Is elevated oxygen uptake (VO2) an indicator of good metabolism in patients with insomnia?

Understanding VO2 and Its Relationship to Metabolism and Insomnia

VO2 (oxygen uptake) is not an indicator of good metabolism in insomnia but rather reflects elevated metabolic rate due to hyperarousal, which is a pathophysiological feature of insomnia disorder.

What is VO2?

• VO2 represents the volume of oxygen extracted from inspired air in a given period of time, expressed in milliliters per minute or liters per minute 1
• In steady state, oxygen uptake equals oxygen consumption, which is the amount of oxygen utilized by the body's metabolic processes 1
• VO2max or VO2peak is considered the best measure of cardiovascular fitness and exercise capacity 1

Relationship Between VO2 and Metabolism

• VO2 directly reflects metabolic rate as it measures the oxygen utilized for metabolic processes 1
• Higher VO2 indicates increased metabolic activity, which can be beneficial during exercise but may be pathological in other contexts 1
• Normal resting VO2 is approximately 3.5 ml/minute per kilogram (about 250 ml/minute in an average individual) 1

VO2 Elevation in Insomnia: The Hyperarousal Connection

• Patients with insomnia exhibit hyperarousal in multiple domains, including an elevated metabolic rate throughout the 24-hour cycle 2, 3, 4
• Studies have shown that insomnia patients have consistently elevated whole-body VO2 measured at intervals across the day and throughout the night compared to normal sleepers 4
• This elevated VO2 persists even after excluding periods containing wake time or arousals during the night, indicating a fundamental metabolic dysregulation 4

Metabolic Dysregulation in Insomnia

• Insomnia is associated with quantitative metabolic dysregulation, supporting the hyperarousal hypothesis 2
• Specific metabolic alterations include elevated amino acid and energy metabolites, reduced branched-chain amino acid catabolic products, and approximately 10% increased glucose accumulation during the night 2
• This state of metabolic desynchrony is likely involved in the pathophysiology of insomnia and/or mediates its impact on health outcomes 2, 5

Clinical Implications

• The elevated metabolic rate (increased VO2) in insomnia is not beneficial but rather represents a pathological state of hyperarousal 3, 4
• This hyperarousal state may be responsible for both the daytime symptoms (confusion, tension, depression, decreased vigor) and the nocturnal poor sleep in insomnia patients 4
• Experimental studies using caffeine to induce physiological arousal and increased VO2 in normal subjects produced symptoms consistent with those seen in patients with primary insomnia 3

Measurement Considerations

• VO2 measurement requires specialized equipment to measure oxygen extraction from inspired air 1
• In clinical settings, VO2 is often normalized by body weight in kilograms, though this may not be the most appropriate frame of reference for comparing metabolic rate across subjects of different sizes 1
• Factors affecting VO2 measurement include age, sex, body size, training status, and presence of disease 1

Treatment Implications

• Treatment strategies for insomnia should target the 24-hour hyperarousal state rather than focusing solely on improving nighttime sleep 4
• Both pharmacological and behavioral interventions for insomnia may have direct metabolic effects that should be considered 5

In conclusion, elevated VO2 in insomnia patients reflects a state of pathological hyperarousal rather than good metabolism. This metabolic dysregulation is present throughout the 24-hour cycle and contributes to both the sleep disturbance and daytime symptoms characteristic of insomnia disorder.