Supplements and Sertraline.
Sertraline, sold under the brand names Lustral, Zoloft, is a selective serotonin reuptake inhibitor (SSRI): it raises synaptic serotonin by blocking its reuptake.
Sertraline is the most prescribed SSRI in England, around 9 million items per year per NHSBSA. It raises synaptic serotonin by inhibiting the serotonin reuptake transporter, with relatively low affinity for other monoamine systems. The supplement interactions of greatest clinical concern are serotonergic and additive. St John's Wort is a hard exclude per the BNF and MHRA. 5-HTP is a hard exclude on theoretical and case-report grounds. Tryptophan, rhodiola, and at higher doses saffron extract and SAMe, also stack on the same pathway. Serotonin syndrome is rare but recognisable. Tremor, hyperthermia, clonus, agitation. Sertraline is metabolised mainly by CYP2B6 and CYP2C19, so the CYP3A4 interactions that dominate the calcineurin inhibitor pages do not apply here. Discontinuation needs taper, not stop. SSRI withdrawal symptoms are real and documented in NICE NG222, and any planned change should run through the prescribing GP rather than a supplement schedule.
Below are the 8 documented pairs we have explicitly assessed against Sertraline in the Distil database: 2 red and 6 amber. The pairs cluster around 2 mechanisms: Additive serotonergic activity and CYP-mediated metabolism. Every call is cited to either a clinical reference (PMID) or the British National Formulary. Anything not on this list is either still to be assessed or beyond our database scope. The checker beneath surfaces assessments by supplement, and the missing-item form at the bottom of the page routes any uncatalogued supplement into our next curation pass.
Documented interactions
Last reviewed 22 June 2026. Each interaction below lists the evidence its assessment drew on: some rest on studies of the exact pair, others on mechanism evidence, where a citation may support one part of the reasoning rather than the exact combination. The evidence line on each entry says which.
Additive serotonergic activity
Red Does 5-HTP interact with ?
5-HTP is the precursor your body uses to make serotonin. Combined with an SSRI like sertraline, it can cause serotonin syndrome (agitation, sweating, tremor, confusion). Do not combine.
Evidence: Supported by human study data.
Red Does St John's Wort interact with ?
St John's Wort and sertraline both raise serotonin levels. Combined, they can cause serotonin syndrome (agitation, sweating, tremor, raised heart rate, confusion). Do not combine.
Evidence: Supported by human study data.
Amber Does Ashwagandha interact with ?
Ashwagandha has mild effects on serotonin pathways that overlap with sertraline. Most people tolerate the combination but watch for restlessness, jaw tension, or sleep disruption.
Evidence: Based on an established mechanism, with no direct study of this exact combination yet.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does L-Tryptophan interact with ?
Tryptophan is the building block your body uses to make serotonin, so adding it to sertraline raises serotonin from both directions. The combination can cause agitation, sweating, tremor, shivering, muscle twitching, or a racing heart. Do not stack them without your GP's involvement.
Evidence: Limited human data, based on case reports and a known mechanism.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does Rhodiola Rosea interact with ?
Rhodiola has mild effects on serotonin pathways that can add to sertraline's. Most people tolerate the combination, but watch for restlessness, sweating, tremor, or a racing heart, and talk to your GP before stacking them, especially if your dose has recently changed.
Evidence: Limited human data, based on case reports and a known mechanism.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does SAMe interact with ?
SAMe has its own antidepressant, serotonin-related activity, which may add to sertraline's. Most people tolerate the combination, but watch for restlessness, sweating, tremor, shivering, or a racing heart, and tell your GP before stacking them, especially if your sertraline dose has recently changed.
Evidence: Limited human data, based on case reports and a known mechanism.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does Saffron Extract interact with ?
Saffron has antidepressant effects in its own right, which may add to sertraline's. Most people tolerate the combination but discuss it with your GP before stacking, especially if your dose has recently changed.
Evidence: Limited human data, based on case reports and a known mechanism.
CYP-mediated metabolism
Amber Does Bergamot Extract (BPF / Bergavit40) interact with ?
Bergamot can affect liver enzymes that help clear sertraline from the body, which could shift sertraline blood levels in either direction. Flag this to your GP before combining.
Evidence: Limited human data, based on case reports and a known mechanism.
What this list does not say. Pairs not flagged here are not implicitly safe. They are either not yet in our database, or fall outside our inclusion scope (food-supplement interactions only; for drug-drug interactions, the BNF is authoritative). Use the checker below to surface any supplement, and submit a missing item if you take something we have not catalogued.
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How we grade severity, choose what's in scope, and what we exclude.
Every call on this page is reasoned. We publish the full rubric for severity tiers, the medication inclusion logic, the evidence grades we accept, and what we deliberately leave out. About three thousand words. Worth reading once if you use this tool more than occasionally.
Read the full methodologyA full supplement review, built around you, not a generic stack.
The free checker answers one interaction question at a time. A Distil report reviews the bigger picture: your goals, diet, medications, current supplements and any blood results you provide, then shows what appears worth keeping, changing, adding or leaving out.
- what your diet already covers, so you are not adding a capsule for something food is already handling
- which evidence-graded compounds are worth considering for your goals, and which were considered but left out
- what to keep, change or stop from what you already take, plus the order to introduce anything new
- how your medications and complete supplement stack fit together, with daily timing and a clear point for reassessment
The interaction check is one section of the full report. You also get the reasoning behind each recommendation and the evidence references used.
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