androgen receptors (blocking access of testosterone and DHT from entering prostate cells), and has been shown to
block the translocation of the cytosol androgen receptor to the nucleus (blocks the transport of the cytosol receptor
to the nucleus, thus blocking the androgenic effect on the nucleus of the cell).29,30,31,32,33 Saw Palmetto extract may
also reduce the number of androgen receptors in the prostate cell membrane, an action shown to be mediated
through the effect of Saw Palmetto extract on the nuclear DNA of prostate cells (inhibiting the genetic expression of
androgen receptor synthesis and transport to the cell surface). This effect would also minimize the degree to which
androgen hormones could influence the prostate gland. 45
c. Anti-Estrogenic Effects: Higher circulating estrogens in the male body (usually due to increased abdominal fat, as
fat cells convert androstenedione to estrone hormone) has been shown to potentially contribute to BPH. Estrone
inhibits the hydroxylation (breakdown or detoxification) and subsequent elimination of DHT. Hence, DHT can
accumulate more easily within prostate cells. Saw Palmetto extract has been shown to significantly lower cellular
(cytosol) and nuclear estrogen and progesterone receptors on the prostate gland in men suffering from BPH,
compared to the placebo group. In the prostate gland, progesterone receptor activation is linked to increased
estrogenic activity. It has been suggested that the anti-estrogenic effect of Saw Palmetto extract is a primary
feature of its therapeutic effect on reducing BPH. 33 In a double-blind placebo-controlled study, it was shown that
of the 35 men suffering from BPH who were treated with Saw Palmetto extract compared to placebo, biopsies of
their prostate gland demonstrated a significantly lower number of estrogen and progesterone receptors after
treatment with Saw Palmetto for 3 months. This implies that Saw Palmetto extract may also exert an anti-estrogen
and anti-progesterone effect by reducing the available number of these receptors within the prostate cell
membrane. 48
d. Anti-Inflammatory Effects: Saw Palmetto extract has been reported to inhibit both the cyclooxygenase and
lipoxygenase enzyme pathways, which may provide an anti-inflammatory effect and partial relief of BPH symptoms.
The conversion of arachidonic acid to pro-inflammatory prostaglandins (PG-2 series) and other related
leukotrienes and eicosanoids, is catalyzed by the cyclooxygenase and 5-lipoxygenasase enzymes. 34
e. Phytoestrogen Effect - Saw Palmetto extract has been shown to compete with endogenous estrogens for receptor
sites.
35,36
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Polycystic Ovarian Disease and Hirsutism
Saw Palmetto extract appears to have both anti-androgenic and anti-estrogenic effects. This may also be beneficial in
cases of polycystic ovarian disease (both for treatment and prevention of recurrence) as well as for hirsutism , in
women.
4
Prostate Cancer Treatment
Some recent evidence suggests that Saw Palmetto extract may be a useful complementary intervention in cases of
prostate cancer. Recently the Journal of Clinical Oncology reported that a Saw Palmetto extract formulation (also
containing six other Chinese herbs) was able to markedly reduce PSA (Prostate Specific Antigen) levels in patients
with advanced prostate cancer (n=32). Al least an 80 percent reduction in PSA levels occurred in patients with
androgen-dependent prostate cancer (26 patients attained undectable or anorchid PSA levels) and a 50 percent
reduction in PSA levels occurred in the androgen independent-prostate cancer patients. This study carried out at the
Memorial Sloan-Kettering Cancer Center used Saw Palmetto dosages that were approximately three to nine times
higher than typically used to treat BPH.Some recent evidence suggests that Saw Palmetto extract may be a useful
complementary intervention in cases of prostate cancer. Recently the Journal of Clinical Oncology reported that a
Saw Palmetto extract formulation (also containing six other Chinese herbs) was able to markedly reduce PSA
(Prostate Specific Antigen) levels in patients with advanced prostate cancer (n=32). Al least an 80 percent reduction in
PSA levels occurred in patients with androgen-dependent prostate cancer (26 patients attained undectable or anorchid
PSA levels) and a 50 percent reduction in PSA levels occurred in the androgen independent-prostate cancer patients.
This study carried out at the Memorial Sloan-Kettering Cancer Center used Saw Palmetto dosages that were
approximately three to nine times higher than typically used to treat BPH.
Adverse reactions to these high doses included pulmonary embolism, hypertriglyceridemia, allergic reactions, leg
cramps, nausea, diarrhea, impotence, loss of libido, hot flashes, breast tenderness, and enlargement.
However, researchers conclude that it is “generally well tolerated”, but should not be routinely recommended to
patients with a history of cardiovascular disease. 37
Dosage and Standardized Grade
1. Benign Prostatic Hyperplasia (BPH): Usual dosage is 160 mg, twice daily (std to 85-95 percent fatty
acids and sterols), or 320 mg, twice per day (standardized to 45% fatty acids and sterols). 8-21
N.B.: This is equivalent to approximately 10 gms of crude berries.1
2. Prostate Cancer Support: Refer to Journal of Clinical Oncology 2000;18(21):3595-3603, article by
Small E.J. et al. (dosage 3-9 times higher than for BPH). 37
3. Polycystic Ovarian Disease and Hirsutism: Consider the same dosage as used for BPH in men
Adverse Side Effects, Toxicity and Contraindications
Detailed toxicology studies with Saw Palmetto extract carried out on various animals indicate that the extract has no
toxic effects.
At BPH treatment doses, Saw Palmetto extract is safe and no significant side effects have been noted. 4
Gastrointestinal upset is rare, but occurs on occasion.17
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The FDA in the United States lists Saw Palmetto as a herb of unknown safety. However, in Germany and Austria
more than 90 percent of BPH cases are treated by physicians with phytonutrient formulations (most of which contain
Saw Palmetto extract).1, 38,41
A systematic review of the literature reveals that Saw Palmetto extract is associated with fewer adverse treatment
events than is the drug finasteride, including a 1% occurrence of erectile dysfunction versus 5% for finasteride. 7 Saw
Palmetto extract does not appear to affect serum levels of testosterone, Follicle-stimulating hormone or Luteinizing
hormone. 39 Clinical trials have shown that Saw Palmetto extract is essentially non-toxic. In a 3-year study, only 34 of
the 435 subjects using Saw Palmetto extract reported any side effect, which most commonly was mild gastrointestinal
distress. 44
Drug-Nutrient Interactions
Theoretically, Saw Palmetto extract may antagonize the effects of hormone replacement therapy and oral
contraceptives in women, if they choose to use Saw Palmetto extract for polycystic ovarian disease or hirsutism. 1
However, no stated drug-nutrient interactions for Saw Palmetto exist at this time. 43, 44
Pregnancy and Lactation
During pregnancy and lactation, the only supplements that are considered safe include standard prenatal
vitamin and mineral supplements. All other supplements or dose alterations may pose a threat to the
developing fetus and there is generally insufficient evidence at this time to determine an absolute level of
safety for most dietary supplements other than a prenatal supplement. Any supplementation practices
beyond a prenatal supplement should involve the cooperation of the attending physician (e.g., magnesium
and the treatment of preeclampsia.)
References: Pregnancy and Lactation
1. Encyclopedia of Nutritional Supplements. Murray M. Prima Publishing 1998.
2. Reavley NM. The New Encyclopedia of Vitamins, Minerals, Supplements, and Herbs. Evans and
Company Inc. 1998.
3. The Healing Power of Herbs (2nd edition). Murray M. Prima Publishing 1995.
4. Boon H and Smith M. Health Care Professional Training Program in Complementary Medicine.
Institute of Applied Complementary Medicine Inc. 1997.
1. Newall CA, Anderson LA, phillipson JD. Herbal Medicines: A Guide for Health Care Professionals. London: The Pharmaceutical Press
1996:p296
2. Leung A, Foster S. Encyclopedia of Common Natural Ingredients used in Food, Drugs and Cosmetics. 2nd ed. New york, NY: John Wiley
and Sons 1996:p649
3. Awang DVC. Saw palmetto, African prune and stinging nettle for benign prostatic hyperplasia (BPG). Canadian Pharmaceutical Journal
1997; November:p37-44,p62
4. Murray MT. The healing Power of herbs. Rocklin, CA: Prima Publishing 1992:p246
5. Benign Prostatic Hyperplasia. Medical Post; Oct 17,2000
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6. Paubert-Braquet M, Richardson FO, Servent-Saez N et al. Effect of Serenoa repens extract (Permixon) on estradiol/testosterone-induced
experimental prostate enlargement in the rat. Pharmacological Research 1996;34(3-4):171-9
7. Ishani W et al. Serenoa repens for benign prostatic hyperplasia (Cochrane Review Abstract) nov 6 1998;medscape.com
8. Cirillo-Marucco E, Pagliarulo A, Tritto G et al. Extract of Serenoa repens (PermiconR) in the early treatment of prostatic hypertrophy.
Urologia 1983;5:1269-77
9. Tripodi V, Giancaspro M, Pascarello M et al. Treatment of prostatic hypertrophy with Seronoa repens extract. Medical praxis 1983;4:41-6
10. Greca P, Volpi R. Experience with a new drug in the medical treatment of prostatic adenoma. Urologia 1985;52:532-5
11. Crimi A, Russo A. Serenoa repens for the treatment of the functional disturbances of prostate hypertrophy. Medical Praxis 1983;4:47-51
12. Braeckman J. The extract of Seronoa repens in the treatment of benign prostatic hyperplasia: A multicentre open study. Current Therap
Research 1994;55(7):776-85
13. Romics I, Schmitz H, Frang D. Experience in treating benign prostatic hypertrophy with sabal serrulata for one year. International Urology
and Nephrology 1993;25(6):565-69
14. Boccafoschi, Annoscia S. Compariosn of Serenoa repens extract with placebo by controlled clinical trial in patients with prostatic
adenomatosis. Urologia 1983;50:1257-68
15. Emili E, Lo Cigno M, Petrone U. Clinical trial of a new drug for treating hypertrophy of the prostate (Permixon). Urologia 1983;50:1042-8
16. Champault G, Bonnard AM, Cauquil J, Patel JC. Medical treatment of prostatic adenoma. Controlled trial: PA 109 vs. placebo in 110
patients. Annales d’Urologe 1984;18:407-10
17. Tasc A, Barulli M, Cavazzana A et al. Treatment of obstruction in prostatic adenoma using an extract of Serenoa repens. Double-blind
clinical test vs. placebo. Minerva Urologica E Nefrologica 1985;37:87-91
18. Vahlensieck WJ et al. Benign prostatic hyperplasia – Treatment with Sabal fruit extract. A treatment study of 1,334 patients. Fortschritte
der Medizin 1993;111:323-6
19. Pannunzio E et al. Serenoa repens in the tratment of human benign prostatic hypertrophy (BPH). Journal of Urology 1987;137:p226A
20. Adriazola Semino m et al. Symptomatic treatment of benign hypertrophy of the prostate. Arch Esp Urol 1992;45:211-3
21. Carraro JC, Raynaud JP, Koch G et al. Comparison of phytotherapy (Permixon) with finasteride in the treatment of benign prostate
hyperplasis: A randomized international study of 1,098 patients. Prostate 1996;29:231-40
22. Carilla E et la. Binding of Permixon, a new treatment for prostatic benign hyperplasia, to the cytosolic androgen receptor in the rat
prostate. J Steroid Biochem 1984;20:521-3
23. Sultan C et al. Inhibition of androgen metabolism and binding by a liposterolic extract of Serenoa repens B in human foreskin fibroblasts.
J Steroid Biochem 1984;20:515-9
24. Briley M, Carilla E et al. Inhibitory effect of Permixon on testosterone 5-alpha-reductase activity of rat ventral prostate. British Journal of
Pharmacology 1984;83(suppl):p401
25. Delos S, Iehle C, Martin PM, Raynaud JP. Inhibition of the activity of ‘basic; 5-alpha-reductase (type 1) detected in DU 145 cells and
expressed in insect cells. Journal of Steroid Biochemistry and Molecular Biology 1994;48(4):347-52
26. Delos S, Carsol JL, Ghazarossian E et al. Testosterone metabolism in primary cultures of human prostate epithelial cells and fibroblasts.
Journal of Steroid Biochemistry and Molecular Biology 1995;55(3-4):375-83
27. Iehle C, Delos S, Guirou O et al. Human prosatic steroid 5 alpha-reductase isoforms—a comparative study of selective inhibitors. Journal
of Steroid Biochemistry and Molecular Biology 1995;54(5-6):273-9
28. Rhodes L, Primka RL, Berman C et al. Compariosn of Finasteride (Proscar), a 5a reductase inhibitor and various commercial plant
extracts in in vitro and in vivo 5a reductase inhibition. The Prostate 1993;22:43-51
29. El-Sheikh MM, Dakkak MR, Saddique A. The effect of permixon on androgen receptors. Acta obstetrica et Gynecologica Scandinavica
1988;67:397-9
30. Ravenna L, Di Silverio F, Russo MA et al. Effects of the lipiosterolic extract of Serenoa repens (Permixon) on human prostatic cell lines.
Prostate 1996;29(4):219-30
31. Wilson JD. The pathogenesis of benign prostatic hyperplasia. American Journal of Medicine 1980;68:745-55
32. Carilla E, Briley M, Fauran Fea. Binding of Permixon, a new treatment for prostatic benign hyperplsia, to cytosolic androgen receptor in
rat prostate. Journal of Steroid Biochemistry 1984;20:521-3
33. Di Silverio F et al. Evidence that Serenoa repens extract displays antiestrogenic activity in prostatic tissue of benign prostatic hypertrophy.
Eur Urol 1992;21:309-14
34. Breu W, Hagenlocher M, Redl K et al. Anti-inflammatory activity of Sabal fruit extracts prepared with supercritical carbon dioxide, in vitro
antagonists of cyclooxygenase and 5-lipoxygenase metabolism. Arzneimittelforschung 1992;42(4):547-51
35. Elghamry MI, Hansel R. Activity and isolated phytoestrogen of shrub palmetto fruits (Serenoa repens Small), a new estrogenic plant.
Experientia 1969;25:828-9
36. Di Silverio F, D’Eramo G, Lubrano C et al. Evidence that Serenoa repens extract displays an antiestrogenic activity in prostatic tissue of
benign prostatic hypertrophy patients. European Urology 1992;21:309-14
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37. Small EJ et al. Prospective trial of the herbal supplement PC-Spes in patients with progressive prostate cancer. JCO 2000;18(21):3595-
3603
38. McPartland JM et al. Benign prostatic hyperplasia treated with saw palmetto:a literature search and an experimental case. J Am Osteop
Assoc 2000;100(2):89-96
39. Casarosa C, Cosci di Coscio M, Fratta M. Lack of effects of a liposterolic extract of Serenoa repens on plasma levels of testosterone,
FSH, and luteinizing hormone. Clinical Therapeutics 1988;10:585-88
40. Gerber GS et al. Saw palmetto (serenoa repens) in men with lower urinary tract symptoms: effects on urodynamic parameters and
voiding symptoms. Urology 1998;51(6):1003-7
41. MacDonald A et al. Systematic review of cernilton for the treatment of benign prostatic hyperplasia. Br J Urol 1999;85:836-941
42. Sokeland J et al. A combination of Sabal and urtica extracts verus finasteride in BPH: a comparison of therapeutic efficacy in a one-year
double-blind study. Urologe CA 1997;36:327-33
43. Healthnotes Online. Healthnotes Inc 2000. www.healthnotes.com: Saw Palmetto
44. Natural Product Encyclopedia. www.consumerslab.com: Saw Palmetto
45. Ravenna L et al. Effects of the lipidosterolic extract of serenoa repens (permixon) on human prostatic cell lines. Prostate 1996;29(4):219-
30
46. Delos S et al. Testosterone metabolism in primary cultures of human prostate epithelial cells and fibroblasts. J Steroid Biochem &
Molecular Biol 1994;48(4):347-52
47. Paubert-Braquet M et al. Effect of serenoa repens extract (permixon) on estradiol/testosterone-induced experimental prostate
enlargement in the rat. Pharmacol Res 1996;34(3):171-9
48. Di Silverio F et al. Evidence that serenoa repens extract displays an antiestrogenic activity in prostatic tissue of benign prostatic
hypertrophy patients. European Urologv 1992;21(4):309-14
49. Wagner H et al. Immunostimulatin lactation of polysaccharides (heteroglycans) from higher plants. Arzneimittelforschung
1985;35(7):1069-75
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Shiitake Mushroom
General Features
Shiitake Mushroom (Lentinus edodes) has been used in traditional Chinese medicine for thousands of years, as is the
case with reishi and maitake mushrooms. All of these mushrooms contain specific polysaccharides (e.g., beta glucans)
that are known to modulate immune system activity and provide other health-promoting effects. Recently, researchers
have begun to test Shiitake Mushroom in clinical trials with humans to help validate its traditional use in Chinese
medicine and confirm its biological activity suggested by experimental studies.1 Shiitake mushrooms grow on the
trunks and stumps of trees. They are native to many parts of Asia, but are now cultivated throughout the world
(including the United States) for medicinal use. The fruiting body is used medicinally.1,2
Principle Active Constituents
The primary active constituent is reported to be a polysaccharide called lentinan, which is contained in Shiitake
Mushroom preparations, referred to as Lentinus Edodes Mycelium Extract (LEM). Thus, commercially available LEM is
a rich source of polysaccharides and lignans from the shiitake mushroom.2 Lentinan is a beta-glucan polysaccharide
isolated from shiitake mushrooms, which has been used as the principle agent in recent human studies.3
Clinical Application and Mechanism of Action
Experimental evidence has shown that a purified fraction of LEM, rich in shiitake lignans, stimulates the immune
system by activating macrophage cells and increasing the proliferation of bone marrow cells, and it inhibits the
cytopathic effects of HIV-1 virus in vitro.4,5 LEM has also shown that it increases lymphokine-activated killer (LAK ) cel
activity by 42-56.9% in vitro (when combined with interleukin 2), which may be of importance in the complementary
support of cancer therapy.6
1. AIDS (HIV – Infection)
M. Gordon et al, have administered lentinan or placebo to HIV patients using I.V. method, in three small phase I/II
placebo-controlled trials. Overall, lentinan treatment produced an increase in the number of CD4 cells ( T-helper
cells ) and, in some patients, neutrophil activity. In one of the studies lentinan was used in conjunction with
didanosine, which proved to be effective in raising the CD4 count by 142/mm3 on average, over a twelve-month
period. In contrast, there was a decrease in the CD4 count in those patients receiving the didanosine alone. There
were no significant side ef ects in the lentinan treatment group in regards to anemia, leukopenia, pancreatitis or
neuropathy. Based on these findings, these researchers recommend a larger, longer clinical trial of lentinan in
combination with didanosine in HIV patients, free of opportune infection.7
2. Cancer Treatment Support
Several trials studying cancer patients have investigated the effects of lentinan as a cancer treatment support
intervention. Repeated injections of lentinan have been shown to have beneficial effects on the immune systems of
cancer patients.8,9,10,11,12 Two trials reported that lentinan injections prolonged life in people with a variety of
advanced cancers.13,14 Another trial found that intravenous lentinan increased five-year survival rates in prostate
cancer patients compared with those not given lentinan.15 It is not known whether or not oral consumption of
Shiitake Mushroom extract would yield the same benefits as the injectable method used in these studies.
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3. Genital Warts
Oral supplementation of lentinan has been shown to significantly reduce the recurrence rate of genital warts
(condyloma acuminata). A preliminary trial involving a group of men and women with genital warts found that those
who took 12.5 mg of lentinan per day for two months after laser surgery, had a recurrence rate of only 10.5% as
compared to 47% in the group that did not receive the lentinan.16
Dosage and Standardized Grade
The most current evidence suggests that Shiitake Mushroom extract or lentinan products should be standardized
to 3.2% KS-2 polysaccharides per dose.
Therapeutic applications typically have used 100-400 mg (standardized extract), three times per day, with food.1
Recommended intake of LEM is 1-3 grams, two to three times per day. Purified lentinan is considered a drug in
Japan and is not currently available as an herbal supplement in North America.2
Adverse Side Effects, Toxicity and Contraindications
Shiitake mushrooms have an excellent record of safety, but have been known to induce temporary diarrhea and
abdominal bloating when used in high amounts. It is important to take this product with food.2
Drug-Nutrient Interactions
1. Immunosuppressive Medications (e.g., cyclosporin): As shiitake mushrooms and its extracts (e.g., LEM) are
known to stimulate the immune system, they are contraindicated in cases where patients are taking
immunosuppressive drugs.4,5
2. Didanosine: Shiitake Mushroom extract has been shown to enhance the efficacy of didanosine in HIV patients
when administered intravenously, and thus should be considered for use in these cases.
Pregnancy and Lactation
During pregnancy and lactation, the only supplements that are considered safe include standard prenatal
vitamin and mineral supplements. All other supplements or dose alterations may pose a threat to the
developing fetus and there is generally insufficient evidence at this time to determine an absolute level of
safety for most dietary supplements other than a prenatal supplement. Any supplementation practices
beyond a prenatal supplement should involve the cooperation of the attending physician (e.g., magnesium
and the treatment of preeclampsia.)
References: Pregnancy and Lactation
1. Encyclopedia of Nutritional Supplements. Murray M. Prima Publishing 1998.
2. Reavley NM. The New Encyclopedia of V