Such a great topic! It seems that Intermittent Hypoxia can be a benefit and Chronic Intermittent Hypoxia, a detriment...with a possible threshold from protective value to pathology.
My husband was an airline pilot for 20 years and was dx with PD a few years after he left. Your thoughts about hypoxia spiked my curiosity whether the therapeutic benefits that athletes gain from intermittent hypoxic training could apply to flight crews and high altitude. Apparently, the intermittent hypoxic training with athletes has had remarkable results of increased performance and proposed protection from diseases. There are well documented studies on pilots and hypoxia; however, I was not able to find any studies or correlations with proposed protection from diseases. In my opinion, this would make a great study!
Invited Review: Physiological and pathophysiological responses to intermittent hypoxia
The clinical use of intermittent hypoxic training is most recognized by Russian physicians as a therapeutic modality useful in priming the patient for the stress of a host of disease processes. The rationale is based on the cross-protective value of adaptations to one stress providing resistance to another stress (44,54, 84). Adaptation to stress results in enhanced expression of stress proteins and antioxidant systems that can then provide protection against the generalized stress of disease (53).
The next paper is one of the the most comprehensive studies of it's kind. People who live in higher altitudes such as Colorado tend to live longer and have less heart disease. These results are theorized to be the result of lower oxygen levels and synthesized vitamin D, due to increased solar radiation at higher altitudes.
Living at High Altitude Reduces Risk of Dying from Heart Disease: Low Oxygen May Spur Genes to Create Blood Vessels
This last paper is a good read and states that the antioxidant uric acid can act as an Iron chealator.
The Promise of Neuroprotective Agents in Parkinson’s Disease
Uric acid (UA) is a natural antioxidant that can reduce oxidative stress by acting as a scavenger of free radicals and an iron chealator (Ames et al., 1981; Davies et al., 1986; Yu et al., 1998; Hink et al., 2002). Urate suppresses oxyradical accumulation (Yu et al., 1998), inhibits cytotoxic activity of lactoperoxidase (Everse and Coates, 2004), and protects against DA-induced apoptosis (Jones et al., 2000). UA has been found to suppress oxidative stress and prevent dopaminergic cell death in animals (Duan et al., 2002). In addition, slower rates of clinical progression were observed in untreated early stage PD patients who have higher plasma, serum, and cerebrospinal fluid (CSF) concentrations of UA (Schwarzschild et al., 2008; Ascherio et al., 2009). In contrast, lower levels of urate were present in CSF (Tohgi et al., 1993) and post-mortem in the SNpc of patients with PD (Church and Ward, 1994). In a population-based cohort study of 4,695 participants aged 55years and older, higher serum levels of UA were associated with a significantly decreased risk of PD (de Lau et al., 2005). Urate therapy reduced the risk of PD in a dose-dependent manner (de Lau et al., 2005; Schwarzschild et al., 2008). Additionally in a prospective study of subjects with early stage PD there was a 49% reduction in the progression of the disease with high urate intake (Schwarzschild et al., 2008).
Also included in this paper: (we are thinking of either trying to participate in this trial or doing a trial run with Isradipine)
The dihydropyridine L-type calcium channel blocker Isradipine has been reported to reduce hypoxia-induced activation of Ca2+-dependent xanthine oxidases, monoamine oxidases, cytosolic phospholipase A2, and cyclo-oxygenases (COX-2) along with a decrease in free radical generation and cytochrome-crelease (Barhwal et al., 2009). Increased expression of calpain, caspase-3, (Barhwal et al., 2009), and glutamate-induced neurotoxicity (Pizzi et al., 1991) was also inhibited by Isradipine.