5-HTP vs St John's Wort for Perimenopause Mood: A Practical Comparison
5-HTP and St John's Wort are both used for low mood in perimenopause. Learn how they differ, what the evidence shows, and which suits your situation.
Why Women Look for Supplement Support in Perimenopause
Low mood, irritability, and anxiety are among the most commonly reported perimenopause symptoms, and they significantly affect quality of life. Some women prefer to try supplement-based approaches before or alongside medical options. Two supplements that come up frequently in this context are 5-HTP and St John's Wort. Both are marketed for mood support, both act on serotonin pathways, and both are available without prescription in most countries. However, they work differently, carry different risks, and suit different circumstances. Understanding the distinction before choosing one matters, particularly given the potential for interactions with other medications.
What 5-HTP Is and How It Works
5-HTP stands for 5-hydroxytryptophan, a compound the body makes from tryptophan, an amino acid found in food. It is the direct precursor to serotonin, meaning the body converts 5-HTP into serotonin in a single step. Taking 5-HTP as a supplement is thought to raise serotonin availability in the brain, which may improve mood, reduce anxiety, and support sleep. It is derived commercially from the seeds of the Griffonia simplicifolia plant. The evidence base for 5-HTP and mood is modest. Some small trials show benefit for depression and anxiety, but large, high-quality trials are limited. It is generally taken in doses between 50 and 200mg per day, often starting low to avoid gastrointestinal side effects such as nausea.
What St John's Wort Is and How It Works
St John's Wort is a flowering herb, Hypericum perforatum, with a much longer history of use for low mood. It has a stronger evidence base than 5-HTP, particularly for mild to moderate depression, with a number of trials showing it comparable to antidepressants for this indication. Its active constituents, particularly hypericin and hyperforin, appear to inhibit the reuptake of serotonin, dopamine, and noradrenaline, a mechanism similar to how some antidepressants work. It is typically taken in standardised extract form at doses of 300mg three times daily. It is licensed as a herbal medicine for low mood in several European countries and is recommended in some European clinical guidelines for mild to moderate depression.
Key Differences in Safety and Interactions
The most important practical difference between these two supplements is their interaction profile. St John's Wort is a potent inducer of cytochrome P450 enzymes in the liver, which means it speeds up the breakdown of many medications. This can reduce the effectiveness of hormonal contraceptives, anticoagulants like warfarin, some HIV medications, immunosuppressants, and certain antidepressants. Women using HRT should be aware that St John's Wort may theoretically affect hormone levels, though evidence specific to HRT interactions is limited. It should not be combined with SSRIs due to the risk of serotonin syndrome. 5-HTP has fewer known drug interactions but should still not be combined with SSRIs or MAOIs due to the same serotonin excess risk.
Which Is More Studied for Perimenopause Specifically
Neither supplement has been studied extensively in perimenopause-specific trials, which is a limitation worth acknowledging. Most evidence for both comes from general depression and anxiety studies. There is some observational evidence that St John's Wort may help reduce hot flash frequency alongside mood improvement, which would make it more broadly useful in perimenopause. A few small trials have looked at it in combination with other herbs for menopausal symptoms with positive results. 5-HTP's potential benefit for sleep may be particularly relevant in perimenopause, where disrupted sleep is a major driver of mood problems. If insomnia is prominent alongside low mood, 5-HTP taken in the evening may offer a dual benefit worth discussing with a doctor.
Practical Considerations When Choosing
The choice between the two depends heavily on individual circumstances. If you take any prescription medication, particularly contraceptives, anticoagulants, or antidepressants, St John's Wort should be avoided due to interaction risk. 5-HTP is not interaction-free but has a more manageable profile for most women. If your primary goal is mood improvement with some evidence behind it, St John's Wort has the stronger clinical record. If sleep and anxiety are as much of a concern as low mood, 5-HTP may be worth a trial. Neither should be used without informing your GP, particularly if you are also discussing HRT or other perimenopausal treatments. Starting with one at a time, rather than combining them, makes it easier to assess what is helping.
Tracking Mood to Know What Is Working
Whether you try 5-HTP, St John's Wort, lifestyle changes, or a combination, the only way to know if something is making a difference is to track your mood consistently over time. Perimenopausal mood can fluctuate with the hormonal cycle, meaning that a good week might reflect a favourable hormonal phase rather than a supplement benefit. Logging mood daily in an app like PeriPlan, alongside your symptoms, gives you a more reliable picture over weeks and months. If you can see that your mood scores improved after starting a supplement and remained higher across different hormonal phases, that is meaningful evidence. That record is also useful to share with your GP when reviewing whether to continue, adjust, or change your approach.
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