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Dhb

Also known as: DHB, dihydro-berberine, Dihydroberberine

Overview

Dihydroberberine (DHB) is a reduced derivative of berberine, a naturally occurring isoquinoline alkaloid found in plants like Berberis species. While present in nature, DHB is primarily produced synthetically or via microbial metabolism for use as a dietary supplement. It is classified as a botanical alkaloid supplement and is specifically aimed at improving metabolic health, particularly glucose regulation and lipid metabolism. A key characteristic of DHB is its significantly higher bioavailability compared to berberine, leading to greater plasma concentrations at lower doses. This enhanced absorption is due to its improved intestinal permeability and reduced first-pass metabolism. Although research on DHB is still emerging and has fewer human clinical trials than berberine, there is growing interest due to its pharmacokinetic advantages. The current evidence, while limited, is promising, with preliminary studies suggesting modest but statistically significant improvements in glycemic control and potential lipid profile benefits.

Benefits

Dihydroberberine (DHB) offers several potential benefits, primarily related to metabolic health, largely due to its superior bioavailability compared to berberine. The most significant primary effect is its ability to achieve significantly higher plasma berberine levels (up to 22-fold increase) at equivalent or lower doses, which is crucial for its efficacy. Human trials have shown modest but statistically significant reductions in insulin area under the curve (AUC) by approximately 2.5% and glucose AUC by about 1%, indicating improved glycemic control. These effects are particularly relevant for individuals with metabolic syndrome, type 2 diabetes, or dyslipidemia. While direct evidence for DHB's lipid-modulating effects is still developing, secondary benefits are inferred from extensive berberine research, which shows improvements in lipid profiles, including an increase in HDL cholesterol by about 1.37 mg/dL. The effect sizes are generally small to moderate, but their clinical significance may accumulate over time with consistent use. Effects have been observed in trials lasting 8 to 12 weeks, though longer-term data are currently lacking.

How it works

Dihydroberberine (DHB) exerts its therapeutic effects primarily by being converted to berberine in the body. Once converted, berberine acts through several key mechanisms. A primary pathway involves the activation of AMP-activated protein kinase (AMPK), a master regulator of cellular energy homeostasis, which helps improve insulin sensitivity and modulate lipid metabolism. DHB also influences hepatic glucose production, reducing the liver's output of glucose, and enhances peripheral glucose uptake by cells. Furthermore, it may modulate the gut microbiota, potentially influencing species like Akkermansia and Bacteroides, which are linked to metabolic health. The key advantage of DHB lies in its markedly enhanced absorption and plasma levels compared to berberine, attributed to its improved intestinal permeability and reduced first-pass metabolism, allowing for more efficient delivery of the active compound.

Side effects

Dihydroberberine (DHB) is generally well tolerated in short-term studies, with its safety profile expected to be similar to or potentially better than berberine due to the lower effective doses required. Common side effects, primarily gastrointestinal in nature, such as mild nausea and diarrhea, have been reported with berberine, and while DHB data are limited, similar or fewer occurrences are anticipated. No serious adverse events have been reported in the available small trials. However, caution is advised regarding potential drug interactions, as DHB, like berberine, may interact with cytochrome P450 substrates and P-glycoprotein substrates. This necessitates careful monitoring when co-administered with medications such as anticoagulants and hypoglycemics. Contraindications include pregnancy, lactation, and severe hepatic or renal impairment due to a lack of sufficient safety data in these populations. Data for special populations like children and the elderly are also lacking, suggesting caution and extrapolation from berberine's known effects.

Dosage

Preliminary data suggest that a daily dosage of 200 mg of Dihydroberberine (DHB) may be effective, which is significantly lower than the typical berberine doses ranging from 500-1500 mg per day. The optimal dosage for DHB has not yet been definitively established, but human trials have demonstrated that 200 mg of DHB provides a significant pharmacokinetic advantage over 500 mg of berberine. The maximum safe dose for DHB is currently unknown, though berberine is generally considered safe at doses up to 1500 mg/day; further studies are needed to determine the safety of higher DHB doses. In trials, twice-daily dosing is common to maintain consistent plasma levels. DHB is often formulated as a stabilized salt or complex to enhance its stability and absorption. Its chemical structure inherently improves absorption, and the gut microbiota may further influence its metabolism and efficacy. There are no established cofactors, but some research suggests that probiotics might modulate its effects via the gut microbiota.

FAQs

Is DHB safer than berberine?

Early evidence suggests DHB may have similar or improved tolerability compared to berberine, primarily because lower doses are effective. However, more extensive safety data are needed to confirm this.

How quickly does it work?

Glycemic improvements with DHB have been observed within 8 to 12 weeks in small clinical trials, indicating a relatively short-term onset of effects.

Can DHB replace berberine?

DHB is considered a more bioavailable alternative to berberine, potentially offering similar benefits at lower doses. However, clinical evidence for DHB is still emerging and less extensive than for berberine.

Are there long-term studies?

Currently, there are no large-scale, long-term randomized controlled trials (RCTs) specifically on DHB available, limiting understanding of its long-term effects and safety.

Research Sources

https://blog.priceplow.com/supplement-research/dihydroberberine-vs-berberine – This source describes a small, acute human trial on GlucoVantage DHB involving 5 healthy adults. It reported significantly higher plasma berberine levels (22x) and modest reductions in insulin AUC (2.5%) and glucose AUC (1%) post-meal. The study is preliminary due to its very small sample size and short duration, serving primarily as hypothesis-generating research.
https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2022.1013055/full – This meta-analysis and systematic review on berberine, encompassing 34 studies with over 1000 adults, found that berberine significantly increased HDL cholesterol by 1.37 mg/dL and improved other lipid and glucose parameters. While not directly on DHB, it provides indirect evidence for the potential benefits of the active compound berberine, to which DHB converts.
https://pmc.ncbi.nlm.nih.gov/articles/PMC11171481/ – This experimental study, including in vitro and human components, investigated the pharmacokinetic and metabolite profiling of DHB. It revealed that DHB leads to different metabolite profiles and a higher conversion rate to active berberine compared to direct berberine supplementation, suggesting potential positive effects on gut microbiota. This source provides mechanistic insights into DHB's superior bioavailability.