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Medicinal uses and athletic applications of Ephedra (ma huang)

In Asian medicine, ephedra is the chief herbal drug for treatment of asthma and bronchitis. This herb is one of the oldest and most widely used Chinese herbs, having been employed for thousands of years in traditional Chinese medicine (TCM) as a primary component of multi-herb formulas prescribed to treat bronchial asthma, cold and flu, cough and wheezing, fever, chills, lack of perspiration, headache, and nasal congestion.
In Asian medicine, ephedra is the chief herbal drug for treatment of asthma and bronchitis


Ephedra, also known as “ma huang”, is a dioecious, drought- and frost-resistant, perennial, evergreen shrub. It is native to central Asia and distributed throughout China, Tibet, India, Japan, Southern Siberia, Spain, Sicily, and Afghanistan (Morton, 1977; Grieve, 1979; Budavari, 1996; Leung and Foster, 1996). E. distachya is found in Europe, and there are ten Ephedra species reported from North America which include E. trifurca or E. viridis, E. nevadensis and E. americana (Morton, 1977).

Several Ephedra species have been cultivated experimentally in Australia, Kenya, England, and the US (Grieve, 1979; Budavari, 1996; Leung and Foster, 1996), but commercially important species are available mostly in China, northwestern India and northern Pakistan (Morton, 1977; Nasir and Ali, 1987; Tyler et al., 1988). Ephedra is quite rich in species and genetic diversity with extreme morphological proliferations.

The high degree of overlapping traits does not allow the species to be identified using only conventional tools. Hence, only 9 species (E. ciliate, E. regeliana, E. pacyclada, E. wallichii, E. gerardiana Syns E. distachya, E. przewalskyi, E. procera Syn E. Nebrodensis, E. sarcocarpa, E. monosperma) were provisionally recognized from Pakistan (Nasir and Ali, 1987), which needs further confirmation. The use of DNA technology could be the most appropriate tools in this regard.

Ephedrine

Ephedra alkaloids are popular components of many nutritional supplements, with approximately 3 billion doses sold in 1999. They are found in several plant species, including Ephedra sinica, E. intermedia, and E. equsetina, collectively known as Chinese ephedra or ma huang, and Sida cordifolia. Purified forms of these substances include ephedrine, pseudoephedrine, norephedrine, methylephedrine, norpseudoephedrine, and methylpseudoephedrine. Phenylpropanolamine is a synthetic compound functionally similar to the ephedra alkaloids in effect and use.

Epidemiology

One study of commercial fitness center clients reported ephedra use within the past 3 years in 109 of 511 subjects, which would extrapolate to a national use by 2.8 million American recreational athletes. A National Collegiate Athletic Association (NCAA) study of the drug and supplement use habits of 21,000 college students from 713 NCAA member institutions in 2001 showed an increase in ephedrine use from 3.5% to 3.9% compared with rates in 1997. Men's lacrosse (5.5%) and women's gymnastics (8.3%) had the highest rate of ephedrine use among NCAA athletes. The major reasons to use supplements as reported by athletes are improved athletic performance (27.3%), improved physical appearance (27.3%), and weight control (19.7%). More than half of these college athletes started using nutritional supplements before finishing high school.

Pharmacological actions

Ephedrine and related alkaloids produce sympathomimetic effects, including vasoconstriction; increased heart rate; and stimulation of central nervous system. Ephedrine decreases gastric emptying, possibly contributing to reduction of food intake. Ephedra herb preparations are shown to produce dilated bronchi, and induce perspiration (diaphoretic), and diuresis (diuretic). Ephedra-caffeine herb combinations are shown to increase thermogenesis and weight loss in obese patients.

Ephedra alkaloids are sympathomimetic agents that act as both α and β adrenergic agonists, and enhance the release of norepinephrine from sympathetic neurons. Ephedra alkaloids cross the blood-brain barrier and are a potent central nervous system (CNS) stimulator. Functionally, the ephedra alkaloids are similar to amphetamines, although weaker. The relative balance of α and β receptors determines their net effect. Sympathetic stimulation can cause excitatory effects in some tissues, and inhibitory effects in others. Stimulation of α receptors in vascular smooth muscle leads to contraction and vasoconstriction. β1 receptors, primarily found in cardiac tissue, may lead to increased heart rate and myocardial strength when stimulated. Stimulation of β2 receptors in bronchial smooth muscle causes bronchodilatation, and vasodilatation in skeletal muscle

Uses

Respiratory System

• Mild bronchospasms in adults and children over the age of six (Blumenthal et al.,1998)

• Bronchodilator in treatment of bronchial asthma (WHO, 1999)

Ear Nose and Throat

• Nasal congestion due to hay fever, allergic rhinitis, acute coryza (rhinitis), common cold, sinusitis (WHO, 1999)

Obesity/Weight Management

• Increased weight loss and thermogenesis (Boozer et al., 2002, 2001; Belfie et al., 2001; de Jonge et al., 2001; Greenway, 2001; Liu et al., 1995; Astrup et al., 1986; Pasquali et al., 1985)

Other potential uses

• Uses in Traditional Chinese Medicine (TCM) include common cold marked by chilliness and mild fever, headache, stuffed and running nose, general aching, but no sweating; edema in acute nephritis; bronchial asthma (PPRC, 1997).

• Ephedra dietary supplements are frequently used by athletes as performance enhancing agents (This use is highly controversial and has been the subject of numerous athletic groups’ attempts to ban or restrict dietary supplements containing ephedra for this application.) (IOC, 2001; Anon., 2001c; NCAA, 2001)

Anxiety and restlessness, hypertension, glaucoma, impaired cerebral circulation, adenoma of prostate with residual urine accumulation, pheochromocytoma, thyrotoxicosis, pregnancy, anorexia, diabetes, heart disease, insomnia, stomach ulcers, children, renal failure. Patients with the following conditions or symptoms should consult a healthcare provider before using ephedra: difficulty urinating, prostate enlargement, thyroid disease, depression or other psychiatric condition, or if using a monoamine oxidase (MAO) inhibitor, any other prescription drug, or an OTC drug containing ephedrine, pseudoephedrine or phenylpropanolamine (PPA) (ingredients found in certain allergy, asthma, cough/cold, and weight control products). (PPA has been removed from the OTC market, but consumers might still possess older PPA-containing drug products.)

Exceeding recommended dosage will not improve therapeutic benefits and may cause serious adverse health effects. Patients should discontinue use and call a health care professional immediately if they experience rapid heartbeat, dizziness, severe headache, shortness of breath, or other similar symptoms.

Pregnancy and lactation: Ephedra is not recommended for use during pregnancy or lactation.

Adverse effects

Insomnia, motor restlessness, irritability, headaches, nausea, vomiting, disturbances of urination, tachycardia; higher dosages (greater than the equivalent of 300 mg ephedra alkaloids per day) may produce a drastic increase in blood pressure, cardiac arrhythmia, and development of dependency. Isolated reports of adverse events, some serious, including stroke and death, have been received by the FDA.

One highly publicized review of selected events reported to the FDA concluded that the adverse event reports (AERs) do not establish causality and cannot be used to quantify risk. Recent evidence submitted to the FDA shows no association between clinically significant adverse events and doses of under 100 mg of ephedra alkaloids per day.

An epidemiological analysis of the AERs showed no greater incidence of seizures, strokes, and myocardial infarctions (MIs) in persons consuming dietary supplements containing ephedrine alkaloids than that expected in the general U.S. population. In addition, the FDA advises that AERs alone do not provide a scientific basis for assessing the safety of dietary supplements containing ephedrine alkaloids.

Athletic applications

With their stimulant properties and sympathomimetic actions, ephedra alkaloids have been perceived as lending unfair advantages to athletes when used in supplement form. Many athletes use substances containing ephedra alkaloids because of perceived benefits of increased energy, decreased time to exhaustion, and potential thermogenic properties with increased metabolism, increased fat loss, and improved muscle strength. Studies investigating the use of ephedra alkaloids at standard dosages have not supported their perceived performance-enhancing properties. However, some studies looking at the use of ephedrine and caffeine together have supported potential ergogenic effects.

Sidney and Lefcoe studied the use of ephedrine and the effect on cardiorespiratory endurance, maximal oxygen uptake, and ratings of perceived exertion, lung function, anaerobic capacity, speed, reaction time, hand-eye coordination, and muscle function. When compared with placebo, there were no statistically significant differences. They did, however, find that blood pressure and heart rate were significantly elevated.

DeMeersman et al. evaluated the effects of ephedrine use on 10 subjects during a cycle ergometer test. They assessed various cardiorespiratory variables, as well as ratings of perceived exhaustion and found no statistically significant advantage for ephedrine use over placebo. Interestingly, their research was prompted by an IOC investigation of an American athlete who tested positive for ephedrine use from incidental inhaler use for asthma during the 1972 Olympics. He was forced to return his gold medal based on the assumption that the ephedrine offered him an unfair advantage, a decision challenged by DeMeersman et al. on the basis of this research.

Similar studies have evaluated the potential effects of pseudoephedrine at both standard doses and doses that are higher than recommended. Gill et al. evaluated the effect of a 180-mg dose of pseudoephedrine administered 45 minutes prior to exercise on short-term maximal exercise performance.

Subjects completed a series of tests, including isometric knee extension, bench press at one repetition maximum (1RM) and 70% of 1RM, and a 30-second maximal cycle ergometry test. Subjects taking pseudoephedrine experienced increased maximum torque during isometric knee extension, improved peak power during cycle performance, and improved lung function when compared with placebo. Bench press tasks and total work during the cycle test were not significantly changed


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