Therapeutic alternative of the ketogenic Mediterranean diet to improve mitochondrial activity in Amyotrophic Lateral Sclerosis (ALS): A Comprehensive Review

Abstract

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease whichis pathogenically based on the mitochondrial alteration of motor neurons, causing progressive neuron death. While ALS is characterized by enormous oxidative stress, the Mediterranean diet has been seen to have high antioxidant power. Therefore, the aim of this study is to determine how the Mediterranean diet can improve mitochondrial activity, establishing the specific nutrients and, in addition, observing the pathogenic mechanisms related to the disease that would achieve this improvement.To this end, a comprehensive review of the literature was performed using PubMed.KBs have been observed to have a neuroprotective effect to improve energy balance, increasing survival and the number of motor neurons. This ketogenesis can be achieved after following a Mediterranean diet which is associated with great benefits in other neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and ALS. These benefits are due to the high antioxidant power especially based on polyphenols contained mainly in olive oil, wine, nuts, or berries. In short, KBs could be considered as a promising option to treat ALS, representing an alternative source to glucose in motor neurons by providing neuroprotection. In addition, treatment results can be improved as ketogenesis can be achieved (increase in KBs) by following a Mediterranean diet, thanks to the high antioxidant properties which, at the same time, would improve the high oxidative stress that characterizes the disease. K E Y W O R D Samyotrophic lateral sclerosis, ketone bodies, mediterranean diet, mitochondria | INTRODUC TI ONNeurons are cells in charge of transmitting information through chemical and electrical signals, therefore requiring a high level of energy in the brain. This use of energy represents between 20% and 25% of the total oxygen consumed by the body, of which approximately half is used to generate membrane potentials. At the same time, they maintain ion gradients for neurotransmission, the main source of said percentage

Ketogenic diet and ketone bodies enhance the anticancer effects of PD-1 blockade

“…Several diseases involving alterations in mitochondrial metabolism, such as epilepsy 29 , diabetes mellitus type II, obesity, neurological disorders and cancer, may benefit from KD [30][31][32][33] . However, most of the knowledge on the beneficial effects of KD on cancer relies on a cellautonomous vision of malignancy, as well as on epidemiological studies rather than experimental animal models.…”

Does conserved domain SOD1 mutation has any role in ALS severity and therapeutic outcome?

“…1 Centre for Systems Biology and Bioinformatics, Panjab University, Chandigarh, India. 2 Department of Biotechnology, Goa University, Taleigao Plateau, Goa, India. 3 Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India.…”

“…It can be characterized by progressive degeneration of both upper and lower motor neurons (amyotrophic) leading to hardening of lateral columns and creeping paralytic condition (lateral sclerosis). For ALS patients, maximum duration of survival is around 3-5 years [1,2]. As the disease progresses, phosphorylation of neurofilaments stimulates the accumulation of bunina and lewy bodies in pathophysiology of ALS patients consequently induce inflammation in perikarya and proximal axons.…”

“…Spheroids and ubiquitinylated strands can also stimulate the inflammation in these patients later which can be mediated through triggered response of microglia and astrocytes [3]. Terminal stage in ALS patients can feature failure of cardio-respiratory system after 2-5 years of onset of disease, resulting into death [2].…”

Neuroprotective Effect of Ketone Metabolism on Inhibiting Inflammatory Response by Regulating Macrophage Polarization After Acute Cervical Spinal Cord Injury in Rats

“…It was proven to be effective in the clinical treatment of pharmaco-resistant epilepsy, especially in children (Kverneland et al, 2017). Furthermore, ketogenic metabolism presented a beneficial effect in Alzheimer's disease (Pawlosky et al, 2017), Parkinson's disease (Norwitz et al, 2019), traumatic brain injury (Prins and Matsumoto, 2014;Wood et al, 2018), and amyotrophic lateral sclerosis (Zhao et al, 2006;Caplliure-Llopis et al, 2019).…”