Aortic & peripheral vascular disease
Nutritional L-Citrulline and Tetrahydrobiopterin in Peripheral Artery Disease: A Phase II Randomized Trial (CIPER Study)
Authors' conclusion
L-citrulline and, when ADMA levels are pathological, H4Bip are effective nutritional interventions in patients with PAD warranting further confirmatory trials.
Study context
- Population
- Patients with peripheral artery disease (PAD) in Australia and Germany, stratified by plasma levels of ADMApatients with PAD in whom preinterventional ADMA levels were measured
- Participants
- 51 patients
- Comparison
- L-citrulline vs placebo
- Primary endpoint
- Mean changes in absolute claudication distance (dACD), in % of control
Primary result
As reported in the abstract
L-citrulline
20.11%
± 4.50%
Placebo
5.73%
± 2.74%
P = 0.011
Further findings
- Mean percentage dACD with further addition of H4Bip
- 28.15% · mean percentage dACD · ± 6.84%
- Mean percentage dACD with further addition of H4Bip — P
- P = 0.021
- Mean percentage dACD with further addition of H4Bip: only in patients with preinterventional pathological ADMA levels
Pathological preinterventional ADMA levels (>0.4 μM)
- Patients with pathological ADMA levels (>0.4 μM)
- 34
Mean plasma L-citrulline and L-arginine levels with L-citrulline supplementation, compared with placebo
- L-citrulline
- from 41.8 ± 2.7 μmol/l to 246.3 ± 67.3 μmol/l (P = 0.004)
- L-arginine
- from 75.2 ± 4.2 μmol/l to 119.2 ± 6.9 μmol/l (P < 0.0001)
Original publication
Nutritional L-Citrulline and Tetrahydrobiopterin in Peripheral Artery Disease: A Phase II Randomized Trial (CIPER Study). JACC Adv. Published 21 February 2025. doi:10.
Summarised from the published abstract; every number is checked against it