Bioenergetic Support for the Tired Heart: Co-Enzyme Q10, L-Carnitine and D-Ribose

good evening our spring 2005 lecture series continues with tonight's discussion bioenergetic support and ATP restoration of the tired heart we'll talk about coenzyme q carnitine ribose taurine arginine and poly Kosan all there are many other nutritional agents that are a value but we'll run out of time my name is James Roberts I'm board-certified in internal medicine and cardiology I've been practicing invasive and clinical cardiology in Northwest Ohio the past 19 years and I'm the medical director of comprehensive heart care the ECP center of Northwest Ohio and the advanced magnetic Research Institute of Northwest Ohio the goal of all physicians involved in the care the patient with cardiovascular disease is the same the goal of all therapies applied to the patient with cardiovascular disease is the same I don't care if we're doing open-heart surgery or stents or external counter pulsation or Mme or chelation therapy or phosphoryl choline or whether we're giving you coenzyme q our common goal is to increase the content of ATP within the patient's heart cells to myocytes and to enhance the ability of those cells to regenerate ATP on their own ATP is critically important it's it's it's this common goal of all of us involved in the discipline of cardiovascular medicine because ATP is the only source of energy that can be used to drive forward useful chemical reactions in the heart it's all we've got ATP adenosine triphosphate is composed of an adenine base this is the same adenine that's in our DNA and RNA to which is attached ribose to five carbon sugar to which is attached three phosphate groups cleavage of the terminal phosphate two phosphate bond of ATP releases chemical energy that is then used to drive forward useful chemical reactions of the heart this is the only source of energy to fuel your biochemistry we need ATP for the heart to contract we actually need more ATP for the heart and our blood vessels to relax we need ATP to man the ionic pumps that keep the proper ratio of sodium potassium across the cell membranes in our heart we need ATP to pump calcium out of the cell to allow the cell to relax for the heart to relax for your blood vessels relax we need to use ATP if the heart needs to make new proteins new structural proteins or if the heart needs to regenerate ATP we can spent we have to spend ATP ATP is the only source of energy for the biochemical reactions in our heart so you think we've had a lot of it but we really don't the average heart contains 700 milligrams of ATP at a heart rate of 60 beats a minute we're going to utilize 70 milligrams a second so are 700 milligrams last 10 seconds about 10 heartbeats we need more than 10 heartbeats a day we go through about we have about 86,000 heartbeats a day so 6 million milligrams of ATP are utilized so each molecule of ATP must be recycled or regenerated by the heart 10,000 times so mother nature did not endow us with a large storage capacity for ATP no she endowed us with a basically unlimited ability to regenerate our ATP when it comes to ATP energy we have just-in-time production and transport this is sleek and efficient but it also means that everyone in this room is just 10 seconds away 10 heartbeats away from total energy failure that is if you can't recycle and regenerate your ATP we need not just enough ATP to fuel the next cycle of cardiac contraction relaxation relaxation we need a high ATP because a high content of ATP within the cell drives for useful chemical reactions if the ATP content in the cell begins to fall off first we we have trouble with our calcium pump so the heart can't relax the heart will be stiff your arterial smooth muscle can't relax oh you'll have high blood pressure later on the sodium potassium pump we have trouble there so we're gonna retain sodium that have edema finally when the ATP content is really low we can't contract and as the ATP content Falls one by one cell your functional mechanisms become depressed eventually leading to the death of the cell now how we need to keep this high content of ATP how are we going to do it we've only got 10 seconds of ATP in the heart phospho cracking serves as a reservoir of high energy phosphorus phospho cratan ii cannot be used to drive for two useful chemical reaction in the heart but phosphoric ratney can donate a phosphorus group to ADP to make ATP that gives us 20 seconds of energy reserve after that we need to generate new energy the heart prefers to burn fatty acids and to a lesser extent sugar molecules glucose molecules in the presence of oxygen in the mitochondria of the cells that's the furnace of the cell this is the process of oxidative phosphorylation our most efficient means of burning calories to regenerate ATP now we have if we're exercising within our own personal aerobic range we have a nearly unlimited capability of up regulating ATP recycling to meet our needs as our heart rate and blood pressure rises with exercise the rate pressure product when we have you on a treadmill every few minutes we increase the speed in the grade your rate pressure or product is rising we can respond by increasing oxygen utilization to burn sugar and fat so we can we can match we can generate energy to match the body's increase in the to fuel the next heartbeat while at the same time maintaining a high ATP content of the cell we need not just enough ATP to meet the increased needs of exercise we have to meet the increased needs of exercise and maintain a high content of ATP in the cell for reparative processes now what about this guy he has a high-grade blockage in the circumflex coronary artery we need oxygen to burn the sugar and fat to regenerate ATP so when he's exercising and this heart muscle needs more ATP it doesn't have enough oxygen you need oxygen to burn sugar and fat so he will have a deficiency of ATP in this section of the heart and that will make him short of breath and it'll make him hurt and it'll make his stress tests abnormal we put you on the stress test we see how far you can go when you get to the point where the cells can't make enough ATP because they don't have a good oxygen supply we'll see your EKG change the farther you the shorter your exercise duration the shorter your exercise duration before your EKG becomes abnormal suggests more advanced cardiovascular disease that makes sense the more severe the blockage the less will be your treadmill time to Shorter's your treadmill time until it's abnormal because you don't have enough oxygen to burn sugar and fat to make ATP but your treadmill time is not determined solely by the blockages the blockages deprive you of oxygen which you need more than oxygen make ATP I'm going to show you several studies where they didn't open up the patient's arteries but they gave them agents that improved ATP regeneration such as coenzyme q carnitine carnitine and ribose and they went an extra minute your treadmill becomes abnormal not just due to poor blood flow but due to insufficient ATP production it's oxygen just one of the things we need it's an important thing but it's not the only thing we need to make ATP and we got to keep a high level of ATP because you know if we wait for the heart pump function fall we've waited way too long so how do we deal with this problem all of my patients suffer from ATP deficiency either that got blocked artery for their hearts under strain we biopsy their heart they're gonna be low in ATP well how do we deal with this it's sort of a supply demand problem not enough ATP to meet the demands well we can decrease the demand I can give you drugs that lower your heart rate and blood pressure lower the contractility of the heart so the heart needs less ATP they can get by with less I can tell you not to exercise that's always a way to deal with your angina or I could increase your ability to generate ATP I can improve the blood supply to the heart if oxygen deficiency is part of the problem we'll reoxygenate you with and you plasti or bypass we can medically open up your arteries some of the things we'll talk about essential phospholipids heavy metal detoxification Mme which we'll be talking about in a few weeks probably works v all these mechanisms we can improve or restore efficient mitochondrial function with coenzyme q + carnitine which we'll talk about tonight or we can accelerate reconstitution of the adenine nucleotide pool which will do with ribose or next week we'll talk about indirectly improving the oxygen supply with the ECP with the ECP we're not operating on on you or opening up arteries we're generating natural bypasses so if you can't have a surgical bypass or a balloon angioplasty with the ECP we form natural bypasses that's a means of reoxygenate against our heart muscle and if oxygen deficiency was the problem keeping you from making ATP if we reoxygenate you you can make more ATP your chest pain will improve you'll be able to walk farther than a treadmill but I've been doing external counterpulsation for about seven years now there's a thousand of us in the United States and I was the 22nd so I've been doing this a long time I'm up to about 7 or 50 patients and I've learned that simply reoxidation the patient is not good enough the problem is not just oxygen deficiency its ATP deficiency all my patients with chronic core disease their heart muscles will be low in the cofactors and enzymes required to use oxygen to burn the sugar and fat to make ATP they will be low in coenzyme q their adenine nucleotide pool will be deficient wo and carnitine so if i want to get a really good response with external counter pulsation i will treat my patients for their metabolic dysfunction I'll use coenzyme q and con gene to optimize mitochondrial function I'll use ribose to speed up reconstitution to add new nucleotides get better quicker they stay better longer thus my interest in metabolic cardiology and tonight's talk and I have some recommendations as to how you can help your body regenerate ATP we have specific recommendations from the literature for antigen corneas ease heart failure cutting off the improving outcome falling bypass renal insufficiency claudication hypertension cardiac fatigue minor arrhythmia post heart attack status and mortality and will go through all these studies tonight and you have the numbers in your handout coenzyme q has everyone heard of coenzyme q in terms of bio energetic medicine coenzyme q is the most widely appreciated by physicians and laypeople alike this is the chemical structure of coenzyme q it's a fat soluble vitamin with the structure similar to that of vitamin k it stabilizes the cell membranes it blocks phospholipase enzymes don't want to disrupt the cell membrane it's a great antioxidant our primary metabolic antioxidant it's cabbages free radicals it inactivates superoxide it regenerates vitamin E vitamin E always works better with coke you than without and it's good we want stable cell membranes we want antioxidant antioxidant function but tonight we're gonna be talking about coenzyme q all in energy generation it is a primary mitochondrial electron transporter critical and ATP generation now what we're doing when we're burning sugar and fat were snipping them down into two carbon fragments then we will strip an electron from the carbon atom and we're going to take the energy of that of an electron bond and from the foods we eat and utilize that to make more ATP so we're going to convert food energy into useful ATP biochemical energy so we're gonna strip the electrons and we have to transport them on a system call the electron transport system in the mitochondria and two at two steps of electron transport we have coenzyme q without coenzyme q we don't have electron transport we would be dead in ten seconds without coenzyme q we cannot regenerate ATP energy intensive organs use a lot more coenzyme q then then then then less energy intensive organs the heart the kidney the liver and the brain are burning up the most calories they are the richest and coenzyme q however they will also suffer if you are coenzyme q deficient because they need the most but it's not a problem we can get coins thank you from our diet from kidney liver brain you know of animals or muscles of animals and we can make it I mean obviously if it's critical like Mother Nature has endowed us with the ability to make it now we burnt we snipped these carbon and sugar carbon chains down to two carbon fragments and we burn them but if we don't need to burn them because we've had a big meal we don't need the calories we can build with them we these little to carbon acetyl groups can be bound together to make things such as cholesterol and coenzyme q is formed as an offshoot of the cholesterol generation pathway so I can make cholesterol all I want and as long as I can make cholesterol and it's unimpeded I can make coenzyme q which is a good thing now the heart under strain is always low in coenzyme q mother nature designed us to make enough coins on queue to meet the needs of a normal heart she never anticipated coronary disease heart attacks high blood pressure valve disease the heart under strain is being called upon to burn more sugar and fat than mother nature ever planned on the heart under strain you know if you lost 40 percent your heart with a heart attack the rest of the hearts working overtime to pick up the slack you're not going to have enough coenzyme q and you're gonna become coenzyme q deficient so almost everybody with advanced heart diseases coins I'm Q deficient thus supplementation would make sense and we have randomized double-blind studies in the cardiology literature showing the value of coenzyme q in Cornie disease improving outcome flow and heart attack following bypass surgery improving symptoms and mortality and heart failure and cardiomyopathy improving endothelial function lowering blood pressure lowering blood pressure improving lipids and insulin sensitivity following unstable angina it's a benefit in end-stage renal disease migraine headache Parkinson disease and statin myopathy and we have open studies that were not double-blind showing benefits in diastolic dysfunction statin diastolic dysfunction arrhythmia hypertrophic remedy mitral valve prolapse at in athletic performance I'm going to review some of these studies with you let's talk about cardiomyopathy in heart failure what's cardiomyopathy think of cardiomyopathy is muscular dystrophy of the heart the heart muscle is punk it's not pumping well anymore why do we have it the two leading causes appear to be viral invasion and heavy-metal overload if your mercury overloaded you might turn eight and acute viral infection into a chronic autoimmune attack on the heart we're seeing more and more cardiomyopathy the heart is Punk as the cardiomyopathy advances you may go into heart failure the heart's not pumping blood forward so there's poor blood flow to your limbs so you're tired poor blood flow to the kidney so the kidney responds by retaining sodium if blood dams up behind the heart you can be short of breath with exercise if the blood dance dams up behind the right heart you have ankle swelling those are the signs of congestive heart failure so advanced cardio myopathy will cause heart failure but any insult to the heart a large heart attack uncontrolled high blood pressure a bad valve whatever um as the heart begins to fail you will develop congestive heart failure how do we rate the severity of congestive heart failure due to cardiac aughs we look New York Heart Association functional class and ejection fraction now New York Heart Association class four is you're having symptoms at rest you may need oxygen you're pretty sick your one-year mortality used it was about 50% class one you're doing great you can play tennis class two and three are in between ejection fraction is the percentage of blood cells the heart ejects with each beat if if your heart fills with a hundred cc's of blood and then it ejects 50 CCS the ejection fraction is 50 percent that's normal if you've had a massive heart attack you might eject only 25 percent of the blood with which the heart fills so your ejection fraction is 25 percent when we're treating you what we want to do is make your ejection fraction go up and make your functional class go down and that shows that you're getting better now I mentioned that the heart under strain is a low and coenzyme q and i can back that up here we're gonna look at blood coenzyme q levels here we're gonna look at heart muscle biopsy coenzyme q levels in normal people or people that have class 1 heart failure you have a normal level class to heart failure class 3 and for the blood level of coins I'm Q is falling the heart muscle level of coenzyme q is falling so advanced heart disease cardiomyopathy and heart failure it's associated with low coenzyme q in the blood and low PO enzyme q in the heart a number of studies have been done to see will coenzyme q supplementation improve outcome in people with heart failure and cardiomyopathy a few of the studies have not shown a positive effect and when i read those studies with interest and in general those studies use low doses of coenzyme q or they treated people who are doing pretty well who couldn't get a lot better but the preponderance of studies when you use an adequate dose of coenzyme q and you treat really sick people they've showed a benefit in symptoms in function and above all in mortality let's start with coenzyme q therapy and heart failure back in 1990 180 patients with class for heart failure you know our one-year mortality rate then in 1991 was 50% they had heart fair due to multiple heart attacks or some people had dilated cardiomyopathy they took all comers they had at least two admissions of the hospital 75% of the subjects were enrolled in the study after as they were being discharged from the hospital for a heart failure admit their ejection fraction was their average ejection fraction was 20% which is really pretty bad poor response to standard drug therapy the best that we had in 1991 do a baseline assessment then randomized them to receive usual therapy or usual therapy same doctors and nurses plus coenzyme q 100 milligrams a day and you follow them for eight years and let's find the usual therapy group there was no symptomatic benefit no significant heart rate and ejection fraction amongst the survivors they also saw that deterioration in the placebo group in the controls was associated with a further drop in colons I'm Q so if your coenzyme q levels dropped that means you are headed for trouble in the co q group their level rose from 0.7 to 2.1 after 60 days if their one-year check their heart rate was 9% lower because their heart was functioning better didn't need to be so so frequently their ejection fraction in risen by 76% from 21 to 38% absolute points that's pretty darn good 78% in turn improve in terms of ejection fraction or functional class 11 of the night he improved after 2 weeks the average response time was 40 days with nutritional medicine we have to be patient and we all we all understand it Grubbs work quick nutritional work slowly but steadily let's look at survival in the usual therapy group um half died at one year and only one patient was alive at five years which is what you would expect in the Co Q group 73 survived one year half were still alive at 5 years 29 were still alive at 8 years clear benefit with mortality this was the first time anyone ever showed that a physician in intervention something that the doctor prescribed would improve mortality that's the very first time now with the drugs we use today coreg the ACE inhibitors pentoxifylline spur lactone they will improve mortality but up until 5 to 10 years ago we had nothing in conventional medicine that improved mortality but for many for at least 10 years now we've had coenzyme q some of the patients did better with coenzyme q than others they were called responders some didn't do as well either it was too little too late or maybe their problem wasn't coenzyme q responsive but if you look at the responders 94% were alive at 1 year 50 at 5 years 38 % at 8 years a clear benefit in terms of symptoms and ejection fraction and mortality now we have this was back in 1991 before modern day drug therapy modern today drug therapies improved so the question is will coenzyme q still add well let's look at people in whom modern-day drug therapy had not worked 32 patients with end-stage heart failure on the waiting list for a cardiac transplant they're all on all the politically correct drugs you do a baseline assessment randomize them to receive placebo or coenzyme q 60 milligrams a day in a gel form we have out at three months randomized double-blind protocols fall so there's no bias the coenzyme q levels were incredibly low you got to be at least one that these people had advanced heart failure they were very very low placebo therapy didn't make the co q level go up but it quadrupled with therapy it would have been nice to even have it higher but it did rise with therapy no effect on ejection fraction atrial natriuretic factor which is a marker of pump function or an inflammatory marker called TNF alpha but in terms of symptoms there was a big improvement if you have heart failure you have to get up at night and empty your bladder a lot we call that nocturia that progressed with placebo therapy it improved with Coke you fatigue worsened with placebo therapy improved with Coke you effort shortness of breath improved a little bit with placebo it improved a lot more with Co Q New York Heart Association functional class did not change with placebo it fell from 3.1 to 2.4 with Co Q and that's a bit highly significant how far you could walk in six minutes a functional a measurement of meaningful to you and your quality of life deteriorating with placebo and improve with Co Q so in the worst patients in whom standard drug therapies not working coenzyme q does work conclusions coke Q levels are decreased in proportion assertive disease in people with crazy myopathy and heart failure blood levels respond rise in response to supplementation later on I'll show you the tissue levels rise in response to supplementation coke q supplementation above and beyond conventional therapy reduce the symptoms increases ejection fraction most importantly prolongs your life Co Q and Angela now what is angina it's a shutdown in energy metabolism due to oxygen deficiency a supply demand mismatch you have a narrowing impeding blood and oxygen supply to the heart not enough oxygen you can't make ATP actually it's a supply demand mismatch for ATP but in our quantity patients where the major problem is not enough blood and oxygen Co Q levels are reduced in people with chronic Corney disease if you're currently if you have recurrent ischemia lack of oxygen that drains your metabolism and your heart will be low in Co Q it will be wasted the people who need Co Q the most have the least multiple studies document a benefit with supplementation now first of all corny patients are Co Q deficient I said that I have to be able to prove it we're going to take 30 patients of the corneas yz9 teenage mash healthy controls none are on statins which wastes coenzyme q the coenzyme q levels are 2.5 than the normal healthy people they're only 0.8 in the coronary patients if we look at the ratio we have some coenzyme q in our LDL as an antioxidant and um the ratio of LDL to Co Q was a lot higher in the patients they were low in coenzyme q so their LDLs were more likely to be oxidized aggravating the corny disease and they had less H less coenzyme q in their heart so you can't you know regenerate your ATP and that makes sense so if the coronary patients are low in Co Q and you need coenzyme q to make energy let's supplement and see the ranch and gets better patients with stable effort Angela and Anna no blockage you give them 150 milligrams of coke you a day or placebo ver weeks um placebo therapy did nothing the blood level rose appropriately with therapy treadmill time increased by over a minute by 18 percent time to ST segment depression increased by almost two minutes forty five percent now we didn't open up the arteries we just gave them the cofactors they needed to make the moat get the most miles per gallon of the oxygen available the most molecules of ATP for every molecule of oxygen available we tuned up the engine engine a felf frequency fell from five point three to two point five episodes every two weeks nitroglycerine requirement fell from two point six to one point three they got better by improving their bioenergetic status now in conventional medicine we think of angina as supply demand for oxygenated blood that's the way I was treated well that's the way I was I was taught um so does coke you decrease the oxygen demand like a drug or does it increase the oxygen supply like Ancha plastic let's look at this 15 substance known corny disease all of stable angina reproducible abnormal exercise EKGs you do a baseline stress EKG quantify the degree of ST depression and then repeat the stress EKG following Coke Q 600 milligrams a day for four days with SIBO for four days or 90 minutes after a single dose of Pindell all a beta-blocker or Isis or by nine nitrate a long-acting nitroglycerin and what you find here here we're gonna we're gonna run you on the treadmill and your blood pressure will rise and fall your heart rate will rise and fall here we have before therapy and the placebo you see placebo has no effect coenzyme q lowers your blood pressure and heart rate response to exercise only minimally the drugs lowered a lot that's how drugs work they lower your heart rate and blood pressure so you can exercise more but your heart's not working as high you don't need as much blood and oxygen the drugs work by decreasing demand for ATP coenzyme q really didn't but the effects were the same this is cumulative ST segment depression with placebo here's coke q and the the drugs they're basically there was no statistically significant difference so coke you worked as well as the two drugs now the the improvement in your exercise duration correlated with the change the rise in your coenzyme q level people who had low blood Co Q levels that went up a lot they're the ones that got the the better improvement the treadmill parameters the more you need coke q the better will be your spots that makes sense drug therapy works by decreasing oxygen demand lowering your heart rate and blood pressure the long-acting nitrates give you some nitric oxide to dilate your arteries but really they're working by decreasing demand coke q lowers your heart rate and blood pressure a little bit and because it's an antioxidant it keeps you from degrading your nitric oxide but it really it's working by increasing the efficiency of Oxford utilization more miles per gallon more ATP molecules form four oxygen molecules that can make it through the blocked arteries improving the efficiency of your metabolic engine many other studies have shown same benefits on exercise time and your frequency nitro use functional class improves no major effect on oxygen demand heart rate and blood pressure or blood supply Co Q works by improving the efficiency of energy metabolism thus it will be additive to any drug therapy that one could think of um Co Q is a benefit in angina no sickness or nuisance side effects benefits should be additive to conventional therapy statin drugs waste coenzyme q where do we get Co Q from our diet from organ meats of animals that's where they have all their coke you and their mitochondria and we tell you not to eat those foods so we're gonna have to rely on our body making it and it's easy to make coenzyme q if you can make cholesterol the statin drugs block this step there HMG co-reductase inhibit so if you take a statin drug that's going to keep you from making your normal amount of coenzyme of cholesterol it's gonna lower your coenzyme q production by 50% period is that a problem crave a call and zocor if you take those your cholesterol is gonna fall by 40% and so will your coenzyme q level in healthy volunteers and the healthy volunteers were making plenty of coenzyme q they did not have any side effects so the FDA cleared these drugs for human use because normal volunteers had no problems with a loco Q but if you have heart disease and your Co Q levels are low to begin with is that going to be an issue or not you can lower the cholesterol via other means quest r and blocks cholesterol absorption from the gut it'll lower your cholesterol but not will not affect Co Q only the statins lab rats treated with methyl Cora statin they have lower blood levels and heart Co Q content if you add a coke you supplement you can restore the Co Q levels back to baseline without adversely affecting the cholesterol so if you take a statin and you want to lower your cholesterol and it lowers your Co Q you can take co Q and rectify the situation you'll still get the benefits of the statin it'll keep your cholesterol down now um rats on a really high cholesterol diet had early cardiac muscle dysfunction because high cholesterol levels like that damaged the cell membrane they gave them coke q which protects the cell membrane heart function normalized then they left him on the high cholesterol diet and added zocor a statin and there was aggravation of a pump dysfunction versus high cholesterol level alone high cholesterol level and zocor produce reversible cardiac dysfunction even before Corney disease develops in these laboratory animals what about in humans metal core there the paper came out in the literature they looked at a bunch of people with borderline hearts they had advanced cardiomyopathy ejection fraction 30% they're walking and talking and doing okay but they're on the brink you give a metal core they went into heart failure associate with the drop in coke you you stop the metalcore they got better or if you gave them coke you they got better and it was in the literature they did another so they took a young healthy person a runner and did some sophisticated test of cardiac pump function put them on methyl core repeated the studies and this healthy runner couldn't perform as well why ran out of coenzyme q statin drugs cause muscle aching and they will make your one of the markers is your CPK enzyme so if you have your on a stat and your muscles are aching we may draw a CPK level your liver chemistry's can can become abnormal you know muscles and liver need a lot of coke you you take it away you can have dysfunction so when we put you on a statin we're always asking you are you having muscle aching we're always monitoring your liver chemistry's now so I'm gonna suggest if you take a statin take coenzyme q as well you know if if there's a patient with preexisting cardiac dysfunction I will recommend Co Q if you get muscle aching or your CPK Rises also if you if your liver chemistry's rise will give you Co Q and will also give you celebra and and n-acetylcysteine antioxidants to protect the liver this way you can take the stat and get the benefits while we're attenuating some of the downsides now let's talk about a formal study of coenzyme q & statin myopathy 41 patients with muscle pain attributed to statin therapy how many of you have had muscle aching due to a statin a few people it's it's very frequent in my practice a lot of people just can't take statins because of muscle aching so what we're gonna do we're gonna ask them to record the severity of muscle pain at a ten point scale will measure the CPK which is released by enzymes randomized these symptomatic people to receive vitamin e four units today are Co Q hundred milligrams a day worry about it 30 days the CPK did not change and did not correlate with the degree of muscle pain the CPK really isn't a good marker of statin myopathy there was no change in LDL cholesterol and they had left these people on the statin the pain level um actually worsened slightly on vitamin e vitamin e wasn't very valuable but it fell significantly with coke you 15% of the patients improve their muscle aching resolved with vitamin E 86% with coenzyme q coenzyme q and staten diastolic dysfunction now you need an ATP for the heart to contract you need more energy for the heart to relax you don't have enough energy got a stiff heart we call this diastolic dysfunction and it doesn't feel well and you may become short of breath 14 asymptomatic patients they have healthy hearts they're all set to begin statin therapy because their cholesterol side do a baseline kokyu level do an echo of the heart and ultrasound and look at various measures of diastolic function treat them all with lipitor 20 milligrams a day repeat the echo at 3 to 6 months and look and see if at least one of these parameters of diastolic function which became abnormal while on statin therapy and if there was some diastolic dysfunction from the statin you add coenzyme q 100 milligrams three times a day keep them on the lipitor to see if the coenzyme q will rectify the situation reevaluate three months findings with lipitor now 71% of these normal healthy people demonstrated a deterioration in at least one echo parameter so 71% suffered an element of diastolic dysfunction is a direct side effect of the statin therapy um before that did not have diastolic dysfunction they had greater than average levels of coenzyme q going into the study so coin sank for you was protecting them findings with lipitor and coke Q on coke q 89 percent had reversal of at least one lipitor induced echo abnormality you want a high na ratio it fell with statin and you were rescued with Co Q the e wave deceleration time you want a low-level it worsened with statin and then you were at least partially rescued with Co Q the ice of illumination I'm rose with statin and you know abnormal and then there was a rescue so if you are taking a statin drug you're probably gonna have a little bit of stiffness to your heart so maybe you know I've been recommending if you're gonna take a statin you've got a bad heart you ought to take coke you I think I'm gonna recommend if anyone takes a statin they should take coke you to prevent these problems from occurring you get the best of the drugs without the downsides um now what if you had to pick one or the other coenzyme q vs statin we don't have to do that some people are drug only medicine everything else is expensive urine I also have colleagues that just hate drugs they get angry with me for using drugs its vitamins only we can get the best of both but let's say you just had to pick coke you versus your statin which would work best 25 men with endothelial dysfunction as we'll discuss at a later lecture this is the most important determinant of your outcome if your annual theme is working well you're gonna do great if it's not working well you're doomed measure it baseline flow of endothelial function Co Q levels and then all these subjects receive it random order service statin which is a statin coenzyme Q or statin and coenzyme q and what you find after taking a single dose of the statin your coke Q levels fall by 29% flow meaning they'sa dilatation which is a hundred times more important than your cholesterol level or your Co Q level this is the thing the real the reality of your cardiovascular system it was it was abnormal in those that were gonna receive the statin and it improved on the statin statins will improve endothelial function that's one of the reasons they work the group assigned to coq you got just as good a response so Co Q and statin therapy will seem to help you to the same degree and if you take both which is what most of my patients do you get a similar benefit so if you had to pick one or the other it would be a toss-up but we can just have you take both and get the best of all worlds kokyu and hypertension you know it takes energy for the vascular smooth muscle in the arteries of your body to relax not enough energy they remain constricted and you have high blood pressure we're gonna take 50 subjects um 52 subjective essential hypertension 20 head low co2 levels that might have been the culprit treat them with coke q 100 milligrams a day plus usual therapy usual therapy alone nothing happened with usual therapy alone usual therapy plus Co Q their systolic fell from 167 148 their diastolic from 97 to 91 this has been repeated and your exercise heart rate and blood pressure response also will be blunted with co q co q in athletes here they took professional basketball players in Italy the equivalent like the Italian NBA admit season and they gave them placebo or coke q 1 her milligrams day for 40 days their coke Q levels rose maximal oxygen uptake with exercise which is your peak aerobic performance in these professional athletes on coke you improved by 18 percent the resting ejection fraction improved their diastolic function improved why would an athlete need coke q because they're overdoing it mother nature did not plan on us running up and down the basketball court every night they over they've been burning too much sugar and fat they ran out of coke q so most professional athletes are taking coenzyme q the Tour de France cyclists if you measure their coenzyme q levels during the racing season when they're over taxing themselves that will be low during the offseason their coins I'm Q levels rise long-distance runners you do stress test before and after giving them coke q 100 milligrams stick for 40 days treadmill time increased by 18 percent treadmill distance by 13% so long-distance runners are going to become deficient in the cofactors need to generate energy in the same way as the car to the coronary patient they're not over exercising they just you know they're running out of their coenzyme Q and carnitine they more so heart patients and athletes will benefit from kokyu coenzyme q and cardiac arrhythmia if you carry out a heart attack in an animal and you pretreat with coenzyme q they're less likely to have arrhythmias coenzyme q decreases your risk of arrhythmia falling open-heart surgery here's a study where they took people with PVCs extra heartbeats premature ventricular contractions due to a number of different cardiac ailments gave him 150 milligrams of Co Q over two to four weeks there was a 50% reduction in PV C frequency and cardiomyopathy 25% of those with prior heart attack 32% of those with other cardiac disease 8% reduction in this people with a normal heart they were probably treating the underlying heart problem as opposed to treating the arrhythmias but as the heart got stronger it became more electrically stable fewer arrhythmias what about improving um outcome after open heart surgery you know if I send my patient for open heart I want to do everything I can to ensure that they're gonna have a good response this study was done in 20 patients at high risk for cardiac surgery they were all seniors their ejection fraction was low they all had low Co Q levels you know the heart cap two weeks before the surgery and at the time with a heart cath you randomized them to usual therapy or usual therapy + Co Q 100 milligrams a day two weeks before the procedure 30 days after the bypass and you monitor them various points in their course the blood coenzyme q level was low at the time of the heart cath tweaks the placebo therapy it didn't go up two weeks ago q it went up a lot this is cardiac cooling when the open-heart surgery is occurring then they finished the open-heart surgery and rewarm the heart here we have the surgical recovery room as we'll discuss later when you have open-heart surgery your heart is deprived of oxygen for several hours there's a great deal of free radical stress and you're gonna burn up your coenzyme q so with the stress of surgery you can see the coenzyme q level falls in both groups but in the supplemented group it starts out really high and doesn't fall nearly as much so at the end of surgery in a surgical coveri room the supplemented group had kokyu levels two to three times that of the untreated people if you measure the tissue coenzyme q you didn't do it at baseline at the time of the heart cath but as you begin the surgery you can show that tweaks of coenzyme q increase the amount of coenzyme q of the heart muscle the coenzyme q content of the heart muscle fell with the surgical procedure from the free radical stress reperfusion ischemia reperfusion injury didn't fall as much if you were supplemented how much ATP is in your heart remember the whole goal goal of this is to maintain high levels of ATP in the heart you can see that just two weeks of coenzyme q increased the ATP content of the heart they cruise through surgery without degrading ATP the placebo patients they're going downhill they have a successful open heart but they don't have much ATP afterwards because of the free radical stress now ejection fraction now that's all interesting biochemistry I think it's fascinating but you want to know what's it gonna do for my outcome what about my ejection fraction the ejection fraction was poor in both groups like 30 to 32 percent two weeks of placebo therapy didn't help but two weeks of coenzyme q increased their EF from 32 to 36 percent now following surgery you can see the ejection fraction Falls than the placebo therapy the bypass went well but because of the stress of the surgery the free radical stress their ejection fractions were poor they're gonna struggle in the surgical ICU look what happened with the coenzyme q patients they respond to reoxygenate like gangbusters we're get off we have a lot of coke q we're gonna make a lot of ATP our ejection fraction rises to 42% which group is going to do better in the placebo group complicated course all needed considerable and sustained inotropic support drugs to whip the heart in short a balloon pump was needed for severe heart failure in for free went into kidney 30 to dialysis a rhythm was frequent recovery over 15 to 30 days to die to pump failure in the co q group uncomplicated recovery arrhythmia and frequent no balloon pumped no dialysis no deaths which group would you want to be in I would say Co Q but you can say well it was a small study and it was done in Europeans so it doesn't count so here's the study from North America 122 patients scheduled for bypass tweaks before randomized to placebo or Co Q 3 interval grams a day at surgery you're gonna remove heart muscle and look at various metabolic parameters and what you find in the supplemented patients there's more coenzyme q in their myocardium and there's more in the mitochondria that's really where it's working so you take it it gets into the heart it gets into the furnaces of the cell where you're doing your electron transport mitochondrial respiratory efficiency and an index of the ability of the mitochondria to generate energy was better in the Co Q patients troponin release when the heart is under strain from a heart attack or unstable and open heart surgery the cell membranes can rupture as they die and they leak troponin so if we see a hyper troponin level in your blood that's a bad sign it means the cells are dying off and it was a lot higher in the placebo group they looked at the ability of the heart cells the rate at which they would recover they're squeezing ability it was better in Co Q the length of stay in the ICU was shaved from one point seven to one point four days length of stay in the hospital was shaved by a full day coenzyme q is not expensive it improves your outcome and it gets you out of the hospital a day earlier you'd think that the hospital's we want to give you coenzyme q they get you out a day earlier they're gonna make a lot more money we want you to be on coenzyme q we're not too concerned about how many days you spend on the hospital we like this idea of you coming through surgery with a better ejection fraction not eating balloon pump and dialysis and not dying so we'll recommend coenzyme q let's look a fact of coke q on oxidative stress blood pressure and insulin and sensitivity people with unstable corny disease 60 middle-aged patients with high blood pressure with the cute corny aziz on stay Blanche and a small heart attack all receive standard drug therapy diet and lifestyle you're going to randomize them to placebo or Coke you thirty milligrams in the gel form you're going to reevaluate at eight weeks vitamin e levels and vitamin C levels rise with placebo therapy as you get farther out from the unstable Angela there's a lot of free radical stress so as you have a chance to recover your E&C levels will rise they rise a lot more in the kokyu group now we're not giving you ENC but we're giving you coke you a powerful antioxidant to squash the free radicals so if they don't degrade your own E&C so the levels rise now on dialysis a marker of free radical stress the bad guys are winning it fell a lot more with koku so it's a powerful antioxidant systolic blood pressure fell from 168 to 153 nothing happened with placebo diastolic blood pressure fell with coke you not with placebo your blood sugar levels the fasting sugar was 140 at baseline and after eight weeks of placebo it fell to 129 after eight weeks of koku it was 94 post-meal sugar also fell more insulin levels if you have a high insulin level it means you have insulin insensitivity basically the mechanism of type 2 diabetes when you're under oxidative stress from an acute Corney event you may have some insulin resistance insulin levels didn't fail minimally um with placebo therapy they fell a lot more with Co Q and the insulin the glucose ratio a marker of insulin and sensitivity improved more with Co Q so we're getting a lot of metabolic benefits of coenzyme q outside of the heart itself triglycerides fell HDL went up coenzyme q and kidney failure you know it's great for the heart I think we've established that the kidney is an energy intensive Oregon it's going to make a lot of ATP will the kidney under strain be low in Coke you will supplementation be evaluated as in the heart kidney dysfunction is a surge with free radical stress an toxin deficiency and Athiya dysfunction cardiovascular disease antioxidants protect against kidney dysfunction due to x-ray dye we talked about vitamin C and an acetylcysteine vitamin e in the space study decreases cardiac event rate progression or renal insufficiency we'll talk about tissues of gace inhibitors at a later talk will coenzyme q help we're gonna take 21 patients with end-stage kidney disease there cracking was 9 or above that's very high normals up to 1.5 they were all on dialysis or advised to begin dialysis soon they've been stable for 4 weeks you randomized them to get coenzyme q in the gel form 180 milligrams a day or placebo and you evaluate at baseline and at 4 weeks and what you see vitamin E and vitamin C levels rise with coke you because you're sparing your squash and free radicals maladye alibi'd the bad marker false so there's less free radical stress be awaiting creatinine are the laboratory parameters we use to gauge kidney function the higher the Vianney creating the worse your kidneys a normal buin is about 25 it was in the mid 80s tonight he's in both groups pretreatment with SIBO therapy didn't do much it fell to 46 with Co Q creatinine fell from 11 to 5.1 it fell by 50% cratan clearance is our most precise measure of kidney function it should be a hundred it was about 10% at baseline placebo did nothing it tripled with Co Q so kidney function tripled with Co Q urine output improved percent of patients requiring dialysis basically 70 percent at baseline four weeks of placebo therapy 90 percent of them needed dialysis four weeks of coenzyme q the requirement for dialysis fell from 73 percent of the patients to 36 percent of the patients it works as well in the heart and the kidney as it does in the heart improving outcome following heart attack 144 heart attack patients all get standard medical therapy randomize them to Co Q 120 milligrams a year z-bo reevaluated 28 days and it one year double-blind protocol followed so there could be no bias at 28 days 28 percent of the patients on control therapy had recurrent angina a bad sign it means you're at risk for more trouble only 10% of those with kokyu you can see the frequency of heart failure low ejection fraction arrhythmia were blunted non-fatal heart attack Falls from 18 to 7 percent fatal heart attack Falls sudden death Falls cardiovascular death Falls from 13 to 8 percent total events in the first 28 days Falls by 50% from 31 to 15 percent so 16 out of a hundred people who were supposed to have an adverse event were spared with coenzyme q what about it one year one year out from the heart attack 25 percent of those on placebo therapy has sustained on another heart attack only 14 percent with Col Q same relationship with fatal heart attack sudden death stroke need for revascularization what about side effects because all of our drugs can have side effects will coenzyme q cause side effects they a little bit of nausea some people have a little bit of trouble taking in coenzyme q fatigue was worse than the controls than the coenzyme q because your fatigue will be lessened with co q because your heart and your muscles and your kidney and your brain are working better event rate at one year death was 20% with placebo 11 percent with coenzyme q total events 48 percent with placebo 25 percent with coins I'm Q so nine out of a hundred people that should have died in their first year post heart attack were spared with coenzyme q if a drug did this it would be a huge blockbuster there be ads on TV but because coenzyme q did this nobody wants to talk to you about it coins mq and Parkinson disease I'm treating patients with Parkinson disease with my Mme machine so I'm studying Parkinson's disease and learning all I can about it it's a degenerative neurological disorder social with tremor slowness of movement muscular rigid kind of you have a blank face you have trouble with motion it affects a 1% of seniors in the United States the problem is loss of the neurons that make dopamine a neurotransmitter of the substantia that's near the brain that coordinates fine motion um there's a problem with electron transport they're not making enough energy you have below normal blood and platelet kokyu levels um Parkinson's disease is due to free radical damage of these neurons in the substantia and there's a lack of glutathione that key antioxidant has been used up there is a street drug called mptp that becomes a free radical that can go to the substantia and blow it away that's how young people can present with Parkinson disease as a side effect of the street drug but with everyone else it's due to chronic free radical stress damage of the neurons depletion of glutathione in the substantia now they have faulty electron transport so could kokyu an electron transporter be a value here IV glutathione helps external counter pulsation which improves blood supply to the brain it has an types of effect may help people with Parkinson's Co Q supplementation increases blood platelet and brain Co Q levels could Co Q help in Parkinson's here we're gonna take a tee middle-aged subjects with early Parkinson's none are put on antioxidants none are on anti Parkinson's drugs you do a baseline assessment the you PDR S which is the United Parkinson's disease registry scale and you randomized them to receive Co Q 300 milligrams a day 600 milligrams 1200 or placebo I'll get a multivitamin and vitamin E so and again the ease going to work better with the Co Q and you follow them for 16 months it's a multicenter randomized double-blind protocol and you find you want to have a low score and you can see compared to placebo the high dose scope few patients did well in the total score in activities of daily living in motor function and in mental function so coenzyme q was a value in these in seniors with Parkinson's disease why it's an antioxidant it helps repair and sustain cell membranes it spares other antioxidants it helps regenerate glutathione there's probably other benefits but high-dose kokyu is a value in Parkinson's glutathione is value in parkinson's external counterpulsation appears to be helpful and we'll be treating patients with mme which we'll talk about in a couple weeks so on Co Q significant benefit an antigen a heart fair cutting out the kidney disease statin toxicity Parkinson's disease hypertrophic cardiomyopathy which we didn't talk about clearly improves your outcome following a heart attack or open heart surgery moderate benefit and BP control it is helpful in mitral valve prolapse migraine weight loss helps you with weight loss fatigue state and it's good for athletic performance how do you take kokyu it's in powder or tablet form but it's not well absorbed it's fat soluble so if you're taken in tablet or powder form take it with food or take it with some butter or something like that its absorbed better now the the nutritional companies have come out with coenzyme q in oil a coenzyme q gel and it's better absorb that way idebenone is is a modification of coenzyme Q such that it cannot be oxidized we're going to be switching to idebenone the patent to manufacture coenzyme q is held by companies in Japan we're not allowed to make coke q here co q has been a drug in Japan it just went over the counter the Japanese population is buying up all the co q for themselves our prices are going up idebenone can be made in North America it's probably just as good if not better than Co Q and it's a lot cheaper so we're gonna be I think the benefits of Co Q you can achieve with idebenone as well how do we generate energy in ourselves aerobic glucose metabolism burning sugar in the presence of oxygen makes 36 ATP packets in the absence of oxygen we have to ferment this sugar it's called anaerobic glycolysis you only get two ATP's now that's that's not as good as 36 ATP's but it's better than dying so Mother Nature gave us this so we can generate energy to some degree in the absence of oxygen the heart and the exercising skeletal muscles want to burn fatty acids and we we can only burn fatty acids in the presence of oxygen in the absence of oxygen we cannot generate energy from fatty acids fatty acids and oxygen excess energy all we need for the heart and exercising muscle now how do we burn fatty acids and and the glucose molecules well first of all you know we if we take in the sugar and fat in our diet it'll enter the cells of our heart but that's not where they're burned they're burned in the mitochondria the furnace so fatty acids can't get into the mitochondria these long chains of carbon so we used the carnitine shuttle we bind carnitine to a fatty acid to make a fatty acid carnitine complex that is then shuttled into the mitochondria the fatty acid and the carnitine split we we then split the fatty acid into two carbon groups called acetyl groups and we attached them to Co a and we run them through a cycle through which we strip off the electrons and transport the electrons in the electron transport chain coke Q works here and we generate energy the six carbon glucose molecule is split down to these two carbon acetyl groups they bind a co way to make acetyl co a and we strip off the electrons in a process to requires oxygen what happens when there's no oxygen when oxygen levels in the heart fall they don't have to follow the zero but when they begin to fall we will stop burning acetyl co a acetyl co a is not allowed into the energy extraction cycle and the ratio in the mitochondria of acetyl co a to free co a Rises that's a sign that we're not burning the sugar and fat properly in the presence of oxygen that that ratio the highest seed Okoye to freak away ratio shuts off all the enzymes that are used to burn sugar and fat in the presence of oxygen and it shuts off those enzymes prematurely even when there's still a little bit of oxygen left this is kind of a fault of mother nature but not really why do did Mother Nature give us the ability to ferment glucose and make those two lousy ATP's well because to keep us from dying if we fell into the bottom of the lake and we had some trouble swimming up rather than dying you know because we can't make the 36 ATP's were allowed to ferment glucose and make enough ATP to keep us from dying until we could swim to the surface or if we're running away from a saber-toothed tiger and we go beyond our aerobic range well we can ferment some sugar to maybe get a few more steps and get back into our cave this is an emergency fallback now mother nature your wisdom was saying if there's not enough oxygen around let's not waste energy activating the enzymes that would use oxygen we're going to turn them off and turn on the fermentation enzymes that makes sense well this this works well when you're running away from a saber-toothed tiger or you're swimming up from the bottom of the lake but see mother nature never planned on the situation where only one segment of our body would be oxygen deficient she never planned on having a coronary artery block or having an artery of the brain block okay so the switch is set too tightly so even though there's some oxygen left in the heart in the brain because Mother Nature didn't plan on this that a CO CO a dacoit ratio rises and we shut down prematurely so we may die prematurely or we'll stop exercising prematurely because there's some oxygen there we can't use it because of a high acetyl co a de cuéllar a show now carnitine combined to seal groups lowering the ratio so you have too much acetyl co a you got carnitine as a buffer it forms the cetyl carnitine and freako a the acetyl co a to free Co a ratio Falls and you can turn on the end times that we'll use that oxygen so you don't have enough box you don't have a lot of oxygen there you got some if there's plenty of carnitine you can use those last few oxygen molecules and keep making ATP so you can walk farther you're less likely at pain you're less likely to die but you got to have carnitine what are the consequences of recurrent or severe reductions in blood and oxygen supply high-yield fatty acid and efficient aerobic glucose metabolism ceases ceases prematurely even if some oxygen remains so we start fermenting glucose and that causes acidosis fatty acids aren't burned they accumulate within the cells now the carnitine tries to buy them but you run out of carnitine the fatty acids spill out damage the other cells and all of your carnitine is wasted lining up the fatty acids so if you have a lot of carnitine you're more likely to survive this but this process of recurrent oxygen deficiency waste your carnitine so people who just like coenzyme q people with strained heart some need carnitine the most have the least amount so how are we going to deal with this problem we've talked about improving oxygen supply we talked about decreasing the demand for ATP and we've talked now about improving the efficiency of oxygen utilization kokyu to tune up mitochondria ATP production carnitine lowers the acetyl quite a freak wave ratio promoting the preservation of high yield aerobic energy metabolism even at a low oxygen environment carnitine delays the switch to inefficient low-heeled oxygen independent anaerobic metabolism allows you to use the flash the washes and molecules better and longer so we have studies the same as coenzyme q showing benefits and Corning's ease improving outcome following heart attack heart failure claim off of the claudication blood flow problems with legs is lowers your lipoprotein your triglycerides good and cardiogenic shock improves outcome following a heart attack just as in coenzyme q the more severe your cardiac impairment the lower will be the amount of carnitine in your heart carnitine stores will reduced 50% in cardiomyopathy 80% in acute alcohol or toxic heart diseases carnitine stores are reduced in patients with chronic Corney disease they're extremely low in muscle involved in a heart attack their intermediate values in the border zone there'll be higher content in a normally oxygenated zone can we use carnitine then to treat angina logically we should be able to for studies of carnitine with atrial pacing we've put a pacemaker into your heart and we crank up the rate so you're going to need more ATP energy if you have a blocked artery you don't have enough oxygen you can't make ATP we'll see that you'll get a enough when we get your heart rate up 225 then we repeat the study after giving you carnitine and you'll find you can crank the heart rate up a lot higher before the patient has angina because you're you can help them handle the low oxygen environment the increased demand for ATP how about carnitine and treadmill performance 900 milligrams a quarantine or placebo for 12 weeks and patients with stable angina placebo did nothing total exercise time increased by 12% from eleven point four to twelve point eight minutes another minute coke Q gives you a minute carnitine tends to give you a minute time to ST depression improved by 37% propionyl carnitine is used in Europe propionic acid is part of the it's a co fat it's another cofactor in the in the in what's called the krebs cycle that we use to generate energy and they use it in Europe it's a patented drug 1500 milligrams for two weeks in stable angina patients total work capacity increases by 17 percent exercise time by 10 percent time to ST segment depression by 14 percent carnitine and claudication leg cramping due to poor blood flow to the legs same situation is in the heart you're not making enough ATP would carnitine help 4 grams a day versus placebo for 3 extend claw Decatur's aerobic metabolism was preserved a prolonged absolute walking distance improved by 75% for 174 to 306 meters you don't care about your biochemistry I think it's pretty cool but you care that you can walk twice as far on carnitine because you can still make ATP in a low-oxygen environment carnitine and heart failure hunting levels are oppressed in cardiomyopathy heart failure patients carnitine prevents heart muscle damage in animal models of cardiomyopathy heart failure here we have patients with class two two for heart failure treated with placebo which did nothing or Quora carnitine 900 milligrams a day for eight weeks 55 percent improved by at least one functional class ejection fraction rose and 44 percent shortness of breath with effort was relieved in 44 percent edema resolved in a third overall 66 percent improved here's another study of propionyl carnitine versus placebo and mild to moderate heart failure ejection fraction rose treadmill time improved symptoms improved carnitine in dilated cardiomyopathy mustard history of the heart this study was done in Italy 70 patients with advanced dilated cardiomyopathy class 3 to 4 they're having symptoms at rest or walking up maybe a flight of stairs and they had pure cardiomyopathies they didn't have alcohol toxicity on valve your disease or blocked arteries you're treating them all with the standard drugs digoxin diuretics ACE inhibitors none were on antiarrhythmic drugs you randomized them to receive placebo or carnitine 2,000 milligrams a day in a blinded format over three months than in an open format atrial fib flutter is an is a cardiac arrhythmia which we don't like to see it'll reduce your cardiac function by 20% if you have a normal heart by 40% if you have a weak heart like these people in the placebo group 21 percent developed atrial fibrillation only 2% of those on carnitine developed atrial fibrillation so 7 or 33 of the placebo patients develop cardiovert only 2 responded to medical or electrical cardioversion one of the quarantine patients developed atrial flutter and he responded a cardioversion so is protective against atrial arrhythmias mortality rate 16% with placebo 2% with carnitine the patients in placebo therapy died suddenly or from congestive heart failure only one of the carnitine patients died from arrhythmia so symptoms improve less likely to ever yeah and you're less likely to die if you take carnitine so we've covered a number of the studies I'd like to focus on carnitine improving outcome following heart attack 160 patients consecutive patients admitted to the hospital with a heart attack at the time of discharge randomize them to receive for a year for grams a day at carnitine or placebo otherwise the same care reevaluate at one year now if you look at the current team versus placebo patients one year later they had lower heart rate blood pressure and cholesterol and Jen arrhythmia less frequent in the placebo patients the one-year mortality rate was 12.5% they died of heart failure recurrent heart attack only one of the carnitine patients died and he had a blood clot to the leg wow that's like a thousandfold reduction in one-year mortality by taking carnitine but it was done in Europeans so it doesn't count of course um here's another study you get 56 patients with an acute heart attack and you're gonna give them an IV carnitine or placebo for three days the number of PVCs an hour fell in the placebo patients fell a lot more with carnitine couplets which is two PVCs in a row which we don't like to see fell a lot more with carnitine episodes of ventricular tachycardia a sustained arrhythmia which is which is potentially lethal fell a lot more in carnitine hours with tachycardia fell a lot more so it has an anti rhythmic effect why by preserving heart muscle and improving energy metabolism we don't like to see a heart attack expand if you have a significant heart attack and that area is dead if it's mush it'll expand out and begin to form an aneurysm and that will kind of jerk the remaining heart segments out of sync and give you a mechanical disadvantage it increases your risk of congestive heart failure so we'll quarantine prevent infarct expansion by preserving heart cells here we're gonna take four to 72 patients with heart attacks involving the front wall the heart you do an echo in the emergency room you randomized them to sick grams a day of carnitine versus the sea over a year at the time of hospital discharge on tapas placebo here's carnitine here's the end diastolic volume here's the end systolic volume of the heart at the time of hospital discharge you can already see that in placebo patients their hearts have enlarged more than the carnitine and then over the course of a year they continue to enlarge a lot more than the carnitine so the carnitine is an anti rhythmic and it prevents infarct expansion and then we have another modern-day study 101 consecutive patients with suspected heart attack 80% had a full-thickness heart attack all receive standard medical therapy randomized to placebo or carnitine 2,000 milligrams a day reevaluate at four weeks and you the same basic story with antioxidants and coenzyme q lipid peroxides fall LDH is an enzyme that is leaked out the higher your LDH the more damage it was lower in the carnitine patients CPK is also leaked as a marker like troponin of heart muscle damage it was lower in the in the quarantine patients the QRS score which reflects the electrocardiographic manifestations of a heart attack was lower with carnitine so carnitine just like antioxidants and coenzyme q appears to reduce the size of your heart attack as evidenced by better look at EKGs less release of the enzymes and of course that's fascinating to me biochemically you want to know what effect does that have on outcome at 28 days recurrent angina 36% 12% less heart failure less pump dysfunction less arrhythmia non-fatal recurrent heart attack Falls from 14 to 8 percent cardiovascular death from 12 to 8 percent total events from 26 to 16% similar to coenzyme q um no one has done a study giving humans carnitine and coins I'm Q together with a heart attack and you think that would be a good study to do it just hasn't been done there was a study in rats where they would like one artery and cause an experimental heart attack and they found that it with no pretreatment it takes six minutes to recover and your functions 80% of normal and there's very low ATP if you pretreat with coenzyme Q or carnitine there's a better recovery if you treat with coenzyme Q and carnitine ATP reduction ATP production is not affected adversely carnitine and you know we talked about coins thank you for the heart it also helps the brain it helps the kidney will Conaty new the same actually most of our carnitine is made in the kidney so if you have kidney dysfunction you're not going to have enough carnitine elsewhere in your body 24 patients on dialysis one of the problems with kidney failure is your hemoglobin will fall there's a hormone called erythropoietin that is made in the kidney that tells the bone marrow to make more red blood cells kidneys failing northropi eaten the bone marrow doesn't work and your him a little below so let's see if carnitine will help we're gonna measure the baseline hematocrit a measure of your red count randomized them to receive we're going to your placebo or carnitine 1.6 grams a day and then you follow them and here's the hematocrit in the placebo patients here it is in the carnitine they were making more red cells the hematocrit here in the placebo patients and it's rising so they needed fewer red cell transfusions they needed fewer injections of other pollutant saving a whole lot of money so what works at the heart and it works in the kidney benefits of carnitine reduce the symptoms improves functional status and Anjan claudication decrease the symptoms and increases ejection fraction and exercise time of heart failure it improves the outlook in cardiogenic shock i didn't show you that study improved functional status decreases mortality following heart attack in a patient's cardiomyopathy helps preserve the red cell mass and patient of the kidney failure reduces heart muscle damage an experimental heart attack this likely will hold true with humans and when my patients have heart attacks i always give them coenzyme q n carnitine because i want them to get through this with a high level of ATP because I know that ATP is the only source of energy for the heart and it the ATP level begins to falter one by one critical biochemical reactions will fail and you know if if we can't make ATP you only got ten seconds right and then we've got 20 seconds of fossil creatinine and then we can you know we can we if we have enough oxygen we can burn sugar and fat in the mitochondria make a lot of ATP or failing that we can ferment glucose but let's say we run through all these and we run out of ATP and we got to make it from scratch that is a disaster we were not designed to make ATP from scratch de novo ATP synthesis is a slow and metabolically expensive process it takes nine ATP's to regenerate a new one that's not very good economics and it's a slow process and if we had to regenerate all the ATP in the heart it would take us a hundred days so we don't want to have to make ATP from scratch and we typically don't need to because a cheapy is a renewable energy source when oxygen calories and cofactors are available we have ATP we split off a phosphorous group to make ADP adenosine diphosphate and then we burn some sugar or fat in the presence of oxygen we harness that energy and use that to tack the third phosphate group back onto ADP to make more ATP and we're gonna recycle each of our ATP's I think seventy thousand times a day that is if we have caloric fuel and oxygen when oxygen is not available such as in heart disease or you know running running from marathon to Sparta or running away from a saber-toothed tiger well we split the ATP to get our work done we have ADP and phosphate ADP phosphate no energy we can't make more ATP oh we got a problem here the clock is ticking now we've got only ten seconds left of ATP what happens after that remember phospho creatinine can store a high energy phosphoryl bond phospho crash he will give up a phosphate to ADP to make more ATP that gives us 20 seconds okay well then we're out you know and we can't there's no oxygen to make anymore so what I'm going to do there's a little bit of energy in ADP between the first and second phosphates so two ATP's will combine to make an ATP and an AM piano C mono phosphate so we get a little bit of that eventually though we're gonna split off the final phosphate from AD no see mono festivais to make AD no see now ATP ATP and AM P are charged particles they cannot diffuse out of the cell adenine does not have a charge it doesn't have a phosphate it will diffuse out of the cell never to return so if we burn our ATP down to ad no seen that substrate that building block will be lost from the cell forever but let's say oxygen is resupplied you come to the hospital with your heart attack and we open up your artery and weari supply you with oxygen or the surgeon takes finishes your bypass surgery and reawakens your heart ah we've got plenty of oxygen the mitochondria are still intact we're gonna burn sugar and fat the problem is we don't have any ADP to e phosphorylate recovery of the oxygenation recovery of oxidative phosphorylation not coupled with adp re phosphorylation to ATP gives you nothing and this explains what's called myocardial stunning ischemic stress depletes ATP and the total adenine nucleotide pool we go from ATP to ADP ATP to a.m. P and P goes to ad no seen or these other Khattab lights that leave the cell never to return so each time you have an episode of chest pain you're going to lose a certain percentage of your addy nucleotide pool and it's gone forever well then how come you don't die after so many episodes of angina how do you eventually recover if losing the adne nucleotide pool mother nature must have given us a way of regenerating it and she has and we'll talk about it this is the amount of ATP in your cell as a function of hours of oxygen deprivation this could be a myocardial cell in a petri dish an animal heart subjected to global hypoxia or a segment of your heart supply by a blocked artery over time the ATP content falls off early on the ATP Rises because you can't be phosphorylated then two ATP's combined to make an ATP and a MP so it falls amp e rises and falls in the insect you see the the percentage of the ADI nucleotide pool your building blocks that is burned down to add no seemed to be lost forever here we're gonna see this is oxygen deprivation and at one hour we reopen the artery we supply oxygen it takes a while to get your ATP level back to baseline your new steady states going to be below your healthy baseline the difference is the percentage to add you nucleotide pool that was lost never returned the longer you go without oxygen the greater the percentage of the adenine nucleotide building blocks that are lost the more difficult it will be to regenerate your ATP the loire will be you knew steady-state these cells may not be dead but they're not functioning well because they can't make ATP because they ran out of the adenine nucleotide building blocks so what can we do about this well we can generate ATP anew this is called the de novo synthetic pathway the heart was not designed to make ATP from scratch we weren't designed to have heart disease mother nature didn't anticipate it so this pathway is not highly expressed in the heart you start with ribose a five-carbon sugar it's not present on our diet so we have to convert glucose to six carbon sugar into ribose that takes energy so we get this ribose we tack on two phosphate groups and then we have to build this adenine ring step by step this is a very very very slow process to regenerate all the ATP in the heart from would take a hundred days and it takes 980 PS to make a new building block and if you're in the ICU suffering you don't have any extra energy to spare so this de novo synthetic pathway doesn't work very well for the patient in crisis mother nature though gave us a break if we could get ribose into the cell and if you take ribose or Li or IV we can get it into the heart cells very quickly the ribose will bind to these phosphate groups that are hanging around and you can find some of these Khattab lights and make a MP so the minute you're burning the ADP down to add no seen you can rapidly recycle it if you get ribose from the cell so the minute the oxygen is resupplied and you get good oxidative phosphorylation you can couple that with useful ATP regeneration okay so you're if we open up the artery and resupply you with oxygen your heart will will not be able to use that oxygen to make ATP energy because you burned off the building blocks if we give you ribose you can regenerate your building blocks just like that so the minute we improve your oxygen supply you will respond by making ATP and your heart function will return to normal rapidly this will block stunning if you take an animal let's say you take a dog and you put them on cardiopulmonary bypass so the heart is excised from the rest of the circulation the rest of the organs are being perfused artificially and you shut off the oxygen supply to that heart for 20 minutes that's not long enough to kill the cells but during that 20 minutes of oxygen deprivation all the ATP or a lot of its gonna be burned down to add no seen lost forever okay so you've you depleted the adenine nucleotide pool of the building blocks now you reoxygenate the heart after 20 minutes okay your can generate you know you're supposed to be able to generate energy from sugar and fat you don't have an adenine nucleotide pool so you can see you're still not making ATP at four hours then if you take another group of animals and you put ribose you give them IV ribose so they can rapidly recycle their any nucleotides you reoxygenate them they're making ATP and this will correlate with the more rapid recovery of heart pumping function and diastolic dysfunction following this experimental heart attack in animals well that's kind of interesting what about in humans think about on pump open-heart surgery many of you have probably had open-heart surgery during open-heart surgery your heart is excluded from the rest of the circulation and your brain and your kidney the rest of your body is perfused with the bubble pump oxygenator now the surgeons can't operate on a beating heart so your heart is arrested so it's still and it's getting no oxygen the arteries serving the heart are clamped now when this occurs the heart cells cannot regenerate their ATP and they're gonna burn it all down to ADP A&P add no scene and it's gonna be lost why doesn't the heart dive and during open-heart surgery well because it's arrested it doesn't need as much ATP and oxygen and they put it on ice they freeze it they kind of put your heart in suspended animation that's why the heart doesn't die now if the surgery if the surgery goes too long like eight hours some of the heart muscle will die that's why the surgeons are always in a hurry they do their work and they get out of there because the longer the surgery goes on the greater percentage of the ADI nucleotide pool that will be lost from from the heart okay well they completed their surgery they've done their best to protect the heart keep the adenine nucleotide pool from being depleted but still it is okay they take you off the pump they restart your heart they warm up the heart they restart it they open up these bypass grafts and this is great your problem was not enough oxygenated blood now you've got a brand new blood supply all the oxygen you want your mitochondria are gonna take that oxygen and burn sugar and fat and generate energy and manage your heart going to work well it's not gonna work well because you don't have any agni nucleotides to reef on sporulate so following open-heart surgery even successful open-heart surgery you will struggle you will be in congestive heart failure all the time you will need diuretics to mobilize fluid you may need artificial support you'll need that artificial support until your heart can generate the adenine nucleotide pool again and it does a very that's very very slowly so you'll spend a few days in the ICU what if you give patients ribose here took a bunch of patients with bad pumps scheduled for valve replacement or bypass at the time at the beginning of surgery when they Claus cramp the aorta and begin to choke the cut off the oxygen supply the heart one group got dextrose as a placebo the other group got ribose 70 grams a day then they all have open heart surgery a week after the open heart you repeat their nuclear scan of heart pump function to look at their ejection fraction you'd think a week after the surgery your ejection fraction ought to be a lot higher but 80% of the patients in the control group their ejection fraction was still 15% below baseline they certainly had not recovered only 20% of those on ribose still had pump dysfunction they recovered pump function more rapidly because they were able to use that oxygen and make more ATP because you would regenerate their ante nucleotide pool so if everybody who go undergoes open heart gets ribose they would do a lot better what about in everyday Cornie disease here let's look at ribose and exercise induced ischemia 20 men with stable but severe corny disease they all had abnormal stress tests with angina at about nine minutes you know a maximal stress EKG on day one you do another stress EKG on day two why do you the stress test two days in a row to create a scheme yep and you're gonna burn off some of their adenine nucleotide pool why do you guys sometimes feel rotten for a week after a stress test because when I pushed you like that I burned off your adenine nucleotide pool it takes you a week to make more so they burned down their adenine nucleotide pool randomized them to get three days of rooibos 15 grams four times a day or a dextrose placebo repeat the stress EKG on day five see who's gonna do better time to moderate an shoulda improved by 25 seconds with placebo and that was not statistically significant it improved more 43 percent with ribose and that was statistically significant it's not overly impressive but time to ST segment depression a more objective marker of when ATP is deficient did not change with placebo it increased by our familiar minute with ribose Kopu gives you a minute ribose gives you a minute carnitine you zoom in it so that would translate to better physical functioning in the cornea patient if they take ribose ribose and heart failure 15 patients with advanced heart failure on the basis of multiple mild cardi infarctions from corny disease average ejection fractions 47% randomized to receive over three weeks ribose 15 grams today or dextrose placebo and then you re-evaluate looking at echo measures of diastolic function similar than the statin study the EU a deceleration time atrial contribution electrical feeling improved with ribose but not with placebo left atrial volume though the atria primes the left ventricle the pump the left atria got smaller why did the left atrium get smaller because the the left atrial pressure fell why did the left atrial pressure fall the pressure within the left ventricle fell why did the pressure in the left ventricle fall because the left ventricle became more elastic it relaxed better because it had more ATP and you need ATP for your heart to relax so your heart's gonna feel better and then you would predict those patients would feel better and they did quality of life physical functioning score improved with ribose but not with placebo and you could extrapolate this to all causes of congestive heart failure similar biology so what are the other documented benefits of ribose it accelerates the reconstitution of muscle ATP following exercise enhance the strength and endurance gained with weight training reduce free radical stress with an aerobic exercise improved detection of the schema c'mon car diem there's the benefit in fibromyalgia fibromyalgia is small vessel ischemia to the muscles not enough ATP bank platelets are better preserved and there's a bunch of predicted benefits from ribose these studies haven't been done yet but when they're done they'll show what I think they'll show better outcome after heart attack better outcome after bypass etc whenever post ischemic HEV deficiency is the culprit whenever there's not enough ATP being made because of lack of oxygen or if you push yourself beyond your aerobic threshold and you you you set you start you have to then ferment glucose to make lactic acid if you push yourself farther the mother nature intended wise people to push yourselves you will suffer from ATP deficiency I will give you an example of someone in a severely ATP deficient state this is me at the 26 mile mark of the Cincinnati Flying Pig marathon I was really hurting I wasn't making enough ATP but actually what I did I sipped ribose throughout the race in my water because I knew that would help me reconstitute my ATP and it allowed me to finish the marathon so I can give all the credit to ribose I work pretty hard too but it makes a nice story doesn't it turning six you patients with advanced heart tear on standard drug therapy randomized them to taurine two grams three times their placebo and placebo had no effect on symptoms whereas shortness of breath palpitations crackle heart size did improve with tari so timing is helpful in heart failure New York Heart Association functional class improved in 28% on tiring only 10% on placebo physician assessment also showed that adding taurine in helped why should Terry work it's the most abundant free Emil acid in the heart it is concentrated in the heart muscle plasma at a ratio of two hundred to one it has a positive inotropic effect it helps the heart squeeze better it enhances the positive inotropic effect of a drug digitalis and it protects the heart from digitalis toxicity it's a ditch talus buffer it protects the heart when there's not enough calcium but it also protects the heart when there's too much calcium it's a calcium buffer it's involved in magnesium homeostasis if you don't have enough tari you can't hold on your magnesium you got a lot of tarring you'll hold on your magnesium it it has a beneficial effect on endothelial function it activates nitric oxide synthase which we'll talk about tar levels rise and the heart under strain but just like coenzyme q + carnitine in the ADI nucleotide pool it's lowered in the oxygen deprived target let's look at tarring + Co Q in post mi outcome 51 the corner cave care patients with suspected heart attack I'll receive standard therapy randomized at a dattari 6 grams a day in coking 120 milligrams a day or placebo fall for 28 days and basically it's the same story as an hour prior of in the coenzyme q in the carnitine Mallen dialdehyde a marker free radical stress falls e and c are spared CPK there's less CPK leak the QRS looks better so it looks like they're having smaller heart attacks complication of event rate at 28 days again there's there's fewer complications and events at 28 days total complications 81% with placebo 24% with Co Q and karna team death and repeat heart attack Falls from 31 to 12% so tari is a big winner arginine if we're gonna spend two sessions on our gene endothelial function I'll just summarize here our gene improves or restores endothelial function it will neutralize any risk factor that wants to damage the endothelium it is the universal antidote to anything that causes a no Thea dysfunction in Corney patients symptoms improved in heart failure patients they improve their objection fraction rises claw Decatur's do better in experimental atherosclerosis it protects the it's plaque build up does a better job than statins Pali Coast and all is a sugarcane extract it is a primary therapy in Cuba because it's very very inexpensive and Pali Coast all will improve lipid values lowers blood pressure blocks platelet aggregation has an antioxidant effect blunts abnormal smooth muscle proliferation protects the endothelium and that's a different lecture on them on the use of poly coastal and prevention we're talking about the use of poly tonight poly Co so in treatment of advanced cardiovascular disease and I'm going to show you that it improves blood flow parameters in patients with cerebral vascular disease increases walking parameters and claw Decatur's improves nuclear stress studies and cornea patients decreases event rate and asymptomatic patients decreases event rate in patients with known cardiovascular disease here let's look at pali coast on people with plugged blood vessels of their brain people with cerebral vascular disease 22 subjects with admirable ultrasound studies you do the baseline assessment put them on a low-fat diet randomize them to pali coast and all five milligrams twice a day or matching placebo reevaluate in one year and it was a double blinded protocol now effect on lipids placebo therapy didn't do much their triglycerides rose by 31 percent they rose on pali coast small but not as much cholesterol and LDL fell HDL went up on pali coast and all desirable effects carotid arteries 46 percent of the patients demonstrated an improvement a regression of disease in their carotid arteries only 18 percent of those on placebo 36 percent some of those on placebo showed progression in one artery only nine percent on poly Kosan all those are the carotid arteries serving the front of the heart same situation the vertebral arteries serving the back of the heart or a composite so in in placebo there was more disease progression in the pali coast of all group there was a net lessening in the amount of plaque certainly a good idea Polly costal intermittent claudication poor blood the legs 50 subjects with staple claudication on their ankle brachial ratio was 0.5 to 0.9 1 is normal if it's 0.5 that means blood flow to the leg is 50% of normal we want to make the ankle breaker ratio go up you put them on a on an exercise program you're asking to stop smoke you put them on a standard diet you take your baseline parameters randomized to polyclonal 10 milligrams twice a day or placebo twice a day and what you find how your initial claudication distance how far you can walk before your legs start to hurt placebo didn't do a whole lot but it doubled it tripled with poly Kosan all absolute walking distance how far you could go before you had to stop through the pain not much happened with placebo they could walk a lot farther with poly Kosan all ankle brachial ratio did not change with the SIBO it improves slightly with poly Kosan all because you're opening up arteries subjective improvement in leg pain 70 percent of the patients on poly Kosan L felt that are only 10 percent of those on placebo so it sure works well but we have to ask is it safe many of the drugs that we give you have benefits but then they have side-effects we even have to ask this about nutritional therapies um let's look at safety and tolerability in the placebo group 41 percent had to quit the study 14 for administrative reasons they were leaving the area but 28 percent stopped due to an adverse event 40 percent of the subjects had some sort of adverse event for mild tense severe in the besi bo group there were two deaths two transient ischemic attacks two heart attacks one on stable angina one stroke one surgery one uncle one uncontrolled hypertension and that's the natural history of these people they're not healthy people on placebo therapy the you know a certain percentage you're gonna have events we want to make sure that the Pali Coast on all group doesn't have more events than the placebo of course to make sure it's not dangerous so let's see what happened there fifteen percent withdrew from the study all for administrative reasons 11 percent reach reported a total of four adverse events to add excess stomach acid one had trouble phone asleep one was nervous no heart attacks no strokes no deaths so obviously there's not a safety issue there it improves blood flow to the legs and resolves those symptoms but because it's improving blood flow and every artery in the body you're gonna get a better outcome on Polly Coulson one coins these 45 Corney patients all with ischemic abnormal stress perfusion studies a four-week run in period you the baseline studies randomized to receive were 20 months pali coast and all five milligrams twice a day pali coast in all and aspirin twice a day or placebo and aspirin twice a day Riya that would over 20 months now we're gonna compare your stress daily and baseline to 20 months in placebo and aspirin 64% worsened Pali Coast and all 25% worsened Pali Coast on aspirin 27% worsened only 7% of those on placebo and aspirin improved their stress family made it look better but a third of those on Pali Coast all improved 46% on Pali Coast and on at and aspirin treadmill time didn't change with aspirin alone it improved from 8.4 to 10 minutes with pali coast and all it improved even further from seven point eight to ten point two with pali coast and all and aspirin ST segment depression on the exercise EKG progressed over 20 months with aspirin alone not with poly coastal or poly coastal and aspirin ejection fraction or the the lipids with placebo and aspirin the LDL and the cholesterol went up in both Poli coastal groups that fell that makes sense ejection fraction did not change significantly with aspirin therapy from 54 to 56 percent with pali coast nought rose from 55 to 60 percent Pali Coast on aspirin 53% to 61 percent Pali Coast and I was pretty good stuff aspirin has benefits we can take both and get the best effects angina frequency fell significantly in both pali coast on pod coastal and aspirin functional class improved only in those with pali coast and on pali coast all and sprint now over the two years before the patients were enrolled in the study basically 90% of them in sustain an event they had cardiovascular disease over the 20 months of the study on 29% of those on aspirin had an event one cardiovascular death - unstable angina one develop heart failure with poly Coast and all alone 8% had an event one non-fatal heart attack Pali Coast no and aspirin no events so we can't take the best of nutritional medicine we can listen to what the drug medicine people tell us we put them together we get what we want no events so with poly coast and all benefits with lipid control and in in treating active cardiovascular disease improves blood flow parameters some patients with cerebral vascular disease increases walking parameters and claw Decatur's improve stress thallium findings and coronary patients decreases future event rate in asymptomatic subjects decreases event rate in patients with known cardiovascular disease the common goal of all physicians involved in the care of the patient with cardiovascular disease is to increase the content of ATP in the heart muscle and to improve the patient's ability to regenerate their own ATP because if the ATP level Falls one by one important chemical reactions will fall off we can deal with this problem by decreasing the demand for ATP we can mechanically improve the oxygen supply but we've talked about tonight is improving the restoring efficient mitochondrial function etc reconstitution a D nucleotide pool so you can get more miles per gallon more ATP energy particles per oxygen molecule from the option available and this bio energetic support can be added on to any drug or surgical therapy and it's going to have an additive benefit on outcome and we have some recommendations that I've taken from the literature the settings that I presented you these are the doses used in those studies for angina heart failure post bypass outcome renal insufficiency claudication hypertension cardiac fatigue and arrhythmia and improving outcome following heart attack and decreasing your likelihood of dying after a heart attack and that's all I have to stay on say on this subject thank you very much for your attention

Channel: James Roberts

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Id: oCl4kZs4kvQ

Length: 106min 49sec (6409 seconds)

Published: Thu Jan 31 2019