"Ephedra-free" diet pills often substitute synephrine for ephedra/ephedrine. Synephrine is the main "active" compound found in the fruit of a plant called Citrus aurantium. The fruit is also known as zhi shi, green orange, sour orange or bitter orange in other parts of the world. Synephrine is chemically very similar to the ephedrine and pseudo-ephedrine found in many OTC cold/allergy medications and in weight loss and energy supplements which contain Ma Huang.

Because synephrine is a stimulant, similar to caffeine and ephedrine, it is thought to have similar effects in terms of providing an energy boost, suppressing appetite and increasing metabolic rate and caloric expenditure. In traditional Chinese medicine zhi shi is used to help stimulate the Qi . Although synephrine and several other compounds found in zhi shi are structurally similar to ephedrine and are known to act as stimulants, zhi shi does not appear to have the same negative central nervous effects of ephedra. Through its stimulation of specific adrenergic receptors (beta-3, but not beta-1, beta-2 or alpha-1), zhi shi is theorized to stimulate fat metabolism without the negative cardiovascular side effects experienced by some people with Ma Huang.

The effects of synephrine alone or in combination with other ingredients such as kola nut and guarana (both are caffeine sources) or with salicylates such as white willow (a natural form of aspirin) generally fall into the category of acting as a mild stimulant. The extract of citrus aurantium, in addition to synephrine, also contains tyramine and octopamine. Octopamine may be related in some way to appetite control, as it is thought to influence insect behavior by stopping bugs from eating the citrus fruit. Importantly, each of these related compounds (synephrine, ephedrine and octopamine) can result in elevated blood pressure. A recent study conducted in dogs suggests that synephrine and octopamine can increase metabolic rate in a specific type of fat tissue known as brown adipose tissue. This effect would be expected to increase fat loss in humans – except for one small details – adult humans don’t have brown adipose tissue.

As it stands now, citrus aurantium extract exists as one of the most over-hyped ingredients on the weight loss scene. There are some interesting theories on how it might work to increase metabolic rate and promote weight loss, but most are couched in pseudo-scientific mumbo jumbo and none are backed by any credible scientific evidence of effectiveness in humans.

Both isolated synephrine and citrus aurantium extract have been shown to raise blood pressure in animal studies. Until more studies are conducted on the safety, pharmacology and efficacy of citrus aurantium as a thermogenic supplement, it should be treated as an ingredient with mild stimulant properties and should be avoided by individuals with cardiovascular concerns such as hypertension.