1/1/2014 again, its comforting that no new evidence of hepatotoxicity of genuine black ohosh; or kava; or (USA-grade) Herbalife products have been reported the past two years.
Teschke ea from Germany make the important point that herbaltoxicity is likely due to the “kava paradox”, that no toxicity is reported with ancient time-tested herbal remedies used appropriately by tradition in their fresh natural state and their countries of origin eg Pacifi islands; ,
but that adverse events occur with commerial eg alcohol-extracted and often preserved and old preparations, and in untested combinations with other substances especially statins, ethanol, and unknown viruses. .
The Herbalife company has just had to publish again an update rebuttal of bad papers wrongly implicating and accusing Herbalife. Their summary says:
16 March 2012 it is comforting to note that there have been no new reports the past year of toxicity from these products.
In fact some lab work seems to favour black cohosh for cancer prevention;
2 Feb 2011
Since June 2010 there have been no new cases of toxicity from Black Cohosh, herbalife or kava reported on Pubmed.
BLACK COHOSH: BEGGING THE QUESTION OF INDICATION- NEED.
The new literature analysis Suspected black cohosh hepatotoxicity: no evidence by meta-analysis of randomized controlled clinical trials for isopropanolic black cohosh extract by Naser et al from Yale , and Germany(the main producer of black cohosh BC products)- begs the question.
As this colunm has previously reviewd about BC, women have died from or needed liver transplants after taking it.. Hence most Authorities have Black Box warning requirements Recurrences of liver reaction have been reported on rechallenge. These scattered cases can be argued away on metanalysis, but they cannot be ignored. One death or acute liver failure is unacceptable when BC is never an essential drug without other safe options.
Another study also published now (Wang ea from the FDA Centre for Drug Evaluation ) http://www.ncbi.nlm.nih.gov/pubmed/20920542 contradicts the German metanalysis with more basic toxicological data: “Computational analysis of positively predicted constituents showed … specifically, protocatechuic acid from black cohosh… predicted positive for liver toxicity endpoints also confirmed with literature findings”
Black cohosh is not physiological hormone replacement, BC is recommended by its proponents solely for menopause symptoms (it has no other benefits) for up to 6 months.
So why risk, use black cohosh at all?
Appropriate balanced hormone replacement – preferably human hormones, not xenohormones ie hormones not found in the healthy women, and not by swallowing it- is indicated permanently in all women .
As previouslly pointed out in this column, the International Menopause Society has summed it up in putting approriate HRT as the main agent(s) for menopause symptoms as well as for its permanent multisuystem benefits; and the human hormone gamma-aminobutyric acid GABA as the only alternative that is both safe and cleearly proven better than placebo for improving both hot flashes and sleep, anxiety. Used appropriately and with sensible monitoring and dose titration, all such hormone balance has no longterm risks.
MDICOLEGAL LIABILITY: under the new Conumae Protection Act CPA in South Africa, the pendulum has gone ridiculously too far. irrespective of the onus on manufacturers and promoters of any product, the onus is on the end-prescriber, end-dispenser to warn consumers of potential risks, and any consumer claim for consequent damages is legally against only the final and retail supplier.
So no supplier of black cohosh is protected against consequent liability unless he gets a signed waiver from the purchaser after the recorded warning about its potential toxicity.
16 June 2010
there are no new adverse toxicity reports on Hebalife, black cohosh or kava so far in 2010 .
Both Herbalife, and black cohosh products, remain marketed and in demand in South SAfrica.
There are no new serious adverse reports or concerns published on Pubmed or Google about Herbalife products in 2009.
On Pubmed there were 2 new cases of liver and coagulation problems associated with black cohosh in mid2009, from a Germanic and an Italian institute; and 14 hepatitis cases associated with kava ingestion confirmed from around the world .
4 Jan 2009
This review is not about benefit of black cohosh (independent trials show none for menopause symptoms) or Herbalife (trials support that Herbalife is indeed a weight loss aid), or kava (it is a confirmed anxiolytic analgesic euphoriant); but about toxicity potential however rare – considering that none of these products can make any claim to being a necessity.
Contamination aside, there are no new relevant reports on Herbalife the past two months on Pubmed,
but indeed 4 new reports on black cohosh; and one on kava.
Lessons for black cohosh and Herbalife may be learnt from kava. Kava-kava was hastily banned eg in Europe and South Africa early this decade owing to reputed association with hepatotoxic deaths. But on careful study these toxicity claims appear to be uncertain.
The claimed benefits of kava are analgesic, euphoriant and relaxant, without addiction potential. The four trials of Kava (between 1991 and 2003, in Italy and Germany) confirmed that kava has anxiolytic benefits in the menopause syndrome.) . The hepatotoxicity (not reported from the source – Polynesia – unless taken by alcoholics) was reported largely from western countries, where commercially sold kava extract was apparently differently extracted, and from the aerial leftovers of the kava; whereas in Polynesia it is extracted only from the root. A recent website from the NIH shows it is not banned there, but expresses much caution.
A careful analysis of kava hepatotoxicity by Teschke ea in Germany last month again finds little evidence of toxicity if kava is taken from a reputable manufacturer at prescribed dose and for short duration – as applies equally to alcohol, and most drugs.
An objective NICUS Nutritional Institute of University of Stellenbosch Report critical of Herbalife is quoted verbatim in the Summer 2008 Newsletter of the Association of Dieticians of SA. NICUS- a world authority in Nutrition – confirms it stands by this report. It could thus be taken as a directive (to condemn Herbalife)- to dieticians for whose professional advice some patients wrongly substitute diet supplements; where these modalities- careful professional diet advice and counselling, and supplements- are actually complementary..
But there does not appear to be any more evidence to condemn Herbalife than there was a year ago. As far as Pubmed and Google reveals, the reports [to date end of 2008 on Pubmed) of adverse effects were from 4 discrete European regions [ Iceland; Switzerland; Spain & Israel) , apparently wth locally formulated Herbalife, not the USA main factory product, leading to assumption of a local production fault. There appear to have been 2 cases of liver failure in some 33 affected patients, in one of whom liver transplant became necessary but the patient died.. .
One cannot condemn all babyfood because some is deliberately adulterated with melamine by ruthless Chinese sham factories. Commercial babyfood is arguably a necessity for many.
We await an updated rebuttal from Herbalife in the new year- but there does not seem to be anything for them to add to their rebuttal of last year..There has been no published evidence to justify update on Herbalife during 2008.
The accusation (by one patient, and a convicted fraudster, Minkow) of a claimed lead-contaminated Herbalife batch in California has, strangely, generated no updates for months now- but on the wiki herbalife update , it says “In August 2008, Minkow retracted all accusations against Herbalife and removed any mention of the company from his Web site.” – there is no report of whether Herbalife bought his silence or not , which is a pity- see also. ; but see also heavy flak against Minkow , suggesting that his whole campaign was a successful bear scam to profit from Herbalife shares.
The current Wiki Herbalife review also quotes a new trial validating benefit for weightloss. Caveat Emptor.
It may be asked why a Nutritional authority like NICUS: warns against Herbalife but not against the potentially fatal black cohosh. New independent analyses are both for and against them:
Analyses of case reports from Univ Florida (Palacio 2009) and Italy (Borrelli 2008) recommend caution about black cohosh for humans in view of adverse case reports; while a German analysis (Teschke 2008) exonerates black cohosh in every single case till then.
A trial from USA (Davis 2008) found that “black cohosh significantly increased the incidence of lung metastases in tumor-bearing mice compared with mice fed the isoflavone-free control diet”.
Clearly the valid divergence of opinion comes down to complex statistics of probability.
Black cohosh has been associated with severe liver failure and transplantation in a number of women on a number of continents, for which reason the local Health Products Association, like all responsible authorities , finally agreed and issued recommendations that Black Cohosh label must be black-boxed- there is no justification for it’s sale as a useful product, unlike the role than can be argued for food substitute powders.
So why should anyone use black cohosh for menopause symptoms (when it’s benefit seems to be largely placebo, with grave doubt about safety) , when there are proven safe symptom relievers eg GABA (no adverse reports); or lowdose balanced appropriate parenteral human sex hormones (no adverse reports, and have numerous longterm multisystem benefits- which neither black cohosh nor GABA can claim..).
This review is not about benefit, but safety. Regulators remain silent about drastically curtailing sale of the most lethal substances in widespread unregulated (and unnecessary) use- paracetamol, other nonsteroidal anti-inflammatories, statins for uncomplicated mild-to-moderate lipidemia, alcohol, tobacco and sugar, and pollution of everything by industrial adulteration with synthetic (often estrogenic) endocrine disruptors and virtually all fast foods with cornstarch and/or sugar.
The hysterical approval of diethylstilbestrol DES by the FDA by 1950, and for a massive 1950 maternity trial against all evidence (even though it’s toxicity was recognized by 1953, it’s sale anywhaere was finally banned only 20 years later) continues to torment the original myriads of guineapig women, their children and now grandchildren. These scandals are dictated by individual opportunist, corporate and governmental greed, and indifference to medical evidence and prevention.
The analogy for black cohosh, kava and Herbalife is perhaps:
#the ~20year delays before the FDA would licence the lifesaving lithium salt, and metformin, in USA;
#the ~5year hysteria over HRT after the Women’s Health Initiative – when the over-estimated risks of inapproriate use of OHT in elderly women were stupidly and harmfully (for thousands of women) extrapolated to young women and other HRT preparations;
#the melamine- baby milk formula catastrophe – the problem for the latter was exclusively some contaminated babyfood batches made in China especially for the lucrative export market. .
The jury can thus be considered as still out on both black cohosh, kava and Herbalife, until manufacturers of commercial products (not traditional preparations of eg kava and black cohosh taken by residents who grow these) can produce evidence, confirm that the risk was limited to specific batches of the commercial product and adherence to accepted recommendations, and not due to other possible risk factors.
LIVER DAMAGE IN EUROPE ASSOCIATED WITH HERBALIFE USE:
4 Sept 2007 Review
The following reports below of HerbaLife-associated liver failure appear on Medline – from Spain, then Israel and Switzerland.
:The July 2007 reports of the two dozen Herbalife-associated hepatitis cases from Israel & Switzerland reveal that liver problems occurred after about 5 months on the products; and that relapse occurred in about 20% on rechallenge with Herbalife ie in this percentage the association is proven.
Herbalife results for weight control have been reported as good. The only problem is historical according to the current Wikipedia entry: “Some of the original Herbalife weight loss products contained the active ingredient Ma Huang or Sida cordifolia, two herbs containing ephedrine alkaloids.
Adverse reactions involving the company’s Thermojetics original green tablets were recorded by the U.S. Food and Drug Administration and Herbalife subsequently stopped using ephedrine in its products in the face of rising insurance premiums. The U.S. FDA banned supplements containing ephedra in 2004.“
It is possible that the case reports below are unrelated to Herbalife itself , or that in those countries ephedra-containing Herbalife was still in use at the time, or that potentially hazardous herbs etc were added locally.
From Yahoo.com, there is an authoritative rebuttal from Iceland dated February 2007.
A score of drugs and herbs can cause liver damage, topical ones – albeit rarely- include mushrooms; black cohosh and kava – see a recent list.
Drugs like ticrynafen, methyldopa and cerivastatin were discarded among other reasons because of liver problems, which are among many reasons why necessary sex hormone contraception and replacement should rather not use designer patent ie synthetic drugs, and especially not by mouth (hepatic first pass effect).
So it is always difficult to blame a single product, as the ongoing debate about black cohosh shows – which many “first world” regulators have “black boxed” ie added a compulsory warning to black cohosh warnings.
As with black cohosh, with a rare adverse event report, users of such products must weigh up for themselves.
As they say, since Herbalife tends to be custom-made in each country, with numerous ingredients (some undisclosed), it is so far impossible to incriminate whether the cause was local product corruption, or some appreoved component, of which the known possible culprits are ephedra and camelia.
Other known hepatotoxic herbs like black cohosh, kava and mushrooms were not mentioned. A few of the patients had viral hepatitis. Only 7 cases had also taken other known potential liver sensitizers – some synthetic sex hormones (4), aspirin (3), statin (1) and hydrochlorothiazide(1), of which 2 cases had positive recurrence of hepatitis on rechallenge with Herbalife.
UCT Medicines Information Centre is unaware of any such problems locally, and can recollect only perhaps 2 queries about Herbalife in some 23 years. Clarification is awaited from Herbalife headquarters.
From Swiss data the estimated incidence was below 2 cases per million Herbalife users, but both studies were based only on hospital records.
Considering the severe global problem of hepatitis from other causes (due to alcohol; obesity/diabetes (steatohepatitis, sulphonylureas, glitazones); numerous infections; carbon tetrachloride; synthetic sex hormones (oral contraception and postmenopausal hormone therapy) , mushrooms, antibiotics and antivirals, , autoimmune disease, antiepileptics, nifedipine, amitryptiline, allopurinol, nonsteroidal anti-inflammatories including aspirin and paracetamol , black cohosh, kava, antifungals and paracetamol), and that the rare adverse association of herbalife with liver damage may well have been limited only to Herbalife products made in those three “European” countries at that time, there is clearly no cause for alarm about Herbalife – just awareness.
The urgent problem of endemic liver disease is rather the avoidance of infections and potentially hazardous antimicrobials; mushrooms; carbon tetrachloride, alcohol excess; sale pf paracetamol without inclusion of protective vitamins and N-acetyl cysteine; and avoidance of potential hepatotoxins which are rarely if ever justified considering their risks, and safe effective alternatives available for eg statins, sulphonylureeas, glitazones, black cohosh, kava, non-steroidal anti-inflammatories; oral sex hormones; and sulphonylureas.
The centuries-proven plant galega officinalis (extract) metformin after 85years of modern use remains the only drug proven in longterm use to both reduce liver damage, lipidemia, thrombosis, adiposity and insulin resistance, and thus almost halve the incidence of new diabetes, hypertension/vascular disease, cancer and thus all-cause premature medical mortality.
Thus appropriate general use of metformin with long-proven vitamins, minerals, biologicals, safe herbs, fish oil and systemic human sex hormones – combined with prudent lifestyle and largely natural fresh foodstuffs- – does away with most of the well-known potential hepatitis drug risks listed above.
In defence of free market enterprise and choices, those who choose convenience safe proven food substitutes or other complementary products as part of an acceptable balanced regime advocated by suppliers like Herbalife do well, they should just be sure of the ingredients and supplier; and they should report and discuss what they use with some knowledgable up-to-date healthcare provider.
Response from Herbalife
Herbalife’s South Africa CEO responds reassuringly:
Herewith a statement from Herbalife in response to the issues raised by yourself earlier in the week:
While we are aware of reports of abnormal liver function blood tests such as those reported by Dr. Oneta, our extensive consultation with internationally recognised liver experts has led repeatedly to the conclusion that these associations in time cannot be linked to any Herbalife product.
These small numbers of reports are anecdotal and millions of satisfied customers all over the world have been using our products for more than 27 years. All Herbalife products are formulated and manufactured in accordance with strict standards overseen by the Herbalife Scientific Advisory Board, which is chaired by David Heber, M.D., Ph.D., F.A.C.P., F.A.C.N. Quality control is overseen by our Scientific Affairs Group, chaired by Y. Steve Henig PhD and made up of an international panel of experts in nutrition and botanical dietary supplements.
Herbalife products, which are now sold in 65 countries, are formulated, registered and labelled in accordance with the regulatory requirements in every market where sold. All Herbalife products are safe to consume as directed.
Many consumers who choose to use Herbalife weight-management products for weight loss are overweight, some significantly so. Pre-existing medical conditions such as obesity and diabetes can be associated with non-alcoholic fatty liver disease, a disorder that may return certain types of abnormal blood test results. These test results, therefore, may have nothing to do with any herbal supplement, but rather are the result of a pre-existing medical condition. In addition, it is possible for an individual to have an allergic reaction to our products, the same way one might to any food product; for example, strawberries or shellfish. Herbalife supports the recommendation that consumers visiting their doctors for medical treatment inform them of any supplements they may be taking.
As a socially responsible company, we operate an adverse event reporting procedure that deals with the small number of queries we have from doctors and consumers and we operate an open dialogue policy with the medical community. All adverse event reports are investigated thoroughly in consultation with the consumer and the physician (if they are available) to fully understand the facts. None have resulted in the compulsory withdrawal of any product, ever. In the United States, Herbalife actively lobbied Congress to pass legislation mandating the submission of all dietary supplement and over-the-counter drug serious adverse events to the Food & Drug Administration. That new law takes effect December 22, 2007.”
J Hepatol. 2007 Oct;47(4):521-526. Herbal does not mean innocuous: Ten cases of severe hepatotoxicity associated with dietary supplements from Herbalife((R)) products. Schoepfer AM, ea.University Hospital Bern, Switzerland.
METHODS: To determine the prevalence and outcome of hepatotoxicity due to Herbalife((R)) products. A questionnaire was sent to all public Swiss hospitals. Reported cases were subjected to causality assessment using the CIOMS criteria. RESULTS: Twelve cases of toxic hepatitis implicating Herbalife((R)) preparations (1998-2004) were retrieved, 10 sufficiently documented to permit causality analysis. Median age of patients was 51 years (range 30-69) and latency to onset was 5 months (0.5-144). Liver biopsy (7/10) showed hepatic necrosis, marked lymphocytic/eosinophilic infiltration and cholestasis in five patients. One patient with fulminant liver failure was successfully transplanted; the explant showed giant cell hepatitis. Causality assessment of adverse drug reaction was classified as certain in two, probable in seven and possible in one case(s), respectively. CONCLUSIONS: We present a case series of toxic hepatitis implicating Herbalife((R)) products. Liver toxicity may be severe. A more detailed declaration of components and pro-active role of regulatory agencies would be desirable.
J Hepatol. 2007 Oct;47(4):514-520. Association between consumption of Herbalife((R)) nutritional supplements and acute hepatotoxicity. Elinav E, ea -Hebrew University Medical Center, Israel.
: In 2004, identification of four index cases of acute hepatitis associated with Herbalife((R)) intake led to a ministry of health investigation in all Israeli hospitals. Twelve patients with acute idiopathic liver injury in association with consumption of Herbalife((R)) products were investigated.
RESULTS: Eleven of the patients were females, aged 49.5+/-13.4 y. One patient had stage I primary biliary cirrhosis and another had hepatitis B. Acute liver injury was diagnosed after 11.9+/-11.1 months of initiation of Herbalife((R)) consumption. Liver biopsies demonstrated active hepatitis, portal inflammation rich with eosinophils, ductular reaction and parenchymal inflammation with peri-central accentuation.
. CONCLUSIONS: An association between intake of Herbalife((R)) products and acute hepatitis was identified in Israel. We call for prospective evaluation of Herbalife((R)) products for possible hepatotoxicity.
Med Clin (Barc). 2007 Feb 17;128(6):238-9.
[Hepatotoxicity associated with the consumption of herbal slimming products] Duque JM,ea. [Article in Spanish] Letter