Table 4.

Effects of intermittent hypoxia—IH—on different clinical conditions [35].

Pathology	Effect Observed
Chronic obstructive pulmonary disease	In randomized, double-blind, controlled clinical studies it was demonstrated that mild repetitive acute IH (12–15% O2 for 3–5 min, followed by intervals of 3–5 min of normoxia, 5–9 episodes per day, for 15 days) can produce the following increases: exercise time, baroreflex sensitivity, total hemoglobin, hypercapnic ventilatory response, forced vital capacity and forced expiratory volume in 1 s.
Arterial hypertension	In 56 known patients with stage I-II hypertension, moderate IH reduced heart rate, systolic and diastolic blood pressure and peripheral resistance. IH reduces the symptoms of angina, normalizes microcirculation and lipid metabolism and increases maximal oxygen consumption and exercise tolerance, being proven to be a safe therapy for elderly patients. Increased endothelial NO production that produces the opening of reserve capillaries and vasodilatation can determine the antihypertensive effects of moderate IH (reduced peripheral resistance), reduced sympathetic activity, minimized calcium overload of vascular smooth muscles, improved water and salt metabolism, increased activity of antioxidant enzymes and increased synthesis of angiogenic growth factors, including VEGF and FGF.
Myocardial Infarction	In humans, moderate IH increases maximal oxygen consumption in older men (50–70 years), both with and without coronary artery disease. During submaximal exercise (cycling at 1 W/kg), systolic blood pressure, heart rate, perceived exertion and blood lactate concentration are diminished by IH. Myocardial protection is correlated with the ability of moderate IH to increase coronary blood flow, myocardial vascularity, cardiomyoglobin and antioxidant enzyme expression. IH increases erythropoietin (EPO) concentrations, stimulating erythropoiesis and increasing hematocrit, blood viscosity and platelet count.
Inflammatory/immune responses to IH	Some studies suggest that moderate IH protocols enhance the innate immune system while having a general anti-inflammatory effect. For example, in healthy humans, exposure to the 4 5 min episodes of 10% O2 (5 min interval in room air, 14 days) increases the phagocytic and bactericidal activities of neutrophils, while suppressing the pro-inflammatory mediators TNF-α and IL-4 by more than 90%. These responses, which persisted at least 7 days after IH, may increase the body’s immune defenses without associated inflammation.
Metabolic responses to IH	IH protocols have beneficial effects on metabolism, including decreased body weight, cholesterol, and blood sugar levels, as well as increased insulin sensitivity. Mechanisms of moderate IH-induced weight loss may include increased serotonin and/or leptin levels. Body weight is reduced with moderate IH by increasing hepatic leptin expression and increasing blood leptin concentration. Moderate hypoxia (14.6% O2) reduces cholesterol and blood glucose and increases insulin sensitivity in patients with type 2 diabetes. Hypoxia also increases glycolysis and fatty acid oxidation and mitochondrial enzyme activity and reduces cholesterol synthesis.
Bone	IH has positive effects on bone tissue remodeling. Exposure of rats to IH determined high alkaline phosphatase activity in bone tissue, thus suggesting increased osteoblast activity and new bone formation.