6 Dec 2008
About a year ago, I had to get off antibiotics for about four months, because of rising liver enzyme levels. This is a graph I made, showing the test results and also what I was taking at the time. (Click on it to get a 2x larger version.)
The liver enzyme levels are graphed as the ratio of the test result to the "upper limit of normal", as defined by
the lab; a red line is drawn across the graph at that limit, to show where it lies. My baseline levels seem to be about half that limit. None of the levels shown are indicative of any sort of immediate emergency; that only occurs at much larger ratios. Blood tests for liver enzymes show how much damage liver cells are undergoing; the maximum level I had was less than three times the "upper limit", or less than six times my baseline level. Cells dying at six times the baseline level is no big deal; the liver can easily regenerate cells, provided no gross structural damage occurs. (The so-called "upper limit of normal" is not a limit in any strict sense, but rather a statistical construct which says where most people's results are: it is probably equal to the average plus two standard deviations. Some labs have started calling it the "reference range", to emphasize this.)
Not shown on the graph is the supplement I think was probably mainly to blame for the big rise in liver enzyme levels, which is timed-release niacin. The reason it isn't shown is that I don't have good records of exactly what I took, when; but I know that I switched brands of timed-release niacin, to a brand that had a very slow release, somewhere in between day 325 and day 342, which is about when the big rise in liver enzyme levels started. I could tell by the complete lack of skin flushing that the release was slower for the new brand (Swanson 500mg slow-release, taken twice a day.) As I've mentioned before, I'd read vague references to liver problems being worse with slow-release than with immediate-release niacin, but I didn't quite realize how big the difference was, until I read this paper, which states:
At that time, the lab was being quite delinquent in delivering test results. This was LabCorp, which had just expanded into this area (and into my insurance as preferred provider), and was delivering test results to my neurologist via courier. It's quite bizarre to me that they even offered this nineteenth-century method of delivery, in addition to twentieth-century (fax) or twenty-first-century (Internet) delivery; but it somehow was not only offered, but was the default. Thus there was a week or so of delay between when blood was drawn and test results were delivered. This significantly hurt my treatment. For one thing, I'd already started a pulse of metronidazole, and done two days of it, when word came back that my liver enzyme levels were too high (even before the pulse), and that I should lay off. For another, when my levels kept on rising, even after I'd stopped the metronidazole and rifampin, I was ordered off the rest of the antibiotics. But that action was taken because of a test done a week earlier; my levels right at that point had already fallen to about half their maximum level -- in spite of the fact that I was still taking the same slow-release niacin. (I stopped the niacin, too, when ordered off the rest of the antibiotics.) Then later, the lab managed to not report at all two sets of test results that showed my liver function being normal, which delayed my getting back on the antibiotics by about a month.
Getting off the maintenance antibiotics (in my case, minocycline and azithromycin) doesn't seem to have done me any good, either as regards my liver or otherwise. For about a week after getting off them, I felt very mildly ill. After that, I started to gradually feel better, albeit with the usual ups and downs. I'd been hammering myself (and the Cpn) quite hard, prior to the liver enzyme rise; indeed, the orders to get off rifampin and metronidazole came as a relief. It took about three months before I stopped having the sense that I was gradually getting better; during the fourth and final month of the interlude, I felt about the same. My liver enzyme levels, as can be seen in the graph, followed a similar pattern, getting a bit worse at first, then taking their time coming back down. Although I improved even off the maintenance antibiotics, I think I'd probably have improved faster on them (judging from my experience at other times when I've taken an extended interval between pulses).
The last set of test results graphed here are somewhat above normal, but since then they've returned to normal.
From the graph, it's pretty clear that pulses do contribute to raising my liver enzyme levels; it wasn't just the slow-release niacin which produced the big rise, but rather the sum of the two effects. Some of this is probably inescapable, since Cpn infects the liver, and killing it inside liver cells inevitably damages those cells. Also, pulses give the liver plenty of work to do, cleaning up debris from die-off, and that must stress it somewhat.
The immediate-release (IR) formulations of niacin in usual therapeutic doses almost never cause serious liver injury. ...Half the patients who take niacin SR [sustained release] develop a symptomatic elevation in transaminase [ALT and AST] levels.For me, from now on, it's immediate-release only. (Besides being easier on the liver, immediate-release also seems to be harder on Cpn, at least judging from its effects on me, in increasing die-off symptoms. The only downside is the skin flushing, which is much more intense with immediate-release.)