Does a so-called natural Ozempic exist? Probably not, but something else comes far closer to earning that label than berberine.
Some fitness influencers are calling berberine "Nature's Ozempic" (semaglutide). They say this polyphenol mimics the effects of the popular appetite-suppressing, weight-loss-inducing prescription drug. Does it? Well, first, there is no natural version of the drug. Berberine is a poseur.
It's strange that the TikTok world didn't instead latch onto a much more effective fat-loss polyphenol: cyanidin 3-glucoside or C3G (sold as Indigo-3G (Buy at Amazon)). Choosing berberine over C3G is like casting a Pilates instructor instead of Arnold Schwarzenegger for the role of Conan the Barbarian.
No, C3G doesn't work the same way as Ozempic works. It is, however, way better than berberine in facilitating a host of physique-enhancing riches, some of which are beyond even Ozempic's abilities. But let's first look at berberine and see if there's anything to it.
Berberine: The rise of a poseur
Berberine is a bioactive compound found in several plants, including Berberis, that has been used in traditional medicine. A few clinical trials found that berberine can reduce blood glucose levels and reduce insulin resistance. Most of the buzz, however, arose from a 2020 meta-analysis that found that taking 500 mg of berberine every day for several months caused an average weight loss of about 4 pounds.
That's not bad, but Ozempic and related drugs work astronomically better, causing users to lose between 12 and 15% of their fat mass in around 6 months. Ozempic works by imitating a hormone called GLP-1, which is manufactured in the gut after eating and prompts insulin production. The drug also induces fullness, which is a surefire method to induce fat loss.
Berberine doesn't do that. But it does favorably impact blood glucose and insulin resistance, which can slowly coax some fat loss. It also causes fat loss in another way: it tends to cause diarrhea, which makes people feel too uncomfortable to eat. And another study, this one largely ignored, revealed that berberine-eating rats actually gained weight and experienced an increase in appetite.
Despite this, like most plant polyphenols, it does have valuable anti-inflammatory and antioxidant properties. Now let's compare berberine's effects to those of C3G.
C3G and insulin
C3G, derived from dark berries and black rice, has insulin-like properties that activate insulin receptor substrates, activating insulin-signaling proteins. These signaling proteins stimulate glucose uptake by skeletal muscle cells instead of fat cells. Provided you were lifting at the same time, that means any surplus food you ate (more than maintenance) would be shuttled off to muscle instead of fat.
Furthermore, one of several laboratory experiments involving C3G showed two dosage-related drops in blood sugar (33% and 51%), prompting researchers to remark on how favorably it compared with a pharmaceutical glucose-disposal agent.
C3G and AMPK
Adenosine monophosphate kinase (AMPK) is often called the biochemical "master switch." It's found in every cell in the body and plays a huge role in determining how lean you are, how muscular you are, and even how long you'll live.
Control AMPK and you literally become the master of your domain. C3G increases production of AMPK by a factor of 2.88 (in one study), which increases a massive up-regulation of a "transcriptional activator" known as PGC-1 alpha, which then ramps up exercise capacity, fatigue resistance, and oxygen uptake. Collectively, this leads to a decrease in body fat and an increase in muscle mass (assuming all other contributing factors are optimal).
C3G and adiponectin
Adiponectin is a protein hormone. Activating it causes fat cells to act as if they were another endocrine hormone, and they start to regulate glucose levels and fatty acid breakdown. When C3G is introduced, it induces the release of adiponectin, causing insulin sensitivity to increase (a good thing), inflammation to decrease, and, most impressively, it tells fat cells to disgorge fatty acids into the bloodstream. The result is slimmer fat cells and, accordingly, a slimmer you.
As a bonus, increases in adiponectin influence mitochondria to multiply, in some cases turning metabolically sluggish white fat into the more metabolically active brown fat.
Having more brown fat is good because it burns more calories. It normally kicks in right before you go out into a winter wonderland without your coat, prompting the brown fat to break down blood sugar and molecules of fat, creating a sort of metabolic campfire to keep you warm.
C3G, however, courtesy of adiponectin, causes a breakdown of blood sugar and fat without having to sit naked on a bank of snow. (No, you don't start to shiver after taking C3G, but increases in adiponectin simply cause these brown cells to start burning up more calories.)
C3G and life-extension
While people don't generally take fat-loss supplements to increase their lifespan, it might just be a bonus when it comes to taking C3G.
Remember how C3G can increase levels of AMPK? Well, increased levels of this master switch also mimic the effects of calorie restriction, and calorie restriction is thought to be the most effective way known to increase health and lifespan.
When turned on, AMPK triggers the use of stored energy from fat, enhances the removal of sugar and fats from the blood, reduces cellular inflammation, cleans up cellular junk (preventing errors in transcription of mRNA), and even leads to the formation of new mitochondria, which is a big deal.
More mitochondria mean you could theoretically double your lifespan without experiencing any of the diseases typically associated with old age. That may be overly ambitious, but increases in AMPK are associated with 20 to 30% increases in the lifespan of lab animals. Too bad calorie restriction, at least the type associated with life extension, is counterproductive to lifters and bodybuilders.
Well, C3G, it seems, allows you to not only have your cake but to eat it too. In other words, you could theoretically continue to eat a surplus of calories and still reap the life-extension benefits of a calorie-restriction diet. Let's see berberine do that, or even half of the things C3G/Indigo-3G (Buy at Amazon) can do.
