Metabolic Abnormalities, Dietary Risk Factors and Nutritional Management in Amyotrophic Lateral Sclerosis

Abstract

Amyotrophic Lateral Sclerosis (ALS) is a devastating progressive neurodegenerative disease that affects motor neurons, leading to a relentless paralysis of skeletal muscles and eventual respiratory failure. Although a small percentage of patients may have a longer survival time (up to 10 years), in most cases, the median survival time is from 20 to 48 months. The pathogenesis and risk factors for ALS are still unclear: among the various aspects taken into consideration, metabolic abnormalities and nutritional factors have been the focus of recent interests. Although there are no consistent findings regarding prior type-2 diabetes, hypercholesterolemia and ALS incidence, abnormalities in lipid and glucose metabolism may be linked to disease progression, leading to a relatively longer survival (probably as a result of counteract malnutrition and cachexia in the advanced stages of the disease). Among potential dietary risk factors, a higher risk of ALS has been associated with an increased intake of glutamate, while the consumption of antioxidant and anti-inflammatory compounds, such as vitamin E, n-3 polyunsaturated fatty acids, and carotenoids, has been related to lower incidence. Poor nutritional status and weight loss in ALS resulting from poor oral intake, progressive muscle atrophy, and the potential hypermetabolic state have been associated with rapid disease progression. It seems important to routinely perform a nutritional assessment of ALS patients at the earliest referral: weight maintenance (if adequate) or gain (if underweight) is suggested from the scientific literature; evidence of improved diet quality (in terms of nutrients and limits for pro-inflammatory dietary factors) and glucose and lipid control is yet to be confirmed, but it is advised. Further research is warranted to better understand the role of nutrition and the underlying metabolic abnormalities in ALS, and their contribution to the pathogenic mechanisms leading to ALS initiation and progression.

Could ozone become a complementary therapeutic approach to improve metabolic and endocrine response of ALS patients?

“…O 3 exposure modi ed the expression pro le of hypothalamic neuropeptides altering STAT3 and Akt pathways in TDP-43 A315T mice Since metabolic abnormalities have been reported in both ALS patients 13 and mouse models of ALS [14][15][16][17] , and we previously reported a progressive decline in body weight in TDP-43 A315T mice compared to WT mice 11 , we evaluated if genes involved in metabolism were affected in the hypothalamus of TDP-43 A315T mice compared to WT controls in responses to FA or O 3 exposure (Fig. 1).…”

Amyotrophic Lateral Sclerosis: A Diet Review

“…Metabolic defects have often identified in ALS patients. However, there are controversial opinions of the scientific community: it is not clear if the metabolic alterations are a consequence of ALS or if they could play a role in the disease onset [ 25 , 162 ].…”

“…A correlation among these processes in ALS has been demonstrated with several life-style factors, such as diet, alcohol, tobacco, sedentary lifestyle, or exposure to toxic materials [ 24 ]. Riluzole, an anti-glutamate agent, is the only treatment approved by the US Food and Drug Administration and the European Medicine Agency (EMA) and it can increase the survival of ALS patients by a few months [ 25 ]. However, to date there is no effective cure, but the use of antioxidant compounds could be a potential therapeutic strategy as they could help regulate the crucial biological processes involved in ALS [ 22 ].…”

RNA Deregulation in Amyotrophic Lateral Sclerosis: The Noncoding Perspective

“…These two issues could be intriguingly linked through nutrition. The largely sporadic nature of most ALS cases indicates that extrinsic factors, including diet, may play a relevant role in ALS, representing either a potential risk or a neuroprotective factor [ 141 ]. Growing evidence demonstrates that specific nutritional regimens [ 142 ] or dietary components [ 143 ] may influence the state of ALS patients or mouse models, by affecting at several levels (microbiome, mitochondrial activity, etc.)…”