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NACET Dosing Considerations

N-acetylcysteine ethyl ester (often abbreviated as NACEt or NACET) is a modified form of N-acetylcysteine (NAC), which is a widely used nutritional supplement and clinical antioxidant. 

NACET was invented in an effort to overcome the inherent limitation of NAC bioavailability in the human body: although NAC is water-soluble and is easily absorbed after oral ingestion, it is rapidly metabolized by the liver into non-bioactive forms. In contrast, NACET is fat-soluble and not rapidly metabolized. This crucial difference results in dramatically divergent pharmacokinetics, and NACET has been shown to distribute throughout body tissues much more effectively than NAC [1], and is also more potent as an antioxidant in human red blood cells [2].

Preclinical studies have employed the same doses of NAC and NACET when comparing them to each other [3]. In humans, NAC is often dosed at 500 mg (roughly ¼ teaspoon) per day. However, no clinical studies have been completed to validate NACET dosing guidelines in humans. Thus, researchers are advised to use caution when evaluating doses of NACET for further study. 

Researchers are urged not to exceed the dosing guidelines of NAC when administering NACET (eg. do not exceed 500 mg per day, or roughly a quarter of a teaspoon). Also, it is essential to note that increasing doses of NACET are not necessarily more effective and high doses can actually result in diminished antioxidant capacity compared to lower doses [4].

Additionally, there are important practical considerations to keep in mind. Due to NACET’s poor solubility in water, it is very difficult to mask its smell/taste in water-based beverages. However, products with similar characteristics as NACET can be effectively masked when mixed in foods such as peanut butter, almond butter, or sunflower seed butter.

Despite the fact that NACET is both derived from NAC and then converted back to NAC in the body [4], NACET has not yet been granted status as GRAS (generally recognized as safe) by the FDA, nor has it been approved for any medical indication. As a result, NACET remains a research product only. This stands in contrast to NAC, which is a GRAS-designated nutritional supplement and is also indicated for use in acute care settings for acetaminophen overdose [5].

Buy NACET today so that you have it when you need it.

*The above information is for educational purposes only. These statements have not been evaluated by the Food and Drug Administration. The products described herein are not intended to diagnose, treat, cure, or prevent any disease.

References

  1. D. Giustarini, A. Milzani, I. Dalle-Donne, D. Tsikas, and R. Rossi, “N-Acetylcysteine ethyl ester (NACET): A novel lipophilic cell-permeable cysteine derivative with an unusual pharmacokinetic feature and remarkable antioxidant potential,” Biochem. Pharmacol., vol. 84, no. 11, pp. 1522–1533, Dec. 2012.
  2. A. Böhmer, A. Pich, M. Schmidt, A. Haghikia, and D. Tsikas, “Evidence by chromatography and mass spectrometry that inorganic nitrite induces S-glutathionylation of hemoglobin in human red blood cells,” J. Chromatogr. B Anal. Technol. Biomed. Life Sci., 2016.
  3. T. Uemura et al., “Protective Effects of Brain Infarction by N-Acetylcysteine Derivatives,” Stroke, 2018.
  4. D. Giustarini et al., “N-acetylcysteine ethyl ester as GSH enhancer in human primary endothelial cells: A comparative study with other drugs,” Free Radic. Biol. Med., 2018.
  5. K. J. Heard, “Acetylcysteine for acetaminophen poisoning,” N. Engl. J. Med., 2008.

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