Table 6.
Examples of the effects of intermittent hypoxia exposure with favorable impact in other pathological conditions.
| Subjects | Time of hypoxia | Hypoxia method | Hypoxia dosage | Outcome | References |
|---|---|---|---|---|---|
| Epidemiological study (1965–1972) in 20,000 altitude native men vs. to 130,700 lowlanders (760 m) | Chronic | Altitude | 3,692–5,538 m | ↓Diseases ↓Morbidity rates |
Singh et al., 1977 |
| Rats (n = 24) | 8 h/d for 30 d | HC | 5,000 m | ↑Resistance to epileptogenic action of penicillin | Agadzhanyan and Torshin, 1986 |
| Healthy men (n = 7) (operation Everest II) | 40 d | HC | 7,620 m | ↓T cell function ↓PHA-stimulated thymidine uptake |
Meehan, 1987 |
| Healthy men (n = 8) (operation Everest II) | 4 weeks 5 d at 2,286m 28 d at 7,620 m (gradually) peaks 1–4 h at 8,839 m |
HC | 2,286 m 7,620 m 8,839 m |
↓Phytohemagglutinin-stimulated thymidine uptake and protein synthesis in mononuclear cells ↑Monocytes ↑Plasma IgM & IgA ↓T-cell activation |
Meehan et al., 1988 |
| Essential hypertension patients | 30 min/d, 5 d/wk for 3 wks | HC | 3,500 m | ↓BP ↓Blood vol ↓[Na]serum ↑Microcirculation ↑PO2 tissue ↓cholesterol | Aleshin et al., 1993 |
| Tibetan natives at moderate (M) and high (H) altitudes | Chronic | Altitude | M: 2,000–3,000 m H: 4,000–4,700 m |
↓HR ↓HVR ↓VEmax in group at H altitude |
Ge et al., 1994 |
| Psoriasis affected patients (n = 76) | 4 wk | Altitude | 1,560 m | ↓Psoriasis no changes in plasma cortisol |
Vocks et al., 1999 |
| Neurodermitis patients (n = 31,438) | 4 wk | Altitude | 1,560 m | ↓Dermatosis ↓Psoriasis ↓ECP |
Engst and Vocks, 2000 |
| Coronary patients (n = 46) | 22 sessions 3 h/d | HC | 3,500 m | ↓Total cholesterol ↑HDL ↓LDL ↓VLDL ↓TG |
Tin'kov and Aksenov, 2002 |
| Mice (n = 9) | IHT 5 × (6:6) | NH | FiO2 = 0.06 | ↑EPO; ↑heart HIF-1α | Cai et al., 2003 |
| Obese subjects (BMI > 27) (n = 20) -Hypoxia (n = 10; 8 w + 2 m) -Sham (n = 10; 8 w + 2 m) |
1.5 h/d, 3 d/wk for 8 wk exercising at 60% VO2max | NH | FiO2 = 0.15 (≈2,500 m) FiO2 = 0.201 (≈450 m) |
↓BMI and ↑BW loss ↓cholesterol ↓TG and ↓LDL | Netzer et al., 2008 |
| Healthy men (n = 20) -Hypoxia (n = 10) -Normoxia (n = 10) |
1 h/d, 3 d/wk for 4 wk exercising at 3 mmol/L Lac HR | NH | FiO2 = 0.15 (≈2,760 m) FiO2 = 0.21 (≈SL) |
↓Body fat content ↓TG ↓HOMA-Index fasting insulin and ↓AUCins | Haufe et al., 2008 |
| Atopic dermatitis and psoriasis patients (mini-review) | 12 d−4 wk | Altitude | 1,560 m | ↓Symptoms | Steiner, 2009 |
| Obese men (n = 20) | 1 week | Altitude | 2,650 m | ↓BW ↑BMR ↓Food intake ↑Basal leptin ↓diastolic BP | Lippl et al., 2010 |
| Overweight to obese subjects (n = 24) | 4 wk training under hypoxia at 65% VO2max | NH | FiO2 = 0.15 (≈2,760 m) | ↑Physical fitness ↓Metabolic risk markers ↑Body composition |
Wiesner et al., 2010 |
| Mice (in vivo; lymphoid organs) | Acute 2 h exposure | NH | FiO2 = 0.08 FiO2 = 0.21 FiO2 = 1 (variable in organs: thymus < lymphoid nodes < spleen) |
↑T-cell activation in better oxygenated tissues. T-cell activation in vivo is dependent on localization and decrease with hypoxia |
Ohta et al., 2011 |
| Mice (WT vs. KO) | Myoblast cell culture | NH | 5 vs. 21% | Endogenous EPO promotes satellite activation and functional recovery after muscle injury | Jia et al., 2012 |
| Rats (n = 8) | 3 h/d for 6 d | HC | 5,500 m | Injured excitotoxic brain: ↑EPO ↓Lipid peroxidation ↓Apoptotic cell death |
Costa et al., 2013 |
| Healthy adult sedentary men (n = 28) | 2 × 20 min/d × 3 d/wk for 10 weeks | HC (CVAC) 5 fluctuations/min |
Progressive: SL - 3,048 m (wk 1) SL - 6,096 m (wk 5–10) |
No changes in Hct, [Hb], cholesterol and insulin ↓Fasting plasma glucose ↓Plasma glucose in response to oral glucose tolerance test |
Marquez et al., 2013 |
| Recreationally active mountaineers (n = 10; 3 w + 7 m) | 28 h | Altitude | 3,777 m | ↓Immune response | Oliver et al., 2013 |
| Obese patients (BMI > 30 kg/m2) (n = 16; 4 w + 12 m) | 52 sess of 90 min (8 mo) | NH | Exercise: 3,500 m Rest: 4,500 m |
No added effects by hypoxia to those provoked by moderate intensity exercise | Gatterer et al., 2015 |
| Prediabetic adult patients (n = 11; 6 w + 5 m) | 3 sess/wk for 3 wk | NH (IHT 5:5) | FiO2 = 0.12 (≈4,400 m) | ↑mRNA expression of HIF-1α and target genes ↓Fasting plasma glucose ↓Plasma glucose response to 2 h post-oral glucose tolerance test |
Serebrovska et al., 2017 |
| Trained rats (n = 78) -Basal (n = 6) -Hypoxia (n = 24) -Hypoxia + LAE (n = 24) -Normoxia (n = 24) |
4 h/d for 14 d | HC | 4,000 m | m. soleus: ↑Histological muscle damage recovery No change in fiber types ↓Fiber size ↑Capillarisation ↑VEGF expression ↑Citrate synthase activity ↑PGC-1α |
Rizo-Roca et al., 2017a |
| Trained Rats (n = 78) -Basal (n = 6) -Hypoxia (n = 24) -Hypoxia + LAE (n = 24) -Normoxia (n = 24) |
4 h/d for 14 d | HC | 4,000 m | m. soleus: ↑Mitochondrial biogenesis markers ↑Mitochondrial dynamics markers ↓Oxidative stress ↓Apoptotic signalling |
Rizo-Roca et al., 2017b |
| Rats (n = 28) -Normoxia sedentary (n = 7) -Normoxia + EET (n = 7) -Hypoxia sedentary (n = 7) -Hypoxia + EET (n = 7) |
5 h/d for 4 wk | HC | 6,000 m | ↓Food intake ↓Body weight gain ↓Oxygen consumption Additive effect of IHH+EET |
Cabrera-Aguilera et al., in press |
3 mmol/L Lac HR, heart rate corresponding to the 3 mmol/L lactate value in the FiO2-specific incremental test; Altitude, geographic altitude; AMS, acute mountain sickness; AUCins, Insulin response (area under curve) to oral glucose tolerance test; BMI, body mass index; BMR, basal metabolic rate; BP, arterial blood pressure; BW; body weight; CVAC, Cyclic Variations in Altitude Conditioning; ECP, eosinophil cationic protein; EET, endurance exercise training; EPO, Erythropietin; FiO2, Fraction of inspired oxygen; [Hb], Blood hemoglobin concentration; HC, Hypobaric Chamber; Hct, Hematocrit; HDL, high density lipoproteins; IHT, Intermittent hypoxic training alternating hypoxia with normoxia along the exposure protocol; HOMA-Index, homeostatic model assessment index of insulin resistance; HR, Heart rate; HVR, hypoxic ventilatory response; IHH, intermittent hypobaric hypoxia; IHT (6:6), intermittent hypoxic training, alternating 6 min hypoxia with 6 min normoxia along the session; LAE, light aerobic exercise; LDL, low density lipoproteins; NH, normobaric hypoxia; TG, plasma triglycerides; VEmax; maximal exercise pulmonary ventilation; VLDL, very low density lipoproteins.