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Antioxidant therapies for obstructive sleep apnea: A systematic review and meta-analysis

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Abstract

Purpose

Obstructive sleep apnea (OSA) is a common clinical problem that is associated with adverse cardiovascular outcomes attributed to the oxidative stress due to sympathetic overstimulation. Treatment approaches targeting oxidative stress have been tried by multiple investigators. This systematic review and meta-analysis evaluated the efficacy and safety of such approaches.

Methods

Pubmed and Embase databases were searched for human studies evaluating the utility of antioxidant therapies in patients with OSA.

Results

A total of six studies (five randomized trials and one case–control study) were included, including 160 patients with OSA using N-acetyl cysteine, vitamin C, carbocysteine, superoxide dismutase, vitamin E, allopurinol, and their combinations. There was a significant improvement in flow-mediated dilatation (FMD) following antioxidants, with the pooled effect being 2.16 % (95% CI 1.65–2.67) using the random-effects model (I2 = 0% and p<0.001). It was also associated with a significant reduction in malondialdehyde levels and an increase in reduced glutathione (GSH) levels. There was also a significant improvement in the Epworth sleepiness scale, oxygen desaturation index, and minimum oxygen saturation during sleep without any significant adverse effects.

Conclusion

Antioxidant therapy in patients with OSA is associated with improved endothelial function, reduced oxidative stress, and improved sleep parameters. These results call for future multicentre studies with longer follow-ups to assess the utility of antioxidant therapy in patients with OSA.

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Data availability

Data will be made available on reasonable request.

Abbreviations

AHI:

Apnea-hypopnea index

CI:

Confidence interval

COPD:

Chronic obstructive pulmonary disease

CPAP:

Continuous positive airway pressure

ESS:

Epworth sleepiness scale

FMD:

Flow-mediated dilatation

GSH:

Glutathione

IL-6:

Interleukin 6

IMT:

Intima-media thickness

MDA:

Malondialdehyde

NAC:

N-acetyl cysteine

ODI:

Oxygen-desaturation index

OSA:

Obstructive sleep apnea

OSAS:

Obstructive sleep apnea syndrome

PA:

Progressive augmentation

PRISMA:

Preferred Reporting Items for Systematic Reviews and Meta-Analyses

RCT:

Randomized controlled trial

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

TNF- α:

Tumor necrosis factor-α

vLTF:

Ventilatory long-term facilitation

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Authors and Affiliations

  1. Department of Pulmonary, Critical Care, and Sleep Medicine, All India Institute of Medical Sciences (AIIMS), Ansari Nagar, New Delhi, India, 110029

    Tarun Krishna Boppana, Saurabh Mittal, Karan Madan, Pawan Tiwari, Anant Mohan & Vijay Hadda

Authors
  1. Tarun Krishna Boppana
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  2. Saurabh Mittal
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  3. Karan Madan
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  4. Pawan Tiwari
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  5. Anant Mohan
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  6. Vijay Hadda
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Corresponding author

Correspondence to Saurabh Mittal.

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All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

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PROSPERO ID: CRD42023450687

Supplementary Information

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11325_2024_3050_MOESM1_ESM.png

Supplementary file1 The risk of bias summary for the 5 RCTs. The green dot with the + sign indicates low bias while the red dot with the – sign indicates high risk of bias. An empty box denotes an unclear risk of bias. (PNG 89 KB)

11325_2024_3050_MOESM2_ESM.png

Supplementary file2 The funnel plot of the studies reporting the change in Flow-mediated dilatation as an outcome; SE: standard error, MD: mean difference. (PNG 3 KB)

Supplementary file3 (DOCX 15 KB)

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Boppana, T.K., Mittal, S., Madan, K. et al. Antioxidant therapies for obstructive sleep apnea: A systematic review and meta-analysis. Sleep Breath (2024). https://doi.org/10.1007/s11325-024-03050-z

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