First part of a lecture at the AHG Symposium in Portland, Oregon, 2005, on Food Medicine and Poison. This is a general but practical discussion of the theory and philosphy of herbal practice, based on the author’s clinical experience with cancer: intended for practitioners and students of clinical herbalism. iTunes subscribers will get the podcast automatically when updating subscriptions. Newsreader subscribers and direct web browsing - download MP3 file from link below. 42 minutes duration, 10.3 megabytes.
Food, Medicine, Poison Part One

Remember the recent paper by well known artemisinin researchers Lai and Singh from U-Dub in Washington state (HERBLOG flashback)? Well Holley Pharmaceuticals have made available a sodium butyrate preparation - in capsules. Of course they do not say what the recommended dose of butyrate is - the bad news is that to attain 1.0 millmolar plasma levels that approximate the experimental concentrations that produced a ten fold increase in artemisinin effect - you need to take at least 10 grams (10,000 mg ) a day.In brain tumors, doses up to 20 g /day have been used. The Holley caps contain 600 mg sodium butyrate, so thats about 16-30  caps per day. A lot.

The good news is that butyrate is totally non toxic (its a food ingredient found typically in butter) and is a selective nutrient for colonocytes. At these high doses the main side effect is…body odor. Oh well. 10 x synergy with artemsinin is worth a bit of a stink.

Butyrate acts as a class of anticancer agent called ‘histone deacetylase inhibitors” - and has been used alone and in combination with other drugs as an anticancer therapy. It is not clear whether affecting histones is the mechanism of sensitization to artemisinin - probably not, but at this stage we do not know.

Have you noticed how you can never find a phytochemist or pharmacognoscist when you REEEALY need one? Of course, when you don’t want them, they are in your face - pushing their agenda - remember Varro Tyler?

Well - now we have immunomodulating melanins from green tea , from echinacea, and from Nigella. The phytochemists have not exactly been to the fore of this emerging research which is weird..maybe they are keeping their powder dry. The thing is if the emerging research is right its an almost Copernican upset to the existing world of phytochemistry. Most herbal medicine is based upon secondary compounds - we are not really clear if melanin is a primary or secondary compound..or even if it is a compound at all (as opposed to an extraction artifact based on polyphenolic polymerisation - like tannin condensation - under alkali conditions). You certainly won’t find a chapter on plant melanins in your average botanical chemistry book.

But wait…

Just look at this quote from the Pascoe patent claim on echinacea melanin (US Patent Claim 0050002962 - you can get the full text via google)

The inventors have found only one report of a “melanin-like” materialexhibiting immunostimulatory activity. However, this material could not be conclusively identified as a melanin since nocomposition data was provided to indicate what the structural units were which composed this substance. This material wasisolated from black tea leaves and when orally administered to mice, enhanced the antibody response of spleen cells to sheep redblood cells in as little as two days (Sava et al, 2001). The present inventors have found that green tea contains melanin that has unexpectedly superior activity compared to black tea melanin isolated by the inventors. This suggests that the materialdescribed by Sava et al. is not a melanin product similar in nature to those of the present invention.

In other words, OUR melanin is the patented melanin = the real thing as oposed to your (unpatented) melanin.

Hmm - melanin is not the only brown stuff around here.

Here is another just released paper on herbal melanin from an unusual quarter…a Saudi research group. This time the herbal melanin was extracted from Nigella seeds. These authors spent rather more time than Pugh and Pascoe on trying to characterize the chemistry of their melanin which was derived from an alkali extraction. The effects on inflammatory cytokines and the angiogenic factor VEGF are interesting to say the least…check it out. This is going to get interesting soon.

El-Obeid, A., S. Al-Harbi, et al. (2006). “Herbal melanin modulates tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6) and vascular endothelial growth factor (VEGF) production.” Phytomedicine 13(5): 324-333.
Recent studies have indicated that cytokines can enhance immunogenicity and promote tumor regression. However, the means for modulating cytokine production are not yet fully investigated. In this study we report the effects of a herbal melanin, extracted from Nigella sativa L., on the production of three cytokines [tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6) and vascular endothelial growth factor (VEGF)], by human monocytes, total peripheral blood mononuclear cells (PBMC) and THP-1 cell line. Cells were treated with variable concentrations of melanin and the expression of TNF-alpha, IL-6 and VEGF mRNA in cell lysates and secretion of proteins in the supernatants were detected by RT-PCR and ELISA. Melanin induced TNF-alpha, IL-6 and VEGF mRNA expression by the monocytes, PBMC and THP-1 cell line. On the protein level, melanin significantly induced TNF-alpha and IL-6 protein production and inhibited VEGF production by monocytes and PBMC. In the THP-1 cell line melanin induced production of all three cytokine proteins. These observations raise the prospects of using N. sativa L. melanin for treatment of diseases associated with imbalanced cytokine production and for enhancing cancer and other immunotherapies.

A breath of sanity amidst all the absurd pseudo controversy about whether or not echinacea can prevent or treat the common cold, blah blah blah.Despite, or rather because of, hundreds of thousands of NCCAM dollars pouring down the toilet in pointless and flawed clinical trials, the topic has become emblematic of divisions between opponents and supporters of natural medicine. Panjandrums from both sides of the fence trade hot air pontifications in the literature (and of course by press release - the favorite form of phony scientific self promotion today) on why this or that trial or paper is right or wrong etc, and how the other side does not get it. Unsurprisingly the vast majority of these people are male, and IMHO, even more unsurprisingly - none of them get it.
Move over. Leave it to the women dudes. Professor Sandra Miller of McGill University has quietly produced a brilliant body of work on echinacea based upon a murine model over the last few years which completely transcends the idiotic posturings of the clinical trial driven debates about echinacea as a cold and flu cure. Miller drives a conceptual and practical 32 wheeler through the morass of misconceptions pervading echinacea studies, and she does so as it were a works edition MiniCooper S - with deftness, elegance, superb writing, conceptual clarity and panache in methodology and experimental design that shows a real grasp of the issues regarding the herb as an immunomodulator.

If there is only one herbal paper you read this week - month - year - make sure it is this one in which cell biologist Miller reviews her work on echinacea over the last five years. Of course, it is based on animal studies, and that may be a drawback for some, and personally I still have “veteran” like flashbacks to the mouse room at Harvard Medical School where I worked for a while a long time ago…never again …BUT the value of her findings is huge. NB Compare also to the controversial echinacea melanin paper (HERBLOG thread in March) whose authors seem more concerned about patent claims than echnacea science.
Full text is available free at PubMed Central - yay! Hit the title link to get to it. Enjoy.

Miller, S. C. (2005). “Echinacea: a miracle herb against aging and cancer? Evidence in vivo in mice.” Evid Based Complement Alternat Med 2(3): 309-1

Echinacea has been viewed as an immunoenhancing herb since it became commercially available several years ago. Indeed, its medicinal significance is responsible for billions of dollars in worldwide sales annually. Unfortunately, most of the ‘evidence’ for the purported medicinal efficacy of Echinacea has been anecdotal and, moreover, to this day, there is no formal proof on how to achieve the best results-whether it should be consumed daily throughout life as a prophylactic; consumed by either young or old; or consumed after diseases, such as cancer, have taken hold. Our work over the past 5 years has led to conclusive answers to some of these questions, at least in mice. Our results have shown that daily consumption of Echinacea is indeed prophylactic, extends the life span of aging mice, significantly abates leukemia and extends the life span of leukemic mice. Given that humans are 97% genetically common with mice and that virtually all our basic physiology is identical, it is neither unjustified to extrapolate these observations to humans nor would it be an arduous task to perform many of these studies in humans, thus establishing viable scientific evidence replacing the anecdotal.

Berberine, the yellow alkaloid ingredient of several traditional anticancer herbs such as Oregon grape root has an expanding literature confirming its anticancer properties. Here are a few recent studies…Oregon grape root was an ingredient of the controversial Hoxseys formula, and berberine herbs were included in Eclectic anticancer formula. Click Links for PubMed.

Mantena, S. K., S. D. Sharma, et al. (2006). “Berberine inhibits growth, induces G1 arrest and apoptosis in human epidermoid carcinoma A431 cells by regulating Cdki-Cdk-cyclin cascade, disruption of mitochondrial membrane potential and cleavage of caspase-3 and PARP.” Carcinogenesis.

Mantena, S. K., S. D. Sharma, et al. (2006). “Berberine, a natural product, induces G1-phase cell cycle arrest and caspase-3-dependent apoptosis in human prostate carcinoma cells.” Mol Cancer Ther 5(2): 296-308.

Lin, J. P., J. S. Yang, et al. (2006). “Berberine induces cell cycle arrest and apoptosis in human gastric carcinoma SNU-5 cell line.” World J Gastroenterol 12(1): 21-8.

Lin, C. C., S. T. Kao, et al. (2006). “Apoptosis of human leukemia HL-60 cells and murine leukemia WEHI-3 cells induced by berberine through the activation of caspase-3.” Anticancer Res 26(1A): 227-42.

If, like me, you find the cosmetic excesses of plastic surgery scary - the ignorance of plastic surgeons about herbs is way more so - official. The ASPS (American Society of Plastic Surgeons) published a “study” in February about the dangers of herbs and supplements. In a healthwire press release proclaiming their momentous findings , the ASPS attempted to cosmetically adjust the truth to the point where their operation revealed the grotesque extent of their incomprehension of the subject upon which they are pontificating - here is an excerpt from the ASPS press release quoting study co-author and ASPS member Dr James Bradley of UCLA (of course in SoCal - heartland of cosmetic adjustments to reality)…echinacea is immunosuppressant, glucosamine causes hypoglycemia, etc etc but best of all check out the list of deviant and deadly homeopathic behaviours such as pilates …..of course this execrable garbage would be hilarious …if it were not for real. WHO ARE these people? What planet are they from? Scary.

– Echinacea is often used for the prevention and treatment of viral, bacterial and fungal infections, as well as chronic wounds, ulcers and arthritis. However, it can trigger immunosuppression, causing poor wound healing and infection.

– Glucosamine, often offered in conjunction with chondroitin, contains chemical elements that mimic human insulin, and may artificially cause hypoglycemia during surgery.

In addition to having a greater tendency toward taking herbal supplements, 35 percent of plastic surgery patients were more likely to engage in homeopathic practices, including acupuncture, hypnosis, chiropractic manipulation, massage, yoga and Pilates. Only six percent of the general population practiced homeopathics on a weekly basis.

“Patients should tell doctors about all of the medications they are taking — natural or prescribed. Only then can we safely suggest the appropriate discontinuation period, which can range from 24 hours to one month,” said Dr. Bradley. “Taking this precaution is essential to a safe surgery and smooth recovery.”

For referrals to ASPS Member Surgeons certified by the American Board of Plastic Surgery, call 888-4-PLASTIC (475-2784) or visit http://www.plasticsurgery.org where you can also learn more about cosmetic and reconstructive plastic surgery.