1. A Comparative Analysis of Prevagen® Supplementation and Current Nootropic Agents
Collin Belk, Kelly Ferris, Kirsten Carstarphen, Jace Engstler, Dr. David Roman
Background:
Manufactured & Marketed by Quincy Bioscience starting in 2007
Claims to improve memory and support healthy brain function, sharper mind, and clearer thinking
Available as oral capsules & chewables
Regular (10 mg) & Extra-Strength (20 mg) options
In 2017, the FTC and N.Y. Attorney General files lawsuits against Quincy Bioscience for promoting false claims for Prevagen
Quincy's annual revenue has grown 234% from 2009 to from $5.3 million to $17.8 million
Prevagen: Active Ingredient and MOA
Apoaequorin, a calcium-binding protein found in jellyfish
Proposed MOA: Limit age-related calcium-mediated toxicity of neurons through regulation of intracellular calcium homeostasis
Prevagen: Biological Plausibility
Pharmacokinetic limitations
Digestion
Bioavailability
Blood-Brain Barrier
ISL - AD8 0-2
Apoaequorin
10.86%
t56=4.40
p<.001
Control
3.79%
t32=1.059
p=.298
ISL-DR – AD8 0-2
15.82%
t56=3.010
p=.004
7.41%
t32=1.202
p=.238
ISL-DR – AD8 2-5
13.74%
t42=4.913
8.14%
t36=1.423
p=.163
Modafinil
FDA-approved for treatment of narcolepsy, obstructive sleep apnea and shift work sleep disorder
Drug Class: Central Nervous System Stimulant
MOA: Exact mechanism unknown. Binds to dopamine transporter, thereby inhibiting dopamine uptake
Nootropic Properties:
Molecular weight: 273 kDa
LogP: 0.6
Consistently shown to enhance executive functions, including decision making, planning and fluid intelligence
Inconsistent results observed for short-term memory and learning tasks
Madison Memory Study
Study Design
Randomized, double-blind, placebo controlled
Population
N: 218, aged years old
Cognitive function: AD8 screening test
Normal: 0-2
Impaired: 2-5
Intervention
90 days
1 oral capsule of 10 mg apoaequorin daily
Computerized testing sessions at baseline, day 8, day 30, day 60 and day 90
International Shopping List (ISL)
International Shopping List - Delayed Recall (ISL-DR)
Comparison
1 size and color matched placebo capsule daily
Same computerized testing sessions
Outcome
Change in performance on tasks from baseline to day 90 on:
ISL
ISL-DR
Madison Memory Study: Limitations
Subjective bias and conflicts of interest
Did not directly compare apoaequorin to placebo to show it worked better
Paired t test degrees of freedom different than what would be expected
Did not provide evidence or rationale for apoaequorin’s mechanism in reaching therapeutic target
Donepezil
FDA approved in 1996 for treatment of mild, moderate & severe Alzheimer’s Disease
MOA: Acetylcholinesterase inhibitor
Nootropic Properties:
Good bioavailability & BBB Penetration
Small molecule ( kDa)
LogP 3.6
Shown to have mild improvements assessed cognitive function in Alzheimer’s patients
Inconsistent results in several studies on healthy adults
Amphetamine Salts/ Methylphenidate:
FDA approved in 1996 for the treatment of ADHD
Known as “smart pills” and are believed by many to enhance cognitive ability
MOA: Blocks reuptake of norepinephrine and dopamine and increases their release into extraneuronal space
Results of over 40 laboratory studies consisting of healthy non-elderly adults assessed three types of cognition and concluded the following:
Learning: some enhancement
Working Memory: Some enhancement for lower performers
Cognitive Control: some benefit but limited support for general population
Future Directions:
Study Objectives:
Evaluate claims made about Prevagen by Quincy Bioscience, and determine if these claims are scientifically supported
Compare FDA approved drug targets for nootropic agents and their biologic plausibility compared to Prevagen
Exploration of other natural products used to enhance memory/cognition
What are the current recommendations in the community?
How do pharmacists in this practice setting handle this question?
Community pharmacists’ input on Prevagen
Methods:
Literature review utilizing PubMed
A comparison of nootropic agents, mechanisms of action, pharmacological basis and how it relates to Prevagen’s proposed mechanism and biochemical properties
Effects of commonly used cognitive enhancers such as caffeine and drugs of abuse.
What pharmacies endorse the sale of Prevagen or other “memory enhancing” supplements