Herbs and Nutrients that May Assist

Chromium picolinate
Chromic chloride hexahydrate
Berberine hydrochloride derived from Indian barberry
Berberis aristate, root
Milk thistle
Silybum marianum, seed

Actions

• Reduces the metabolic impacts of visceral fat
• Preserves pancreatic beta islet cell function
• Supports healthy blood glucose levels
• Stimulates muscle and adipose metabolism

Clinical Applications

• Type 2 diabetes mellitus (T2DM)
• Polycystic ovarian syndrome (PCOS)

Indian Barberry and Milk Thistle for Blood Glucose Metabolism and Liver Function Support

Metabolic dysfunction is a growing chronic health issue, affecting up to a quarter of the Asia-Pacific region. [1] This condition is driven by fat accumulation in metabolic organs like the liver and pancreas. This accumulation leads to hepatic insulin resistance, increased glucose production, hyperinsulinaemia, and eventually, pancreatic beta islet cell (β-cell) failure. [2]

To address these issues, berberine hydrochloride, a component of Berberis aristata (Indian barberry), has been shown in vivo to reduce visceral fat. [3-5] This reduction lowers inflammationand oxidative stress, which are key contributors to chronic metabolic dysfunction. [6-8] These mechanisms help improve glucose control and blood lipid profiles in humans, especially when combined with Silybum marianum (milk thistle). [9] Additionally, chromium has been found to support metabolic balance. [10]

Therefore, a blend of berberine hydrochloride, milk thistle, and chromium can help support and maintain healthy metabolic function

Background info­rmation

Addressing the true cause of metabolic dysfunction

Metabolic syndrome is characterised by raised insulin levels and abnormal glucose and lipid metabolism.^[11] These chronic patterns can increase the risk of cognitive impairment, cardiovascular disease, liver disease, and reproductive disorders.^[11-13]

In individuals with abnormal metabolic pathology, an ‘energy overload’ state within the liver and pancreas is often observed.^[2,14-16] This occurs when energy intake exceeds storage capacity, leading to visceral fat accumulation Researchers describe this as the ‘twin cycle’ model, where visceral fat increases glucose synthesis, followed by insulin output. Excess insulin stimulates triglyceride overproduction in the liver, creating a feedback loop of chronic metabolic imbalance (Figure 1).^[2,15-16]

Figure 1: The Twin Cycle: Energy that cannot be stored as glycogen in muscle is converted into triglycerides via lipogenesis. In response to caloric excess, increased hepatic fat accumulation results in an overflow of lipoprotein-bound triglycerides into the pancreas, which can limit insulin output.

Left Unaddressed, Visceral Fat Leads to Organ Damage

Accumulated visceral fat causes tissue damage due to an oversupply of fatty acids within cells. ^[3,7] This upregulates mitochondrial energy synthesis and reactive oxygen species (ROS) output in response to increased fatty acid oxidation.^[3] High ROS levels in the liver and pancreas activate endoplasmic reticulum (ER) stress pathways,^[17] stimulating pro-inflammatory mediators that promote organ damage.^[7,18,19] Additionally, ER stress increases the activity of lipogenic liver enzymes,^[18] leading to greater triglyceride synthesis and more visceral fat.^[18]

Botanical extracts, such as berberine and milk thistle, show promise in breaking this cycle. These extracts have been demonstrated to effectively mitigate the sequence of pathological events^.[3-8]

Enhancing Berberine Absorption: Silymarin Modulates P-glycoprotein Pumps

Despite its therapeutic potential for metabolic dysfunction, berberine has poor oral bioavailability.This is due to intestinal P-glycoprotein (P-gp) mediated gut extrusion processes, which can reduce berberine absorption by up to 90%. Silymarin, a flavolignan from Silybum marianum, can inhibit P-gp and increase berberine uptake (Figure 2). Therefore, combining berberine and milk thistle with standardized levels of flavolignans enhances berberine’s therapeutic bioavailability and clinical effect.^[9]

Actions

Reduces the metabolic impacts of visceral fat

In animals, berberine reduces accumulated liver fat and lowers free fatty acid output in response to excess energy intake.^[3-5,8] In states of energy overload, berberine minimises mitochondrial ROS production,^[4] as well as inflammatory markers in the liver, including interleukin 1-beta (IL-1β), IL-6 and tumour necrosis factor alpha (TNF-α).^[6-8] Additionally, berberine enhances intracellular resilience to ROS^[3] and decreases ER stress,^[7] thereby limiting the activation of genes, and enzymes that upregulate lipogenesis in metabolic dysfunction.^[3,6,7]

These effects are partly linked to the inhibition of bile salt hydrolase enzymes produced by intestinal microbiota which facilitate the breakdown of taurine-conjugated bile acids (TCA).^[5] Increased TCA levels have been shown to stimulate intestinal farnesoid X receptors, leading to lower expression of genes and proteins that promote fatty acid accumulation in the liver.^[5,20] Berberine also induces cytochrome 7A1, an enzyme that converts cholesterol into bile acids, which further promotes intestinal lipid excretion to help rebalance metabolic overload.^[3,5]

Preserves pancreatic β-cell function

Berberine has been shown to protect pancreatic β-cell function in diabetic rodents. By reversing degenerative cell damage within islet mitochondria and ER structures, berberine can enhance insulin synthesis and secretion.^[21] This was linked to offsetting ROS caused by the oxidation of surplus intracellular fat, which drives pancreatic damage. Moreover, studies indicate berberine can increase levels of regulatory sirtuin1 (SIRT1),^[22] an endogenous enzyme that mitigates ER stress[23] to protect β-cell function and insulin output.^[19,24] Collectively, this evidence validates the use of berberine to help mitigate pancreatic damage.^[21]

Supports healthy blood glucose levels

Berberine has been shown to enhance insulin secretion exclusively in hyperglycaemic states.^[21] This indicates its ability to help balance blood sugar with a low risk of triggering hypoglycaemia when combined with other treatments.^[21] Unique in its action, berberine blocks outgoing potassium elimination channels within pancreatic β-cells, which leads to an influx of intracellular calcium that stimulates greater insulin secretion.^[21] Therefore, berberine can effectively protect β-cells while also increasing functional insulin output to manage elevated glucose.

Equally, chromium also supports healthy blood glucose control.^[27] Low chromium levels have been noted in over 50% of individuals with type 2 diabetes mellitus (T2DM),^[28] while its supplementation in these populations leads to improvements in markers of insulin resistance and hyperglycaemia.^[10] Mechanistically, chromium is a nutritional cofactor for insulin signalling molecule, chromodulin, that promotes insulin-cell communication and glucose uptake.^[27] As such, chromium supports insulin function, which enhances the clearance of excess glucose from the blood stream.

Stimulates muscle and adipose metabolism

In response to surplus energy stores, berberine enhances metabolism, shown to reduce total cholesterol (TC) and triglycerides (TGs), as well as lowering fasting glucose and elevated insulin in vivo. ^[8] Further, berberine was shown to increase high-density lipoprotein (HDL) and decrease low-density lipoprotein (LDL). ^[8] These effects highlight berberine’s positive impact on metabolism throughout the body - particularly within muscle ^[3] and adipose tissue.^[29]

Shown to increase mitochondrial biosynthesis in skeletal muscle in vivo, berberine improves metabolic capacity of muscular tissue, which enhances the uptake of lipids and glucose.^[30] This in turn helps stimulate the catabolism of excess energy substrates and improves insulin sensitivity. ^[30] Additionally, berberine increases mitochondrial density in mature adipose tissue in animals, which enhanced energy metabolism while offsetting weight gain following a high-fat diet. ^[29] As such, by upregulating the utilisation of energy within muscle and fat, berberine can help to alleviate metabolic overload and improve insulin sensitivity.

Clinical Applications

Type 2 Diabetes Mellitus (T2DM)

The combination of berberine and silymarin, taken over six to twelve months, has been shown to lower total cholesterol (TC), low-density lipoprotein (LDL), and elevated triglycerides (TGs), while also improving high-density lipoprotein (HDL) levels in patients with T2DM.^[31,32] Interestingly, this combination led to greater improvements in blood lipids compared to metformin treatment.^[32] Additionally, improvements in fasting glucose, postprandial glucose, glycated hemoglobin, fasting insulin, and insulin resistance were reported, comparable to taking 1,500 mg/day of metformin.^[32] This herbal combination has been safely used alongside various metabolic medications, including metaformin, sulfonylureas, insulin and cholesterol-lowering medication.^[9]

Moreover, in a study comparing berberine and silymarin to a placebo alongside a weight loss protocol in T2DM patients, active treatment resulted in a 21.6% greater decline in visceral fat.^[31] Furthermore, chromium has been found to enhance glucose control and support healthy weight management in T2DM,^[10,33] reinforcing the therapeutic value of berberine, silymarin, and chromium in managing metabolic dysfunction. For more clinical results showcasing this combination in T2DM, refer to Table 1.

Polycystic Ovarian Syndrome (PCOS)

PCOS is recognized as both a metabolic condition and a reproductive disorder.^[34] In a study involving 50 patients with an average body mass index (BMI) greater than 31, the combination of berberine and silymarin improved insulin sensitivity, serum lipids, and hyperandrogenism (p<0.01).^[35] Similarly, in 64 PCOS patients, taking 200 μg/day of chromium picolinate over 8 weeks reduced elevated plasma insulin levels by 22.5%, insulin resistance by 25%, and TC levels by 6.2% (p<0.05).^[36] Interestingly, in a study of 92 PCOS women, taking 200 μg/day of chromium picolinate for 12 weeks achieved effects comparable to metformin in supporting pregnancy rates, along with other positive outcomes outlined in Table 1. ^[37] Therefore, ingredients in Indian Barberry and Milk Thistle for Blood Glucose Metabolism and Liver Function Support can help lower blood lipids and elevated blood glucose in patients with metabolic dysfunction, including T2DM and PCOS.

Summary of ingredients:

Table 1: Berberine, silymarin and chromium in diabetes and PCOS

Population	Study Details	Outcome
69 T2DM adults; mean age 67.1, BMI>25.[9]	120 days; single-blind RCT. 1,000 mg/d berberine + 210 mg/d silymarin vs. 1,000 mg/d berberine alongside antidiabetic/ cholesterol lowering medication, low caloric diet and exercise prescription.	Berberine and silymarin had greater effect than berberine alone on reducing: - HbA1c: 1.72 x more effective vs. berberine (-12.3% [-0.99% from 8.02%] vs. -7.1% [-0.56% from 7.81%]; p<0.05). - LDL levels: -16.9% (-0.41 from 2.4 mmol/L; p<0.004), vs. -12.1% (-0.3 from 2.5 mmol/L; p value=NS). Both treatments shared similar effects on (p<0.007): - Fasting glucose: -18.1% and -19% (-1.5 and -1.6 mmol/L from 8.8 and 8.7 mmol/L). - Total cholesterol: -11.05% and -11.9% (-0.5 and -0.55 mmol/L from 4.6 and 4.65 mmol/L). - Triglycerides: -22.6% and -21.6% (-0.39 and -0.37 mmol/L from 1.75-1.78 mmol/L).
109 T2DM adults ; BMI>25 and HbA1c >6.5% and <8.5%.[32]	6 months; double-blind RCT. HbA1c <7.5%: 1,000 mg/d berberine + 210 mg/d silymarin HbA1c >7.5%: 1,500 mg/d berberine + 324 mg/d silymarin vs. 1,500 mg/d metformin; All groups: 600-kcal caloric deficit diet + physical activity.	At six months berberine and silymarin achieved similar outcomes to metformin treatment compared to baseline (p<0.05): - HOMA IR: -25.4% reduction (-1.3 from 5.1) vs. -27% (-1.4 from 5.2). - HbA1c: -6.5% decrease (-0.5% from 7.6%) vs. -8% (-0.6% from 7.5%). - Fasting insulin: -22.3% decline (-3.3 from 14.8 μIU/mL) vs. -21.7% (-3.3 from 15.2 μIU/mL). - Fasting glucose: -6.4% decrease (-0.5 from 7.8 mmol/L) vs. -6.6% (-0.5 from 7.6 mmol/L). - Postprandial glucose: -8.2% reduction (-0.7 from 8.5 mmol/L) vs. -10.5% (-0.9 from 8.6 mmol/L). Berberine and silymarin achieved greater improvements on plasma lipids vs. metformin (p<0.05): - Total cholesterol: -17.8% reduction (-0.91 from 5.1 mmol/L) vs. -7.4% (-0.38 from 5.1 mmol/L). - LDL: -26.6% decrease (-0.85 from 3.19 mmol/L) vs. -10.7% (-0.34 from 3.17 mmol/L). - Triglycerides: -12.2% reduction (-0.21 from 1.72 mmol/L) vs. -6.43% (-0.11 from 1.79 mmol/L).­
85 type 1 diabetics; mean age 30.25, average BMI 22.6.[38]	6 months; double-blind RCT. 1,000 mg/d berberine + 210 mg/d silymarin + insulin vs. placebo + insulin.	Berberine and silymarin improved insulin sensitivity compared to placebo(p<0.05): - HbA1c: -5% decrease (-0.4% from 8.0%) vs. -1.2% (-0.1% from 7.8%). - Decrease in required insulin units: -14.7% vs. -0.05%. - Fasting glucose: -11.5% decrease (-0.95 from 8.2 mmol/L) vs. +2.5% (+0.2 from 7.87 mmol/L). - Postprandial glucose : -12.1% reduction (-1.3 from 10.7 mmol/L) vs. -1.25% (-0.13 from 10.4 mmol/L).
50 women diagnosed with PCOS; mean age 24.2, average BMI >31.[35]	6 months; open label, case-control clinical trial. 1,000 mg/d berberine + 210 mg/d silymarin + usual diet and physical activity­­­.	At six months berberine and silymarin had improved insulin sensitivity, serum lipids and hyperandrogenism(p<0.01): - HOMA IR: -22.2% (-1.2 from 4.4). - Total cholesterol: -9% (-0.36 from 4.03 mmol/L). - LDL: -9.9% (-0.2 from 2.09 mmol/L). - Triglycerides: -4.2% (-0.05 from 1.35 mmol/L). - Hyperandrogenism: Free testosterone (-15.4%) and free androgen index (-46%).
137 patients; mean age 57.9, BMI >29 experiencing adverse effects to statin medications (10 mg/d – 40 mg/d).[39]	6 months; double-blind RCT. 1,000 mg/d berberine + 210 mg/d silymarin vs. placebo Both groups: half-dose of original statin medication + 600 kcal deficit diet.	Compared to placebo, berberine and silymarin greatly minimised dyslipidaemia severity ( - Total cholesterol: placebo +19% (+0.91 from 4.8 mmol/L) vs. berberine and silymarin +4% (+0.2 from 4.9 mmol/L). - LDL: placebo +22.5% (+0.72 from 3.2 mmol/L) vs. berberine and silymarin +2.7% (+0.09 from 3.34 mmol/L). - Triglycerides placebo + 34.4% (+0.37 from 1.08 mmol/L) vs. berberine and silymarin +13.3% (+0.14 from 1.05 mmol/L). Protective effects of berberine + silymarin over dyslipidaemia were associated with improvements in glucose metabolism markers, FPG, fasting insulin and improved HOMA IR (p<0.05).
136 obese T2DM adults; mean age 55.5, average BMI>34).[31]	52 weeks; double-blind randomised, placebo-controlled trial (RCT). 1,000 mg/d berberine + 210 mg/d silymarin vs. placebo in conjunction with a 20%-25% caloric deficit diet + 30 minutes exercise daily.	Compared to placebo, berberine and silymarin treatment achieved greater effects on (p<0.05): ­­ - HOMA IR: -40% (-1.9 from 4.7) vs. -6.5% (-0.3 from 4.6). - HbA1c: -19% (-1.5% from 7.9%) vs. -5.1% (-0.4% from 7.8%). - Total cholesterol: -25% (-1.5 from 6.1 mmol/L) vs. -15% (-0.9 from 6.02 mmol/L). - LDL: -33% (-1.3 from 3.9 mmol/L) vs. -22.2% (-0.87 from 3.9 mmol/L). - HDL: +17% (+0.18 from 1.06 mmol/L) vs. +1.9% (+0.02 from 1.06 mmol/L) - Triglycerides: -25% (-0.56 from 2.23 mmol/L) vs. -7.1% (-0.16 from 2.25 mmol/L). - BMI: -5% greater decrease compared to placebo (-12.3% - [-4.2] vs. -7.35% [-2.5]). - Visceral fat: -21.6% larger decline (-39% - vs. -17.4%). - Waist circumference: -15 cm vs. --6 cm. - Total body fat: -7% bigger decline (-8% vs. -1%).
64 diabetic patients with coronary heart disease; mean age 59.4, average BMI >29.9[10]	12 weeks; double-blind RCT. 200 μg/d chromium picolinate vs. placebo + aspirin and statins, antihypertensive or antidiabetic drugs.	- Chromium achieved 900 g weight loss (p<0.003) compared to a 100 g gain with placebo - Lowered BMI by -0.4 (p<0.006), - Reduced fasting glucose by -7.7% (-0.6 from 7.2 mmol/L; p<0.007) - Reduced plasma insulin by -12% (-1.4 from 11.6 μIU/mL; p<0.001). - HOMA-IR was improved by -13% (-0.5 from 3.8; p<0.001) - hs-CRP was lowered by 13.5% (-0.7 mg/L decline from 5.2 mg/L).
64 PCOS patients; mean age 24.6, average BMI >25.[36]	8 weeks; double-blind RCT. 200 μg/d of chromium picolinate vs. placebo.	- Chromium reduced elevated insulin levels by -22.5% vs. +28.5% with placebo (-3.0 μIU/mL from 13.3 μIU/mL vs.+3.1 μIU/mL; p<0.001). - HOMA-IR was reduced by -25% vs. +32% increase with placebo (-0.7 from 2.8 at baseline; p<0.001). - Improved total cholesterol by -6.2% (-0.25 mmol/L from 4 mmol/L; p<0.03), - Improved normal triglyceride levels by -12.5% (-0.15 mmol/L from 1.2 mmol/L; p<0.008).
92 PCOS patients; mean age 26.6, average BMI >28.[37]	12 weeks; double-blind RCT. 200 μg/d of chromium picolinate vs. 1,500 mg/d metformin.	- Chromium decreased elevated fasting insulin by 9.3% (-1.51 μIU/mL from 16.2 μIU/mL; p<0.001) - Achieved comparable effects to metformin on stimulating ovulation and supporting pregnancy rates.

Note: Pathology has been converted into millimoles per litre of blood (mmol/L) for Aus/NZ/universal interpretation.

Safety Information

Disclaimer: In the interest of supporting Healthcare Practitioners, all safety information provided at the time of publishing is in accordance with Natural Medicine Database (NATMED PRO), renowned for its professional monographs which include a thorough assessment of safety, warnings, and adverse effects.

For further information on specific interactions with medications, please contact Clinical Support on 1800 777 648, or via email, anz_clinicalsupport@metagenics.com

Pregnancy and Lactation

• Likely unsafe; avoid using.[40]

Contraindications

• Contraindicated with cyclosporine; berberine may inhibit cytochome CYP P450 3A4 which metabolises this drug.[40]

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