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Part 1
Acute liver failure (ALF) is a serious and life-threatening condition commonly associated with drugs and herbal products. When it is associated with herbal medicine use, there have been serious alerts in the media to induce fear in consumers. Piper methysticum (kava kava), Larrea tridentata (chaparral) and more recently Cimicufuga racamosa (black cohosh) have been implicated in ALF, although it is not always clear what the true aetiology of these cases has been.
1. In comparison, paracetamol poisoning is the most common cause of fulminant liver failure in the US and the UK.
2. Paracetamol is also the most commonly used over the counter (OTC) pain reliever world wide.
In a recently published study, 79% of people who had accidental paracetamol poisoning reported taking it for pain. William Lee at the University of Texas Southwestern Medical Center in Dallas and his colleagues published data in the December, 2005 issue of Hepatology on patients with acute liver failure who were in a coma. Of the 275 people with acetaminophen poisoning, 8 per cent received a liver transplant, 65 per cent survived without one and 27 per cent died.
3. Paracetamol poisoning is supported by evidence to be damaging to our bodies, and alternatives for pain management need to be acknowledged and accepted among biomedical practitioners, pharmacists and the public.
Although paracetamol is not thought of as a true anti-inflammatory, it is commonly used for muscle aches and headaches. One of the actions of paracetamol is to inhibit the binding of nuclear factor kappa B (NFkB), a transcription factor involved in the encoding and regulations of substance involved in the process of inflammation, including cyclooygenase enzymes. The pathways signalled by NFkB are also involved in the formation of cancers, sepsis, and respiratory distress.
Other natural agents that have activity inhibiting NFkB are N-acetyl cysteine (NAC), apocynin from Picrohiza kurroa and curcumin.4 These compounds are also hepatoprotective and are excellent choices for patients who are transitioning off paracetamol use. Other compounds which can inhibit NFkB are polyphenols from green tea and quercetin.
N-Acetyl Cysteine
One of the ways paracetamol is damaging to the liver is that a metabolite, N-acetyl-p-benzoquinlneimine (NAPQI), uses up all available glutathione (GSH). When enough GSH is present NAPQI is conjunagated with glucuronide or sulphate and eliminated.
The standard treatment for paracetamol poisoning is NAC given within 12 hours. NAC stimulates GSH synthesis and can enhance the activity of glutathione-s-transferase, one of the enzymes responsible for detoxification of xenobiotics. NAC also inhibits NFkB.
NAC has powerful mucolytic activity, and is an appropriate therapy to use when treating respiratory-related inflammation due to infections and influenza. It is also safe for children, who should not use aspirin or salicylates due to the risk of Reye's syndrome. NAC is also appropriate to be given in conjunction with paracetamol.
Picrohiza kurroa
Picrorhiza kurroa is an herb traditionally in for Ayurvedic medicine for liver and lung conditions. Constituents of Picrorhiza include the iridoid glycosides picrosides and kutkoside, nine curcurbitacin glycosides and apocynin, a catechol. Apocynin has anti-inflammatory action by reducing the formation of thromboxane A2 from arachadonic acid.8 Apocynin also prevents NFkB activation, thus inhibiting inflammatory mediators from the COX-2 lines from two different mechanisms. Although Picrorhiza is considered safe to use, it and other herbs containing iridoid glycosides should not be used during pregnancy.
Curcumin
Curcumin is considered to be the most active constituent in Curcuma longa. Curcumin treats both acute and chronic inflammation, and has been found to be as effective as or better than oral steroid medication for treating arthritis. Not only does curcumin inhibit NFkB 4, various laboratory studies have identified a number of different molecules involved in inflammation that are inhibited by curcumin. These molecules include phospholipase, lipoxygenase, cyclooxygenase 2 (Cox-2), leukotrienes, thromboxane, prostaglandins, nitric oxide, collagenase, elastase, hyaluronidase, monocyte chemoattractant protein-1 (MCP-1), interferon-inducible protein, tumor necrosis factor (TNF), and interleukin-12 (IL-12). Curcumin can significantly protect against paracetamol-induced lipid peroxidation in the liver. Curcumin is not soluble in water, and is best taken with a meal that includes fat.
Although targeting NfKB leads to pain relief by reducing activity of COX enzymes, substances acting directly on the prostaglandin pathways via COX should be used when dealing with chronic pain situations. These substances are the fish oil derived fatty acids eicoapentaenoic acid (EPA) and docosahexaenoic acid (DHA), Boswellia serrata and ginger.
Pain is a common symptom that people of all ages seek medical attention for. Medical evidence clearly supports against the use of paracetamol as a safe pain reliever. It is known to cause ALF, and if not treated in time, death. Of all the cases of ALF studied in the recently published Hepatology article, 42% were clearly due to paracetamol poisoning. Alternatives to paracetamol given in this article are recommended because they specifically interact with the same mechanisms for pain and inflammation, and each has a protective effect on the liver. A healthy liver encourages wellness by detoxifying compounds from the environment, synthesizing proteins carriers, including albumin, for hormones and vitamins, producing bile for dietary fat absorption and excretion for toxic metabolites, cholesterol and lipid waste products. There is a naturopathic aphorism that asserts "when in doubt, treat the liver." In the case of anybody who regularly uses paracetamol, this tenet should not be forgotten.
1. Bone K. Black Cohosh: Does It Really Cause Liver Damage? Naturopathy Digest 2005 1:1. http://www.naturopathydigest.com/archives/2006/jan/bone.php
2. Waters E, Wang JH, Redmond HP, Wu QD, Kay E, Bouchier-Hayes D. Role of taurine in preventing acetaminophen-induced hepatic injury in the rat. Am J Physiol Gastrointest Liver Physiol. 2001 Jun;280(6):G1274-9.
3. Larson AM, Polson J, Fontana RJ, Davern TJ, Lalani E, Hynan LS, Reisch JS,
Schiodt FV, Ostapowicz G, Shakil AO, Lee WM; Acute Liver Failure Study Group.
Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study. Hepatology. 2005 Dec;42(6):1364-72.
4. D'Acquisto F, May MJ, Ghosh S. Inhibition of Nuclear Factor Kappa B (NF-B):: An Emerging Theme in Anti-Inflammatory Therapies. Mol Interv. 2002 Feb;2(1):22-35
5. James LP, Mayeux PR, Hinson JA. Acetaminophen-induced hepatotoxicity.
Drug Metab Dispos. 2003 Dec;31(12):1499-506.
6. Kelly GS. Clinical applications of N-acetylcysteine. Altern Med Rev. 1998 Apr;3(2):114-27.
7. Picrorhiza kurroa. Monograph. Altern Med Rev. 2001 Jun;6(3):319-21
8. Engels F, Renirie BF, Hart BA, Labadie RP, Nijkamp FP. Effects of apocynin, a drug isolated from the roots of Picrorhiza kurroa, on arachidonic acid metabolism. FEBS Lett. 1992 Jul 6;305(3):254-6.
9. Barbieri SS, Cavalca V, Eligini S, Brambilla M, Caiani A, Tremoli E, Colli
S. Apocynin prevents cyclooxygenase 2 expression in human monocytes through NADPH oxidase and glutathione redox-dependent mechanisms. Free Radic Biol Med. 2004 Jul 15;37(2):156-65.
10. Sodhi V. Turmeric, A powerful Anti-inflammatory. Ayurvedic Science Updates, Modern Science validating Ancient Medicine. http://ayush.com/articles/turmeric.htm
11. Donatus IA, Sardjoko, Vermeulen NP. Cytotoxic and cytoprotective activities of curcumin. Effects onparacetamol-induced cytotoxicity, lipid peroxidation and glutathione depletionin rat hepatocytes. Biochem Pharmacol. 1990 Jun 15;39(12):1869-75.
Lorinda Sorensen ND. - FXMed
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