→What causes brain fog →What the evidence shows →Beyond supplements →Frequently asked questions →References

Oestrogen fluctuation

Oestrogen supports serotonin, dopamine, and acetylcholine activity, promotes neuronal energy metabolism, and has anti-inflammatory effects in the brain. As it fluctuates unpredictably during perimenopause, cognitive function can feel inconsistent from day to day. Neuroimaging research has documented transient changes in brain metabolism and white matter integrity during this transition (Mosconi et al., Scientific Reports, 2021). A 2025 systematic review of 82 neuroimaging studies confirmed that oestrogen levels are consistently linked to changes in brain network structure and function across the menstrual cycle, puberty, postpartum, and the menopausal transition, with particular plasticity in the hippocampus and amygdala (Ruehr et al., Frontiers in Neuroendocrinology, 2025).

Sleep disruption

Poor sleep impairs memory consolidation, attention, and information processing. Sleep disruption is common during perimenopause and is one of the most significant contributors to brain fog. Addressing sleep is often the most impactful first step.

Increased neuroinflammation

Oestrogen has anti-inflammatory effects in the brain. As it declines, low-grade neuroinflammation can increase, contributing to cognitive symptoms.

Nutritional gaps

Deficiencies in vitamin D, B vitamins, magnesium, and omega-3 fatty acids are all associated with cognitive symptoms. In perimenopausal women, where overall nutritional demands shift, these gaps become more clinically relevant.

The brain uses creatine as a rapid energy buffer via the phosphocreatine system. When neurons are under metabolic stress, including from sleep deprivation or hormonal change, adequate brain creatine helps maintain cognitive performance.

The most notable recent development is the CONCRET-MENOPA trial (Korovljev et al., Journal of the American Nutrition Association, 2025), the first RCT to examine creatine specifically in perimenopausal and menopausal women with brain fog. It is worth being precise about what it tested: 36 women were split across a low-dose creatine hydrochloride group (750mg daily), a medium-dose creatine hydrochloride group (1,500mg daily), a combined creatine hydrochloride plus creatine ethyl ester group (400mg of each), and placebo, over 8 weeks. The medium-dose creatine hydrochloride group showed the clearest benefit: significantly improved reaction time, a 16.4% increase in frontal brain creatine levels, favourable changes in lipid profiles, and a trend toward reduced mood swings, compared with placebo.

This trial used creatine hydrochloride, not the more widely available and researched creatine monohydrate, and at doses (750 to 1,500mg daily) considerably lower than the 3 to 5g daily typically used in monohydrate research. Whether creatine monohydrate at standard doses produces the same effect on brain fog specifically in perimenopausal women has not been directly tested. Separately, a systematic review and meta-analysis of creatine supplementation more broadly, predominantly using monohydrate at standard doses across various populations, found modest benefits for memory (Prokopidis et al., Nutrition Reviews, 2023), and a separate trial found that a single, very large dose of creatine monohydrate (0.35g per kg body weight, taken once, well above a typical daily dose) improved cognitive performance during acute sleep deprivation in young adults (Gordji-Nejad et al., Scientific Reports, 2024). That trial does use monohydrate, but the single-bolus dosing approach is different again from either the CONCRET-MENOPA protocol or standard daily supplementation, so it doesn’t directly resolve the form-and-dose question either. Together this builds a reasonable, genuinely encouraging case for creatine and cognition, but the specific form, dose, and population match matters, and it is too early to say monohydrate at standard daily doses replicates what the CONCRET-MENOPA trial found in this population.

DHA is the primary structural fatty acid in brain cell membranes, essential for neuronal integrity and synaptic function. A 2022 systematic review found generally positive effects of omega-3 supplementation on cognitive function in adults (Dighriri et al., 2022), though perimenopause-specific trial evidence is limited. Given that omega-3 also supports cardiovascular health, it is one of the more broadly relevant nutrients for this life stage. We cover the evidence, forms, and product options in detail in our omega-3 guide.

Magnesium L-threonate is specifically formulated to cross the blood-brain barrier more effectively than other magnesium forms. Preclinical studies showed significant increases in brain magnesium concentration and cognitive improvements. Human trials have been positive for memory and cognitive clarity, though the evidence base remains smaller in scale than for magnesium glycinate and sleep, which we cover in our magnesium guide. L-threonate is a distinct form aimed at cognitive support rather than sleep specifically.

B vitamins, particularly B12, B9, and B6, are essential for neurotransmitter synthesis and homocysteine regulation. B12 deficiency is a directly reversible cause of cognitive symptoms. The evidence is clearest where deficiency is present rather than as a general cognitive enhancer. B12 deficiency is more common in women on plant-based diets, those taking metformin, or those with gut absorption issues.

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Lion’s Mane contains compounds that stimulate nerve growth factor (NGF) synthesis in preclinical research, which is mechanistically relevant to neuroplasticity, though this does not on its own establish a cognitive benefit in humans. Human evidence is still limited. A small double-blind pilot study found improvements in stress and cognition over 28 days in young adults with self-reported cognitive difficulty (Docherty et al., Nutrients, 2023), but this was a small, preliminary study rather than a large confirmatory trial, and there is no perimenopause-specific research on Lion’s Mane. Product quality also varies considerably between brands, with many products using mycelium-on-grain fillers that substantially dilute the active compounds rather than whole fruiting body extracts. On the current evidence, Lion’s Mane is best considered an area of ongoing research rather than an established option.

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Is perimenopause brain fog permanent?

For most women, no. Research tracking cognitive function through the menopausal transition consistently shows that function tends to restabilise in post-menopause. Brain fog during perimenopause is typically transient and related to hormonal fluctuation rather than permanent cognitive decline.

Should I try creatine for brain fog, and if so, which form?

This is genuinely unresolved. The only trial in perimenopausal and menopausal women specifically (CONCRET-MENOPA) used creatine hydrochloride at 1,500mg daily, not the more commonly available creatine monohydrate at the 3 to 5g doses used in most other creatine research. Creatine generally has a strong safety record across decades of research in both men and women, and the CONCRET-MENOPA trial reported no severe adverse effects at any dose tested. But because of the form and dose mismatch, we are not able to point to a specific, evidence-matched product recommendation for brain fog specifically. If you want to explore this, discussing it with your GP or healthcare provider, and being clear-eyed that you would be extrapolating beyond what has actually been tested, is the honest starting point.

What is the difference between magnesium glycinate and magnesium L-threonate?

Magnesium glycinate is best for sleep, anxiety, and general magnesium repletion. Magnesium L-threonate is specifically formulated to cross the blood-brain barrier and is aimed at cognitive support rather than sleep. They address different goals and can be taken alongside each other.

How long before nutrient changes make a difference to cognitive symptoms?

In the CONCRET-MENOPA trial, benefits from creatine hydrochloride were measured after 8 weeks of daily use. B vitamins may show effects within a few weeks where a genuine deficiency is present. Magnesium L-threonate human trials have generally used durations of 4 to 12 weeks. Consistency matters more than timing, and addressing sleep and blood sugar alongside any supplement tends to produce more noticeable results than a supplement alone.