Only RCTs. Only ingredients that delay cognitive decline. Here's everything that made the cut.

Two rules, no exceptions: only placebo-controlled RCTs (the highest tier of evidence), and only ingredients shown to delay cognitive decline, not just produce a short-term bump. Here's exactly what cleared that bar, and the studies behind each one.

The Breakdown

01 · Lion's Mane

Lion's Mane

Three separate placebo-controlled trials, 12 to 49 weeks long. What stands out most: in one of them, the benefits reversed once supplementation stopped, which tells you the effect is real and active, not a fluke.

Mori et al., 200916 weeks · RCT

Significant improvement on a cognitive-function scale vs. placebo. Gains reversed after discontinuation.

Wiley Online Library

Li et al., 202049 weeks · RCT + imaging

Improvements across cognitive assessments, blood biomarkers, and neuroimaging vs. placebo.

Frontiers in Aging Neuroscience

Saitsu et al., 201912 weeks · RCT

Significant improvement in cognitive scores vs. placebo.

J-Stage

02 · Magnesium

Magnesium

The trials cover three forms (glycinate, L-threonate, and oxide), and the benefit shows up across all three. That pattern suggests what actually matters is raising blood magnesium levels, not the specific form. I chose glycinate: the largest body of evidence on efficacy and safety, added benefits for anxiety and sleep, and a price that doesn't punish you for taking it daily.

Liu et al., 201612 weeks · L-threonate

Cognitive improvement in people with existing impairment vs. placebo.

PubMed

Zhu et al., 202012 weeks · Glycinate

Significant cognitive gains vs. placebo; 86% of the benefit in over-65s tracked to reduced methylation at two APOE sites, one independently linked to the strongest known genetic risk factor for Alzheimer's.

PubMed

03 · B Vitamins

B Vitamins (B6, Folate, B12)

This is the one that actually moved the needle on brain structure, not just test scores: it slowed brain atrophy itself.

Smith et al., 2010 (VITACOG)2 years · RCT

The B-vitamin group showed 30% slower brain atrophy than placebo over two years.

PubMed

Douaud et al., 2013 (PNAS)Sub-study · Imaging

Protected the gray-matter regions most vulnerable to Alzheimer's, up to a 7-fold reduction in shrinkage, strongest in those with elevated baseline homocysteine.

PNAS

04 · Lithium Orotate

Low-Dose Lithium Orotate

The one from the next video, and the most surprising evidence in the formula. Most of psychiatry's lithium data uses lithium carbonate at psychiatric doses; this is a fraction of that dose, in the orotate form, and the human trials run far longer than anything else in this category.

Forlenza et al., 2011 / 201912 mo · RCT + follow-up

Reduced cognitive decline and lowered CSF tau vs. placebo, with stability confirmed in extended follow-up.

PubMed

Damiano et al., 202310+ years later

A decade on, those originally given lithium retained substantially better cognitive and functional status.

PubMed

LATTICE (Gildengers et al., 2026)2 years · RCT

Halved the rate of verbal-memory decline vs. placebo, one of the earliest abilities to slip with age.

JAMA Neurology

Nunes et al., 201315 mo · Microdose, 300µg

Even at a microdose, the lithium group held near baseline while the placebo group continued to decline.

PubMed

Most human lithium data uses the carbonate form, so the open question was whether orotate behaves the same way. In animal studies, lithium orotate reaches comparable brain penetration to carbonate. A documented orotate overdose produced a measurable blood lithium level alongside neurological signs, confirming it does genuinely cross into the brain rather than just sitting in an unusually permeable model.