The Awesome Foursome

By Stephen T. Sinatra, M.D., F.A.C.C., F.A.C.N., C.N.S., C.B.T.

Targeted Supplements for the Heart

Supplementation with what I’ve nicknamed, the “awesome foursome,” is the most targeted way of sustaining your heart’s energy needs. Supplements enhance health at the cellular level and provide nutrients necessary for metabolic processes. The “awesome foursome,” consisting of coenzyme Q10 (CoQ10), L-carnitine, D-ribose, and magnesium, individually and collectively help increase energy, or ATP, production in your body by supporting mitochondria within cells.

Everyone needs a sustained and healthy pool of ATP to fuel bodily functions. Cells require large amounts of ATP to contract and relax the heart, maintain cellular ion balance, and synthesize macromolecules like proteins and fats. Your body generates ATP de novo as well as recycles it through a process called oxidative phosphorylation. A much faster process than synthesizing ATP from scratch, recycling is the preferred method of energy production. Eighty to ninety percent of ATP is recycled in the mitochondria, then released into the fluid portion of cells to be used for energy.

Mitochondria require each of the “awesome foursome” to generate ATP. While CoQ10 and L-carnitine are fundamental to the ATP recycling process, D-ribose is necessary for de novo ATP synthesis. Metaphorically, D-ribose helps fill the body’s gas tank while L-carnitine and CoQ10 help the body convert fuel to energy. Literally, D-ribose is a structural component of the ATP molecule, and L-carnitine and CoQ10 help recycle ATP by transporting fatty acids across mitochondrial membranes and shuttling electrons back and forth between enzymes, respectively. Co-Q10 then acts as an antioxidant to protect mitochondrial membranes from free-radical damage. Like a spark plug central to both processes, magnesium “turns on” the enzymes that drive the entire metabolic reaction.

Metabolic Cardiology Basics

Supplementation Helps Prevent “Revolving-Door Medicine”

Depending on the individual, supplementation with any or all of the “awesome foursome” may be the key to maintaining energy and supporting overall health. At around age forty, endogenous production of CoQ10 and L-carnitine generally starts to decrease, explaining why people commonly associate lack of energy with “middle age.”

People suffering from coronary artery disease (CAD) often can’t keep up with the heart’s energy demands. With CAD, the heart continually overworks to pump blood through inflamed and congested blood vessels and ultimately expends energy must faster than the mitochondria can produce it.

If you take pharmaceutical drugs for CVD, you should also supplement with some or all of the “awesome foursome” to prevent nutrient deficiency. Beta blockers, for example, which prove effective in stabilizing people during emergency situations and improving symptoms, inhibit the production of enzymes necessary for CoQ10 synthesis. Since their long term use can impair your ability to make ATP, adjunctive supplementation with CoQ10 can counteract pharmaceutical side effects associated with energy depletion.

Most cardiologists want to avoid practicing “revolving-door medicine,” or repeatedly seeing the same patients come in with the same life-endangering problems. To make this happen, physicians and patients need to do something which moves beyond symptoms of the disease and gets to the “heart of the matter.” Complimenting pharmaceutical treatments with nutritional supports is one way that practitioners can treat symptoms and make a real difference in the underlying pathology of illness (emotional work and stress management are additional means).

Already native to your body, any of all of the “awesome foursome” can safely and effectively be ingested in tandem with cardiac drugs like beta-blockers, calcium channel blockers, nitrates, and ACE inhibitors. Not only will taking energy-enhancing supplements help alleviate negative side effects associated with these drugs, but it might eventually reduce, or even eliminate, your need for such medication.

Please note: although drug interactions are not likely, they are possible. Always consult with your physician before adding nutraceuticals to the program if you are currently taking pharmaceutical drugs for any cardiac condition.

So Many Dietary Supplements – How Do You Choose?

In a nutshell

A healthy ATP energy pool can help keep you feeling youthful. While you can’t take ATP as a pill or vitamin, you can give your body the next best thing: substances with which it can make ATP. Supplementing with the “awesome foursome,” can help boost ATP production and support heart health. By directing nutrition to the cellular level, you can improve your quality of life, especially if you’re taking pharmaceutical medications and/or living with a cardiovascular condition.

People with heart disease often exhibit CoQ10, L-carnitine, D-ribose, and/or magnesium deficiencies. Failing hearts lack adequate energy to drive pump function. As the heart is one of the most responsive organs in the body for targeted nutritional supplementation, practicing metabolic cardiology is a must. By enhancing ATP synthesis and recycling, and promoting more efficient metabolism in mitochondria, the “awesome foursome” helps support heart health. Taking some or all of the “awesome foursome” adjunctive to pharmaceutical treatment can benefit those with a broad spectrum of cardiac conditions like angina, congestive heart failure, ventricular arrhythmia, hypertension, and high cholesterol. Patients should always consult with their physicians before adding nutritional supplements to a pharmacologic program.

Each of these nutrients plays a fundamental role in cellular metabolism, especially in supplying the heart with the energy it needs to preserve its contractile force. While each is independently effective in helping hearts work through the stress of disease, the “awesome foursome,” together, are synergistic.

For more information about the “awesome foursome” and ATP production, check out articles in the Metabolic Cardiology section, as well as my books:

© 2015 HeartMD Institute. All rights reserved.




Leave a Reply


  1. Blanche E. Baker

    on June 23, 2013 at 4:57 pm

    You may be interested to know that my cardiologist was impressed with the improvements in all my labs that he wants to know what I’m taking, and who’s advice I’m following.
    I’ve sent him copies of Health Radar articles, some quoting your comments and a list of all my “additives” from the Health Food Store.
    Inflammation has gone down from 4.5 to 1.3.

  2. Don Pacifico

    on January 5, 2014 at 4:25 pm

    Does the “awesome foursome” help with fibrotic tissue associated with Restrictive Cardiomyopathy

  3. Richard Kurylski

    on January 14, 2014 at 3:54 pm

    Dr Sinatra is always awesome. I wanted to know how CoQ10, L-carnitine and D-ribose are produced. Hope they are not synthetized. And what kind of magnesium is better absorbed because it is in a chemical compound.
    Does the “awesome foursome” help clean a calcified aortic valve that does not close properly? I heard that EDTA together with K2 (MK7) should be used. And probably L-arginine must be taken as well in order not to allow for the blood coagulation. But what doses and how should these be taken? Thank you.

  4. Magkayla Alexander

    on May 10, 2014 at 5:48 am

    Good morning DR. My son is 3-years old was born with TA stenosis, he will be do for the last procedure hopefully, and the dDoctor noticed that his tonsils are getting very big, now they want me to remove them from my son. What should I do?

  5. Richard Sherman

    on June 12, 2014 at 5:02 pm

    Hi Dr Sinatra,

    Read the book on Earthing that reminded me of the book I read 15 years ago approx on the Cholesterol myth. I now have a 100% blocked LAD artery and my Cardiologist agrees that i shouldn’t do anything but monitor it. I take supplements LysineC 1000 6x per day plus Vit C 4000 mg twice. Also Magnesium 500 mg and CoQ10 600 mg per day plus Nattokinase. My Cardiologist has me taking Livalo 1 mg , Amlodipine 2.5 and Metropolo 25mg. Now I’m not feeling as well as i did two weeks ago… Have had EKGs of normal plus CTA test showing calcification. Wanted to know if you could recommend a Cardiologist for another opinion who follows Alternatives as yourself since I see you are retired.. Thanks for all the information ..Appreciated Rich

  6. Richard Sherman

    on June 12, 2014 at 5:04 pm

    I think I don’t feel well now due to the meds.. I workout, eat well and no carbs and also do meditational practice to assist my heart. added this to clarify why i don’t feel well. Had a nuclear stress and another regular to push me to see how well and i did excellent with the blockage.. Have created two bypasses by myself . thanks again

  7. Joe

    on June 24, 2014 at 10:57 pm

    What brands are recommended for the awesome foursome and amounts per day for men and women?

  8. Judy

    on July 19, 2014 at 1:43 am

    If you are over 30 years old, you should be taking Ubiquinol (a form of CoQ10 that makes it easily bioavailable to use by the body).

  9. Christi Cisek

    on November 23, 2014 at 9:04 pm

    Curious what supplements you are taking, how much and how often you take them to reduce your inflammation. Just had my first echo at 50 as I have heart disease on both sides of my family. The stress test was perfect as was the EKG but the echo showed left ventricular inflammation. I am having heart pain daily. I just started Magnesium oil on the bottoms of my feet, am drinking more water and increased my Omega 3 and 6. I’m wondering if I should start the awesome foursome and how often to do it. Any help you could offer would be most appreciated! Thank you!

  10. David Simcho

    on June 26, 2015 at 1:51 pm

    What is a good ATP increase over a 30 day period.

  11. Patricia Canova McNeer

    on August 16, 2017 at 1:41 pm

    Does Dr Sinatra have a vitamin with just the four awesome,S in it? I can not take the fish oil because of the blood thinners I’m on.
    Thank you

  12. HeartMD Editor

    on August 17, 2017 at 10:10 am

    Hi Patricia,

    There is no one formulation that contains all four supplements that Dr. Sinatra recommends (the “awesome foursome” are: CoQ10, L-carnitine, magnesium and d-ribose). There is, however, the Awesome Foursome Kit ( but as you mentioned this does contain a little bit of fish oil. All Dr. Sinatra’s formulations that include L-carnitine and Q10 also contain fish oil since it is such an essential part of his heart health protocol. In your case you would have to take the supplements separately. Additionally, it might be worth checking in with your doctor again if you could take the small amount of fish oil contained in the supplement (a little over a gram). This amount is generally ok to take while on most blood thinners. But again, you would need to discuss that with your cardiologist before deciding.

    Best of health,
    HeartMD Editor

  13. philippa Parish

    on August 15, 2018 at 12:20 pm

    I have a client (I’m a registered Nutritional Therapist in the UK), who has genetic ARVC and has a defibliator fitted under her skin. Could taking the supplements recommended for Cardiac Arrhythmia from Dr Sinatra’s book (The Sinatra Solution) help support her heart function?

  14. Amy

    on August 27, 2018 at 5:41 pm

    What can be used to replace blood thinners? Also is OK to take magnesium along with diuretics and prescribed potassium? Can the magnesium lower blood pressure too low? Other meds taken are digoxin, Metoprolol, lisinopril, Eliquis, atorvastatin, and furosemide: all for congestive heart failure. Taking 100 mg COQ10. At this point in time, all vitals are in the correct range. Do not know what the EF is .

  15. Steve

    on January 2, 2019 at 7:32 am

    Re: Awesome foursome for arrhythmia

    For an individual with annoying PAC’s and no significant underlying disease after full workup (echo, cardiac MRI, Holter), how long should it take for the so called awesome foursome to begin to have an effect?

    Many thanks.

  16. Kimberly

    on July 18, 2019 at 10:11 am

    I have read that anyone over 30 should take COQ10 with ubiquinol. I noticed yours is with ubiquinone. I am 52 and was wondering if it will still work for me. Also, do any of your supplements have D-ribose in it? I can’t find it anywhere. My back story is, I was always very healthy and physically fit. Last fall after working out my heart began racing and pretty much stayed that way for a week. I was told it was fine and to just slow down. Through the winter it happened a few more times. In March of this year I was driving with my son and my HR shot up to 115 for no reason. Again I was told nothing was wrong. A month ago I was exercising (much slower now) and I started having chest pains. At the hospital I was told my troponin levels were slightly elevated. They admitted me, I had a catheterization done. My arteries were clean. I was diagnosed with svt. I was put on Metroprolol which helped but I do not like taking medications so my last dose was two days ago (with the Dr.’s approval). So far I’m doing ok. I’d like to take care of this with supplementation. I’m just not sure what to take. Any help would be greatly appreciated. Thanks

  17. Stella V

    on July 31, 2019 at 4:21 am

    An episode with my left eye caused a diagnosis of TIA. I have been taking the awesome foursome for 10 years due to Chronic fatigue syndrome /ME.
    I have been put on Apixaban because AF is suspected. Is it OK to continue with Awesome foursome as well as Apixaban because without these 4 supplements I have no quality of life.
    Would it also be OK to add Crominex 3+ for my diabetes 2.

  18. Jan

    on September 29, 2020 at 2:22 pm

    Does d-ribose have any negative effect on the kidneys at the recommended dosages?

  19. HeartMD Editor

    on October 8, 2020 at 6:14 pm

    Dr. Sinatra has never seen any research or patient experiences where supplementing with D-ribose had any effect on the kidneys.

  20. Linda E.

    on July 20, 2021 at 2:05 pm

    I have been taking the foursome for almost three ejection fraction went up from 30-35 to 40-45. I will continue on it along with the Lisinopril they want me to take to keep my blood pressure down. The low EF was a reason to implant a defibrillator but now I was told I dont need one…I am hoping my EF will be much higher next time they check in three months. I thank God for this information from Dr. Sinatra telling us how to help our hearts by taking healthy supplements.

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