Can High Doses of NAC Cause Pulmonary Arterial Hypertension? | myPHteam

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Can High Doses of NAC Cause Pulmonary Arterial Hypertension?

Medically reviewed by Angelica Balingit, M.D.
Written by Emily Wagner, M.S.
Updated on February 21, 2024

Supplements can offer a great way to boost your body’s amino acid levels — but with some, it’s possible to get too much of a good thing. For example, N-acetylcysteine (NAC) is a popular supplement marketed for its antioxidant effects — but research has found connections between high doses of NAC and pulmonary arterial hypertension (PAH).

In this article, we’ll cover what NAC is and when it’s commonly used. We’ll also dig a bit more into the scientific research and connection between NAC and PAH. However, it’s important to note that it’s a good idea to talk with your doctor before starting NAC or any other supplement. Some can interfere with your current treatment plan and potentially make your condition worse.

What Is N-Acetylcysteine and When Is It Used?

NAC is a supplement made from the amino acid L-cysteine. Your body turns NAC into cysteine and then into glutathione. This powerful antioxidant helps scavenge or fight free radicals (reactive oxygen species), compounds that can damage your healthy cells and DNA. Oxidative stress caused by free radicals is thought to play a role in many diseases, including heart conditions and cancer.

The U.S. Food and Drug Administration (FDA) doesn’t approve dietary supplements for effectiveness and safety before they’re sold to the public. However, medications must be shown to be safe and effective to gain FDA approval. As a medication, NAC has the FDA’s OK for two approved uses.

First, NAC is approved as an add-on treatment to break down mucus in inflammatory lung diseases, such as cystic fibrosis, asthma, and bronchitis. Studies also show that using an inhaled form of NAC helps reduce the number of flares in people with chronic obstructive pulmonary disease (COPD), although this isn’t an FDA-approved use.

Secod, the FDA has also approved NAC for treating acetaminophen (Tylenol) overdoses. Specifically, NAC helps prevent liver damage from taking too much of this popular painkiller. For this purpose, NAC works best when given intravenously (through a vein) within eight hours of consuming acetaminophen.

Sources of Cysteine and N-Acetylcysteine

Your body makes cysteine from another amino acid, methionine. You can also get more cysteine by adding certain foods to your diet, including:

  • Dairy products, such as Yogurt, cottage cheese, and ricotta
  • Meats, such as turkey, chicken, duck, and pork
  • Grains, such as oat flakes, wheat germ, and granola

N-acetylcysteine is a lab-made form of cysteine that’s available in supplements as capsules, tablets, and powders. You can’t get NAC from foods.

As a treatment, NAC is available as acetylcysteine (Mucomyst), a liquid that’s inhaled using a nebulizer (a machine that turns the drug into a fine mist). Your doctor will provide instructions on how to best use this prescription form of NAC.

Is N-Acetylcysteine Treatment Linked to PAH?

Some studies have pointed to NAC as a potential cause of PAH. However, the results are mixed, and many of the studies were conducted on animals. It’s important to remember that animal models don’t provide a complete picture of how drugs and supplements interact with human bodies.

One 2007 study at the University of Virginia looked at treating mice with NAC. The researchers found that the mice given NAC developed PAH, similar to the effects of chronic hypoxia (low oxygen levels).

So, what caused this drastic change? The mice’s red blood cells turned NAC into other chemicals known as S-nitrosothiols. These chemicals essentially trick blood vessels into thinking the blood contains less oxygen than it actually does. As a result, the small arteries in the lungs begin to narrow. This narrowing raises blood pressure in the lungs and the pulmonary arteries — the blood vessels responsible for bringing oxygen-poor blood from the heart to the lungs. The researchers concluded that NAC treatment can lead to PAH in mice.

N-Acetylcysteine May Help Treat Pulmonary Arterial Hypertension

Despite these findings, no additional studies in humans have shown that NAC increases blood pressure in the lungs. In fact, other researchers have reported that NAC may be useful for treating pulmonary hypertension (PH) and PAH.

Researchers examining rats with PH found that NAC treatment decreased lung inflammation and helped prevent blood vessel narrowing and changes usually seen in PH.

Other effects of NAC included improved heart function in the rats. One complication of PAH is right-sided heart failure, when narrowed blood vessels in the lungs make the right side of the heart work harder to pump blood. Over time, the heart muscle becomes weaker and can’t pump blood as well. The rat study found that NAC treatment improved heart function overall.

Again, it’s important to note that these studies used rats and mice to learn more about NAC’s effects. Now that associations between NAC and pulmonary hypertension have been seen in animals, more studies in humans are needed to confirm these findings.

How Is Drug-Induced Pulmonary Arterial Hypertension Managed?

PAH can be caused by an underlying health condition or exposure to a drug or an illicit substance. Drug-induced PAH accounts for around 10 percent of cases worldwide and may be caused by diet pills, amphetamines, and certain cancer drugs. No evidence shows that NAC supplements can cause PAH, but it’s good to know your treatment options.

Currently, there are no set guidelines for how doctors should treat drug-induced PAH. However, several treatment options can help relieve PAH symptoms and improve lung function.

Some PAH medications target the endothelial cells that line the lungs’ blood vessels. These cells make a small protein called endothelin, which causes blood vessels to narrow.

Endothelin receptor antagonists are a class of drugs that reduce endothelin levels. These medications help blood vessels relax, lowering blood pressure. Examples that may be used for drug-induced PAH include:

Your doctor may prescribe calcium channel blockers, another type of blood pressure medication that relaxes blood vessels, to treat your PAH. Options include:

  • Amlodipine (Norvasc)
  • Diltiazem (Cardizem)
  • Nifedipine (Procardia XL, formerly available as Procardia)

Phosphodiesterase 5 (PDE5) inhibitors improve blood flow in your lungs to relieve PAH symptoms. PDE5 inhibitors include sildenafil (Revatio) and tadalafil (Adcirca).

Prostacyclin analogs and prostacyclin IP receptor agonists help to increase levels of prostacyclin and relieve symptoms of PAH. Options include:

Cardiovascular (heart) problems in PAH can also cause fluid to build up in your feet and legs. You may be given a diuretic, or water pill, to help your kidneys clear out the extra fluid. With less blood and fluid to pump, your heart has less work to do.

If these medications can’t help treat your PAH, your doctor may suggest atrial septostomy, a type of surgery to take pressure off the right side of your heart. In some cases, a lung transplant may be necessary.

Talk to Your Doctor About N-Acetylcysteine and Pulmonary Arterial Hypertension

If you’d like to learn more about NAC and the latest information about how it may affect your PAH, talk with your doctor. They can let you know if taking an NAC supplement may be helpful or interfere with your current treatment plan and present a risk of side effects. It’s always safest to talk with your health care provider before starting a new over-the-counter medication or supplement.

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    Updated on February 21, 2024
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    Angelica Balingit, M.D. is a specialist in internal medicine, board certified since 1996. Learn more about her here.
    Emily Wagner, M.S. holds a Master of Science in biomedical sciences with a focus in pharmacology. She is passionate about immunology, cancer biology, and molecular biology. Learn more about her here.

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