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Herbs for Gout
Eric Yarnell, ND, RH (AHG)
Abstract
Herbs used to prevent and treat gouty arthritis are reviewed in
depth. Colchicum autumnale (autumn crocus) along with other
sources of colchicine, including Gloriosa superba (flame lily),
are described, both for their historicalsignificance and relevance
to the drug colchicine and also for their use as whole herbs. The
reasons for considering whole herbs versus only isolated con-
stituents in the context of Colchicum and colchicine are high-
lighted. Three herbal foods that are helpful for gout are then
discussed: Apium graveolens (celery); Prunus avium (sweet
cherry) and P. cerasus (tart cherry); and Coffea arabica (coffee).
Various Chinese herbal formulas traditionally used for gout and
now the subject of modern research are presented, notably
Chuanhu antigout mixture, Er Miao Wan/San (Two Marvel
Decoction/Powder), and Si Miao Wan (Four Marvels Teapills).
Keywords: gout, herbal medicine, celery, colchicine, cherry,
coffee
Introduction
The ancient malady of gout, while certainly never gone, is
making a huge comeback in modern times. This condition is
particularly prevalent in countries bordering the Pacific Ocean,
but is generally common in all developed nations.
1,2
Research
in China has shown a dramatic increase in gout incidence as-
sociated with rapid industrialization and westernization, with
much higher rates in developed cities, compared to less-
developed cities or rural areas.
3
Gout is far more common in
adult men and postmenopausal women, and is almost never
seen prior to adolescence in men or in premenopausal women.
Classic gouty arthritis (also known as podagra) is recognized
easily, with a sudden onset of excruciating pain and erythema
in the metatarsophalangeal joint of the large toe. However,
gout also can present as acute bursitis or with atypical features
(such as affecting other joints, affecting multiple joints at once,
less-severe pain, or absence of erythema). An online calculator
is available to help clinicians diagnose acute gouty arthritis
correctly (see Gout Diagnostic Criteria).
Gout is clearly the result of people with certain genetic
predispositions being placed in environmental conditions that
result in precipitation of uric-acid crystals. Mutations that
resulted in the inactivation of the uricase gene in modern
humans, some primates, and some New World monkeys ac-
crued 13–24 million years ago.
4
This has left the average,
healthy adult male with an average serum uric-acid level of
around 6 mg/dL, compared to <1 for most other mammals.
5
It
appears that this evolutionary change was beneficial because
uric acid is a powerful antioxidant, accounting for >50% of
the antioxidant capacity in the blood.
6
This may have been
particularly important and beneficial in light of the much-
earlier (40–50 million years ago) loss of the ability for the
hominid line to make vitamin C, which, at the time, was
harmless because of the very high levels of vitamin C in the
diets of human ancestors.
7
As vitamin C levels fell in the diets
of subsequent evolutionary lines, the need for greater antiox-
idant protection was present and the chance loss of uricase may
have filled this role. It is also possible that uricase loss was
beneficial because it helped human ancestors maintain blood
pressure despite extremely low saltlevels.
8
Whatever the rea-
sons might be, it is clear now that some people suffer severely
because of these ancient genetic changes.
The balance between intake and production of the precursors
of uric acid, purines, and renal excretion of uric acid is crucial
in whether or not someone will develop gout. The kidneys
excrete 66%–75% of uric acid, with the gut removing the rest.
Most ( >90%) of patients with gout have trouble excreting
enough uric acid (and are termed “underexcretors”). The
Gout Diagnostic Criteria
A free online calculator that enables clinicians to apply
moderately effective (with a positive predictive value of 64%
and a negative predictive value of 87%) evidence-based di-
agnostic criteria quickly is available at:
http://goutclassificationcalculator.auckland.ac.nz
This website provides entry to the ACR-EULAR Gout Classification
Criteria table, which is downloadable as a pdf.
No superior criteria have yet been developed. The con-
comitant presence of gouty tophi in this study raised the di-
agnostic accuracy to 100%; their presence are essentially
pathognomonic for gout.
_________________
Source: ACR-EULAR Gout Classification Criteria Calculator. The
University of Auckland New Zealand, Medical and Health Sci-
ences. Accessed September 7, 2016.
ACR-EULAR, American College of Rheumatology-European
League Against Rheumatism.
218 DOI: 10.1089/act.2016.29075.eya MARY ANN LIEBERT, INC. VOL. 22 NO. 5
OCTOBER 2016
ALTERNATIVE AND COMPLEMENTARY THERAPIES
URAT1 transporter is critical in the almost-complete re-
absorption of uric acid filtered by the kidneys. The common
gout drug probenecid blocks this transporter, leaving more uric
acid in the urine to be excreted. Amlodipine, atorvastatin, fe-
nofibrate, losartan, and corticosteroids have also all been
shown to be uricosuric. This uricosuric effect results in a
greater risk of uric-acid kidney stone formation, however. Note
that aspirin, diclofenac, and loop and thiazide diuretics have an
antiuricosuric action and increase the risk of gout.
9
Approxi-
mately 10% of patients with gout are overproducers of uric
acid however, with the most extreme cases being in patients
with secondary hyperuricemia caused by chemotherapy or
hemolytic diseases that cause sudden massive releases of pu-
rines from cells.
The mainstay of all gout treatment is reduction of dietary
purine intake, which primarily means reducing intakes of
meats and seafoods.
10
Yet, higher intakes of vegetable sources
high in purines, particularly mushrooms, do not increase the
risk of gout. Overall, vegetable intake reduces the risk of gout
mildly, as do dairy products. Thus, most patients who are prone
to gout should primarily eat a vegetarian diet. Alcohol and
fructose should also be avoided, particularly beer, as these
substances increase the risk of gout significantly. Increased
water intake can assist uric-acid excretion and will help pre-
vent uric-acid kidney stone formation. Weight loss is also re-
commended for patients who are obese, as there is a strong
correlation between obesity and gout risk.
10
Herbal therapies that help prevent and that can be used to
treat acute gout can be used to augment the dietary approach
to gout. While some patients will require medication to stop
acute attacks or prevent future ones, many can do away with
these by using a combination of lifestyle modification and
herbal medicine. Specific useful herbs are discussed in detail
in this article.
Autumn Crocus
The Eurasian native plant Colchicum autumnale (autumn
crocus)—in the Colchicaceae family, which is related to the
lily family—is the source of the first and still widely used
effective drug for acute gout, colchicine. It is not clear when
Figure 1. Mechanisms of action and metabolism of colchicine. NALP-3, NACHT, LRR and PYD domains-containing protein 3; LTB4, leukotriene
B4; PMN, polymorphonuclear leukocytes.
MARY ANN LIEBERT, INC. VOL. 22 NO. 5 219
ALTERNATIVE AND COMPLEMENTARY THERAPIES OCTOBER 2016
autumn crocus’s medicinal properties were first recognized.
Although many sources claim that this herb was mentioned in
the ancient Egyptian Ebers Papyrus, one of the oldest, if not the
oldest extant books that happens to be an herbal formulary, this
appears to be caused by confusion of this plant with Citrullus
colocynthis (colocynth). Dioscorides mentioned autumn cro-
cus in his materia medica (written circa 60 ad), but only to
warn of its poisonous properties. Alexander of Tralles in his
work Therapeutica discussed the use of a medicine he called
Hermodactyl (“finger of Hermes”) for gout, but gave no bo-
tanical description of this plant to clarify what it was.
11
His
description was of the medicine working quickly and specifi-
cally for acute gout while causing catharsis and that carmina-
tives were typically added to counteract the adverse effects of
the medicine. This matches the effects of autumn crocus clo-
sely, thus, there is some support for the ancient origins of the
use of this plant for treating gout.
There were many other unclear accounts of autumn crocus–
like medicines used throughout antiquity, and it was not until
the French military officer Nicolas Husson (who was not a
physician) introduced his “Eau Me
´dicinale” (atea of the corm of
autumn crocus) circa 1783 that indisputable accounts of use of
C. autumnale for gout emerged.
12
This treatment became quite
established in the 1800s as did research showing that it did not
work by increasing excretion of uric acid in the urine or
changing serum levels of uric acid.
13
As of the completion of the
2014 Cochrane meta-analysis, there were still only two small,
low-quality published clinical trials, both supporting the efficacy
of pure colchicine for addressing acute gout.
14
Low-dose col-
chicine (0.5mg every 20 minutes for 1 hour) was just as ef-
fective as high-dose colchicine (up to 4.8 mg over 6 hours).
However, high-dose colchicine caused high rates of adverse
effects, with diarrhea, nausea, and vomiting occurring in *50%
of test subjects (a statistically significantly higher rate than in
placebo or low-dose colchicine groups), while low-dose col-
chicine did not cause any more adverse effects than placebo.
Colchicine, a major active compound in autumn crocus, was
isolated in 1820 by Joseph Bienaime´ Caventou (1795–1877
ad), a French pharmacist, and Pierre-Joseph Pelletier (1788–
1842 ad), a French chemist, who were also famous for iso-
lating many other alkaloids including quinine and caffeine.
Colchicine is technically a pseudoalkaloid because, although it
is synthesized like other alkaloids, the nitrogen in it is not
found in a heterocyclic ring. Colchicine is a fascinating com-
pound that inhibits microtubule polymerization, inhibits mi-
totic spindles, and blocks various inflammatory pathways (see
Fig. 1).
15
Notably, this affects the ability of leukocytes to in-
duce inflammation, particularly in response to uric-acid crys-
tals. Unlike most inhibitors of mitosis, colchicine is active at
concentrations that do not interfere with other critical cellular
metabolic processes, which has made it a crucial tool in the
investigation of cancer, genetics, endocrinology, and many
other processes. For a political commentary on colchicine in
the modern age, see The Politics of Colchicine.
The history of autumn crocus and colchicine is a familiar
one in herbal medicine. A powerful herb has an “active con-
stituent” isolated, which is then presumed to be the only active
compound in the plant. This single molecule is then turned into
a drug with its attendant increased toxicity, while the rest of
the plant or use of the whole herb is then practically ignored. A
growing body of research suggests that this is an error, and that
the whole plant has activity not accounted for by colchicine
alone.
A study in rabbits found that whole autumn crocus corm
powder at a dose of 2.5mg/kg/day was as effective as allopu-
rinol for lowering serum uric-acid levels, an effect not seen with
isolated colchicine.
16
There are other pseudoalkaloids in autumn
crocus in addition to colchicine, including colchicoside and 3-
demethylcolchicine, which have shown interesting effects in
vitro.
17–19
The semisynthetic drug thiocolchicoside has been
approved in some countries as a muscle relaxant, which has
proven to be effective for treating low-back pain and other
similar problems.
20
The semisynthetic colchicine-based drug
demecolcine is used to treat some cancers. Another Colchica-
ceae family, colchicine-containing herb is Gloriosa superba
(flame lily), which is native to Asia and Africa. Crudeextracts of
this herb have been shown to treat pancreatic cancer in mice.
21
Flame lily is also used to treat gout in crude form.
22
All of this
suggests the potential of other aspects of autumn crocus in ad-
dition to its colchicine content for patients with gout. There is a
need to avoid treating autumn crocus with such reductionism if
its true potential is to be realized. These facts also support that
The Politics of Colchicine
Colchicine was in wide use prior to the existence of the
U.S. Food and Drug Administration. When the FDA was created
and regulation of the U.S. pharmaceutical market began, col-
chicine remained available as an inexpensive generic. However,
the FDA had noted the lack of rigorous trials for this and many
other pre-1962 generic pharmaceuticals. In the mid-2000s, the
company URL Pharma did conduct trials and, in 2009, obtained
FDA approval to sell branded colchicine under the name Col-
crys.
Ò
The company received 3-year exclusive rights to sell
Colcrys for treating gout and 7-year rights for treating familial
Mediterranean fever—at a substantial price markup, compared
to the previously available generics (which the FDA forced off
the market). URL Pharma did not prove anything not previously
known about the drug or find anything novel, yet the FDA
received the desired proof and rewarded the company. There is
evidence that the FDA’s actions resulted in a decline of use of
colchicine and a significant increase in patient expenditures
among those who were prescribed the medication, suggesting
a net decrease in patient well-being.
a
In a different, more
patient-centered and less drug company–focused model, the
U.S. government would have paid for trials to prove that
the drug was effective and thus validated the ongoing use of
the inexpensive generics already on the market.
_________________
Source:
a
Kesselheim AS, Franklin JM, Kim SC, et al. Reductions in
use of colchicine after FDA enforcement of market exclusivity in a
commercially insured population. J Gen Intern Med 2015;30:
1633–1638.
220 MARY ANN LIEBERT, INC. VOL. 22 NO. 5
ALTERNATIVE AND COMPLEMENTARY THERAPIES OCTOBER 2016
crude autumn crocus extracts have a place in medicine, although
this needs to be defined better in modern clinical trials.
The U.S. Pharmacopeia, in the late 1800s and early 1900s,
included a 1:10 wt:v tincture of colchicum seed, extracted
using 55% ethanol. The recommended dose was 10–30 minim
(1–2 mL) every 4 hours until pain was relieved or nausea/mild
purgation occurred. It is now more common to use a tincture of
the corm, 1:5 wt:v, at a dose of 3–5 drops twice per day (or less
if diarrhea or vomiting occur). This tincture should be used
with great caution, if at all, in patients with renal failure and
bone-marrow damage. There is no known antidote for autumn
crocus or colchicine overdose.
Colchicine is a CYP3A4 and Pgp substrate. Concomitant use
with CYP3A4 inhibitors (such as the antibiotic clarithromycin
or grapefruit) can lead to significant increases in absorption
of colchicine and death unless the dose is decreased.
23
It is
unknown to what degree this causes problems with whole
autumn crocus, but caution is warranted. Grapefruit could
possibly be used intentionally to reduce colchicine or autumn
crocus use, but the exact doses needed to achieve this have
not been determined.
Antigout C Foods: Celery, Cherry, and Coffee
Another food/medicine that has proven very helpful clini-
cally for patients with gout is common celery (Apium grave-
olens). This Apiaceae family vegetable is also known as a
diuretic and inflammation modulator. Sadly, it has received
little research attention. Phthalides, furanocoumarins, and
terpenoids are believed to contribute to this food’s clinical
activity. Celery extract inhibited xanthine oxidase in vitro in
one study, and celery’s prominent flavonoid constituent lu-
teolin did the same in another.
24,25
In mice treated with
doxorubicin, celery root and leaf juice reduced xanthine oxi-
dase.
26
Celery was historically used as a diuretic, and so might
simultaneously increase urinary excretion of uric acid while
inhibiting its synthesis. A traditional Uighur formula known as
Karapxa Decoction, which contains primarily celery root and
seed along with Cuscuta chinensis (dodder) seed, Cichorium
glandulosum (chicory) root and seed, and Foeniculum vulgare
(fennel) fruit was shown to inhibit xanthine oxidase and reduce
serum uric acid in mice with induced gout.
27
The current author became aware of this property of celery
after hearing the esteemed herbalist and retired scientist from
the U.S. Department of Agriculture, James Duke, PhD, openly
discussing how he was able to stop using medication for his
gout because he used celery. Subsequently, many patients with
gouty arthritis or uric-acid kidney stones have been able to
decrease or eliminate these problems by eating 3–5 stalks of
celery a day. Clinical trials are warranted.
Celery is generally extremely safe. There is a low risk of
photodermatitis in patients with very light skin and high sun
exposure. Some patients are supersensitive to this problem and
will already know it from getting rashes just brushing up
against plants in the Apiaceae family. Using sunscreen and
wearing protective clothing while avoiding direct sun can help
prevent this reaction in sensitive patients.
Back in 1950, a report was published showing that patients
with gout who ate 0.5 lb of fresh, canned, or frozen (but not
sweetened) cherries daily had lower serum uric-acid levels and
fewer acute gout attacks.
28
Based on this single case series,
cherries became a popular gout treatment in alternative med-
icine circles. It was not until 2003 that the next published report
was published. In this study, 10 healthy women ate 2 servings
of 280 g (*8 oz) of sweet Bing cherries after an overnight
fast.
29
Average serum uric-acid levels fell in these women over
the 5 hours after cherry consumption to a level that was sig-
nificantly below baseline. Uric-acid levels did not fall in his-
torical control subjects who consumed grapes, strawberries, or
kiwi at similar or higher amounts. This study is of dubious
relevance to patients with gout, but is important, as many in-
ternet sites claim that only tart cherries are worthwhile, while
this study showed clearly that sweet cherries produced activity
(see Two Types of Cherries).
In 2007, Naomi Schlesinger, MD—then chief of the division
of rheumatology and connective tissue research at Robert
Wood Johnson Medical School in New Brunswick, NJ—and
colleagues published an abstract describing a randomized trial
of tart cherry juice concentrate.
30
Subjects took either 1 tbsp of
tart cherry juice concentrate twice daily or pomegranate con-
centrate at the same dose. After 4 months of treatment, the
subjects in the cherry-juice group had a significant reduction in
acute gout attacks, compared to what occurred in the control
group. Fully 55% of the cherry group had no gout attacks and
were able to discontinue use of nonsteroidal anti-inflammatory
drugs (compared to none of subjects in the control group). This
research was funded by the maker of the cherry juice product,
FruitFast/Brownwood Acres of Eastport, Michigan. In vitro,
Schlesinger reportedly found that the cherry juice inhibited
inflammatory compounds produced in response to uric-acid
crystals. The researchers did not find any lowering of serum
uric acid. The lack of full publication of these results requires a
good deal of skepticism about their validity.
This same doctor and other researchers subsequently pub-
lished information about retrospective studies suggesting that
tart cherry juice concentrate reduced gout attack frequency
without reducing serum uric acid levels.
31,32
In vitro work from
Dr. Schlesinger’s laboratory suggested that cherry juice may
Two Types of Cherries
(1) Tart or sour cherries (Prunus cerasus)—The main variety
in the United States is Montmorency, but Morello
and Amarelle are two other common varieties.
These cherries are most likely native to Iran and
Eastern Europe.
(2) Sweet cherries (Prunus avium)—Major varieties are Bing
and Rainier in the United States, but there are many
others. These cherries are native to Europe and
western Asia.
MARY ANN LIEBERT, INC. VOL. 22 NO. 5 221
ALTERNATIVE AND COMPLEMENTARY THERAPIES OCTOBER 2016
work by inhibiting interleukin-1 production by white blood
cells in response to uric acid.
33
In most cases, these studies
were not presented in detail but only in abstracts, limiting the
ability to assess their methodological rigor.
A cross-sectional study of 633 American adults with gout
conducted via the internet found that self-reported intake of
cherries reduced the risk of a gout attack by 35% compared to
no intake, and intake of cherry extract conferred 45% reduction
in risk compared to no intake.
34
Respondents who reported
allopurinol use along with cherry intake had a 75% reduction in
gout attacks, compared to respondents not taking either. A
similar internet study of 293 American adult visitors to the
Gout and Uric Acid Education Society website found a cor-
relation between self-reported cherry use and lower numbers of
acute gout flares.
35
None of the research on cherry products for gout is suffi-
ciently rigorous to determine if these products are effective.
Given cherry’s incredible safety, however, most patients will
have little to lose other than money from trying it. This is
particularly indicated if other therapies are not working.
Coffee (Coffea arabica), from the Rubiaceae family, has been
studied extensively for coffee’s effects on gout. A meta-analysis
of eleven epidemiologic studies concluded that, despite having
no effect on serum uric-acid levels, coffee consumption reduced
the incidence of gout significantly in a dose-dependent manner.
36
A separate analysis of nine epidemiologic trials found that coffee
did lower serum uric acid, although it took substantially more to
do so in women than men (4–6 cups versus 1–3 cups, respec-
tively).
37
This analysis also found an inverse relationship be-
tween intake of coffee and incidence of gout. Caffeine does not
seem important to the antigout effects of coffee, as decaffeinated
coffee was as effective as caffeinated coffee in these studies. In
vitro, an aqueous extract of roasted coffee beans inhibited xan-
thine oxidase and crypto- and neochlorogenic lactones were
found to be largely responsible for this activity.
38
These com-
pounds are isomers of chlorogenic acid, an abundant lignan de-
rivative found in green coffee, formed principally during
roasting. More research is needed to determine coffee’s mecha-
nism of action, and randomized trials are also warrantedto assess
the clinical role of coffee fully in preventing and treating gout.
Chinese Herbal Formulas
A combination of herbs known as Chuanhu Anti-Gout
Mixture (CAGM) has been studied in at least two clinical trials
in patients suffering from podagra. The complete set of herbs in
this formula could not be identified, but Lonicera japonica
(Japanese honeysuckle, r
en d
ong te
´ng) stem, Polygonum cus-
pidatum5Fallopia japonica (Japanese knotweed, h
u zha
`ng)
root, whose Mandarin Chinese name translates literally as the
evocative “tiger sticks,” and Dioscorea nipponica (Japanese
yam, chu
an sh
an long) rhizome are three of the apparently nine
herbs included in CAGM.
In one double-blinded trial, 176 patients with acute gouty
arthritis were randomized to 250 mL daily of a liquid extract of
CAGM or 0.5 mg of colchicine b.i.d.
39
In each group, a placebo
of the alternative medicine was also given. All patients were
instructed to eat a low purine diet and to drink 2–3 L of water
daily, given 1 g sodium bicarbonate t.i.d. to alkalinize the ur-
ine, and treated with 60 mg of etoricoxib q.d. for acute pain.
After 12 weeks of treatment, recurrence of pain was no dif-
ferent between the groups. Acute joint pain was significantly
less in the CAGM group, compared to what occurred in the
colchicine group, while reduction of erythema and improve-
ment in function of the affected joint was the same between
these groups. Significantly more patients in the colchicine
group suffered adverse effects than the patients in the CAGM
group. Only 2 patients in the CAGM group dropped out of the
trial because of adverse effects (diarrhea, bitter taste), whereas
8 patients in the colchicine group dropped out (diarrhea, liver
damage). A similar clinical trial (reported in English only as an
abstract) with 144 patients resulted in the same conclusions.
40
E
`rMi
ao S
an (Two Marvel Powder), containing 9–12 g of
Phellodendron amurense (Amur corktree, hua
´ng b
ai) bark and
6–9 g of Atractylodes chinensis (black atractylodes, c
ang zhu
´)
prepared root, is a traditional formula used to treat gout in
Chinese medicine. This formula is often mixed with Zingiber
officinale (ginger) juice while it is being prepared. It was first
documented in Da
`nXı
¯Xı
¯nF
a(Essential Teaching of Zhu
Danxi) written by Zh
uD
an-Xı
¯in 1481.* The formula was
traditionally prepared as a decoction (and would be then called
E
`rMi
ao Wa
´n, Two Marvel Decoction), with the amounts cited
above being divided into 3 doses per day in water.
In a mouse model of gout, Two Marvel Decoction was as
effective as allopurinol for lowering serum uric acid.
41
The
formula and Amur corktree alone inhibited xanthine oxidase,
albeit not as potently as allopurinol, while black atractylodes
had no such effect. This suggests that this herb has other
effects—in addition to inhibiting xanthine oxidase—that
contribute synergistically to a superior clinical effect. Two
Marvel Powder, but not its ingredients in isolation, inhibited a
range of inflammatory pathways relevant to gout in vitro.
42
A
study in vitro found that the alkaloids berberine and palmatine
and the glycoside obaculactone accounted for much of the
xanthine oxidase-inhibiting effects of Amur corktree.
43
A combination of Two Marvel Powder and Sı
`Wu
`T
ang (Four
Substances for Women) formula, containing Rehmannia gluti-
nosa (Chinese foxglove, shu
´dı
`hua
´ng)preparedroot,Paeonia
lactiflora (white peony, ba
´isha
´o) root without bark, Angelica
sinensis (dong quai, d
ang guı¯ ) prepared root, and Ligusticum
striatum (Chinese osha, chu
an xi
ong) root, were studied in mice
with induced gout.
44
The two formulas combined were superior
to Four Substances for Women by itself for lowering serum uric
acid and improving kidney function. The combination of the two
formulae also seemed particularly effective for upregulating
organic ion transporters 1 and 3 in the kidney, both of which are
crucial in excretion of uric acid.
*An English translation is available: Yang Shouzhong (translator),
The Heart and Essence of Danxi’s Methods of Treatment, 1993 Blue
Poppy Press, Boulder, CO.
222 MARY ANN LIEBERT, INC. VOL. 22 NO. 5
ALTERNATIVE AND COMPLEMENTARY THERAPIES OCTOBER 2016
Two clinical studies that were published in Chinese used
formulas that contained part or all of Two Marvel Powder.
Details were not available, and these reports were presented
only as parts of a systematic review of Chinese herbal formulas
for gout.
45
One study compared Two Marvel Powder with
several additional herbs to colchicine and allopurinol in 216
patients with gout for 30 days and found both approaches
equally effective for treating acute attacks. The other study
looked at Two Marvel Powder with yet a different set of ad-
ditional herbs in 76 adults with gout, compared to colchicine,
allopurinol, and indomethacin, this time taken for 7–21 days.
Again, these approaches were similarly effective for resolving
acute attacks, but, overall, both treatment groups had far lower
efficacy than reported in the other trial. This provides some
preliminary evidence that Two Marvel Powder and various
combinations with it are clinically effective. More rigorous
trials are warranted. The meta-analysis cited found a total of
17 trials of herbal formulas for gout, and concluded that they
are similar in efficacy to antigout drugs but with far fewer
adverse effects. The extreme variability between these herbal
formulas and study methodologies calls the validity of such a
meta-analysis into question, but it appears that there is pre-
liminary support for Chinese herbs for treating patients who
have gout.
Table 1. Selected Preclinical Reports of Antigout Herbs
Herb & part used Native range Extract & effect Reference(s)
Rhododendron oldhamii (Oldham’s
azalea, zhuan hong du juan) leaf
Taiwan Ethanol extract reduced serum uric acid
in hyperuricemic mice.
Tung, 2015
b
Phyla nodiflora5Lippia nodiflora
(frogfruit) whole plant
Southern United
States & northern Mexico
Methanol extract inhibited xanthine
oxidase in vitro.
Cheng, 2015
c
Smilax riparia (niu wei cai) root China Crude extract reduced serum uric acid
in hyperuricemic mice (synergistic with
allopurinol); inhibits xanthine oxidase;
saponins downregulated URAT1, thus
increasing uric acid excretion
& upregulated OAT1
Wu, 2014
d
Wu, 2015
e
Panax japonicus
a
(Japanese
ginseng) root
Japan Various ginsenosides inhibited xanthine
oxidase in vitro.
Li, 2015
f
Gnaphalium affine (Jersey
cudweed, shu qu cao) aerial parts
East & South Asia Ethanol extract & flavonoids (especially
eupatilin) inhibited xanthine oxidase in vitro.
Lin, 2014
g
Rubia alata5R. lanceolata
(kim kiam chhau)
East & Southeast Asia Methanol extract of root inhibited xanthine
oxidase in vitro & reduced serum uric acid
in mice.
Liu, 2014
h
Chrysanthemum morifolium
(chrysanthemum, ji hua) flower
Asia Flavonoids from flower inhibited xanthine
oxidase in vitro.
Song, 2014
i
Dioscorea collettii var hypoglauca
(tokoro, bi xie) rhizome &
D. Septemloba (seven-lobed yam)
rhizome
Asia Total saponins reduced serum uric acid
while increasing urine levels in rats, with
associated URAT1 downregulation;
also upregulated OAT1.
Chen, 2013
j
Chen, 2016
k
Trikatu, a formula with equal parts
Zingiber officinale (ginger), Piper
longum (long pepper)
&P. nigrum (black pepper)
India Reduced inflammation, pain, & fever caused
by gout in rats.
Murunikkara,
2014
l
a
Misidentified as Panax japlcus in the article, but no such species exists and this is fairly clearly a typographical error.
b
Tung YT, Lin LC, Liu YL, et al. Antioxidative phytochemicals from Rhododendron oldhamii Maxim. leaf extracts reduce serum uric acid levels in potassium oxonate-induced
hyperuricemic mice. BMC Complement Altern Med 2015;15:423;
c
Cheng LC, Murugaiyah V, Chan KL. In vitro xanthine oxidase inhibitory studies of Lippia nodiflora and isolated
flavonoids and phenylethanoid glycosides as potential uric acid-lowering agents. Nat Prod Commun 2015;10:945–948;
d
Wu XH, Yu CH, Zhang CF, et al. Smilax riparia reduces
hyperuricemia in mice as a potential treatment of gout. Am J Chin Med 2014;42:257–259;
e
Wu XH, Wang CZ, Wang SQ, et al. Anti-hyperuricemia effects of allopurinol are
improved by Smilax riparia, a traditional Chinese herbal medicine. J Ethnopharmacol 2015;162 :362–368;
f
Li S, Tang Y, Liu C, et al. Development of a method to screen and isolate
potential xanthine oxidase inhibitors from Panax japlcus [sic] var via ultrafiltration liquid chromatography combined with counter-current chromatography. Talanta 2015;134:665–
673;
g
Lin WQ, Xie JX, Wu XM, et al. Inhibition of xanthine oxidase activity by gnaphalium affine extract. Chin Med Sci J 2014;29:225–230;
h
Liu LM, Cheng SF, Shieh PC, et al. The
methanol extract of Euonymus laxiflorus,Rubia lanceolata and Gardenia jasminoides inhibits xanthine oxidase and reduce serum uric acid level in rats. Food Chem Toxicol
2014;70:179–184;
i
Song HP, Zhang H, Fu Y, et al. Screening for selective inhibitors of xanthine oxidase from Flos Chrysanthemum using ultrafiltration LC-MS combined with
enzyme channel blocking. J Chromatogr B Analyt Technol Biomed Life Sci 2014;961:56–61;
j
Chen GL, Zhu LR, Na S, Li L. Effect of total saponin of Dioscorea on chronic
hyperuricemia and expression of URAT1 in rats [in Chinese]. Zhongguo Zhong Yao Za Zhi 2013;38:2348–2353;
k
Chen Y, Chen XL, Xiang T, et al. Total saponins from Dioscorea
septemloba Thunb. reduce serum uric acid levels in rats with hyperuricemia through OATP1A1 up-regulation. J Huazhong Univ Sci Technolog Med Sci 2016;36:237–242;
l
Murunikkara V, Rasool M. Trikatu, a herbal compound that suppresses monosodium urate crystal-induced inflammation in rats, an experimental model for acute gouty arthritis.
Cell Biochem Funct 2014;32:106–114.
OAT, organic anion transporter; URAT, urate transporter.
MARY ANN LIEBERT, INC. VOL. 22 NO. 5 223
ALTERNATIVE AND COMPLEMENTARY THERAPIES OCTOBER 2016
Sı
`Mia
`oWa
´n(Four Marvels Teapills) is a variant of Two
Marvel Powder first documented in 1904 in the book Che
´ng
F
ang Bia
`nDu
´(Convenient Reader of Established Formulas)
by Zh
ang B
ıng-Che´ ng. Four Marvels Teapills contain Two
Marvel Powder plus Achyranthes bidentata (ox knee, niu
´xı¯)
root and Coix lachryma-jobi var ma-yuen (Job’s tears, yı
`y
ıre
´n)
seed. In this formula, all the ingredients are generally com-
bined in equal amounts and the dose is 6–9 g t.i.d. The formula
can also be prepared as a decoction. In a clinical trial (blinding
not described), 207 patients with gout having acute attacks
were randomized to one of three versions of Four Marvels
Teapills or indomethacin with benzbromarone, a xanthine
oxidase–inhibiting drug little used in the U.S.
46
Symptomatic
improvement was significantly greater in all the herbal formula
groups, compared to the drug controls. All groups had signif-
icant declines in serum uric acid, compared to baseline; no
group was superior to another in efficacy with respect to this
parameter. This lends further evidence to the efficacy of Two
Marvel Powder and the additional herbs included here.
Conclusion
Many herbal medicines and medicinal foods appear to be
helpful or potentially helpful for patients with gout, both to
prevent and treat attacks. Several of the most promising have
been reviewed in this article. Other herbs showing promise in
preclinical research are outlined in Table 1. Clearly, much
more work needs to be done to fully develop herbs for gout, but
the groundwork is in place.
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Eric Yarnell, ND, RH (AHG), is chief medical officer of Northwest Nat-
uropathic Urology, in Seattle, Washington, and is a faculty member at Bastyr
University in Kenmore, Washington.
To order reprints of this article, contact the publisher at (914) 740-2100.
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