Sleep problems continue to be a primary, independent risk factor for mortality and various health conditions, including metabolic syndrome, cardiovascular disease, chronic pain syndromes, mood and cognitive conditions. Although insomnia can be shaped differently, obstructive sleep apnea (OSA) remains one of the most common causes of disordered sleep, affecting over 30 percent of the population. Obesity, male gender, older age, neck circumference, body mass index, and high blood pressure are a few of the risk factors associated with OSA; but an often ignored, yet serious aspect of OSA to the functional medicine practitioner is its strong connection to systemic inflammation. Could inflammation be at the root of the relationship between OSA and cardiovascular morbidity? If so, are we really fighting OSA with the correct tools? Previously, we looked at the association between sleep apnea and metabolic syndrome. Now let’s explore another avenue.
Clinical studies and animal models have uncovered a clinically relevant fact – inflammatory cytokines, including tumor necrosis factor (TNF-α) may be responsible for the link between OSA and cardiovascular morbidity and other comorbidities. When compared to control subjects, the T-cell profile of subjects with OSA indicated a significant intracellular content of proinflammatory cytokines, including TNF-α. Activation of the TNF-α receptors stimulate the secretion of interleukin (IL)-6, followed by the synthesis of C-reactive protein (CRP), a direct measurement of systemic inflammation and cardiovascular risk. In other studies, serum levels of TNF-α directly correlated with the severity of OSA. Not surprisingly, continuous positive airway pressure (CPAP) therapy decreased TNF-α levels, reducing systemic inflammation and risks of comorbid conditions.
Not only can inflammation exacerbate OSA, but the pathophysiology of OSA induces inflammation, creating a circular cycle. Repetitive episodes of apnea (breathing cessation) causes oxidative stress, calling monocytes to action and subsequent inflammation. The increase of inflammatory cells leads to endothelial damage and dysfunction associated with OSA. In response, epithelial progenitor cells are released from the bone marrow to repair the area of damage. An increase in these cells has been linked to cardiovascular disease, which is also marked by endothelial damage, and may provide a partial explanation of the link between these two conditions.
OSA is a risk factor for various neurological conditions, resulting from increased oxidative stress, systemic inflammation, and damage to neurological tissue. Animal studies have shown “chronic intermittent hypoxia increases brain cortical neuronal cell death” and human studies have found significant reductions in gray matter in subjects with OSA. A prospective study of 20 patients with severe OSA and 14 controls investigated the association between systemic inflammation and central nervous system microstructural damage, and found a direct correlation between activation of inflammatory pathways (measured by TNF-α, IL-6, IL-8, and ICAM-1 levels) from hypoxia and injury in the brain’s white matter, specifically.
Systemic inflammation is not only indicated by the presence of proinflammatory cytokines, but can also be measured by blood and tissue levels of omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which counteract the inflammatory response. A deficiency of EPA and DHA has been associated with autonomic dysfunction and cardiovascular morbidity, both of which are linked to OSA.
DHA, specifically, seems to be implicated in OSA. In a cross-sectional study of 350 samples, RBC DHA was inversely related with OSA severity after controlling for age, sex, race, smoking, BMI, alcohol intake, fish intake, and omega-3 supplementation. In fact, “for each 1 standard deviation increase in DHA levels, a patient was about 50% less likely to be classified with severe OSA.” DHA is a major structural component of cell membranes, especially within neurological tissues. Omega-3 fatty acids are well-known to be cardioprotective, neuroprotective, and reduce mortality, all of which are major outcomes of OSA. Studies have reported improved sleep cycles among those with higher DHA levels, suggesting reduced DHA could initiate OSA. Further, it has been suggested that “lower levels of omega-3 fatty acids in neuronal tissues could destabilize the upper airway innervation, musculature, and feedback control systems” becoming a causative agent in the pathophysiology of OSA.
Clearly, omega-3 fatty acids should be a tool used to improve the outcomes associated with OSA and may even improve the severity of OSA. Omega-3 fatty acids are vital for modulating systemic inflammation as they inhibit the production of inflammatory cytokines such as TNF-α and interleukins. Controlling endothelial damage and dysfunction with omega-3 fatty acids can decrease the risks of cardiovascular events and respiratory dysfunction associated with OSA. Stabilizing and repairing the neuronal cell membranes with DHA, EPA, and other membrane nutrients such as glycerophosphocholine (GPC) and phosphatidylserine (PS) will not only reduce cerebral damage associated with OSA, but help support sleep and neuronal communication pathways that could play a role in the etiology of OSA. Omega-3 fatty acids are the gold standard for modulating inflammation and as we discover the role inflammation plays in OSA, omega-3 fatty acids and brain-supportive nutrients should be considered key components of managing this common condition.