St John’s Wort and Nutrient Approaches to Depression
St John’s Wort is a herbal extract. EPA omega-3 and L-methylfolate are single nutrients the body already uses and obtains from food. The two have been studied to answer different questions: St John’s Wort mainly as an alternative to antidepressant medication, and these nutrients mainly for use alongside existing treatment. St John’s Wort also interacts with a wide range of medicines.
Different questions, different answers
St John’s Wort
EPA and L-methylfolate
Is St John’s Wort a nutrient?
No. St John’s Wort is an extract of the plant Hypericum perforatum and contains many plant constituents. EPA omega-3 and L-methylfolate are single, defined nutrients that the body already uses and obtains from food. That is a difference in kind rather than a difference in degree, and it is the reason the two are assessed by different bodies, under different frameworks, against different questions. [1]
What does the evidence say about St John’s Wort for depression?
The US National Center for Complementary and Integrative Health reports that St John’s Wort appears to be more effective than a placebo, and about as effective as standard antidepressant medications, for mild or moderate depression. It also states that it is uncertain whether this holds for severe depression, or for periods longer than twelve weeks. [1] That body of evidence concerns taking St John’s Wort instead of an antidepressant. It is a different question from whether a nutrient helps when it is added to treatment somebody is already receiving.
Can St John’s Wort be taken with an antidepressant?
This is where the two approaches part company most sharply. NCCIH states that St John’s Wort can interact in dangerous, sometimes life-threatening ways with a variety of medicines, and that it can weaken the effects of many medicines including some antidepressants, birth control pills, warfarin, certain statins, ciclosporin, some anti-seizure and heart medicines, and drugs used in HIV and cancer treatment. It further states that taking St John’s Wort with certain antidepressants, or with other drugs that affect serotonin, may lead to increased serotonin-related side effects, which can be serious. [1][2] Anyone taking any medicine should speak to a doctor or pharmacist before taking St John’s Wort. NCCIH describes this as especially crucial for this herb, precisely because it interacts with so many medicines. [1]
What about nutrients alongside an antidepressant?
This is the question the nutrient evidence actually addresses. The 2022 clinician guidelines from the World Federation of Societies of Biological Psychiatry and the Canadian Network for Mood and Anxiety Treatments give adjunctive omega-3 fatty acids their strongest rating for any nutrient in unipolar depression. [3] A meta-review of thirty-three meta-analyses covering 10,951 people, published in World Psychiatry, names eicosapentaenoic acid specifically as carrying the strongest evidence in depression, and reports positive findings from trials of high-dose methylfolate. [4] Two different questions, then, with two different answers.
Where Hedonia sits
Hedonia contains no herbal extracts. It provides three nutrients, i.e. EPA omega-3, L-methylfolate and SAMe, and is a medical food for the dietary management of the nutritional requirements associated with depression, intended for use under medical supervision alongside a physician-directed treatment plan.
References
- National Center for Complementary and Integrative Health. St. John’s Wort: Usefulness and Safety. National Institutes of Health. Last updated May 2025. NCCIH
- Nicolussi S, Drewe J, Butterweck V, Meyer zu Schwabedissen HE. Clinical relevance of St. John’s wort drug interactions revisited. Br J Pharmacol. 2020;177(6):1212-1226. PMID 31742659. PubMed
- Sarris J, Ravindran A, Yatham LN, Marx W, Rucklidge JJ, McIntyre RS, et al. Clinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: the WFSBP and CANMAT Taskforce. World J Biol Psychiatry. 2022;23(6):424-455. PMID 35311615. PubMed
- Firth J, Teasdale SB, Allott K, Siskind D, Marx W, Cotter J, et al. The efficacy and safety of nutrient supplements in the treatment of mental disorders: a meta-review of meta-analyses of randomized controlled trials. World Psychiatry. 2019;18(3):308-324. Open access