Berberine

People often come in already sold on berberine, usually from something they've read. These are the questions our naturopaths ask in store, and they're mostly about what it can't do and who shouldn't take it.

A good fit if

• You're looking at blood sugar and blood fats together, which is where almost all the trial work has been done
• You can take it with meals, two or three times a day, at the doses the trials actually used
• You're comfortable giving it 90 days, because that's when most of the measured change happened
• Your prescriber knows you're taking it and is happy with it
• You'd rather choose the plain HCl form the evidence is built on than a form sold on better absorption

Check with us first if

• You take medicine for blood glucose. Berberine adds to the glucose-lowering effect, and your prescriber needs to know.
• You take a statin. Trials of the two together found bigger changes in blood fats, but herbs containing berberine block the CYP3A4 liver enzyme that clears several statins.
• You take any medicine where small changes in dose matter. Goldenseal-type extracts reduced CYP3A enzyme activity by about 40 per cent over 28 days, so talk to your pharmacist rather than guessing.
• You take metformin. Goldenseal extract cut metformin levels by about 20 per cent at lower metformin doses, though berberine alone didn't.
• You're over 60. The pooled effect was smaller in this group, so set your expectations to match.
• You're already constipated. Constipation was the side effect that came up more often with berberine than with the comparisons.
• You take any prescription medicine. Check with your doctor, pharmacist or our naturopaths before starting.

• Berberine HCl. Best known for: The plain hydrochloride salt, and the form behind nearly every trial pooled in the meta-analyses. Absorption: The weakest of the three. In a direct human comparison, the peak blood level after a 500 mg dose was 0.4 ng/mL. Typical use: 500 mg two or three times a day with meals. If a label just says berberine, this is almost certainly what's in it.
• Berberine Phytosome (berberine phospholipid complex). Best known for: Berberine bound to lecithin, sold at 550 mg a tablet and usually taken twice a day. Absorption: No published study has compared its blood levels directly with the plain salt. The better absorption is the reason for the design, not a measured number. Typical use: 1,100 mg a day. It has its own randomised, double-blind, placebo-controlled trial in 49 people with impaired fasting glucose, which is more than dihydroberberine has.
• Dihydroberberine. Best known for: The reduced form, which turns back into berberine after it's absorbed, sold at roughly a fifth of the milligram dose. Absorption: The only measured direct comparison: 100 mg reached 3.76 ng/mL against 0.4 ng/mL for 500 mg of HCl, with 6.7 times the exposure over two hours. Typical use: 100 to 200 mg. The trial that measured this was only 5 healthy men over two hours, and it found no difference in glucose or insulin.
• Berberine-bearing botanical extract. Best known for: Berberis aristata, Berberis vulgaris, Oregon grape, Coptis, goldenseal and Phellodendron. This is the only way berberine gets into an Australian listed medicine. Absorption: In this evidence, absorption from the whole extract hasn't been compared with the isolated alkaloid. Typical use: Barberry is positive for blood fats across 5 trials and mostly shows no effect on glucose across 7. Berberis aristata with silymarin has 4 trials for blood fats and showed no effect on liver enzymes.
• Berberine with red yeast rice or with silymarin. Best known for: Combination cholesterol formulas, and the versions that actually hold the cholesterol evidence. Absorption: Not measured separately. Typical use: In a 41-trial analysis, combinations did better than berberine alone, which on its own didn't significantly lower LDL at all.
• Berberine ursodeoxycholate (HTD1801). Best known for: An ionic salt of berberine and ursodeoxycholic acid, developed as a possible drug. Absorption: Not comparable. It's a different molecule. Typical use: Tested at 1,000 mg twice a day in a phase 2 study. It isn't a supplement form, and its results tell you nothing about a berberine supplement.

Reference values. There isn't one. Berberine isn't a nutrient, so the NHMRC sets no recommended intake for it, and there's no such thing as a berberine deficiency.

Typical supplemental range. Trial doses are very consistent. Plain berberine HCl was used at 500 mg three times a day (1,500 mg a day) in the first major trial and in a prediabetes pilot, at 500 mg twice a day in a Hong Kong cholesterol trial, and at 1,200 to 1,500 mg a day elsewhere. Berberine phytosome was trialled at 550 mg twice a day, or 1,100 mg a day. Dihydroberberine's only human data used single doses of 100 mg and 200 mg. Anything sold at 400 to 500 mg once a day is below every dose in the major reviews, except for the dihydroberberine and phytosome forms.

Upper level. There's no Australian daily cap for any of the eight permitted plants that contain berberine. The only upper limit the evidence hints at is the opposite of what marketing usually suggests: in an analysis of 28 trials and 2,313 people, the effect became unremarkable above 2 g a day, after 90 days, and in people over 60. There's no dose for children, because there are no trials in children.

Worth knowing. Trials gave it with meals, three times a day, which is also the practical answer for an upset stomach. About one in three people in the original trial had short-lived gut symptoms, usually constipation or loose stools. Most of the measured change happened within 90 days, and the change in inflammation markers showed up within five weeks and at under 1,000 mg a day. What you need depends on your age, diet and health, so talk to one of our naturopaths.

Food first, where the diet allows it.

• Barberry fruit (Berberis vulgaris, dried zereshk), used in Iranian and Middle Eastern cooking: no per-serve berberine figure is available, and the trials used supplemental barberry preparations rather than culinary amounts
• Goldenseal rhizome, Coptis rhizome, Phellodendron bark and Oregon grape root: herbal materials rather than foods; used as extracts, not eaten

If any of these sound like you, talk to one of our naturopaths or your doctor before you start.

• Pregnancy and breastfeeding. Berberis aristata must carry a label warning that it isn't recommended for pregnant or breastfeeding women.
• Children. There's no trial, dose or safety data for children.
• If you take a medicine broken down by CYP3A4. Goldenseal-type extracts blocked CYP3A by around 40 per cent over 28 days.
• If you take a medicine broken down by CYP2D6. The same study found it was blocked by roughly 40 per cent.
• If you take metformin. Goldenseal extract cut metformin levels by about 20 per cent at lower metformin doses.
• If you take medicine to lower blood sugar. Berberine's effect on glucose adds to it, and your prescriber should know.
• If you take a statin cleared by CYP3A4. Talk to a pharmacist before combining them.
• Constipation and diarrhoea are the common side effects; about one in three people had short-lived gut symptoms in the original trial.
• Berberine reduces gut bacteria that make butyrate while increasing gamma-Proteobacteria; what that means for your health is unknown.
• A small number of studies have suggested goldenseal extract may have toxic effects on the nerves and liver, and cause skin reactions to sunlight.
• There's no Australian daily limit for any permitted berberine herb, and the pooled benefit got smaller above 2 g a day.
• If you take prescription medicines, check with your doctor, pharmacist or our naturopaths before you start.