Heart Failure

20%-

10%-

9/94 3/95 9/95 3/96 9/96 3/97 9/97 1/98

Month and Year

This demonstrates the simultaneous drop inplasma CoQIO level and ejection fraction in a

70-year-old female patient started on statin therapy.Note that ejection fraction and CoQIO level increased

after statin therapy was discontinued.

50 I LIFE EXTENSION I FEBRUARY 2008

FIGURE 2. BIOSYNTHETIC PATHWAY LEADINGTO CHOLESTEROL, COENZYME QIO, AND DOLICHOL

Acetyl CoA

HMG CoAHMG-CoAReductase

Blocked byStatin Drugs

Mevalonate

•|—Farnesyl pyrophosphate

ISquaiene

1Dolichol Cholesterol

HXO

H>CO

All statin drugs (HMG-CoA reductase inhibitors)block the biosynthesis of both cholesterol and C0QIO,which explains their common side efTects of fatigue,

muscle pain, and a worsening of heart failure.

these data in Rome, Italy, in Januai-y of 1990.'̂ Shortlyafter my father left the podium, a member of the audi-ence shouted into one of the aisle microphones, "Thisis pharmaceutical terrorism!" To which my fathercalmly responded, "Yes, but who is the terrorist?" Laterthat year in May and in June of 1990, Merck went onto secure two patents that would combine CoQIO withstatin drugs in the same capsule to prevent muscle andliver damage.'' The first of these patents was with co-inventor Michael Brown of Nobel Laureate fame forhis work with low-density lipoprotein (LDL) receptors.Unfortunately, these patents have never been acted onand to this day, the vast majority of physicians andpatients are completely unaware of statin-inducedCoQIO depletion.

The Trouble with Statins

All statin drugs block the biosynthesis of both cho-lesterol and CoQIO, which explains statins' commonside effects of fatigue, muscle pain and muscle weak-ness, and a worsening of heart failure (see figure 2).

Coenzyme QIOand Heart FailureCoenzyme QIO is an antioxidant nutrientessential to energy production, especially inorgans that require vast amounts of energy,such as the heart and brain.

Individuals suffering from congestive heartfailure are often deficient in CoQIO.Supplementing with CoQIO helps improveheart function and relieve the symptoms ofcongestive heart failure,

Cholesterol-lowering statin medications blockthe synthesis of both cholesterol and CoQIO,and may thus lead to CoQIO deficiencies.This may explain the fatigue and muscle painthat can accompany statin use.

Coenzyme Ql 0 deficiency is now exceedinglycommon due to the widespread use ofstatin drugs.

Numerous clinical trials show benefits forcongestive heart failure when blood CoQIOlevels exceed 3.5 mcg/mL.

Patients with congestive heart failure mayabsorb CoQIO poorly. An advanced CoQIOformulation called ubiquinol providesimproved absorption and dramaticallyelevates blood levels.

FEBRUARY 2008 I UFE EXTENSION | 51


When CoQIO levels are lowered by statin drug ther-apy, one of the first changes to occur is a weaken-ing of heart muscle function, known as diastolicdysfunction. This has nothing to do with diastolicblood pressure, but rather represents impairmentin the relaxing or filling phase of the cardiac cycle.After heart muscle contracts, it takes a great deal ofcellular energy, or ATP, to re-establish the calciumgradients such that muscle fibers may relax. Thus, ifdiastolic dysfunction is severe, it can result in con-gestive heart failure.

In 2004, a study published in the American Joumalof Cardiology showed that diastolic dysfunction (heartmuscle weakness) occurred in 70% of previouslynormal patients treated with 20 mg a day of Lipitor^for six months. This heart muscle dysfunction wasreversible with supplemental CoQ 10.̂ Heart failurethat develops after years of statin drug therapy canbe termed statin cardiomyopathy and may well beplaying a role in the epidemic of congestive heart fail-ure in the United States.

It is important for the reader to be aware thatfor every adverse side effect caused by statin drugtherapy, one can find a drug company-sponsored trialconcluding that statins actually benefit the conditionthey may induce. Good examples are studies that sug-gest statins are useful in the treatment of cancer,*'when in fact some studies suggest that they couldbe carcinogenic;'''" another study suggests that sta-tin therapy may be helpful in dementia,'' when otherevidence indicates that statins impair mentalfunction;'^'^finally, studies that conclude statin ther-apy improves heart failure, i"* when in fact it appearsto weaken both skeletal muscle and heart muscle.^'^

In an effort to determine the prevalence ofadverse effects from using statins, we studied50 consecutive new patients, all of whom weretaking a statin drug at the time of their initial visit.'"All 50 patients were found to have one or moreside effects from statin therapy, so we discontinuedtheir statin drugs and began supplemental CoQIO.Patients were followed for an average of 28 monthswith the following observations in the prevalence ofadverse effects:

• A high prevalence of skeletal muscle pain andweakness at 64% on initial visit was reducedto 6% in follow-up.

• Fatigue decreased from 84% to 16%.• Shortness of breath went from 58%

down to 12%.• Memory loss was reduced from 8% to 4%.• Peripheral neuropathy decreased from

10% to 2%.

There were no adverse effects from stopping statindrug therapy with no cases of heart attack or strokeduring follow-up. Overall, there was an improvementin heart muscle function on discontinuation of statintherapy and addition of supplemental CoQ 10. However,due to powerful propaganda surrounding both choles-terol and statin dnag therapy, many patients and physi-cians are afraid to stop statin therapy.

Cholesterol and Heart Disease

Atherosclerosis remains a disease of unknowncause. Many factors more important than choles-terol—such as stress, smoking, hypertension, insu-lin resistance, high triglycerides, diabetes, and lowtestosterone (in men)—contribute to atherosclerosisand cardiovascular disease."'^ Despite this, thetheory that cholesterol is the dominant villainresponsible for atherosclerosis has been promul-gated for over 60 years, making the pharmaceuticalindustry's anti-cholesterol campaign the most profit-able medical myth of all time.

Statin drugs do show some benefit in reducingmortality in individuals with pre-existing coronaryartery disease.^" This benefit occurs irrespectiveof cholesterol lowering and is likely secondary totheir subtle anti-inflammatory or plaque-stabiliz-ing effects.^' The vilification of cholesterol and theassociated aggressive lowering of cholesterol bloodlevels has brought about increasingly severe CoQIOdeficiency in a large number of patients, making itabsolutely critical to restore CoQIO levels in theseindividuals.

52 I LIFE EXTENSION FEBRUARY 2008


Optimal C0QIO Levels Improve Heart Failure

In the early years of our experience with CoQIOtherapy, no one knew the therapeutic or idealplasma level of CoQIO for the treatment of heart(•ailure. Over the course of 25 years, it has becomeclear that maximum improvement in heart functionwill not occur unless plasma levels are greater than3.5 micrograms per milliliter (mcg/mL). By 2006,there were a total of 22 randomized, controlledtrials involving a total of 1,605 patients evaluatingthe therapeutic benefit of supplemental CoQIO incongestive heart failure.'-'^'' The majority of studieswere favorable, showing significant improvementin heart muscle function. Furthermore, there havebeen 34 open-label trials involving 4,221 patientsevaluating the clinical utility of CoQIO in heart fail-ure, and again clear benefits were observed withoutany adverse effect or drug interaction. Despite thesestudies, CoQIO remains obscure to mo.st physiciansand is not routinely used in the treatment of conges-tive heart failure. This is in part due to the pervasiveanli-nutrient bias in conventional medical practice,medical literature, and medical education.

Out of a total of 22 controlled trials of supplemen-tal CoQIO in congestive heart failure, only three havefailed to show significant benefit. The first study byPermanetter et al. failed to measure plasma CoQIOlevels, such that there is no way to know if therapeu-tic CoQIO levels were attained.^'The second trial byWatson et al. demonstrated a mean treatment plasmaCoQIO level of only 1.7 mcg/mL, with only two of the30 patients having a plasma level greater than 2.0 meg/mL.-" Finally, the third study by Khatta et al. demon-strated a mean treatment plasma CoQIO level of 2.2± 1.2 mcg/mL, indicating that some patients on treat-ment had levels as low as 1.0 mcg/mL." Unfortunately,these last two trials with sub-therapeutic CoQIO levelsare the most frequently quoted as evidence for a lackof benefit for CoQIO in heart failure.

Absorption of CoQIO

From the beginning of our experience with CoQ 10in heart failure, we have observed poor absolutionof CoQIO in patients with advanced congestive heartfailure. This is extremely frustrating, because thepatients who are the most ill and have the lowestplasma CoQIO levels show minimal improvementbecause of their inability to absorb CoQIO. It hasbeen our assumption that the fluid retention oredema in the intestine and liver in these critically illpatients has been responsible for this poor absorp-

tion. Up until approximately one year ago, all supple-mental CoQIO in the world has been in its oxidizedor ubiquinone form. In this oxidized state, CoQIO isstable, bright orange in color, and fat-soluble. It isthis property of being fat-soluble that is responsiblefor the difficulty with CoQIO absorption.

A Better Form of CoQIO

After ingestion, immediately after CoQIO crossesinto the first cells lining the small intestine, it isenzymatically converted to its reduced, or ubiquinol,form. So, when we measure plasma CoQIO approx-imately 98-99% of the CoQIO is in this reducedubiquinol form (see figure 3). Kaneka Corporationof Japan has succeeded in making a stable ubiquinolformulation that we have been carefully studyingsince October 2006. Ubiquino! is a white powderrather than orange and is less fat-soluble, making itbetter absorbed.

FIGURE 3. TWO FORMS OF COENZYME QIO:UBIQUINONE AND UBIQUINOL

H.CO

HXO

OXIDIZED COENZYME QIOCoQIO-UBIQUINONE

Of

HXO

REDUCED COENZYME QIOH2CoQ10 UBIQUINOL

Until recently, all supplemental CoQIOwas in the oxidized, or ubiquinone form.

Today, it is possible to obtain dietary supplementscontaining ubiquinol, the reduced form of C0QIO.Ubiquinol is more bioavailable than ubiquinone.

FEBRUARY 2008 I UFE EXTENSION 1 53


Our first patient to be treated with ubiquinol hadsevere heart failure with a 15% ejection fraction (ameasurement of the amount of blood pumped outwith each heartbeat, which is normally 60-65%). Thisgentleman had a sub-therapeutic plasma CoQIO levelof 2.2 mcg/mL on 450 mg per day of ubiquinone. Hisplasma level on 450 mg per day of ubiquinol increased

FIGURE 4. PLASMA COQIO LEVELS CORRELATEWITH SEVERITY OF CONGESTIVE HEART FAILURE

0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30

Time in minutes

Chromatogram of plasma extract from a patientwith severe heart failure. This patient had an ejection

fraction of 15% and plasma level of reduced (ubiquinolCoQIO of 2.2 mcg/mL on 450 mg/day ubiquinone.

^ 30-

0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30

Time in minutes

Chromatogram of plasma extract from the same heartfailure patient following supplementation with ubiquinol.

Ten months of ubiquinol 450 mg/day increasedplasma level of reduced (ubiquinol) CoQIO to

8.5 mcg/mL and improved ejection fraction to 60%.

dramatically to 8.5 mcg/mL and over the subsequent10 months, his ejection fraction increased to 60% witha corresponding dramatic and perhaps life-savingclinical improvement (see figure 4). We now have atotal of seven patients with advanced congestive heartfailure and low plasma CoO 10 levels, despite taking asmuch as 600 mg per day of ubiquinone (the oxidizedform of CoQIO) who have been changed over to theubiquinol (the reduced form) formulation. Our pre-liminary obsei^vations have been very favorable, andit is my strong opinion that supplemental ubiquinolrepresents a major scientific advance in the 50-yearhistoiy of CoQIO research.

Supplementing with CoQIO

I would like to make a few practical commentsbased on 24 years of treating thousands of heart fail-ure patients with supplemental CoQIO in addition tostandard prescription medications. We have seen noside effects and no drug interactions from supplemen-tal CoQIO, but we have observed a gradual lesseningof the requirement for many cardiac medications thatoccurs with an improvement in heart muscle function.For example, we have obsei-ved a significant decreasein the need for diuretics, because of a reduced ten-dency for fluid retention as heart function improves.Also, we have noted a gradual improvement in hyper-tension that occurs as heart function improves, whichmay require a gradual decrease in antihypertensivemedications such as angiotensin-converting enzyme(ACE) inhibitors, a class of blood pressure-loweringmedicines frequently used in heart failure patients.Patients with heart disease should be followed by theirphysicians, particularly when there are any changes inactivity, diet, prescription drugs, or over-the-countersupplements.

I have treated hundreds of patients with CoQIOand have never observed an interaction with warfarin(Coumadin'"). There have been anecdotal reports thatthe combination may increase the risk of bleeding.Individuals who use warfarin should always consulta physician before using CoQ 10.̂ '̂ '̂'

Choosing a CoQIO Formulation and Dosage

Most commercially available CoQIO supplementscomprise ubiquinone. Recommended daily dosagesof this type of CoQlO range from 100 mg to 600 mg.The most advanced CoQIO formulas now containubiquinol, the reduced form of CoQIO, which isdefinitely better absorbed into the bloodstream.^""Recommended daily dosages of ubiquinol range from100 mg to 300 mg.

54 I LIFE EXTENSION I FEBRUARY 2008


Because we know that CoQlO levels tend todecrease with age and we live in a society that con-sumes vei-y little food rich in CoQIO (organ meatslike heart, liver, and kidney), it makes sense tosLipplement with a modest amount of CoQIO(ubiquinone or ubiquinol) beginning in middle age.Those who suffer from congestive heart failure or whouse statin medications should aim to consume higherdoses of CoQIO (ubiquinone or ubiquinol).

Conclusion

Coenzyme QlO's ability to fundamentally improvethe production of energy and the antioxidant defensein evei7 cell of the body has brought about manyremarkable and unexpected improvements in allaspects of human health. This extraordinary moleculehas dramatically changed my own practice ofmedicine and has brought joy to the treatment ofpreviously devastating cardiovascular diseases. •

If you have any questions on the scientificcontent of this article, please call a Life Extension

Health Advisor at 1-800-226-2370.

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alleviating congestive heart failure with coenzyme q10

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