N-Acetyl Cysteine to protect your heart?

N-Acetyl Cysteine to protect your heart?

What is N-AcetylCysteine?

N-AcetylCysteine (NAC), also known as N-acetyl-L-Cysteine or simply acetylcysteine, is a cysteine derivative in which a nitrogen atom is attached to the acetyl group.

N-Acetyl Cysteine has its advantages in pharmaceutical overdose (of paracetamol / acetaminophen ), as a nephroprotective and mucolytic agent, microbiological use, use in psychiatry, etc. It’s useful in situations that can improve by sulfate repletion through cysteine or other amino acids related to sulfur.

What is homocysteine?

Homocysteine is a cysteine homologue and is synthesized inside our body from methionine. It’s a non-protein α-amino acid and can be converted to cysteine through certain vitamin-B or recycled to methionine.

Elevated levels of homocysteine are dangerous and enhance endothelial cell injury leading to atherogenesis in blood vessels via inflammation, resulting in ischemia. When the plague due to atherogenesis blocks the blood vessels of the heart, it results in cardiac ischemia and heart attack.

Usually men have higher levels of homocysteine than women. The homocysteine levels increase with age too. In west, average homocysteine levels are between 10 to 12. Homocysteine levels may reach up to 20 in elderly or in people having low vitamin-B intake.

Homocysteine level above 15 µmol/L is called hyperhomocysteinemia and is a medication condition that may lead to increased risk of developing various diseases including neuropsychiatric disorders, fractures, thrombosis, cardiovascular diseases, renal diseases, etc.

High levels of homocysteine are seen mostly in people with high animal protein intake and less leafy vegetables or fruits. Leafy vegetables and fruits are a source of vitamin-B and folic acid that help our body to fix and get rid of homocysteine, keeping its levels in control.

 

High levels of Homocysteine and Cardiovascular system

High levels of homocysteine affect cardiovascular system of our body by endothelial cells injury. Endothelial cells are the inner most lining of the blood vessels. When the inner lining of the blood vessel is injured, there is an inflammation as a response. This inflammation leads to the formation of a plaque, which can directly reduce the diameter of the blood vessel at that point, hindering the flow of the blood and thus the supply of oxygen and nutrition along with other constituents of blood to the organs where the vessel leads.

Even worse, if the plaque gets dislodged it starts flowing with the blood and can block any vessel anywhere in the body, resulting in blockage of the blood supply to any organs where that vessel leads. If this happens in the heart, cardiac ischemia and heart attack occurs, if it blocks a vessel in brain then stroke may happen and so on.

High levels of homocysteine are also believed to enhance the blood clotting by acting on platelets, further enhancing the risk of cardiovascular or related diseases.

Atherosclerosis

How does NAC help reduce homocysteine?

Elevated homocysteine levels are associates with cardiovascular diseases and can’t be lowered significantly with vitamin-B supplements only.

Almost 80% of Homocysteine is bound to a protein in blood. The free homocysteine is easily metabolized and cleared from the body whereas the protein bound homocysteine keeps on accumulating in the blood and having negative health affects. N-Acetyl cysteine displaces homocysteine from that protein’s binding site probably due to disulfide interchange reactions. As a result, a mixed low molecular weight cysteine and N-Acetyl cysteine disulfides are formed. These compounds are believed to have more metabolic bioavailability and a high renal clearance, resulting in removal of homocysteine from the plasma. However, the decrease in homocysteine levels through N-Acetyl Cysteine is dose related [1].

A study published in 2006 [2] studying affect of intravenous N-Acetylcysteine on hemocysteine concentration in plasma during haemodialysis in end stage renal disease (ESRD) patients concluded that N-Acetylcysteine normalizes the plasma concentration of hemocysteine during hemodialysis resulting in improved pulse pressure and overall condition of patient with end stage renal failure (ESRD) and can be considered a promising approach to reduce the risk of cardiovascular diseases in vulnerable patients.

 

Effective dose of N-Acetylcysteine

A study on N-Acetyl Cysteine affect on plasma Homocysteine concentration of patients undergoing hemodialysis published in 2009 [3] concluded that oral NAC was sufficient and safe to lower the hemocysteine levels in blood plasma. However they found that doses below 600 mg per day for a month were not effective while dose above 1800mg per day caused complications for gastrointestinal tract without any further affect than a daily dose of 1200 mg per day.

Another study performed in 2003 on healthy individuals in three groups, given different doses of N-Acetylcysteine also found that the affects were dose related in lowering the plasma homocysteine levels, with more reduction in the group with higher dosage. [4]

Note that the dose is dependent on the requirement of the individual patient and an expert should be consulted before starting taking N-Acetylcysteine regularly.

 

Is supplementation of zinc and copper recommended with frequent NAC use?

A study published in 1990 [5] on affects of oral N-Acetylcysteine on the excretion of trace metals including zinc, copper, magnesium and iron for short term (2 weeks) concluded that there was no obvious loss of these elements from the body.

However it’s believed that the long term use of N-Acetylcysteine does affect the trace elements excretion from the body and they should be supplemented. Consult your doctor before taking any supplement including N-Acetylcysteine alone or any of the trace elements including zinc and copper. Also, the safety of N-Acetylcysteine is unknown for pregnancy and therefore should be avoided during pregnancy. During pregnancy always use medicine or supplements after consulting your physician.

 

References:

 

  1. Plasma homocysteine and thiol compound fractions after oral administration of N-acetylcysteine. (http://www.ncbi.nlm.nih.gov/pubmed/7809573)
  2. Intravenous N-Acetylcysteine During Haemodialysis Reduces the Plasma Concentration of Homocysteine in Patients With End-Stage Renal Disease (http://www.medscape.com/viewarticle/531816)
  3. Does N-Acetyl Cysteine Have a Dose-Dependent Effect on Plasma Homocysteine Concentration in Patients Undergoing Hemodialysis? (http://numonthly.com/?page=article&article_id=892)
  4. Urinary and plasma homocysteine and cysteine levels during prolonged oral N-acetylcysteine therapy. (http://www.ncbi.nlm.nih.gov/pubmed/12711838)
  5. Does N-acetylcysteine increase the excretion of trace metals (calcium, magnesium, iron, zinc and copper) when given orally? (http://link.springer.com/article/10.1007%2FBF02657052)