High Protein Diet and Huntington's Disease

<div><p>Huntington’s disease (HD) is a neurodegenerative disorder caused by the <i>huntingtin</i> (<i>HTT</i>) gene with expanded CAG repeats. In addition to the apparent brain abnormalities, impairments also occur in peripheral tissues. We previously reported that mutant Huntingtin (mHTT) exists in the liver and causes urea cycle deficiency. A low protein diet (17%) restores urea cycle activity and ameliorates symptoms in HD model mice. It remains unknown whether the dietary protein content should be monitored closely in HD patients because the normal protein consumption is lower in humans (~15% of total calories) than in mice (~22%). We assessed whether dietary protein content affects the urea cycle in HD patients. Thirty HD patients were hospitalized and received a standard protein diet (13.7% protein) for 5 days, followed by a high protein diet (HPD, 26.3% protein) for another 5 days. Urea cycle deficiency was monitored by the blood levels of citrulline and ammonia. HD progression was determined by the Unified Huntington’s Disease Rating Scale (UHDRS). The HPD increased blood citrulline concentration from 15.19 μmol/l to 16.30 μmol/l (<i>p</i> = 0.0378) in HD patients but did not change blood ammonia concentration. A 2-year pilot study of 14 HD patients found no significant correlation between blood citrulline concentration and HD progression. Our results indicated a short period of the HPD did not markedly compromise urea cycle function. Blood citrulline concentration is not a reliable biomarker of HD progression.</p></div

Blood citrulline concentration during follow-up of Huntington’s disease (HD) patients.

<p>Blood citrulline concentration was measured every 6 months and was compared at each time point with the concentration in non-HD controls (dotted line). The N value in the bar represents the number of collected data at each point (A). All data were normalized to the baseline value and show the progression pattern (B). Data are presented as mean ± standard deviation, *<i>p</i> < 0.05, ***<i>p</i> < 0.001 by <i>t</i> test.</p

Influence of dietary protein content on the urea cycle in Huntington’s disease (HD) patients.

<p>Blood citrulline (A) and ammonia (B) levels in HD patients given the standard protein diet (13.7%) and high protein diet (26.3%). The data for the 23 non-HD subjects (Con) were taken from a previous report [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0127654#pone.0127654.ref013" target="_blank">13</a>]. All HD patient data were plotted. Data are presented as mean ± standard deviation (SD) and were analyzed by paired <i>t</i> test. *<i>p</i> < 0.05.</p