Galectin-3, Training, and Exercise: How Physical Activity Shapes Cardiac Fibrosis Risk

What Is Galectin-3 and Why Does It Matter for the Heart?

Galectin-3 is a protein involved in inflammatory and fibrotic processes. Researchers measure it in blood to investigate associations with heart-failure severity and outcomes. A circulating concentration is not a direct measurement of how much scar tissue is present in the heart. [1]

In the HF-ACTION biomarker analysis, higher baseline galectin-3 was associated with poorer exercise capacity, worse kidney function and other indicators of more severe heart failure. Its association with outcomes weakened after accounting for established predictors, particularly NT-proBNP. This matters when deciding whether another test adds useful information. [1]

Galectin-3 Versus BNP and NT-proBNP

BNP and NT-proBNP have established roles in heart-failure assessment. The 2022 AHA/ACC/HFSA guideline describes additional biomarkers of inflammation and remodeling as potentially providing prognostic information, while noting that an additional management benefit has not been established. It does not provide a galectin-3 target for adjusting an exercise program. [2]

Galectin-3 Normal Range and Optimal Targets

The BGM Galectin-3 test was cleared as an aid to prognosis in patients already diagnosed with chronic heart failure, used with clinical evaluation. Its validation evaluated groups defined by 17.8 and 25.9 ng/mL. These are clinical study categories for that assay and population, not universal boundaries between a healthy and unhealthy athlete. [3]

A lab's reference interval and a study's prognostic threshold answer different questions. Interpretation should use the actual laboratory report, method and clinical setting. Comparing results from different assays can make a change difficult to interpret.

Is Below 12 ng/mL an Established Optimal Level?

The studies cited here do not establish a universal goal below 12 ng/mL or a HealthRX.com protocol that improves outcomes by achieving it. Being in a lower biomarker group in an observational analysis does not prove that deliberately moving a person into that group produces the same outcome.

The CORONA galectin-3 substudy included 1,462 older participants with ischemic systolic heart failure. Associations with outcomes were no longer significant after NT-proBNP entered the adjusted model. Its results cannot establish a fitness target for healthy people. [4]

How Exercise and Training Affect Galectin-3

The most useful distinction is between a sustained training program and the immediate response to one demanding workout. A second distinction is between gene expression and the amount of protein measured in blood.

Does Aerobic Exercise Consistently Lower It?

Some studies support a decrease after training, but they do not establish a reliable percentage reduction for every patient. In the 2026 study, aerobic exercise involved supervised treadmill sessions three times weekly. Resistance exercise also reduced the measured biomarker. The study assessed eight-week changes in young sedentary women, not reversal of cardiac fibrosis in heart-failure patients. [6]

Exercise capacity can improve without a specified galectin-3 change. Choosing a useful program therefore requires attention to the person, the clinical goal and sustainable training, rather than treating a single laboratory value as the main outcome.

Is HIIT Better Than Moderate Training?

The 2020 comparison found larger changes in galectin-3 gene expression with HIIT. It did not establish a 22% fall in circulating galectin-3 in a 62-person HFpEF trial, nor did it demonstrate fewer heart-failure events. Those endpoints should not be substituted for what the researchers actually measured. [5]

Resistance Training

The 2026 trial provides direct, small-study evidence that resistance training can affect circulating galectin-3. It does not prove that resistance exercise is half as effective as aerobic exercise, or establish a combined regimen that produces additive biomarker reductions. [6]

Why Galectin-3 Can Rise After Exercise

In a study of 19 marathon runners, 27 ultratrail runners and 14 recreational runners, concentrations changed after the run and galectin-3 returned toward baseline during the three-hour recovery period. A sample taken immediately after an event can therefore answer a different question from a resting sample. [8]

A 2023 study of 20 trained men also found increases after strenuous interval exercise in both runners and cyclists. These short-term responses do not, by themselves, establish permanent cardiac damage. [9]

In a 2026 study of 36 male long-distance runners, galectin-3 rose substantially after a marathon. Associations with atrial function were exploratory. This adds evidence that collection timing matters, while leaving questions about long-term significance unresolved. [10]

Galectin-3 in Heart Failure: Prognosis and Treatment Response

What HF-ACTION Actually Shows

The main HF-ACTION trial randomized 2,331 medically stable people with reduced-ejection-fraction heart failure to usual care with or without aerobic training. Its primary unadjusted analysis did not show a statistically significant reduction in all-cause death or hospitalization; prespecified adjusted analyses showed modest benefit. The study supports exercise in an appropriate heart-failure care plan. [11]

The separate galectin-3 analysis assessed baseline samples from 895 participants. It was an analysis of prognosis, not a demonstration that exercise lowered galectin-3 by 2.1 ng/mL at twelve months in a 480-person subgroup. [1]

Serial Measurements

CORONA and COACH analyses associated rising galectin-3 with worse subsequent outcomes. The investigators assessed 1,329 and 324 participants, respectively, and examined a 15% change threshold. That threshold was part of a prognostic analysis. It does not establish that a 15% reduction after training proves that cardiac fibrosis has reversed. [12]

HFpEF and Other Clinical Factors

A study of 592 previously hospitalized heart-failure patients found prognostic information from galectin-3, including in a smaller preserved-ejection-fraction subgroup. Its findings do not prove that every elevated result is caused by cardiac fibrosis or that galectin-3-guided exercise improves clinical outcomes. [13]

Kidney function, other biomarkers and the overall clinical picture affect interpretation. The HF-ACTION findings illustrate why higher galectin-3 and poorer kidney function can occur together without making the result a specific measure of myocardial scarring. [1]

Medications and the Biomarker

Heart-failure medicines are chosen for demonstrated clinical benefits and individual suitability. The evidence discussed here does not establish universal galectin-3 reductions of 15-20% with mineralocorticoid antagonists or 10-15% with SGLT2 inhibitors, or prove that exercise replaces those treatments by producing a similar biomarker change. [2]

Galectin-3 Testing: Practical Considerations

A useful test has a defined question: will it add information that changes the assessment or plan? The BGM test's established use concerns prognosis in diagnosed chronic heart failure. That indication does not establish routine screening for every person over 45 with metabolic risk factors. [3]

For repeated results, document the assay, laboratory, clinical condition and relation to recent exercise. A fixed three-to-six-month testing schedule or a mandatory companion panel is not established by the training studies above. The purpose of repeating the test should be clear before interpreting a change as success or failure.

Building an Exercise Program

An exercise program should focus on function, symptoms, participation and an appropriate progression of activity. For heart failure, supervised training and cardiac rehabilitation can provide a structured approach. A universal three-phase program based on galectin-3 thresholds has not been validated by the cited trials. [2,11]

The practical question is whether the program is improving the outcomes that matter to the person. A lower biomarker may be interesting, but it should not replace the assessment of exercise capacity or the management of an established heart condition.