Slo Niacin/Elevated Liver Enzymes

[GaMan]

I'm 52 and have never have had high liver enzymes. Took 500 mg of Slo Niacin for about a month between 12/15/13 and 1/15/14 and ALT went from 36 to 60, AST from 39 to 63, and GGT from about low 30's to 110!! based on blood testing done 1/15/14.  Previous normal liver bloodwork from chemistry profile was from physical back in late July of 2013. Only a social drinker (few beers on weekend). Also consumed 3 grams/day of omega 3 supplements and was on a relatively low carb diet during this period. Pretty sure the sustained release Niacin may be culprit but anyone familiar with anything else that would raise these three enzymes as noted above. I have stopped the Slo Niacin. What's a reasonable time to recheck blood after getting off the Niacin....a month?  Also, note that BUN/Creatine just slightly high and ALP, Bilirubin, A/G,Albumin, etc liver markers were all normal. I'll also be seeing Dr for followup this coming week.

Thanks.

[GaMan]

In addition to the 500 mg's of SLO (sustained release Niacin) note that I was also getting 225 mg's of regular niacin in a B complex. I''ll recheck blood in a few weeks.'  

[mikesimon]

Niacin

Hepatotoxicity

Niacin in doses above 500 mg daily causes transient, asymptomatic elevations in serum aminotransferase levels in up to 20% of people.  The elevations are rarely greater than 3 times the upper limit of the normal range and usually resolve spontaneously even with continuation of the drug.  The effect is partially dose related and is more common with doses above 3 g/day.  In some patients, there is an overall decrease in serum proteins synthesized by the liver and, in some instances, coagulopathy with an increase in prothrombin time and decline in serum albumin, coagulation factors and apolipoproteins.  These changes resolve rapidly upon stopping therapy and may not recur with lower doses.

Niacin can also cause serious hepatotoxicity, but this is uncommon.  Significant hepatotoxicity is particularly common with high doses of sustained release niacin.  In many cases, the injury becomes apparent after a dose increase or after switching from the regular crystalline to a sustained release form.  The pattern is primarily hepatocellular, although cases with a cholestatic pattern have been described.  The patients present with jaundice, itching, nausea, vomiting and fatigue.  When the injury is the result of switching from the crystalline to the sustained release form, the injury may present acutely within days or a few weeks with a prodromal period of nausea, vomiting and abdominal pain, that is followed by jaundice and pruritus.  Early during the injury serum aminotransferase levels are very high and then usually fall rapidly with discontinuation or dose lowering.  The clinical phenotype resembles acute hepatic necrosis, suggesting a direct toxic effect.  Imaging studies of the liver may reveal areas of hypodensity ("starry sky liver") interpreted as focal fatty infiltration that resolves after stopping the drug.  Liver biopsy typically shows varying degrees of centrolobular necrosis with only mild inflammation.

Mechanism of Injury

The mechanism of hepatotoxicity is assumed to be an intrinsic toxic reaction related to high serum levels of niacin that overwhelm the high affinity, low concentration nicotinic acid receptors (that are responsible for the flushing response).  The finding that niacin can be restarted at lower doses after an episode of clinically apparent injury indicates that the hepatic damage is unlikely to be idiosyncratic or due to hypersensitivity.

Outcome and Management

Niacin hepatotoxicity appears to be dose dependent and more common with the sustained release form of the drug.  Hepatotoxicity is less common with regular, crystalline niacin or extended release niacin.  Most cases are mild and resolve rapidly upon stopping the medication, although in some instances, the injury is acute and severe and progresses to liver failure that is fatal or requires emergency liver transplantation.  Complete resolution of the clinical symptoms is expected within days of stopping niacin, whereas serum enzyme elevations may require several weeks or months to resolve.  Rechallenge with the same form leads to rapid recurrence and should be avoided.  If the injury occurred after switching to a SR formulation, the crystalline form of niacin may be restarted at a lower dose and with caution.

See:  http://livertox.nih.gov/Niacin.htm