Berberine: A Look at the Potential Benefits of this Versatile Supplement

Berberine May Support Your Weight Loss Efforts

Since a berberine supplement can activate AMPK, it can have minor effects on weight loss. In particular there seems to be a small preference for fat loss with berberine supplementation. However, these effects do appear to be mild, and will not lead to very significant weight loss by itself. Instead, a berberine supplement should be taken alongside an already existing healthy exercise and diet regimen, and within this context, it may help support weight loss.

Berberine May Support Your Mood and Cognition

Berberine appears to support both mood and cognition. The main mechanisms of action here appear to occur through a receptor called sigma-1, potassium current blockade, monoamine oxidase A and B inhibition and acetylcholinesterase inhibition. 

The sigma-1 receptor is a fairly unique receptor that appears to modulate a wide variety of biological activities. The sigma-1 receptor is known as an endoplasmic reticulum (ER) chaperone, this means that within the ER, which is one of the main organelles in cells besides the mitochondria, sigma-1 binds to various targets and quite literally ‘chaperones’ their activity. Normally, sigma-1 is bound to another ER chaperone called BiP. Upon activation of the sigma-1 receptor, it releases from BiP and freely floats around the ER. Free sigma-1 preferentially binds to the IP3 receptor. This IP3 receptor modulates Ca2+ efflux from the Ca2+ stores in the ER. The problem with the IP3 receptor is that it is rapidly degraded after it is activated by IP3, but sigma-1 prevents this degradation due to its chaperone activity. This ultimately makes more Ca2+ available to the mitochondria and receptors that require Ca2+influx such as the NMDA receptor. The NMDA receptor modulates many cognitive functions, such as the encoding of long term memories through a process called long term potentiation (LTP). Furthermore, activation of the sigma-1 receptor causes an increase in BDNF levels. BDNF is a protein that is very important for modulating how the brain changes, and decreased levels of BDNF are associated with low mood and overall decreased cognition.

Berberine appears to be a positive modulator of the sigma-1 receptor, which means that berberine makes sigma-1 receptors more sensitive. This increased sensitivity causes the sigma-1 receptor to be activated much more readily. Due to this, berberine can modulate Ca2+ efflux and influx whilst also increasing BDNF levels. This is likely what causes  berberines mood suppporting effect and is also responsible for a large portion of its neuroprotective and cognition enhancing effects.

Berberine also causes the blockade of potassium currents in the brain which allows various receptors to become activated more readily. This is especially important in regards to the NMDA receptor. On top of this, berberine inhibits acetylcholinesterase, which may promote levels of the neurotransmitter, acetylcholine. Acetylcholine plays a vital role in cognition, and thus, elevating its levels can help promote healthy cognitive function.  Berberine also appears to have a very mild effect on the monoamine oxidase enzymes. These enzymes break down dopamine and serotonin, and thus by blocking their activity at a very low level, we can expect to see somewhat higher levels of dopamine and serotonin in the brain. Taking all of this together, it has the potential to be very beneficial for supporting healthy mood and cognition

Molecular Formula

C20H18NO4

Molecular Weight

372.82 Daltons 

Hydrogen Acceptor Count

4 

Hydrogen Donor Count

0 

LogP

-0.18 

Lipinski’s Rule of Five

 Yes 

pKa

2.47 

Solubility 

Not water soluble 

Visual 

Bright yellow, fluoresces under UV 

Smell 

Very faint tea 

Taste 

Very bitter, bile like

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