Brain Health & Cognitive Aging

Written by Dr. Ryan Kneessi, ND

The mechanisms this protocol supports

Brain cells depend on mitochondria for a constant supply of energy, and their membranes are built from fats such as DHA and from choline. Healthy membranes support synaptic plasticity, which is the brain’s ability to form and strengthen connections.

Methylation keeps homocysteine in a healthy range, and the brain is also sensitive to low-grade inflammation, sometimes called neuroinflammation. Nerve growth factor signaling supports the maintenance of neurons as we age.

Research has linked higher omega-3 status with better cognitive aging, and in the VITACOG trial B vitamins were linked with slower brain atrophy in older adults with mild cognitive impairment who had high homocysteine and good omega-3 status. This protocol supports those mechanisms alongside sleep, exercise and social connection, which matter just as much.

What is in the protocol

The exact products and directions are listed in the Fullscript plan, and here is what each one is commonly used to support.

• ProOmega-D from Nordic Naturals provides the omega-3 fats EPA and DHA along with vitamin D. DHA is one of the main structural fats in the brain.
• Methyl-Guard Plus from Thorne provides active folate, B12 and B6, which support healthy homocysteine metabolism.
• Creatine from Thorne supports the rapid recycling of ATP, the energy currency of muscle and brain cells. Studies have linked it with better short-term memory, and they suggest a possible benefit for older adults and people under stress.
• NeuroMag from Designs for Health provides magnesium L-threonate, a form of magnesium developed to raise magnesium levels in the brain.
• CDP Choline from Klaire Labs provides citicoline, which supplies building blocks for brain cell membranes and the messenger acetylcholine.
• Lion’s Mane from Real Mushrooms provides a mushroom extract with compounds that encourage nerve growth factor in lab research, and small human trials have explored it for mild memory complaints.

Related protocols you may find helpful include Sleep & Overnight Repair and Longevity Foundation.

How to use it thoughtfully

Please talk with your provider before starting, especially if you take medications, are pregnant or nursing, or have a health condition. This page does not list amounts, so follow the label or the specific guidance your provider gives you. When you can, add one product at a time so it is easier to notice how you feel. Sleep, nourishing food, daily movement and stress care are the foundation, and supplements are meant to build on them.

Fish oil may affect bleeding, so tell your provider if you take a blood thinner or have surgery planned. Methylated B vitamins can feel stimulating for some people, so it helps to start slowly. If you have a history of bipolar disorder, please ask your provider before taking methylfolate. New or worsening memory changes deserve a full medical evaluation.

What the research shows

This protocol has not been tested as a whole in a clinical trial, so the studies below cover its main ingredients.

In the VITACOG trial, published in 2010, 271 adults over 70 with mild cognitive impairment took folic acid, B12 and B6 or a placebo for two years, and 168 had brain scans. Brain shrinkage averaged 0.76% a year with B vitamins compared with 1.08% with placebo, and the benefit was larger in people with higher homocysteine. Brain shrinkage is a scan measure, not the same as memory or daily function.

A 2015 follow-up analysis by Jernerén and colleagues found that B vitamins slowed brain shrinkage by 40% compared with placebo only in people with higher blood omega-3 levels, and had no clear effect in those with low omega-3s. This was a secondary analysis, so it suggests the nutrients work together rather than proving it.

Lion’s mane was tested by Mori and colleagues in 2009 in 30 Japanese adults aged 50 to 80 with mild cognitive impairment. Those taking 3 grams a day of mushroom powder for 16 weeks scored higher on a cognitive scale than placebo, but scores dropped again four weeks after stopping. With 15 people per group, this is very early evidence.

Frequently asked questions

Sources

• Tan ZS, et al. Red blood cell ω-3 fatty acid levels and markers of accelerated brain aging. Neurology 2012. PMID: 22371413. https://pmc.ncbi.nlm.nih.gov/articles/PMC3286229/
• Smith AD, et al. Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial. PLoS One 2010. PMID: 20838622. https://pmc.ncbi.nlm.nih.gov/articles/PMC2935890/
• Jernerén F, et al. Brain atrophy in cognitively impaired elderly: the importance of long-chain ω-3 fatty acids and B vitamin status in a randomized controlled trial. Am J Clin Nutr 2015. PMID: 25877495. https://pubmed.ncbi.nlm.nih.gov/25877495/
• Avgerinos KI, et al. Effects of creatine supplementation on cognitive function of healthy individuals: A systematic review of randomized controlled trials. Exp Gerontol 2018. PMID: 29704637. https://pmc.ncbi.nlm.nih.gov/articles/PMC6093191/
• Mori K, et al. Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double-blind placebo-controlled clinical trial. Phytother Res 2009. PMID: 18844328. https://pubmed.ncbi.nlm.nih.gov/18844328/

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