How can I lower my galectin‑3 level?

Lowering Galectin-3 Levels: Evidence-Based Approach

The most effective strategy to lower galectin-3 levels is to initiate guideline-directed medical therapy for heart failure with ACE inhibitors or ARBs (or ARNI), beta-blockers, and aldosterone antagonists in selected patients, as these medications address the underlying cardiac inflammation and fibrosis that drive galectin-3 elevation. 1

Understanding Galectin-3 as a Biomarker, Not a Treatment Target

Current clinical guidelines do not recommend targeting galectin-3 levels directly for therapeutic intervention. 1 Instead, galectin-3 serves as a prognostic biomarker that reflects ongoing cardiac inflammation and fibrosis 1. The American Heart Association and ACC/AHA guidelines classify galectin-3 measurement as a Class IIb recommendation (may be considered) for additive risk stratification in chronic heart failure, but not as a therapeutic target 1.

Why Galectin-3 Elevation Matters

• Galectin-3 is secreted by activated macrophages and stimulates fibroblast proliferation and collagen deposition, leading to pathological cardiac remodeling 1
• Elevated levels (>25.9 ng/mL) predict rapid heart failure progression, hospitalization, and death independent of symptoms and other laboratory measures 2
• The biomarker reflects cardiac inflammation, with increases occurring when inflammatory cells infiltrate the myocardium 3

Evidence-Based Treatment Strategy

Primary Intervention: Optimize Heart Failure Therapy

The renin-angiotensin system inhibition strategy is the cornerstone for addressing the pathophysiology that drives galectin-3 elevation. 1

• Initiate ACE inhibitors (Class I, Level of Evidence A) to reduce morbidity and mortality in heart failure with reduced ejection fraction 1
• Alternative: ARBs if ACE inhibitors are not tolerated (Class I, Level of Evidence A) 1
• Consider ARNI (angiotensin receptor-neprilysin inhibitor) as superior alternative (Class I, Level of Evidence B-R) 1
• Add evidence-based beta-blockers in conjunction with renin-angiotensin system inhibition 1
• Include aldosterone antagonists in selected patients to further reduce cardiac fibrosis 1

Mechanism of Action

These medications work by:

• Reducing neurohormonal activation that drives cardiac inflammation 1
• Decreasing myocardial wall stress that triggers galectin-3 release 3
• Attenuating the inflammatory cascade that leads to macrophage activation and galectin-3 secretion 1

Disease-Specific Considerations

Etiology Matters for Galectin-3 Elevation

The mechanism of galectin-3 increase varies by underlying cardiac condition. 3

• In fibrotic cardiomyopathy and ischemia-reperfusion injury: Cardiac inflammation drives direct cardiac release of galectin-3 into circulation, creating a trans-cardiac gradient 3
• In dilated cardiomyopathy without inflammation: Cardiac galectin-3 content increases 50-fold, but circulating levels may remain normal due to absence of inflammatory cell infiltration 3
• With enhanced β-adrenoceptor activation: Isoproterenol-induced stress elevates both cardiac and plasma galectin-3 through inflammatory mechanisms 3

Critical Clinical Pitfall

Do not assume elevated galectin-3 always reflects cardiac disease—renal dysfunction independently raises circulating levels. 3 In patients with hypertrophic cardiomyopathy or dilated cardiomyopathy, plasma galectin-3 increases only when renal dysfunction is present, and no trans-cardiac gradient exists 3.

Monitoring Strategy

Serial galectin-3 measurements provide prognostic value but should not drive treatment decisions. 1, 2

• Measure galectin-3 before hospital discharge for heart failure patients 2
• Consider outpatient evaluation approximately twice per year for stable symptoms 2
• A doubling of galectin-3 over 6 months identifies high-risk patients warranting intensified care management, regardless of baseline value 2

What Does NOT Work

There is no FDA-approved therapy specifically targeting galectin-3 reduction. 4, 5 While experimental research explores galectin-3 inhibition as a therapeutic approach to prevent cardiac inflammation and fibrosis, this remains investigational 5.

Targeting specific galectin-3 thresholds during hospitalization is not practical or safe and has not been tested in prospective large-scale trials 1. Clinical assessment and adherence to guideline-directed medical therapy should be the emphasis 1.

The Bottom Line

Focus on treating the underlying heart failure with proven guideline-directed medical therapy rather than attempting to lower galectin-3 as an isolated target. 1 The renin-angiotensin system inhibition strategy with ACE inhibitors/ARBs/ARNI, combined with beta-blockers and aldosterone antagonists, addresses the cardiac inflammation and fibrosis that drive galectin-3 elevation 1. Use galectin-3 levels for risk stratification and prognostication, not as a therapeutic endpoint 1, 2.