Ribose, the sugar of life (Pt. 2)

D-Ribose in cardiovascular disease

The heart could be said to be the most metabolically active organ in the body, requiring a large volume of oxygenated blood flow to continually supply its tremendous demand for ATP. Oxygen deprivation due to heart disease or stress depletes energy from the heart and will quickly empty the heart’s energy reserves. The good news is that the heart is also the most responsive organ to supplementation. D-Ribose is particularly effective in this respect and the reason why it shows such promise in treating heart patients. D-Ribose increases the energy pool and promotes the metabolic health of the tissue (1). Medical and scientific literature has repeatedly confirmed that D-Ribose can be effective in treating patients with congestive heart failure, coronary artery disease, angina, ischemic cardiomyopathies and for those recovering from cardiac intervention such as aortic valve repair, coronary artery bypass graft surgery and angioplasty.

D-Ribose in congestive heart failure

Hearts with congestive heart failure are severely energy depleted, in many occasions up to 30%. Because the loss of energy is progressive, it is not evident until there is severe failure. Congestive heart failure is also characterized by the loss of the more efficient energy pathway in favor of the less efficient, which causes:

  1. Stress in the heart
  2. Ventricular pump failure caused by diastolic dysfunction
  3. Thickening of ventricular walls

Because D-Ribose supports the heart’s ability to preserve and rebuild its energy pool, it helps provide the heart with the energy it needs to do its job. D-Ribose also helps reduce free radical formation by salvaging ATP breakdown products. Both of these actions are critical for congestive heart failure patients in which low energy output, free radical stress and cardiac arrhythmia dominate.

The effectiveness of D-Ribose in treating congestive heart failure was proven in a study done in 2003 reported in the ‘European Journal of Heart Failure’. In this study D-Ribose supplementation resulted in a highly significant improvement in:

  1. Atrial contribution to left ventricular filling: More blood was able to flow into the relaxed ventricle, making it possible for more blood to pump to the rest of the body.
  2. Reduced left atrial dimension: Less back-up of blood that is associated with congestion.
  3. Greater flow rate across the valve separating the left atrium and the left ventricle: More blood flow to the ventricle.
  4. Ventricle relaxation, which allows it to fill more easily and reduces diastolic dysfunction.

This study showed that D-Ribose supplementation improved diastolic heart function (less shortness of breath), quality of life and exercise capacity in coronary artery disease and congestive heart failure in 90% of patients.

D-Ribose in coronary artery disease

Vascular disease has a profound effect on energy metabolism, with a reduction of as much as 40% in patients with chronic cardiac ischemia. Heart attacks or surgery can deplete the energy pool even further, by 50% or more. Since normal heart function requires large amounts of energy and since the energy stores of the heart are limited to sustain only a few seconds of contraction, supplementation is key.

In myocardial ischemia there is a severe and chronic depletion of the energy stores due to inadequate oxygenated blood flow that can take up to ten days to rebuild. Even when normal circulation is restored through surgery, this can lead to extended post-ischemic heart dysfunction. This energy strain depletes ATP and it is ironically exacerbated when blood flow is restored. The new blood flow pulls these energy substrates out of the cell leaving it energy deprived. Dr. Sinatra has seen how many patients who have surgery to open their coronary arteries get actually worse for up to two weeks after the surgery. These patients become very fatigued, and during this time of recovery, the lack of energy reserves puts them at great risk.

On the other hand, those patients that are not candidates for this kind of surgery, remain in a chronic stage of energy depletion   and their heart function worsens progressively to congestive heart failure if the energy metabolism does not improve. “Restoration of the energy pool ….can only be accomplished through the pathway of energy metabolism regulated by the availability of D-Ribose” (1). This reduces fatigue, increases exercise tolerance and enhances quality of life. All this information was first reported in a 1992 study published by the British medical journal ‘The Lancet’. The subjects in this study had chronic coronary artery disease in at least one main coronary artery and a history of angina induced by normal daily activities. Three of them had had heart attacks. These patients were randomly given either D-Ribose or a placebo of glucose for three days. The group that were given D-Ribose performed significantly better when compared to baseline tests, while there was no improvement in the group that was given glucose. The conclusion of this study was clear: D-Ribose supplementation effectively increased cardiac energy metabolism in only three days, controlled the onset of angina and improved exercise tolerance in chronically diseased patients.

Another study from the University of Minnesota showed that D-Ribose is valuable after a heart attack. The study was conducted in animals because it was too invasive to be done in humans. After four weeks of treatment with D-Ribose, animals showed better heart function than those given a placebo. This study showed that by increasing the energy level of the heart, the heart muscle could function better and be less affected by the stress of a heart attack.

Another study showed that D-Ribose also helps reduce the development of pulmonary hypertension in ischemic hearts. The study showed that D-Ribose significantly reduced the development of heart failure on the right side of the heart, allowing the heart to pump blood to the lungs more easily.

D-Ribose in Peripheral vascular disease

Peripheral vascular disease (PVD) results from arterial clogging, especially in the arteries feeding blood to the legs. It leads to severe leg pain even with mild exercise. The same pain that patients with congestive heart failure feel due to the heart being unable to pump blood out to the extremities.

Similar energy depletion occurs in leg muscles during PVD, in congestive heart failure and in coronary artery disease. In all three cases oxygen deprivation leads to a depletion of the tissue energy pool because an adequate volume of oxygenated blood cannot be supplied to the heart muscle. This energy depletion disrupts the normal function of the muscle, leading to fatigue, soreness, and stiffness that can become so severe that patients cannot stand and walk.

D-Ribose has been shown both in human and animal studies to greatly accelerate energy synthesis in skeletal muscle. By accelerating energy synthesis muscles are better equipped to keep up with the energy demand, improve their physiology and reduce pain. While D-Ribose supplementation will not increase blood flow to the tissues, it allows muscles to manage the balance between energy supply and demand more effectively.

Myocardial protection and recovery in cardiac surgery

There are three major cardiac interventions that have to do with restoring blood flow to the heart:

  1. Traditional coronary artery bypass graft (CABG) surgery: During this kind of cardiac surgery, the body’s temperature is lowered to decrease metabolism and reduce cardiac energy loss. The body’s blood supply is then rerouted to the bypass pump so the heart can be stopped for surgery, while the body continues to receive oxygenated blood from the pump.
  2. “Off pump” CABG: During ‘off pump’ procedures, on the contrary, the body is cooled, but the blood is not rerouted to the bypass pump and the heart is not stopped. This is also called ‘beating heart surgery’ and it places less metabolic strain on the heart, muscles and brain.
  3. Percutaneous transluminal coronary angioplasty (PTCA): PTCA is a procedure where a balloon is placed into the clogged artery and expanded, which breaks apart the plaque and eliminates the clog. While the balloon is expanded, blood flow stops to a portion of the heart and an ischemic event is the immediate result. This ischemic event, although short, also stressed cardiac energy metabolism to the limit.

All these three interventions cause the heart to become ischemic and put it under extreme metabolic stress. All of them also provide an immediate restoration of highly oxygenated blood to the heart which can cause some issues.

There have been numerous animal and human studies that researched the role of D-Ribose in protecting the heart during surgery and helping it recover after cardiac intervention. Some research has shown that bathing the stopped heart in a solution with D-Ribose preserves energy metabolites and slows the energy drain during traditional CABG surgery. Other studies have shown that the metabolic state of the heart prior to surgery is the main factor affecting functional cardiac recovery following the procedure and that the preservation of the energy pool in the heart before surgery is crucial for a successful outcome. Still other studies have shown that keeping donor hearts for transplant bathed in a D-Ribose solution can be an effective way to preserve the tissue energy pool and promote cardiac function following transplant.

Giving patients D-Ribose before and after cardiac intervention has proven very effective. In one study, giving it intravenously to patients following aortic valve repair enhanced cardiac recovery. Other studies show that giving energy to the heart before surgery improves the surgical outcome and helps the heart pump blood more easily and completely following the surgical intervention.

Reperfusion

It is defined as the restoration of blood flow to the heart. In this technique, massive amounts of oxygen-rich blood flow into regions of the heart that previously had been deficient. Reperfusion can happen spontaneously if an arterial clog or blood clot breaks away from the vessel wall or it can be done surgically when a surgeon ‘replumbs’ the heart during CABG, opens a clogged vessel , or when a clog-buster agent is used to dissolve away the clots.

There is a downside to reperfusion, when this fresh supply of oxygenated blood is delivered under high-oxygen tension, it brings an excessive amount of oxygen to the previously starved tissue. All this oxygen must be broken down by the cells, creating inevitable and harmful byproducts called ‘reactive oxygen species’ (ROS). What is more, the increased flow of blood that comes with reperfusion washes huge amounts of energy substrates away from the cell and some of these energy metabolic byproducts contribute to free-radical formation in the presence of too much oxygen.

This process can place so much oxidative stress on the tissue being rescued that causes a condition called ‘reperfusion injury’. D-Ribose can counter-balance this harmful effect because it helps control free radical formation by salvaging some of the energy substrates before they can be washed away, not allowing them to escape the cell.

Adverse reactions

When taken as directed, D-Ribose has been proven to be safe. However, because there is not enough published data on pregnant women, nursing mothers and very young children, Dr. Sinatra recommends these populations to refrain from taking D-Ribose.

Also, because D-Ribose lowers blood sugar levels temporarily, insulin dependent diabetics should have their blood sugar monitored so they do not accidentally overdose with insulin.

On an empty stomach, D-Ribose can cause minor light-headedness in a large dose (10 mg.), therefore, it is best taken with food.

Summing up

Because the heart is in such a need for energy, D-Ribose, together with a heart healthy diet and the products you can find in the ‘Healthy Hearts Club’, can make a great difference in energy levels, as we have seen. This is especially important in the case of heart disease, which depletes energy in heart cells.

References:

(1) Sinatra, Stephen T. The Sinatra Solution: Metabolic Cardiology. Laguna Beach, CA: Basic Health, 2011. 145-177. Print.

D-Ribose, the sugar of life (Pt. 1)

We have seen how proper circulation is key for heart health. Good circulation carries nutrients and oxygen, both of which are essential for energy production. L-carnitine assists the body in taking fats into the part of the cell that manufactures ATP (the energy provider for all cells in the body). Another nutrient that is essential for energy metabolism is D-Ribose, which we already saw is one of the components of ATP.

Dr. Sinatra, in his many years as a cardiologist has seen how D-Ribose has helped his patients. He explains that D-Ribose can be used by the body to rebuild the energy pool once it has been depleted. It can also accelerate energy recovery during and following cardiac ischemia because it “supplies the energy needed by the heart to allow full ventricular relaxation during the diastolic phase of the heartbeat.” (1)

Something like stress and heart disease can cause lack of oxygen and blood flow, conditions under which D-Ribose cannot be made fast enough to replace the lost energy in our organs. This is the reason why improving circulation is key to energy production, and the reason why the ‘Heart and Body Extract’ is such an important piece of the puzzle in restoring energy metabolism. Taken together with D-Ribose and L-carnitine, it can bring our heart health protocol to a whole new level.

In today’s blog, we will look at D-Ribose, what it is and all the functions it has in the body.

Ribose in energy metabolism

Depletion of cellular energy is well known in cardiovascular diseases like congestive heart failure, coronary artery disease, aortic valvular disease, peripheral vascular disease and certain types of cardiomyopathy. When considering heart and circulatory diseases, the effect of D-Ribose supplementation on maintaining energy levels cannot be overstated. Let us remember some basics of energy metabolism.

Every cell in our body uses up a great deal of energy. The energy unit is known as ATP as we saw in previous blogs, and it has D-Ribose as one of its components. Exercise, stress and disease can put a burden in the body’s energy metabolism, especially the heart, depriving it of oxygen. Without oxygen, the energy pathways do not work efficiently to make energy. The heart cells then must rely on glucose to fulfill their entire energy requirements, and they become very reluctant to change from glucose metabolism to D-Ribose synthesis. This is further complicated by the fact that the cell has no glucose to spare. Until the mechanisms of energy metabolism return to normal and take pressure off glycolysis, and until the cells develop the enzymes needed for D-Ribose synthesis, the process of making D-Ribose is slowed down, especially under stress. This translates in severe weakness and fatigue for up to a week after exercise. However, when D-Ribose is added to the health routine, the cells are able to recover well enough to make energy at a faster rate.

What exactly is D-Ribose?

The chemical name of D-Ribose is ‘D-ribofuranose’, a simple five-carbon sugar made in every cell in the body. Because of this chemical composition, D-Ribose cannot be used by the body in the normal carbohydrate metabolism pathway, which uses a six-carbon sugar like glucose. Instead D-Ribose, is conserved by the cell for its primary role: rebuilding the energy pool. D-Ribose is unique among sugars because it is the only sugar used by the body to regulate and control this vital metabolic pathway.

D-Ribose synthesis happens in every cell in the body but it is a slow process and varies according to the tissue. At the cell level the manufacture of D-Ribose begins with glucose and involves a series of biochemical reactions that follow a complex metabolic pathway known as ‘pentose phosphate pathway’ (PPP).

Although D-Ribose is found naturally in the body, it cannot be stored, instead, cells must make it every time it is needed. Several organs make their own D-Ribose to manage their own needs, like the heart, skeletal muscle, nerve tissue, brain, etc. However, under stress there is a reduction in oxygen and blood flow. Under conditions of low oxygen, D-Ribose cannot be made fast enough to replace lost energy in each of the organs. If this oxygen and/or blood flow deficits become chronic, as is the case of heart disease, tissues can never can make enough D-Ribose and cellular energy levels are constantly depleted. This is the reason why improving circulation is key to energy production, and the reason why the ‘Heart and Body Extract’ is such an important piece of the puzzle to restore energy metabolism.

According to Dr. Sinatra, D-Ribose has been shown to be beneficial by reducing the time the heart needs to rebuild cellular energy and normalizing diastolic cardiac function from 10 days to 1-2 days. Without D-Ribose supplementation, hearts are forced to slowly make their own D-Ribose before energy synthesis can proceed. Once D-Ribose is present in the cell, energy recovery can proceed quickly.

When it comes to food sources, D-Ribose is found in meats, especially veal, but not in enough quantities to contribute to its role. Therefore, for those people suffering from any heart condition, neuromuscular disease, peripheral vascular disease, etc supplementation is key. When D-Ribose is ingested, it is quickly and easily absorbed through the digestive tract and into the blood and then the tissues. About 97% of supplemental D-Ribose is absorbed and it reaches steady state in the blood in 3-12 minutes, depending on the dose. It also moves easily from blood to tissue. Virtually all of the D-Ribose absorbed into the blood is used by tissues, only 5% is excreted through urine.

D-Ribose in the cell has several very important functions:

  1. Drives the synthesis of energy compounds
  2. Controls the production of DNA and RNA (the genetic materials)
  3. Influences the synthesis of certain vitamins and co-enzymes crucial to cellular function

Of all the sugars in nature, D-Ribose is the only one that performs these functions.

A brief history of D-Ribose

Although D-Ribose is one of the most widespread substances in the body, it took several decades for scientists to pinpoint what its role was. It was in 1944 when Japanese researchers, doing some experimentation with laboratory mice and rabbits, discovered that D-ribose was converted in the liver. This first discovery triggered further research in other laboratories in the world and it was reported that D-Ribose was a primary intermediate in an important metabolic pathway, the ‘pentose phosphate pathway’ (PPP). The PPP is of great importance for:

  1. The body ‘s energy synthesis
  2. The production of genetic material
  3. To provide material used by certain tissues to make fatty acids and hormones

This information led to the isolation of a purified enzyme called ribokinase from calf liver. This enzyme is key in allowing D-Ribose to enter the ‘pentose phosphate pathway’.

In 1969 researchers in the ‘Department of Anatomy’ at McGill University, Montreal used radioactively labeled D-Ribose injected into young rats to finally determine that D-Ribose could be removed from the blood tissue and metabolized into physiologically important compounds in the cell. Techniques for analyzing blood D-Ribose levels were developed at about the same time, revealing normal circulation levels of D-Ribose to be between 0.5 and 1.0 mg per 100 milliliter of blood.

Many years of research had to follow before researchers in Munich, Germany reported that energy-starved hearts could recover their energy levels if D-Ribose was given prior to, or immediately after ischemia (oxygen deprivation). In 1978 these researchers reported that a similar phenomenon occurred in skeletal muscle. At the same time, it was learned for the first time that the energy draining effects of some drugs that make the heart beat more strongly (isotropic drugs) could be lessened if D-Ribose was given along with the drug. These researchers proved that D-Ribose assisted the body in energy synthesis. More research proved that D-Ribose administration greatly improved the energy recovery in ischemic, hypoxic, or cardiomyopathic hearts and muscles and improved functional performance of the tissue. In addition, studies showed that L-Carnitine helped the action of many heart drugs.

The most significant studies showed that D-Ribose supplementation played a key role in energy restoration and return of diastolic cardiac function. The results of these studies led to the first two U.S patents issued for the use of D-Ribose to treat ischemic tissue.

In 1989, the first organized clinical trial of D-Ribose in human subjects was conducted, which showed the great effect of D-Ribose has on a muscular disorders.

All these new discoveries created a torrent of worldwide clinical investigations on the possible benefits of D-Ribose on heart disease, disorders affecting muscle energy metabolism, arthritis, athletic performance and neuromuscular disease. The first clinical study on the role of D-Ribose for heart disease was published in 1991. In this study, it was theorized that D-Ribose could be used to enhance the diagnosis of cardiovascular disease, and that portions of the heart that were alive but not functional could be assisted by increasing their energy level. It was known that these portions of the heart simply hibernate, and they conserve energy until they have enough blood flow and oxygen to turn up their energy metabolism. This discovery allowed cardiologists to wake up hibernating segments of the heart and allowed them to locate them better by giving them a ‘roadmap’ to follow during surgery.

In 1992 another clinical study was published showing that D-Ribose supplementation to patients with severe stable coronary artery disease increased exercise tolerance and delayed the onset of moderate angina. This study included 27 men with heart disease for 3 days only. Even in that short period of time, D-Ribose increased the amount of time they could exercise on a treadmill before they had ischemic changes or before the onset of moderate exercise related angina. Since this study, the benefits of D-Ribose administration have been reported for cardiac surgical recovery, treating congestive heart failure and neuromuscular disease, restoring energy to stressed skeletal muscle , controlling free radical formation in hypoxia. Other benefits that were reported were improved oxygen utilization efficiency of heart and muscles.

Other studies done by the ‘European Journal of Heart Failure’ investigated the effects of D-Ribose administration in patients with congestive heart failure. They showed that D-Ribose improved diastolic functional performance of the heart, increased exercise tolerance and significantly improved the quality of life of patients participating in the study.

Another study reported on the benefits of D-Ribose in both healthy and sick hearts. In healthy individuals, D-Ribose increased the anaerobic energy reserves of the heart and delayed the onset of irreversible ischemic injury by 25%. It also proved that giving D-Ribose to hypertrophied hearts improved ventricular function and normalized contractility of the ventricle.

In 2004, a study conducted by two of the leading muscle physiologists in the world, Jens Bangsbo and Ylva Hellsten, proved that D-Ribose increased energy metabolism in stressed skeletal muscle and accelerated recovery of the energy pool once it was depleted. This is significant in congestive heart failure and peripheral vascular disease because they relate to the heart muscle.

Research continues today.

How and when to supplement with D-Ribose

Since D-Ribose is not stored in cells in its free form, there is no normal levels in tissue, and therefore D-Ribose deficiency does not exist. Instead, cells are faced with the task of making it in response to a specific metabolic demand. And this is where the problem is, because making D-Ribose is a slow time-consuming and rate limited process.

Factors that have to be taken into account to know whether or not to supplement with D-Ribose are:

  1. Exercise: Athletes place a great amount of strain on their muscle energy metabolism. Repeated exercise drains energy in the muscles, promoting free radical production. Exercise tolerance is also very personal, someone who has a sedentary life will become more oxygen deprived with just a little exercise in which case the energy reserves of the muscle will be depleted.
  2. Age: With age the health of the mitochondria suffers, therefore even a minor level of stress can have a dramatic effect on cellular energy stores. A great percentage of the population over the age of 45 both male and female shows signs of diastolic cardiac dysfunction. This is specially the case of patients with high blood pressure and women with severe mitral valve prolapse. D-Ribose supplementation increases the cardiac energy reserve and can help the heart restore normal diastolic cardiac function if early signs of diastolic dysfunction exist.
  3. Use of certain drugs: Inotropic drugs, which work by making the heart beat harder put a big strain in the heart by limiting its ability to supply enough energy to support the extra metabolic stress placed on it by the drug. This kind of drug has been shown to drain the heart’s energy reserve, making it run out of energy. Research shows that supplementing with D-Ribose can reduce the energy drain common with inotropic agents without having any negative impact on the activity of the drug.

Studies have shown that any amount of D-Ribose given to an energy starved cell will give it an energy boost. Even a small dose of 500 mg can increase energy by 100%. Larger doses have been shown to increase the synthesis of energy in muscle between 340% and 430%. This increase was even the case when muscles were actively working.

The amount of D-Ribose needed depends on the type of condition we are dealing with. For chronic fatigue and shortness of breath as a result of heart disease the amount is different than for cases of poor peripheral blood flow, soreness from strenuous exercise, chronic fatigue syndrome or fibromyalgia.

An adequate dose of D-Ribose usually results in symptom improvement very quickly, within a day or a few days. If the relief is not immediate, the dosage should be increased until the patient feels better. Dr. Sinatra often takes into consideration the following in order to determine the right dose:

  1. How energy depleted are the cells: Have they been depleted for long as in the case of chronic disease or is it a temporary cause like is the case of exercise?
  2. What is the circulatory status of the patient? Are they healthy or do they have heart disease, peripheral vascular disease, fibromyalgia, neuromuscular disease or other conditions that affect the delivery of oxygen to the cells?

In general, athletes can benefit from a small dose before and after exercise to attenuate soreness in the muscles and stiffness. Before exercise, D-Ribose gives muscle a boost needed to salvage energy compounds as they are being broken down by the muscle. After exercise it allows new energy synthesis to proceed quickly, aids in recovery and improves the physiological health of the muscle. A usual dose is 1 tsp (5 grams).

For patients with heart disease or circulatory conditions that chronically affect oxygen delivery the answer is not that straightforward. Because D-Ribose does not stay in the blood long, around 30 minutes only, the amount of D-Ribose must be large enough to get into the affected tissue. This is not a problem if the person has normal blood flow, because D-Ribose is quickly delivered to stressed tissue. However, if heart or muscles are low in oxygen due to poor circulation or clogged arteries, more D-Ribose will be needed to allow enough of it to work its way through into the energy starved portions of the heart.

Another concern to consider is the energy drain in cells and tissues. Increasing oxygen delivery and maintaining it is key to D-Ribose supplementation because without oxygen energy metabolism cannot be kept. This is why improving circulation is crucial, without proper circulation the patient will continue to run out of oxygen. This also means that D-Ribose must be taken everyday. According to Dr. Sinatra, it is not enough to take it until the patient feels better. Missing just one or two days will have a serious impact on cellular energy levels, which will quickly feel as fatigue, weakness, and loss of quality of life.

The dosage will be very personal as every patient has his or her own pathological conditions, but a general recommendation can be made as follows:

5-7 grams (1 tablespoon) daily as a preventative measure for cardiovascular disease, or for athletes or healthy people doing strenuous activity.

7-10 grams daily for patients with congestive heart failure, ischemic cardiovascular disease, peripheral vascular disease, patients recovering from heart surgery or heart attack, for treatment of stable angina pectoris, and for athletes working out in chronic high intensity exercise.

10-15 grams daily in divided doses of about 5 grams each, for patients with advanced congestive heart failure, patients awaiting heart transplant, patients with dilated cardiomyopathy , frequent angina, fibromyalgia or neuromuscular disease.

Once the patient starts seeing results, the dose can be lowered slightly until a maintenance level is reached, taking into account that changes in lifestyle like increased exercise will require the dose to be adjusted.