Huperzine A: A Natural Nootropic

Huperzine A is a compound, specifically a naturally occurring sesquiterpene alkaloid, that functions as an acetylcholinesterase inhibitor. If that seems like a bunch of big words, don’t worry, we’ll translate in a moment.

First, a nod to its origins: it is found in certain kinds of firmoss, especially the “toothed clubmoss”, Huperzia serrata, which grows in many Asian countries.

What’s an acetylcholinesterase inhibitor?

Let’s do this step-by-step:

• An acetylcholinesterase inhibitor is a compound that inhibits acetylcholinesterase.
• Acetylcholinesterase is an enzyme that catalyzes (speeds up) the breakdown of acetylcholine.
• Acetylcholine is a neurotransmitter; it’s an ester of acetic acid and choline.
  • This is the main neurotransmitter of the parasympathetic nervous system, and is also heavily involved in cognitive functions including memory and creative thinking.

What this means: if you take an acetylcholinesterase inhibitor like huperzine A, it will inhibit acetylcholinesterase, meaning you will have more acetylcholine to work with. That’s good.

What can I expect from it?

Huperzine A has been well-studied for a while, mostly for the prevention and treatment of Alzheimer’s disease:

• New insights into huperzine A for the treatment of Alzheimer’s disease
• Huperzine A: Is it an Effective Disease-Modifying Drug for Alzheimer’s Disease?
• Huperzine A and Its Neuroprotective Molecular Signaling in Alzheimer’s Disease

However, research has suggested that huperzine A is much better as a prevention than a treatment:

❝A central event in the pathogenesis of Alzheimer’s disease (AD) is the accumulation of senile plaques composed of aggregated amyloid-β (Aβ) peptides.

Ex vivo electrophysiological experiments showed that 10 μM of Aβ1-40 significantly decreased the effect of the AChE inhibitor huperzine A on the synaptic potential parameters. ❞

~ Dr. Irina Zueva

Source: Can Activation of Acetylcholinesterase by β-Amyloid Peptide Decrease the Effectiveness of Cholinesterase Inhibitors?

In other words: the answer to the titular question is “Yes, yes it can”

And, to translate Dr. Zueva’s words into simple English:

• People with Alzheimer’s have amyloid-β plaque in their brains
• That plaque reduces the effectiveness of huperzine A

So, what if we take it in advance? That works much better:

❝Pre-treatment with [huperzine A] at concentrations of 50, 100, and 150 µg/mL completely inhibited the secretion of PGE2, TNF-α, IL-6, and IL-1β compared to post-treatment with [huperzine A].

This suggests that prophylactic treatment is better than post-inflammation treatment. ❞

~ Dr. Thu Kim Dang

Source: Anti-neuroinflammatory effects of alkaloid-enriched extract from Huperzia serrata

As you may know, neuroinflammation is a big part of Alzheimer’s pathology, so we want to keep that down. The above research suggests we should do that sooner rather than later.

Aside from holding off dementia, can it improve memory now, too?

There’s been a lot less research done into this (medicine is generally more concerned with preventing/treating disease, than improving the health of healthy people), but there is some:

Huperzine-A capsules enhance memory and learning performance in 34 pairs of matched adolescent students

^This is a small (n=68) old (1999) study for which the full paper has mysteriously disappeared and we only get to see the abstract. It gave favorable results, though.

The effects of huperzine A and IDRA 21 on visual recognition memory in young macaques

^This, like most non-dementia research into HupA, is an animal study. But we chose to spotlight this one because, unlike most of the studies, it did not chemically lobotomize the animals first; they were and remained healthy. That said, huperzine A improved the memory scores most for the monkeys that performed worst without it initially.

Where can I get it?

As ever, we don’t sell it, but here’s an example product on Amazon for your convenience

Enjoy!

There are two main mechanisms of action by which sparkling water is considered to help satiety and/or weight loss; they are:

1. It “fills us up” such that we feel fuller sooner, and thus eat less, and thus (all other things being equal) perhaps lose weight
2. The carbon dioxide is absorbed into the bloodstream, where (as a matter of chemistry) it improves glucose metabolism, thus lowering blood sugars and indirectly leading (potentially) to weight loss, but even if not, lowered blood sugars are good for most people most of the time, right?

However, there are just a few problems:

Full of gas?

Many people self-report enjoying sparkling water as a way to feel fuller while fasting (or even while eating). However, the plural of “anecdote” is not “data”, so, here be data… Ish:

❝In order to determine whether such satiating effects occur through oral carbonic stimulation alone, we conducted modified sham-feeding (SF) tests (carbonated water ingestion (CW), water ingestion (W), carbonated water sham-feeding (CW-SF), and water sham-feeding (W-SF)), employing an equivalent volume and standardized temperature of carbonated and plain water, in a randomized crossover design.

Thirteen young women began fasting at 10 p.m. on the previous night and were loaded with each sample (15ºC, 250 mL) at 9 a.m. on separate days. Electrogastrography (EGG) recordings were obtained from 20 min before to 45 min after the loading to determine the power and frequency of the gastric myoelectrical activity. Appetite was assessed using visual analog scales. After ingestion, significantly increased fullness and decreased hunger ratings were observed in the CW group. After the load, transiently but significantly increased fullness as well as decreased hunger ratings were observed in the CW-SF group. The powers of normogastria (2-4 cpm) and tachygastria (4-9 cpm) showed significant increases in the CW and W groups, but not in the CW-SF and W-SF groups. The peak frequency of normogastria tended to shift toward a higher band in the CW group, whereas it shifted toward a lower band in the CW-SF group, indicating a different EGG rhythm.

Our results suggest that CO₂-induced oral stimulation is solely responsible for the feeling of satiety.❞

~ Dr. Maki Suzuki et al.

Now, that’s self-reported, and a sample size of 13, so it’s not the most airtight science ever, but it is at least science. Here’s the paper, by the way:

Oral Carbonation Attenuates Feeling of Hunger and Gastric Myoelectrical Activity in Young Women

Here’s another small study with 8 people, which found that still and sparkling water had the exact same effect:

Effect of carbonated water on gastric emptying and intragastric meal distribution

However, drinking water (still or sparkling) with a meal will not have anywhere near the same effect for satiety as consuming food that has a high water-content.

See also: Some Surprising Truths About Hunger And Satiety ← our main feature in which we examine the science of volumetrics, including a study that shows how water incorporated into a food (but not served with a food) decreases caloric intake.

As an aside, one difference that carbonation can make is to increase ghrelin levels—that’s the hunger hormone (the satiety hormone is leptin, by the way). This one’s a rat study, but it seems reasonable that the same will be true of humans:

Carbon dioxide in carbonated beverages induces ghrelin release and increased food consumption in male rats: implications on the onset of obesity

…which is worth bearing in mind even if you yourself are not, in fact, a male rat.

The glucose guzzler?

This one has simply been the case of a study being misrepresented, for example here:

Fizzy water might aid weight loss by providing a small boost to glucose uptake and metabolism

The idea is that higher levels of carbon dioxide in the blood mean faster glucose metabolism, which is technically true. Now, often “technically true” is the best kind of true, but not here, because it’s simply not useful.

In short, we produce so much carbon dioxide as part of our normal respiratory processes, that any carbon dioxide we might consume in a carbonated water is barely a blip in the graph.

Oh, and that article we just linked? Even within the article, despite running with that headline, the actual scientists quoted are saying such things as:

❝While there is a hypothetical link between carbonated water and glucose metabolism, this has yet to be tested in well-designed human intervention studies❞

~ Professor Sumantra Ray

Note: the word “hypothetical” means “one level lower than theoretical”. This is very far from being a conclusion.

And the study itself? Wasn’t even about carbonated water, it was about kidney dialysis and how the carbon dioxide content can result in hypoglycemia:

The mechanism of hypoglycemia caused by hemodialysis

…which got referenced in this paper (not a study):

Can carbonated water support weight loss?

…and even that concluded:

❝CO₂ in carbonated water may promote weight loss by enhancing glucose uptake and metabolism in red blood cells.

However, the amount is so small that it is difficult to expect weight loss effects solely from the CO₂ in carbonated water.

Drinking carbonated water may also affect blood glucose measurements.❞

Note: the word “may”, when used by a scientist and in the absence of any stronger claims, means “we haven’t ruled out the possibility”.

What breaking news that is.

Stop the press! No, really, stop it!

So… What does work?

There are various ways of going about actually hacking hunger (and they stack; i.e. you can use multiple methods and get cumulative results), and we wrote about them here:

Hack Your Hunger

Enjoy!