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Dihydroberberine: Benefits, Side Effects, and Optimal Dosage

Updated October 31 2024. Dihydroberberine has surfaced as a compelling natural compound gaining traction in health and wellness circles. Derived from berberine, dihydro-berberine presents itself as a fresh variant believed to offer enhanced bioavailability and effectiveness. Because of its enhanced absorption, promoters advocate dihydroberberine (known as GlucoVantage) as providing superior benefits for managing health conditions, such as metabolic disorders and cardiovascular ailments. While its therapeutic potential appears promising, grasping its intricacies is essential, as with any supplement. This review explores both its potential benefits and cautions, navigating the evolving landscape of dihydroberberine research, illuminating potential side effects, and providing insights into recommended dosages for optimal health outcomes.

What Is Berberine?

For at least 5,000 years, people have traditionally used berberine, a bioactive compound extracted from various plants, notably Berberis shrubs (also known as barberry), in Ayurvedic and Chinese medicine.

These days, people primarily take berberine for its potential to improve cardiovascular health, aid in blood sugar regulation, reduce cholesterol, and promote weight loss. Some propose that berberine may benefit appetite suppression, although human clinical trials have not confirmed this.

However, one drawback of berberine is its low bioavailability as a dietary supplement. In other words, not much that's consumed orally can be

used by the body to lower blood sugar or cholesterol.

It's estimated that the oral bioavailability is about 0.68%. Put another way, if you swallowed a 500 mg berberine supplement, only 68% (340 mg) would be absorbed into the circulation. Berberine's chemical structure also makes it difficult for the molecule to enter cell membranes.

Berberine Forms In Supplements

In dietary supplements, people can purchase the herbal substance as capsules or powder, typically in its salt form in these versions:

  1. Berberine hydrochloride (HCL)
  2. Berberine sulfate

Berberine HCL is popular in dietary supplements because it dissolves better in water, although berberine fumarate appears slightly better.

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However, all forms have low absorption (about 68%). To compensate, supplement manufacturers may add black pepper (piperine or Biopiperine) to berberine capsules to boost absorption.

Another form, called berberine phytosome, combines the extract with phospholipid fat to enhance absorption when taken on an empty stomach.

Dihydroberberine, detailed below, is a downstream metabolite that promises to be better absorbed and more potent than traditional forms. This synthetic form is not found in nature.

How To Increase Berberine Absorption

Avoid taking it on an empty stomach unless the supplement is in a phytosome form. Instead, taking 30 minutes before or with meals that contain fat will boost absorption. However, the bioavailability would still be less than 100%.

Berberine In Foods

Food Berberine Content (per 3.5 oz)
Barberries ~1,200 mg
Tree Turmeric ~1,000 mg
Goldthread ~500 mg
Coptis Chinensis ~1,500 mg
Indian Barberry ~1,000 mg

The roots of goldenseal (Hydrastis canadensis) contain a small amount of berberine, estimated to be about 25 mg per 1000 mg of root powder, making it an inefficient source of this herbal medicine.

What Foods Reduce Berberine Absorption

Grapefruit, Seville oranges, and Tangeolos are foods that interfere with berberine absorption. These foods contain nutrient chemicals called furanocoumarins, which interfere with a family of critical metabolism enzymes called cytochrome P450.

Additionally, foods high in soluble fiber, such as oatmeal, can interfere with the absorption of berberine and dihydroberberine. Fiber slows down stomach emptying, reducing how quickly berberine enters the intestines. Additionally, research suggests that calcium-rich foods such as cow's milk, kefir, and yogurt block berberine absorption.

Alcohol also seems to interfere with berberine absorption.

Foods Potential Impact on Berberine Absorption
Grapefruit juice Contains compounds that may inhibit intestinal enzymes potentially affecting absorption.
Dairy products (e.g., milk, cheese) Calcium in dairy products may form insoluble complexes with berberine, reducing absorption.
High-fiber foods (e.g., whole grains, legumes) Dietary fiber may delay gastric emptying and decrease absorption of berberine.
Coffee and tea Some compounds in coffee and tea may interfere with absorption processes in the GI tract.
Spices and herbs (e.g., turmeric, cinnamon) Some spices and herbs contain bioactive compounds that may affect absorption mechanisms.
Alcohol Excessive alcohol consumption may interfere with GI function and absorption.
Processed foods High levels of additives or preservatives in processed foods may affect absorption.
Refined carbohydrates (e.g., white bread) Foods high in refined carbohydrates may affect gastric emptying and absorption
Carbonated beverages Carbonation may alter gastric pH and affect absorption

What is Dihydroberberine?

Dihydroberberine (DHB) is a bioactive form of berberine. When metabolizing berberine, our bodies form dihydroberberine. More specifically, enzymes such as cytochrome P450 reductases and other hepatic enzymes mainly convert the precursor substance, berberine, into dihydroberberine in the liver. Additionally, the microbes in the intestinal gut convert berberine to DHB as well, proving that, at least in animals, the microbiome acts as an “organ” for DHB production.

Dihydroberberine vs. Berberine Absorption.

While berberine is often touted as a natural form of Ozempic, challenges like high dosage requirements and gastrointestinal discomfort have spurred interest in its derivative, dihydroberberine.

It's been widely circulated that dihydroberberine is up to 5x more bioavailable than conventional berberine, giving it the nickname “super berberine.” However, there isn't direct evidence suggesting that dihydroberberine is exactly five times more bioavailable across all studies. That said, research suggests that it is more absorbable, with at least one study reporting that dihydroberberine was 3.25 to 4.8 times better absorbed in rats.  This has led some to propose dihydroberberine be investigated as a new drug.

Dihydroberberine For Blood Sugar Reduction

Researchers have conducted over 100 clinical trials on classic berberine regarding blood sugar management and diabetes. Many of these studies reveal that supplementation reduces blood glucose and improves insulin function. For example, in one study, 36% of people taking the supplement were reported to have a remission in metabolic syndrome. Given its improved absorption, it makes sense that dihydroberberine would have similar effects at lower dosages. But is that true?

To answer this, researchers recruited five healthy men and gave them :

  1. a placebo (resistance dextrin)
  2. 500 mg traditional berberine
  3. 100 mg dihydroberberine
  4. 200 mg dihyddroberberine

None of the men involved had diabetes or blood sugar problems. After each supplement, the men consumed a test meal containing 30 g (1 oz) of glucose and measured their blood sugar for up to 2 later. After 90 minutes, 100 mg of dihydroberberine was absorbed six times better than regular berberine, and the effect was even more significant (22X better) for the 200 mg dose! However, neither dose of dihydroberberine lowered blood sugar better than the placebo or regular berberine.

Does Dihydrobererine Lower Cholesterol?

Berberine has been shown to reduce PCSK9 levels. This is similar to how powerful LDL-lowering cholesterol drugs like Repatha function. However, berberine does not appear to cause muscle pain like some have reported with the drug.

In one meta-analysis involving 20 clinical trials, researchers concluded that berberine supplements, when used alongside lifestyle modification (diet and exercise), outperformed lifestyle changes alone in lowering hyperlipidemia problems such as elevated LDL cholesterol and triglycerides.

Furthermore, when used together, the herbal supplement enhanced the effectiveness of statin medications like simvastatin (Zocor), indicating a synergistic effect. However, it's essential to note that evidence supporting berberine doesn't necessarily guarantee the same for dihydroberberine. So far, there's no good proof that this new form effectively reduces cholesterol or LDL.

Dihydroberberine & Weight Loss

Some research studies have documented that people taking 500 to 1500 mg of berberine, in addition to diet and exercise, may lose an extra 2 to 4  pounds per month. Additionally, reports that berberine increases GLP-1 has led some to speculate that it fosters weight loss similar to that of Ozempic (Semaglutide). However, it has not been proven that dihydroberberine augments GLP1 levels.

Take home message: the proof that berberine promotes weight loss is scarce, and there is even less evidence for DHB.

How Do You Use Dihydroberberine?

When attempting to improve insulin sensitivity or lower cholesterol, take DHB 30 minutes between meals.  Avoid taking it during fasting because food improves absorption. Keep in mind that the same foods that can interfere with berberine might also be problematic for DHB.

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Dihydroberberine Optimum Dosage

In clinical trials, researchers often administer conventional berberine at a dosage of 1500 mg per day (500 mg, taken three times daily). At least one company-sponsored clinical trial has revealed that 100 mg and 200 mg of dihydroberberine (GlucoVantage brand) raised blood levels at least 20 times as high as 500 mg of berberine HCL.

In theory, this might mean a much smaller dose, say 300 mg of dihydroberberine, might work as well as 1500 mg of traditional berberine. However, research needs to verify this and the best dosage. A drawback of this study was that it involved only 5 healthy men who did not have metabolic syndrome.

GlucoVantage Dihydroberberine

When starting any new dietary supplement, begin by taking less than recommended for at least the first week to adapt and minimize possible negative side effects.

What Is The Best Kind of Dihydroberberine?

GlucoVantage is a DHB supplement derived from Indian barberry (Berberis Aristata). This appears to be the only proprietary form that researchers have clinically evaluated. Some evidence suggests this proprietary form is more absorbable at lower dosages. People who took 100 mg and 200 mg of GlucoVantage had higher concentrations of berberine in their blood two hours after eating than people who consumed 500 mg of regular berberine.

All supplement companies using this form will display “GlucoVantage” on their labels. GlucoVantage is a product from the NNB Nutrition company in Nanjing, China. The more precise company name is Nanjing Nutrabuilding Bio Tech Co Ltd. This company holds US patent number 10278961B2, which deals with the administration of berberine metabolites.

Brands I Like

I like these three brands based on their company reputation, price, lack of heavy metals, and independent potency testing.

Solaray Vital Extracts Berberine

Swanson Berberine

GlucoVantage Super Berberine

How Much Dihydroberberine Works?

Research suggests that amounts of 100 mg and 200 mg raise levels in the blood as well as 500 mg of traditional berberine. However, this doesn't necessarily mean the lower dose works as well at improving glucose or hyperlipidemia symptoms.

Dihydroberberine Side Effects

Limited evidence does not reveal significant side effects in healthy humans. That said, exercise caution if you are not healthy or if you are pregnant, nursing or take any medications such as:

Is Dihydroberberine A Legit Alternative To Berberine?

Although DHB has gained popularity, researchers have primarily conducted most human clinical trials on traditional berberine. In theory, DHB might work as well as berberine at lower dosages. However, human studies need to confirm this.

Delve deeper with these berberine reviews.

Berberine side effects

Weight loss research

Cholesterol-lowering research

Is berberine a natural PCSK9 inhibitor?

What Do You Think?

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