General Features
Natives of the South Pacific have used a nonalcoholic drink made from Kava root as a ceremonial and social drink for
centuries. Kava was valued for its mellowing effects and to encourage socializing by these native groups. It has been
cultivated over the years for such purposes by Pacific Islanders as first reported by Captain James Cook on his historic
voyages through the South Seas. The Kava beverage first causes a numbing and astringent effect in the mouth,
followed by a relaxed sociable state where fatigue and anxiety are lessened. Eventually a deep restful sleep ensues
from which one is said to awaken the next morning refreshed and without symptoms of a hangover. Excess intake can
produce a stupor and dizziness, a condition described as Kava abuse. 26
In 1966, European scientists interested in Kava’s sedative and intoxicant effects isolated its kavalactone constituents,
which have been found to produce sedative, pain-killing, and anticonvulsant properties. Kava is a member of the
pepper family and its rootstock or rhizome (underground stem) is used for medicinal purposes. Its most well defined
application is in regards to its ability to reduce feelings of anxiety and as a natural sedative. 1, 9,10, 11
Principle Active Constituents
Kava-lactones, also known as Kava-pyrones – these consist of fat soluble resins such as dihydrokavain, which have
been found to produce sedative, painkilling and anticonvulsant effects. Other Kava-lactones include kavain,
methysticin, and dihydromethysticin. 1, 9, 12,13,14.
Clinical Application and Mechanism of Action
1. Anxiety
Kava-lactones have been shown to have natural sedative properties by influencing GABA (gamma amino benzoic
acid) receptors, in a similar fashion as does benzodiazepines (e.g, valium), but appears to modulate the limbic
system emotional processes rather than affect parts of the brain affected by benzodiazepines. 15, 16The limbic
system is the primitive part of the brain that controls our emotions and survival instincts. 10
At least six, well-designed, clinical studies have provided evidence that Kava extract can be an effective
intervention in the management of anxiety, from non organic causes (e.g., not appropriate for anxiety secondary to
hyperthyroidism). These studies have tested Kava extract against placebo, against hormone replacement therapy
in the treatment of anxiety associated with menopausal symptoms, and against common drugs used to treat
anxiety, such as oxazepam, bromazepam, and other standard benzodiazepines. In one of the smaller trials,
involving 52 anxiety patients, 81% of the subjects treated with Kava extract rated the treatment as very good or
good. In the study of menopausal women, the Kava group reported better overall relief from anxiety than did the
groups given hormone replacement therapy or placebo. When tested head-to-head against anti-anxiety drugs from
the class of benzodiazepines, the Kava group reported the same level of improvement as provided by these proven
medications. In total, these studies have followed more than 400 patients and suggest that Kava is an effective
intervention for the treatment of anxiety from non-organic causes. However, Kava’s anti-anxiety effects may not
manifest themselves until the eight week of continuous supplementation, although some studies indicate a benefit
along these lines within the first week of treatment. The German Commission E states that Kava is useful for
relieving “states of nervous anxiety, tension, and agitation”. 17,18,19,20,21,22,23,24,11
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Of special note is the fact that unlike benzodiazepines, Kava does not seem to impair reaction time or alertness
when taken in divided doses throughout the day for the treatment of anxiety, at recommended intake levels.
2. Insomnia
Kava is known to have sedative effects at specific levels of intake, which have prompted its use as a natural
treatment for insomnia. This effect is also considered to be mediated through its influence of the limbic system. 10
In one placebo-controlled study of 12 healthy volunteers Kava extract was shown to improve the ability to fall
asleep at a dose of 300 mg per day (yielding 210 mg of Kava-lactone content). It also lengthened the deep sleep
phase and shortened the wakeful phases in sleep, according to EEG recordings (electro-encephalogram). These
effects are looked upon favorably compared to effects on sleep induced by benzodiazepines and barbituate drugs.
Kava administration also increased the density of sleep spindles, an effect, which is comparable to medical
sedative drugs. 26
Dosage and Standardized Grade
Kava extract should be standardized to contain a set percentage of Kava-lactone content. High-yielding products
contain 70% Kava-lactone content as a rule
1. Anxiety (mild to moderate cases) – 45-70 mg Kava-lactones, three times daily. Up to 240 mg per day of
Kava-lactone intake has been used for this purpose. The total daily dose should not exceed 300 mg. 9,10,11,26
2. Insomnia – 180—210 mgs of Kava-lactones one hour before bed time.1,2,3
According to the German Commission E monograph Kava should not be taken for more than three months without
the advice of a physician. 27
Adverse Side Effects, Toxicity and Contraindications
Liver Damage: Over the years there has been some suggestion that Kava use may induce liver damage in long-term
users, as evidenced by the yellowing of the skin that occurs in some Kava users. 28 However, this was considered to
be a skin reaction by many authorities and concern about liver injury was not strongly considered. As such, Kava was
generally regarded as a safe supplement until recently. 27 However, in November 2001, German authorities reported
24 cases of liver damage associated with the use of Kava in Germany. Liver problems included hepatitis, liver failure,
and cirrhosis. Of these, one person died and three required a liver transplant. 29 The 1998 edition of the German
Commission E Monographs does not mention liver disease in its discussion of Kava’s side effects. 27 Since that
publication date, four case reports of Kava-induced liver toxicity have appeared in medical journals. In two of these
cases, severe liver failure resulted in the need for a liver transplant. 30,31,32,33 Of interest is the fact that in most, but
not all of these cases, patients were taking other medications, which are known to cause liver damage as an
established side effect. This may imply that Kava potentiated the liver-damaging effects of these drugs in these cases
and that the use of Kava in the absence of such medications may not pose the same degree of risk of liver injury. 34
However, some of the cases of Kava-related liver disease cannot be explained by the concomitant use of other drugs.
9
Other investigations have implicated Kava as an agent that can produce liver injury. A survey of the aboriginal
community in Australia revealed that heavy Kava users were at higher risk of developing liver damage, as
evidenced by laboratory studies, than were non- users and occasional users of Kava. Risk of liver injury was
directly related to the amount of Kava consumed. 35
In Germany, Canada and the United States, governments are have considered banning the use of Kava, due to
reports from Europe indicating that taking Kava at recommended intake levels can induce severe liver injury, even
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in occasional users. At this time, Kava is still available without a prescription in many parts of the world, but experts
suggest that individuals seek appropriate monitoring of liver enzymes by their physician if they intend to use this
herbal agent on any level of frequency. Anyone with pre-existing liver disease or taking other drugs known to
cause liver damage, or consuming alcohol on a regular basis, should avoid the use of Kava altogether. 11
On December, 18, 2001 the Food and Drug Administration (FDA) in the United States informed health care
practitioners that it was launching an investigation to determine if Kava supplementation poses a health threat to
human health. The agency noted that German and Swiss health authorities had reported approximately 25 cases
of serious liver toxicity, related to Kava consumption. This initial communication was to serve as a data-gathering
tool and was not issued as a warning or alert. “ Although there are currently no published reports of liver toxicity in
the U.S., the FDA has indicated that it has received adverse event reports through its MEDWATCH system that
potentially links Kava to liver damage.” 41
Other Side Effects: Long-term use (few months to a year) can produce Kava dermopathy (scali skin eruptions) on
the palms, soles, forearms, back and shins. High doses (7310 gms per week) may decrease serum albumin,
protein, urea, bilirubin, platelet count and lymphocyte count.1,2,3,4 Kava may temporarily turn skin yellow, create mild
gastrointestinal disturbances, induce an allergic skin reaction, such as a rash and/or produce pupil enlargement in
long-term users. 28,36,37 Short-term Kava studies (4 –7 weeks) at usual intake doses have not shown any
significant side effects other than the occasional report of gastrointestinal upset or skin rash. 38
Acute Dystonic Reactions: Kava should not be use by individuals who have had acute dystonic reactions, which
consist of spasms in the muscles of the neck and movements of the eyes. These problems are related to the
neurotransmitter dopamine, according to popular beliefs, and are typically caused by antipsychotic drugs, which
affect dopamine. Kava may trigger these reactions in patients with a known history of dystonic reactions. 40
Drug-Nutrient Interactions
Kava supplementation is reported to potentiate the effects of the following medications leading to excess sedation and
thus, should not be taken concurrently:
Sedative medications ( benzodiazepines)42, 43
Alprazolam – a reported case possibly lead to coma in a patient combining Kava with this drug. 44
Antidepressant drugs 42
Diphenydramine – an over-the-counter drug that induces sedation 41,42
Alcohol – some reports suggest that Kava can increase alcohol’s damaging effects to the heart, nervous system, liver,
immune system, kidneys and other organs. It is advisable not to combine Kava intake with the consumption of alcohol.
48,49,50
Antipsychotic drugs – Kava may increase risk of dystonic reactions if combined with these drugs. 11
Levodopa – patients with Parkinson’s disease taking levodopa should avoid Kava as Kava’s effects on the dopamine
system may reduce the effectiveness of levodopa. 11
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Pregnancy and Lactation
During pregnancy and lactation, the only supplements that are considered safe include standard prenatal
vitamin and mineral supplements. All other supplements or dose alterations may pose a threat to the
developing fetus and there is generally insufficient evidence at this time to determine an absolute level of
safety for most dietary supplements other than a prenatal supplement. Any supplementation practices
beyond a prenatal supplement should involve the cooperation of the attending physician (e.g., magnesium
and the treatment of preeclampsia.)
References: Pregnancy and Lactation
1. Encyclopedia of Nutritional Supplements. Murray M. Prima Publishing 1998.
2. Reavley NM. The New Encyclopedia of Vitamins, Minerals, Supplements, and Herbs. Evans and
Company Inc. 1998.
3. The Healing Power of Herbs (2nd edition). Murray M. Prima Publishing 1995.
4. Boon H and Smith M. Health Care Professional Training Program in Complementary Medicine.
Institute of Applied Complementary Medicine Inc. 1997.
1. Singh Y, Kava: An Overview, J Ethnopharmacol 37, 1992, 13-45.
2. Holm E, et.al., Studies on the Profile of the Neurophysiological Effects of D.L.-kavain: Cerebral Sites of Action and Sleep-Wakefulness-
Rhythm in Animals, Arzneimittel-Forsch 41, 1991, 673-683.
3. Lindenberg D and Pitule-Schodel H, D, L-kavain in Comparison with Oxazepam in Anxiety Disorders. A Double-blind Study of Clinical
Effectiveness, Forschr Med 108, 1990, 49-50, 53-54.
4. Kinzler E, Kromer J, and Lehmann E, Clinical Efficacy of a Kava Extract in Patients with Anxiety Syndrome: Double-blind Placebo
Controlled Study Over 4 Weeks, Arzneimittel-Forsch 41, 1991, 584-588.
5. Warnecke G, Neurovegetative Dystonia in the Female Climacteric. Studies on the Clinical Efficacy and Tolerance of Kava Extract WS
1490, Forschr Med 109, 1991, 120-122.
6. Norton SA and Ruze P, Kava Dermopathy, J Am Acac Dermatol 31, 1994, 89-97.
7. Ruze P, Kava-induced Dermopathy: A Niacin Deficiency, Lancet 336, 1990, 1442-1445.
8. Mathews JD, et.al., Effects of the Heavy Usage of Kava on Physical Health: Summary of a Pilot Survey in an Aboricinal Community, Med
J Aust 148, 1988, 548-555.
9. Healthnotes, Inc. 2001. www.healthnotes.com: Kava
10. Dietary Supplement Information Bureau. www.content.intramedicine.com: Kava
11. Natural Product Encyclopedia. www.consumerslab.com: Kava
12. Meyer HJ, Kretzschmar R. Kawa pyrone—a new kind of substance group of central muscle relaxants of the mephenesin type [translated
from German]. Klin Wochenschr 1966;44:902-3
13. Klohs MW, keller F, Williams RE et al. A chemical and pharmacological investigation of Piper methysticum Forst. J Med Pharm Chem
1959;1:95-103
14. Bruggemann VF, Meyer HJ. Studies on the analagesic efficacy of the kava constituents dihydrokavain (DHK) and dihydromethysticin
(DHM) [in German; English abstract]. Arzneimittelforschung 1963;13:407-9
15. Jussofie A, Schmiz A, Hiemke C. Kavapyrone enriched extract from Piper methysticum as modulator of the GABA binding site in different
regions of rat brain. Psychopharmacology (Berl) 1994;116:469-74
16. Boonen G, Haberlein H. Influence of genuine kavapyrone enantiomers on the GABAA binding site. Planta Med 1998;64:504-6
17. Volz HP, Kieser M. Kava-kava extract WS 1490 versus placebo in anxiety disorders—a randomized placebo-controlled 25-week
outpatient trial. Pharmacopsychiatry 1997;30:1-5
18. Kinsler E, Kromer J, Lehmann E. Effect of a special kava extract in patientw with anxiety-,tension-, and excitation states of non-psychotic
genesis. Double blind study with placebos over 4 weeks [translated from German]. Arzneimittelforschung 1991;41:584-8
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19. Warnecke G, Pfaender H, Gerster G et al. Efficacy of an extract of kava root in patients with climacteric syndrome. A double blind study
with a new mono-preparation [translated from German]. Z Phytother 1990;11:81-6
20. Warnecke G. Psychosomatic disorders in the female climacterium, clinical efficacy and tolerance of kava extract WS 1490 [translated
from German]. Fortschr Med 1991;109:119-22
21. Malsch U, Klement S. Randomized placebo-controlled double-blind clinical trial of a special extract of kava roots (WS 1490) in patients
with anxiety disorders of non-psychotic origin [abstract]. Eur Phytojournal [serial online]. 2000;1. Available
at:http://www.escop.com/issue_1. Accessed May 10, 2001
22. Woelk H, Kapoula O, Lehri S et Al. The treatment of patients with anxiety. A double blind study: dava extract WS 1490 versus
benzodiazepine [translated from German]. Z Allg Med 1993;69:271-7
23. Cropley M, Cave Z. Effect of kava and valerian on physiological responses to psychological stress assessed under laboratory conditions
[abstract]. FACT 2001;6:76
24. De Leo V, la Marca A, Morgante G et al. Evaluation of combining kava extract with hormone replacement therapy in the treatment of
postmenopausal anxiety. Maturitas 2001;39:185-8
25. Munte TF, Heinze HJ, Matzke M, Steitz J. Effects of oxazepam and an extract of kava roots (Piper methysticum) on event-related
potentials in a word-recognicition task. Pharmacoelctroencephalog 1993;27:46-53
26. Principles and Practice of Phytotherapy. Mills S and Bone K. Churchill Livingstone. 2000: 456-58
27. Blumenthal M, Busse WR, Goldberg A et al. (eds.) The Complete Commission E Monographs: Therapeutic Guide to Herbal Medicines.
Boston MA: Integrative Medicine Communications 1998:156-7
28. Jappe U, Franke I, Reinhold D, Golinick HPM. Sebotropic drug reaction resulting from kava-kava extract therapy: A new entity? J Amer
Acad Dermatol 1998:38:104-6
29. Stafford, Ned. Germany may ban kava kava herbal supplement. Reuters Nov.19 2001
30. Escher M, Desmeules J, Giostra E, Mentha G. Hepatitis associated with kava, a herbal remedy for anxiety. BMJ 2001;322:p139
31. Kraft M, Spahn TW, Menzel J et al. [Fulminant liver failure after administration of the herbal antidepressant Kava-Kava.] Dtsch Med
Wochenschr 2001;126:970-2 [in German].
32. Strahl S, Ehret V, Dahm HH, Maier KP. [Necrotizing hepatitis after taking herbal remedies.] Dtsch Med Wochenschr 1998;123:1410-4 [in
German]
33. Russmann S, Lauterburg BH, Helbling A. Kava hepatotoxicity. Ann Intern Med 2001;135:68-9 [letter]
34. Information provided by the German Federal Institute for Drugs and Medical Devices.
35. Mathews JD, Riley MD, Fejo L et al. Effects of the heavy usage of kava on physical health: summary of a pilot survey in an aboriginal
community. Med J Aust 1988;148:548-55
36. Schmidt P, Boehncke WH. Delayed-type hypersensitivity reaction to kava-kava extract. Contact Derm 2000;42:363-4
37. Blumenthal M, Busse WR, Goldberg A et al (eds.) The Complete Commission E Monographs: Therapeutic Guide to Herbal Medicines.
Boston MA: Integrative Medicine Communications 1998:156-7
38. Schulz V, Hansel R, Tyler VE. Rational Phytotherapy: A Physician’ Guide to Herbal Medicine. 3rd ed. Berlin, Germany: Springer-
Verlag;1998:p71
39. Schelosky L, Raffauf C, Jendroska K et al. Kava and dopamine antoginism [letter]. J Neurol Neurosurg Psychiatry 1995;58:639-40
40. National Nutritional Foods Association Update. December 21, 2001. Kava safety concerns raised.
41. Jussofie A et al. Kavapyrone enriched extract from piper methysticum as modulator of the GABA binding site in different regions of rat
brain. Psychopharmacology (Berl). Dec 1994;116(4):469-74
42. Klohs MW. Chemistry of Kava. Psychopharmacol Bull 1967;4(3):p10
43. Almeida JC et al. Coma from the health food store: Interaction between Kava and Alprazolam. Ann Intern Med Dec1996;125(11):940-1
44. Jamieson DD et al. Positive interaction of ethanol and kava resin in mice. Clin Exp Pharmacol Physiol Jul1990;17(7):509-14
45. Cantor C. Kava and alcohol. Med J Aust Nov1997;167(10):p560
46. Herberg KW. Effect of Kava-special extract WS 1490 combined with ethyl alcohol on safety-relevant performance parameters. Blutalkohol
Mar1993;30(2):96-105
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Licorice (Glycyrrhiza Glabra)
General Features
Licorice is a perennial shrub, whose roots and underground horizontal stems called rhizomes are used medicinally. 1
Licorice originated in the Mediterranean and Middle East, where it has been used as flavoring agent since at least 500
B.C. 22 Most of the Licorice candy available in North America today contains no Licorice, but rather is flavored with
anise oil. 21 When taken in high enough amounts (two to three weeks, at a dose of 1,000 mg of glycyrrhizin content)
the glycyrrhizin constituent of Licorice produces effects similar to those of the hormone aldosterone, causing fluid
retention, increased blood pressure, and loss of potassium. 23, 24 Thus, the long-term use of Licorice products
containing glycyrrhizin can result in serious side effects and requires appropriate monitoring by a health professional.
Some Licorice products used for the treatment of stomach ulcers and canker sores have the glychrrhizin removed and
are referred to as de-glycrrhizinated Licorice (DGL). These products are not associated with the same adverse side
effects noted for whole Licorice products or Licorice extracts containing glycrrhizin. 23 As Licorice is known to produce
anti-inflammatory effects, contains phytoestrogens, regulates adrenal hormones, stimulates antibody production,
stimulates mucous production in the esophagus, and provides antioxidant protection to liver cells, this herb has been
used therapeutically for a vast number of health conditions over the years by alternative practitioners.22, 1 However,
the risk of serious side effects from the use of Licorice makes this herbal supplement (with the exception of DGL) a
less desirable natural intervention for many conditions than the use of other herbal agents that are known to provide
similar health benefits, without risk of serious adverse reactions. 22,23,24
Principle Active Constituents
1. Terpenoids: these include glycyrrhizin (also called glycyrrhizinic or glycrrhizic acid), which yields glycrrhetinic acid
(also called Glycyrrhetic or glycrretic acid), as well as other terponoids. Terpenoids are steroid-like compounds that
can affect steroid function in the body and, may also account for some of Licorice’s phytoestrogen effects on certain
tissues.1
2. Flavonoids and Isoflavonoids: these provide the antioxidant properties and some of the phytoestrogen properties of
Licorice products. The flavonoids found in Licorice also participate in the healing of peptic ulcers, a proven
application for DGL.1
3. Coumarins: the presence of these constituents, increase the chance of developing photo-sensitivity–induced
dermatitis, and possibly bleeding disorders (internal bleeding), due to their effects on inhibiting platelet
aggregation.1,22
Clinical Application and Mechanism of Action
1. Premenstrual Syndrome (PMS)
Licorice contains phytoestrogens (isoflavones and glycyrrhetinic acid), which have the ability to influence estrogen
metabolism. Phytoestrogens generally have 1/20 and 1/100 the potency of the body’s estrogen.1,2 PMS symptoms
have been associated with an increased estrogen to progesterone ratio.1 Licorice supplementation has been
shown to improve symptoms of PMS, likely through its effects on toning down the influence of endogenous
(produced in the body) estrogens, on breast, uterine and other tissues. 1,2,3 However, other herbal agents such as
Black Cohosh and Chasteberry extract are also effective agents in the management of PMS and do not impose the
same degree of adverse side effects associated with the use of Licorice. As such, they may be wiser choices for
the management of PMS (see Black Cohosh, Soy Isoflavones and Chasteberry in this document)
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2. Anti-inflamma