Milk Thistle and Digoxin: Are They Safe Together?

observational-study PMID: 16221754

Quick Summary: This research looked at whether taking milk thistle or black cohosh with the heart medicine digoxin could cause problems. The study found that milk thistle and black cohosh didn't significantly change how the body processed digoxin.

Does Milk Thistle Affect Digoxin?

This study aimed to see if milk thistle or black cohosh could affect how the body uses digoxin, a medicine used to treat heart problems. The researchers were particularly interested in a protein called P-glycoprotein (P-gp), which helps move drugs out of the body. Some herbs can change how P-gp works, which could affect how much digoxin is in your system.

Study Details

Who was studied: 16 healthy adults.

How long: Participants took milk thistle or black cohosh for 14 days.

What they took:

Milk Thistle: 900 mg daily
Black Cohosh: 40 mg daily
Digoxin: A single dose before and after taking the herbs.

What This Means For You

The good news is, this study suggests that milk thistle and black cohosh, at the doses used, are unlikely to significantly interfere with digoxin. This means that if you're taking digoxin and considering milk thistle or black cohosh, this study doesn't raise major red flags. However, it's crucial to talk to your doctor before combining any supplements with your medications. They can give you personalized advice based on your health and the specific products you're using.

Study Limitations

Small Study: The study only included a small number of people, so the results might not apply to everyone.

Short Timeframe: The study only looked at the effects over a short period. Long-term use could have different results.

Healthy People: The study only involved healthy people, not those with heart conditions.

Specific Products: The study used specific brands and dosages of milk thistle and black cohosh. Other products might have different effects.

Important Note: This information is for educational purposes only and is not a substitute for professional medical advice. Always consult with your doctor or other qualified healthcare provider if you have questions about a medical condition or before making any decisions about your health or treatment.

Key Findings

This 2006 study found that milk thistle (900 mg/day) and black cohosh (40 mg/day) supplementation did not significantly alter digoxin pharmacokinetics in healthy humans. Rifampin (a P-gp inducer) reduced digoxin exposure (AUC_0–3, AUC_0–24, C_max by >20%, p < 0.01), while clarithromycin (a P-gp inhibitor) increased these parameters (p < 0.01). Milk thistle showed a trend toward increasing digoxin AUC_0–3 and AUC_0–24 (p = 0.06), but not statistically significant. The authors concluded neither herb is a potent P-gp modulator in vivo, contrasting with the strong effects of rifampin and clarithromycin.

Study Design

This was a controlled observational crossover study involving 16 healthy volunteers (no demographic details provided). Participants were randomized to receive milk thistle, black cohosh, rifampin (600 mg/day for 7 days), or clarithromycin (1,000 mg/day for 7 days) in a sequence with 30-day washout periods between interventions. Digoxin (0.4 mg oral dose) was administered pre- and post-supplementation, and serum concentrations were measured over 24 hours using chemiluminescent immunoassay. Pharmacokinetic parameters included AUC, C_max, CL/F, and elimination half-life.

Dosage & Administration

Milk thistle was administered at 900 mg/day (standardized extract), and black cohosh at 40 mg/day for 14 days. Rifampin (600 mg/day) and clarithromycin (1,000 mg/day) were given for 7 days as positive controls. All supplements and drugs were taken orally. Digoxin was administered as a single 0.4 mg oral dose (Lanoxicaps) before and after each supplementation period.

Results & Efficacy

Rifampin: Reduced digoxin AUC_0–3 (23%), AUC_0–24 (19%), and C_max (21%) (p < 0.01 for all).
Clarithromycin: Increased digoxin AUC_0–3 (32%), AUC_0–24 (28%), and C_max (25%) (p < 0.01), prolonged elimination half-life (p < 0.01), and reduced CL/F (p < 0.01).
Milk thistle: No significant changes in AUC, C_max, CL/F, or half-life. However, AUC_0–3 and AUC_0–24 approached significance (p = 0.06), suggesting a weak or non-significant trend toward reduced P-gp activity.
Black cohosh: No statistically significant effects on any pharmacokinetic parameter.

Limitations

Small sample size (n=16) may limit power to detect subtle interactions.
Short supplementation duration (14 days) might not fully capture long-term herb-drug effects.
Healthy volunteers only; results may not generalize to patient populations with comorbidities or altered metabolism.
Single-dose digoxin assessment; repeated dosing could yield different outcomes.
Specific formulations tested: Findings may not apply to other milk thistle/black cohosh products with varying phytochemical profiles.

Clinical Relevance

For individuals taking digoxin (e.g., for heart failure or arrhythmias), this study suggests milk thistle (900 mg/day) and black cohosh (40 mg/day) do not pose clinically significant herb-drug interactions via P-gp modulation. However, the near-significant trend with milk thistle (p=0.06) warrants caution, as higher doses or prolonged use might theoretically influence digoxin levels. Supplement users should still consult healthcare providers, particularly when combining with narrow-therapeutic-index drugs like digoxin, as individual variability may exist. The study supports the safety of these supplements in the context of P-gp substrate interactions but does not rule out other mechanisms of interaction.

Source: PubMed | Date: 2006 | Type: Observational crossover study.