Berberine (which I wrote about here) is a herbal supplement obtained from a number of different plants, which Chinese medicine has used for perhaps thousands of years. Its physiological mechanism most resembles metformin, the world’s most prescribed diabetes drug. It lowers blood glucose, activates AMPK, and does a seemingly endless number of other beneficial things. And berberine may reduce cardiovascular risk.
Endothelial cells are those cells that line arteries and are very important for cardiovascular health. When the cells lining arteries don’t function well, this is known as endothelial dysfunction.
“The vascular endothelium, which regulates the passage of macromolecules and circulating cells from blood to tissues, is a major target of oxidative stress, playing a critical role in the pathophysiology of several vascular diseases and disorders.”
Vascular endothelial cells have a finite lifespan and can enter a state of senescence and promote atherosclerosis. Maintaining youthful and healthy endothelial cells in the lining of arteries is essential for cardiovascular health.
Older or senescent endothelial cells produce lower amounts of nitric oxide, the important signaling molecule that inititates the relaxation of blood vessels and keeps them youthful.
So how do we keep our arteries youthful?
Berberine increases the production of nitric oxide, which in turn plays a key role in the regulation of endothelial progenitor cells (EPCs). These cells mature and replace older endothelial cells, ensuring the arteries stay flexible and youthful.
Researchers took a look at the effect of berberine on EPCs: Berberine-Induced Upregulation of Circulating Endothelial Progenitor Cells Is Related to Nitric Oxide Production in Healthy Subjects.
First, what I liked about this study. It was done in humans, so we know that this works and not just in rats or mice. Second, berberine is not well-absorbed into the circulation. I’ve seen a number of studies in which berberine was injected at high doses into rats or mice, and I doubt we can meaningfully extrapolate those results to humans taking oral doses. This study used healthy people taking berberine orally.
The subjects were 20 healthy people, average age 54, with no cardiovascular disease and taking no medication. They took 400 mg of berberine 3 times a day for 30 days. Then they looked at EPCs, as well as their activity, and the level of nitric oxide in the blood.
Berberine therapy resulted in a dramatic increase in EPCs. See chart below.
The number of EPCs rose 50%.
Results for proliferative, adhesive, and migratory activity of EPCs were similar.
Also, blood glucose, LDL cholesterol, and blood pressure all declined.
The researchers found that EPC numbers and activity were strongly correlated with increased nitric oxide in blood, so that may be how berberine works to promote EPCs.
As noted, EPCs are strongly and negatively correlated with cardiovascular risk. An article in the New England Journal of Medicine tells the story: Circulating Endothelial Progenitor Cells, Vascular Function, and Cardiovascular Risk.
“…endothelial progenitor cells may provide a circulating pool of cells that could form a cellular patch at the site of denuding injury or serve as a cellular reservoir to replace dysfunctional endothelium…
To test this hypothesis, we measured the activity of endothelial progenitor cells in relation to cardiovascular risk factors and endothelial function in a group of healthy volunteers. These subjects had no symptoms associated with atherosclerosis or active ischemia.”
For the result, see chart below.
“The nature and size of our study do not permit us to determine whether low levels of endothelial progenitor cells can accurately predict subsequent cardiovascular events… Establishing a definitive cause-and-effect relation requires studies in which the levels of endothelial progenitor cells are experimentally manipulated and the biologic or therapeutic effects assessed. Rather, we believe our data suggest that circulating endothelial progenitor cells have a role in vascular homeostasis. We further speculate, but cannot prove, that continuous risk-factor–induced injury may lead to the eventual depletion of circulating endothelial progenitor cells. Interestingly, recent studies in animals have suggested that the exhaustion of stem cells may be an important determinant of a number of age-related conditions. Future studies will therefore be needed to determine whether this postulated risk-factor–induced exhaustion of circulating endothelial progenitor cells is a factor in the pathogenesis of cardiovascular disease.”
While the effect of berberine appears important, we can only say that the number and activity of EPCs is associated with lower cardiovascular risk. That seems important enough. Berberine’s additional actions on blood glucose, LDL, and blood pressure certainly seem to substantiate that.
You can read a review of the metabolic and cardiovascular effects of berberine here.