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Berberine

Berberine is a quaternary ammonium salt from the protoberberine group of benzylisoquinoline alkaloids found in the roots, rhizomes, stems, and bark of plants such as Berberis (e.g. Berberis vulgaris – barberry, Berberis aristata – tree turmeric, Mahonia aquifolium – Oregon-grape, Hydrastis canadensis – goldenseal, Xanthorhiza simplicissima – yellowroot, Phellodendron amurense[2] – Amur cork tree, Coptis chinensis – Chinese goldthread, Tinospora cordifolia, Argemone mexicana – prickly poppy, and Eschscholzia californica – Californian poppy. Due to berberine’s strong yellow color, Berberis species were used to dye wool, leather, and wood. Wool is still dyed with berberine today in northern India.[3

Purpose?

Berberine activates an enzyme called Adenosine Monophosphate-Activated Protein Kinase (AMPK) while inhibiting Protein-Tyrosine Phosphatase 1B (PTP1B).

AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity.

In live cells, berberine localizes in mitochondria. Its mitochondrial localization is consistent with inhibition of complex I of respiratory chain, decrease of ATP production, and subsequent activation of AMPK, which leads to suppression of mTOR signaling.[11]  (Wikipedia)

Why Supplement?

  • 19 Health Benefits
  • Berberine is under investigation to determine whether it may have applications for treating arrhythmia, diabetes,[7] hyperlipidemia,[8] inflammation[9]and cancer. Berberine exerts class III antiarrhythmic action.[10] There is some evidence that berberine may have anti-aging (gero-suppressive) properties.[11][12] Berberine is already being used as an ‘Insulin Sensitizer’ which is able to provide better glycaemic control in most of the users [Only upon prescription of a qualified physician]. (Wikipedia)
  • Some research has been undertaken into possible use against methicillin-resistant Staphylococcus aureus (MRSA) infection.[14] Berberine is considered antibiotic.[15][16]When applied in vitro and in combination with methoxyhydnocarpin, an inhibitor of multidrug resistance pumps, berberine inhibits growth of Staphylococcus aureus[17] and Microcystis aeruginosa,[18] a toxic cyanobacterium. (Wikipedia)
  • Berberine is supplemented for its anti-inflammatory and anti-diabetic effects. It can also improve intestinal health and lower cholesterol. Berberine is able to reduce glucose production in the liver. (Examine)
  • Berberine is one of the few supplements with human evidence that establishes it to be as effective as pharmaceuticals. (Examine)
  • Berberine vs MetFormin

Positive Impact on Microbiome (from Microbiomemastery)

– Gut bacteria can convert berberine into a more absorbable form, increasing its bioavailability
– Berberine has a large impact on the microbiome: Large initial reduction overall, by inhibiting bacterial cell division
– Negative effect on many potential pathogens: Proteobacteria (E. coli, Shigella, Salmonella, Klebsiella, Proteus, Vibrio), Staphylococcus, etc.
– Increases the relative proportion of some key beneficial groups: Clostridia (butyrate producers), Bifidobacteria, possibly Lactobacilli
– Berberine can also inhibit Candida and other potential opportunistic pathogens and parasites

Positive Impact on Microbiome (from Enzymedica)

  • One of the biggest changes seen in the microbiome with berberine supplementation is that the quantity of the beneficial bacteria Akkermansia muciniphila in the gut increases. This bacteria plays a critical role in gut health because it is a key factor responsible for mucin thickness. Mucin lines the gut, protecting the intestines from damage.
  • A thinning or absent mucin layer is associated with increased intestinal permeability (leaky gut) and inflammation. The greater the colonization of the Akkermansia muciniphila bacteria, the less incidence of obesity, diabetes, metabolic syndrome and low-grade chronic inflammation. In other words, when the levels and activity of this bacteria are low, these disorders seem to take root.
  • The assumption is that these disorders are associated with altered gut barrier function due to reduced mucin protection, which leads to the absorption of many gut-derived toxins that trigger a cascade of different systems that promote chronic inflammation and insulin resistance.
  • Berberine has been shown to reverse a lacking gut barrier, along with the absorption of gut-derived toxins that comes with it, by promoting the growth of Akkermansia muciniphila—leading to an improved intestinal barrier, reduced circulating levels of gut-derived toxins and a significant reduction in inflammation.
  • Another helpful bacteria boosted by berberine is Bifidobacterium—beneficial to intestinal health, it reduces absorption of gut-derived toxins and inflammation.

Dosage?

  • High doses of berberine taken acutely, due to their poor intestinal uptake rate, may cause cramping and diarrhea; for this reason, berberine should be taken in multiple doses throughout the day (Examine)
  • Supplements range from 500mg to 1200mg per pill (Amazon)
  • Human and animal research demonstrates that 1500mg of berberine, taken in three doses of 500mg each, is equally effective as taking 1500mg of metformin or 4mg glibenclamide, two pharmaceuticals for treating type II diabetes. (Examine)
  • It can also cause abdominal discomfort (nausea, distension) if taken on an empty stomach. (SelfHacked)
  • The bioavailability of berberine is low.[13]  (Wikipedia)

Which vendor?

  • ConsumerLab conducted a thorough berberine provider evaluation and Amazing Formulas (also, Amazon’s top recommendation) has the lowest cost and provides true berberine HCL. Many of the Goldenseal products had poor quality.

Side Effects and Adverse Interactions?

  • The main side effects are related to digestion, and there are some reports of cramping, diarrhea, flatulence, constipation and stomach pain (Healthline)
  • Berberine can increase bilirubin levels and should not be taken by pregnant or nursing women.
  • Berberine may interact with microlide antibiotics such as azithromycin and clarithromycin at hERG channels on the heart, leading to serious cardiotoxicity (Examine)
  • Berberine interacts with organic anion transporter proteins, which may limit tissue uptake of metformin (Examine)
  • Berberine is known to inhibit CYP2D6, CYP2C9, and CYP3A4, which can lead to a host of drug interactions, some of which can be serious (Examine)
  • Berberine microbiome cautions: (from Microbiomemastery)
    • It can cause an initial broad-spectrum reduction in microbiome, similar to antibiotics
    • It may reduce the diversity of the microbiome, also similar to antibiotics
    • The microbiome composition (degree of dysbiosis) varies among individuals, so berberine is likely to have differing effects depending on these inter-individual differences

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