K
KAYA
| Other Common Name: | Kava kava |
| Botanical Name: | Piper methysticum |
| Family: | Piperaceae |
| Plant Part Used: | Root (rootstock) |
PRESCRIBING INFORMATION
| Actions | Anxiolytic, hypnotic, anticonvulsant, mild sedative, skeletal muscle relaxant, spasmolytic, local anesthetic, mild analgesic, antipruritic (topically) | |
| Potential Indications | ||
Two postmarketing surveillance studies involving 3029 and 4049 patients found adverse events occurred in 2.3% and 1.5%, respectively, of patients during treatment with standardized kava extract. The doses of kava contained 120 to 240 mg and 105 mg of lactones, respectively. A meta-analysis noted that standardized kava extract is relatively safe with two studies, representing 31% of the studied patients, not reporting any adverse events in those treated with kava.1
A dry, scaly, pigmented skin condition known as kava dermopathy is a well-known side effect of excessive and chronic use of kava but is unlikely to occur after normal therapeutic use. The rash quickly regresses if kava intake is ceased. Dermatitis after oral administration of kava at the lower therapeutic doses has been reported.
A group of German neurologists described four cases of patients who developed clinical signs suggestive of dopamine antagonism after taking kava. Overdose of kava (without concurrent alcohol use or petrol sniffing) causing generalized choreoathetosis (involuntary movement disorder) has been reported in an Aboriginal Australian.2
Associations with heavy kava use reported in the Australian medical literature from 1988 to 1999 include ischemic cardiac events and sudden cardiac death.2,3 These events have not been definitively linked to excessive kava use and the possibility of concurrent alcohol abuse, and the involvement of other socioeconomic factors cannot be ruled out.
A pilot survey investigating the effects of heavy kava use published in 1988 indicated that no epidemiological evidence was found to link sudden deaths with kava use.4
A report published in 2000 by a Swiss government regulatory agency described nine cases of hepatotoxicity attributed to kava.
All cases involved the consumption of a high dose acetone extract standardized to 70% kava lactones. The product has been subsequently banned. The author rated the risk of hepatotoxicity as rare but serious.5 German regulatory authorities reported cases of hepatotoxicity involving ethanolic kava extracts,6 and kava products were subsequently removed from the market in this and several other countries. Good evidence exists that the hepatotoxicity was immunemediated. A deficiency of the drug-metabolizing enzyme CYP2D6 (which occurs in 9% of the population) might be a predisposing factor.7
* Kava has also been used in traditional herbal medicine for treating insomnia. (6)
** This dose range is extrapolated from British Pharmaceutical Codex 1934, the British Herbal Pharmacopoeia 1983, and the author’s education and experience.
SUPPORTING INFORMATION
• A meta-analysis assessing seven randomized, double-blind, placebocontrolled trials found that kava extract significantly reduced anxiety (compared with placebo). The dosage of standardized kava extract prescribed varied and contained 60 to 240 mg per day of kava lactones. The duration of treatment ranged from 1 to 24 weeks. One trial investigated the reduction in anxiety for preoperative patients who received kava extract the night before and 1 hour before surgery.1 The authors of one of the trials14 included in this meta-analysis concluded that the efficacy and tolerability of standardized kava extract recommend it as an alternative to tricyclic antidepressants and benzodiazepines for treating anxiety.
• Kava lactones and standardized kava extracts demonstrated activity equivalent to oxazepam and bromazepam (benzodiazepine drugs) in patients with anxiety in double-blind, placebo-controlled trials. The daily dose ranged from 210 to 400 mg of kava lactones. Side effects were higher in the patient groups assigned the conventional drugs.
• Kava has also been shown to have therapeutic benefit in cases of situational anxiety. In a randomized, double-blind, placebo-controlled trial, standardized kava extract taken for 1 week significantly reduced anxiety compared with placebo in patients awaiting the results of medical diagnostic tests for suspected breast carcinoma. Fatigue, introverted behavior, excitability, and depression were decreased, and alertness was increased in patients receiving kava extract. The administered daily dose of kava contained 150 mg of kava lactones and corresponded to approximately 2.5 g of dried root.15
• Preliminary findings suggest a beneficial effect of kava on baroreflex control of heart rate (BRC). Significantly more patients with generalized anxiety disorder exhibited improved BRC following treatment with kava compared with a placebo. No effect was observed on respiratory sinus arrhythmia, a measure of the heart rate changes occurring with respiration. Patients in the study were a subgroup of a larger randomized, double-blind trial and received standardized kava extract or placebo for 4 weeks.16
• Two postmarketing surveillance studies involving over 3000 patients each found standardized kava extract improved nervousness, restlessness, anger, sleep disturbances, menopausal complaints, muscle tension, and sexual disturbances. Undesirable side effects included allergic reactions, gastrointestinal complaints, headache, and dizziness. The daily dose of extract ranged from that containing 105 mg to 240 mg of kava lactones for 4 and 7 weeks, respectively.
• In a placebo-controlled trial, standardized kava extract (containing 105 to 210 mg kava lactones for 1 day) improved several aspects of the sleep cycle. The measurements were favorable when compared with orthodox sedatives such as benzodiazepines and barbiturates.
• In a pilot study, patients with stress-induced insomnia were treated in each phase for 6 weeks with kava, then valerian, then a combination of kava and valerian, with washout periods between each treatment phase of 2 weeks. Total stress severity was significantly relieved by the kava and valerian single treatments (stress was measured in three areas:social, personal, and life events). Insomnia was significantly relieved by the combination of kava and valerian.17
• A randomized, placebo-controlled, double-blind trial of patients with neurovegetative symptoms associated with menopause found standardized kava extract for 8 weeks (containing 210 mg/day of kava lactones) produced a significant reduction in anxiety (symptoms and severity of symptoms), depression, and menopausal symptoms. (This trial was included in the previously mentioned meta-analysis.)
• Kava plus HRT significantly reduced menopausal anxiety compared with HRT alone in a controlled trial.18
• In a single-blind, placebo-controlled study with healthy volunteers, kava improved cognitive performance and stabilized emotional disposition without causing sedation. The study was conducted over 5 weeks and included washout, placebo, kava, and rebound placebo phases. Volunteers were administered a daily dose of standardized extract containing 210 mg of kava lactones, increasing to 420 mg over a 2-week period.
• Despite its relaxing properties, a single dose of standardized kava extract (containing 120 mg of kava lactones) was shown to increase performance in mental alertness tests compared with diazepam (10 mg) and placebo in a randomized, double-blind, crossover, clinical study involving healthy volunteers. In other studies of similar design, conflicting results have been obtained. Standardized kava extract (containing 420 mg/day of kava lactones) for 5 days did not significantly change the quality and speed of responses to psychometric tests, whereas oxazepam (3 days of placebo, 15 mg on the day before testing and 75 mg on the morning of testing) significantly decreased responses. However, standardized kava extract had a positive effect on the allocation of attention and processing capacity, compared with a reduced response produced by oxazepam in healthy volunteers.
• A double-blind study involving healthy volunteers concluded that patients are not exposed to additional side effects or risks (in terms of mental performance and general well being) while taking kava extract (containing 240 mg/day of kava lactones) plus a benzodiazepine, as compared with taking the benzodiazepine alone (9 mg/day bromazepam).
• In a placebo-controlled, double-blind study, no negative effects on safety-relevant performance were caused by combining standardized kava extract with ethanol. In fact, kava tended to counter the adverse effect of alcohol on mental concentration. No significant changes were found in performance capability (in terms of operating machines and driving) in the healthy volunteers studied. The daily dose of kava administered contained 210 mg of kava lactones and the trial was 8 days in length. In a more recent randomized, placebocontrolled trial, acute administration of a very high dose of kava combined with alcohol potentiated both the perceived and measured impairment of motor and cognitive function produced by alcohol alone. Kava was administered as the traditional aqueous extract (1 g/kg body weight);the dose of lactones was not defined.19
• Clinical trial results indicated that kava extracts and lactones are not suitable alone for treating epilepsy.
• An epidemiological study analyzing data obtained in the 1980s from the South Pacific region suggests a close inverse relationship between cancer incidence and kava consumption (the more kava is consumed by the population, the lower the cancer incidence will be). The results imply that kava may be an effective cancer chemoprotective agent, but no other conclusions can be made until further research is completed. Kava consumption is unlikely to be solely responsible for the low cancer rate in these islands.20
Except when specifically referenced, the following book was referred to in the compilation of the pharmacologic and clinical informationMills S, Bone K. Principles and Practice of Phytotherapy: Modern Herbal Medicine. Edinburgh: Churchill Livingstone, 2000.
1 Pittler MH, Ernst E. J Clin Psychopharmacol. 2000;20:84-89.
2 Spillane PK, Fisher DA, Currie BJ. Med J Aust. 1997;167(3):172-173.
3 Young MC, et al. Med J Aust. 1999;170(9):425-428.
4 Mathews JD, et al. Med J Aust. 1988;148(11):548-555.
5 Stoller R. Schweiz Arztezeit. 2000;81(24):1335-1336.
6 Stafford N. Germany may ban kava kava herbal supplement, Yahoo News. URL: http://dailynews.yahoo.com, Nov 19, 2001.
7 Russmann S, Lauterburg BH, Helbling A. Ann Intern Med. 2001;135(1):68-69.
8 Felter HW, Lloyd JU. King’s American dispensatory, ed 18. Portland: Eclectic Medical Publications, 1905. rev 3, reprinted 1983
9 British Herbal Medicine Association’s Scientific Committee. British herbal pharmacopoeia. Bournemouth: BHMA, 1983.
10 Titcomb M. J Polynes Soc. 1948;57:105-171.
11 Lebot V, Merlin M, Lindstrom L. Kava—the Pacific elixir: the definitive guide to its ethnobotany, history and chemistry. New Haven: Yale University Press, 1992.
12 Cambie RC, Ash J. Fijian medicinal plants. Melbourne, Australia: CSIRO Publishing, 1994.
13 World Health Organization. Medicinal plants in the South Pacific. Manilla: WHO Regional Office for the Western Pacific, 1998.
14 Volz HP, Kieser M. Pharmacopsychiatry. 1997;30:1-5.
15 Neuhaus W, et al. Zentralbl Gynakol. 2000;122(11):561-565.
16 Watkins LL, Connor KM, Davidson JRT. J Psychopharmacol. 2001;15(4):283-286.
17 Wheatley D. Human Psychopharmacol. 2001;16(4):353-356.
18 De Leo V, et al. Maturitas. 2001;39(2):185-188.
19 Foo H, Lemon J. Drug Alcohol Rev. 1997;16:147-155.
20 Steiner GG. Hawaii Med J. 2000;59(11):420-422.
21 Blumenthal M, et al, editors. The complete German Commission E monographs: therapeutic guide to herbal medicines. Austin: American Botanical Council, 1998.
KOREAN GINSENG
| Botanical Name: | Panax ginseng |
| Family: | Araliaceae |
| Plant Part Used: | Root |
PRESCRIBING INFORMATION
| Actions | Adaptogenic, tonic, immune modulating, cardiotonic, male tonic, cancer preventative, cognition enhancing | |
| Potential Indications |
Based on appropriate evaluation of the patient, practitioners should consider prescribing Korean ginseng in formulations in the context of:
• Improving physical and mental performance and well being; improving general performance under stress (2,4,5)
|
|
Excessive doses of Korean ginseng can cause overstimulation, and symptoms of ginseng abuse syndrome (GAS) have been reported in independent studies. GAS is defined as hypertension together with nervousness, euphoria, insomnia, skin eruptions, and morning diarrhea and is thought to be related to Korean ginseng’s interaction with glucocorticoid production in the body.
Korean ginseng may cause side effects related to an estrogenlike activity in women, and cases of mastalgia and postmenopausal bleeding have been reported.
Ginseng is widely used, and several other rare adverse reactions have been reported that are, at best, possibly related to ginseng or may otherwise reflect contamination, adulteration, or coincidence. These conditions include Stevens-Johnson syndrome, diuretic resistance, cerebral arteritis, mania, and mydriasis.
* This dose range is also extrapolated from British Herbal Pharmacopoeia 1983, the British Herbal Compendium 1992, and from clinical trials.
SUPPORTING INFORMATION
When referred to in the following points, red ginseng is Panax ginseng that has been steamed before drying.
• Although some negative findings have been reported, the majority of clinical trials have found that Korean ginseng increases physical performance. Physical performance and visual and auditory reaction times were significantly increased in a randomized, double-blind, placebo-controlled trial using Korean ginseng extract administered for 12 weeks to people aged 22 to 80 years. Male athletes significantly increased their aerobic capacity and significantly reduced their blood lactate levels and heart rate while taking Korean ginseng in randomized and nonrandomized, double-blind, placebo-controlled trials and in uncontrolled trials. These trials were conducted by the same research group over a 9-week period. The daily dose of Korean ginseng extract administered was 200 mg/day (containing 4% ginsenosides and equivalent to approximately 1 g/day of dried root).
• Randomized, double-blind, controlled trials have shown that Korean ginseng significantly improves quality of life and well being measures while under stress, including alertness, relaxation, appetite, fatigue levels, sleep quality, recovery from the common cold and bronchitis, and significantly decreases systolic blood pressure compared with controls. Two of these trials compared Korean ginseng combined with vitamins and minerals against placebo. One trial compared this combination against vitamins and minerals, and another trial compared Korean ginseng on its own against placebo. The Korean ginseng, vitamin, and mineral combination was superior to the vitamins and minerals alone. In two of these trials, the daily dose was equivalent to between 0.4 and 1.0 g of dried root, which was administered for up to 4 months.
• The Korean ginseng, vitamin, and mineral combination improved REM sleep in elderly volunteers in a double-blind, placebo-controlled trial. Reaction time and decision-making were improved in elderly volunteers taking red ginseng (1.5 g/day) in a double-blind crossover trial.
• A combination containing Ginkgo extract (120 mg/day standardized to 24% ginkgo flavone glycosides) and Korean ginseng extract (200 mg/day standardized to 4% ginsenosides) demonstrated improvement in the working and long-term memory of healthy, middle-aged volunteers over 14 weeks in a multicenter, double-blind, placebo-controlled trial.8 Three single, increasing doses of standardized Korean ginseng extract produced a dose-dependent improvement in several aspects of memory when compared with placebo in healthy young volunteers. The trial was of randomized, double-blind, crossover design.9
• Korean ginseng extracts significantly improved cell-mediated immune function (chemotaxis, phagocytic activity, and intracellular killing) in a double-blind, placebo-controlled trial involving healthy volunteers. A standardized extract (200 mg/day, equivalent to approximately 1 g/day of root and containing 4% ginsenosides) was compared with 200 mg/day of aqueous extract for 8 weeks. A randomized, double-blind, placebo-controlled study demonstrated significant prevention of influenza and the common cold for Korean ginseng over placebo in volunteers also receiving an antiinfluenza vaccination. The Korean ginseng group demonstrated significantly higher antibody titers and natural killer cell activity. Extract doses equivalent to approximately 1 g per day of root containing 4% ginsenosides were given for 12 weeks. In a more recent randomized, double-blind, placebo-controlled trial, treatment with Korean ginseng extract for 4 months improved the immune response (IgM and IgA antibody levels) to influenza vaccination in healthy volunteers.10
• Korean ginseng extract (equivalent to approximately 1 g/day of root) improved the immune response of alveolar macrophages isolated from chronic bronchitis patients in a placebo-controlled, single-blind trial. In a randomized, controlled trial involving patients with chronic bronchitis, Korean ginseng combined with antibacterial drugs reduced the bronchial bacterial count faster than antibacterial drugs alone. The daily dose of Korean ginseng extract was 200 mg standardized to contain 4% ginsenosides. The duration of the trial was 9 days.11
• Controlled and uncontrolled trials have found ginseng may be of value in treating HIV infection. The dosage used in one of the uncontrolled studies was 5.4 g per day of red ginseng powder.
• Significant improvement in cerebrovascular circulation was observed in patients with moderate cerebrovascular deficit treated with either Korean ginseng extract (containing 4% ginsenosides and equivalent to approximately 1 g/day of root) or the drug hydergine (3 mg/day) when compared with placebo under double-blind conditions over a period of 3 months.
• A combined Korean ginseng and Ginkgo product (containing 4 mg/day ginsenosides and 28.8 mg/day ginkgo flavone glycosides) improved circulation and lowered blood pressure in a small, placebo-controlled, single-dose study in healthy volunteers. A controlled trial involving patients with congestive heart failure found red ginseng improved biochemical and hemodynamic parameters. Greater improvement was noted when the herb was combined with digoxin. Erectile function and HDL cholesterol were significantly improved in elderly men with psychogenic impotence treated with red ginseng (1.8 g or 2.7 g for 2 months) in a placebo-controlled study.
• Red ginseng (6g/day) improved psychological test scores in post-menopausal women with symptoms of fatigue, insomnia, and depression when compared with baseline values. The improvement was at least partially the result of an antistress effect, as demonstrated by a decrease in the cortisol/dehydroepiandrosterone (DHEA) ratio.12 In a randomized, double-blind, placebo-controlled trial, postmenopausal women reported improvement in quality-of-life measures, including depression and well being, after treatment with standardized Korean ginseng extract (containing 4% ginsenosides, equivalent to approximately 1 g/day of root). No benefit over placebo was observed for physiological parameters, including FSH and estradiol levels and endometrial thickness.13
• Epidemiological studies have found an inverse relationship between Korean ginseng intake and cancer in South Korea, where Korean ginseng tea is consumed as frequently as coffee. A case-controlled study on 1987 pairs found that the relative risk for cancer for Korean ginseng users was 50% lower than for those who did not use Korean ginseng. The incidence of cancers of the lung, lip, oral cavity, and pharynx were substantially lower in smokers who were Korean ginseng users compared with smokers who were not. The incidences of cancers of the breast, cervix, bladder, and thyroid gland were not affected by Korean ginseng. Prospective cohort studies found decreased risk of cancer for participants who had consumed Korean ginseng compared with nonconsumers. Ginseng consumption was also linked to decreased risk for gastric and lung cancers.14,15
• Daily supplementation of red ginseng (1.8 g) for 4 weeks in smokers resulted in a linear increase in plasma antioxidant concentration compared with values obtained from smokers administered a placebo. In this randomized trial, Korean ginseng treatment also decreased markers of DNA oxidative damage.16
• A randomized, double-blind, placebo-controlled study involving patients with cervical cancer who were undergoing radiation therapy found that Korean ginseng (5 g/day for 5 weeks) exerted a protective effect on bone marrow depression and significantly elevated platelet count.
• Sperm count, sperm motility, total testosterone, free testosterone, and dihydrotestosterone (DHT) rose substantially, and prolactin levels decreased after 3 months of ginseng treatment in men with idiopathic low sperm count and low sperm count associated with varicocele. The control group mirrored these responses on a smaller scale. Red ginseng extract significantly improved erectile dysfunction compared with the drug trazodone, which demonstrated a similar effect to placebo in a randomized trial.
• Pregnant women taking ginseng had a significantly lower incidence of preeclampsia than their matched controls. The control group had higher mean blood pressures in the second and third trimesters.
• In a randomized, double-blind, placebo-controlled study involving patients with non-insulin–dependent diabetes, Korean ginseng extract taken for 8 weeks significantly improved patients’ fasting blood glucose, mood, vigor, well being, and psychomotor performance.
• Only minor benefit was observed in a single-blind, placebo-controlled trial involving patients with essential hypertension treated with red ginseng root (4.5 g/day for 8 weeks).17 In a small, controlled trial, red ginseng improved the vascular endothelial dysfunction in patients with hypertension, possibly through increasing the synthesis of nitric oxide.18
Except when specifically referenced, the following book was referred to in the compilation of the pharmacological and clinical informationMills S, Bone K. Principles and Practice of Phytotherapy: Modern Herbal Medicine. Edinburgh: Churchill Livingstone, 2000.
1 Zhu M, et al. J Pharm Pharmacol. 1999;51:175-180.
2 Pharmacopoeia Commission of the People’s Republic of China. Pharmacopoeia of the People’s Republic of China, English ed. Beijing: Chemical Industry Press, 1997.
3 Bensky D, Gamble A. Chinese herbal medicine materia medica. Seattle: Eastland Press, 1986.
4 British Herbal Medicine Association. British herbal compendium. Bournemouth: BHMA, 1992.
5 British Herbal Medicine Association’s Scientific Committee. British herbal pharmacopoeia. Bournemouth: BHMA, 1983.
6 Felter HW, Lloyd JU. King’s American dispensatory, ed 18. Portland: Eclectic Medical Publications, 1905. rev 3, reprinted 1983
7 Attele AS, Wu JA, Yuan CS. Biochem Pharmacol. 1999;58(11):1685-1693.
8 Wesnes KA, et al. Psychopharmacology. 2000;152(4):353-361.
9 Kennedy DO, Scholey A, Wesnes KA. Phytomed. 2000;7(supp 2):105.
10 Gundling K, et al. Altern Ther Health Med. 2001;7(3):104.
11 Scaglione F, Weiser K, Alessandria M. Clin Drug Invest. 2001;21(1):41-45.
12 Tode T, et al. Int J Gynaecol. 1999;67:169-174.
13 Wiklund IK, et al. Int J Clin Pharmacol Res. 1999;19(3):89-99.
14 Yun TK, Choi SY, Lee YS: Second International Cancer Chemo Prevention Conference, Berlin, April 28-30, 1993.
15 Yun TK, Choi SY. Proc Annu Meet Am Assoc Cancer Res. 1996;37:1906.
16 Lee BM, Lee SK, Kim HS. Cancer Lett. 1998;132(1-2):219-227.
17 Han KH, et al. Am J Chin Med. 1988;26:199-209.
18 Sung J, et al. Am J Chin Med. 2000;28(2):205-216.
19 Blumenthal M, et al, editors. The complete German Commission E monographs: therapeutic guide to herbal medicines. Austin: American Botanical Council, 1998.
