Loss of Muscle Mass and Function in Heart Failure: Can Amino Acids Help?

Heart failure develops when cardiac muscle becomes weakened. Loss of muscle mass and function is prominent in heart failure. In heart failure patients, conventional dietary intake has little or no beneficial effect on muscle protein. This is called anabolic resistance. A balanced mixture of essential amino acids (EAAs) can help overcome anabolic resistance.

Heart failure develops when the cardiac muscle becomes weakened. However, the term heart failure itself covers a broad array of conditions, though they all result when your heart no longer pumps blood as well as it should.

Heart failure is also often referred to as congestive heart failure. However, congestive heart failure refers specifically to a type of heart failure in which the heart’s pumping action becomes so compromised that it can no longer coordinate blood flow out of the heart with blood returning through the veins. This congestive heart failure results in fluid backing up and accumulating in the lungs and body tissues.

Heart failure reduces exercise capacity, which in turn leads to progressive muscle weakness and negative lifestyle changes, including a vicious cycle of sedentary behavior and weight gain, with subsequent development of metabolic abnormalities such as diabetes. Loss of muscle mass and function is also prominently seen in heart failure patients.

Most individuals over the age of 65 have some degree of heart failure, or stage 1 heart failure, which is characterized by shortness of breath during recreational exercise activities. Stage 1 heart disease is not usually diagnosed as a significant clinical problem. Stages 2, 3, and 4, however, are much more serious and may significantly impair the ability to perform activities of daily living and ultimately cause death.

But these stages don’t develop overnight. Let’s take a look at how the heart is supposed to function and what leads to the condition known as heart failure.

Normal Heart Function

The heart works by circulating blood through its four chambers: two atria and two ventricles. The right atrium takes in oxygen-poor blood from the body and pumps it to the right ventricle, which in turn sends blood to the lungs. By contrast, the left atrium receives oxygen-rich blood from the lungs and pumps it to the left ventricle, which then sends blood out to the entire body.

When this process is disrupted, signs of heart failure start to become noticeable. In addition, changes can be seen on one side of the heart or the other—or even both.

Causes of Heart Failure

When the heart muscle itself becomes too weak or stiff to pump blood effectively, heart failure results. This can be caused by a variety of disorders, from congenital heart defects to disease. However, many of the conditions that can lead to heart failure lie within our ability to control—or at least mitigate.

By far, the most common cause of heart failure is coronary artery disease, a condition that results in hardening and narrowing of the arteries due to the buildup of cholesterol and plaque on the arterial walls.

According to the Centers for Disease Control and Prevention (CDC), over 370,000 people in the United States die of coronary artery disease each year. That’s an average of one in seven deaths that can be attributed to this disease.

However, there are also many other conditions that have been implicated in the development of heart failure. These include:

Types of Heart Failure and Associated Symptoms

The main pumping chambers of the heart are the ventricles (left and right). When these become stiff or are stretched (dilated) to the point where they’re weakened and can no longer pump blood efficiently, you’ve entered the realm of heart failure.

Heart failure itself can be classified into two major categories: left-sided and right-sided.

Left-Sided Heart Failure

The left ventricle supplies most of the heart’s pumping action, and it’s consequently the largest and most muscular of the heart’s four chambers. Not surprisingly, heart failure most commonly affects the ventricle on the left side.

As alluded to earlier, the left ventricle can become so damaged that it can no longer pump oxygen-rich blood out to the body fast enough to keep up with the oxygen-poor blood returning to the heart through the veins. When this occurs, blood begins to back up in the lungs. This accumulation of fluid may result in several symptoms:

  • Shortness of breath
  • Weakness
  • Fatigue
  • Foot and ankle swelling

Left-sided heart failure can also be further divided into two subtypes: systolic and diastolic.

Systolic Heart Failure

In systolic heart failure, or heart failure with reduced ejection fraction (HFrEF), the left ventricle becomes enlarged and too weak to contract normally, which reduces its ability to pump the blood effectively.

Diastolic Heart Failure

In diastolic heart failure, or heart failure with preserved ejection fraction (HFpEF), the left ventricle loses its ability to relax properly after a contraction and can therefore no longer fill up with enough blood during the period of rest between beats.

Right-Sided Heart Failure

Right-sided heart failure usually occurs as a result of left-sided failure, as the backup of blood in the lungs causes the ventricle on the right side to have to work harder, which can result in its weakening over time.

Right-sided failure can also be a secondary effect of lung disease, such as chronic obstructive pulmonary disease (COPD) and pulmonary hypertension, or occur as a result of right ventricular damage from a heart attack.

While the symptoms of left- and right-sided heart failure are similar, the severity of symptoms seen with right-sided failure can be much greater.

For example, the fluid retention seen with right-sided heart failure may spread from the feet and ankles to the abdomen, or even the chest. The buildup of fluid in the abdomen may even be severe enough to result in tenderness and enlargement of the liver. In fact, 90% of patients with ischemic hepatitis (shock liver) have at least some right-sided heart failure.

People with right-sided heart failure may also experience loss of appetite (anorexia) and loss of consciousness (syncope) with exercise due to the heart’s inability to keep up with the demands of vigorous activity.

Pharmaceuticals for Heart Failure Treatment

Of course, optimal treatment of heart failure involves addressing the underlying cause. Pharmacologic treatment options predominantly target the heart’s ability to contract. A variety of drugs may be used for this purpose, with varying degrees of success. However, treating heart failure pharmacologically may be quite complex, particularly in the elderly, who are the most common sufferers of this disease.

More than 50% of individuals over the age of 65 with heart failure have at least four other significant health problems that may also require pharmacologic therapy. These additional conditions and therapies may complicate heart failure therapy.

Adverse responses to pharmacologic heart failure therapy are also not uncommon. In fact, the most common drugs for heart failure treatment, angiotensin-converting enzyme (ACE) inhibitors and beta blockers, can adversely affect muscle function.

Heart Failure Fact: Despite the expenditure of millions of dollars and years of time and effort, no large-scale clinical study of a single drug therapy has demonstrated a substantial beneficial outcome for the most common form of heart failure, in which the principal problem is the failure of the heart to relax after a contraction.

This disappointing reality may reflect the difficulty of treating a syndrome with diverse causes, pathologic responses, and multiple associated chronic diseases using an entirely drug-oriented approach.

Skeletal Muscle Function and Heart Failure

There are multiple reasons for impaired physical functional capacity in heart failure. But most attention has focused on the inability of the heart to pump an adequate amount of blood, which consequently results in less oxygen and nutrients being delivered to the skeletal muscles.

Most heart failure treatments are aimed at improving cardiac function. Unfortunately, drugs that target cardiovascular function have often failed to influence exercise capacity.

However, science has shown that physical training in individuals with heart failure can improve exercise tolerance by improving skeletal muscle function even if heart function is not improved.

Likewise, testosterone treatment, which enhances skeletal muscle function but does not affect heart function, has also been shown to improve exercise capacity in heart failure patients.

Deficiencies in skeletal muscle function are common to all forms of heart failure, and it’s becoming clear that these deficiencies play an important role in pathophysiologic responses.

To further elucidate this, let’s discuss three aspects of skeletal muscle function that are altered in heart failure.

1. Muscle Mass and Strength

Heart failure induces a loss of muscle mass and strength by accelerating muscle protein breakdown. However, the loss of muscle mass is often not initially evident since many heart failure patients are overweight or obese, although in end-stage heart failure, the loss of muscle becomes painfully obvious.

This loss of muscle mass and strength in heart failure occurs in large part because the body’s normal response to dietary protein is altered.

In healthy individuals, dietary protein stimulates the production of new muscle protein. By contrast, in heart failure patients, conventional dietary intake has little or no beneficial effect on muscle protein. This is called anabolic resistance.

2. Energy Production

In people with heart failure, the organelles in muscle where energy is produced (mitochondria) don’t function normally. This is because the capacity of skeletal muscle mitochondria to produce the energy needed to perform physical activity—specifically, the ability to oxidize (combine chemically with oxygen) fatty acids for energy—is impaired in heart failure.

This is in large part due to a deficiency in the ability of fatty acids to enter the mitochondria. Incomplete oxidation of fatty acids leads to the accumulation of muscle products that impair normal metabolic function.

3. Blood Flow

Heart failure also leads to a disruption in the normal regulation of blood flow to the muscles. The amount of blood supplied to muscle tissue is normally tightly tied to the muscle’s metabolic demand. When the demand for oxygen and energy substrates (molecules acted on by an enzyme) increases with exercise, muscle blood flow increases proportionately.

However, the normal increase in muscle blood flow that occurs during exercise is reduced in heart failure patients. This diminished ability to appropriately regulate muscle blood flow is caused by the decreased production of nitric oxide (NO)—the principal vasodilator in skeletal muscle that helps widen blood vessels and increase blood flow.

Thus, whereas the decreased capacity of the heart to deliver adequate blood to peripheral tissues clinically defines heart failure, diminished skeletal muscle mass, strength, and oxidative capacity play important roles in the impairment in physical function.

Amino Acids and Heart Failure

We’ve seen how heart failure can send patients into an anabolic resistant state. Now we’re going to discuss how a balanced mixture of essential amino acids (EAAs) can help overcome anabolic resistance in heart failure.

Many studies have led to this discovery. Let’s highlight the key findings.

First, it’s been shown that only EAAs are necessary to promote muscle protein synthesis, or the building of muscle protein. (For example, check out this study my colleagues and I published in the American Journal of Clinical Nutrition.)

In addition, in a study my colleagues and I published in the American Journal of Physiology-Endocrinology and Metabolism, it was shown that a formulation of concentrated EAAs was able to overcome anabolic resistance and stimulate muscle protein synthesis.

It’s also been shown that the action of any one EAA or subgroup of EAAs is not effective in stimulating muscle protein synthesis. For example, neither the three branched-chain amino acids (leucine, isoleucine, and valine) nor leucine alone is effective in this regard, as evidenced by a 2017 study published in the Journal of the International Society of Sports Nutrition.

Finally, a balanced mixture of EAAs has been shown to effectively stimulate muscle protein synthesis in heart failure patients who have received no benefit from a popular meal replacement beverage designed and marketed specifically for support of patients with this condition.

Specific Amino Acids for Heart Failure

Four amino acids have shown particular benefit when included as part of a balanced formulation of EAAs. These are:

  • Citrulline
  • Arginine
  • Leucine
  • Carnitine

Although not an essential amino acid, citrulline is an amino acid that, when added to a mixture of EAAs, targets the impaired regulation of muscle blood flow that occurs in heart failure. In fact, consumption of this amino acid is the most effective way to promote NO production—the key to increasing blood flow to muscles during activity.

Dietary supplementation with arginine can also be an effective approach for increasing NO production. However, there are limitations in the use of supplemental arginine. Because of rapid uptake and the metabolism of this amino acid by the liver, a large dose is necessary to significantly increase NO production, and this can cause significant gastric distress.

In contrast to arginine, citrulline is well tolerated and has, again, been shown to stimulate NO production effectively in individuals with heart failure.

We’ve already discussed how heart failure results in a limited capacity of skeletal muscle mitochondria to produce energy via fatty acid oxidation and how this directly impacts the ability to perform physical activity.

This impairment is particularly problematic for individuals with heart failure, as it is this process that provides the energy necessary to perform the low-intensity exercise involved in activities of daily living.

However, amino acids can address several aspects of mitochondrial function. For instance, EAAs stimulate the production of enzymes in mitochondria that are involved in the metabolic reactions that produce energy.

In addition, the amino acid leucine stimulates the production of new mitochondria, and the amino acid carnitine can improve the transport of fatty acids into the mitochondria.

As we have seen, amino acids have the ability to address the three major ways heart failure impairs muscle function. Again, these three ways are:

  • Accelerated breakdown of muscle protein
  • Poor regulation of muscle blood flow
  • Impaired production of energy

In light of this ability, not only do EAAs show great promise for enhancing heart health, but they can also be effective in mitigating the causes of and risk factors for heart failure.

And when combined with a healthy lifestyle, these aptly named building blocks of life may even result in improvement in both the symptoms of heart failure and, most importantly, quality of life.

Author: Dr. Robert Wolfe

Robert R. Wolfe, PhD, has researched amino acid and protein metabolism for more than 40 years. His work has been continuously funded by the National Institutes of Health since 1975. He has published more than 550 scientific articles and 5 books that have been cited more than 60,000 times according to Google Scholar.

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