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Trials typically incorporate biomarker endpoints such as ER/ER ratios, aromatase activity, plasma isoflavone or polyphenol concentrations, immune cell phenotyping, cytokine panels, oxidative stress markers and microbiome profile which are used to provide mechanistic read-outs of supplement activity and to inform patient stratification approaches (231)

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This mitochondrial failure is the direct biochemical driver of the profound, debilitating fatigue and post-exertional malaise (PEM) that patients experience after even minor physical or cognitive exertion