In recent correspondence, Dr. Stratton has been discussing reports in the medical literature that certain antibiotic agents can cause liver damage or failure. Noting that these agents are typically the most potent anti-chlamydials, he has drawn some important hypotheses from this that anyone on an antibiotic protocol should know about.
His cautionary note is that use of some of the new, powerful agents against Cpni must be carefully monitored, and that a more gradual treatment for many is advisable. His observations also affirm the importance of supplementsi in their liver-protective role.
Dr. Stratton notes:
"A recent report of Ketek causing liver failure has crystallized some thoughts that I have had for some time. Cpn can infect the liver and the kidney, but in particular the liver is a target due to the Kupfer cells. Any drug that acts against Cpn (including statins) will therefore in some patients cause hepatic damage or even hepatic failure. The better the activity against Cpn of the agent (or combination of agents), the more likely the liver damage. Even penicillamine can cause liver damage, as does Augmentin.
"Surprisingly, the only anti-chlamydial agent that did not cause hepatitis in some patients was NACi. In fact, NAC is recognized as being protective. See attached references. My conclusion is that NAC should be the first agent in an anti-chlamydial regimen and should be a constant part of the therapy for this protective effect, not to mention it’s effect against elementary bodies. This, of course, is another reason to go slowly, but liver damage has been seen with only a few days of Ketek, for example. Notice the NAC in the Clarithromycin-induced hepatic injury in the end seemed protective in that transplantation was not needed. I think this caveat needs to be in the therapy Website. Although we have not seen hepatitis in any of our patients at Vanderbilt, soon or later this could happen."
Dr. David Wheldoni concurs that this is a very important observation by Dr. Stratton, noting that it takes someone of Dr. Stratton’s depth of understanding about Cpn’s affect on body systems to recognize these reports as possibly Cpn related (ie not necessarily toxicity originating from the drug itself). Dr. Wheldon notes that, in addition to NAC, supplementsi such as Alpha-Lipoic Acid, acetyl-L-carnitine, selenium and zinc, are also important liver protectors. These all have been recommended supplements for people taking a combination antibiotic protocol for Cpn.
Dr. Wheldon also noted that in his protocol, recommendations for using agents such as doxycycline, azithromycin and NAC were considered both because of their antichlamydial affect, but are less known for liver toxic. Dr. Wheldon also patterned his protocolo after Dr. Stratton’s early recommendations to start gradually and add to the combination only as patients tolerate die-off.
References:
Isoniazid- and rifampicin induced oxidative hepatic injury– protection by N-acetylcysteine
Attri, S. et al
Human & Experimental Toxicology (2000) 19, 517-522
Long-term ethanol administration enhances age-dependent modulation of redox state in different brain regions in the rat: protection by acetyl carnitine.
Calabrese V, Scapagnini G, Latteri S, Colombrita C, Ravagna A, Catalano C, Pennisi G, Calvani M, Butterfield DA.
Int J Tissue React. 2002;24(3):97-104.
Brief Communication: Severe Hepatotoxicity of Telithromycin: Three Case Reports and Literature Review
Kimberly D. Clay, MD, MPH; John S. Hanson, MD; Scott D. Pope, PharmD; Richard W. Rissmiller, MD; Preston P. Purdum III, MD; and Peter M. Banks, MD
21 March 2006 | Volume 144 Issue 6 |
Carolinas Medical Center, Charlotte Gastroenterology and Hepatology, Carolinas HealthCare System, and Carolinas Pathology Group, Charlotte, North Carolina.
Fulminant Liver Failure Associated with Clarithromycin
Andreas Tietz, Markus H Heim, Urs Eriksson, Stephan Marsch, Luigi Terracciano, and Stephan Krähenbühl
The Annals of Pharmacotherapy_2003 January, Volume 37, 57-60
Role of nutritional fatty acid and L-carnitine in the final outcome of thioacetamide hepatotoxicity
Sanjay Chanda and Harihara M. Mehendale
Vol. 8 October 1994 The FASEB Journal 1061-1068
Mitigation of oxidative stress in cyclophosphamide-challenged hepatic tissue by DL-alpha-lipoic acid.
Selvakumar E, Prahalathan C, Mythili Y, Varalakshmi P.
Mol Cell Biochem. 2005 Apr;272(1-2):179-85.
Feeding acetyl-L-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress
Tory M. Hagen, Jiankang Liu, Jens Lykkesfeldt, Carol M. Wehr, Russell T. Ingersoll, Vladimir Vinarsky, James C. Bartholomew, and Bruce N. Ames
1870 –1875 PNAS February 19, 2002 vol. 99 no. 4 www.pnas.org
Abrogation of Nuclear Factor-Involved in Zinc Inhibition of Lipopolysaccharidei-Induced Tumor Necrosisi Factor- Production and Liver Injury
Zhanxiang Zhou, Lipeng Wang, Zhenyuan Song, Jack T. Saari, Craig J. McClain, and Y. James Kang*
American Journal of Pathology, Vol. 164, No. 5, May 2004
Dr. Stratton Cautions on Protecting the Liver
Submitted by Jim K on Tue, 2006-02-07 21:35.»
- Printer-friendly version
- Login or register to post comments
- Email this page
This was posted on Lymenet
This was posted on Lymenet today.
I have been wondering about this interaction btwn anti-oxidants and abxi treatments for a while, so I'd really like opinions on this.
On a side note: I remember reading that probiotics in the gut were needed for metronidazolei to metabolise properly. Opinions on this as well?
Nelly
Milk Thistle interferes with Flagyl Absorption?
Found this info in an undated California Lyme Disease Association publication. http://www.nutritionworkshop.com/html/LYME%20DRUG%20INTERACTIONS.htm I copied the pertinent paragraph below: "Milk thistle, an herb used to support liver function, contains a group of bioflavonoids called silymarin. Silymarin may inhibit intestinal P-gp and liver CYP3A4. Surprisingly, concomitant administration of milk thistle significantly decreased the absorption of metronidazole (a drug used to treat the spore form of Borrelia).[6] This interaction could not have been predicted from knowledge of the herb's effects on drug metabolizing enzymes. Moreover, vitamin C (500 mg/day) and vitamin E (400 units/day) decreased the effectiveness of metronidazole in treating H. pylorii infection of the stomach.[7] The mechanism of this interaction is unknown but suggests that anti-oxidants should not be used with metronidazole therapy." Is this true, and if so, what do you use to protect your liver while taking flagyl? Thanks,
posted 09 February, 2006 12:43
Yep, looks like it's true. I think that Mlk Th and anti-oxidants are a big reason why babs Tx fails so much. Artemisinin works by oxidizing, and people are greatly reducing the effects of it, and possibly Mepron, by taking these supps within 4 hrs of the meds.
Here's what the Townsend letters had to say about it: "A common misconception concerning milk thistle (Silybum marianum) is that, since it is a liver herb, it is likely to increase the metabolism and clearance of many drugs due to enhanced hepatic detoxification. This is certainly fueled by in vitro studies showing this effect (1) and an in vivo study in rats where high doses increased phase I hepatic metabolism. Oral administration of silymarin (100 mg/kg/day) to rats resulted in a significant increase in the activity of the mixed-function oxidation system (cytochrome P450; aminopyrine demethylation, p-nitroanisole demethylation). However, an experimentally-induced reduction in activities of the mixed-function oxidation system and glucose-6-phosphatase could not be prevented by pretreatment with silymarin. In human volunteers, treatment with silymarin (210 mg/day for 28 days) had no influence on the metabolism of aminopyrine or phenylbutazone. (2) Concentrated milk thistle (silymarin) extract at commonly administered doses did not interfere with indinavir therapy in patients with HIV. (3) In other words, despite the findings of in vitro and in vivo studies, there was no evidence from clinical studies that milk thistle extract increases phase I/II liver metabolism. The reason behind this discrepancy is probably that normal clinical doses are not high enough to achieve the effects shown at the artificially high doses used in experimental models. But a study has recently been published which, on the face of it, appears to challenge this position. (4) A clinical study was undertaken in 12 healthy volunteers. At first, subjects received metronidazole (Flagyl; a substrate for cytochrome CYP3A4 and CYP2C9) alone at a dose of 400 mg every 8 h for 3 days. On day 4, blood and urine were collected at different time points and metronidazole levels were measured. After a washout period of one week silymarin was given at a daily dose of 140 mg for 9 days. From day 7 both silymarin (140 mg/day) and metronidazole (3 X 400 mg/day) were given till the 9th day. On day 10, blood and urine were collected as above and the levels of metronidazole and its metabolite were measured. Administration of silymarin increased the clearance of metronidazole and its major metabolite, hydroxy-metronidazole (HM) by 29.51% and 31.90% respectively, with a concomitant decrease in half-life and maximum concentration. Urinary excretions of acid-metronidazole, HM and metronidazole were all decreased." Here's some more interaction info: http://www.nutritionworkshop.com/html/LYME%20DRUG%20INTERACTIONS.htm
Nelly (France-neuroLyme and ????)
Nellly- Interesting
Nellly- Interesting comment. I'll see if our experts have anything to say about it. On the face-validity, though, any of us taking metronidazolei pulses for Cpni can attest that it's bloody effective, if die-off reaction tells us anything. If it's being interfered with at all it doesn't seem like much. On the other hand, since I tend to do a Vitamin C flush day 3 of a tinidazole pulse, that much antioxidanti could lower the effective blood levels for the rest of the pulse, so I might go ffrom two a day back to my previous regimen three a day on those last two days.
On Wheldon/Stratton protocol for Cpn in CFSi/FMSi since December 2004.
I, more than anyone, will
I, more than anyone, will attest that metroi/tinidazole works BLOODY well too!
In fact I have been saying this for ...24 years ...only :) In fact it is the only abxi that seriously impact my symptoms.
As you might rembember, I am still trying to determine what my exact infectious cocktail is. I had many tick-bites and EM rash 24 years ago, many tick-bites after that and imidazoles ALWAYS give me clear-cut improvements for the first few days, followed by the (to be expected?) massive headaches. My history is far too complex to be gone into at this stage, but I had/have severe symptoms in virtually every body organs and systems, including lots of heart and neuroi symptoms.
If I look back, what I have been trying to do for the last so many years is try and use imidazoles in the best possible way to ensure the best possible outcome whilst minimising deleterious effects. I think this forum will help me work out how to juggle the abxi better.
BTW: I haven't yet discovered how to change settings, my eyes are sore and the print of what I write is tiny
Nelly (France-neuroLyme and ????)
Size of type is a common
Size of type is a common complaint- I am not good on comp but find a "view", should be a dropbar and a choice of size of type. Mine is at the top left.
Ignorance is voluntary bad luck. Lauritz S. A true Viking
If you come to a fork in the road, take it. Yogi Berra
This milk thistle thing is