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There is no clinical consensus on timing

Peer review discussions suggest potential relevance for endothelial and microvascular dysfunction

doi:10.1126/science.1245938

Depletion of irisin diminishes intestinal microbial diversity, and exogenous irisin supplementation significantly improves the pathological manifestations of microbiota dysbiosis [179]

Yes, gradually over several weeks to months, maintaining results requires ongoing use or periodic cycles