By Dale Bredesen, MD

Step one of enhancing your brain is enacting the fundamental protocols for preventing cognitive decline: a clean diet, abundant exercise, high-quality sleep, and avoidance of chronic stress (in contrast, acute stress with resolution is not nearly as damaging, and may actually be supportive—a process called hormesis).

Additionally, brain-training programs are both fun and useful for honing your thought process. BrainHQ is the program with the most scientific support, and this includes many programs for memory, processing speed, executive function, and other cognitive skills. Other options include Elevate, Dakim BrainFitness, and Lumosity, among others. For many people, especially teenagers, 20-somethings, and 30-somethings, these actions may be enough.

You can tell based on a cognoscopy—blood tests that evaluate the critical parameters for cognition and cognitive risk, coupled with an easy online cognitive screen such as CNS Vital Signs or Cogstate. There is increased risk after age 40 for impaired cognition, so more aggressive interventions may be called for.

Step two of enhancing your brain involves enlisting a personalized array of nootropic (cognitive enhancing) agents, many of which have multiple mechanisms of action.

A Brain-Enhancing Pharmacopoeia

Enhancing neurotransmission by acetylcholine: This neurotransmitter is critical for conveying messages between and from neurons. Supplements that may assist its work include huperzine A (derived from Chinese club moss, Huperzia serrata), Bacopa monnieri (also known as brahmi, a traditional Indian medicinal plant), citicoline, alpha-GPC, and lecithin, an essential fat found in many foods, including eggs. 

Enhancing cyclic AMP:  Adenosine monophosphate (AMP) is an important messenger for brain plasticity. Caffeine, an adenosine inhibitor, boosts cyclic AMP, as does L-theanine—an amino acid found in tea and certain mushrooms.

Optimizing glutamatergic vs GABAergic transmission: Glutamate is the most common neurotransmitter in the body. Gamma-aminobutyric acid (GABA) suppresses excess signaling by neurons. An overabundance of glutamate over GABA is associated with anxiety, depression, restlessness, inability to concentrate, headaches, insomnia, fatigue, and increased sensitivity to pain. You can restore balance with valerian (a medicinal root extract), vitamin B6, and lemon balm, and by taking GABA directly.

Supporting mitochondrial function: Mitochondria are the energy production units (organelles) inside the cells of your body. They are critical to cognition and indeed to all metabolism. Endogenous ketones, derived from breaking down your adipose tissue, are converted to acetyl-CoA and metabolized by mitochondria. Exogenous ketones (such as ketone salts or esters) also provide energy, but lack some of the advantages of endogenous ketones, such as the associated anti-inflammatory effect. The goal is to create metabolic flexibility, so that your mitochondria can metabolize either carbohydrates or fats/ketones.

Even More Useful Supplements

Useful supplements include ubiquinol (also sold as coenzyme Q10, or CoQ10), PQQ (pyrroloquinoline quinone, which increases mitochondrial number), R-lipoic acid (an antioxidant and enabling molecule also found in spinach and broccoli), ALCAR (acetyl-L-carnitine—a metabolism-supporting amino acid), creatine (which provides energy), and nicotinamide riboside—a form of vitamin  B3 that increases NAD+ (nicotinamide adenine dinucleotide). Methylene blue holds promise as another method to enhance mitochondrial function.

Supporting neurotransmission by dopamine: In the brain, dopamine is a primary signaling molecule that is especially associated with the “reward” pathway that reinforces certain behaviors; loss of dopamine-producing cells contributes to Parkinson’s disease. Supplements that may aid dopamine production include tyrosine and phenylalanine (two essential amino acids), and vitamin B6.

Supporting synaptic structure: A healthy brain depends on a robust cellular infrastructure. To help maintain the physical condition of your neurons, try citicoline and its chemical relative, alpha-GPC (glycerylphosphorylcholine), as well as DHA (docosahexaenoic acid)—an omega-3 fatty acid found in fish, especially cold-water fish.

Improving mental focus: Supplements that may help sharpen your thinking include gotu kola (a traditional Chinese and Ayurvedic herb), shankhpushpi (an Ayurvedic medicine), and pantothenic acid (vitamin B5). Additionally, many people report success from therapeutic hot/cold treatment, alternating between a hot sauna and cold water to stimulate the sensory response and also enhance mitochondrial function.

Enhancing brain-derived neurotrophic factor (BDNF): This essential protein promotes the formation and maintenance of neurons in the body. You can boost your BDNF with whole coffee fruit extract (WCFE) and dihydroxyflavones (7,8-DHF).  There is also a simple and pleasurable technique that boosts BDNF while providing many other physical and psychological benefits—exercise—and there are some enhancements of exercise, such as EWOT (exercise with oxygen therapy) and KAATSU—a technique that uses bands to increase the physiological response to exercise). 

Enhancing nerve-growth factor (NGF): Along with BNDF, NGF is critical to the growth, maintenance, and survival of nerve cells. NGF-promoting supplements include Hericium erinaceus (lion’s mane mushroom), ALCAR, and specific strains of bacteria in the gut microbiome (eg, some bifidobacteria), which can be boosted by taking probiotics.

Enhancing sirtuin 1 (SIRT1): Recent research indicates that this protein stimulates autophagy and provokes an antiaging response in laboratory animals. It is being explored more broadly as an antiaging mediator, and it also enhances the synaptoblastic (anti-Alzheimer’s) signaling of the amyloid precursor protein, APP. You can increase SIRT1 function by taking resveratrol (found in grapes and red wine, but also in many berries), nicotinamide riboside, NMN (nicotinamide mononucleotide, a derivative of niacin), and NAD+. You can also stimulate your body’s production of NAD+ with exercise and fasting.

Promoting blood flow: Ginkgo has been shown to increase blood flow by stimulating production of nitric oxide, which dilates the blood vessels. Nitric oxide can also be increased by L-arginine, Neo40, beetroot extract, and arugula.

Improving mood: In some cases, you can go straight to the desired effect—and do it without the common drugs that have significant side effects. Saffron is a natural antidepressant; it appears to work by increasing serotonin levels. Lemon balm has also been shown to be effective.

Reducing chronic stress: Acute stress, with resolution, is something we all deal with, and it does not impede cognition. However, the unrelenting chronic stress that so many of us experience is associated with brain atrophy. There are many methods to address this, from meditation to yoga to social interactions (admittedly more difficult during the pandemic) to music to shinrin-yoku (the Japanese technique of “forest bathing”), and others—whatever brings you joy, relaxation, and fulfillment.

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Dale Bredesen, MD, is internationally recognized as an expert in the mechanisms of neurodegenerative diseases such as Alzheimer’s disease, and the author of the New York Times bestsellers The End of Alzheimer’s (Avery, 2017) and The End of Alzheimer’s Program (Avery, 2020). He has held faculty positions at UC San Francisco, UCLA, and the University of California San Diego, and directed the Program on Aging at the Burnham Institute before coming to the Buck Institute for Research on Aging in 1998 as its founding president and CEO. He is currently a professor at UCLA.

Adapted and reprinted with permission from The First Survivors of Alzheimer’s, by Avery, an imprint of Penguin Publishing Group, a division of Penguin Random House, LLC. Copyright © 2021 by Dale Bredesen, MD.