St. John's Wort Gastrointestinal Side Effects
St. John's wort causes mild gastrointestinal symptoms as its most common GI adverse effect, though these occur infrequently and are generally well-tolerated. 1
Specific GI Symptoms
The gastrointestinal symptoms associated with St. John's wort include:
- Nonspecific gastrointestinal complaints (most common GI manifestation) 1
- Nausea 2
- Diarrhea 3
- General digestive discomfort 4
These symptoms are characterized as mild in nature across multiple high-quality guidelines 1.
Clinical Context and Frequency
The 2016 American College of Physicians guideline emphasizes that St. John's wort is better tolerated than second-generation antidepressants (moderate-quality evidence), with GI symptoms being part of a limited adverse effect profile 1.
In a large 1-year safety study of 440 patients, only 6% of adverse events were possibly or probably treatment-related, with gastrointestinal complaints being among the most common alongside skin reactions 4. A systematic review confirmed that the incidence of adverse reactions with St. John's wort is similar to placebo 2.
Important Clinical Considerations
Beyond GI effects, clinicians should be aware that St. John's wort:
- Induces cytochrome P450 3A4, causing significant drug-drug interactions 1, 5
- Is contraindicated with MAO inhibitors and serotonin reuptake inhibitors 1
- May reduce efficacy of oral contraceptives and immunosuppressants 1
- Can cause photosensitivity (though extremely rare) 2
The GI symptoms are generally self-limiting and do not require discontinuation in most patients, making St. John's wort one of the better-tolerated options for mild to moderate depression when drug interactions are not a concern 2, 3.