How does one study the effect of a dietary supplement on cognition? I've really enjoyed this talk by Molly Crockett: Beware neuro-bunk. The speaker outlines the limitations of modern neuroscience when accessing the effectiveness of dietary supplements intended to enhance cognition. I believe the speaker mentioned that 68% of (americans?) take dietary supplements for a variety of reasons.

I've done some research, and these compounds typically go into "neuro enhancing" products:


DMAE
GABA
N-Acetyl-L-Tyrosine
Vinpoceitine
5-HTP
Vitamin B complex


This got me thinking: How does one assess the effectiveness of dietary supplements on cognition? These are low- dose compounds that may be taken at random times of a day, combined with assorted other supplements. How does one study the effects of something like that? Is there a "gold standard" study that I can take a look at to understand how this is done?

What I'm interested in is how do they account for the time of day, and other supplements/drugs/activity that happened and followed the study.

When thinking about "real psychoactive drugs", their effect is much more profound, and thus easier to study, with a fairly well defined  onset times, intensity curves. For example, I can go to erowid.org and see curves like the one below for





With a graph like that, one can with a reasonable certainty estimate the duration and intensity of effects. But what about dietary supplements? Is it just big placebo?
To the general question of how to test the claims , there's a couple things you want to show:


1) that the body absorbs the supplement (measure the absorption rate)
2) that the supplement crosses the blood brain barrier 
3) that the
supplement actually plays the role of agonist, antagonist, or
allosteric modulator (or possibly even has a toxic effect).  These
are biochemical roles that depend on molecular properties like shape
and charge distribution, as well as kinetic interactions (chemistry).
4) that the interaction of the ligand or effector (or toxin) with the
receptor (or system) that's being affected by the supplement produces
a cognitive benefit.


The first three are feats of biochemistry, the fourth of behavioral/psychological biology.  So this is a complicated interdisciplinary task in the first place.  Now if we want to consider all the control situations (especially 4) it becomes even more complicated.

Known cognitive benefits are come from substances like caffeine, nicotine, chocolate (it has theobromine), amphetamines, and other stimulant-like drugs.  

GABA, on the other hand, exists naturally in the brain.  It's part of an integrated molecular system and is tightly controlled by the citrus cycle (aka Krebs Cycle) and the GABA shunt.  If you have more of it, but you don't need it, your body will just break it down or convert it (it's part of a very dexterous set of metabolic molecules).

The best cognitive benefit you can get is simply from eating right, not having nutrient deficiencies, omega 3's are good for long-term brain health.  Circulatory health is good for long-term brain health (so exercise and less cholesterol).  Pretty much all your typical healthy habits.  Most of the evidence for the nutrititional/exercise claims I provided in this thread