Best Supplements for Mood During Perimenopause
Struggling with mood swings or low mood in perimenopause? These evidence-backed supplements may help, from saffron and magnesium to omega-3 and B6.
How Perimenopause Affects Mood
Mood changes during perimenopause are not just psychological. They are rooted in biology. Oestrogen has a direct influence on serotonin, dopamine, and GABA, the neurotransmitters that regulate emotional tone, motivation, and calm. As oestrogen fluctuates and ultimately declines, the brain's chemical environment becomes less stable. This is why many women who have never experienced depression or anxiety find themselves struggling for the first time in their forties. Sleep disruption adds another layer, because poor sleep impairs emotional regulation independently of hormones. Supplements cannot replace hormones or act as antidepressants, but some have solid evidence for supporting mood through complementary pathways.
Saffron
Saffron is one of the more surprising entrants to the mood supplement space, but the evidence base is now substantial enough to take seriously. Multiple randomised controlled trials have found saffron extract to be as effective as low-dose antidepressants for mild to moderate depression, with a more favourable side effect profile. The active compounds crocin and safranal appear to modulate serotonin reuptake. In the context of perimenopause, a 2021 trial specifically in perimenopausal women found significant improvements in mood and reductions in hot flash frequency with 30 mg of saffron extract daily. Saffron is generally well tolerated, though it should be avoided at high doses in pregnancy and is not a replacement for medical treatment in moderate to severe depression.
Magnesium
Magnesium plays a fundamental role in nervous system regulation, and deficiency is associated with anxiety, irritability, and low mood. The connection between magnesium and mood involves its role in GABA receptor function. GABA is the main inhibitory neurotransmitter in the brain, and when GABA activity is reduced, the nervous system becomes more excitable, leading to anxiety and restlessness. Magnesium glycinate is often recommended for mood support because glycine itself has calming properties. Several observational studies have found associations between low dietary magnesium and higher rates of depression. While large-scale trials are still limited, magnesium is inexpensive, safe at standard doses, and commonly deficient in women eating typical Western diets.
Omega-3 Fatty Acids
Omega-3 fatty acids, particularly EPA (eicosapentaenoic acid), have some of the strongest evidence among any supplement for mood support. EPA appears to reduce neuroinflammation, which is increasingly understood as a driver of depression. Meta-analyses of clinical trials consistently find that omega-3 supplementation, with a higher EPA to DHA ratio, produces meaningful reductions in depressive symptoms. For perimenopausal women, omega-3s offer additional benefits for cardiovascular health and joint comfort. A typical dose in mood research is 1 to 2 grams of EPA daily, often from fish oil. Those following plant-based diets can access EPA via algae-based supplements, which also avoid concerns about fish sourcing and heavy metal contamination.
Vitamin B6
Vitamin B6 is essential for the synthesis of serotonin, dopamine, and GABA, and low levels are associated with irritability, anxiety, and low mood. The relationship between B6 and mood has been known for decades, partly through research on premenstrual symptoms where B6 supplementation showed consistent benefit. During perimenopause, when hormonal volatility is high, ensuring adequate B6 may help support neurotransmitter production. Most B-complex supplements contain B6, but it is worth checking the dose, because the form matters. Pyridoxal-5-phosphate (P5P) is the active form and is better absorbed than pyridoxine hydrochloride. Long-term supplementation above 50 mg daily of pyridoxine has been linked to nerve-related side effects, so moderation is sensible.
Ashwagandha and Rhodiola
Adaptogenic herbs offer a different approach to mood support by targeting the stress axis rather than neurotransmitters directly. Ashwagandha has shown reductions in anxiety scores in multiple trials, likely through its effects on cortisol regulation. Rhodiola rosea is better studied for fatigue-related low mood and has shown benefits for burnout, emotional exhaustion, and concentration in several well-designed trials. Both herbs are available as standardised extracts, which is important because herb quality varies widely. They are generally well tolerated but are not recommended for those with certain autoimmune conditions or those taking prescription antidepressants without first consulting a doctor. Using an app like PeriPlan to track mood patterns over time can help you identify whether a supplement is having a real effect.
When Supplements Are Not Enough
It is important to be clear that supplements work best as part of a broader approach. Regular physical activity has a stronger evidence base for mood improvement than most supplements and should be a foundation rather than an afterthought. Sleep quality matters enormously, and addressing night sweats or sleep disruption often produces more dramatic mood improvements than any supplement. If low mood or anxiety is significantly affecting daily life, talking to a GP or mental health professional is the right step. Hormone therapy is also worth discussing with a doctor, as it addresses the hormonal root cause of mood changes in a way that supplements cannot replicate. Supplements sit within a toolkit, not at the top of it.
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