Details
| Originalsprache | Englisch |
|---|---|
| Aufsatznummer | 101590 |
| Fachzeitschrift | JACC: Advances |
| Jahrgang | 4 |
| Ausgabenummer | 3 |
| Publikationsstatus | Veröffentlicht - März 2025 |
Abstract
Background: Peripheral artery disease (PAD) is a major public health concern due to its high prevalence, severe impact on individuals' health and quality of life, and substantial economic burden. Pharmacological interventions are still limited with numbers needed-to-treat ranging from 6 (cilostazol) to 50 (aspirin, statins, and vorapaxar). Objectives: This randomized, placebo-controlled, double-blinded crossover interventional trial aims to measure the effect of L-citrulline and tetrahydrobiopterin (H4Bip) on walking distance in patients with PAD, stratified by plasma levels of asymmetric dimethyl L-arginine (ADMA), the endogenous inhibitor of endothelial nitric oxide (NO) synthase. Methods: We measured preinterventional ADMA levels in 51 patients with PAD in Australia and Germany with mean changes in absolute claudication distance (dACD) as the primary outcome upon orally supplementing the L-arginine precursor, L-citrulline (3 g) twice daily for 12 weeks, and, in one arm, additionally H4Bip (0.45 g) once per day for a further 2 weeks. Results: Preinterventional ADMA levels were pathological (>0.4 μM) in 34 patients. Supplementation with L-citrulline significantly increased the mean plasma levels of both L-citrulline and L-arginine, from 41.8 ± 2.7 μmol/l to 246.3 ± 67.3 μmol/l (P = 0.004) and from 75.2 ± 4.2 μmol/l to 119.2 ± 6.9 μmol/l (P < 0.0001) respectively, when compared with placebo. dACD in % of control was significantly improved by L-citrulline vs placebo (20.11% ± 4.50% vs 5.73% ± 2.74%, respectively; P = 0.011). Further addition of H4Bip increased the mean percentage dACD to 28.15% ± 6.84% (P = 0.021), but only in patients with preinterventional pathological ADMA levels. Conclusions: L-citrulline and, when ADMA levels are pathological, H4Bip are effective nutritional interventions in patients with PAD warranting further confirmatory trials.
ASJC Scopus Sachgebiete
- Medizin (insg.)
- Kardiologie und kardiovaskuläre Medizin
Ziele für nachhaltige Entwicklung
Zitieren
- Standard
- Harvard
- Apa
- Vancouver
- BibTex
- RIS
in: JACC: Advances, Jahrgang 4, Nr. 3, 101590, 03.2025.
Publikation: Beitrag in Fachzeitschrift › Artikel › Forschung › Peer-Review
}
TY - JOUR
T1 - Nutritional L-Citrulline and Tetrahydrobiopterin in Peripheral Artery Disease
T2 - A Phase II Randomized Trial (CIPER Study)
AU - Sedding, Daniel
AU - Schmidt, Tim M.
AU - Bähre, Heike
AU - Bavendiek, Udo
AU - Casas, Ana I.
AU - Chen, Suzi
AU - Thao-Vi Dao, Vu
AU - Elbatreek, Mahmoud H.
AU - Gutzki, Frank
AU - Hahn, Andreas
AU - Kleikers, Pamela
AU - Krahn, Thomas
AU - Macchiusi, Cecilia
AU - Martin, Catherine
AU - Mucke, Hermann
AU - Nogales, Cristian
AU - Schmidt, Beate M.L.
AU - Seifert, Roland
AU - Sonnenschein, Kristina
AU - Tongers, Jörn
AU - Thol, Jens
AU - van der Arend, Inés
AU - van Kuijk, Sander M.J.
AU - Wingler, Kirstin
AU - Wu, Michael
AU - Bauersachs, Johann
AU - McGrath, Barry
AU - Schmidt, Harald H.H.W.
N1 - Publisher Copyright: © 2025
PY - 2025/3
Y1 - 2025/3
N2 - Background: Peripheral artery disease (PAD) is a major public health concern due to its high prevalence, severe impact on individuals' health and quality of life, and substantial economic burden. Pharmacological interventions are still limited with numbers needed-to-treat ranging from 6 (cilostazol) to 50 (aspirin, statins, and vorapaxar). Objectives: This randomized, placebo-controlled, double-blinded crossover interventional trial aims to measure the effect of L-citrulline and tetrahydrobiopterin (H4Bip) on walking distance in patients with PAD, stratified by plasma levels of asymmetric dimethyl L-arginine (ADMA), the endogenous inhibitor of endothelial nitric oxide (NO) synthase. Methods: We measured preinterventional ADMA levels in 51 patients with PAD in Australia and Germany with mean changes in absolute claudication distance (dACD) as the primary outcome upon orally supplementing the L-arginine precursor, L-citrulline (3 g) twice daily for 12 weeks, and, in one arm, additionally H4Bip (0.45 g) once per day for a further 2 weeks. Results: Preinterventional ADMA levels were pathological (>0.4 μM) in 34 patients. Supplementation with L-citrulline significantly increased the mean plasma levels of both L-citrulline and L-arginine, from 41.8 ± 2.7 μmol/l to 246.3 ± 67.3 μmol/l (P = 0.004) and from 75.2 ± 4.2 μmol/l to 119.2 ± 6.9 μmol/l (P < 0.0001) respectively, when compared with placebo. dACD in % of control was significantly improved by L-citrulline vs placebo (20.11% ± 4.50% vs 5.73% ± 2.74%, respectively; P = 0.011). Further addition of H4Bip increased the mean percentage dACD to 28.15% ± 6.84% (P = 0.021), but only in patients with preinterventional pathological ADMA levels. Conclusions: L-citrulline and, when ADMA levels are pathological, H4Bip are effective nutritional interventions in patients with PAD warranting further confirmatory trials.
AB - Background: Peripheral artery disease (PAD) is a major public health concern due to its high prevalence, severe impact on individuals' health and quality of life, and substantial economic burden. Pharmacological interventions are still limited with numbers needed-to-treat ranging from 6 (cilostazol) to 50 (aspirin, statins, and vorapaxar). Objectives: This randomized, placebo-controlled, double-blinded crossover interventional trial aims to measure the effect of L-citrulline and tetrahydrobiopterin (H4Bip) on walking distance in patients with PAD, stratified by plasma levels of asymmetric dimethyl L-arginine (ADMA), the endogenous inhibitor of endothelial nitric oxide (NO) synthase. Methods: We measured preinterventional ADMA levels in 51 patients with PAD in Australia and Germany with mean changes in absolute claudication distance (dACD) as the primary outcome upon orally supplementing the L-arginine precursor, L-citrulline (3 g) twice daily for 12 weeks, and, in one arm, additionally H4Bip (0.45 g) once per day for a further 2 weeks. Results: Preinterventional ADMA levels were pathological (>0.4 μM) in 34 patients. Supplementation with L-citrulline significantly increased the mean plasma levels of both L-citrulline and L-arginine, from 41.8 ± 2.7 μmol/l to 246.3 ± 67.3 μmol/l (P = 0.004) and from 75.2 ± 4.2 μmol/l to 119.2 ± 6.9 μmol/l (P < 0.0001) respectively, when compared with placebo. dACD in % of control was significantly improved by L-citrulline vs placebo (20.11% ± 4.50% vs 5.73% ± 2.74%, respectively; P = 0.011). Further addition of H4Bip increased the mean percentage dACD to 28.15% ± 6.84% (P = 0.021), but only in patients with preinterventional pathological ADMA levels. Conclusions: L-citrulline and, when ADMA levels are pathological, H4Bip are effective nutritional interventions in patients with PAD warranting further confirmatory trials.
KW - ADMA
KW - arginine
KW - citrulline
KW - nitric oxide synthase
KW - peripheral artery disease
KW - tetrahydrobiopterin
UR - http://www.scopus.com/inward/record.url?scp=85218783224&partnerID=8YFLogxK
U2 - 10.1016/j.jacadv.2025.101590
DO - 10.1016/j.jacadv.2025.101590
M3 - Article
AN - SCOPUS:85218783224
VL - 4
JO - JACC: Advances
JF - JACC: Advances
IS - 3
M1 - 101590
ER -