Padma

Ingredients:
Bengal quince [Aegle marmelos (L.) Corrêa] fruit
Allspice [Pimenta officinalis Lindl., syn. P. dioica (L.) Merr.]
fruit
Colombine (Aquilegia vulgaris L.) aerial part
Marigold/calendula (Calendula officinalis L.) flower
Cardamom [Elettaria cardamomum (L.) Maton] fruit
Clove [Syzygium aromaticum (L.) Merr. & L.M. Perry]
flower
Costus (Indian) [Saussurea lappa (Decne.) C.B. Clarke, syn.
Sassurea costus (Falc.) Lipsch.] root
Ginger lily (Hedychium spicatum Sm.) rhizome
Lettuce (Lactuca sativa L.) leaf
Iceland moss (Cetraria islandica L. Ach.)
Licorice (Glycyrrhiza glabra L.) root
Neem/margosa (Azadirachta indica A. Juss., syn: Melia
azadirachta L.) fruit
Myrobalan (Tropical almond) (Terminalia chebula Retz.)
fruit
Ribwort/English plantain (Plantago lanceolata L.) aerial
part
Knotgrass (Polygonum aviculare L.) aerial part
Golden cinquefoil (Potentilla aurea L.) aerial part
Red sandalwood (Pterocarpus santalinus L. f.) heart wood
Country mallow/heartleaved sida (Sida cordifolia L.) aerial
part
Valerian (Valeriana officinalis L.) root
Gypsum/calcium sulfate
Dextro-camphora/natural camphor


Padma® 28 (recipe No. 28 of the Padma recipe series) is an herbal
remedy consisting of 22 ingredients prepared according to Tibetan
medicine principals. The recipe was brought to St. Petersberg, Russia
in the middle of the nineteenth century by a physician/monk, Sultim
Badma. The original formula has been altered with its entry into
Western Europe, in that some of the ingredient plants from Tibet and
India have been substituted with plants from Europe. The European
version has been tested in numerous clinical studies and is registered
as a drug in Switzerland. It is indicated for symptoms of poor circulation,
including tingling, formication (feeling of insects crawling on
the skin), feeling of heaviness, and tension in the arms and legs, as
well as numbness of the hands and feet (Saller and Kristof, 1997).

 
The formula available in the United States is Padma® BASIC,
which is Padma 28 minus one ingredient. The missing ingredient is
aconite tuber (Aconitum napellus L.), which is considered an “unsafe
herb” in the United States, subject to import restriction (CADHS,
1996). Thus, Padma BASIC is a blend of 19 herbs plus camphor and
calcium sulfate. Padma BASIC is manufactured in Switzerland by
PadmaAG, and distributed in the United States by EcoNugenics Inc.
Although Padma 28 and Padma BASIC are not equivalent, their ingredients
are very similar, and the products are both made by the
same manufacturer. Thus, we decided to include Padma BASIC in
this listing. Another product for sale in the United States that is also
similar to Padma 28 is Adaptrin, manufactured by Pacific BioLogic.


 Experimental studies with Padma 28 indicate that it may have antioxidant
and anti-inflammatory properties (Saller and Kristof, 1997).
We reviewed two trials that included adults with multiple sclerosis or
children with recurrent respiratory tract infections. However, the majority
of the studies (six) that we reviewed focused on the ability of
Padma 28 to treat symptoms of circulatory disorders.


Intermittent claudication is a symptom that occurs when the blood
supply is adequate to meet the needs of the exercising muscle. This
occurs most commonly due to occlusive arterial disease, also known
as peripheral arterial disease, or more commonly known as peripheral
arterial occlusion (PAO). PAO is a condition in which narrowing of
the arteries, generally caused by atherosclerosis, limits the blood supply
to the legs. Early stages of the disease are without symptoms, but
later stages are associated with leg pain and muscle cramps upon
walking, and ultimately, ischemic ulceration, gangrene, and tissue
loss. The stages have been classified in a system according to
Fontaine: Stage I represents those who are asymptomatic with isolated
arterial stenosis of the lower limb; Stage II is mild to moderately
severe leg pain and muscle cramps upon walking; Stage III are those
with pain while resting; and Stage IV are those with ulcerations and
gangrene (Dicter et al., 2002). The Padma studies included patients
with Stage II of the disease. After the subject walks a “pain-free distance,”
cramplike ischemic pains begin. These pains eventually force
the subject to stop walking, determining the “maximal walking distance.”
Upon rest, the legs recover from deficiencies of blood and oxygen,
the pain disappears, and the subject can again walk a certain
distance (Schrader, 1985).

Iberogast

Ingredients:
German chamomile (Matricaria recutita L.) flower
Clown’s mustard (Iberis amara L.) plant
Angelica (Angelica archangelica L.) root and rhizome
Caraway (Carum carvi L.) fruit
Milk thistle (Silybum marianum [L.] Gaertn.) fruit
Lemon balm (Melissa officinalis L.) leaf
Celandine (Chelidonium majus L.) aerial part
Licorice (Glycyrrhiza glabra L.) root
Peppermint (Menthae × piperita L.) leaf




Iberogast™ is named for the herb Iberis amara L. (commonly
called bitter candytuft or clown’s mustard plant), the principal ingredient
in this formula containing a total of nine plant extracts.
Iberogast, also known as STW 5, is manufactured in Germany by
Steigerwald GmbH, and distributed in the United States by Enzymatic
Therapy.



Iberogast has been tested in several trials for its ability to benefit
dyspepsia. Symptoms of dyspepsia include belching, sour eructation,
frequent or excessive passage of gas, abdominal fullness, vague abdominal
pain, epigastric burning, nausea, and unsatisfactory evacuation.
Three different subtypes of functional dyspepsia have been described,
attributing the symptoms to ulcers, dysmotility, or some
unspecified cause. Symptoms can be rated according to the gastrointestinal
symptom (GIS) score, a sum of ten dyspepsia symptoms.



Dyspepsia (Indigestion)

We reviewed two trials that compared Iberogast with either metoclopramide
or cisapride in treatment for functional dyspepsia. A single-
blind, drug comparison trial included 77 patients with functional
dyspepsia given either Iberogast or metoclopramide (both 20 drops
three times daily) after meals for up to two weeks. As a result, an almost
parallel improvement in dyspepsia symptoms was observed in
both groups. A statistically significant change compared to baseline
was reached for symptoms (pressure/pain, nausea, belching, heartburn,
stomach cramps, vomiting, fullness, and lack of appetite) between
days three and seven (Nicolay, 1984). The trial did not score
well in the quality rating because it was single-blind (the two liquids
were different colors) and the randomization process was not adequately
described.

Gerifrote

First nine of a total thirty ingredients (for more information, see the
Product Profile):

Chyavanprash concentrate
Cow-itch plant (Mucuna pruriens [L.] DC.) seed
Gotukola (Centella asiatica [L.] Urb.) leaves
Shatavari (Asparagus racemosus Willd.) root
Loosestrife (Asparagus adscendens Roxb.) root
Ashwagandha (Withania somnifera [L.] Dunal.) root
Arjuna (Terminalia arjuna [Roxb. ex. DC.] Wight & Arn.)
bark
Elephant creeper (Argyreia speciosa [L. f.] Sweet) root
Licorice (Glycyrrhiza glabra L.) root


Geriforte® is manufactured by The Himalaya Drug Company in
India, and distributed in the United States by Himalaya USA. Each
tablet contains 1.005 g of a proprietary herbal blend of thirty ingredients
(see the product report for a full list of ingredients). The current
recommended dose is one tablet twice a day (Himalaya USA, 2002).
A prior formulation of Geriforte, label dated May 1999, also cited 12
mg vitamin C and 40 mg calcium. No details of the product used in
the following trial were included in the trial report. Geriforte is also
available under the name of GeriCare®.



Menopausal Symptoms

The benefits of Geriforte were assessed in a small controlled study
that included 25 women with postmenopausal depression and symptoms
of headache, vague body ache, hot flashes, chest pain, palpitations,
personality change, insomnia, loss of appetite, weight loss, and
others. The study participants were given placebo for six weeks and
then Geriforte (two tablets three times a day) for six weeks. They
were evaluated every week during the 12-week period. Geriforte was
effective in reducing symptoms of headache, hot flashes, insomnia,
and improved self-confidence compared to placebo (Damle and
Gore, 1983). However, the study was not well described and appeared
to have significant methodological limitations. Thus, according
to our reviewer, Dr. Tieraona Low Dog, any potential benefit for
menopausal symptoms cannot be determined from this trial.


No significant side effects were reported and no abnormalities
were revealed by laboratory tests. Epigastric distress was reported in
six patients (24 percent) in the initial phase of the study. The study report
explained that this side effect disappeared with a reduction in
dose, but did not give any further details such as how much the dose
was reduced (Damle and Gore, 1983).

Gastrim

Ingredients:

Crowfoot (Aconitum palmatum D. Don.) root
Black pepper (Piper nigrum L.) fruit
False black pepper (Embelia ribes Burm. f.) fruit
Ginger (Zingiber officinale Rosc.) rhizome
Triphala:
Amalaki (Emblica officinalis Gaertn.) fruit
Vibhitaka (Terminalia bellerica [Gaertn.] Roxb.) fruit
Haritaki (Terminalia chebula Retz.) fruit rind
Mint (Mentha arvensis L.) leaves
Lemon (Citrus limon [L.] Burm. f.) fruit
Papaya (Carica papaya L.) fruit



Gastrim® (previously called Gasex®) is manufactured by the
Himalaya Drug Company in India, and distributed in the United
States by Himalaya USA. Gastrim is also available under the name
GastriCare®. The current product label lists the ten herbal ingredients
indicated earlier. Also listed on the label, in the category of other
ingredients, are purified conch shell ash and purified cowrie shell ash.
The recommended dose is one to two 515 mg tablets, before meals or
as needed.

The material used in one of the clinical trials is described as tablets
containing 214 mg total ingredients. The dose in the trialwas two tablets
three times a day, for a total of 1.28 g per day. The ingredients and
their quantities were listed in one trial report as Aconitum palmatum
(65 mg), Piper nigrum (19 mg), extract of Embelia ribes (22 mg), extract
of Triphala (22 mg), extract of Zingiber officinale (22 mg),
cowrie bhasma (purified cowrie shell ash) (32 mg), and shankh
bhasma (purified conch shell ash) (32 mg)—all prepared in the juices
and decoctions of Mentha arvensis, Moringa pterygosperma, Carica
papaya, Citrus limon, etc. (Chandra et al., 1978). The other clinical
trial did not provide a list of product ingredients (Mishra and Singh,
1981). The current product differs from that described in the trial in
that Moringa pterygosperma is not mentioned on the label.


Dyspepsia (Indigestion)

A trial included 100 patients with symptoms of dyspepsia (indigestion)
who were given either Gasex or placebo for two weeks. The
dose of Gasex was two tablets three times daily for one week, and
then two tablets twice daily for the second week. Thirty-six of the 50
patients in the placebo group did not have any response after two
weeks and were switched to Gasex treatment. Of all the subjects
given Gasex, 71 of 86 were judged as having a good to excellent therapeutic
response (Mishra and Singh, 1981). Our reviewers, Drs.
Karriem Ali and Richard Aranda, commented that the crossing over
of the placebo nonresponders to the treatment arm, without any distinction
in the reporting of the results, obscures the purpose of having
a placebo group.


Postoperative Gastric Distress

Another trial with Gasex studied 150 women recovering from
gynecological surgery. Treatment began on the postoperative day at
the onset of bowel sounds, with either Gasex (two tablets three times
daily) or vitamin B complex tablets as placebo, and continued for one
to two weeks. All patients taking Gasex showed considerable improvement
in symptoms compared to the controls. In the Gasex
group, a good to excellent response was observed in 95 percent of patients
with abdominal discomfort, and in 88 percent with flatulence,
compared to 14 percent and 4 percent of the control group, respectively
(Chandra et al., 1978). The randomization and blinding processes
were inadequate, and the use of vitamin B complex as placebo
was not explained.

2nd Wind Recovery After Exercise

Ingredients:
Ginseng (Panax ginseng C.A. Meyer) root
Cordyceps [Cordyceps sinensis (Berk.) Sacc.]
Reishi mushroom [Ganoderma lucidum (Curtis: Fr.) P.
Karst.]
Enoki mushroom [Flammulina velutipes]
Siberian ginseng [Eleutherococcus senticosus (Rupr. &
Maxim.) Maxim.] root
Tangerine (Citrus reticulata Blanco) peel


2ndWind™ is a proprietary blend of six different ingredients: ginseng
(root extract), cordyceps (fermentation), reishi mushroom (fermentation),
enoki mushroom (fermentation), Siberian ginseng (root
extract), and tangerine (peel extract). It is manufactured and distributed
by Botanica BioScience Corporation.


2ndWind is formulated to accelerate recovery after exercise by enhancing
the clearance of lactic acid (lactate) from the muscles during
and after exercise. Lactic acid is produced during exercise, and its
accumulation in muscles can result in soreness and fatigue. With intense
exercise, lactic acid buildup can reduce blood pH and cause a
condition known as acidosis. Thus, enhancing the clearance of lactic
acid is a key principle in increasing athletic performance, and is a
means to speeding recovery from exercise. Lactate measurements in
the blood give an indirect, but reliable indication of lactate levels in
muscle cells (Burke, 1996).



2nd Wind
Recovery After Exercise

Two unpublished, placebo-controlled clinical studies were reviewed.
In the first study, including 20 healthy young males, 1 g of
the formula per day caused a statistically significant increase in the
clearance of lactic acid in the blood following exercise after two
weeks of treatment compared to baseline measurements. Clearance
of lactic acid in the placebo group did not improve (Burke, 1996). The
second study, with 12 healthy students given 1.35 g 2ndWind or placebo
daily for five weeks, also reported comparatively less lactic acid
in the blood following exercise. The plasma pH following exercise
appeared to be more stable in the treatment group as well (Seifert,
Burke, and Lahr, 1998). A review by Dr. Mary Hardy found that neither
study established therapeutic benefit due to an inadequate description
of the methods and results in the trial reports.

Cystone

Ingredients:

Shilapushpa (Didymocarpus pedicellata R. Br.) leaves
Pasanabheda (Saxifraga ligulataWall.) root
Rough chaff tree (Achyranthes aspera L.) seed
Indian madder (Rubia cordifolia L.) root
Ash-colored fleabane (Vernonia cinerea [L.] Less.) whole
Umbrella’s edge (Cyperus scariosus R. Br.) tuber
Sedge (Onosma bracteatumWall.) aerial parts
Mineral pitch


Cystone® tablets contain a combination of seven herbal extracts
and mineral pitch, a total of 540 mg per tablet. Current labels suggest
a dose of one to two tablets twice daily, for a total quantity of 1.08 to
2.16 g per day. Cystone is manufactured by The Himalaya Drug
Company in India, and distributed in the United States by Himalaya
USA. Cystone is also available under the name UriCare®. The current
Cystone product label lists the ingredients indicated previously.
The material used in the clinical study had the same name, but contained
an additional ingredient: Hajrul yahood bahsma.



Cystone is an herbal formula tested in the treatment of kidney and
bladder stones. Urinary tract stones form in the bladder and kidney.
Human urine is saturated with calcium oxalate, uric acid, and phosphates
that normally remain in solution. However dehydration, urinary
stasis, pH changes, foreign bodies, and infection can lead to the
formation of stones. Stones are hard buildups of mineral composed
mostly of calcium salts, uric acid, or struvite (phosphate of magnesium
and ammonia). Treatment depends upon differentiation between
the various stone types as well as recognition and control of
any underlying metabolic diseases or structural abnormalities of the
urinary tract (Pizzorno and Murray, 1999).

Kidney stones

Kidney and Bladder Stones

The effect of Cystone on patients with kidney and bladder stones
(nephroureterolithiasis) was studied in a four-arm, open, clinical trial
including 100 participants. Two groups were given Cystone (two tablets
three times daily) and either encouraged to drink plenty of liquids
or given forced diuresis (intravenous liquids). Two control groups
were given antispasmodics and also either encouraged to drink plenty
of fluids or given forced diuresis. In the Cystone treatment groups, 76
and 80 percent, respectively, of participants were able to pass their
stones over a period of one to six months and thereby avoid surgery.
In the control groups given antispasmodics, only 20 and 28 percent,
respectively, were able to avoid surgery (Misgar, 1982). However,
due to poor methodological flaws, including the lack of characterization
of the size of the kidney and bladder stones in the various treatment
groups, our reviewers, Drs. Elliot Fagelman and Franklin Lowe,
found the benefit to be undetermined.


No adverse effects were reported in a clinical trial in which 50 subjects
were given two tablets three times daily for six months.

valerian

Valerian

Other common names: Garden heliotrope, garden valerian
Latin name: Valeriana officinalis L. [Valerianaceae]
Latin synonyms: Valeriana exaltata J.C. Mikan
Plant part: Root



Valerian species grow worldwide. The root (or more precisely the
underground parts including the rhizome, roots, and stolons) of European
valerian, Valeriana officinalis L., is used as an official drug in
many European countries. There is no scientific agreement regarding
valerian’s active constituents, but sesquiterpenes, valerenic acid, and
acetoxyvalerenic acid have been used as quality control markers, usually
described simply as valerenic acid. Pharmaceutical products are
produced mainly from aqueous extracts or aqueous alcoholic extracts.
The two extract types are not equivalent. The aqueous extracts
are based on traditional teas with an herb to extract ratio of 5:1 (2 g
herb resulting in 400 mg extract). Aqueous alcoholic extracts are often
made with 70 percent ethanol, and have an herb to extract ratio of
4 to 7:1 (Schulz, Hänsel, and Tyler, 2001).

Valerian products are commonly formulated with lemon balm,
hops, or passionflower. In fact, the German Commission E has approved
the use of combinations in fixed proportions of passionflower
herb, valerian root, and lemon balm, as well as valerian with hops
(see the Information from Pharmacopoeial Monographs section)
(Blumenthal et al., 1998).

Valeriana officinalis

Traditional uses for valerian products include states of tension,
restlessness, irritability, unrest, and insomnia. Insomnia, is one of
several sleep disorders, defined as difficulty falling asleep, difficulty
sleeping through the night, frequent night awakenings, early awakening,
or unrefreshing sleep. It is most commonly a transient problem of
less than two weeks, but it can also be chronic. Primary insomnia is a
sleeping problem not associated with any other health problem. Secondary
insomnia is related to a health condition, such as depression,
heartburn, cancer, asthma, pain, or related to administration of a medication
or alcohol.

Sleep stages have been defined according to polysomnographic recordings,
including electroencephalograms (EEG). Stage 1 sleep is
the transition from drowsy wake to sleep, and Stage 2 is light sleep.
Stages 3 and 4 are deep sleep, also known as slow wave or delta sleep.
REM (rapid eye movement) sleep occurs in Stage 5, in which dreaming
 occurs. Sleep stages occur in cycles throughout the night (Pagel
and Parnes, 2001).

 Sedative/hypnotic agents are commonly prescribed to treat insomnia.
The benzodiazepines (i.e., flurazepam, oxazepam, trizolam) are
very effective at inducing sleep, but they also can suppress REM
sleep, may result in dependence, and can cause hangover effects the
morning after. Ethanol can assist with sleep, but can cause tolerance,
dependency, and diminished sleep efficiency and quality. Antihistamines
can help, but may lead to daytime sleepiness. Antidepressants
have also been used with some success if the individual also has
symptoms of depression (Pagel and Parnes, 2001).

st john's wort

Saint johns wart flowers

Latin name: Hypericum perforatum L. [Clusiaceae]
Plant parts: Flower, leaf

St. John’s wort is an herb with bright yellow flowers, whose benefit
in treating psychiatric disorders may have been recognized by Paracelsus
during the Renaissance. St. John’s wort is native to Europe,
North America, South America, and Asia. Most contemporary preparations
of St. John’s wort are aqueous alcoholic extracts with plant/
extract ratios of 4 to 7:1. St. John’s wort products have been characterized
and standardized to the content of hypericin and hyperforin. The
dried buds, flowers, and distal leaves contain 0.2 to 0.3 percent and 1 to
4 percent of these constituents, respectively (Schulz, Hänsel, and Tyler,
2001).

st johns wort

Hypericin content is often measured using ultraviolet (UV) spectroscopy
using a method described by the German Pharmaceutical
Codex (Deutscher Arzneimittel-Codex [DAC]) that determines the
total quantity of a class of compounds called dianthrones, which includes
hypericin, psuedohypericin, protohypericin, and protopseudohypericin.
The UV spectroscopy results are quoted as total hypericin.
These constituents are also analyzed using high performance liquid
chromatography (HPLC), a system that allows for measurement of
individual constituents. Measurements generated from UV and HPLC
analysis are not interchangeable and should not be confused. The
other ingredient commonly used to characterize St. John’s wort products,
hyperforin, is quantified using HPLC analysis.


The most common indication treated with St. John’swort is mild to
moderate major depression. The essential feature of a major depressive
episode, as defined in the DSM-IV (Diagnostic and Statistical
Manual of Mental Disorders, Fourth Edition), is a period of at least
two weeks during which depressed mood or the loss of interest in
nearly all activities is observed (American Psychiatric Association,
1994). Additional symptoms of depression include changes in appetite
or weight, sleep, and psychomotor activity, decreased energy,
feelings of worthlessness or guilt, difficulty concentrating, or recurrent
thoughts of death or suicidal ideation. Major depressive episodes
can be mild, moderate, or severe. Depressive disorders are also defined
in theWorld Health Organization’s (WHO) International Classification
of Diseases, Tenth Revision (ICD-10) (WHO, 1992). Some
of the reviewed trials had inclusion criteria according to earlier
versions of these manuals: DSM-III and ICD-9.


The Hamilton Depression Rating Scale (HAM-D) is an observer
rating scale used to evaluate the degree of depression, and is often
used to evaluate the success of treatment. The physician interviews
the patient and assigns a score based on the severity of 17 or 21 items.
The definition of therapeutic success is usually a 50 percent reduction
in the total HAM-D score or a total score less than ten.


The usual treatment for depression includes psychotherapy and
antidepressant medication, which includes selective serotonin reuptake
inhibitors (SSRI), tricyclic antidepressants, and, more rarely,
monoamine oxidase inhibitors.

The majority of the reviewed studies indicate that St. John’s wort
extracts may be a viable treatment option for patients with mild to
moderate depression. However, some recent trials have not shown
any efficacy compared to placebo, casting doubt upon the benefit for
depression. However, we must keep in mind that at least one-third of
published clinical trials of approved antidepressants are negative for
efficacy (Thase, 1999). Nevertheless additional studies are required
to explore treatment for longer than eight weeks.

Two mode-of-action studies explored the effect of LI 160 and WS
5570 on pituitary hormone secretion as a means of exploring the effects
on neurotransmitters. The theory is that antidepressants that act
via noradrenaline reuptake inhibition pathways stimulate growth hormone
secretion, whereas those that act via serotonin reuptake inhibitors
stimulate prolactin. Cortisol secretion is increased by both noradrenaline
and serotonin reuptake inhibitors. In addition, plasma
levels of growth hormone can be elevated by dopamine reuptake inhibitors.
A small, one-day study with eight healthy males exploring
the mode of action of LI 160 found that administration of one dose of
2,700 mg LI 160 extract caused an increase in plasma concentrations
of growth hormone, a decrease in prolactin levels, and no effect on
cortisol levels compared to placebo. The authors of this study interpreted
the results to be due to an increase in the dopamine function
(Franklin et al., 1999). In contrast, another study found that administration
of 300 or 600 mg WS 5570 had no effect on prolactin levels,
only a minimal, inconsistent effect on growth factor levels, and a significant
effect on cortisol levels. The authors of this study suggested
an effect on noradrenaline and serotonin reuptake inhibitors due
mainly to the constituent hyperforin. Further, they suggested that the
discrepancies between the two studies might be a function of dose
(Schüle et al., 2001).

Saw palmetto Prostate & Bladder Health Support

saw palmetto botanical

Other common names: Sabal palm
Latin name: Serenoa repens (W. Bartram) Small [Arecaceae]
Latin synonyms: Sabal serrulata (Michx.) Nutt. ex Schult. &
Schult. f.; Serenoa serrulata (Michx.) G. Nichols.
Plant part: Fruit



Saw palmetto is native to North America and grows wild in Texas,
Louisiana, South Carolina, and Florida. Traditionally, Native Americans
in this region used the berries for food and as a tonic (USP,
2000). In addition, the berries have been used for more than 100 years
to treat benign prostatic hyperplasia. Modern saw palmetto preparations
contain lipids extracted from the powdered berries. The primary
ingredients include saturated and unsaturated fatty acids (mostly free
fatty acids), as well as free and conjugated plant sterols (Schulz,
Hänsel, and Tyler, 2001).

saw palmetto tree

Saw palmetto preparations have been assessed in clinical studies
for the treatment of symptomatic benign prostatic hyperplasia (BPH),
also known as benign prostatic hypertrophy and prostatic adenoma.
BPH is a nonmalignant enlargement of the prostate that is common in
men over 40 years of age. Symptoms include increased urinary urgency
and frequency (diuresis: increased formation and release of
urine; and nocturia: frequent and/or excessive urination at night), urinary
hesitancy, intermittency, sensation of incomplete voiding, and
decreased force of the urine stream. BPH is linked with a normal
change in hormone levels that occurs with aging. Testosterone levels
decrease while estrogen levels remain constant. This change is implicated
in BPH since estrogens induce hyperplasia (cell growth) in laboratory
experiments. Further, BPH is associated with an increase in
the activity of 5-alpha-reductase, the enzyme that converts testosterone
to dihydrotesterone (DHT). The levels of DHT are not increased,
but the number of androgen receptors seem to be. DHT has a greater
affinity for androgen receptors than testosterone and is thought to
stimulate prostatic growth. However, the pathology of BPH is not
completely understood. Although BPH is associated with prostate
enlargement, the size of the gland is not necessarily indicative of the
degree of obstruction of the urethra and the extent of symptoms
(Schulz, Hänsel, and Tyler, 2001; Barrett, 1999).

Several different rating systems have been developed to characterize
the symptoms of BPH: the International Prostate Symptom Score
(IPSS), the American Urological Association (AUA) symptom score,
the Vahlensieck classification, and the Alken classification.
The IPSS is derived from a questionnaire regarding urinary urgency,
frequency, hesitancy, intermittency, sensation of incomplete
voiding, and force of urine stream (Schulz, Hänsel, and Tyler, 2001).
The AUA symptom score is also a composite score obtained from
seven questions covering frequency, nocturia, weak urinary stream,
hesitancy, intermittence, incomplete emptying, and urgency (Barry et
al., 1992).



The Vahlensieck classification has four stages based upon symptoms:
Stage I is characterized by no voiding difficulties, no residual
urine, and a urine flow of more than 15 ml per second; Stage II is
characterized by transient voiding difficulties and urine flow between
10 and 15 ml per second; Stage III is characterized by constant voiding
dysfunction, urine flow less than 10 ml per second, residual urine
greater than 50 ml, and a trabeculated (ridged) bladder; and Stage IV
is characterized by residual urine volume of more than 100 ml and
bladder dilatation (Schulz, Hänsel, and Tyler, 2001).

The Alken classification has three stages. Stages I to III are similar
to Vahlensieck Stages II through IV. Stage I is the irritative stage,
characterized by an increase in the frequency of urination, pollakiuria
(abnormally frequent urination), nocturia, delayed onset of urination,
and weak urinary stream. Stage II is the residual urine stage, characterized
 by the beginning of the decomposition of the bladder function
accompanied by formation of residual urine and the urge to urinate.
Stage III is the regressive-obstructive stage, characterized by decomposition
of the bladder, vesicular overflowing, continuous drip incontinence,
and damage to the urinary system and kidneys due to
regressive obstruction (Löbelenz, 1992).

Predominant pharmaceutical treatments of BPH include alphareceptor
blockers and 5-alpha-reductase inhibitors. Alpha-adrenergic
receptor blockers (e.g., prozosin, terazosin) are thought to relax
smooth muscles in the bladder neck and within the prostate and thus
reduce symptoms. Five-alpha-reductase inhibitors (e.g., finasteride)
prevent the transformation of testosterone to DHT, thus increasing
levels of testosterone and reducing levels of DHT (Barrett, 1999).

Suggested pharmacological actions for saw palmetto include antiandrogenic,
anti-inflammatory, antiproliferative, and smooth muscle
relaxation. Saw palmetto preparations have been shown to inhibit 5-
alpha reductase, as well as the binding of DHT to androgen receptors.
However, questions remain as to whether these actions, demonstrated
in vitro, are clinically relevant (Barrett, 1999).

Red yeast rice

Other common names: Hong qu
Latin name: Monascus purpureus Went. [Monascaceae]



Red yeast rice is a traditional Chinese fermented product made
from a red yeast, Monascus purpureus Went., that is grown on rice.
Documentation of the use of red yeast rice extends back to the Tang
dynasty in 800 A.D. Red yeast rice products contain a group of compounds
called the monacolins, which are a family of polyketides. The
monacolins have been identified as inhibitors of an enzyme involved
in the endogenous biosynthesis of cholesterol, 3-hydroxy-3-methylglutaryl
coenzymeA (HMG-CoA) reductase. One of the monacolins,
monacolin K, is identical to lovastatin. Lovastatin is a common cholesterol-
lowering statin drug that is manufactured by Merck and Co.,
Inc., West Point, Pennsylvania (Heber et al., 1999; Schulz, Hänsel,
and Tyler, 2001).


Cholestin™ capsules are manufactured by Pharmanex, a subsidiary
of Nu Skin Enterprises, Provo, Utah. The capsules contained 600
mg red yeast rice product, including 0.4 percent monacolins by
weight (RY-2), approximately half of which (0.2 percent) were monacolin
K. Recent court action by Merck, due to the similarity of
monacolin K in Cholestin to lovastatin (mevinolin) in Mevacor®,
blocked the sale of Cholestin as originally formulated in the United
States. The original Cholestin, containing red yeast rice, is still available
in other countries. The new U.S. formulation includes, as a substitute,
a beeswax extract called policosanol. According to Pharmanex,
policosanol is a safe and effective ingredient that successfully
maintains existing normal cholesterol levels, although the new formulation
has not been tested clinically. Each capsule of Cholestin
sold in the United States now contains 15 mg policosanol (beeswax
extract 5:1).


 
Monascus purpureus Went. yeast is called Xue-zhi-kang in Chinese.
The Xue-zhi-kang product (RY-1) produced by Wei-Xin Company
(China) delivered a daily dose of 1.2 g red yeast rice containing
13.5 mg total monacolins.
The red yeast rice product called Zhitai, produced by WBL Peking
University Biotech Co. Ltd. (China) delivered 10-13 mg total monacolins
in a 5 g daily dose. According to a spokesperson from Pharmanex,
the former two products were prototypes studied in the development of
the original Cholestin.



Hyperlipidemia (Elevated Blood Lipid Levels)

A double-blind, placebo-controlled, randomized trial included 83
subjects with slightly elevated cholesterol (total serum cholesterol
204 to 338 mg/dl, LDL cholesterol 128 to 277 mg/dl, triacylglycerol
55 to 246 mg/dl, and HDL cholesterol 30 to 95 mg/dl). Participants
received either 2.4 g red yeast rice (Cholestin) or placebo for 12
weeks and were put on the American Heart Association’s Step I diet.
After eight and twelve weeks, total serum cholesterol and LDL cholesterol
measurements in the treatment group decreased significantly
from baseline and in comparison to placebo. The reduction in total
cholesterol in the treatment group after 12 weeks compared with
baseline was roughly 40 mg/dl. Triacylglycerol levels also decreased
at week 8 in comparison to placebo, and at weeks 8 and 12 in comparison
to baseline. HDL cholesterol levels did not alter significantly in
either group (Heber et al., 1999).

Pygeum

Other common names: African plum
Latin name: Prunus africana (Hook. f.) Kalkman [Rosaceae]
Latin synonyms: Pygeum africanum Hook. f.
Plant part: Bark




Pygeum bark has been traditionally used in central and southern
Africa to assist bladder and urinary function. In this traditional use,
the bark is ground into powder and mixed with milk. Modern formulation
of this botanical is a lipophilic extract of the bark. At least three
types of active compounds may be responsible for the therapeutic action
of the extract: pentacyclic terpenes, phytosterols, and ferulic acid
esters (Schulz, Hänsel, and Tyler, 2001).

Tadenan® is manufactured in France by Laboratoires Fournier.
The capsules contain 50 mg of a lipophilic extract of pygeum bark.
Tadenan is not sold in the United States.
Pigenil contains a pygeum bark extract (PrunuSelect™) manufactured
by Indena S.p.A., Italy. This extract has a plant to extract ratio
of 180:1, and is standardized to contain 11.7 to 14.3 percent sterols as
beta-sitosterol. Pigenil, in 50 mg capsules, was originally manufactured
by Inverni della Beffa in Italy. This product is not available in
the United States.


Prostatonin® contains extracts of both pygeum bark and nettle
(Urtica dioica L. spp. dioica) roots. This product is manufactured by
Pharmaton S.A. in Switzerland, and is sold in the United States by
Pharmaton Natural Health Products. It is available in softgel capsules
containing 25 mg pygeum extract, PY102 (200:1), and 300 mg nettle
extract, UR102 (5:1).


Pygeum preparations have been assessed in clinical studies for the
treatment of symptomatic benign prostatic hyperplasia (BPH), also
known as benign prostatic hypertrophy and prostatic adenoma. BPH
is a nonmalignant enlargement of the prostate common in men over
40 years of age. The symptoms of BPH include increased urinary urgency
and frequency, urinary hesitancy, intermittency, sensation of
incomplete voiding, and decreased force of the stream of urine. BPH
is linked with a normal change in hormone levels that occurs with aging.
Testosterone levels decrease while estrogen levels remain constant.
This change is implicated in BPH, since estrogens induce hyperplasia
(cell growth) in laboratory experiments. Further, BPH is
associated with an increase in the activity of 5-alpha-reductase, the
enzyme that converts testosterone to dihydrotesterone (DHT). The
levels of DHT are not increased, but the number of androgen receptors
seems to be. DHT has a greater affinity for androgen receptors
than testosterone, and is thought to modulate prostatic growth. However,
the pathology of BPH is not completely understood, and although
BPH is associated with prostate enlargement, the size of the
gland is not necessarily indicative of the degree of obstruction of the
urethra and the extent of symptoms (Barrett, 1999).


Predominant pharmaceutical treatments for BPH include alphareceptor
blockers and 5-alpha-reductase inhibitors. Alpha-receptor
blockers (e.g., prozosin, terazosin) are thought to relax smooth muscle
in the bladder neck and within the prostate, and thus reduce symptoms.
Five-alpha reductase inhibitors (e.g., finasteride) prevent the
transformation of testosterone into DHT. The rationale for this treatment
is that prostate enlargement may be linked to activation of androgen
receptors by DHT and a reduction in testosterone levels
(Barrett, 1999).


The clinical mode of action of pygeum has not been established,
but biochemical studies indicate that it has anti-inflammatory activity
and may inhibit 5-alpha-reductase. Nettle root extract, which is combined
with pygeum extract in the product Prostatonin®, may have
similar activity. Preparations of grass pollen and saw palmetto have
also been assessed clinically for treatment of BPH, and more information
about these botanicals is given in their sections in this book.
The mechanism of action of these botanicals is also not established,
but grass pollen has demonstrated anti-inflammatory activity, and
may reduce the growth of epithelial cells and fibroblasts. Suggested
pharmacological actions for saw palmetto include antiandrogenic,
anti-inflammatory, antiproliferative, and smooth muscle relaxation
(Marandola, et al., 1997; Awang, 1997; Barrett, 1999).

Red Clover

Latin name: Trifolium pratense L. [Fabaceae]
Plant part: Leaf

Red clover is a member of the pea family, and is an extensive agricultural
crop. The leaves and flowers contain a class of compounds
called isoflavones that includes formononetin, daidzein, and genistein.
Red clover products are characterized and standardized according
to the quantity and composition of these isoflavones (Kelly, Husband,
and Waring, 1998).

Clinical studies have been conducted with a standardized extract
of red clover leaves. This extract is incorporated into tablets called
Promensil™, manufactured by Novogen Laboratories Pty Ltd.,
NSW, Australia, and distributed in the United States by Novogen
Inc., Stamford, Connecticut. The tablets are characterized as containing
40 mg isoflavones, including biochanin (24.5 mg), formononetin
(8.0 mg), genistein (4 mg), and daidzein (3.5 mg). One of the studies
(Samman, 1999) used an unnamed Novogen product with a very similar
composition. The tablets contained 43 mg isoflavones, consisting
of biochanin A (25.7 mg), formononectin (9.3 mg), genistein (4.3
mg), and daidzein (3.7 mg).


Some plants in the pea family, including red clover and soy, contain
isoflavones that have weak estrogenic activity. With the waning
of estrogen levels in menopause, these phytoestrogens are thought to
help compensate and thus reduce the symptoms that may include hot
flashes, sweating, cardiovascular complaints, fatigue, vertigo, muscle
 and joint pain, urinary incontinence, vaginal dryness, and atrophy
of the vaginal epithelium. Other symptoms of a psychological nature
may include irritability, forgetfulness, anxiety, depression, sleep disturbances,
and reduced libido. Menopausal symptoms occur when a
woman’s ovaries no longer contain eggs. The resulting decline in
ovarian function causes a reduced production of estrogen and progesterone,
and a corresponding increase in follicle stimulating hormone
(FSH) and luteinizing hormone (LH) (Murray and Pizzorno, 1999).

An Asian diet is estimated to deliver 25 to 45 mg total isoflavones
per day, whereas the Western diet is estimated to contain less than 5
mg. Epidemiological data imply that the lower incidence of menopausal
symptoms in Japanese women compared withWestern women
may be related to an enhanced dietary intake of soy isoflavones. A soybased
diet is also thought to explain the relatively low incidence of cardiovascular
disease in Southeast Asia, since the diet is correlated with
low levels of plasma cholesterol (Glazier and Bowman, 2001; Barnes,
1998).

 Menopausal Symptoms

The first menopausal study was a well-designed, three-month trial
including 35 women (40 to 65 years of age) with at least three hot
flashes a day, who were distributed into three groups: placebo; 40 mg
red clover extract (one tablet Promensil); and 160 mg red clover extract
(four tablets Promensil). No significant difference was observed
in the incidence of flashes between the three groups after three
months. Therewas also no difference in vaginal pH or serum levels of
FSH or sex hormone binding globulin (SHBG), a hormone-binding
protein (Knight, Howes, and Eden, 1999). Our reviewer, Dr. Tieraona
Low Dog, noted that the control group had increased urinary isoflavone
levels, indicating an inadvertent intake of dietary isoflavones
that would be a major flaw for the study.

The second study was a relatively good, randomized, double-blind
crossover study that enrolled 51 women with more than three hot
flashes a day. Subjects were given either one tablet Promensil daily or
placebo for three months, with the two treatment phases separated by
a month’s washout period. No significant difference was observed
between groups in reduction of hot flashes, levels of SHBG, vaginal
swab, or ultrasound examinations (Baber et al., 1999). Again the
study lacked control of dietary sources of isoflavones.

Milk thistle

Other common names: Mary’s thistle
Latin name: Silybum marianum (L.) Gaertn. [Asteraceae]
Plant part: Seed


Milk thistle is native to southern Europe and northern Africa. The
plant part that is used medicinally is the ripe fruit (seed) with the outer
covering (pappus) removed. The seed contains about 2 to 3 percent of
the active constituent silymarin, a mixture of four isomers: silybin
(also spelled silybinin) (50 percent), isosilybinin, silydianin, and
silychristin. Studies conducted on silymarin have shown that it promotes
liver-tissue regeneration, and has antitoxic effects on the liver
(Schulz, Hänsel, and Tyler, 2001).

Legalon® is manufactured in Germany by Madaus AG. Legalon
contains a standardized extract of milk thistle seeds that is characterized
as containing 80 percent silymarin (140 mg silymarin per 173 to
186.7 mg extract). Legalon was previously distributed in the United
States by Nature’sWay Products, Inc., under the name of Thisilyn®.
Silipide, produced by Inverni della Beffa in Italy, contains a milk
thistle seed extract, IdB 1016, also known as Siliphos®, that is manufactured
by Indena S.p.A. Siliphos is a complex of silybin combined
with phosphatidylcholine containing 29.7 to 36.3 percent silybin. An
initial pilot study was conducted on a product with a molar ratio of
silybin to phosphatidylcholine of 1:1 (Buzzelli et. al., 1993). The current
product is manufactured with a ratio of silybin to phosphatidylcholine
of 1:2. Siliphos is sold in the United States under the
names UltraThistle™ and Maximum Milk Thistle™ by NaturalWellness.
Silimarina® is manufactured in Romania by Biofarm. Each 700
mg tablet contains the equivalent of 35 mg silybin. The clinical study
report claims that Silimarina is a copy of Legalon.
One trial was conducted on a product simply described as silymarin,
using a dose of 800 mg daily. No further description was available.


Milk thistle preparations have been tested for their ability to treat
symptoms of liver disease caused by alcohol, other toxins, or viral infections.
The major liver diseases are hepatitis, cirrhosis, and dysfunctions
related to bile secretion. Hepatitis is characterized as an inflammation
of the liver that can be present with or without cirrhosis.
Forms of viral hepatitis include hepatitis A, B, and C. Cirrhosis is a
state in which the tissue in the liver breaks down, becoming fatty and
fibrous. Liver disease can be acute (short term) or chronic (long term)
leading to cirrhosis and eventually to liver failure (Morazzoni and
Bombardelli, 1995; Habib, Bond, and Heuman, 2001).

 

The clinical symptoms of liver disease are jaundice (yellowing of
the skin), enlarged liver, ascites (pooling of fluid in the abdominal
cavity), and encephalopathy (breakdown of brain tissue leading to
impaired consciousness). Liver disease is characterized by a buildup
of liver enzymes in the blood. These enzymes include aspartate
aminotransferase (AST, also known as glutamic oxalacetic transaminase
or GOT), alanine aminotransferase (ALT, also know as
glutamic pyruvate transaminase or GPT), gamma-glutamyl transferase
(GGT), and alkaline phosphatase. Three laboratory parameters
are used routinely to assess liver function: serum bilirubin, serum albumin,
and plasma prothrombin time. The yellow coloring characteristic
of jaundice is caused by a buildup of bilirubin in the blood. Bilirubin
is a yellow pigment formed by the breakdown of red blood cells
that is normally secreted by the liver in bile. Plasma prothrombin time
(international normalized ratio [INR], a blood clotting index) is a useful
indicator of liver function, since it is dependent upon blood clotting
 factor VII, which is produced by the liver (Habib, Bond, and
Heuman, 2001).



 
The presence and severity of cirrhosis has been graded using an index
called the Child-Turcotte-Pugh (CTP) score. The CTP score is
the sum of five parameter scores (prothrombin time, bilirubin, albumin,
ascites, and encephalopathy). Lower CTP scores of relatively
healthy subjects are classified as Child’s Class A, moderate scores are
classified as Child’s Class B, and the high scores of subjects requiring
liver transplants are classified as Child’s Class C (Habib, Bond, and
Heuman, 2001). Milk thistle has generally been used to treat those
with cirrhosis categorized as Child’s Class A.

Lemon Balm

Other Common Names: Balm, bee balm, Melissa balm
Latin Name: Melissa officinalis L. [Lamiaceae]
Plant Part: Leaf


The genesis of the lemon balm product Herpilyn®, indicated for
the topical treatment of herpes infections, was the discovery of antiviral
properties of the herb in a cell culture assay. The traditional use
for lemon balm is reflected in the German Commission E’s approval
of oral preparations for nervous sleeping disorders and gastrointestinal
complaints (Schulz, Hänsel, and Tyler, 2001).
A standardized preparation of lemon balm leaves is manufactured
by Lomapharm, Rudolf Lohmann GmbH KG, Emmerthal, Germany.
Lomaherpan® cream contains 1 percent of a dried aqueous extract
called Lo-701 (ratio of leaf to extract 70:1). The product in the United
States, distributed by Enzymatic Therapy under the name of
Herpilyn®, contains the same lemon balm extract, Lo-701. In addition,
it contains 1 percent allantoin, which is a monographed ingredient
for over-the-counter (OTC) fever blister medications. The product
tested in the two clinical trials reviewed here did not contain
allantoin.

We reviewed two controlled clinical studies that examined the
ability of Lomaherpan to reduce the symptoms of herpes simplex, a
viral lesion that can occur on the lips of the mouths (cold sores), on
the genitals (genital herpes), or on the skin. Herpes infections are
characterized by local outbreaks with itching followed by blisters and
inflammation, which usually heal in a few days, sometimes producing
scabs in the process. Herpes is often treated with antiviral agents
such as acyclovir, which, when given orally, can reduce virus shedding,
symptoms, and time to healing. Such agents appear to have less
benefit when given topically (Hardman et al., 1996).

Herpes simplex


Arecent study included 66 adults with a history of recurrent herpes
of the lips (orolabial herpes). The subjects were administered Lomaherpan
or placebo cream (2 mm) four times daily at the first sign of an
outbreak. Participants were monitored for five days following an outbreak,
with symptoms on day 2 being the primary end point. The
Lomaherpan cream produced a significant reduction in the symptom
score compared with placebo on day 2. However, overall symptom
scores for the five-day periods were not different for the two groups
(Koytchev, Alken, and Dundarov, 1999). Our reviewer, Dr. Richard
O’Connor, considered that the small improvement observed after two
days might not be clinically relevant.
The second placebo-controlled, double-blind study examined a total
of 116 outpatients, both children and adults, with herpes lesions on
multiple sites, including the lips, skin, and genitals. Patients were instructed
to apply cream two to four times daily to the affected site
over a maximum of ten days (on average five) until the lesion was
healed. A significant reduction in redness (rubor) and swelling was
observed on day two, but no significant difference in symptoms of
blisters, scabbing, erosion, pain, or course and extent of the lesions.
However, a significant increase in healing time compared with placebowas
seen in a subgroup of patients (67) with herpes on the lips of
the mouth (Wolbling and Leonhardt, 1994). The evidence for benefit
in this trial was weakened by poor methodological descriptions in the
report.

kava

Other Common Names: Kava kava, kava peper, awa,
yangona
Latin Name: Piper methysticum G. Forst. [Piperaceae]
Plant Part: Root



A water extract of ground kava root (actually a rhizome or underground
stem) has been used traditionally in the Pacific islands in
religious ceremonies and at social events. Modern commercial preparations
are usually made by extraction with ethanol or acetone. Pharmacological
studies have profiled the constituent kavapyrones, also
known as kavalactones, which are thought to be responsible for the
anxiety-relieving effect of kava (Schulz, Hänsel, and Tyler, 2001).
Laitan®, produced by Dr.Willmar Schwabe GmbH & Co., Karlsruhe,
Germany, contains an extract (WS 1490) prepared with acetone
and standardized to 70 percent kavalactones.
Two studies used aqueous extracts prepared by soaking either 30 g
root in 500 ml water or 200 g root in 1,000 ml water.
Kavatrol™, produced by Natrol, Inc., is sold in capsules containing
200 mg root extract including 60 mg kavalactones (30 percent)
and 50 mg dried plant material each of hops (Humulus lupulus L.)
flowers, passionflower (Passiflora incarnata L.) aerial parts (aboveground
parts), schizandra [Schisandra chinensis (Turcz.) Baill.]
fruits, and chamomile (Matricaria recutita L.) flowers.


Kava is used traditionally to make a ceremonial beverage. It has
been tested clinically most often for its use to treat anxiety. Anxiety is
a vague, unpleasant emotional state with qualities of apprehension,
dread, stress, and uneasiness. The presence and severity of characteristic
anxiety symptoms are often measured using the Hamilton Anxiety
Rating Scale (HAM-A), a standard and well-established clinician
rated scale with 14 items. The total item score is the “gold-standard”
measure used to establish and compare the efficacy of new treatments
for general anxiety disorder. Benzodiazepines are commonly used to
treat anxiety, but are associated with adverse effects such as dependence,
sedation, and memory impairment (Hardman et al., 1996).
Ten controlled trials on the use of kava were reviewed. Six studies
were conducted on anxiety. Five of these studies, which used the
product Laitan, were well-designed studies that reported significant
effects. The sixth study, which used the product Kavatrol, showed a
trend toward efficacy. The other four studies on cognitive functioning
and sleep were poorly designed, and although kava had no obvious
effect on cognitive performance, any definite conclusion would be
premature.


Anxiety

A kava product that also contains small amounts of four other botanicals,
Kavatrol, was tested for its effect on anxiety in 60 subjects.
A dose of two (200 mg) capsules were given twice daily, the equivalent
of 800 mg extract per day, or 240 mg kavalactones. Subjects evaluated
their own degree of stress in a Daily Stress Inventory and a
State-Trait Anxiety Inventory. According to the authors, the study indicated
that kava reduced the stress associated with the daily hassles
of life (Singh et al., 1998). However, our reviewers deemed the study
to be flawed due to a lack of description of the type of anxiety, coupled
with the fact that no assessment of the anxiety state was made by
a physician.



Cognitive Functioning

The effects of kava on cognitive function were tested in two poorquality
trials that used aqueous extracts of the root. The first study
compared the effects of two different doses of kava to controls who
consumed no kava in open-label experiments on 27 healthy college
students. The lower dose was an aqueous extract prepared from 30 g
root, and the second dose varied with the weight of the subject (1 g
per kg body weight, or 70 g for a 150 lb person). After a single administration,
neither kava dose altered the speed of activation of verbal
information in long-term memory or alertness (Russell, Bakker, and
Singh, 1987). The second study used a slightly higher dose of kava,
equivalent to 100 g root. In this placebo-controlled study with 24 subjects,
one dose of kava produced feelings of intoxication, body sway,
and a trend toward reduced cognitive performance (Prescott et al.,
1993).

Horse chestnut

Latin name: Aesculus hippocastanum L. [Hippocastanaceae]
Plant part: Seed



Native to the Near East, the horse chestnut tree was brought to
northern Europe in the sixteenth century. As early as the 1800s, horse
chestnut seed extracts were used therapeutically in France. Although
preparations of other parts of the tree have been used medicinally,
only the efficacy of the dried seeds has been proven. Powdered dried
seeds contain 3 to 5 percent saponins, and powdered hydroalcoholic
extracts of the seeds contain 16 to 20 percent triterpene glycosides (a
class of saponins), calculated as aescin (escin). Aescin, itself a mixture
of several glycosides derived from two triterpenoid aglycones, is
believed to be the main active constituent of horse chestnut seed extract
(Schulz, Hänsel, and Tyler, 2001).

Horse chestnut has been used traditionally as an herbal remedy for
chronic venous insufficiency, and numerous clinical trials support
that use. Chronic venous insufficiency (CVI) is characterized by
chronic inadequate drainage of venous blood and venous hypertension,
which results in leg edema, dermatosclerosis (hardening of the
skin), and feelings of pain, fatigue, and tenseness in the lower extremities.
As a result, patients often require hospitalization and surgery,
for instance, for symptomatic varicose veins. Pharmacological therapies
and/or leg compression with specialized stockings or surgery are
the treatment options (Pittler and Ernst, 2002).

CVI is divided into three stages according to the degree of severity.
The symptoms of Grade I, according toWidmer and Marshall, are dilation
of the veins of the feet and a tendency for edema. Grade II is defined
by additional symptoms, including pigmentation of the skin,
hypertrophy of the skin corneal layer, and hardening of the skin.
Grade III is characterized by leg ulcers, either healed (IIIa) or unhealed
(IIIb). In the early stages of CVI (Grade I), the veins have not
suffered any permanent damage, and pharmacological therapy may
reduce the leakage of fluid from the veins. At the later stages of CVI
(Grades II and III), the disease process involves the larger veins, and
ultimately the damage to the veins is irreversible (Ottillinger and
Greeske, 2001). Studies reviewed here included patients with CVI
Grades I or II. One study, on a generic product, included patients with
CVI Grade II according to Hach. Although we found no information
on this scale the description of symptoms were similar to Grade II according
toWidmer and Marshall. They were obstructive edema, possible
tropic skin changes, and venous capacity and/or venous return
outside normal limits (Diehm et al, 1992).

 Chronic Venous Insufficiency

Venaforce was reported to statistically reduce ankle edema, but not
subjective symptoms of heaviness, pain, burning, itching, or pins and
needles in the legs. This placebo-controlled study included 52 subjects
with CVI Grades I or II. Treatment consisted of six tablets, containing
120 mg aescin, per day for six weeks (Shah, Bommer, and
Degenring, 1997).


 Chronic Venous Insufficiency

A well-conducted, placebo-controlled trial with 39 patients with
CVI (Stage II according to Hach) reported a statistical reduction in
mean leg volume after six weeks of treatment, both before and after
edema provocation, compared to placebo. Treatment was an unbranded
extract delivering 150 mg aescin per day (Diehm et al., 1992).


 Hematoma

Escin gel containing 2 percent aescin was compared to placebo in
an experimentally induced hematoma model. Hematomas are swellings
filled with blood that can form as the result of physical trauma to
the body, causing damage to blood vessels beneath the skin. In this
study, hematomas were induced in 70 healthy volunteers by subcutaneous
injection of 2 ml of the subjects’ own blood. Treatment with
10 g of gel or placebo followed within five minutes. Sensitivity measurements
were taken from one to nine hours after treatment. As a result,
the Escin gel statistically reduced pain at all time points compared
to placebo (Calabrese and Preston, 1993). Our reviewer, Dr.
Mary Hardy, criticized the model because the subcutaneous injection
of blood does not produce all of the parameters as a bruise or
hematoma acquired through trauma. Thus, she rated the possible benefit
as undetermined.

Hawthorn

Other common names: English hawthorn; May tree; white
thorn
Latin name: Crataegus laevigata (Poir.) DC. and C. monogyna
Jacq. as well as other species [Rosaceae]
Latin synonyms: Crataegus oxyacantha L. = C. laevigata
Plant parts: Leaf, flower


Hawthorn, a tall shrub that grows throughout Europe, was first
documented as having medical use in the first century A.D., but the
plant’s use as a heart medicine can only be traced back to the 1600s.
The two primary species are Crataegus laevigata (Poir.) DC. and C.
monogyna Jacq. However, other species have been used medicinally,
and to make matters more complex, the two primary species are
known to hybridize (Upton, Graff, Williamson, et al., 1999). Therapeutic
efficacy has been documented most reliably for the leaves and
flowers. The dried, berrylike fruits have also been used, either alone
or in combination with the leaves and flowers. The main constituents
of hawthorn are identified as procyanidins, flavonoids, triterpenoids,
catechins, aromatic carboxylic acids, and amino and purine derivatives.
For quality control purposes, the flavonoid content and/or the
oligomeric procyanidin content are determined. The leaves and flowers
contain approximately 1 percent flavonoids and 1 to 3 percent
oligomeric procyanidins (Schulz, Hänsel, and Tyler, 2001).

Hawthorn has been studied for its clinical use in the treatment of
early stage heart failure, which is also called cardiac insufficiency.
Heart failure is defined as the inadequate supply of oxygen and nutrients
to the body as the result of heart disease. Animal studies indicate
that hawthorn preparations increase the contraction of the heart muscle,
increase the integrity of the blood vessel wall, and improve the
flow of blood to the heart without changing heart rate or aggregation
of red blood cells (Loew, 1997).

The New York Heart Association (NYHA) has classified heart
failure in four stages. Patients with Class I heart failure have cardiac
disease but are able to conduct ordinary physical activity without limitation.
Class II is defined as a slight limitation of ordinary physical
activity due to fatigue, palpitation, dyspnea, or anginal pain. Class III
is defined as marked limitation of physical activity even on light exertion.
Patients with Class IV heart failure are unable to carry on any
physical activity without discomfort—they may experience symptoms
of congestive heart failure even at rest (Cochran Foundation,
1997). Many of the clinical studies using hawthorn have been conducted
on patients with Class II disease.


The American Herbal Pharmacopoeia (AHP) lists hawthorn leaf
and flowers for the treatment of Class I and II cardiac insufficiency,
hypertonic heart with and without signs of coronary insufficiencies,
myocardial insufficiencies, arrhythmia, cerebral insufficiency, mild
hypertension, and patients with a history of myocardial infarction. It
is also distinguished as having the ability to potentiate the effects of
cardiac glycosides. The actions listed by the AHP include: increases
coronary and myocardial perfusion, lowers peripheral resistance, and
has economizing action with respect to oxygen and energy consumption;
it is positively inotropic, positively dromotropic, negatively
chronotropic, and negatively bathmotropic; and hawthorn is considered
to be an antiarrhythmic, an antioxidant, a diuretic, a hypocholesterolemic,
a hypotensive, and a sedative (Upton, Graff, Williamson,
et al., 1999). The AHP has also published a monograph on hawthorn
berry with similar indications (Upton, Graff, Bencie, et al., 1999).

Green Tea

Latin name: Camellia sinensis (L.) Kuntze [Theaceae]
Latin synonyms: Thea sinensis L.
Plant part: Leaf

Chinese legend has it that tea was discovered in 2700 B.C. when a
gust of wind blew some tea leaves into a kettle of boiling water. A
competing legend advanced by the British East India Company
claims tea originated in India and not China (Gutman and Ryu, 1996).
Green tea and black tea are both derived from the young shoots
(the first two or three leaves plus the growing bud) of Camellia
sinensis (L.) Kuntze. The teas are differentiated by their method of
processing. Heating the freshly picked leaves shortly after harvest
produces green tea. This process inactivates enzymes (polyphenol
oxidases) that form the dark pigments associated with black tea. The
heated leaves are then rolled to squeeze the juices to the surface of the
leaf and dried using hot air. Black teas are produced by a natural enzymatic
fermentation of the leaves that occurs after harvest (Gutman
and Ryu, 1996).


A cup of green tea usually contains 300 to 400 mg polyphenols.
Polyphenols are a large class of mildly acidic compounds with antioxidant
properties. Polyphenols can be divided into many subclasses,
including catechins, an example of which is epigallocatechin gallate
(EGCG) (Gutman and Ryu, 1996).

Studies of green tea as tea solids or extracts have been conducted
exploring its use in weight loss and as an antioxidant useful in reducing
cardiovascular risk factors, in alleviating the adverse effects of renal
insufficiency, and in reducing the negative effects of cancer therapy
on blood cells. On balance, green tea extracts and green tea have
positive effects on metabolism and antioxidant activity. However, the
impact of these effects on health outcomes remains to be determined.

Weight Loss

A study exploring green tea’s effect on weight loss was conducted
using Exolise, one capsule three times daily. This mechanistic study
showed an increase in energy expenditure over a 24-hour period with
Exolise compared to placebo. The energy expenditure was 4 percent
above the stimulatory effects produced by equivalent amounts of caffeine
found in Exolise (Dulloo et al., 1999). Although this carefully
controlled study demonstrated thermogenic activity and promotion
of the oxidation of fat, the results were of questionable significance
for clinical weight management. A follow-up study with moderately
obese subjects did report weight loss as a result of treatment. How
ever that study did not include a control group, and thus did not qualify
for review in this book (Chantre and Lairon, 2002).

Cardiovascular Risk Factors/Antioxidant Activity

Potential antioxidant activity was explored in two studies comparing
green and black teas. In a study with 45 participants, the daily
consumption of six cups of green or black tea (Lipton tea solids, 0.5 g
in 150 ml water) over a four-week period did not lead to any effect on
serum lipid concentrations, resistance of low-density-lipoproteincholesterol
(LDL) to oxidation, or to markers of oxidative damage to
lipids. However, consumption of green tea led to a slight increase in
total antioxidant activity in plasma (van het Hof et al., 1997). The
other study included 21 adults who received six different treatments
on six different days with at least two days in between treatments.
The administration of a single dose of 2 g of green or black tea solids
(Lipton) in 300 ml water led to a significant increase in plasma catechin
levels and in plasma antioxidant activity one hour later. The rise
in total catechins was greater with green tea than black tea, as expected
based on the higher content of catechins in green tea compared
to black tea. The addition of milk to either green or black tea did not
affect results (Leenen et al., 2000). These studies were both rated as
low in quality due to a lack of blinding and poor descriptions of the
randomization process.


 Hematopoietic Effects of Cancer Therapy

A study examined the potential protective effect of a green tea
polyphenol extract (Xin Nao Jian) on the damage to the development
and formation of blood cells due to cancer radiation therapy or chemotherapy.
Sixty cancer inpatients with a normal blood cell profile
undergoing their first treatment were included in the study. They were
given 200 mg of extract three times daily, another herbal formula for
improving blood quality (Sha Gan Chun), or no additional treatment
for one month. Total white blood cell counts improved in the green
tea group but declined in the Sha Gan Chun group after five weeks
 and in the control group after three weeks. No significant changes
were observed in hemoglobin levels or platelet counts in any group
(Walsh, 1997a). Our reviewer, Dr. David Heber, commented that the
effects of green tea on lymphocyte stabilization and immune function
deserve further study. This study was limited by inadequately described
statistical methods and a small sample size.



 Renal Insufficiency

In another study, Tegreen was given in the same dose (200 mg
three times daily) to patients with chronic renal insufficiency for
three months. Renal function (as measured by blood urea nitrogen)
was improved, erythrocyte superoxide dismutase activity was significantly
increased, and plasma lipid peroxide levels were significantly
decreased. The author of the study commented that the benefits of
Tegreen to this population were due to its antioxidant activity and free
radical scavenging activity (Walsh, 1997b). Although it had some serious
methodological flaws, this study remains a good guide for future
studies.

 Cardiovascular Risk Factors

A small study using a green tea concentrate, Polyphenon E, measured
the effect of 300 mg extract twice daily, the equivalent of seven
to eight cups of tea, on markers of antioxidant activity in the blood
compared to untreated controls. After one week, plasma catechin levels
were measurable, whereas they were not detectable at baseline.
No effect was reported on the concentration of plasma lipids or on
lipid peroxides compared to baseline. However, an increase in resistance
to oxidation of LDL-cholesterol was measured ex vivo (Miura
et al., 2000). The study was weak due to the small sample size and the
lack of blinding and randomization of patient populations.