Compliance and Genetic Variability Are Determinants of the Success of l-Arginine/l-Citrulline Supplementation in High Altitude-A Pilot Study.
Eduardo Pena, Samia El Alam, Juliane Hannemann et al.
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In 30 seconds
This pilot randomised controlled trial tested whether l-arginine/l-citrulline (A/C) supplementation limited the rise in pulmonary arterial pressure (PAP) during chronic intermittent hypoxia. Twenty male volunteers were assigned to A/C or placebo for 6 months, with PAP assessed by echocardiography. A/C produced a trend toward a smaller increase in PAP, but the result was exploratory and interpretation was limited by poor supplement adherence. Blood l-arginine initially rose in the A/C group, then declined by month 6; genetic haplotypes were also associated with differences in ADMA or l-arginine responses.
Key findings
- A/C supplementation showed a trend toward a diminished increase in PAP during chronic intermittent hypoxia.
- Blood l-arginine increased at month 1 in the A/C group but subsided by month 6 amid poor compliance.
- Individuals with 2 or more alleles of a previously described DDAH1/2 haplotype had a higher increase in ADMA during chronic intermittent hypoxia.
- The increase in blood l-arginine was attenuated in carriers of a previously described ARG1/2 haplotype.
Why it matters
The findings suggest that both adherence and genetic variability may influence biochemical and pulmonary pressure responses to A/C supplementation under intermittent hypoxia. This is relevant when interpreting supplementation studies and highlights the need to distinguish a potentially useful signal from a reliable clinical effect. The pilot results are exploratory and do not establish that supplementation prevents high-altitude pulmonary hypertension.
What to keep in mind
This was a pilot study of 20 male volunteers, and poor adherence limited interpretation of the 6-month supplementation findings.