More from the Magical Molecule: Berberine
The gift from Nature that keeps on giving.
Video # 4 Berberine Treats Atherosclerosis in Humans (Small Study)
In this amazing study the researchers demonstrate how berberine was able to reduce atherosclerotic plaque when administered for 4 months at 1 gm daily dose. The study says berberine treats atherosclerosis via a vitamin-like effect, down regulating the choline TMA- TMAO production pathway in gut microbiota.
Study: https://www.nature.com/articles/s41392-022-01027-6
Plaques in the blood vessels can, over time, continue to enlarge and can eventually rupture, causing heart attacks, strokes, and many other issues. Even simply narrowing the blood vessels and disrupting the Dynamics of the cardiovascular system.
The image above shows how plaques shrank in size after 4 months of treatment. The study had 21 patients.
There also were patients treated with standard drugs like Statins to reduce cholesterol and blood thinners like Clopidogreland aspirin, and their plaques continued to increase in size. The berberine patients were the ones whose plaque sizes actually decreased.
Another marvelous outcome for Berberine!
Results quoted from the study:
The average plaque score in patients was decreased by 3.2% after oral BBR (0.5 g, bid) for 4 months (*P < 0.05, n = 21); the score value was slightly increased (by +1.9%) after treatment with conventional drug combination, including rosuvastatin, aspirin, as well as clopidogrel sulfate or ticagrelor (n = 12) if needed. c The average carotid intima-media thickness was reduced by 3.2% after oral treatment with BBR (P = 0.067), and the value was slightly increased (by +2.0%) in the combination therapy. d The average carotid plaquelength in patients was decreased by 2.2% in either oral BBR (0.5 g/bid) group or combination drug group after 4 months on therapy. e TMA and TMAO level in faeces and plasma samples of patients went down after 4 months BBR treatment; the TMA/TMAO levels in plasma were lowered by 37% / 35% (***P < 0.001; *P < 0.05), and TMA/TMAO levels in faeces decreased by 38%/29% (*P < 0.05; *P < 0.05)
Plaques start to develop under the intima-media layer of the artery and make a bulge in the blood vessel that reduces the capacity of the artery for blood flow.
The study resulted in an average reduction of the intima-media thickness of 3.2 percent after oral treatment and the value was slightly increased by 2% with the combination (berberine+ statins+ bloodthinners) therapy where the average carotid plaque length was decreased by 2.2% in the berberine oral group or combination drug group after four months of therapy.
That’s a huge deal.
How did Berberine do this?
When taken orally, Berberine is only about 1% bioavailable in our circulation. However the effect of berberine is quite large. So there may be something in the gut that is augmenting the effect.
The researchers found that berberine was actually entering the microbiota and changing the behavior of the microbiota through which it helped reduce the atherosclerotic plaques and reduce the potential for cardiovascular events.
How did berberine work with microbiota?
When we eat red meat or organ meat we produce phosphatidylcholine and that enters the microbiota in the GIT (gastrointestinal tract). So inside these microbial creatures the phosphatidylcholine is changed to or converted to choline by an enzyme called cut C or choline PMA liaise. This enzyme converts choline to TMA. TMA is then further converted to TMAO by another enzyme called flavin containing monooxygenase or FMO.
SUMMARY
When we eat red meat or organ meat, our microbiota produce TMA and TMAO. Two enzymes are involved in this process. TMA and TMAO are known to cause vascular inflammation and atherosclerosis. There are many studies currently that are targeting microbiota to determine if we can help the microbiota produce fewer inflammatory mediators.
Guess what Berberine does?
When berberine enters the microbio bacteria, it is converted to dihydroberberine. Berberine is an unstable molecule, so the hydrogen atoms used in the conversion from Berberine to dihydroberberine actually go back and forth between berberine and dihydroberberine allowing the hydrogen ions to be absorbed by the two enzymes (CutC and FMO) which disables them and disrupts their function. The result is that this particular bacteria will not produce as much TMA and TMAO which will mean that in our circulation these elements TMA and TMAO will not be present in larger quantities and the inflammation of the blood vessels will not occur.
TMA can also go to the liver and be converted to TMAO there as well, and it was thought that it may be a function of the liver but it turns out that the liver’s contribution is really more like 1%.
It’s all in the microbiota.
In China and other places they use berberine as a regular part of their supplement regime. How many more medical products do we know that actually reduce the plaque size (other than recommending weight loss), which would start pulling the lipid related products out of the system. Berberine is a cheap over-the-counter supplement that actually works!
I’ll let the ABSTRACT sum it up…
“Trimethylamine-N-oxide (TMAO) derived from the gut microbiota is an atherogenic metabolite. This study investigates whether or not berberine (BBR) could reduce TMAO production in the gut microbiota and treat atherosclerosis. Effects of BBR on TMAO production in the gut microbiota, as well as on plaque development in atherosclerosis were investigated in the culture of animal intestinal bacteria, HFD-fed animals and atherosclerotic patients, respectively. We found that oral BBR in animals lowers TMAO biosynthesis in intestine through interacting with the enzyme/co-enzyme of choline-trimethylamine lyase (CutC) and flavin-containing monooxygenase (FMO) in the gut microbiota. This action was performed by BBR’s metabolite dihydroberberine (a reductive BBR by nitroreductase in the gut microbiota), via a vitamine-like effect down-regulating Choline-TMA-TMAO production pathway. Oral BBR decreased TMAO production in animal intestine, lowered blood TMAO and interrupted plaque formation in blood vessels in the HFD-fed hamsters. Moreover, 21 patients with atherosclerosis exhibited the average decrease of plaque score by 3.2% after oral BBR (0.5 g, bid) for 4 months (*P < 0.05, n = 21); whereas the plaque score in patients treated with rosuvastatin plus aspirin, or clopidogrel sulfate or ticagrelor (4 months, n = 12) increased by 1.9%. TMA and TMAO in patients decreased by 38 and 29% in faeces (*P < 0.05; *P < 0.05), and 37 and 35% in plasma (***P < 0.001; *P < 0.05), after 4 months on BBR. BBR might treat atherosclerotic plaque at least partially through decreasing TMAO in a mode of action similar to that of vitamins.”
NB: The reduction of TMA and TMAO in faeces is important because it is another proof along with the reduction in plasma, that the microbiota were modulated.
We will continue to find more magic from Berberine. Stay tuned!
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