5 Supplements to Support Brain Health in Midlife

If you've ever walked into a room and forgotten why you're there, or struggled to find a word that's right on the tip of your tongue, you're in very good company. Changes in brain health are common in midlife, especially for women navigating perimenopause and menopause. And while brain fog can feel like a personal failing, the research tells a different story.

Brain health is shaped by a combination of lifestyle factors, and many of those are modifiable. This post looks at five supplements with the strongest evidence base for supporting brain health in midlife, plus two emerging options worth knowing about.

Why midlife is the right time to focus on brain health

The biological processes underpinning dementia and cognitive decline can begin decades before symptoms appear. Research consistently shows that midlife is also when lifestyle interventions are most likely to make a meaningful difference. This doesn't mean every memory slip signals something serious. It does mean this is the right time to take brain health seriously, before problems develop rather than after.

Build the foundations first

Before any supplement conversation, it's worth naming what the evidence consistently supports as the most powerful drivers of long-term brain health.

Real food, particularly a diet rich in whole foods, healthy fats, and adequate protein, reduces inflammation and supports neuronal function.

Strength training and regular movement increase blood flow to the brain and support the production of BDNF, a protein critical for neuron health.

Optimal sleep is when the brain clears metabolic waste via the glymphatic system, making it arguably the single most important brain health behaviour of all.

Stress reduction matters too: chronic cortisol impairs memory and hippocampal function over time.

And adequate sunlight, which supports both vitamin D synthesis and circadian rhythm regulation, is consistently underrated in this space.

Supplements work best when these foundations are already in place. They are not a shortcut around the basics; they are a targeted addition on top of them.

5 supplements with evidence to support brain health

1. Omega-3 fatty acids (DHA and EPA)

Omega-3 fatty acids, and in particular DHA (docosahexaenoic acid), are structural components of brain cell membranes. They are the most extensively researched cognitive supplement in the world, and the evidence holds up under scrutiny.

A 2025 systematic review and dose-response meta-analysis of 58 randomised controlled trials found that omega-3 supplementation was associated with significant improvements in attention, perceptual speed, primary memory, visuospatial function, and global cognitive ability in adults. 

The evidence is strongest for people with suboptimal baseline intake, which includes many women who don't eat oily fish regularly. A daily intake of 1,000 to 2,000 mg of combined EPA and DHA from a quality supplement is a reasonable starting point.

Read the study: https://doi.org/10.1038/s41598-025-16129-8

2. Creatine monohydrate

Creatine is best known in fitness circles for its role in muscle power, but it has a compelling second story in brain health. The brain is a high-energy organ, and creatine plays a central role in regenerating ATP (the brain's primary energy molecule), particularly during cognitively demanding periods.

A 2024 systematic review and meta-analysis of 16 RCTs found that creatine monohydrate significantly improved memory and attention in adults. Processing speed also improved significantly. Subgroup analyses found greater benefit in females and those aged 18 to 60, making this supplement particularly relevant for women in midlife.

Creatine is well-tolerated at 3 to 5 g per day and is one of the safest, most well-researched supplements available. It also sits at the intersection of two of Real Life Medicine's core pillars: brain health and muscle health, making it an efficient choice for midlife women.

Read the study: https://doi.org/10.3389/fnut.2024.1424972

3. Magnesium L-threonate

Most forms of magnesium don't cross the blood-brain barrier efficiently, which limits their usefulness for brain health specifically. Magnesium L-threonate is different: it was developed with the specific goal of elevating magnesium concentrations within the brain, and the research supports that it achieves this.

A 2026 randomised, double-blind, placebo-controlled trial in 100 adults found that six weeks of Magnesium L-threonate  was associated with a 7.5-year estimated reduction in cognitive brain age, along with significant improvements in overall cognitive performance, working memory, episodic memory, and reaction time.

Participants with poor sleep also showed improvements in sleep-related impairment 

If you're already taking a standard magnesium supplement, know that the form matters here. Magnesium L-threonate is a distinct product and won't be labelled the same as magnesium glycinate or oxide.

Read the study: https://doi.org/10.3389/fnut.2025.1729164

4. Bacopa monnieri (brahmi)

Bacopa monnieri, also known as brahmi, has been used in Ayurvedic medicine for cognitive support for centuries, and modern research is building a solid evidence base behind it. Its active compounds, the bacosides, appear to support synaptic repair and nerve transmission.

A meta-analysis of nine randomised controlled trials in 518 adults found significant improvements in speed of attention:  Bacopa's primary benefit seems to be is in the speed and efficiency of cognitive processing 

Read the study: https://doi.org/10.1016/j.jep.2013.11.008

A more recent 2026 network meta-analysis of 29 RCTs also found that high-dose Bacopa (600 mg or more per day) significantly outperformed both Ginkgo biloba and placebo for working memory and short-term memory

The main practical caution is gastrointestinal side effects at higher doses - taking it with food helps.

5. Ginkgo biloba (EGb 761)

Ginkgo biloba is one of the most widely used cognitive supplements globally, and the evidence base is substantial, though more nuanced than many people realise. The standardised extract EGb 761 is the form used in clinical research, and its mechanisms include antioxidant activity, anti-platelet effects, and improved cerebral blood flow.

A 2026 Cochrane systematic review of 82 RCTs involving more than 10,600 participants found that for people with existing dementia, there may be small to moderate benefits at six months for global clinical status, cognition, and activities of daily living.

For people with mild cognitive impairment, the evidence suggests Ginkgo probably has little to no effect on global status or cognition at six months 

For women in midlife without existing cognitive impairment, Ginkgo's evidence base is less compelling than that of omega-3 or creatine.

It is best positioned for women who already have subjective memory complaints or early cognitive decline.

One important safety note: Ginkgo interacts with anticoagulant medications, so speak with your GP before starting it if you are on blood thinners.

Read the study: https://doi.org/10.1002/14651858.CD013661.pub2

Two emerging options worth knowing about

Lion's mane mushroom (Hericium erinaceus)

Lion's mane has a mechanism unlike any other supplement on this list. Its bioactive compounds, hericenones and erinacines, appear to stimulate nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF): proteins that govern the growth, maintenance, and survival of neurons.

A 2025 systematic review of clinical and laboratory evidence confirmed neuroprotective, anti-inflammatory, and antioxidant properties, with evidence supporting improvements in cognitive assessment scores in adults with mild cognitive impairment, and emerging benefits for mood, anxiety, and sleep 

Human RCT evidence is still limited in scale, but the safety profile is generally good. Lion's mane is particularly appealing for women who want support for mood and stress resilience alongside brain health, given the NGF pathway's role in the limbic system.

NAD+ precursors (NMN and NR)

NAD+ (nicotinamide adenine dinucleotide) is a coenzyme essential for energy production, DNA repair, and mitochondrial function, and levels decline by roughly 50% between the ages of 40 and 60. Supplementing with NAD+ precursors such as NMN aims to restore these levels.

The animal evidence is compelling across multiple disease models, including Alzheimer's disease, vascular dementia, and age-related cognitive decline 

Human clinical trial data is emerging but not yet at the level of omega-3 or creatine for cognitive outcomes 

Use all supplements Wth Caution

Supplements deserve the same respect as pharmaceutical medications. They all have interactions and dosage requirements. Please remember to tell your doctor and pharmacists about any supplements you may be taking.

About us

We are Dr Mary Barson and Dr Lucy Burns, the founders of Real Life Medicine. We help women who have been on every diet under the sun optimise their health without feeling miserable or deprived.

We do this with our three-step framework:

• Strategies to improve your metabolism
• Brain-based skills to overcome self-sabotage
• Tools to make it easy to implement

With this comes increased energy, vitality, and confidence. At Real Life Medicine, we believe in the power of small steps. You don't have to do all the steps at once.

We go further into this in My Metabolic Action Plan (MyMAP).

This step-by-step programme is the map to improved metabolic health that not only supports weight loss and increases your energy levels and mood, but also helps reduce the risk of chronic disease in the future.

Find out more about My Metabolic Action Plan

This content is for general information purposes only and does not constitute medical advice. Please speak with your healthcare provider before making changes to your healthcare.