Focus more on Neurological Perspectives

1. INTERMITTENT FASTING
BENEFICIAL OR HARMFUL ?
ADE WIJAYA, MD – OCTOBER 2018
MOREFOCUSON NEUROLOGICAL PERSPECTIVE

2. INTRODUCTION
 Caloric restriction vs total caloric desistance
 Total caloric desistance: intermittent fasting and alternate daily fasting
 Intermittent fasting (total caloric desistance) is a method of energy deprivation
 Reduce the risk of atherosclerosis, metabolic dysregulation, and cognitive dysfunction, also extend
longevity
Horne BD, Muhlestein JB, Anderson JL. Health effects of intermittent fasting: hormesis or harm? A systematic review. The American journal of clinical nutrition. 2015 Jul 1;102(2):464-70.

3. INTERMITTENT FASTING
 Complete fasting every other day (Bruce-Keller et al., 1999; Anson et al., 2003);
 70% energy restriction every other day (Johnson et al., 2007; Varady et al., 2015);
 Consuming only 500–700 cal two consecutive days/week (Harvie et al., 2011);
 Restricting food intake to a 6–8 h time period daily, which has also been termed ‘time restricted feeding’
(TRF) (Chaix et al., 2014).

4. MECHANISM
 The body uses fats for energy during TCD,
reducing adipose mass and resulting in a small,
long-term reduction in risk after each fasting
episode
 Nutritional stress during TCD, at least in part,
results in cellular level repairs, functional
optimization, and metabolic rejuvenation that
may improve long-term health by reducing
cardiovascular risk factors and acting on the
metabolism of glucose via Forkhead Box A genes
Horne BD, Muhlestein JB, Anderson JL. Health effects of intermittent fasting: hormesis or harm? A systematic review. The American journal of clinical nutrition. 2015 Jul 1;102(2):464-70.

5. METABOLIC CHANGES DURING FASTING PERIODS
 Maintenance of blood glucose levels in the low normal range
 Depletion or reduction of glycogen stores
 Mobilization of fatty acids and generation of ketones, a reduction of circulating leptin and often
elevation of adiponectin levels
 Behavioral changes: Increased alertness/arousal and increased mental acuity
(Johnson et al., 2007; Wan et al., 2010; Fon et al., 20

6. Johnson et al., 2007; Wan et al., 2010

7. Horne BD, Muhlestein JB, Anderson JL. Health effects of intermittent fasting: hormesis or harm? A systematic review. The American journal of clinical nutrition. 2015 Jul 1;102(2):464-70.

8. Mattson MP, Longo VD, Harvie M. Impact of intermittent fasting on health and disease processes. Ageing research reviews. 2017 Oct 1;39:46-58.

9. STUDY ON NEUROLOGICAL DISORDERS
 When rats are maintained on ADF for several months prior to administration of kainic acid, their
hippocampal neurons are more resistant to degeneration and learning and memory deficits were
ameliorated (Bruce-Keller et al., 1999).
 Rats on ADF are also more resistant to 3NPA and malonate, exhibit less motor dysfunction and less
degeneration of striatal neurons, suggesting a potential therapeutic application to patients with HD
(Bruce-Keller et al., 1999)
 Mice maintained on ADF for several months are more resistanttoMPTP as indicated by reduced loss of
dopaminergicneurons and improved functional outcome in a PD model (Duan and Mattson, 1999).
 IF has been reported to improve outcome in animal models of traumatic injury to the nervous system, as
well as in models of peripheral neuropathy

10. STUDY ON NEUROLOGICAL DISORDERS
 IF can protect neurons against dysfunction even in the presence of A and Tau pathologies may include
reductions in oxidative stress, preservation of mitochondrial function and increased neurotrophic factor
signaling and autophagy because:
 IF induces the expression of antioxidant enzymes and neurotrophic factors including BDNF and FGF2
(Arumugam et al., 2010); BDNF stimulates mitochondrial biogenesis (Cheng et al., 2012);
 IF up-regulates autophagy (Godar et al., 2015); neurotrophic factors and interventions that bolster
mitochondrial bioenergetics (Mark et al., 1997; Caccamo et al., 2010; Liu et al., 2013) and autophagy
(Majumder et al., 2011; Lin et al., 2013) can protect neurons in experimental models of AD.

11. STUDY ON NEUROLOGICAL DISORDERS
 ADF can reduce brain damage and improve functional outcome in animal models of stroke (Yu and
Mattson, 1999; Arumugam et al., 2010).
 Up-regulationof expression of neurotrophic factors (BDNF and FGF2), antioxidant enzymes (heme
oxygenase 1) and protein chaperones (HSP70 and GRP78) (Arumugam et al., 2010).
 Reduced levels of proin- flammatory cytokines (TNF, IL1- and IL6) and suppression of the
‘inflammasome’ (Arumugam et al., 2010; Fann et al., 2014).
 Reductions in levels of leptin and increased levels of ketones may also contribute to neuroprotection by
IF in stroke models (Manzanero et al., 2014)

12. INTERMITTENT FASTING AND ISCHAEMIC STROKE
Fann DY, Ng GY, Poh L, Arumugam TV. Positive effects of intermittent fasting in ischemic stroke. Experimental gerontology. 2017 Mar 1;89:93-102.

13. SUMMARY
 Reduced levels of insulin and leptin which parallel increases in insulin and leptin sensitivity;
 Reduced body fat; elevated ketone levels;
 Reduced resting heart rate and blood pressure, and increased heart rate variability (resulting from
increased parasympathetic tone)
 Reduced inflammation; increased resistance of the brain and heart to stress (e.g., reduced tissue damage
and improved functional outcome in models of stroke and myocardial infarction); and resistance to
diabetes
 IF can protect against the metabolic syndrome and associated disorders including diabetes and
cardiovascular disease, neurological disorders, and probably cancers and multiple sclerosis.