Best Supplements for Perimenopause Mood Changes

Understanding Perimenopausal Mood Changes

If you have noticed that your emotional landscape has changed, that you are more irritable, more anxious, quicker to tears, or simply feel less like yourself, you are not imagining it. Mood changes are among the most commonly reported and least talked about features of perimenopause.

The mechanisms are multiple. Estrogen influences serotonin, dopamine, and norepinephrine, all neurotransmitters that regulate mood, motivation, and emotional regulation. As estrogen fluctuates, these systems fluctuate with it. Progesterone, which also declines during perimenopause, has calming effects on the nervous system through GABA pathways. Sleep disruption compounds everything, since even one night of poor sleep measurably increases emotional reactivity.

The supplements below address specific aspects of these mechanisms. They are not treatments for clinical depression or anxiety disorders, which require professional evaluation. But for the mood variability, irritability, and low-grade anxiety that characterize the perimenopausal hormonal rollercoaster, several have real evidence behind them.

Magnesium Glycinate: The GABA Connection

Magnesium is required for GABA receptor function. GABA is the primary inhibitory neurotransmitter, the one that slows down neural activity and produces a calming effect. When magnesium is low, GABA signaling is less efficient, and the nervous system runs hotter. Anxiety, irritability, and difficulty quieting a racing mind all become more likely.

Magnesium deficiency is common. Chronic stress and poor sleep both deplete it faster. Studies examining magnesium supplementation in people with mood symptoms and poor sleep consistently find improvements in both. One study in perimenopausal women found that magnesium supplementation reduced anxiety and improved sleep quality.

Magnesium glycinate is the form most used in mood and sleep research. The glycine component is itself a calming amino acid that enhances the effect. Studies have examined doses ranging from 200 to 400 mg of elemental magnesium daily. It is best taken in the evening. Serum magnesium tests often look normal even when benefit is real, so clinical response over 4 to 6 weeks is a better indicator than the lab value alone.

Ashwagandha: Cortisol and the HPA Axis

Ashwagandha (Withania somnifera) is an adaptogenic herb with a growing and reasonably solid evidence base for stress reduction. It works primarily by modulating the hypothalamic-pituitary-adrenal (HPA) axis, the central stress response system. During perimenopause, the HPA axis often runs in a state of chronic mild activation due to sleep disruption, hormonal volatility, and the psychosocial stressors of midlife.

Multiple randomized controlled trials have found that ashwagandha supplementation reduces cortisol levels, lowers perceived stress scores, and improves anxiety compared to placebo. Studies have examined doses between 300 and 600 mg of a standardized root extract daily. The KSM-66 and Sensoril extracts are the most studied forms.

Ashwagandha should be used cautiously if you have autoimmune conditions, thyroid disorders, or are pregnant. It interacts with thyroid medications and immunosuppressants. Start with a lower dose and give it at least 4 weeks of consistent use before evaluating whether it is helping.

Saffron: Unexpected but Evidence-Backed for Mood

Saffron is primarily known as a spice, but its active compounds, particularly safranal and crocin, have demonstrated antidepressant-like effects in multiple clinical trials. The mechanism appears to involve serotonin reuptake inhibition, similar in concept to how SSRI medications work, though considerably weaker in effect.

Several meta-analyses examining saffron supplementation have found it significantly reduces symptoms of mild to moderate depression compared to placebo, with effect sizes comparable to low-dose antidepressant medication in some studies. One trial specifically examined perimenopausal women and found improvements in depression and hot flash frequency with saffron supplementation.

Studies have used doses of 30 mg per day of standardized saffron extract. This is a very small amount compared to culinary use. Pure saffron supplements are available, but quality varies widely, as saffron is one of the most adulterated spices in the world. Third-party tested products from reputable brands are important here. Saffron should not be used during pregnancy and may interact with antidepressant medications.

Omega-3 Fatty Acids: EPA Specifically for Mood

Omega-3 fatty acids are divided into two main forms: EPA and DHA. Both are important for overall health, but EPA appears to be the more mood-relevant compound. EPA reduces neuroinflammation, supports serotonin signaling, and has been shown in multiple studies to reduce symptoms of depression, particularly in those with elevated inflammation markers.

The connection to perimenopause is relevant because low-grade inflammation increases during this transition. Inflammatory cytokines interfere with serotonin and dopamine signaling and contribute to mood changes. EPA's anti-inflammatory activity addresses mood via a different pathway than saffron or magnesium, making them complementary rather than redundant.

Look for omega-3 supplements with an EPA-to-DHA ratio of at least 2:1 for mood support. Studies have examined doses of 1 to 2 grams of EPA daily. Fish oil, algal oil (plant-based, from microalgae), and krill oil all provide EPA and DHA. Quality matters: choose products with third-party testing for heavy metals and oxidation.

Vitamin D: The Mood Connection

Vitamin D receptors are found throughout the brain, including in regions involved in mood regulation. Deficiency is associated with higher rates of depression and seasonal mood changes. During perimenopause, when mood is already more variable, having low vitamin D can compound symptoms in ways that are not always recognized.

The evidence that vitamin D supplementation improves mood in people who are deficient is consistent, though the effect in those who are already sufficient is minimal. This makes testing before supplementing particularly useful. A serum 25-hydroxyvitamin D test tells you whether you are in the deficient, suboptimal, or sufficient range.

If you are deficient (below 20 ng/mL), supplementation of 2,000 to 4,000 IU daily is commonly recommended to raise levels, with periodic retesting. Vitamin D3 combined with vitamin K2 is often recommended together, as K2 helps direct calcium appropriately and may reduce cardiovascular concerns at higher vitamin D doses.

B Vitamins: Methylation and Neurotransmitter Production

The B vitamin family is essential for the production of serotonin, dopamine, and norepinephrine. Specifically, B6 is required for converting tryptophan to serotonin, and B12 and folate are both involved in methylation, a biochemical process that is central to neurotransmitter synthesis, DNA repair, and gene expression.

Low B6, B12, or folate can produce mood symptoms that look and feel similar to depression. These deficiencies are more common than widely recognized, particularly in those on plant-based diets, those with digestive issues, or those taking medications like oral contraceptives or metformin that deplete certain B vitamins.

A quality B-complex that includes activated forms (methylcobalamin for B12, methylfolate for folate, and pyridoxal-5-phosphate for B6) is the most practical way to address potential shortfalls. These activated forms work for people with the MTHFR genetic variant that impairs converting standard folic acid into the active form the body uses.

When to See a Healthcare Provider Instead

Supplements can meaningfully support mood during perimenopause when symptoms are driven by nutritional shortfalls, elevated cortisol, sleep disruption, and mild hormonal mood variability. They are not appropriate as a sole treatment for clinical depression or anxiety disorders.

Consider seeking professional evaluation if: your mood changes are severe or significantly interfering with your daily function, relationships, or work; you are having thoughts of self-harm or hopelessness; symptoms have persisted for weeks without any improvement; or if supplements have not helped after 6 to 8 weeks of consistent use.

Hormone therapy, antidepressants at appropriate doses, and therapy (particularly CBT) all have strong evidence for perimenopausal mood management and are appropriate options to discuss with your provider. Supplements work best as part of a broader approach, not as an alternative to clinical care when clinical care is what is needed.

Log your mood daily alongside sleep and symptoms in PeriPlan so you can bring concrete pattern data to your healthcare provider rather than trying to remember how you felt three weeks ago.

This content is for informational purposes only and does not replace medical advice. Always consult your healthcare provider about your specific situation.