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!

Is Berberine Nature’s Ozempic/Wegovy?

Berberine is a compound found in many plants. Of which, some of them are variations of the barberry, hence the name.

It’s been popular this past couple of years, mostly for weight loss. In and of itself, something being good for weight loss doesn’t mean it’s good for the health (just ask diarrhoea, or cancer).

Happily, berberine’s mechanisms of action appear to be good for metabolic health, including:

• Reduced fasting blood sugar levels
• Improved insulin sensitivity
• Reduced LDL and triglycerides
• Increased HDL levels

So, what does the science say?

It’s (mostly!) not nature’s Wegovy/Ozempic

It’s had that title in a number of sensationalist headlines (and a current TikTok trend, apparently), but while both berberine and the popular weight-loss drugs Wegovy/Ozempic act in part on insulin metabolism, they mostly do so by completely different mechanisms.

Wegovy and Ozempic are GLP-1 agonists, which mean they augment the action of glucagon-like-peptide 1, which increases insulin release, decreases glucagon release, and promotes a more lasting feeling of fullness.

Berberine works mostly by other means, not all of which are understood. But, we know that it activates AMP-activated protein kinase, and on the flipside, inhibits proprotein convertase subtilisin/kexin type 9.

In less arcane words: it boosts some enzymes and inhibits others.

Each of these boosts/inhibitions has a positive effect on metabolic health.

However, it does also have a slight GLP-1 agonist effect too! Bacteria in the gut can decompose and metabolize berberine into dihydroberberine, thus preventing the absorption of disaccharides in the intestinal tract, and increasing GLP-1 levels.

See: Effects of Berberine on the Gastrointestinal Microbiota

Does it work for weight loss?

Yes, simply put. And if we’re going to put it head-to-head with Wegovy/Ozempic, it works about half as well. Which sounds like a criticism, but for a substance that’s a lot safer (and cheaper, and easier—if we like capsules over injections) and has fewer side effects.

• Weight Loss Outcomes Associated With Semaglutide Treatment for Patients With Overweight or Obesity ← Wegovy and Ozempic are both brand names of semaglutide
• The effect of berberine supplementation on obesity parameters: A systematic review and meta-analysis of randomized controlled trials ← a good recent research review giving clear data on many factors
• Lipid-lowering effect of berberine in human subjects and rats ← this is an older study, 2012, but it gives 3-month weight loss percentages rather than discrete values in the abstract, so it’s easier to compare to the semaglutide study without grabbing a calculator

❝But more interestingly, the treatment significantly reduced blood lipid levels (23% decrease of triglyceride and 12.2% decrease of cholesterol levels) in human subjects.

However, there was interestingly, an increase in calcitriol levels seen in all human subjects following berberine treatment (mean 59.5% increase)

Collectively, this study demonstrates that berberine is a potent lipid-lowering compound with a moderate weight loss effect, and may have a possible potential role in osteoporosis treatment/prevention.❞

(click through to read in full)

Is it safe?

It appears to be, with one special caveat: remember that paper about the effects of berberine on the gastrointestinal microbiota? It also has some antimicrobial effects, so you could do harm there if not careful. It’s recommended to give it a break every couple of months, to be sure of allowing your gut microbiota to not get too depleted.

Also, as with anything you might take that’s new, always consult your doctor/pharmacist in case of contraindications based on medications you are taking.

Where can I get it?

As ever, we don’t sell it, but you can check out the berberine of one of our sponsors if you like, or else find one of your choosing online; here’s an example product on Amazon, for your convenience.

Enjoy!