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Calorie restriction in biosphere 2: alterations in physiologic, hematologic, hormonal, and biochemical parameters in humans restricted for a 2-year period

[6] Vukojevi J, et al

Unlike heavy-metal pigmentation, which affects the free gingival margin, smokers melanosis develops on the attached gingiva

Most patients tolerate the treatment well

Extended use isnt well-studied in humans, so most experts recommend cycling it, typically 48 weeks on, followed by a few weeks off, to support safety and effectiveness.

Dose adjustment is not recommended in patients with mild-severe renal impairment (eGFR = 15-89 mL/min/1.73 m 2 ), but use is not recommended for patients with end-stage renal disease (127)