New Science: Health Benefits of Caffeine

Systemic lupus erythematosus (SLE) is an autoimmune disease with a diverse manifestation and a complex, often fatal, course. A new study published in Rheumatology investigated the role of caffeine in reducing endothelial dysfunction in SLE.

About the study
The study comprised 31 SLE patients (30 females and 1 male) who did not have any other CVD risk factors such as past or present smoking, CVD, chronic renal failure, or abnormal blood glucose or cholesterol levels. The median age was 43 years, and the typical disease duration was 18 months.

SLE autoantigens and serum complement C3 and C4 levels were measured. A food frequency questionnaire was utilized to estimate caffeine use.

The percentage of circulating endothelial progenitor cells (EPC) was evaluated in SLE patient samples. In a second set, blood samples from healthy volunteers who had not consumed caffeine were processed in vitro to determine the amount of EPC colony-forming units (CFU).

The samples were subsequently evaluated following SLE serum therapy, with and without caffeine exposure (at two dosages, 0.5 mM and 1 mM). The SLE sera came from people who did not consume caffeine.

Autophagy and apoptosis were investigated in EPCs co-cultured with coffee, with and without SLE sera. The researchers also investigated the A2AR/SIRT3/AMPK pathway and its link to EPC dysfunction.

SLE patients had a median EPC % of 0.03 and consumed 166 mg of caffeine per day. Coffee was the primary source, accounting for a median of 160 mg per day. Those taking glucocorticoids and those suffering with neuropsychiatric lupus had the lowest EPC percentages. The higher the daily caffeine use, the greater the EPC %.

Healthy samples were treated with SLE sera.
EPCs cultivated with SLE sera had poor morphology and a lower number of CFUs than non-treated EPCs. They also had poor colony organization. Caffeine exposure restored colony structure, enhanced EPC shape, and boosted CFU counts.

Autophagy Effects
SLE serum therapy reduced the autophagy-associated molecule LC3-II, which reverted to normal after coffee administration at either dosage.

SLE serum therapy raised p62 levels, a molecule destroyed during autophagy, whereas caffeine restored normal levels, indicating reduced autophagy. These alterations persisted even after treatment with the lysosomal inhibitors E64d and pepstatin.

The researchers attributed these findings to autophagy failure or blockage in SLE. Autophagy is essential for cardiovascular health, and its lack may contribute to endothelial dysfunction in SLE. Previous research has shown that enhanced autophagy accelerates EPC maturation, highlighting its critical involvement in the formation of new blood vessels.

Apoptosis Effects
Annexin V (AV) and Bcl-2 were tested for apoptosis. Similarly, SLE serum treatment resulted in an initial increase in the percentage of AV-positive cells, which then decreased after coffee administration. Bcl-2 levels fell after being exposed to SLE sera, but were restored after coffee administration.

Signaling effects
Caffeine also reversed the SLE sera-induced rise in A2AR levels. The SIRT3-AMPK pathway is critical for suppressing endothelial dysfunction by reducing vascular inflammation. Thus, caffeine may have a favorable effect on endothelial health via this mechanism.

Conclusion
Caffeine improved endothelial function in SLE patients and healthy donor EPCs treated with SLE sera.

These findings support previous research indicating that caffeine inhibits oxidative stress-induced senescence by activating the A2AR/SIRT3/AMPK pathway. Caffeine treatment in vitro boosted EPC survival by inhibiting apoptosis and increasing autophagy via this signaling route.

For more information: Caffeine improves systemic lupus erythematosus endothelial dysfunction by promoting endothelial progenitor cells survival, Rheumatology, https://doi.org/10.1093/rheumatology/keae453