Is Berberine Nature’s Ozempic? A Have a look at GLP-1 Agonists


Except you’ve been dwelling below a rock, you’ve probably heard of Ozempic (semaglutide) by now.

Berberine vs Ozempic

Is Berberine “Nature’s Ozempic”? We check out their mechanisms as GLP-1 agonists, and reply, “Sure, considerably.” This text compares and contrasts the 2.

This fats loss drug has taken the mass media by storm, due to testimonials (and speculated use) by various celebrities in movie, tv, and modeling. Proponents declare it’s the miracle weight reduction tablet the world has been ready for.

We now have to confess, the scientific trials look fairly good on the floor. One research reviews Ozempic can trigger weight lack of 4% to six.2% physique mass in diabetics, with an much more spectacular impact dimension of 6.1% to 17.4% in non-diabetics.[1] One other reviews that after 68 weeks of weekly therapy with Ozempic, 86.4% of members misplaced 5% or extra of their physique weight, and 69.1% misplaced 10% or extra.[2] These are fairly severe numbers; shedding 10% or extra of your physique mass could be life-changing.

When one thing like that is invented (or found), it’s frequent to search for pure alternate options within the dietary complement business, particularly people who have an extended historical past of protected use. Within the case of Ozempic, berberine is the ingredient that many have in contrast it to.

So on this article, we focus on the mechanisms behind Ozempic, and if berberine shares those self same mechanisms.

How Ozempic Works: GLP-1 Agonist

Regardless of the hype surrounding Ozempic, its mechanism of motion isn’t novel. Medical science has identified for many years about its goal, the glucagon-like peptide-1 receptor (GLP-1R).[1,2] Extra particularly, it’s a GLP-1R agonist – it prompts the receptor, slightly than inhibiting it. The essential purpose GLP-1R agonism works for weight reduction is that GLP-1 regulates urge for food.[3]

Ozempic / Semaglutide Appetite Suppression

By activating the GLP-1 receptor, Ozempic / semaglutide suppresses urge for food.[3]

Not solely does GLP-1 have an effect on urge for food signaling in key mind areas, probably serving to discourage compulsive consuming, it might probably even have a mechanical impact in your feeling of satiety by delaying gastric emptying.[3] By holding your meals in your abdomen longer, you are feeling fuller longer (within the inset graph, it’s known as “mechanical distention”).[3]

Fairly cool, proper? Nicely, Ozempic’s GLP-1R agonism is definitely not distinctive. It most likely received’t shock you to be taught that a number of different compounds a few of them dietary dietary supplements — act on GLP-1R as properly.

So what’s the deal? With different GLP-1R agonists already on the market, does Ozempic actually deserve all the eye it’s getting?

Berberine: Nature’s Ozempic?

A research printed in July of 2023 means that berberine is a kind of different GLP-1R agonists.[4] This research has been making the rounds on social media, main many outstanding influencers, each inside and outdoors the complement world, to ask: is berberine nature’s Ozempic?

As we speak, we wish to take this chance to reply: Sure, at the least partially, berberine is like “nature’s Ozempic”. In fact, they’re not precisely the identical, and we’re not claiming that berberine is simpler than Ozempic – however for some use circumstances, we’re not going to assert it’s much less efficient, both.

As an alternative, let’s lay out some proof, and allow you to be the choose. First, what is this molecule present in quite a few dietary dietary supplements?

Berberine, a pure plant alkaloid, has been a complement business mainstay for over a decade, due to its highly effective anti-diabetic results[5,6] that may result in wholesome weight reduction.[7,8] Our most in-depth protection on the ingredient is in our article titled Berberine: The Greatest Glucose Disposal Ingredient Simply Bought Higher, which launched the world to dihydroberberine, a simpler type of the ingredient mentioned later.

However for now, keep on this web page, get a short overview on berberine, and let’s dig immediately into the GLP-1 query:

Nature’s finest glucose disposal agent

Because the title of the article linked above suggests, berberine is commonly used as a glucose disposal agent,[9] because it helps enhance the physique’s utilization of glucose. The alkaloid improves the shuttling of blood sugar out of the blood and into cells – ideally muscle tissues in somebody who workout routines.

Berberine vs. Metformin

One may very simply argue that berberine outperformed metformin in most measures![10] However at this dose, there are some considerations to handle, that are coated afterward on this article.

This gives an anti-diabetic impact by supporting higher insulin sensitivity, which is vital as a result of insulin resistance — attributable to our processed meals, poisonous environments, and lack of bodily exercise — is extremely related with our ongoing societal metabolic syndrome.[11-13]

Relating to these mechanisms, we’ve got to convey up the research the place berberine outperformed frequent antidiabetic drug metformin — with fewer unwanted effects.[10] The authors of that research be aware that “berberine exhibited an similar impact within the regulation of glucose metabolism” (as measured on HbA1c and blood glucose ranges when fasted and after consuming), it even regulated lipid metabolism greater than metformin.

So notice with this GLP-1 / Ozempic hype that this isn’t the primary time berberine has been in comparison with a pharmaceutical drug.

Nevertheless, there’s extra to berberine than simply its insulin sensitizing results. It seems the GLP-1 mechanism is at play too:

Berberine – GLP-1 agonist

The analysis group has identified since 2009 — and maybe longer — that berberine is a GLP-1 agonist, selling GLP-1 amide secretion.[14] A sequence of analysis research by means of the 2010s then repeatedly, efficiently, and safely demonstrated these results in preclinical trials – each in vitro and in vivo.[15-17]

Berberine GLP-1

Berberine upregulates GLP-1.[15]

Whereas the brand new research printed not too long ago in 2023 provides to the data base, it’s a research printed in 2019 that gives probably the most useful perception explaining what we meant by the phrase anti-diabetic up above.[15] That is the research we’ll concentrate on, however the different research cited above could be learn for extra background.

On this experiment, researchers induced diabetes in mice by feeding them a excessive fats weight-reduction plan (HFD) for 16 weeks.[15] On the finish of this feeding interval, half the HFD-fed mice have been randomly assigned to obtain berberine. A 3rd group of lean, wholesome mice served because the non-berberine management set.

When the researchers in contrast the three teams, they discovered that the enterocytes (intestinal cells) of the non-berberine HFD group secreted considerably much less GLP-1 than the wholesome controls.[15]

This isn’t stunning since GLP-1 downregulation is a identified characteristic of diabetes.[18,19] Impaired GLP-1 secretion and signaling is a large drawback for anybody, however notably a diabetic. Over time, the overeating inspired by GLP-1 downregulation can exacerbate the underlying metabolic dysfunction of diabetes, inflicting the disastrous adverse suggestions loop that so many obese people have discovered themselves coping with.

…however berberine restores GLP-1!

What’s exceptional, nevertheless, is that berberine therapy restored GLP-1 secretion within the HFD-fed mice.[15]

Berberine Enhances GLP-1 Signaling

A better look: In diabetic mice, berberine therapy truly enhanced GLP-1 signaling, growing it to above baseline.[15]

What’s even extra spectacular is that the berberine-treated HFD group truly had a larger serum GLP-1 degree than the lean, wholesome controls![15] So berberine didn’t simply reverse the diabetes’ impact on GLP-1 signaling, it truly left the mice, at the least with respect to GLP-1 signaling, higher off than earlier than.[15]

As an fascinating aspect be aware, GLP-1 appears to do that at the least partly by activating bitter style receptors.[16] So black espresso followers the world over can rejoice – you’ve been (at the least barely) vindicated by this department of science.

Style receptors are simply a part of the story, although. There’s a way more fascinating half, and it has to do with mitochondria, one among our favourite topics right here on the PricePlow Weblog.

Berberine restores enterocyte mitochondrial perform

By the top of the research, mice within the HFD, non-BBR group had roughly twice as a lot ATP simply hanging out of their intestinal tissue, in comparison with the opposite two teams. At first, this would possibly sound like an excellent factor – who doesn’t need extra ATP? It’s the “vitality foreign money” molecule, proper? However, as is commonly the case in biology, it’s not essentially that easy.

Berberine ATP Consumption in Intestinal Tissue

Berberine therapy elevated ATP consumption within the mice’s intestinal tissue, which means a restoration of regular mitochondrial respiration.[15]

Because it seems, ATP overproduction could be attributable to consuming too many energy, as in a excessive fats weight-reduction plan. This is one thing that ought to make intuitive sense – your mitochondria flip energy into ATP, so when you eat too many energy, then logically we might count on your mitochondria to make an excessive amount of ATP. And, the truth is, that is precisely what occurs within the intestines.

What occurs subsequent is fairly ugly. That additional ATP units in movement a sequence of occasions that enhance mitochondrial oxidative stress, and finally destroys {the electrical} membrane potential that mitochondria want for regular respiration. This results in mitochondrial injury — on this case, in cells of the digestive system.[15]

This technique of mitochondrial injury by means of vitality overproduction is known as mitochondrial overheating.[15]

Berberine protects towards this mitochondrial overheating

Luckily, berberine truly protected the mice’s mitochondria from that injury by lowering ATP manufacturing, even within the presence of the additional caloric vitality![15] Therefore, the title of the research we’ve been discussing, “Berberine is related to safety of colon enterocytes from mitochondrial overheating”.[15]

So, it appears that evidently a enormous a part of berberine’s general profit comes from restoring mitochondrial perform – a standard theme among the many finest dietary dietary supplements.

What about in people?

Proof of berberine’s GLP-1 agonism in people stays preliminary. A 2021 randomized managed trial did discover elevated GLP-1 exercise in topics taking berberine, however couldn’t decide if berberine induced the impact immediately or not directly.[20]

Nevertheless, as an editorial opinion, we provide that the above preclinical analysis is fairly good assist for a berberine-driven impact – particularly since we’re already fairly accustomed to berberine’s different unbelievable results in people.

Different Similarities: Elevated Insulin Secretion… (generally)

Berberine PricePlow

Berberine is a pure plant alkaloid proven to enhance glycemia / glucose disposal and lipids by boosting insulin sensitivity. Considered one of its mechanisms is thru GLP-1 activation

There’s one other similarity between berberine and semaglutide (the unbranded chemical title of Ozempic), however they don’t at all times behave the identical. Semaglutide is an incretin mimetic that will increase insulin secretion,[21] and berberine normally will increase it as properly.[6,22-25] Nevertheless, there are at the least a few research the place berberine decreased insulin secretion.[26,27] Why isn’t it as constant on this trend?

The distinction appears to be that berberine will increase high-glucose dependent insulin,[6,25] that means that it’s simpler when glucose is current. Living proof, within the two research the place serum insulin ranges have been decrease, the blood checks have been taken in a fasted state.[26,27]

Semaglutide, nevertheless, appears to extra reliably enhance insulin secretion, even in a fasted state whereas the dieters are consuming much less.[28] Usually, this may be a priority, since insulin could be thought-about the “vitality storage hormone”, however its urge for food suppressive properties (on account of delayed gastric emptying) tilt the scales in the direction of extra weight reduction — the purpose the place it’s turn into extra than simply antidiabetic drug.

Then again, berberine’s impact may very well be what lots of our readers researching sports activities diet need, since they’re making an attempt to maintain carbohydrate consumption excessive for efficiency and muscular hypertrophy causes, however could not at all times need insulin circulating at different occasions of the day. Elevated insulin does, in any case, cut back fats oxidation,[30,31] so timing the hormone’s launch ought to be taken into consideration by these making an attempt to successfully burn fats.

Finally, which means that berberine’s results as an insulin secretagogue will likely be diminished on lower-carbohydrate diets (though the GLP-1 mechanism remains to be in play). It’s going to undoubtedly be most efficient in diabetic / prediabetic populations, with some nice use circumstances for carbohydrate lovers. This can be nice information, relying in your scenario.

Berberine’s different advantages

Moreover, there’s analysis in people demonstrating berberine’s different anti-diabetic advantages.

For instance, when berberine is taken with a meal, it has been proven to considerably lower peak blood glucose ranges.[9,32-34] The mechanism of motion appears to be selling mobile glucose uptake by activating an enzyme known as adenosine monophosphate kinase (AMPK).[35,36]

Berberine additionally appears to have favorable results on blood ldl cholesterol and triglycerides, which is to be anticipated since AMPK promotes fats uptake as a lot as glucose uptake.[37]

Berberine

Berberine is probably probably the most underrated complement on the planet. It creates a improbable sequence of metabolic reactions that each carb-user ought to learn about.

Different research have discovered that berberine can[9,32-35,38]:

  • Inhibit gluconeogenesis[36]
  • Forestall the absorption of dietary carbohydrates[36]
  • Enhance microbiome well being[39]
  • Lower oxidative stress[40]
  • Scale back systemic irritation[40]

Nature’s metformin

Wrapping up our dialogue of berberine and metabolic well being, we wish to remind everybody of the research the place berberine metformin by way of glycemic management for kind 2 diabetics.[10]

So, so long as we’re asking, “Is berberine nature’s Ozempic?”, we must also ask if berberine is nature’s metformin. The reply to that query can be a possible sure, however that’s the topic of one other article.

Because it stands proper now, it appears that evidently Ozempic / semaglutide is extra highly effective than berberine as a GLP-1 agonist, whereas berberine (when dosed properly sufficient) can compete with metformin by way of glycemia and lipids.

Berberine and weight reduction

Now for the massive one, and the rationale most individuals are right here. One human research discovered that, on common, 500 milligrams of berberine, taken orally for 12 weeks, produced a 2.3% discount in weight.[10]

Berberine Effects

Berberine considerably improved each lipid and metabolic attribute measured![9]

Admittedly, this can be a smaller impact dimension, however the research period was additionally shorter than what we’ve seen in Ozempic scientific trials.

The opposite factor to notice is that berberine-driven weight discount got here with a 1.1% lower in waist-to-hip ratio, and a 3.6% lower in physique fats proportion – sturdy indications that berberine is torching fats, not muscle or bone mass.[10]

Meta-analyses of berberine literature have discovered comparable outcomes, with comparable impact sizes.[41,42]

Right here’s the factor, nevertheless. There’s a technique to make berberine even higher — each by way of efficiency and lowering its draw back of requiring a comparatively massive 1.5 gram every day doses for max results.

GlucoVantage Dihydroberberine – A Higher Berberine

May berberine be made much more efficient for weight reduction than we noticed in that 12 week research?

We predict the reply is sure – In response to the meta-analyses we cited, some research used doses starting from 1,000 to 1,500 milligrams a day and noticed higher outcomes.

Why, then, is berberine no more typically touted as a miracle weight reduction complement? (Except for the Spring/Summer season 2023 TikTok craze, in fact.)

Berberine at scientific doses has GI penalties!

The reply is that such massive clinically-verified doses of berberine include issues. For instance, within the research we cited the place berberine went up towards metformin, 35% of topics had vital gastrointestinal upset when taking the 1,500 mg/day dose (three capsules price).[10]

That’s a reasonably large incidence fee. If we wish berberine to compete with one thing like Ozempic, researchers have to discover a technique to enhance the dose, enhance the efficiency/bioavailability, and cut back these unwanted effects.

GlucoVantage Dihydroberberine Bioavailability

We’ve lengthy stated that GlucoVantage dihydroberberine has 5x the bioavailability if conventional berberine.[43]

That’s the place dihydroberberine, bought as GlucoVantage by NNB Diet, is available in.

Dihydroberberine (DHB) is a lot extra bioavailable than unusual berberine and achieves comparable results at vastly smaller doses.

As its title suggests, DHB is produced by including a hydrogen ion to the berberine molecule – which is one thing your physique was going to do anyway! Cause being, dihydroberberine is of course made within the human digestive tract as a berberine metabolite — it’s produced when the intestine microbiome hydrogenates berberine in order that it might probably take in it.

The explanation intestine flora convert berberine into DHB is as a result of, in contrast to berberine, DHB can move by means of intestinal tissue, which permits it to achieve the bloodstream. As soon as it’s within the blood, DHB will get transformed again into berberine, whereupon it has the cool, anti-diabetic results we’ve been speaking about.[43]

Right here’s a easy diagram of berberine’s digestive course of:

Berberine (intestine) → dihydroberberine (gut) → berberine (bloodstream)

Because it seems, that first conversion step is a bottleneck on this complete course of. That’s why massive doses of berberine trigger GI upset: intestine flora sometimes can’t convert it into DHB quick sufficient to forestall irritation. That is very true of people that want berberine probably the most – people with diabetes or pre-diabetes sometimes have poor intestine well being and decreased microbiome range.[44]

As a result of DHB sidesteps the conversion bottleneck, it’s 5 occasions extra bioavailable than commonplace berberine.[43] (You’ll be able to learn our article titled 5x Extra Bioavailable: Why Dihydroberberine is “The Higher Berberine” for extra info on that research).

Dihydroberberine Converts To Berberine

Amazingly, dihydroberberine converts again into berberine, and also you finally find yourself with extra![43]

DHB’s helpful results additionally final longer than these of unusual berberine.[45,46]

Analysis reveals that DHB can present the identical advantages as berberine, with a a lot smaller dose:

  • Improved glucose uptake, notably in diabetics[10,47]
  • Elevated insulin sensitivity[48]
  • Improved glucose utilization by muscle cells[49,50]
  • Higher physique composition[10,51]

Wish to be taught extra? Learn our GlucoVantage / Dihydroberberine content material

The explanation you don’t hear as a lot about dihydroberberine is as a result of it’s dearer to fabricate, and too many dietary complement firms sadly take the cheaper route. Dihydroberberine is patented[52] and bought as GlucoVantage from NNB Diet, which is the first technique to get it. However at a decrease price, it’s additionally a decrease dose.

Dihydroberberine vs. Berberine

Merely put by the researchers: “DhBBR [Dihydroberberine] has a greater intestinal absorption than BBR.”[43]

We wrote about GlucoVantage DHB in our article titled GlucoVantage: Dihydroberberine for Superior Insulin Sensitivity. NNB Diet is a companion of PricePlow’s and a sponsor of this text, however we’re being trustworthy after we say we’ve seen work tremendously for blood sugar management and weight reduction.

Dihydroberberine Dosage

The efficient Dihydroberberine Dosage is 30% the dose of ordinary berberine, giving it much more functions and fewer GI discomfort!

If you happen to’d prefer to strive GlucoVantage by itself, try Alpha Lion’s Positive aspects Sweet GlucoVantage. Regardless of the title, which admittedly could also be a bit off-putting to those that don’t know the lighthearted Alpha Lion model, this can be a trusted and examined type of GlucoVantage that means that you can strive it alongside the remainder of your weight-reduction plan routine.

We do not, nevertheless, encourage anybody to take berberine or dihydroberberine alongside Ozempic or different GLP-1 agonists.

Click on by means of if you wish to be taught extra about this superb, pro-metabolic complement, however please learn our conclusion first, as a result of we wish to emphasize protein consumption earlier than leaving.

Some closing ideas

It’s clear that Ozempic is making large waves all through the world. A lot, the truth is, that we’re seeing the whole fats burner class of dietary dietary supplements shrink at retailers — shops are starting to dedicate much less shelf house to weight reduction due to this drug. That is the stark actuality, the drug class is clearly attaining outcomes.

With that stated, we nonetheless love berberine (and dihydroberberine) due to its higher physique of analysis and longer historical past of security. It’s not but clear what long-term pharmaceutical GLP-1 agonist drug use appears like from a security perspective.

Maintain protein excessive it doesn’t matter what you do!

A few of the frequent criticisms of Ozempic are that it could result in muscle losing[53] and weight achieve returns as soon as discontinuing the drug.[54] Nevertheless, if we’re being trustworthy, those self same issues can occur with berberine use!

Berberine vs. Ozempic

Cause being, a big portion of those results are by means of urge for food suppression. And with that, if one doesn’t manually intervene, comes a pure discount in protein consumption. We don’t have to remind our readers that no matter what weight-reduction plan you select, a excessive protein:vitality ratio have to be maintained – above all else!

We will argue about varied poisonous processed oils, herbicide-laden carbohydrates, and the opposite fat-soluble molecules in our diets that drive insulin resistance all day lengthy, however no matter the place you stand on these, or whether or not you’re into low-fat or high-fat weight-reduction plan, you should hold protein excessive.

Our hope is that analysis on each berberine and Ozempic will likely be printed displaying profitable DEXA scans that preserve muscle tissue with high-protein diets, and when that’s the case, we’ll be a bit extra assured within the extra aggressive interventions. Nevertheless, we nonetheless have considerations for long-term excessive insulin secretion, which appears to be extra of a priority with Ozempic than berberine.

Till there’s extra long-term information, we urge excessive warning, and at all times recommend life-style change over all else. In spite of everything, no matter whether or not it’s a dietary complement or pharmaceutical drug, you don’t wish to be on a weight reduction intervention for the remainder of your life.

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