Dong Quai: A Review

August 1999; Volume 1: 65-69

By Michael D. Rotblatt, MD, PharmD

Dong quai (also known as dang gui, tang kwei, or chinese angelica root) is a popular traditional Chinese medicine, frequently used in formulations for gynecologic disorders. In the United States, it is often labeled simply for "female balance and well being." Dong quai is used to treat menopausal symptoms, premenstrual syndrome, amenorrhea, and dysmenorrhea, and is also used as a general female tonic.

Source and Identity

Dong quai is a member of the Apiaceae (Umbelliferae) family, which includes parsley, carrots, and parsnips (as well as poison hemlock).1 Chinese dong quai (Angelica sinensis) is the most widely used species. A. acutiloba (Japanese dong quai) and A. gigas (Korean dong quai) have been used for similar medicinal purposes, but are not as highly regarded in China. A. archangelica (European angelica) and A. atropurpurea (American angelica) are utilized in Western herbal medicine, and are also used as flavoring agents in foods, desserts, and beverages (including Benedictine). With all Angelica species, the roots and rhizomes are the most extensively used parts of the plant.2 Only A. sinensis (Chinese dong quai) will be discussed here.

Dong Quai in Traditional Chinese Medicine

One of the earliest Chinese herbal writings, Lei Gong’s Treatise on Preparation of Materia Medica (588 A.D.), described dong quai: "…it is warming to the body, and it is non-poisonous. The root is used medicinally as a strengthener of the heart, lung, and liver meridians; it is a tonic of the blood and promotes blood circulation; it regulates the menstrual cycle and stops menstrual pain; it lubricates the bowel.…"3

Chinese women have long used dong quai oral preparations for general health promotion and to treat abnormal menstruation, dysmenorrhea, anemia or "blood deficiency" patterns, and childbirth difficulties.1-5 Administration by injection (IV, IM, or into acupuncture sites) has also been used by 20th century Chinese physicians to treat pain syndromes, thromboangiitis obliterans, chronic pelvic infections, Raynaud’s disease, rheumatoid arthritis, stroke, allergic rhinitis, and many other disorders, although proof of efficacy has not been established.3,6,7

Dosage

The dose of dong quai is usually 4-15 g in many oral formulations.1,4,8,9 Like other Chinese medicines, dong quai is traditionally used in combination with many other herbs (usually four or more) due to a belief in synergy and balance of herbal constituents. Because Western medicine focuses on single chemical components, North American consumers can also purchase dong quai as a single herbal preparation that contains about 0.5 g/capsule.

Pharmacology

In the last 50 years, many studies investigating the pharmacologic actions of A. sinensis have been published. Dong quai (and a variety of extracts and chemical constituents such as ferulic acid and polysaccharides) demonstrates biologic activity in a wide range of in vitro and animal experiments. (See Table 1 for a summary of some of these pharmacologic studies, drawn primarily from the Chinese medical literature.) Although these experiments can provide clues for further clinical research, activity in animals may be very different than activity in humans (differences in dose, route of administration, species specificity, etc.).

Table 1-Reported Pharmacologic Effects of Dong Quai or Components*

Actions Information about Study
Gynecologic (see text):
Inhibits uterus contractions Volatile oil component; animals, IV and in utero
Strengthens uterus contractions Water-soluble component; animals, IV route
Cardiovascular:
Increases coronary blood flow Anesthetized dogs, dose = 2 g/kg IV
Decreases myocardial ischemia Injection, anesthetized animals
Increases myocardial ischemia Injection, conscious dogs
Anti-arrhythmic activity Variety of animals, IV route
Decreases blood pressure; vasodilation Rapid action, short duration; IV route
Decreases atherosclerosis formation Rats fed dong quai as 5% of diet
Hematology:
Promotes hematopoiesis Rats; polysaccharide component
Inhibits platelet aggregation Rats; 20 g/kg crude drug IV
Increases coagulation time Rats fed dong quai PO; in vitro test of blood
Decreases blood viscosity and fibrinogen levels; increases PT Dong quai injected into human patients with "acute ischemic apoplexy"
Decreases thrombus propagation Rats
Immune System:
Increases function of macrophages Mice; SQ and PO routes
Increases IL-2 production Dong quai and ferulic acid component
Immunosuppressant effect Rats; inhibits production of antibodies
Miscellaneous:
Antibacterial effects Weak in vitro activity against several bacteria
Inhibits experimental liver damage Variety of animals
Protects against radiation damage Mice; polysaccharide component
Increases and decreases contractions of intestine and bladder Dogs, rabbits; IV water-soluble extract
Relaxes bronchial smooth muscle Guinea pigs; specific chemical constituents
Analgesic Decreases writhing reaction in mice (similar to salicylate)
*These pharmacologic effects are examples of findings from the Chinese medical literature and do not include all studies.
Source: Summarized from references 3, 6, 7, 10, 22, 23.

In the 1950s, two distinct extracts were shown to have contrasting effects on uterine muscle activity in animal experiments with both pregnant and non-pregnant cats, dogs, and rabbits.3,6,10 A volatile oil component of dong quai was found to inhibit spontaneous uterine contractions in isolated uteri (less marked effect was seen after intravenous administration in vivo). In contrast, a water-based or alcohol-based component given intravenously strengthened and increased uterine contractions in vivo. A more recent study of ferulic acid, one of the main chemical components of A. sinensis, found oral doses of 300 mg/kg to have an inhibitory effect on contractions of the rat uterus.11 Among Chinese practitioners and herbalists searching to scientifically substantiate Traditional Chinese Medicine (TCM), these studies supported their belief that dong quai may help to "normalize" or "correct imbalances" of uterine muscle contractions in women.

Is Dong Quai a Phytoestrogen?

Dong quai is not considered estrogenic in TCM, but modern Western herbalists often ascribe estrogenic effects to this herb. A casual survey of women’s health books in a metropolitan bookstore found that nine of 12 sources which discuss dong quai believe that it works either via an herbal estrogen (phytoestrogen) effect or by otherwise regulating female hormones. However, this is probably incorrect. In Chinese pharmacologic studies from several decades ago, no estrogenic effects were seen on vaginal smears of mice, and rodents fed dong quai as 5% of their diet did not develop increased uterine weights.3,6 Based on these investigations, Chinese scientists concluded that dong quai was not an estrogenic stimulant.6

In a 1998 U.S. study, dong quai was found not to bind to estrogen receptors (ERs) in vitro, nor did it stimulate cell proliferation in ER-positive human breast cancer cells.12 However, contrasting results were presented by researchers at a March 1998 meeting of the American Association for Cancer Research (as yet unpublished).13 Dong quai did bind to estrogen receptors in these in vitro experiments, and adding the herb to the feed of oophorectomized rats also increased uterine weight, again raising the possibility that the herb has an estrogenic effect in vivo.

The only human trial that addressed this question did not find an estrogenic effect. At a Kaiser Permanente Medical Center in Oakland, California, Hirata and colleagues studied 71 postmenopausal women with hot flashes in a well-designed, randomized, double-blind, placebo-controlled trial.14 In this study, subjects were randomized to treatment with a placebo or 4.5 g/d of a standardized dong quai root product (500 mg/capsule; 3 capsules tid) for 24 weeks. Subjects were evaluated for serum hormone concentrations, vaginal cell maturation, endometrial proliferation with transvaginal ultrasono- graphy, and menopausal symptoms with a self-reported diary of hot flashes and a menopausal index score (the Kupperman index). There were no statistically significant differences between the dong quai group and the placebo group in any parameter that was tested. Participants were unable to distinguish between herb and placebo, and both groups noted similar side effects during the study. Based on this well-designed study, dong quai (in a dose of 4.5 g/d) does not appear to have any significant estrogenic effects.

Is Dong Quai Clinically Effective?

Dong quai-containing formulas (in combination with other herbs) have been reported to be effective in the Chinese medical literature for dysmenorrhea, amenorrhea, menopausal symptoms, pelvic infections, premenstrual syndrome, hepatitis, COPD, chronic glomerulonephritis, and others.5,6,15 Most of these studies rely partially or completely on the TCM theories of diagnosis and treatment, and these studies (usually case series) are methodologically inadequate.

Based on the well-designed trial by Hirata et al, described above, dong quai by itself is no more helpful than placebo for relieving menopausal symptoms.14 This study has been criticized by advocates of TCM because traditional Chinese practitioners would never prescribe dong quai alone. The authors of this study are working with TCM practitioners to re-test dong quai in a mixture prescribed according to TCM principles.

Toxicity

Dong quai is not known to have serious side effects. Herbalists often state that it has mild laxative properties, which is most likely based on ancient Chinese writings that it "lubricates the bowel." Based on experiments in animals, Chinese scientists are concerned that dong quai may similarly affect the uterus and blood coagulation of humans, and thus recommend that it be avoided in menorrhagia, early pregnancy, and bleeding disorders.3 In rabbits, large oral doses of dong quai (2 g/kg bid) slightly decreased the prothrombin time (PT) of a single dose of SQ warfarin, but increased the PT in animals that had taken warfarin for several days.16 Warfarin kinetics were not affected, and the contrasting results of this study are difficult to interpret.

Because dong quai contains furanocoumarins (e.g., psoralen), some feel that users should be cautioned about potential photosensitization (occasionally seen in people who collect plants that contain these chemicals), or even about the potential photocarcinogenic or mutagenic effects of psoralens.17-19 However, to put this in the proper perspective, these chemicals are also found in many edible plants, such as parsnip, celery, and parsley.18,20 Also, coumarins are only slightly soluble in water, so aqueous preparations are relatively safe. Alcohol extracts would be expected to contain larger amounts of coumarin and may be more problematic. Safrole is another minor chemical component of dong quai that, in high concentrations (such as in sassafras oil), can cause hepatocellular carcinoma in rodents.17,20,21 However, safrole is also reported as a minor component in a variety of common plants and spices, including nutmeg, ginger, and black pepper.21

Although injecting the herb or drinking a concentrated extract may have toxic potential, the crude herb and usual extract forms appear to have few if any side effects. There are no documented cases of toxicity from dong quai. Hirata’s controlled study did not demonstrate any adverse effects. Although gas, burping, and headache were all reported, the incidence of these symptoms was similar in the placebo group.

Conclusion

Based on long historical use and limited clinical study, dong quai appears to be safe. Beneficial claims have been based on TCM theory, in vitro and animal experiments, and uncontrolled clinical trials. The only controlled trial to date demonstrated no estrogenic activity and no effect on menopausal symptoms. Its effect on menstrual irregularity has not been tested. The use of dong quai in combination with other herbs (as traditionally used) has not yet been tested in a methodologically adequate clinical trial. For evidence-based practitioners, the question of whether dong quai has any clinical benefits or is effective in traditional combination formulas awaits future controlled clinical investigations.

Dr. Rotblatt is an Assistant Clinical Professor of Medicine at the UCLA School of Medicine.

References

1. Foster S, Chongxi Y. Herbal Emissaries: Bringing Chinese Herbs to the West. Rochester, VT: Healing Arts Press; 1992.

2. Murray MT. The Healing Power of Herbs. 2nd ed. Rocklin, CA: Prima Publishing; 1995.

3. Zhu DP. Dong quai. Amer J Chin Med 1987;15: 117-125.

4. Bensky D, Gamble A. Chinese Herbal Medicine: Materia Medica. Seattle, WA: Eastland Press; 1993.

5. Belford-Courtney R. Comparison of Chinese and western uses of Angelica sinensis. Aust J Med Herbalism 1993;5:87-91.

6. Chang H-M, But PP-H. Pharmacology and Applications of Chinese Materia Medica. Vol. 1. Philadelphia, PA: World Scientific; 1986.

7. Chen JYP. Pharmacologic actions and therapeutic uses of ginseng (Panax ginseng, Angelica sinensis). Intl J Chin Med 1984;1:23-27.

8. Hsu H-Y, et al. Oriental Materia Medica: A concise guide. Long Beach, CA: Oriental Healing Arts Institute; 1986.

9. Yeung H-C. Handbook of Chinese Herbs and Formulas. Los Angeles, CA; 1985.

10. Qi-bing M, et al. Advances in the pharmacological studies of radix Angelica sinensis (Oliv) Diels (Chinese danggui). Chin Med J 1991;104:776-781.

11. Ozaki Y, Ma J-P. Inhibitory effects of tetramethyl- pyrazine and ferulic acid on spontaneous movement of rat uterus in situ. Chem Pharm Bull 1990;38: 1620-1623.

12. Zava DT, et al. Estrogen and progestin bioactivity of foods, herbs, and spices. Proc Soc Exp Biol Med 1998;217:369-378.

13. Fackelmann K. Medicine for menopause: Researchers study herbal remedies for hot flashes. Science News 1998;153:392-393.

14. Hirata JD, et al. Does dong quai have estrogenic effects in postmenopausal women? A double-blind, placebo-controlled trial. Fertil Steril 1997;68:981-986.

15. Zhiping H, et al. Treating amenorrhea in vital energy-deficient patients with Angelica sinensis-Astragalus membranaceus menstruation-regulating decoction. J Tradit Chin Med 1986;6:187-190.

16. Lo ACT, et al. Danggui (Angelica sinensis) affects the pharmacodynamics but not the pharmacokinetics of warfarin in rabbits. Eur J Drug Metab Pharmaco- kinetics 1995;20:55-60.

17. Anon. Dong quai. In: The Review of Natural Products. St. Louis, MO: Facts and Comparisons; March 1997.

18. Ivie GW, et al. Natural toxicants in human foods: Psoralens in raw and cooked parsnip root. Science 1981;213:909-910.

19. Foster S, Tyler VE. Tyler’s Honest Herbal. 4th ed. New York, NY: Haworth Herbal Press; 1999.

20. Peirce A. The American Pharmaceutical Association Practical Guide to Natural Medicines. New York, NY: William Morrow & Company; 1999.

21. Abel G. Safrole—General Discussion. In: De Smet PA, ed. Adverse Effects of Herbal Drugs. Vol 3. Berlin: Springer Verlag; 1997:105-122.

22. Huang KC. The Pharmacology of Chinese Herbs. 2nd ed. New York, NY: CRC Press; 1998.

23. Noe JE. Angelica sinensis: A monograph. J Naturopath Med 1997;(winter):66-72.