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Dihydroberberine vs Berberine
Berberine is one of the best known and most effective natural Glucose Disposal Agents (GDA) available. Berberine has been used for thousands of years, with origins in Chinese and Ayurvedic medicine. Berberine is a bioactive plant supplement and is best known for its abilities to improve blood glucose disposal, insulin efficiency, lipid metabolism and even body composition.Although berberine’s effectiveness is impressive, it does come with some shortcomings, including its high dose requirements and gastrointestinal distress. However, these shortcomings can be overcome with a more effective form of berberine known as dihydroberberine (DHB), an active derivative metabolite. Simply stated, dihydroberberine is what Berberine coverts into before it’s digested! This article will compare the effectiveness of berberine compared to dihydroberberine.
The Difference between Dihydroberberine & Berberine
Berberine is a bioactive plant derivative that belongs to a class of compounds called alkaloids.
Dihydroberberine is one of the 17 active metabolites of berberine, which is produced naturally in the body via a reduction process that occurs after ingestion of berberine by gut microbes. Dihydroberberine is then converted back to berberine after absorption by the intestines.
Supplementation with dihydroberberine could therefore remove this rate-limiting step of microbial reduction and mitigate potential gastrointestinal distress that some experience with berberine supplementation. This GI distress is likely the result of poor absorption and or the microbial reduction process.In addition, the structure of dihydroberberine (which contains multiple hydrogen bonds), allows for better bioavailability and absorption and easier binding at the cellular level than berberine.1 Compared with supplementing with berberine, dihydroberberine has 5 times more intestinal absorption, which means you would need to take 5 times the amount of berberine to get the same result as with dihydroberberine!2 In addition, dihydroberberine is also longer acting in the body—eight hours compared to just four hours with berberine.2
Comparing Insulin & Blood Glucose Disposal
One of the main benefits of berberine is its ability to help control blood glucose levels in the body. When blood glucose levels and insulin levels are elevated, fat oxidation or fat burning can decrease. Berberine works by activating the pathways of AMP-activated protein kinase (AMPK), which can help increase blood glucose breakdown and utilization, insulin sensitivity and fat oxidation and inhibit fat cell growth.
Treatment with berberine has been shown in numerous studies to have significant hypoglycemic, blood glucose lowering benefits.3 An animal study in mice compared the effects of berberine and dihydroberberine for improving insulin sensitivity.2Mice were fed a high-fat diet and treated with either 100 mg/kg/day of dihydroberberine or 560 mg/kg/day of berberine. The dihydroberberine group experienced improvements in adiposity, triglyceride buildup and a 44 percent increase in insulin sensitivity compared to berberine.2 At the same dose, berberine had no effect on adiposity or glucose tolerance. To elicit the same response with berberine required five times the amount compared to dihydroberberine.2 The enhanced bioavailability of dihydroberberine is considered the reason for its enhanced benefits.
Lipid Metabolism & Binding Affinity with Dihydroberberine
A target for weight loss is pancreatic lipase (PL). One of the most popular pancreatic lipase inhibitors is the drug Orlistat, which is used for the management of obesity. Blocking lipid metabolism via pancreatic lipase can decrease hydrolysis and absorption of dietary fats.
One simulation model study compared the inhibitory effect of berberine vs. dihydroberberine on pancreatic lipase.4 Berberine had a similar pattern of binding interactions as dihydroberberine, but berberine had lower binding affinity, which suggests it has a lower inhibitory action compared to dihydroberberine on pancreatic lipase.4 Although both had substantial pancreatic lipase inhibition, dihydroberberine had a higher inhibitory effect than regular berberine. Dihydroberberine therefore may be considered a more effective weight-loss aid than berberine when it comes to fat metabolism.
Anti-Inflammatory Action of Dihydroberberine
Another identified benefit of berberine is its anti-inflammatory properties. Dihydroberberine has been shown to reduce cardiovascular inflammation. As many readers of Muscle Insider know, reducing plaque size and vulnerability of plaque rupture with a comprehensive diet and exercise plan is the target for prevention of cardiovascular problems.
A study compared the efficacy for improving atherosclerosis by berberine and dihydroberberine.5 In the in vitro study (done in a test tube), dihydroberberine group showed greater inhibitory effects on expression of both macrophages and foam cells, an indicator of early stages of atherosclerosis, when compared to berberine.
In an in vivo study (done in a living organism), the researchers found that dihydroberberine reduced aortic atherosclerotic lesion size and improved plaque stability when compared with a control group. Berberine at the same dosage, however, did not provide the same effects on atherosclerosis. The results of this study show that dihydroberberine could have more pronounced anti-inflammatory effects on cardiovascular health than berberine.5
The Verdict – Dihydroberberine vs. Berberine
Although berberine is an effective agent for improving insulin and blood glucose disposal and has anti-inflammatory and fat metabolism benefits, dihydroberberine has been shown to be more effective because it has five times more bioavailability, twice the lasting rate and requires smaller doses.
NNB Nutrition are the inventors of GlucoVantage dihydroberberine which is the first commercially available brand of dihydroberberine. This is engineered from natural non-GMO Berberis aristate using a special enzymatic process that converts to 97% dihydroberberine. In fact, NNB Nutrition’s production method actually replicates the process used by your body to make dihydroberberine in the gut! GlucoVantage is lab-tested for purity and requires a small dose of 100 to 200 milligrams taken up to three times daily before meals to elicit its blood glucose lowering effects.
GlucoVantage can be combined with stimulant-free weight loss, blood sugar control, ketogenic and low-carb supplements. In addition, dihydroberberine has been shown to enhance ketone activity in a human pilot study when combined with exogenous ketone beta-hydroxybutyrate (BHB) making it ideal for stacking with BHB salts.6 Dihydroberberine could potentially increase ketone activity by 2 to 3 times more than exogenous ketone supplements alone, which is another reason to consider dihydroberberine over just berberine.
Want to know more about GlucoVantage and NNB Nutrition? Visit www.nnbnutrition.com.
- Pingali S, Donahue JP, Payton-Stewart F. Weak C-H···X (X = O, N) hydrogen bonds in the crystal structure of dihydroberberine. Acta Crystallogr C Struct Chem. 2014 Apr;70(Pt 4):388-91. doi: 10.1107/S2053229614003751.
- Turner N, Li JY, Gosby A, et al. Berberine and its more biologically available derivative, dihydroberberine, inhibit mitochondrial respiratory complex I: a mechanism for the action of berberine to activate AMP-activated protein kinase and improve insulin action. Diabetes. 2006 Mar;55(3):708-15. doi: 10.2337/diabetes.55.03.06.db05-0312.
- Dong H, Wang N, Zhao L, Lu F. Berberine in the treatment of type 2 diabetes mellitus: a systemic review and meta-analysis. Evid Based Complement Alternat Med. 2012;2012:591654. doi: 10.1155/2012/591654.
- Mohammad M, et al. Inhibition of pancreatic lipase by berberine and dihydroberberine: an investigation by docking simulation and experimental validation. Med Chem Res. 2013. 22: 2273-8. doi: 10.1007/s00044-012-0221-9
- Chen J, Cao J, Fang L, et al. Berberine derivatives reduce atherosclerotic plaque size and vulnerability in apoE-/- mice. J Translat Med. 2014. 12: 326. doi: 10.1186/s12967-014-0326-7.
- Lowery R, et al. USPTO, 2017 October; WO2017184789A1.
- W. Hua et al., Determination of berberine in human plasma by liquid chromatography-electrospray ionization-mass spectrometry. J Pharm Biomed Anal 44, 931-937 (2007).
- P.-L. Tsai, T.-H. Tsai, Hepatobiliary excretion of berberine. Drug Metab Dispos 32, 405-412 (2004).
- G.-y. Pan, G.-J. Wang, X.-D. Liu, J. P. Fawcett, Y.-Y. Xie, The involvement of P-glycoprotein in berberine absorption. Pharmacol Toxicol 91, 193-197 (2002).
- R. Feng et al., Transforming berberine into its intestine-absorbable form by the gut microbiota. Sci Rep 5, 12155 (2015).
- R. Feng et al., Gut Microbiota-Regulated Pharmacokinetics of Berberine and Active Metabolites in Beagle Dogs After Oral Administration. Front Pharmacol 9, 214 (2018).