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There are new lines of evidence that endogenous synthesis of creatine is not sufficient for humans under many physiological (e.g., exercise, pregnancy and lactation) and pathological (e.g., tissue injury, ischemia, and diabetes) conditions

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Other documented findings include a tendency toward IGF-1 receptor desensitization with prolonged, continuous exposure, transient fluid retention in early study phases, and at supraphysiological exposure levels examined in some research acromegaly-like tissue changes

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