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Dark chocolate acutely improves walking autonomy in patients with peripheral artery disease
Lorenzo Loffredo1, Ludovica Perri1, Elisa Catasca1
1Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy (L.L., L.P., E.C., P.P., M.B., C.N., S.B., R.C., F.V.).
Background:
NOX-2, the catalytic subunit of NADPH oxidase, has a key role in the formation of reactive oxidant species and is implicated in impairing flow-mediated dilation (FMD). Dark chocolate exerts artery dilatation via down-regulating NOX2-mediated oxidative stress. The aim of this study was to investigate whether dark chocolate improves walking autonomy in peripheral artery disease (PAD) patients via an oxidative stress-mediated mechanism.
Methods And Results:
FMD, serum levels of isoprostanes, nitrite/nitrate (NOx) and sNOX2-dp, a marker of blood NOX2 activity, maximal walking distance (MWD) and maximal walking time (MWT) were studied in 20 PAD patients (14 males and 6 females, mean age: 69±9 years) randomly allocated to 40 g of dark chocolate (>85% cocoa) or 40 g of milk chocolate (≤35% cocoa) in a single blind, cross-over design. The above variables were assessed at baseline and 2 hours after chocolate ingestion. Dark chocolate intake significantly increased MWD (+11%; P<0.001), MWT (+15%; P<0.001), serum NOx (+57%; P<0.001) and decreased serum isoprostanes (-23%; P=0.01) and sNOX2-dp (-37%; P<0.001); no changes of the above variables were observed after milk chocolate intake. Serum epicatechin and its methylated metabolite significantly increased only after dark chocolate ingestion. Multiple linear regression analysis showed that Δ of MWD was independently associated with Δ of MWT (P<0.001) and Δ of NOx (P=0.018). In vitro study demonstrated that HUVEC incubated with a mixture of polyphenols significantly increased nitric oxide (P<0.001) and decreased E-selectin (P<0.001) and VCAM1 (P<0.001).
Conclusion:
In PAD patients dark but not milk chocolate acutely improves walking autonomy with a mechanism possibly related to an oxidative stress-mediated mechanism involving NOX2 regulation.
Clinical Trial Registration Url:
http://www.clinicaltrials.gov. Unique identifier: NCT01947712.
Insights
Dark chocolate consumption significantly enhances walking ability in peripheral artery disease (PAD) patients by reducing oxidative stress and regulating NOX2 activity. This improvement in walking autonomy is linked to increased nitric oxide production.
Area of Science:
- Cardiovascular Research
- Nutritional Science
- Oxidative Stress Biology
Background:
- NADPH oxidase (NOX-2) plays a critical role in reactive oxygen species generation, contributing to impaired flow-mediated dilation (FMD).
- Dark chocolate is known to reduce NOX2-mediated oxidative stress and promote arterial dilation.
- Peripheral artery disease (PAD) is characterized by reduced walking capacity, often linked to oxidative stress.
Purpose of the Study:
- To investigate the effect of dark chocolate on walking autonomy in PAD patients.
- To determine if improvements in walking are mediated by a reduction in oxidative stress via NOX2 regulation.
Main Methods:
- A single-blind, cross-over study involving 20 PAD patients randomly assigned to consume 40g of dark chocolate (>85% cocoa) or milk chocolate (≤35% cocoa).
- Measurements included flow-mediated dilation (FMD), serum isoprostanes, nitrite/nitrate (NOx), soluble NOX2-derived peptide (sNOX2-dp), maximal walking distance (MWD), and maximal walking time (MWT).
- In vitro studies assessed the impact of polyphenols on nitric oxide, E-selectin, and VCAM1 in human umbilical vein endothelial cells (HUVEC).
Main Results:
- Dark chocolate consumption significantly increased MWD (+11%) and MWT (+15%), serum NOx (+57%), and decreased serum isoprostanes (-23%) and sNOX2-dp (-37%).
- Milk chocolate consumption did not yield significant changes in these parameters.
- Increased epicatechin and its metabolite were observed post-dark chocolate intake, and in vitro studies showed increased nitric oxide and decreased E-selectin and VCAM1.
Conclusions:
- Acute consumption of dark chocolate, but not milk chocolate, improves walking autonomy in PAD patients.
- The mechanism appears to involve the regulation of oxidative stress pathways, specifically NOX2 activity and nitric oxide production.
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