Cheap supplements really CAN protect your brain from dementia, says top neurologist DR DAVID PERLMUTTER. Here's what to take, how to tweak your diet - and what to ask your doctor

Drug companies have spent billions over the past two decades in the hunt for an Alzheimer’s ‘magic pill’ – a medication that will truly alleviate this terrible disease.Largely, though, these efforts have been unsuccessful because – as I discussed last week in the first part of an exclusive adaption of my new book, Brain Defenders – researchers have been focused on the wrong thing.Rather than effective treatment for Alzheimer’s requiring the removal of sticky beta-amyloid plaques in the brain – as we have been told ad nauseam – it is the excessive activation of the brain’s specialised immune cells, called the microglia, that’s far more significant.Microglia, which are found in the brain and spinal cord, normally exist in their M2 state where they clean up dead cells, fight infections and help keep brain tissue healthy.But they can be overly triggered by a number of factors – eg ageing, infection, poor diet and lifestyles that drive gut inflammation which passes up to the brain – that transform them into their M1 state.This transformation can lead to a cascade of consequences inside the brain, with M1 microglia attacking the cells and synapses (tiny gaps between the nerve cells which allow them to pass messages between each other) as well as causing those beta-amyloid plaques.Excitingly, however, as well as being positively influenced by lifestyle changes – such as regular exercise and a high-fibre, low ultra-processed food (UPF) diet – there is growing evidence that microglia can also be optimised through some medications, many available already.These drugs span a broad range of categories, including those used in diabetes treatment, such as metformin; immunomodulators (which stimulate or suppress immune function to prevent organ rejection in transplants); and antidepressants. By strategically using supplements, you can fill gaps in your nutrition and give your microglia an extra edge, says Dr David Perlmutter Dr Perlmutter, a US neurologist, recommends some medications that optimise microgliaWhile much of this research remains in its early stages, it highlights the intense focus on microglial optimisation as a promising avenue for future Alzheimer’s prevention and treatment. Aside from these medications, research also indicates that common dietary supplements can drive healthier microglia activity.Of course, I’m not suggesting that you can out-supplement poor diets which are strongly linked to microglia activation. Nor am I saying you should consider taking clinical medication for any other purpose than your doctor has prescribed.But – as a neurologist of more than 40 years standing, who specialises in treating people with Alzheimer’s and other neurodegenerative diseases – I am truly encouraged by the potential the drugs and supplements detailed below have in the fight against Alzheimer’s.Here, then, is my deep dive into the most promising medication being researched in this field – as well as the variety of supplements you can choose from (perhaps taking one or two after consulting with your doctor) to safeguard and enhance your brain function by protecting your microglia.Medication Metformin Metformin gained prominence in the 1950s as a treatment for type 2 diabetes.Initially thought to work by reducing glucose production in the liver, further research has revealed it has positive effects on turbo-charging our mitochondria, the tiny energy powerhouses inside our cells, which help keep our microglia in the supportive M2 state.Metformin also boosts our cells’ insulin sensitivity, preventing glucose levels building up in the blood.This helps reduce microglial overactivation, thus aiding cognitive enhancement.Studies, including one published in 2024 in the journal Clinical Diabetes and Endocrinology, show a link between metformin and a reduced risk of dementia. In the US a series of nationwide clinical trials at 14 leading research institutions, involving 3,000 people aged 65 to 79, is expected to get under way soon.Set to last six years and called the Targeting Aging with Metformin (TAME) trial, it’s designed to explore metformin’s potential as an anti-ageing drug – part of which being its impact on Alzheimer’s.I believe the trial’s findings are likely to find metformin a prime candidate for preventing age-related cognitive decline.GLP-1 agonistsWithout question, the biggest pharmaceutical game changer recently is GLP-1 agonist drugs such as Ozempic.As well as reducing appetite, the profound ability of the drugs to change the shape and function of microglial cells for the better is nothing short of miraculous.A 2023 study in the International Journal of Medical Sciences showed GLP-1s directly bind to microglia and reduce their activation, thereby decreasing the release of damaging pro-inflammatory cytokines – small proteins which act as chemical messengers – which can then cause inflammation in the brain (neuroinflammation), which is linked to Alzheimer’s as it triggers the creation of M1 microglia.There is also evidence these drugs increase levels of BDNF (brain-derived neurotrophic factor), a protein which acts as a kind of fertiliser for our neurons (brain cells).A notable 2024 study published in Alzheimer’s & Dementia analysed medical records of more than one million patients with type 2 diabetes – it revealed that those treated with Ozempic had a significantly lower risk of being diagnosed with Alzheimer’s compared to those on other diabetes medications.Further supporting these findings, a clinical trial led by Imperial College London in 2024 investigated the effects of liraglutide (brand name Saxenda) on patients already diagnosed with mild Alzheimer’s.Participants who received daily liraglutide injections for more than a year exhibited 18 per cent less cognitive decline and a 50 per cent reduction in brain cell loss, compared to the placebo group. These results indicate that GLP-1 drugs may slow neurodegeneration in Alzheimer’s patients.All this said, however, we should remember that GLP-1 is an impressive hormone produced naturally in our body.Dietary changes – such as eating high-fibre foods, reducing sweeteners and added sugars and UPFs – can promote healthy GLP-1 levels without medication. However, if GLP-1s are officially proven to have meaningful effects in treating diseases such as Alzheimer’s or Parkinson’s, then yes, I am very much all in for them being used clinically.Minocycline A commonly used antibiotic, minocycline has garnered attention for its anti-inflammatory properties.Recently, it’s been found to inhibit the activation of microglia, thereby reducing damaging neuroinflammation.A 2024 Chinese study on mice demonstrated that minocycline effectively protected microglia from adopting their damaging M1 phenotype, even when challenged with a powerful pro-inflammatory stimulus (in this case, a compound called lipopolysaccharide, a standard way of creating inflammation in a research setting).Dimethyl fumarate This is an oral medication approved for the treatment of MS. Dimethyl fumarate (brand name, Tecfidera) – it works by activating the NRF2 signalling pathway in the brain which, when under stress from toxins, switches ‘on’ defence systems that reduce inflammation and help regulate the immune system in the brain by targeting M1 microglia.This helps MS but may also assist Alzheimer’s.Supplements By strategically using supplements, you can fill gaps in your nutrition and give your microglia an extra edge.Always consult with a healthcare professional before starting any new supplement, especially if you have underlying health conditions or take medications.Here are some of the most important of the supplements that I think are worth considering (you’ll find another 15 in my book).Omega 3 The most useful omega 3 is docosahexaenoic acid (DHA), an essential fatty acid.DHA makes up as much as 20 per cent of the brain’s total fat content, where it serves as a key structural component of neuronal membranes and enhances communication between brain cells. It has powerful anti-inflammatory properties, helping to reduce chronic neuroinflammation by supporting microglia.DHA also boosts BDNF – lower levels of this correlate with Alzheimer’s risk. This may explain how DHA protects against age-related cognitive decline, as suggested in a 2017 study in mice in the journal Scientific Reports.For optimal brain health, studies suggest a daily intake of 1,000 to 2,000 mg of DHA. The best supplemental source is cod liver oil. For vegetarians, there is an algae-based alternative.The best dietary sources include wild-caught fatty fish (salmon, sardines, mackerel). Interestingly, farmed Atlantic salmon may have higher levels of DHA than wild – around 1,700 mg per 100g serving. Free range eggs may contain 100 to 150mg of DHA per egg.Creatine Creatine helps shuttle energy to areas where demand is greatest, such as the brain’s synapses. It also enhances our mitochondria, which helps microglia remain in a supportive M2 state. In a 2025 pilot study, researchers at the University of Kansas Medical Center administered 20g of creatine per day for eight weeks to 19 Alzheimer’s patients. Testing revealed statistically significant improvements in participants’ cognitive abilities.Future studies with larger sample sizes and control groups are warranted but, for now, this research offers exciting preliminary evidence that improving the brain’s energy production machinery holds promise in the fight against Alzheimer’s disease. Dosage is around 5g a day, with a maximum of 10g.Anyone with kidney disease or who takes nephrotoxic drugs (ie drugs that can affect kidney function, which includes some cancer drugs, antibiotics and immunosuppressants) should first consult a doctor.Magnesium A mineral that supports hundreds of biochemical reactions, including nerve and muscle function, magnesium also helps with relaxation and stress reduction, which indirectly benefits microglia by enhancing mitochondrial function.There are several types of magnesium but magnesium threonate is thought to be best for cognition as it also contains L-threonic acid, a compound which helps the magnesium travel from the gut into the brain.Dietary sources include leafy greens, nuts and wholegrains. Dosage is 200 to 400mg daily, while those with kidney disease, who are pregnant or have a heart condition should first consult their doctor.Probiotics Given what we know about the connection between the gut microbiome and the brain, and its influence on our microglia – in brief, a deficient gut microbiome has been proven to provoke inflammatory symptoms in your brain – taking a high-quality probiotic makes sense.Look for a product that contains a wide array of different strains with a high CFU (colony forming unit) count, which indicates the live bacteria content, of at least 50 billion. Some people experience mild bloating or gas but these generally resolve with continued use.MitoQ10 This is a synthetic form of the antioxidant coenzyme Q10, which is produced naturally by the body, and has been designed to protect mitochondria. Early studies suggest it can reduce neuron death in Alzheimer’s. Dosage is 10mg per day. Possible side-effects include nausea. Check with your doctor before taking it if you are pregnant or have kidney, liver or heart issues.Sprouted Himalayan tartary buckwheat A true ‘superfood’, sprouted Himalayan tartary buckwheat is rapidly gaining attention for its exceptional health benefits, thanks to its rich polyphenol content, which act as powerful antioxidants, supporting mitochondria.In a pilot study published in Frontiers of Nutrition in 2024, participants consuming a polyphenol-rich supplement derived from Tartary buckwheat for 90 days exhibited significant improvements in epigenetic (tiny changes within the body that turn genes on and off) age markers and immune cell profiles. Dosage is one teaspoon daily. Polyphenols may interact with statins, certain antidepressants and immunosuppressant medications.Adapted from Brain Defenders by David Perlmutter (Yellow Kite, £18.99), to be published August 27. © David Perlmutter 2026. 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