Calf raise exercise improves mitochondrial function in peripheral artery disease

A new exercise protocol might improve walking performance through better mitochondrial function in patients with peripheral artery disease, according to the PhD thesis of Michel van Schaardenburgh.


  1. One bout of continuous pain-inducing calf raise exercise stimulates mitochondrial respiration in patients with intermittent claudication.
  2. Regular calf raise exercises for eight weeks improves pain-free and maximal walking distance in these patients.
  3. Positive or negative exercise responses seem to relate to changes in mitochondrial function after exercise.


Thesis:  The effect of ”Five plus” exercise upon walking performance and mitochondria in patients with intermittent claudication
Candidate: Michel van Schaardenburgh
Time: June 15, 2018 at 12:15
Place: St. Olavs Hospital, Medical Technical Research Center: Auditorium MTA
Link to university website (in Norwegian)


“Five plus” is a novel exercise protocol where patients with peripheral artery disease perform continuous calf raises followed by five extra repetitions after initiation of pain.

(1) One bout of “five plus” increases mitochondrial respiration supported by complex II in the calf muscles of patients with peripheral artery disease11 patients and 11 healthy older adults participated in the study. The increased mitochondrial respiration following the exercise session was limited to complex II in the patients, whereas the control group experienced several other and more long-lasting effects on mitochondrial function.

(2) Eight weeks of “five plus” performed three time a day improves walking performance. After the exercise period, the 14 patients could walk 44 meters longer without pain, and improved their maximal walking distance by 99 meters and peak walking time by 104 seconds. In the control group who performed traditional walking exercise, there were no significant improvements.

Furthermore, claudication onset time and mitochondrial volume-density improved following “five plus” exercise. There were no changes in blood flow variables after the exercise period, indicating that the exercise effect on walking performance was due to improved mitochondrial function.

(3) Patients who responded negatively to exercise on walking performance had more advanced peripheral artery disease, and showed several decreases in markers of mitochondrial function following eight weeks of exercise. On the other hand, positive responders increased mitochondrial capacity. The study indicates that changes in walking performance after exercise relate to changes in mitochondrial function in this patient group.


(1) van Schaardenburgh, M., Wohlwend, M., Rognmo, Ø., & Mattsson, E. J. (2016). Mitochondrial respiration after one session of calf raise exercise in patients with peripheral vascular disease and healthy older adultsPloS one11(10), e0165038.

(2) van Schaardenburgh, M., Wohlwend, M., Rognmo, Ø., & Mattsson, E. (2017). Calf raise exercise increases walking performance in patients with intermittent claudicationJournal of vascular surgery65(5), 1473-1482.

(3) van Schaardenburgh, M., Wohlwend, M., Rognmo, Ø., & Mattsson, E. J. (2017). Exercise in claudicants increase or decrease walking ability and the response relates to mitochondrial functionJournal of translational medicine15(1), 130.

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