How can niacin cause liver damage

Drug-induced hepatotoxicity can be classified as either a direct hepatotoxic mechanism or an immune-mediated mechanism that is caused by a drug or its metabolites. The injury from the drug in question will then result in hepatitis, cirrhosis, cholestasis, steatosis, sinusoidal damage, or a blending of these presentations.

Once niacin enters the liver, it is metabolized by either conjugation or amidation see Figure. The amidation pathway is associated with hepatotoxicity and is classified as a high-affinity and low-capacity pathway.

Thus, if niacin is available in smaller concentrations over time, such as with a SR formulation, the amidation pathway is unlikely to be saturated. Because it is a high-affinity pathway, this will be the primary means for metabolism whenever SR niacin is administered. When this pathway is primarily used, the series of oxidative and reductive reactions result in the production of nicotinamide adenine dinucleotide NAD , which is associated with niacin's hepatoxicity.

About Us Disclaimer Contact Us. Toggle navigation. Please enter text to search. Search by Outlines. Set Search Limits. Drug-induced liver injury can occur through direct hepatotoxicity or an immune-mediated hepatotoxic mechanism.

Niacin may be metabolized by either a conjugative or amidation pathway. The hepatotoxicity of niacin is most associated with the sustained-release formulation and the production of nicotinamide adenine dinucleotide via the amidation pathway. Blood gas and a chemistry panel should be ordered, in addition to a complete blood count, liver panel, and prothrombin time.

As with any other potentially toxic ingestion, the physician should screen for co-ingested substances. While a specific nicotinic acid level can be ordered, the results will not come back in time to alter management, and should not be relied on to make the diagnosis.

There is rarely an imaging study that would have any utility in the diagnosis of niacin toxicity. Finally, it is important to remember that a diagnosis of niacin toxicity should be one of exclusion. The emergency department assessment begins with rapid assessment and stabilization of the airway, breathing, and circulation, in addition to finger-stick glucose, oxygen saturation, and core temperature.

Re-warming for hypothermia, dextrose infusion for hypoglycemia, in addition to intravenous crystalloid volume replacement may be necessary. In rare cases, a bicarbonate drip may be indicated, or vasopressor support. Some severe cases have required transfusion of fresh frozen plasma or packed red blood cells. In patients who develop severe hepatotoxicity, consultation with gastroenterology is necessary for consideration of N-acetylcysteine NAC therapy and possible liver transplant.

While the flushing can be alarming to the patient, it is self-limiting and does not require medication, although it would be responsive to the anti-prostaglandin properties of non-steroidal anti-inflammatory drugs such as aspirin or ketorolac. Nevertheless, in most cases, discontinuation of the niacin product, along with reassurance and follow-up, will be the only treatment indicated.

The approach to the consideration of other possibilities when screening for niacin toxicity is to consider other conditions that present with flushing, with or without associated gastrointestinal symptoms [15] :. In cases involving liver damage, the extensive differential for elevated liver function tests would be applicable.

The clinician must consider:. Flushing is self-limited and usually requires no treatment. Most patients, even those who sustain significant elevations of liver function tests, do very well so long as they discontinue the niacin, especially the SR formulations. The flushing, headache, lightheadedness, itching, nausea, and vomiting are self-limited as long as the patient stops the supplement. Hypotension, coagulopathy, and metabolic acidosis improve with supportive therapy. Complications of niacin toxicity are limited to liver injury in rare cases.

Occasionally, this can progress to fulminant hepatic failure necessitating transplantation or resulting in death. It is essential to ask the patient about over-the-counter medications and supplements. One would use the history to explore the specific type of vitamin compounds, especially if there is a slow-release preparation. It is important to find out what is motivating the patient to take the supplement, especially if they found the information on the internet.

The clinician must keep in mind that niacin toxicity is a diagnosis of exclusion. Many other conditions can cause liver damage, including other dangerous ingestions.

The current clinical context is such that niacin is now less common in the treatment of hyperlipidemia, so it would less likely appear as prescribed patient medication. It would more likely be a supplement. The clinician has many resources available to help detect potentially dangerous supplements that patients are taking. Consult a toxicologist when needed, or Poison Control Centers are available around the clock to provide support.

Journal of the American College of Cardiology. Part I: Alternative Niacin Regimens. Current atherosclerosis reports. Heart British Cardiac Society. However, on further history taking by the senior resident, in the absence of family and friends, the patient openly volunteered information regarding his recent use of niacin and purpose of its use. Only then could a presumptive cause of his ALF be determined with discontinuation of the extensive diagnostic evaluation. The differential diagnosis for ALF in the pediatric population is broad and often an underlying etiology is not identified.

However, as seen in our case, extensive history taking and an understanding of Internet trends may aid in determining the causes of disease presentation in the adolescent population. Our patient developed ALF secondary to the use of niacin as a way to help mask the results of an upcoming urine drug screen. Awareness of this and similar practices is vital to providers giving medical care to this population. The authors declare that there is no conflict of interests regarding the publication of this paper.

Ellsworth et al. This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Article of the Year Award: Outstanding research contributions of , as selected by our Chief Editors. Read the winning articles. Journal overview. Ellsworth , 1,2 Katelyn R. Anderson, 1 David J. Hall, 1 Deborah K. Freese, 3 and Robin M. Academic Editor: Y.

Received 18 Dec Accepted 07 Jan Published 12 Feb Abstract A year-old male was transferred to the pediatric intensive care unit for evaluation of acute liver failure. Introduction The Internet as a source of medical information and advice impacts the care that pediatricians provide for their patients [ 1 , 2 ]. Discussion Our case is a unique description of an adolescent presenting to our hospital with ALF secondary to niacin induced toxicity.

Figure 1. Results of a Google search regarding topics related to niacin and drug tests. References C. Pandolfini, P. Impicciatore, and M. View at: Google Scholar C. Burgos, A. Bot, and D. View at: Google Scholar J. Backes, R. Padley, and P. Squires Jr. Shneider, J. Bucuvalas et al. Daul and M.