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First, publication bias and small-study effects cannot be excluded, and many trials do not stratify by obesity, phenotype, or baseline 25(OH)D, key modifiers of response

They are most effective when paired with balanced nutrition and exercise

Dysfunctional endothelial cells are less effective at producing anticoagulant substances like nitric oxide and prostacyclin, increasing thrombosis risk

Marom EM, Moran C, Kim ES, Swisher SG

However, despite encouraging early laboratory findings, its clinical development was discontinued in 2007 after failing to demonstrate significant weight-loss efficacy in large-scale human trials

Most researchers prefer the without DAC version for these reasons, despite needing more frequent use