Vitamin D in Heart Failure: Where's the Benefit and Where's the Confusion?

Nutrients published a review with the telling title “Vitamin D Supplementation in Heart Failure-Confusion Without a Cause?” The authors analyze why vitamin D deficiency is so common in patients with heart failure (HF), through what mechanisms it can theoretically worsen the course of the disease (RAAS activation, inflammation, oxidative stress, calcium homeostasis disorder), and what randomized trials and meta-analyses have actually shown. The key conclusion is neat: in people with severe D deficiency and/or reduced ejection fraction, supplements can improve individual surrogate indicators, but routine administration to all patients with HF is not yet supported by solid evidence on “hard” outcomes (mortality, hospitalizations).

Background of the study

Heart failure (HF) remains a leading cause of hospitalization and mortality, and vitamin D deficiency is common in these patients, ranging from physical inactivity and infrequent sun exposure to comorbidities and medications. Biologically, this seems plausible: vitamin D is involved in the regulation of the RAAS, inflammation, oxidative stress, and myocardial calcium homeostasis. Hence the hope that correcting the deficiency can improve the course of HF, but the clinical picture has proven to be heterogeneous—this “node” is examined in the review in Nutrients.

Large randomized data do not support the idea of universal preventive supplementation: in the VITAL-HF substudy, vitamin D supplementation did not reduce hospitalizations for HF, and a meta-analysis of 21 RCTs (>83,000 participants) showed no reduction in MACE, CV or all-cause mortality with supplementation. That is, for a broad, mostly vitamin D-replete population, there is no “cardio benefit.”

At the same time, there are “signals” in individual groups: in the VINDICATE RCT in patients with HFrEF, a year of cholecalciferol (100 mcg/day) improved left ventricular remodeling parameters (ejection fraction and size), although this did not translate into “hard” outcomes. Such results suggest that the potential benefit, if any, is more likely in patients with reduced EF and severe D deficiency, and not “in everyone”.

Hence the “confusion”: studies differ in dose, duration, baseline 25(OH)D levels, and HF phenotypes (HFrEF, HFpEF), and observational associations do not equal causation. The conservative conclusion of the review is that it is reasonable to measure 25(OH)D and specifically correct the deficiency in patients with HF; there is no evidence yet to prescribe vitamin D routinely to everyone to improve the prognosis of heart failure itself.

Why is this important?

HF remains one of the leading causes of hospitalization and mortality, despite impressive progress in basic therapy (RAAS/ARNI inhibitors, beta-blockers, mineralocorticoid receptor antagonists, SGLT2 inhibitors). Due to the high prevalence of vitamin D deficiency in patients with HF, the temptation to “plug the hole” with supplementation is great - but this only makes sense if supplementation actually improves prognosis. The review systematizes the conflicting results and helps to separate biological plausibility from clinical benefit.

What the clinical data say

• On “hard” outcomes in the general population – neutral. A large meta-analysis of 21 RCTs (>83 thousand participants) showed no reduction in the risks of MACE (heart attack, stroke, CV death) or total mortality with vitamin D. In the VITAL-HF component (a substudy of VITAL), vitamin D supplementation did not reduce hospitalizations for HF.
• There are signals of LV remodeling. The VINDICATE RCT (100 mcg D3/day, 1 year, HFrEF) improved ejection fraction and reduced LV dimensions, although tolerability and survival were not affected; a meta-analysis of remodeling RCTs showed similar “echo-beneficial” effects without a convincing effect on clinical events.
• Observational studies - associations, not causation. Low 25(OH)D levels are associated with worse LV structure/function and risk of HF (including HFpEF), but genetic and confounding factors preclude this from being evidence of benefit of universal supplementation.
• Conclusion of the review. In CH, vitamin D should be considered selectively - in case of documented deficiency - but not as a universal supplement "just in case".

Mechanisms: Why does the heart need vitamin D at all?

The authors remind that vitamin D is involved in the regulation of:

• RAAS and vascular tone (theoretical reduction of hyperactivation),
• inflammation and oxidative stress (downregulation of proinflammatory pathways),
• myocardial calcium homeostasis (contractility, excitability),
• musculoskeletal function (sarcopenia is a common companion of heart failure).
  The biology is compelling, but consistent effects on patient outcomes, not just laboratory and echocardiographic markers, are needed to change practice.

Who does it potentially help (and how exactly)

• Patients with overt D deficiency: logically expected to improve surrogate parameters and well-being (muscle weakness, fatigue), especially in the setting of HFrEF - but effect on mortality/hospitalizations not proven.
• HFrEF under dense modern therapy: possible improvements in LV remodeling parameters (according to RCT), without confirmed effect on “hard” outcomes.
• HFpEF/HFmrEF: data are limited and heterogeneous; there are no universal recommendations for supplementation.

Where science is still “stalling”

• Inconsistency in RCTs: doses, formulations, duration, baseline 25(OH)D levels and heart failure phenotypes vary - it is not surprising that results are variable.
• Associations ≠ causation: low D may be a marker of disease severity/sedentary status rather than its driver. Carefully stratified trials by HF phenotypes and vitamin D status are needed.
• "Hard" endpoints: Neither large RCTs nor meta-analyses have yet shown a convincing reduction in mortality and hospitalizations.

Practical guidelines for patients and physicians

• Not for everyone. The review and large RCTs do not support the idea of "giving vitamin D to every HF patient for the sake of the heart." First - measuring 25(OH)D and correcting the deficiency according to standard cardio-endocrine guidelines.
• The goal is to close the deficiency, not to "treat HF with vitamin". It is reasonable to eliminate deficiency (especially severe) - for the sake of musculoskeletal health and potential metabolic benefits; expecting a reduction in mortality/hospitalizations specifically due to D is premature.
• Let's look at the context. D is just one piece of the puzzle: proven basic therapy for heart failure (and control of sodium, weight, activity) takes priority, and supplements are discussed specifically.

What to check next

• Stratified RCTs by HF phenotypes (HFrEF vs HFpEF), age, comorbid conditions, and baseline 25(OH)D levels.
• Optimal doses/formulations and duration with emphasis on safety (calcium/renal outcomes) and clinical hard endpoints.
• Combination strategies where correction of D deficiency complements rehabilitation, treatment of sarcopenia and nutritional support.

Review source: Kampka Z., Czapla D., Wojakowski W., Stanek A. Vitamin D Supplementation in Heart Failure-Confusion Without a Cause? Nutrients 17(11):1839, May 28, 2025. https://doi.org/10.3390/nu17111839