Table 1.
Summary of studies exploring the effects of dietary fasting and TRE in HD
| Study | Models/patients | Intervention | Fasting/feeding time per cycle | Results |
|---|---|---|---|---|
| Duan et al. [85] | N171-82Q HD mice | 3-month ADF | 24-h/24-h | Delayed disease onset; slowed disease progression; ↑ survival; ↑ motor function; ↓ brain atrophy; ↓ mHTT aggregate formation and apoptotic protease activation; normalized blood glucose regulation; ↓ tissue wasting and weight loss; ↑ BDNF and protein chaperone levels in brain |
| Ehrnhoefer et al. [79] | YAC128 HD mice | 1-week TRE | 18-h/6-h | ↓ mTOR; ↑ SIRT1; ↑ neuronal autophagy; ↓ cortical mHTT protein |
| Wang et al. [130] | Q175 HD mice | 3-month TRE | 18-h/6-h | ↑ Circadian locomotor activity; ↑ coordination in onset of sleep; ↑ HRV; ↑ motor function; restoration of HD-relevant markers in striatal gene expression analysis |
| Whittaker et al. [131] | BACHD mice | 3-month TRE | 18-h/6-h | ↑ Circadian locomotor activity; ↑ time spent sleeping during rest phase; ↑coordination in onset of sleep; ↑ HRV; ↑ motor function |
| Phillips et al. [113] | N-of-1, unblinded clinical trial of a 41-year-old male patient with HD | 48-week TRKD | 2 meals/day, 1 h/meal, no snacks | Improvements in motor symptoms, activities of daily living, cUHDRS score, behavioral problems, irritability, mood-related quality of life; no change in cognition; weight remained stable, no reported adverse effects |
HD Huntington’s disease; N171-82Q transgenic mouse model of HD that expresses the N-terminal 171 amino acids of human huntingtin protein with 82 polyglutamine repeats; YAC128 transgenic mouse model of HD that contains a full-length human huntingtin gene modified with a 128 CAG repeat expansion; Q175 transgenic mouse model of HD that contains human huntingtin gene exon 1 sequence with ~ 179 CAG repeats; BACHD transgenic mouse model of HD that expresses full-length human huntingtin gene modified to contain loxP-flanked human mutant huntingtin exon 1 sequence with 97 mixed CAA-CAG repeats; ADF alternate day fasting; TRE time-restricted eating; TRKD time-restricted ketogenic diet; mHTT mutant huntingtin protein; BDNF brain-derived neurotrophic factor; mTOR mechanistic target of rapamycin; SIRT1 sirtuin 1; HRV heart rate variability; cUHDRS composite unified Huntington’s disease rating scale; ↑: increase; ↓: decrease