Two natural compounds, berberine and fisetin, have recently attracted clinical and preclinical attention, potentially playing roles in a holistic, science-led PCOS strategy.

Berberine: A Clinically Validated Insulin Sensitiser for PCOS

WHAT IS BERBERINE?

Berberine is a plant-derived alkaloid found in various herbs used in traditional medicine. In recent years, it has gained prominence for its ability to modulate glucose metabolism, improve lipid profiles, and exert potent anti-inflammatory effects, key factors for women with PCOS.

WHAT DOES THE EVIDENCE SAY?

A controlled clinical trial published by the European Journal of Endocrinology confirmed that “administration of berberine (0.5 grams three times daily) was able to reduce fasting blood glucose, fasting insulin, the homeostasis model assessment of insulin resistance (HOMA-IR), and the area under the curve for insulin in patients with polycystic ovary syndrome (PCOS).” (Wei et al., 2012) This places berberine as a serious contender alongside established pharmaceuticals.

In a direct comparison, the same trial demonstrated a pronounced benefit for lipid metabolism in both animal and human studies. By upregulating LDL receptors in the liver, berberine significantly reduced total cholesterol, triglycerides, and LDL cholesterol, while also increasing HDL cholesterol after just three months of use. While both berberine and metformin improved glucose control, berberine delivered superior results for correcting lipid imbalances—outperforming metformin in this key area according to the study’s findings. This finding is significant for women seeking alternatives to metformin, especially given metformin’s frequent GI side effects.

HOW DOES BERBERINE WORK?

Berberine’s mechanism of action is multifaceted. It activates AMP-activated protein kinase (AMPK), a cellular energy sensor, which in turn enhances insulin sensitivity and improves glucose uptake by the muscles. This is particularly relevant for the estimated 70% of UK women with PCOS who struggle with insulin resistance.

Moreover, berberine demonstrates a cholesterol-lowering effect, reducing both triglycerides and LDL-cholesterol. In clinical practice, this translates to a meaningful reduction in cardiovascular risk, which is elevated in PCOS.

ADDITIONAL BENEFITS: MENSTRUAL REGULARITY AND SAFETY

Not only does berberine support metabolic health, but participants in a clinical study conducted by Department of Public Health, University of Pavia, showed an “improvement of the ovulation rate per cycle“ and “an improvement of the regularity of menstrual cycles when orally administered at a dose of 500 mg twice-per-day for 6 months” (Rondanelli et al 2020). Furthermore, clinical data show berberine is well tolerated.

COMPETITIVE ADVANTAGE: BERBERINE VS. TOPICAL & PRESCRIPTION OPTIONS

While prescription medications like metformin and inositol are common, and topical treatments may help with skin manifestations of PCOS, only a handful of supplements demonstrate robust, direct effects on metabolic and hormonal parameters. Berberine stands out not only for its “comparable efficacy to metformin” but also for its safety profile.

For optimal effect, berberine supplements should be high strength, with superior bioavailability, such as Manapura’s pharmaceutical-grade 500mg Berberine (99.3% purity).

Fisetin: An Emerging Antioxidant in PCOS Support

WHAT IS FISETIN?

Fisetin is a naturally occurring flavonoid found in strawberries, apples, and persimmons. Its role as a potent antioxidant and anti-inflammatory agent is gaining traction in the context of metabolic and reproductive health.

WHAT DOES THE PRECLINICAL EVIDENCE SAY?

In a landmark animal study, rats with letrozole-induced PCOS were treated with fisetin (1.25–2.5 mg/kg). The researchers found that “fisetin treatment caused significant alleviating effects by restoring PCOS-induced alterations” by modulating AMPK/SIRT1 signalling, reducing inflammatory cytokines and oxidative stress markers, and restoring hormonal balance and ovarian morphology” (Mihanfar et al., 2021).

A second rat-based study confirmed that taking fisetin at a high dose resulted in significanty lower testosterone, estradiol and enhances progesterone, demonstrating “the potential of fisetin as a promising therapeutic intervention for the management of PCOS by modulating AMPK/SIRT1 signaling” (Chahal and Kabra 2024).

While these findings are preclinical, they signal an exciting new direction for adjunctive PCOS care.

Frequently Asked Questions: PCOS, Berberine, Fisetin

• Is berberine safe to take with metformin or other PCOS medications?


  According to the observed effects in published clinical studies, berberine does not appear to interfere with other PCOS medications and is generally well tolerated. However, always consult your healthcare practitioner before starting any new supplement.

• How long does it take to see results with berberine?


  Clinical trials typically report meaningful improvements in insulin sensitivity, glucose levels, and lipid profiles within 3-6 months of daily supplementation.

• Can fisetin help with PCOS symptoms in humans?


  While most fisetin research is currently in animal models, its antioxidant and anti-inflammatory effects show promise for managing ovarian inflammation and hormonal imbalance—two key drivers of PCOS.

Takeaway: A Science-Led Approach to PCOS Management

The emerging clinical and preclinical evidence for berberine and fisetin in PCOS is robust and compelling:

• BERBERINE is now recognised as a clinically validated, well-tolerated insulin sensitiser with efficacy comparable to first-line therapies.
  
  
• FISETIN represents an exciting new direction, targeting ovarian inflammation and hormonal dysregulation.
  
  

As with all supplements, the quality and bioavailability of the product are paramount. Manapura’s high-strength, independently tested formulas deliver pharmaceutical-grade purity and potency, backed by rigorous supply chain and quality certifications.

Always consult your healthcare practitioner before introducing new supplements to your regime.

For those in the UK looking for science-backed support in managing PCOS, both berberine and fisetin offer promising, evidence-led options to consider alongside standard medical care.

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