With Codex churning and rechurning
this spring of 2007, I fear that, if
not vigilant, we may ultimately lose some of our better medicinal
herbs. We've all but lost ephedra; kava-kava is endangered in
the American market place. I doubt that the Food and Drug Administration
(FDA) and Big Pharma (pharmaceutical firms) would be disappointed
if all of our promising herbs were made "prescription only." They
would probably applaud such a move, eliminating some herbs that could
compete well against their expensive and dangerous "evidence-based," FDA-approved
drugs, the studies funded mostly by the pharmaceutical firms. I honestly
believe that, on average, the herbs are better for the American consumer's
health and pocketbooks than the pharmaceuticals, in spite of their "evidence
base." Remember that Government Accounting Office (GAO) statistics
show that half the FDA-approved drugs will be recalled in their first
decade [GAO 1990]. So the evidence is half-wrong to begin with. The
frightening possibility of "prescription only" herbs has
me searching the literature for food farmaceuticals – i.e., commonly
eaten foods – that the FDA would be less likely to relegate to
the "prescription only" category.
I have long urged third-arm clinical trials comparing our more promising
herbs against competing pharmaceuticals and placebo. And in some
cases, the herb
comes out very competitive, e.g., saffron vs. Imipramine (Akhondzadeh et
al. 2004), St. John's-wort vs. Zoloft (Hypericum Depression Trial
2002), and saw palmetto vs. Prosgar (Zlotta et al. 2005). We have seen successful
trials of milk thistle and interferon (both mentioned below) for hepatitis
(Gramenzi et al. 2007; Zlotta et al. 2005). Too bad they weren't compared
with each other and placebo in a third-arm trial. Milk thistle is significantly
cheaper and has fewer side effects; it may well be competitive in efficacy.
Having lost two of my USDA coworkers and a Maine friend to melanoma, and
having experienced some puzzling epitheliomas and keratoses myself, I'd like
to voice in this Townsend Letter a plea for
a third-arm trial. I suggest a trial comparing the best pharmaceutical for
melanoma with winged beans shoots
or roots, the best-known sources of betulinic acid (Duke 2007) and with placebo.
Ironically, two of the young folks helping me get the winged bean into my
Green Farmacy Garden this May are also melanoma survivors.
Years ago, I remember getting all excited after reading in The
New York Times that betulinic acid worked better on murine melanomas
than the drug most commonly used to treat melanoma. More recently and more
specifically, we read, "Betulinic
acid has proven to be the most effective antitumor agent among more than fifty
natural lupanes" (Tolstikova et al. 2006). What we don't read in
the abstracts, unless we read carefully, is that most all the positive studies
are in vitro and may not translate in in vivo studies. That's why I,
almost naively spiritual about homeostasis, stridently suggest a third-arm,
in vivo trial – in vivo in humans – after proving the safety of
such a food farmaceutical in vitro and in vivo in animals. Perhaps absurd,
perhaps not. There will be many trials comparing melanoma drugs with other
melanoma drugs and other melanoma herbs with placebo. Why not take the food
farmaceutical as placebo, if you don't believe it has any potential as
an herbal medicine? I do! I believe there's a good chance betulinic acid
will prove competitive. The evidence base for many pharmaceuticals is often
no stronger than that for its herbal competitors. We won't really know
until they have been compared in unbiased third-arm clinical trials.
Spiritual herbalists consider me a chemical reductionist. I know little of
chemistry. Conversely, chemical reductionists consider me a spiritual flake.
I know little of spirituality and Christianity, although I was once baptized
and I have done some biblical reading. It does take almost a leap of faith
(often useful in desperate situations like late stages of melanoma) to hope
that a food farmacy combo like winged bean, best source of betulinic acid,
and milk thistle, unique source of silymarin, might be healthier and cheaper,
if not as efficacious, as the chemotherapeutic dacarbazine (DTIC) and interferon
(Web MD 2007). Yes, I think they should be clinically compared. I stress
whole herb, not isolated betulinic-acid and silymarin.
After a week of reading on melanoma, I decided that winged bean (shoots or
roots, not seeds, though all are edible), though not well known analytically,
is one of the more promising food farmaceuticals for melanoma. Since poorly
known analytically, there is not much more phytochemical evidence to recommend
it. My analytical colleague, Dr. Peter Kaufman, University of Michigan, will
be analyzing winged bean for the phytoestrogens daidzein and genistein, which
also show anticancer activities that could be useful in melanoma. These estrogens
are present in the Biblical beans, i.e., chickpea, faba bean, and lentils
(Duke 2007). I suspect they'll be found in winged bean, perhaps at lower
Reported Activities for Betulinic Acid
Looks like this chemical and the winged bean should be of interest to the
Bill and Melinda Gates Foundation, as this rapidly growing weedy nitrogen-fixing
legume, presumably of African origin, has attributes that could help with
the Gates Foundation-targeted diseases in Africa: HIV, leishmaniasis, malaria,
and tuberculosis. Here are its listed activities (Duke 2007): anthelminthic,
antiangiogenic, anticancer, anticarcinomic, antichagas, antidermatophytic,
antiedemic, antigliomic, anti-HIV (14.8 uM), antiinflammatory, antileukemic,
antimalarial (IC50=1926 ug/ml), antimelanomic, antimycobacterial (MIC =25
ug/ml), antimyelomic, antineuroblastomic, antinociceptive, antioxidant, antiplasmodial
(IC50=1926 ug/ml), antiproliferant, antisarcomic, antiseptic, antituberculosic
( MIC =25 ug/ml), antitumor, antiviral (14.8 uM), apoptotic, bactericide,
cytotoxic (50100 ppm), fungicide, hepatoprotective, NFkappaBinducer, NOgenic,
eNOSgenic, phospholipase A2 inhibitor, protisticide, topoisomerase II inhibitor,
and trypanocide (Duke 2007).
My faith-based friends might also resort to immune-boosting (through meditation,
stress reduction, prayer, and even intercessory prayer [Harding 2001], and
some Biblical Food Farmacy to deal with melanoma). Spiritually, they might
view themselves as an in vitro "test tube" with the Master Medic
using some of the Master's natural medicines:
(1) Grape contains several antimelanomic
phytochemicals (betaionone, betulinic acid, coumarin, geraniol, luteolin,
pterostilbene, quercetin, rutin) and five
antimetastatic compounds (alphalinolenic acid, coumarin, quercetin, rutin,
(2) Garlic contains at least five
antimelanomic compounds (apigenin, geraniol, quercetin, rutin, s-allyl-l-cysteine)
(ajoene, alphalinolenic acid, apigenin, quercetin, rutin), not to mention
a dozen immunomodulators. Garlic is also said to repel negative
Pomegranate contains the antimelanomic betulinic acid and the antimetastatic
ursolic acid. But it has shown strong synergic anticancer activities
in recent studies.
(4) Walnut contains the antimelanomics
the latter also antimetastatic, as is the omega-3- fatty acid in
(5) Flax contains the antimelanomics
apigenin and luteolin and
alphalinolenic acid and apigenin.
(6) Faba Beans contain the antimelanomic
estrogenic isoflavones daidzein and genistein.
(7) Milk Thistle
contains the antimelanomic (and antimetastatic) apigenin, luteolin,
and quercetin. And is
very competitive with interferon in hepatoprotection.
these Biblical herbs, which your genes have known for maybe
six millennia, if not six million
years, may contain many genetically familiar phytomedicines
also contribute. For this much longer list of ancillary
phytochemcials in these Biblical species,
possibly contributing to relief of melanoma, see the Multiple
Activities Menu (MAM) listed in the sidebar.
Faith-Based Antidepressant Salad Dressing
Melanoma, once advanced, has some pretty depressing statistics. Omega-3s are
good for depression and may even help with the melanoma as well. The faith-based
patient may want fish oil with saffron, 30 mg equivalent in antidepressant
activity to 100 mg imipramine (Akhondzadeh et al. 2004); or the vegetarian
faith-based might prefer flaxseed or walnut oil. I'd add flowers of the
St. John's wort to my antidepressant oil-and-vinegar salad dressing.
We would have a triple whammy against the depression. Remember that the three-armed
study (placebo vs. St John's wort vs. Zoloft) of 2002 showed that the
St. John's wort had fewer side effects than Zoloft (Hypericum Depression
Trial Study Group 2002). But placebo won, as so often happens in studies of
depression. But in 2002, it was St. John's wort alone; now I suggest
an omega-3 oil extraction of saffron and St. John's wort flowers, the
triple whammy. I'll wager it would defeat Zoloft soundly as an antidepressant.
James A. Duke, PhD, Botany
Economic Botanist, US Department of Agriculture (retired)
Akhondzadeh S, Fallah Pour H, Afkham K,
Jamshidi AH, Khalighi Cigaroudi F. Comparison of Crocus sativus L.
and imipramine in the treatment
of mild to moderate depression: a pilot double-blind randomized trial.
BMC Complement. Altern. Med. 2004;Sep;24:12.
Duke, JA. 2007. Phytochemical Database. Available at: http://www.ars-grin.gov/duke.
Accessed May 15, 2007.
General Accounting Office. FDA Drug Review Postapproval Risks, 19761985. April
Gramenzi A, Andreone P, Cursaro C, Verucchi G, Boccia S, Giacomoni PL, Galli
S, Furlini G, Biselli M, Lorenzini S, Attard L, Bonvicini F, Bernardi M. A
randomized trial of induction doses of interferon alone or in combination with
ribavirin or ribavirin plus amantadine for treatment of nonresponder patients
with chronic hepatitis C. J. Gastroenterol. 2007;42(5):3627.
Harding OG. The healing power of intercessory prayer. West
Indian Med J. 2001;50(4):26972.
Hypericum Depression Trial Study Group. Effect of Hypericum perforatum (St
John's wort) in major depressive disorder: a randomized controlled trial. JAMA.
Polyak SJ, Morishima C, Shuhart MC, Wang CC, Liu Y, Lee DY. Inhibition of Tcell
inflammatory cytokines, hepatocyte NFkappaB signaling, and HCV infection by
standardized silymarin. Gastroenterology. 2007;132(5):192536.
Tolstikova TG, Sorokina IV, Tolstikov GA, Tolstikov AG, Flekhter OB. Biological
activity and pharmacological prospects of lupane terpenoids: I. Natural lupane
derivatives [Article in Russian]. Bioorg Khim. 2006;32(1):4255.
Zlotta AR, Teillac P, Raynaud JP, Schulman CC. Evaluation of male sexual function
in patients with Lower Urinary Tract Symptoms (LUTS) associated with Benign
Prostatic Hyperplasia (BPH) treated with a phytotherapeutic agent (Permixon),
Tamsulosin or Finasteride. Eur. Urol. 2005;48(2):26976.
WebMD. Melanoma Guide. Medications. WebMD Medical Reference from Healthwise.
Available at: http://www.webmd.com/melanoma-skin-cancer/melanoma-guide/Skin-Cancer-Melanoma-Medications.
Accessed May 20, 2007
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