ast month we chatted with Dr. Stephen Sinatraabout new nutrients to keep the heart and arterieshealthy, particularly a nutrient called propionyl-

L-carnitine (PLC). This month, we will focus on metabolic cardiology and how adenosine triphosphate(ATP), and thus its precursors, the carnitines, CoQ-10and D-ribose, is the bottom line in heart health. Anybodywith any type of cardiovascular disease has a heart that isalways leaking ATP. The body can’t make it back fastenough by de novo (from the beginning) synthesis! Ittakes too long and the ATP leakage is faster. It’s all aboutATP and less about oxygen!

Cardiologists are always thinking about oxygen in theheart–and oxygen is important–but oxygen is only thestepping-stone to ATP. Oxygen is only a tool–but a vitalone–in the production of energy via ATP. But, it is not theoxygen that provides the energy of life–it’s the ATP.“Life” depends on the body utilizing energy to drive thevital biochemical reactions of life. In the “living”process, “free energy” is needed to power reactions thatotherwise would not occur. The chemicals would just sitthere, unreacted. The Energy needed to cause the chemi-cals is obtained from the release of chemically storedenergy. Energy is a force, not a compound. The principlesource of “free energy” in the body is a special high-energy phosphate group (high-energy bond phosphate).

In order for “life” to occur, or for muscles to move andperform mechanical work or exercise, or for the heart tobeat, “free energy” must be liberated through a chemicalreaction where ATP is split into adenosine diphosphate(ADP) and the high-energy bond phosphate group (thesource of free energy).

In previous chats with Dr. Sinatra, we have discussedthe emerging field of metabolic cardiology and how it issaving lives and improving the quality of life in heartpatients. Metabolic cardiology is a sub-specialty of car-diology that deals with the very core of heart diseaseitself–the biochemical changes in cardiac cells by whichenergy is provided for vital processes and activities.

Actually, metabolic cardiology is more than energizingand powering the heart because the same factors energizeand power all of the cells in the body. Metabolic cardiol-ogy applies to preventing and overcoming fibromyalgia,chronic fatigue and Syndrome X, just as it does to allaspects of heart disease.

In the introduction to Dr. Sinatra’s new book, TheSinatra Solution (Basic Health 2005) cardiologist Dr. JimRoberts points out several shortcomings of conventu-al cardiology and how it was missing the boat in terms ofnot being able to stop the continual decline in heart func-

tion even after arteries had been stented or by-passed andproper medications given. Why didn’t wall motion returnto normal? Why was there a functional delay in recovery?

Dr. Roberts comments, “Now we know the answer toall these questions–it is energy depletion. The ischemia... burns off the adenine nucleotide pool, the source ofcellular energy. Hibernating regions of the heart don’tcontract because they lack energy–they’re alive, but theydon’t have a large enough energy supply to contract.”

Stephen T. Sinatra, M.D., F.A.C.C., F.A.C.N., C.N.S., isa board-certified cardiologist and a certified bioenergeticpsychotherapist, with more than 27 years of experiencein helping patients prevent and reverse heart disease. Healso is certified in anti-aging medicine. He is a fellow ofthe American College of Cardiology and former chief ofcardiology at Manchester Memorial Hospital where hewas director of medical education for 18 years. Dr.Sinatra is also assistant clinical professor of medicine atthe University of Connecticut School of Medicine.

At his New England Heart & Longevity Center inManchester, CT, Dr. Sinatra integrates conventional med-ical treatments for heart disease with complementarynutritional, anti-aging and psychological therapies thathelp heal the heart. He is uniquely qualified to giveadvice on nutritional supplements and the heart. Dr.Sinatra is one of the few medical doctors who formulateshis own vitamins. He is expert in dosage, absorption,how to pick quality ingredients, and the effects of com-bining supplements with cardiac medications.

Dr. Sinatra has authored and/or co-authored severalbooks on heart disease and is the editor of the monthlynewsletter on heart health, The Sinatra Health Report.His most recent book is the aforementioned The SinatraSolution. Additional information can be found on hiswebsite at www.drsinatra.com.

Passwater: You are always at the forefront of metaboliccardiology. In previous chats, we have traced your evolu-tion of metabolic cardiology from CoQ-10 to the “TwinPillars of Heart Health,” to the triad of CoQ-10, carni-tine and D-ribose, and even to the “Awesome Foursome,”which adds magnesium to the previous three. How did theevolution of your research and therapies come about?

Sinatra: I have been using CoQ-10 for some 20years–ever since around the time that Dr. EmileBliznakov came out with his 1987 book The MiracleNutrient: Coenzyme-Q-10 in 1986 Actually, my firstexposure to CoQ-10 was in 1982 when I read an articlein the Annals of Thoracic Surgery. I have been using

Dr. Richard Passwater,who has offices in Berlin,

MD, has authored sev-eral books on nutrition,including The New Su-

pernutrition, Cancer Pre-vention and Nutritional

Therapies, Selenium Against Cancer and

AIDS, and Selenium as Food & Medicine. For

More information on the topic covered in this col-umn, and/or other news

and developments in thefield of nutrition, visit the

columnist at his web-site–www.drpasswa-

ter.com

By Richard A. Passwater, Ph.D.

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Metabolic Cardiology-It’s All About ATP - Part 2

An Interview withDr. Stephen T. Sinatra, M.D., F.A.C.C.

L

WHOLEFOODS • APRIL 2006 37

CoQ-10 in my practice since 1985 or 1986.I have been using the carnitines for 10 years.

Specifically, I used L-carnitine at first, thenadded acetyl-L-carnitines about five years ago.I have been aware of the role of L-carnitine inthe mitochondrial turnover of ATP since the late1980’s or early 1990’s. There have been manyvery interesting studies published on the car-nitines in the cardiovascular journals since thenabout how heart cells deficient in carnitine andCoQ-10 cannot perform adequately.

Now an improved heart-specific carnitinecalled propionyl-L-carnitine (PLC) is availableand my patients are gaining even more benefit.

I have been using D-ribose for about threeyears now. I learned about D-ribose at a meetingon aging from fellow cardiologist Dr. JimRoberts, who wrote the introduction to mybook.

Passwater: What is the magical metabolic“Triad” for metabolic cardiology?

Sinatra: Coenzyme Q-10, collectively car-nitines (as there are three carnitines). There is L-carnitine, acetyl-L-carnitine which gets moreinto the brain than the heart, and there is PLC,which has a very fast half-life (the time requiredfor the quantity to fall to half of its initial value).PLC gets inside the heart and other muscles(both peripheral muscle and carnitinemuscle)–this is a very heart-selective carnitine.

Any of the carnitines will increase ATPturnover and that’s why they are important in thetriad of metabolic cardiology.

The third nutrient in the Triad is D-ribose,which really provides the precursor. This is thefive-sided sugar that combines with adenineand three phosphate groups to make the ATPmolecule.

In fact, you can take patients–I saw this writ-ten up years ago–and put them on CoQ-10 on atreadmill and you’ll get about a minute longerbefore they experience ischemia. The samething is true of L-carnitine, and the same thingalso is true of D-ribose.

All of these studies have been done individu-ally where you can do a crossover study, double-blind, do a washout, and all of a sudden you geta minute longer on the treadmill by using one ofthese nutrients.

No one, to my knowledge has done a study ofall three nutrients together. I want to do such astudy to see if the combination synergisticallyresults in even longer time. They are going togive people a much better quality of life andreduce a lot of human suffering.

Now, if you do a biopsy on ailing hearts, andyou measure carnitine and CoQ-10 levels, theyare diminished. That literature is old. Drs. G.Littaru and K. Folkers showed this about 40years ago.

Passwater: So as this strategy hasevolved–CoQ-10 and carnitine as the “TwinPillars”–to which you added D-ribose?

Sinatra: Then there is the fourth nutrient, mag-nesium, and we have what I call the “AwesomeFoursome.” However, I have always usedmagnesium as a cardiologist even during myresidency and fellowship in cardiology. So Ihave been using magnesium for some 30 years.Most doctors are already familiar withmagnesium.

As for my involving awareness of thesenutrients, carnitine and CoQ-10 were literallyplaced in my path. I read the literature and, as acardiologist, I wanted to see if they would helpmy patients. As you know from writing yourbooks, the best way to become very informedon a subject is to give lectures to othercardiologists wishing to know more about yourtreatment and then write a book on that subject.Publishers asked me to gather my lectures in amore reader-friendly format for both patientsand cardiologists. Writing the books made mereally appreciate the complexities of thenutrients.

One thing I did learn from writing the booksand using the therapies on thousands of mypatients and subscribers to my newsletter, manyof whom write to tell me about their successwith carnitine and CoQ-10 and the positivefeedback about what these substances havedone for their lives. So when you take in the lit-erature, and use the nutrients every day in yourpractice, you get a flavor of how these vitalnutrients are really working. Then as you learn

more and more about them, your comfort levelincreases and that why I’m really enthralledabout this newest generation of carnitines.

Passwater: You mentioned that there is quite abit about CoQ-10 and L-carnitine in the med-ical literature. Yet, if I were to pick up the phonebook and call every cardiologist in my area, Idoubt that I would find more than one in 100who knew anything about L-carnitine and heartdisease. That’s because there are no drug sales-men knocking on their doors telling them aboutthe benefits of the carnitines. The cardiologistswill be very informed about heart pharmaceuti-cals as they are patent-protected profitabledrugs that pay for the drug companies’ invest-ment in sending out salespeople to educate thedoctors. Nutrients have no such patent protec-tion and resulting profit.

Sinatra: Yes, this is how many, if not most, doc-tors receive their continuing education in thiscountry. The pharmaceutical representative willcome to the doctor’s office, show him of her theresults of a double-blind clinical trail, hand outsome free samples, suggest that they be tried onpatients and may even buy the doctor and hisstaff lunch, spending extended time with themto explain more intricacies about the medicine.But this is not going to happen with nutrientsbecause of the patent issue that limits the prof-itability that supports this type of education.

Meanwhile, there is a glimmer of hope. TheAmerican College of Nutrition has an exam forany doctor who wants to become certified nutri-tion specialist (CNS). They can take this exam.I can tell you this: I am on this examinationcommittee, and I will lobby to have thesenutraceutical substances on the exam. I thinkthey are so vital for cardiovascular and generalhealth that they need to be included on boardexaminations so that physicians come to under-stand their vital interplay.

Passwater: You are also invited to speak at var-ious meetings and symposia of physicians whoare also very interested in complementing theirtreatments with nutrients. You often speak at theeducational symposia at the American Collegefor the Advancement in Medicine (ACAM), theAmerican Association of Anti-Aging Medicine(A4M), Expo East, Expo West, etc. Thus, you areconstantly educating physicians about how tocomplement their practice with nutrients. Still,you, personally, can reach only a minority ofthose who should be learning about the benefitsof these heart-healthy, artery-healthy nutrients.Your books certainly help to educate a fewphysicians who have open minds, but I believethat, possibility even more important, are thetestimonies of your readers and patients whocall their doctors to explain how CoQ-10, or

WHOLEFOODS • APRIL 200638

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“CoQ-10,carnitine, or

D-ribose enablespatients to last

longer on a treadmill.”

carnitine, or D-ribose, or fish oil havehelped them.

In addition to your books and newsletters, youhave been kind enough to discuss these topicswith us over the years. I have posted manyof our chats on my website at www.drpasswa-ter.com. I particularly would like to refer ourreaders to the following topics:

• CoQ-10 (Jan.-Feb. 2004) (http://www.drpas-swater.com/nutrition_library/Sinatra_1.html)

• The Twin Pillars (April 2004) (http://www.drpasswater.com/nutrition_library/Sinatra_3.html)

• Soft plaque and hard plaque (Aug 2004)(http://www.drpasswater.com/nutrition_library/Sinatra_5.html)

• Real causes of heart disease inflammation,homocysteine, Ox-LDL (July 2004)

• Fish oil and arteries (2004)• Nutrients for blood pressure (http://www.

drpasswater.com/nutrition_library/Sinatra_4.html)

In addition, I have posted several articles onCoQ-10 with various researchers, includingDrs. Bill Judy and Emile Bliznakov, and D-ribose with Dr. John St. Cyr (http://www.drpass-water.com/nutrition_library/John_St_Cyr.html).

Sinatra: When I lecture at theseconferences–and the conferences are beingattended by more and more doctors–there arenow about 3,000-4,000 doctors who go to theseconferences. Especially the A4M. What is veryinteresting is that these doctors come up to meand say with surprise, “You’re a board-certifiedconventional cardiologist.” Once they see that Ihave the same credentials that they have, theyrelax and listen.

In fact one cardiologist told me the other daythat one of his patients gave him my book. Heasked me, “What’s your background?” When Isaid, “Well, just like you, I sent 10 years in theCath Lab,” he immediately became interested.Like the rest of us, doctors tend to respect peo-ple who are just like they are, and who have hadthe same kind of training and initiation.

I think the pendulum is starting to turn.Instead of, as you said, finding one in 100 whoknows about nutritional therapies, now it mightbe five or 10 out of 100. And I’m optimistic thatover the next five years it’s going to bemaybe 50-50.

Passwater: What is the “bottom line” on meta-bolic cardiology?

Sinatra: I have been taking care of cardiacpatients for 30 years, and I am only now begin-ning to realize what the bottom line might be. Ididn’t realize this until I was writing my newbook, The Sinatra Solution. As I was trying towrite a clear explanation, I had this incredible“Aha!” moment. It was almost as if a light bulb

was switched on over my head!Here, the, is what I believe the bottom line of

metabolic cardiology can be: Anybody withcardiovascular disease–I don’t care if it’s some-one with a bypass or stent, or someone withhypertensive cardiovascular disease with alarge left ventricular or mitrovalve prolapse ormitral regurgitation, or a diabetic with highinflammatory involvement (any or all of theabove conditions where the heart is compro-mised in some way)–the heart is always leakingATP!

The bottom line is that the body can’t makeATP back fast enough by de novo synthesis! Ittakes too long and the ATP leakage is fasterthan the replacement process.

So what I’ve learned in the cardiovascularpopulation is that it is always playing catch up!These patients cannot get enough ATP in theircardiac cells because the ischemic or compro-mised heart is always leaking ATP that it isgone from the cytoplasm forever!

It is burned to uric acid and other metabolites.What I have learned as a clinical cardiologist isthat it is all about ATP. It’s not about oxygen!Cardiologists are always thinking about oxygenin the heart–and oxygen is important–but oxy-gen is only the stepping-stone to ATP.

Passwater: Perhaps I should repeat my themeon ATP once again. “Life” depends on the bodyutilizing energy. In the “living” process, “freeenergy” is released from chemically storedenergy. Energy is a force, not a compound. Theprincipal source of “free energy” in the body isin the high-energy bond phosphate group.

In order for many thousands of biochemicalreactions to occur or for muscles to move toperform mechanical work or exercise, “freeenergy” must be liberated through a chemicalreaction where ATP is split into adenosinediphosphate (ADP) and the high-energypyrophosphate (P) group (the source offree energy).

Let’s talk a little about ATP leakage since thisis so important to the new understanding ofmetabolic cardiology.

When ATP is broken down to ADP with theenergized phosphate P group being cleaved

that’s where our energy comes from. It’s thatcleavage of the phosphate group.

What happens in ischemia is that the Krebscycle (citric acid cycle) shuts down.

Sinatra: Yes, basically, the Krebs cycle

becomes poisoned, so to speak. Enormous lev-els of ADP are generated which can’t regenerateback to ATP. Then AMP is formed. With thehigh levels of AMP, this diffuses (leaks) out intocytoplasm of the cell. The last-ditch effort of thecell in ischemia is to form adenosine. Adenosineis like a vasodilator to keep the cell fortifiedwith oxygen. When adenosine is released, whathappens is that the vital adenine nucleotides arediffused out of the cell forever as they aredegraded to uric acid and other by-products.

The figure below shows this process.The body cannot make back the ATP fast

enough. De novo synthesis of ATP can take

weeks–some researchers say up to 100 days (ittakes a long time to make ATP by de novosynthesis). What I have learned about metaboliccardiology is this– there is a constant leakage ofATP in ischemia. Now remember, a lot of thesepatients have silent ischemia, so they don’t evenknow they have it. This is especially true whenleft ventricular hypertrophic cardiomyopathy ofthe heart is involved, or even in diabetes wherethe symptoms of ischemia go unnoticed becauseof diminished pain fibers associated with thediabetes.

“In anyonewith

cardiovasculardisease, the

heart is alwaysleaking ATP.”

WHOLEFOODS • APRIL 200640

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WHOLEFOODS • APRIL 2006 41

ATP gets depleted in the cardiac cells andthese patients develop enormous deficits.Fatigue and shortness of breath become majorproblems; angina is a problem; arrhythmia is aproblem.

The task is to get them back the ATPthey need.

Passwater: How do you stop the ATP leakage?Can you recycle the ADP before the purines leakout and are lost forever? What is the Sinatrasolution for this?

Sinatra: What you have to do is give them D-ribose, which is the rate-limiting step in ATPproduction. You also give them carnitine to helpwith ATP turnover in the mitochondrial mem-brane. Remember that the amount of ATP in thecell is small relative to the amount of energythat the cell needs to perform its normal work;so the ATP supply must be replenished (turnedover) continually to keep a constant supplyof energy available.

Passwater: How do you measure how muchATP is available in comparison to how muchis needed?

Sinatra: It would be convenient if we had anATP gauge like cars have gasoline gauges, butwe don’t. However, we do have several ways inwhich to measure ATP availability biochemical-ly. I prefer two systems. The first is called theadenylate energy charge. The adenylate energycharge of the cell is calculated based on the con-centration of ATP available to fuel the variousfunctions of the cell, divided by the total con-centration of all energy substrates in thecell(called the total adenine nucleotide, orTAN, pool.)

This relationship distinguishes between theconcentration of immediately utilizable energyand the total pool of substrates that are availableto make energy. In normal hearts with plenty ofblood flow and oxygen, the amount of ATP,ADP and AMP in the cell is kept in a carefullybalanced ratio, and the adenylate energy chargeis about 1. Normally, cells have about 10 timesmore than ATP than ADP, and about 100 timesmore ATP than AMP. A sick heart will however,have a much lower adenylate energy chargebecause the ATP concentration and all otherenergy substrate concentrations will bedepressed and ratio of ATP, ADP and AMP willbe out of balance. Using this measurement, ahealthy heart might register about 0.998 andischemic heart might register 0.180. This isquite a difference and makes it easy to deter-mine heart health.

A second measure of energy in cells deter-mines the amount of energy available to actual-ly complete all of the energy-consuming reac-tions of the cell. This is called the cell’s chemi-cal driving force, and it’s measurement is called

Reprinted with permissionfrom April 2006

WholeFoods Magazine.

Dr. StephenT Sinatra,

M.D.,F.A.C.C

the free energy of hydrolysis of ATP. The meas-urement of free energy of hydrolysis determinesthe total amount of cellular energy that is avail-able to perform cellular work. It’s akin to deter-mining the amount of electrical energy presentin a battery. Think of it like this: Measuring theamount of energy in your battery will tell you ifthere is enough power to start the car, turn onthe headlights, and run the radio. Similarly,measuring the amount of energy in the celldetermines id there’s enough energy to drivecontraction, ion regulation, and molecularsynthesis.

Passwater: That is indeed very interesting, butif you don’t mind, I’ll pass on how this measure-ment is made for the time being.

What I would like to talk about instead aresome studies suggesting that creatine can helpwith ATP turnover in the heart. Have youworked with creatine yet?

Sinatra: There’s no reason why people withcompromised hearts can’t use creatine. I willhave to give creatine a good look as I continueto evolve metabolic cardiology and ATPproduction.

Passwater: Creatine has also been shown tohelp with ATP recycling in the brain.

Sinatra: Yes. Creatine is indeed of interest.

Passwater: Well, you have certainly made greatstrides with metabolic cardiology and the“Sinatra Solution.”

Sinatra: Thank you. Based on all of the results inthe medical and scientific literature, as well as theresults from my practice, carnitines, CoQ-10 andD-ribose should be considered by every reputablecardiologist who wishes to improve his or herpatients’ quality of life and survival rate. Mymessage has been to reduce human sufferingusing whatever vitamins, mineral and nutraceuti-cals, in addition to the latest medicines and tech-niques. Now my mission is to teach cardiologistsacross the country about ATP and the heart. WF

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