National Toxicology Program

EXPOSURE INFORMATION

Production and Producers:

Yohimbe grows in the jungles of West Africa (Cameroon, Congo, and Gabon). Yohimbe bark consists of the dried bark of the trunk and/or branches of Corynanthe yohimbe (syn. Pausinystalia yohimbe). Yohimbine, which constitutes about six percent of yohimbe bark, is also present in the related species P. macroceras, P. paniculata, and P. trillesii. Although yohimbe has been used medicinally since ancient times, yohimbine was first isolated in 1896 and its correct constitution was not identified until 1943 (Mekkawi & Al-Badr, 1972; PDR Herbal, 1998).

The total synthesis of yohimbine has been reported (vanTamelen et al., 1958; Florey, 1972; Goodman, 1988; Shi, 1989; Budavari, 1997). vanTamelen and coworkers (1958) achieved synthesis of yohimbine through a 23-step process.

Yohimbe bark and extract are available from Charles Bowman & Co., Mini Star International, Inc., Motherland Herb-Pharm, Inc., QBI (Quality Botanicals Ingredients, Inc.), and Stryka Botanics Co., Inc. (McCoy, 1998).

Yohimbine is available from The Graymor Chemical Co., Inc., Pharmline, Inc., SPS Alfachem, Paul Schueller International, Inc., and B.I. Chemicals, Inc. (Kuney, 1997; McCoy, 1998).

Yohimbine hydrochloride is available from BCN Chemicals, Inc., B.I. Chemicals, Inc., Boehringer Ingelheim KG, CPB International, Inc., Flavine International, Inc., Maypro Industries, Inc., Mini Star International, Inc., Monomer-Polymer & Dajac Labs, Inc., Motherland Herb-Pharm, Inc., Nuova Linnea, Inc., Ria International, SST Corp., Schweizerhall, Inc., Spectrum Bulk Chemicals, Division of Spectrum Quality Products, Inc., Synkem Div. de Plasto S.A., and Westco Chemicals, Inc. (Kuney, 1997; Hunter, 1998; McCoy, 1998; Nuova Linnea, 1999).

In the 8-month period from September 1998 to May 1999, the Port Import/Export Reporting Service (PIERS) reported yohimbine and yohimbine hydrochloride imports of 547 and 52 pounds, respectively (Dialog Information Services, 1999b).

Yohimbine hydrochloride is listed in the EPA’s Toxic Substances Control Act (TSCA) Inventory (NLM, 1999).

Use Pattern:

Health food stores in the US have carried yohimbe for many years. Both the crude bark and its purified compounds have a history of popular use for supposed aphrodisiac properties. Pharmacologists have generally disparaged the use of yohimbine as an aphrodisiac that produces a true stimulation of libido (Clark et al., 1984). In recent years, the market has shifted from aphrodisiacs to enhancers of athletic performance (Clark et al., 1984; Kowalchik & Hylton, 1987; Owen et al., 1987; Betz et al., 1995; Africanfly, 1999; Angelfire, 1999; Bodybuild, 1999; Dialog Information Services, 1999b).

Yohimbine and yohimbe extracts are used to treat impotence, a disorder that occurs in 1.2 to 2 percent of the male population. Yohimbe has also been used extensively in veterinary medicine for treatment of impotent breeding stallions (Clark et al., 1984; Kowalchik & Hylton, 1987; Owen et al., 1987; Sandler & Aronson, 1993; Betz et al., 1995; Africanfly, 1999; Angelfire, 1999; Aphrodisiacal Drugs, 1999; PDR, 1999).

Yohimbine is an a-2 adrenergic antagonist that inhibits norepinephrine release, decreasing sympathetic overflow from the central nervous system (Buffum, 1985). Its peripheral nervous system effect is to increase cholinergic and decrease adrenergic activity. In male sexual performance, erection is linked to cholinergic activity and to a -2 adrenergic blockade (Mekkawi & Al-Badr, 1972; PDR, 1999).

Yohimbine affects impotence by dilating the blood vessels of the skin and mucous membranes, thus bringing the blood closer to the surface of the sex organs, resulting in increased peripheral genital vasocongestion. It also increases the reflex excitability of the lower region of the spinal cord. For the treatment of erectile impotence, the recommended dose of yohimbine is 16.2 mg (yohimbine hydrochloride) a day taken in three divided doses. The suggested treatment period is no more than 10 weeks. The yohimbe bark is taken as a sweet tea, smoked, or sniffed (Clark et al., 1984; Kowalchik & Hylton, 1987; Lacomblez et al., 1989; Betz et al., 1995; PDR, 1999).

Yohimbe has been as an antidiuretic, for angina pectoris, as a hallucinogen, and for treatment of atherosclerosis. Yohimbine also exerts a stimulating action on the mood and may increase anxiety. It has a mild anti-diuretic action and reportedly does not significantly influence cardiac stimulation and other effects mediated by b-adrenergic receptors (Clark et al., 1984; Kowalchik & Hylton, 1987; Lacomblez et al., 1989; Atala & Amin, 1991; Betz et al., 1995; PDR, 1999).

Between 1979 and 1999, the US Patent and Trademark Office issued 5 patents involving yohimbe and 420 involving yohimbine (US Patent and Trademark Office, 1999a,b).

Human Exposure:

The primary exposure of humans to yohimbe occurs through its use as an herbal supplement. Approximately one third of the US adult population or approximately 60 million consumers, have increasingly used alternative pharmaceutical preparations to prevent or treat illnesses (Tanaka, 1997).

There is potential for worker exposure to yohimbe during the growing, harvesting and processing of the plants. For the purposes of quantifying the costs of food labeling regulations, the FDA (1997) estimated that there were 250 herbal/botanical firms; the number of firms producing yohimbe products was not identified

No listing was found for yohimbe or yohimbine in the National Occupational Exposure Survey (NOES), which was conducted by the National Institute for Occupational Safety and Health (NIOSH) between 1981 and 1983.

Environmental Occurrence:

Yohimbe (Corynanthe yohimbe), a member of the Rubiaceae family, is a tall evergreen tree that grows in the jungles of west Africa (Cameroon, Congo, and Gabon) (Betz et al., 1995; PDR Herbal, 1998). Information on controlled cultivation was not found in the available literature.

Regulatory Status:

Since 1994, dietary supplements have been regulated under the Dietary Supplement Health and Education Act (DSHEA). For dietary supplements on the market prior to October 15, 1994, the DSHEA requires no proof of safety in order for them to remain on the market. The labeling requirements for supplements allow warnings and dosage recommendations as well as substantiated "structure or function" claims. All claims must prominently note that they have not been evaluated by the FDA, and they must bear the statement "This product is not intended to diagnose, treat, cure, or prevent any disease" (Croom & Walker, 1995).

The FDA classifies yohimbe as an unsafe herb, containing "the toxic alkaloid, yohimbine, and other alkaloids" (Duke, 1985). In Germany, Commission E, an expert panel that evaluates the uses of herbal medicines, did not recommend the therapeutic administration of yohimbe bark and its preparations because of insufficient proof of efficacy and the unforeseeable correlation between risk and benefit (Blumenthal, 1998).