**3. Herbs and dietary supplements used in weight loss**

### **3.1. Açaí (***Euterpe oleracea***)**

The açaí berry is harvested from the palm species *Euterpe oleracea* and is used mainly for dietary consumption as whole fruit, juice, or as a flavoring and coloring agent [27]. The fruit, widely used in Brazil, has gained in popularity as a food product and dietary supplement in the past several years, mainly due to its antioxidant and anti-inflammatory effects related to high polyphenol content[122-126].Althoughthere is little scientific evidence to supportthe berry for any of its purported health benefits, it can be found in several dietary supplements promoted for weight loss. In a pilot study investigating the effect of açaí supplementation on metabolic parameters in healthy overweight patients, the authors found a significant decrease in fasting glucose, insulin and cholesterol levels and a mild decrease in LDL-cholesterol and ratio of total cholesterol to HDL-cholesterol [127]. However, the authors did not assess weight loss in this study and therefore the activity of açaí as an anorectic agent cannot be determined. There have been no reported adverse drug interactions or interactions with others herbs and açaí [27].

#### **3.2. Bitter orange (***Citrus aurantium, Citrus naringin, synephrine***)**

Bitter orange is the fruit of *Citrus aurantium* or *Citrus naringin*, used as both a food product and the medicinal properties of the juice and peel [27]. There are multiple active constituents in bitter orange including several flavonoids (e.g. naringin) and the adrenergic agonists syn‐ ephrine and octopamine [128-134]. Synephrine is structurally similar to ephedrine, therefore prompting the replacement of ephedra with bitter orange in weight loss supplements, although the fruit has been used dichotomously as both an appetite stimulant and for weight loss [27]. However, there is insufficient evidence to confirm the efficacy of bitter orange as an anti-obesity agent, especially given its inclusion in combination products [27].

Interactions with bitter orange are varied. Synephrine, like ephedrine, is known to cause adverse cardiovascular effects at high doses, the risk of which are heightened when combina‐ tion products also including caffeine are ingested and therefore patients taking cardiac medications should be cautioned on its use [135, 136]. Some evidence demonstrates that bitter orange can inhibit cytochrome P450 3A4, although to a lesser extent than with grapefruit [137-140]. A 76% increase in AUC was observed following administration of 10 mg extended release felodipine administered with 240 mL Seville orange juice compared to control [139]; while a significant increase in indinavir tmax was observed with administration of 8 ounces of Seville orange juice compared to control [140]. Because synephrine and octopamine, both endogenous substances, can interact with monoamine oxidase there is a theoretical interaction of bitter orange with MAOIs [141, 142].
