Dihydroberberine is the solution to glucose metabolism?

Every compound out there has two different parts: it's pharmacodynamics and its pharmacokintetics. Pharmacodynamics is essentially how it works in the body. Think of this as the mechanism the compound uses to cause effects to the body. Pharmacokinetics is essentially how it move around the body. Think of this as how it gets absorbed, transported, metabolized, and then excreted. Most people like to simplify it all down. However, how a compound works in the body, and where it works in the body, both really matter to the effects. Sometimes it doesn't even need to technically enter the body to work, as many things just affect the GI tract itself, but never get into systemic circulation. Berberine is one of those compounds that has both central, peripheral effects, and external GI effects. This means that the pharmacokinetics of the berberine form matter a lot, as taking normal berberine HCL is going to mostly affect the GI tract, whereas taking a different form like dihydroberberine will have more systemic and central effects. Normal berberine HCL has a lot of its effects from modulating the microbiome in the small intestine.

Gut microbiome-related effects of berberine and probiotics on type 2 diabetes \(the PREMOTE study\)

The mechanism of berberine alleviating metabolic disorder based on gut microbiome

Effects of berberine and metformin on intestinal inflammation and gut microbiome composition in db/db mice

These effects are mostly due to berberine acting directly in the small intestine. If you use a form that more rapidly enters the bloodstream, then you will alter the effects in the small intestine, and increase the effects in the other parts of the body. With berberine, you can do that in a number of ways. We offer berberine HCL with silymarin, as that has shown to improve bioavailability and have complimentary effects with one another.

Metabolic effect of berberine–silymarin association: A meta-analysis of randomized, double-blind, placebo-controlled clinical trials

A Descriptive Review of the Action Mechanisms of Berberine, Quercetin and Silymarin on Insulin Resistance/Hyperinsulinemia and Cardiovascular Prevention

Efficacy of Nutraceutical Combination of Monacolin K, Berberine, and Silymarin on Lipid Profile and PCSK9 Plasma Level in a Cohort of Hypercholesterolemic Patients

Effects of a Combination of Berberis aristata, Silybum marianum and Monacolin on Lipid Profile in Subjects at Low Cardiovascular Risk; A Double-Blind, Randomized, Placebo-Controlled Trial

The improvement in berberine bioavailability by silymarin is mostly due to its P-glycoprotein inhibiting properties. Then it also goes on to have direct complimentary effects in the body. The main issue with silymarin is that most milk thistle extracts out there have silychristin in them, which adversely affects thyroid function.

Silychristin, a Flavonolignan Derived From the Milk Thistle, Is a Potent Inhibitor of the Thyroid Hormone Transporter MCT8

This was actually brought to our attention by a Redditor on our sub, so we decided to develop a low silychristin milk thistle, which we have moved to now in our berberine/silymarin product. This strategy help improve the bioavailability of berberine, and enhance its effects, but fundamentally keep the molecular structure of berberine the same.

https://nootropicsdepot.com/berberine-hcl-silymarin-tablets/

Then we also offer berberine phytosome. This uses a strategy of creating a phospholipid complex of berberine with pea protein, sunflower lecithin, and grapeseed extract. This also helps improve the pharmacokinetics of berberine without fundamentally changing the chemical structure of berberine itself. It has also been studied to do that in humans.

Graph

Berberine phospholipid exerts a positive effect on the glycemic profile of overweight subjects with impaired fasting blood glucose (IFG): a randomized double-blind placebo-controlled clinical trial

This change not only increases bioavailability, but also extends the effects over a longer period. It's like a controlled release formulation.

https://nootropicsdepot.com/berberine-phytosome-capsules-550mg/

So these are the two solutions to berberine bioavailability we have gone with so far, as they fundamentally don't change the chemical structure of berberine. It's still berberine entering the body and working like it normally does. What dihydroberberine does to improve bioavailability is to actually chemically alter the molecule, making a completely different chemical structure. This strategy works because making that change alters the solubility profile of the molecule, but also prevents it from binding to the normal enzymes that break berberine down and lower bioavailability. This is why I consider it a different thing. It's very similar to our Curowhite product. That takes the curcuminoids in curcumin, and hydrogenates them. This removes the conjugated pi system, which is why it removes the orange color. However, it also improves bioavailability for the same reason dihydroberberine alters it. The chemical structure is fundamentally different, so it completely changes the pharmacokinetics, but also some of the pharmacodynamics. I am not opposed to that, as I think making changes like that is a cool way to improve effects. However, I treat them as different molecules from each other, as they are different chemically. Does that make sense?