| Model . | Reference . | Type of DR . | DR effects on inflammatory or other brain pathology markers . | DR effects on cognitive or motor functions . | DR effects on imaging measures . |
|---|---|---|---|---|---|
| Aging | |||||
| Rodents | Morgan et al., 1999; Lee et al., 2000 | 30–40% DR | ↓ Age-related increased of activation markers on microglia (e.g., MHCII) or astrocytes (e.g., GFAP); ↓ inflammatory genes | ||
| Kaur et al., 2008 | IF | ↓ Age-related changes in brain expression of NCAM, PSA-NCAM, and GFAP | |||
| Singh et al., 2012 | IF | ↓ Protein oxidative damage; ↑ markers of synaptic plasticity in the hippocampus | Ameliorates motor coordination, cognitive skills | ||
| Nonhuman primates | Qin et al., 2006 | 30% DR | ↓ Aβ deposition | ||
| Willette et al., 2010 | 30% DR | Attenuates the relation between IL-6 and brain volume loss | Attenuates the relation between IL-6 and brain volume loss | ||
| Willette et al., 2012 | 30% DR | Attenuates the negative correlation between homocysteine and global gray matter volume | Attenuates the negative correlation between homocysteine and global gray matter volume | ||
| Colman et al., 2009; Kastman et al., 2012; Sridharan et al., 2012; Sridharan et al., 2013 | 30% DR (University of Wisconsin study) | ↓ Age-related astrogliosis (↓ GFAP in hippocampus and entorhinal cortex) | Preserves motor performance | No effect on corpus callosum integrity; ↑ FA in several white matter regions; ↓ GM volume loss; ↓ brain iron accumulation | |
| Humans | Leclerc et al., 2020; Witte et al., 2009 | 25–30% DR | Ameliorates memory performance | ↓ C reactive protein and insulin levels | |
| Blumenthal et al., 2010; Smith et al., 2010 | DASH diet (Appel et al., 1997) and DR | Improves cognitive function | |||
| AD | |||||
| Rodents | Patel et al., 2005; Wang et al., 2005; Wu et al., 2008; Schafer et al., 2015 | 30–40% DR | ↓ Aβ and phospho-tau deposition; ↓ astrocyte activation | Improved performance in cognitive tests | |
| Halagappa et al., 2007; Brownlow et al., 2014 | Different DR regimens based on individual calorie consumption; 35–40% DR | No effects | Improved age-related behavioral impairments; rescued associative memory deficits | ||
| Humans | Horie et al., 2016 | DASH diet + DR 500 kcal/d or 25% DR | Improvement in cognitive functions | ||
| PD | |||||
| Rodents | Duan and Mattson, 1999 | IF | ↓ Damage to SN neurons | ↓ Motor deficits | |
| Maswood et al., 2004 | 30% DR | ↑ Levels of dopamine and dopamine metabolites in the striatal region | ↑ Locomotor activity | No differences in presynaptic dopaminergic activity in vivo | |
| Armentero et al., 2008 | IF | No effect on nigrostriatal degeneration | |||
| Griffioen et al., 2013 | IF | NA | Ameliorates autonomic function | NA | |
| Nonhuman primates | Maswood et al., 2004 | 30% DR | ↑ Levels of dopamine and dopamine metabolites in the striatal region | ↑ Locomotor activity | No differences in presynaptic dopaminergic activity in vivo |
| ALS | |||||
| Rodents | Pedersen and Mattson, 1999 | IF | Accelerates disease onset and shortens disease duration | ||
| Hamadeh et al., 2005 | 40% DR | Accelerates disease onset | |||
| MS | |||||
| Rodents | Esquifino et al., 2007 | 66% | Alters lymphocytes composition in lymphoid organs, ↓ IFN-γ production | Prevents EAE | |
| Piccio et al., 2008 | 40% DR | ↑ Corticosterone and adiponectin; ↓ leptin and IL-6 | Ameliorates EAE clinical course | ||
| Kafami et al., 2010 | IF | Ameliorates EAE clinical course and reduces incidence of disease | |||
| Cignarella et al., 2018 | IF | ↓ Th17 cells, ↑ T regulatory cells in small intestine lamina propria, altered gut microbiota | Ameliorates EAE clinical course and reduces incidence of disease | ||
| Jordan et al., 2019 | IF | ↓ Monocyte infiltration in the spinal cord, ↓ TNFα, IL-1β, CXCL2, and CXCL10 | Ameliorates EAE clinical course and reduces incidence of disease | ||
| Humans | Saadatnia et al., 2009 | Ramadan fasting | Well tolerated, no differences in relapse rate | ||
| Etemadifar et al., 2016 | Ramadan fasting | Improves physical health and mental health composites of QOL | |||
| Choi et al., 2016 | FMD + Mediterranean or ketogenic diet | Improves QOL | |||
| Fitzgerald et al., 2018 | 22% DR or IF | Improves mood | |||
| Cignarella et al., 2018 | IF | ↓ Leptin | |||
| Model . | Reference . | Type of DR . | DR effects on inflammatory or other brain pathology markers . | DR effects on cognitive or motor functions . | DR effects on imaging measures . |
|---|---|---|---|---|---|
| Aging | |||||
| Rodents | Morgan et al., 1999; Lee et al., 2000 | 30–40% DR | ↓ Age-related increased of activation markers on microglia (e.g., MHCII) or astrocytes (e.g., GFAP); ↓ inflammatory genes | ||
| Kaur et al., 2008 | IF | ↓ Age-related changes in brain expression of NCAM, PSA-NCAM, and GFAP | |||
| Singh et al., 2012 | IF | ↓ Protein oxidative damage; ↑ markers of synaptic plasticity in the hippocampus | Ameliorates motor coordination, cognitive skills | ||
| Nonhuman primates | Qin et al., 2006 | 30% DR | ↓ Aβ deposition | ||
| Willette et al., 2010 | 30% DR | Attenuates the relation between IL-6 and brain volume loss | Attenuates the relation between IL-6 and brain volume loss | ||
| Willette et al., 2012 | 30% DR | Attenuates the negative correlation between homocysteine and global gray matter volume | Attenuates the negative correlation between homocysteine and global gray matter volume | ||
| Colman et al., 2009; Kastman et al., 2012; Sridharan et al., 2012; Sridharan et al., 2013 | 30% DR (University of Wisconsin study) | ↓ Age-related astrogliosis (↓ GFAP in hippocampus and entorhinal cortex) | Preserves motor performance | No effect on corpus callosum integrity; ↑ FA in several white matter regions; ↓ GM volume loss; ↓ brain iron accumulation | |
| Humans | Leclerc et al., 2020; Witte et al., 2009 | 25–30% DR | Ameliorates memory performance | ↓ C reactive protein and insulin levels | |
| Blumenthal et al., 2010; Smith et al., 2010 | DASH diet (Appel et al., 1997) and DR | Improves cognitive function | |||
| AD | |||||
| Rodents | Patel et al., 2005; Wang et al., 2005; Wu et al., 2008; Schafer et al., 2015 | 30–40% DR | ↓ Aβ and phospho-tau deposition; ↓ astrocyte activation | Improved performance in cognitive tests | |
| Halagappa et al., 2007; Brownlow et al., 2014 | Different DR regimens based on individual calorie consumption; 35–40% DR | No effects | Improved age-related behavioral impairments; rescued associative memory deficits | ||
| Humans | Horie et al., 2016 | DASH diet + DR 500 kcal/d or 25% DR | Improvement in cognitive functions | ||
| PD | |||||
| Rodents | Duan and Mattson, 1999 | IF | ↓ Damage to SN neurons | ↓ Motor deficits | |
| Maswood et al., 2004 | 30% DR | ↑ Levels of dopamine and dopamine metabolites in the striatal region | ↑ Locomotor activity | No differences in presynaptic dopaminergic activity in vivo | |
| Armentero et al., 2008 | IF | No effect on nigrostriatal degeneration | |||
| Griffioen et al., 2013 | IF | NA | Ameliorates autonomic function | NA | |
| Nonhuman primates | Maswood et al., 2004 | 30% DR | ↑ Levels of dopamine and dopamine metabolites in the striatal region | ↑ Locomotor activity | No differences in presynaptic dopaminergic activity in vivo |
| ALS | |||||
| Rodents | Pedersen and Mattson, 1999 | IF | Accelerates disease onset and shortens disease duration | ||
| Hamadeh et al., 2005 | 40% DR | Accelerates disease onset | |||
| MS | |||||
| Rodents | Esquifino et al., 2007 | 66% | Alters lymphocytes composition in lymphoid organs, ↓ IFN-γ production | Prevents EAE | |
| Piccio et al., 2008 | 40% DR | ↑ Corticosterone and adiponectin; ↓ leptin and IL-6 | Ameliorates EAE clinical course | ||
| Kafami et al., 2010 | IF | Ameliorates EAE clinical course and reduces incidence of disease | |||
| Cignarella et al., 2018 | IF | ↓ Th17 cells, ↑ T regulatory cells in small intestine lamina propria, altered gut microbiota | Ameliorates EAE clinical course and reduces incidence of disease | ||
| Jordan et al., 2019 | IF | ↓ Monocyte infiltration in the spinal cord, ↓ TNFα, IL-1β, CXCL2, and CXCL10 | Ameliorates EAE clinical course and reduces incidence of disease | ||
| Humans | Saadatnia et al., 2009 | Ramadan fasting | Well tolerated, no differences in relapse rate | ||
| Etemadifar et al., 2016 | Ramadan fasting | Improves physical health and mental health composites of QOL | |||
| Choi et al., 2016 | FMD + Mediterranean or ketogenic diet | Improves QOL | |||
| Fitzgerald et al., 2018 | 22% DR or IF | Improves mood | |||
| Cignarella et al., 2018 | IF | ↓ Leptin | |||
Summary of the main studies on the effects of DR on aging and neurodegenerative and neuroinflammatory diseases. FA, fractional anisotropy. GM, gray matter; NA, not applicable; NCAM, neural cell adhesion molecule; PSA, polysialylated; QOL, quality of life; SN, substantia nigra.