It seems that the Zeolite MLM people are just getting more persistent. We have already pointed out that this material in its fibrous form is associated with serious carcinogenicity (mesothelioma). Quite puzzling for a material that is supposed to be the latest miracle cure for cancer, but zealots don’t usually worry about bothersome details; in fact both zeolite distributors who approached our clinic demanding audience were blissfully unaware of the fact at all. As mentioned before, the main real world use of the stuff is as a cheap throw away substitute for activated charcoal in removing toxic metals from industrial waste water in third world countries that cannot afford the superior efficacy of charcoal due to its expensive recycling costs. The main ingredients are inorganic (it is ground up volcanic ash) principally aluminium and silicon; both these elements are associated with significant toxicity in humans.

The zeolite zealots are claiming all sorts of magical anticancer properties for zeolites based on a composite paper by 15 authors from Zagreb published in 2001. Before going into the paper, the initial question that should be asked by anyone taking zeolite as an oral medicine is – are zeolites absorbed following oral ingestion? The likelihood is, as with most mud, charcoal, clay etc, that internal ABSORPTION of the stuff is minimal. Even earthworms, adept at extracting soil nutrients, poop mud out. Charcoal and clay are both administered clinically in humans by mouth to ADSORB poisons from the gut, and are completely eliminated without being absorbed into the body at all.

No figures are available at all for the absorption of the zeolite material in animals or humans. The toxicology “studies” in the Croation paper gave rats a diet enriched with zeolite for months but if the stuff is 100% pooped out that hardly establishes lack of toxicity merely lack of absorption. No toxicity studies were done on injecting the animals to obtain the massive concentrations used in the in vitro cell line studies. The underwhelming in vitro cell line study results of zeolite were only observed at high concentrations (50mg/mL) studies. Apparently the tests at 0.5 mg/mL and 5.0 mg/mL were without effect. How could these concentrations possibly be achieved by oral dosing of zeolite? The answer is obvious – they can’t. The zeolite zealots having undergone a religious conversion experience are focussed on downline and the pot of gold at the end of the downline rainbow, and are apprently unconcerned with mundane biological realities. The bottom line is, zeolite is likely not absorbed at all. (If it was you would likely be in trouble from aluminum or silicon toxicity.) Either way, meaningful data establishing absorption levels or toxicity is unavailable.

To be continued.

This diagram is referred to in the podcast on advanced cancer (part 1) . The scheme is based upon the published and unpublished work of many researchers and clinicians. In practice the phases may overlap in time. Botanical medicines are especially appropriate for stage 2-6, while conventional approaches predominate for 1+4.

Podcast in three parts of a 90 minute talk given by JT at the South West Conference on Botanical Medicine 2005 on treatment of advanced cancer. This is Part 1, which starts with a brief introduction/bio/context and covers copper reduction as an anti-angiogenic therapy. Parts 2 and 3 of this talk cover artemisinin and Vitamin C with Vitamin K3. (iTunes subscribers will receive directly when updating subscriptions… others can download from the link below.)

Advanced Cancer Podcast.mp3

File size 7.9 Mb. Duration 34 minutes. mp3 format.

Its been one of those weeks for anyone following “health news feeds” in mass media. First we find out that saw palmetto does not work according to the NEJM. A trial using the herb for BPH symptoms failed to find a significant effect, and in the same issue, the Editors slammed herbal medicine as being misleading to consumers! Meanwhile, across the pond, the BMJ published a “metastudy” (everyone’s favorite) on melatonin, and found that it was not proven to be effective for anything…sleep, jet lag or anything else. Another Editorial slammed the use of dietary supplements. Meanwhile, after decades of harmful promotion of “lo-fat” products by physicians who know nothing about nutrition a huge long term trial revealed there was “no cardiovascular benefit” to “lo-fat” approaches. Silence.

Meanwhile back at the biotech factory, Genentech announced massive price rises in the cost of Avastin as the FDA extended its approval beyond colon cancer. The (underwhelming) drug can now cost $40,000 + for a course of treatment. In England, you can’t even get herceptin by taking the NHS to court.

Don’t worry: the FDA is protecting its citizens as usual…The NY Times today revealed how the FDA Director unprecedently “over-ruled” a unanimous opinion by its science committee and approved an implantable electric device that is completely unproven which can now be prescribed for treatment of refractory depression.

Is there something wrong with this picture?

Do not adjust your sets, there is a fault in reality.

The value of elevated PSA results in screening for prostate cancer has become increasingly controversial. (This should be distinguished from use of PSA as a marker for actual prostate cancer progression). A novel test is set to replace PSA as a predictive screening test - using the PCA3 or DD3 gene which is overexpressed in >95% prostate cancer. The test is particularly accurate in the “grey” zone of PSA values between 4-10 ng/mL. The dilemma with this mildly elevated PSA is whether to biopsy (possibly unneccessary) or whether to wait ( possibly letting a cancer grow) and retest PSA. Rapid results with very high specificty and predictivity can be obtained from a urine sample collected after prostatic massage to ensure shedding of prostate cells in the specimen. Currently offered by one lab only in the US, the test currently bills at $450.00. The lab turns round the data in 24 hours. Brilliant development for all those working with urological cancer.

Check out Bostwick Labs uPM3 test

An newly published open access article reports a survey of physicians from 6 hospitals in Trinidad. More than 60% accepted that herbs have beneficial health effects. Practical and prescribing knowledge of herbs lagged far behind acceptance. The survey also included a list of top herbs considered useful by the surveyed docs; Cannabis sativa came in third place, following Lemon Grass and Ginkgo. Seems like they are way ahead on the island…

A gap between acceptance and knowledge of herbal remedies by
physicians: The need for educational intervention
Yuri N Clement*, Arlene F Williams, Kristi Khan, Tricia Bernard,
Savrina Bhola, Maurice Fortuné, Oneil Medupe, Kerry Nagee and
Compton E Seaforth

Access full text: BMC Complementary and Alternative Medicine

The real depths of the drivel published by J Anal toxicology claiming ginkgo interactions cause fatal seizures can now be truly appreciated.

The swimming man report (Kupiec and Raj):

• failed to establish whether a seizure even occurred
• failed to establish whether ginkgo was even used
• failed to establish an interaction with anticonvulsants took place

The theoretical arguments about mechanism were all incorrect, namely

• CYP450 2C9 effects: solid experimental evidence against
• “ginkgo nut toxin”: irrelevant, does not occur in leaves.
• GABA inhibition: speculative and conflicts with known data

The circumstantial support for their thesis is slender:

• One unreplicated rodent study injecting more than 10x normal dose potentiated strychnine induced convulsions (unindexed Indian Journal Pharamcology report).
• Case report by Granger in 2001 which suggests a possible association between two cases of breakthrough seizure with valproate maintained patients and concurrent ginkgo use (Granger sensibly admitted absence of plausible mechanism and failure to demonstrate causality - A S Granger, Age and Ageing 2001;30;523-525)

Against which they failed to mention the substantial (overwhelming) evidence that

• ginkgo is neuroprotective (animal and human studies)
• gingko is protective against cerebral ischemia (stroke) damage (animal and human studies)
• ginkgo constituents (bilobalide) PREVENT seizures (animal studies)
• demographic of users suggests primarily aging population due to cerbrovascular benefits, cognitive benefits, memory and anti-dementia benefits. This population is more likely to suffer seizures than many…
• but tens of millions doses ginkgo extracts prescribed every year, no seizures reported.
• Tens of Dozens of clinical trials, no seizure adverse effects ever observed.

Nor do they account for drug/interaction factors such as

• possible polymorphisms of drug metabolizing enzymes
• other factors effecting serum drug level variation (individual, diet, lifestyle, etc)
• breakthrough seizures occur at therapeutic and sub therapeutic drug levels
• association, even if proven (which this case is not) is not causation.

For the editors of this journal to “peer review” (ha ha) the text and approve a title that asserts fatal seizure(s) note the plural! were caused by this herb is a classical demonstration of the cynical use of the [title] field of MEDLINE to engender an anti-herb pseudo-literature which in reality expresses only how bankrupt, blinkered and bigoted are its perpetrators.

Bottom line: is there a connection between ginkgo use and breakthrough seizures? It seems very unlikely, and certainly lacks evidence and a plausible mechanism in terms of drug interaction with anticonvulsant meds. If anything the currently available evidence is overwhelmingly opposed to the idea. Absence of proof is not proof of absence. A few simple experimental studies would clarify things, but funding and interest in such studies is not generally available. However, the issue should be discussed and analyzed with at least a modicum of rigor, objectivity and clarity, so that informed review of the data and treatment decisions can be made by practitioners and consumers alike.

In Herbal Hypotheses 2 - entitled MEDLINE and the Mainstream Manufacture of Misinformation I suggested in the conclusion of the paper that the times they are a’changin for the better, due to the potential of the combined effects of the Open Access Movement in medical publishing, together with progressive search engines such as Google and Google Scholar’s ambitions to rank and retrieve academic information without vested interest or bias and which is freely accessible to anyone using the web.

We should now add the power of bloggers, specifically herbloggers, into the equation. If you perform a Google search for ginkgo and seizures, or ginkgo, seizures, case report, etc you will find that Henriette Kress’s blog is top of the pile, with a post pointing to this HERBLOG’s critique of the ginkgo (swimming man) case report. And since what goes around comes around, the HERBLOG demolition of this execrable paper is now accessible to anyone searching Google for information about ginkgo and seizures.

In a microcosm, this is shows the potential countercultural power of the movement against mainstream antiherbal propaganda. yay!.

(more…)

Watchout for “zeolite”. Zeolite is being touted as the latest MLM snake oil… at least down here in Southern Oregon where due to high unemployment and a high proportion of gullible wealthy folk there are lot of people involved in pushing MLM health products from Rain Forest Herbs to “glyconutrients” and stem cell supplements.

I was asked by a patient whether they should take zeolite ( a “volcanic” mineral complex) for their malignancy. A quick down dirty MEDLINE search revealed that zeolite, unlike most MLM scams has hundreds of studies relating to cancer. OOops! I thought for a split second as the downloads started coming that I had been mistaken. Until I started reading them - they are all about how zeolite CAUSES cancer!!

Not only does zeolite cause cancer, it causes pleural mesothelioma. Mesothelioma is the most deadly and almost untreatable form of lung cancer known, and is associated with exposure to asbestos and silicon fiber. The form of zeolite that causes meothelioma is fibrous, and is not the powdered crystal form pushed by the MLMers. But they have been told by their “UPLINE” marketors that zeolite cures cancer (among other things). Like babes in arms the new recruits sally forth promoting a “cancer cure” that causes mesothelioma. Well, ok the “fibrous” form causes mesothelioma not the powdered product. So would you eat ground up asbestos rather than inhale the fiber form? At least have a sales-chat line ready to explain away the embarrassing facts of the carcinogenic properties of the material to people who are not complete morons.

Now, I believe in the inalienable constitutional right of the American citizenry to inflict self abuse by any means, whether high velocity automatic weapons or MLM products. At least as consenting adults in private. What is objectionable is touting them as snake oil cure-alls to people with a cancer diagnosis. And especially my patients.

A single Croatian lab has recently put out TWO lame studies claiming limited antioxidant and anticancer effects for this material. The studies are so underwhelming that one wonders how they were even financed. Half a clove of garlic probably has more anticancer effects than a volcano full of zeolite, and is a lot better for your lungs too. Hmmm. What else is zeolite used for? Well as a silicate based mineral complex (= mud) it has physical adsorbent properties - a little like charcoal or bentonite clay. It can therefore complex certain metal ions, and has been used in industrial animal husbandry (=factory farming) for these purposes. Needless to say, that makes it a miracle “detox”agent - and detox = “cancer cure”.
Caveat emptor!

SO far we have discovered

• There is no proof that swimming man had a seizure in the pool.
• There is no proof that he was consuming ginkgo at the time.
• The main proposed mechanisms of interaction (ginkgo nut toxicity or CYP450 2C9 induction) are complete nonsense.

There is a large body of work that shows that ginkgo extracts are neuroprotective in a number of ways. They lower brain damage resulting from ischemia, they protect neurones against oxidative damage, they protect mitochondrial membranes in the brain, they help correct several parameters involved in Alzheimer’s pathology (beta-amyloid, alpha secretase, cytochrome C oxidse deficiency) etc etc.
There is no evidence from clinical trials or post-marketing consumer surveillance that ginkgo has any toxicity related to seizures or lowering the seizure threshold. Given the herb is used by elderly people especially, and those with brain damage in particular the likelihood of such effects emerging is should be increased if they really exists…but..wait for it…there is experimental evidence that GINKGO REDUCES SEIZURES.

A series of animal studies by Sasaki and coworkers established that bilobalide (one of the main terpene constituents of ginkgo) when given by mouth at low doses for 40 days leads to increases in brain GABA and glycine (both inhibitory neurotransmitters) and reduced seizures induced by different stimuli including adminstration of electroshock, pentyltrenezol, isoniazid and high doses of MPN (ginkgo nut toxin see previous post on nuts). This suggests multiple mechanisms of antiseizure activity since these stimuli induce convulsions by different mechanisms.

here are a couple of the studies:

Sasaki, K., K. Wada, et al. (1997). “Bilobalide, a constituent of Ginkgo biloba L., potentiates drug-metabolizing enzyme activities in mice: possible mechanism for anticonvulsant activity against 4-O-methylpyridoxine-induced convulsions.” Res Commun Mol Pathol Pharmacol 96(1): 45-56.

Anticonvulsant effects of bilobalide, one of the constituents of Ginkgo biloba L., on the convulsions induced by 4-O-methylpyridoxine (MPN) were investigated in mice. Bilobalide reduced the duration and incidence of MPN-induced convulsions depending on its dose and the period of treatment. In addition, the anticonvulsant effect was manifested more than 24 hours after treatment and the effect lasted for 7 days after its withdrawal. In mice treated with bilobalide (30 mg/kg, p.o., once a day for 4 days), hepatic 7-methoxycoumarin O-demethylase activity was potentiated, and the disappearance of MPN in blood after MPN injection was faster than in controls. From these results, it is assumed that the anticonvulsant effect of bilobalide against convulsions induced by MPN partly involves modulation of hepatic drug-metabolizing enzyme activity, which leads to accelerated elimination of MPN.

Sasaki, K., S. Hatta, et al. (2000). “Bilobalide prevents reduction of gamma-aminobutyric acid levels and glutamic acid decarboxylase activity induced by 4-O-methylpyridoxine in mouse hippocampus.” Life Sci 67(6): 709-15.

We previously reported that bilobalide, a constituent of Ginkgo biloba L. leaves, protected mice against convulsions induced by 4-O-methylpyridoxine (MPN). To elucidate the mechanism of the anticonvulsant activity of bilobalide, this study examined the effect of bilobalide on MPN-induced changes in the levels of gamma-aminobutyric acid (GABA) and glutamate, and in the activity of glutamic acid decarboxylase (GAD) in the hippocampus, cerebral cortex and striatum of the mouse. GABA levels and GAD activity in the hippocampus and cerebral cortex were significantly enhanced by bilobalide treatment (30 mg/kg, p.o., for 4 days) alone. MPN significantly decreased GABA levels and GAD activity in the three brain regions tested compared with those in the control. Pretreatment with bilobalide effectively suppressed the MPN-induced reduction in GABA levels and GAD activity in the hippocampus and cerebral cortex. On the other hand, there were no significant differences in the glutamate levels in the three regions despite various treatments. These results suggested that bilobalide prevents MPN-induced reduction in GABA levels through potentiation by bilobalide of GAD activity, and this effect of bilobalide contributes to its anticonvulsant effect against MPN-induced convulsions.

Sasaki, K., S. Hatta, et al. (2002). “Effects of chronic administration of bilobalide on amino acid levels in mouse brain.” Cell Mol Biol (Noisy-le-grand) 48(6): 681-4.

We have previously demonstrated that 4-day-treatment of mice with bilobalide, a sesquiterpene of Ginkgo biloba L., increases GABA levels in mouse brain, but, effects of chronic treatment with it are not clear. To study effects of chronic treatment of mice with bilobalide on amino acid levels in the brain, we determined the levels of aspartate, glutamate, serine, glutamine, glycine, taurine and GABA in the hippocampus, striatum and cortex. Bilobalide (3 mg/kg/day) was administered orally to 4-week-old mice for 40 days. Bilobalide treatment resulted in a significant increase in the levels of glutamate, aspartate, gamma-aminobutyric acid (GABA), and glycine in the hippocampus of mice compared with the control. An increased level of glycine after bilobalide treatment was also detected in the striatum. In the cortex, bilobalide increased the GABA level, whereas it decreased the level of aspartate. These changes in the levels of various amino acids may be involved in the broad spectrum of pharmacological activities of the extract of Ginkgo biloba on the central nervous system.

Not only do the authors of the swimming man report NOT mention this evidence, they have found a little known paper in the Indian Journal of Pharmacology (not indexed in MEDLINE) in which injection of a massive dose of ginkgo extract potentiated strychnine induced convulsions in mice. 100mg/Kg of GBE = a human dose of 7 grams of extract ( more than an order of magnitude higher than normal doses and given by injection) was used in a single shot. The Indian study has not been replicated, and is certainly impossible to extrapolate to human oral therapeutic doses.

The point here is that author bias (selective quoting) is obvious. The Sasaki studies are well known and accessible in major journals. It is hard to think the authors could have “overlooked” them while searching for relevant data. (In fact its hard to think the authors did much research at all given the garbage they came up with) The Indian studies they quote are not in MEDLINE at all, and one suspects the authors simply copied the citations from the references in a report of two alleged cases of ginkgo and seizures authored by Granger in 2001. (This latter will be discussed in briefly in the next post.). Minimal scientific standards suggest that if you are making a claim or hypothesis you at least account in some way for the evidence that potentially ( or actually) conflicts with your position. Denial is a government policy not a scientific method.

Are we having fun yet?….
This is nearly over, stay tuned for the final curtain.