Physical Address
304 North Cardinal St.
Dorchester Center, MA 02124
Clusiaceae
General information
The genera in the family of Clusiaceae ( Table 1 ) include St John’s wort and brindleberry (gamboge).
Table 1
Genera of Clusiaceae
| Calophyllum (calophyllum) | Hypericum (St John’s wort) | Platonia (platonia) |
| Clusia (attorney) | Mammea (mammea) | Triadenum (marsh St John’s wort) |
| Garcinia (sap tree) | Pentadesma (pentadesma) |
Garcinia gambogia (brindleberry, gamboge)
Liver
There have been many reports of hepatotoxicity associated with herbal products used for weight reduction. These products, which are sold as dietary supplements, do not usually undergo safety tests before they are marketed [ ].
Proprietary formulations such as Hydroxycut (MuscleTech Research and Development, Inc; Iovate Health Sciences Research, Oakville, Ontario, Canada) and Exilis (Fusion Health Products, Houston, Texas) contain mixtures of ingredients, including Garcinia gambogia .
-
Hydroxycut is said to contain Garcinia gambogia , L-carnitine, chromium picolinate, and guaranà extract; some preparations have also contained MaHuang extract.
-
Exilis is said to contain Garcinia gambogia, Gymnema Sylvestre (Asclepiadaceae), calcium, L-carnitine fumarate, chitosan, green tea extract, conjugated linoleic acid, magnesium chelate, and white kidney bean extract.
The US Food and Drug Administration (FDA) has issued warnings that Hydroxycut products should not be used [ ], because of the possibility of liver damage, of which there have been several reports [ ]. In one case an interaction with montelukast was postulated [ ].
There has been a review of eight patients who developed liver injury after taking Hydroxycut; all were hospitalized, and three required liver transplantation [ ]. Nine other cases with adequate clinical information were obtained from the FDA MedWatch database, including one fatal case of acute liver failure. The usual symptoms were jaundice, fatigue, nausea, vomiting, and abdominal pain. Most patients had hepatocellular liver damage.
Exilis has also been associated with fulminant hepatic failure [ ].
-
A 25-year-old man presented to a walk-in clinic with tea-colored urine and fatigue. He had taken Exilis for less than 3 weeks, and after taking it for 1 week he had developed nausea, vomiting, aches, and fever. His serum aspartate aminotransferase, alanine aminotransferase, and total bilirubin were 1394 U/l, 2362 U/l, and 180 μmol/l (10.5 mg/dl) respectively. He underwent cadaveric liver transplantation.
The principal hepatotoxic ingredient of Garcinia gambogia is thought to be hydroxycitric acid. However, it has been pointed out that 14 different formulations of Hydroxycut have been marketed, that only eight contained hydroxycitric acid, and that products of this sort contain numerous ingredients [ ]. For example, green tea (Camellia sinensis), present in some of these formulations, has also been associated with hepatotoxicity [ ].
Hypericum perforatum
Hypericum perforatum (devil’s scourge, goat weed, rosin rose, St John’s wort, Tipton weed, witch’s herb) contains the naphthodianthrones hypericin and pseudohypericin, flavonoids, such as hyperoside, isoquercitin, and rutin, and phloroglucinols, such as adhyperforin and hyperforin. It is effective in mild to moderate depression [ ].
Systematic reviews
A meta-analysis of 23 randomized, controlled trials of St John’s wort showed that the herbal extract is more effective than placebo for mild to moderate depression, but that current evidence was inadequate to establish whether St John’s wort is as effective as standard antidepressants [ ]. In clinical trials, St John’s wort appeared to have fewer short-term adverse effects than some conventional antidepressants, but information on long-term adverse effects is lacking.
In a meta-analysis of three randomized, placebo-controlled studies with very similar methods in 594 patients with mild to moderate depression, who took 900 mg/day of a standardized Hypericum extract for 6 weeks, the numbers of patients who had adverse effects were similar with Hypericum and placebo [ ]. Specifically, Hypericum was devoid of sedative or anticholinergic effects and did not cause gastrointestinal or sexual problems, which can be a problem with conventional antidepressants.
Two reviews have systematically addressed the safety of St John’s wort. One showed that the most common adverse events were gastrointestinal symptoms, dizziness, confusion, tiredness, sedation, and dry mouth [ ]. A second review compared the adverse effect profile of St John’s wort with those of conventional antidepressants [ ]. The adverse effects of St John’s wort were fewer and less serious than those associated with conventional antidepressant drugs.
A review of all reported adverse reactions associated with St John’s wort has shown that it has an encouraging safety profile [ ]. Adverse effects reported in clinical trials were invariably mild and transient: gastrointestinal symptoms (8.5%), dizziness/confusion (4.5%), tiredness/sedation (4.5%), and dry mouth (4.0%). Synthetic drugs used in comparative trials were burdened with significantly higher rates of adverse effects. Data obtained from the WHO Collaborating Center for International Drug Monitoring (the Uppsala Monitoring Centre, UMC) are summarized in Table 2 .
Table 2
Reports to the UMC of adverse reactions to St. John’s wort (up to May 1998)
| System | Number of cases |
|---|---|
| Cardiovascular (edema) | 2 |
| Cardiovascular (bradycardia) | 1 |
| Respiratory | 4 |
| Nervous system | 5 |
| Nervous system (stroke) | 1 |
| Psychiatric | 15 |
| Hematological (coagulation) | 4 |
| Gastrointestinal | 2 |
| Liver | 4 |
| Urinary tract (interstitial nephritis) | 1 |
| Skin (allergic reactions) | 16 |
| Skin (conjunctivitis) | 1 |
| Reduced therapeutic response | 1 |
Cardiovascular
A 41-year-old man who had taken St John’s wort had a hypertensive crisis after taking cheese with red wine [ ]. St John’s wort is a monoamine oxidase inhibitor, and the authors believed that this explained how the concomitant use of a tyramine-rich food with St John’s wort had caused this problem.
Nervous system
The mechanism of action of St John’s wort in depression is not understood, but serotonin re-uptake inhibition is one possibility, for which evidence is increasing. In one case this may have led to the serotonin syndrome in a 33-year-old woman who developed extreme acute anxiety after taking only three doses of extracts of St John’s wort and recovered after withdrawal [ ].
-
A 40-year-old man with a history of anxiety disorder and depression presented with flushing, sweating, agitation, weakness of the legs, dry mouth, tightness in the chest, and inability to focus [ ]. He was taking clonazepam (0.5 mg bd) and had started to take St John’s wort 10 days before. He had previously had two similar episodes after having taken sertraline.
The authors concluded that self-medication with St John’s wort, which has SSRI activity, had caused the serotonin syndrome.
You're Reading a Preview
Become a Clinical Tree membership for Full access and enjoy Unlimited articles
If you are a member. Log in here