Keeping your metabolism balanced, naturally


From tradition to modern science: the effectiveness of berberine

Keeping your metabolism balanced, naturally

Berberine is a plant alkaloid with a long history of medicinal use in both Ayurvedic and Chinese medicine.

It is present in Hydrastis canadensis (goldenseal), Coptis chinensis (coptis or goldenthread), Berberis aquifolium (Oregon grape), Berberis vulgaris (barberry) and Berberis aristata (tree turmeric). The berberine alkaloid can be found in the roots, rhizomes and stem bark of these plants.

Berberidaceae, the barberry family of the buttercup order (Ranunculales), comprises 14 genera and 701 species of perennial herbs and shrubs.1 In the Berberidaceae family, the genus Berberis comprises 450–500 species, which represent the main natural sources of berberine.

Among the various species of Berberis genus, Berberis aristata DC is one of the most important species because of its numerous medicinal properties.

Its occurrence has been reported in the subtropical areas (1800–3000 m above sea level) of the mountain states of Uttarakhand and Himachal Pradesh. It has been used in various crude drug formulations and in different traditional and homeopathic medicines since ancient times.

Berberis has various pharmacological actions. It has been used in traditional medicine for its antimicrobial, antiprotozoal, antidiarrhoeal and antitrachoma properies.2

Berberine is a quaternary ammonium salt derived from isoquinoline and its health benefits in multifactorial conditions are supported by reliable scientific literature, including controlling healthy blood levels.3

Specifically, berberine’s proven effectiveness in the treatment of multifactorial conditions is related to its so-called pleiotropic “cloud effect,” which simultaneously targets both root causes (such as low-grade chronic inflammation, oxidative stress, gut microbiota modulation) and markers (insulin levels) through the modulation of several cellular targets (such as AMPK, mitochondria, insulin receptors, key metabolic and proinflammatory enzymes, etc.).

This helps to optimise peripheral blood metabolite profiles by modulating plasma sugar, insulin and lipid levels, and acting as a valuable contributor to metabolic well-being.4

Indena’s solution for berberine’s Achilles’ heel

Like many natural compounds, berberine suffers from poor bioavailability. This is because of several factors: poor absorption from the gut (<5%), rapid metabolism in the body, conversion to ionic form under physiological conditions, self-aggregation at low pH values, low solubility in the gastrointestinal tract, its inability to permeate the gut wall and P-glycoprotein (Pgp) efflux in the epithelial cell membrane.

For these reasons, high dosages are traditionally recommended for berberine, which then results in low tolerability and gastrointestinal side-effects.

To manage these issues, which plague many natural ingredients, Indena developed Phytosome®, the proprietary biomimetic strategy for the delivery of natural ingredients that allows the human body to absorb them in the best possible way.

It is a fundamental asset and an internationally recognised scientific reference for the delivery of natural active ingredients. Phytosome combines food-grade sunflower-derived lecithin with botanical and natural substances that maintain the original components’ profile and benefits.

Keeping your metabolism balanced, naturally

Lecithins are natural surfactants that, together with bile salts, contribute to the physiological absorption of compounds and form the lipid bilayer structure of cell membranes.

As an amphipathic molecule consisting of a positively charged head group and a tail of two neutral acyl moieties, lecithin acts as an inhibitor of self-aggregation, making natural compounds — in a dispersed state — more readily absorbed.

Numerous scientific studies have proven that the Phytosome system offers optimised human pharmacokinetic profiles and effectiveness compared with non-formulated equivalent compounds.

Knowing, respecting and enforcing the uniqueness of nature, Indena designs and formulates every single Phytosome according to the properties of the specific natural ingredient to optimise its health benefits.

Working on berberine, Indena developed BERBEVIS, a new and innovative Phytosome composition based on scientifically proven evidence:

  • berberine in a protein-rich rhizome extract showed better intestinal absorption and plasma exposure than pure berberine, which is why Indena decided to include a natural vegetable (pea) protein carrier within the Phytosome matrix
  • the inclusion of a naturally powerful antioxidant such as grape seed extract within the Phytosome matrix may protect the intestinal mucosa against the known gastrointestinal adverse effects of traditional berberine, optimising its tolerability profile.5

Remarkably, a human pharmacokinetic study has confirmed that BERBEVIS can optimise berberine bioabsorption, improving the substance’s bioavailability on a molar basis and with observed dose linearity.

In vitro studies have been also been done to further investigate both the bioaccessibility and tolerability of Indena’s BERBEVIS.

Bioaccessibility is often associated with bioactive compounds and represents the amount of an ingested nutrient that is released from a matrix to become available for absorption after undergoing the digestion process.

It was important to verify the tolerability of the berberine Phytosome compared with traditional Berberis extracts, which, owing to their poor oral absorption, need to be used at high dosages that result in gastrointestinal discomfort.

The in vitro studies results showed that

  • the Phytosome formulation enhances berberine solubility in gastrointestinal fluids
  • the Phytosome formulation has better bioaccessibility than an unformulated Berberis extract, improving the amount of berberine released into the gastrointestinal tract and available for absorption
  • the Phytosome formulation has a higher safety profile than an unformulated Berberis extract with no negative impact on intestinal membranes
  • BERBEVIS appears to be suitable for long-term administration.

Your natural ally for a healthy metabolism

Medicinal plants may well provide a useful source of new oral hypoglycaemic compounds for the development of pharmaceutical entities or as a dietary adjunct to existing therapies.

Few of the plants used for the treatment of diabetes, however, have received scientific or medicinal scrutiny; even the WHO expert committee on diabetes recommends that this area warrants further attention.2

To check the effectiveness of the berberine Phytosome’s ability to maintain healthy blood glucose levels, BERBEVIS has been used to supplement the diet of subjects enrolled in a human PCOS (Polycystic Ovary Syndrome) study, which aims to measure the whole range of marker modulation for the first time.

PCOS is a complex, multifactorial, endocrine-metabolic disorder. In a PCOS subject, their metabolic health is mainly impaired by insulin resistance (IR) — the body’s inability to respond to the amount of insulin produced by the pancreas — leading to unhealthy and excessive blood sugar levels that can potentially be harmful.

According to the study’s multiple endpoint data, BERBEVIS supplementation emerged as the winning multitarget approach to metabolic health maintenance thanks to an effective positive effect on blood sugar levels. In summary

  • it effectively optimises insulin levels after as few as 30 days of treatment
  • it noticeably modulates the blood sugar profile, optimising both blood glycaemia and insulin
  • a favourable safety profile was reported, with no major adverse events.

Furthermore, the following secondary endpoints were reported:

  • BERBEVIS effectively supports metabolic health, having a positive effect on blood lipid profile, body composition and fostering the redistribution of adipose tissue — even in subjects who are not following a low-calorie diet
  • it promotes hormonal balance
  • it has a positive effect on low-grade chronic inflammation by balancing major inflammation biomarkers
  • it’s also helpful for healthy skin, acne being a typical condition of PCOS that significantly affects quality of life.

All in all, BERBEVIS is a potent, natural health food ingredient that might help with blood sugar control in a plethora of multifactorial challenges, which represents one of our time’s principal global health targets.


  2. V. Chander, et al., The Journal of Phytopharmacology 6(1), 53–58 (2017).
  3. X. Feng, et al., Theranostics 9(7), 1923 (2019).
  4. W-J. Kong, et al., Pharmacology & Therapeutics 209, 107496 (2020).
  5. B-L. Ma, et al., Scientific Reports 6(1) 1–11 (2016).