Nutrition and Dietary Supplements in Motor Neuron Disease

doi:10.1016/j.pmr.2008.03.001

Physical Medicine and Rehabilitation Clinics of North America

Volume 19, Issue 3, August 2008, Pages 573-589

https://doi.org/10.1016/j.pmr.2008.03.001 Get rights and content

Compromised nutrition leading to weight loss is a common and significant problem in the amyotrophic lateral sclerosis (ALS) patient population. The benefit of aggressive and early nutritional therapy can profoundly influence the disease course, quality of life, and survival. This article reviews the role of nutrition, both as sustenance and treatment for patients who have ALS. Self-medication with dietary supplements has become increasingly popular within this patient population. Despite their popularity, the efficacy of these compounds has been largely unsupported by formal clinical trials. Available data will be highlighted to provide a basis upon which to advise patients requesting guidance.

Section snippets

The role of nutrition in motor neuron disease

Compromised nutrition leading to weight loss is a common and significant problem in the amyotrophic lateral sclerosis (ALS) patient population. Malnutrition and consequent weight loss are significant negative prognostic indices to survival [1], [2], [3]. The benefit of aggressive and early nutritional therapy can profoundly influence the disease course, quality of life, and survival.

This article reviews the role of nutrition, both as sustenance and treatment for patients who have ALS.

Nutrition and survival

The consequences of malnutrition in patients with ALS are well known. Inadequate dietary intake can exacerbate catabolism and atrophy of respiratory muscles, weaken the immune system, and contribute to infection [12], [13]. Weight loss and below-normal body mass index (BMI) resulting from deficient energy intake among ALS patients are correlated with shortened survival [14]. Several more recent studies confirm the observation that weight loss (and/or malnutrition), defined as BMI ≤ 18.5 kg/m²,

Nutraceuticals, functional foods, and dietary supplements

“Nutraceuticals,” “functional foods” and “dietary supplements” are terms used to describe chemical components of foods that may display unique, disease-fighting pharmacokinetics and pharmacodynamics when ingested in amounts above that of one's typical diet [23]. The emergence of nutraceutical use within the patient population has defined a growing and substantial treatment modality. Often such dietary supplements are self-prescribed based on theoretic benefits or anecdotal reports, addressing

Oxidative injury

Oxidative damage is thought to be a major contributing factor in the death of motor neurons [28]. Oxidative injury can have both a primary role and a secondary role triggered by other mechanisms mentioned below. Reactive oxygen species (ROS) include superoxide, hydrogen peroxide (H₂O₂), hydroxyl free radicals (OH), and nitric oxide (NO). ROS readily react with lipids, proteins, and DNA to induce cellular damage [29], [30], [31]. The high metabolic activity of neurons leads to considerable ROS

Vitamin E

Reports of alpha-tocopherol, an isomer of vitamin E, as a trial therapy for ALS date back to the 1940s when Lou Gehrig received weekly intramuscular injections as putative therapy [47]. Despite the absence of documented clinical benefit in controlled trials, vitamin E continues to be among the most popular of the dietary supplements. This is likely the result of preclinical data, the association of vitamin E and motor neuron disease from other species, and the ease of availability with few or

Summary

The benefits of aggressive nutritional support in affecting disease course and survival are well documented. Enteral nutrition is best thought of as an early adjunctive therapy, rather than as a late palliative therapy. The patient population has embraced the use of dietary supplements in the form of vitamins, nutraceuticals, and functional foods, often despite the absence of documented efficacy. The axiom that “the absence of proof does not equate to the proof of absence” [97] has fueled

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Rehabilitation is an integral component of comprehensive care for individuals with neuromuscular disease. Rehabilitation focuses on optimizing quality of life and facilitating function and independence to the greatest extent, and for the longest duration, possible. A rehabilitation program can include exercise, adaptive and mobility devices, pain and symptom management, and anticipatory planning for the patient and family. Especially in progressive neuromuscular diseases, palliative care collaboration provides a valuable additional layer of support for complex symptom management and advance care planning.
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Neurodegenerative diseases are one of the major health concerns at present in the older age population across the globe. Reports suggest that aberrant production of mutated form of protein aggregates in the brain leads to onset of these diseases. Till date, the well-studied neurodegenerative diseases are Alzheimer disease (AD), Parkinson disease (PD), Huntington disease (HD), and Amyotrophic lateral sclerosis (ALS). Mitochondrial dysfunction, reactive oxygen species accumulation, neuroinflammation, and apoptosis are the hallmarks of pathophysiological response of neurodegenerative diseases. The pharmacotherapies available to alleviate the symptoms of these diseases have several side effects. In this scenario, several natural compounds found in edible items, termed as nutraceuticals, are gaining ground on account of their pleiotropic antioxidant and antiinflammatory properties, and their ability to modulate the activities of kinases and phosphatases. Herein, we focus on the mechanism of various neurodegenerative diseases and the mechanisms of well-known natural components enriched in dietary substances.
Galactosemia: opportunities for novel therapies
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Galactosemia is an inherited metabolic disease affecting enzymes of the Leloir pathway of galactose metabolism. There are four types: type I (galactose 1-phosphate uridylyltransferase; GALT), type II (galactokinase; GALK1), type III (uridine diphosphate [UDP]-galactose 4’-epimerase; GALE), and type IV (galactose mutarotase; GALM). The range of symptoms is wide, ranging from almost asymptomatic to life-threatening damage to the liver, kidneys, and brain. Severely affected patients suffer cognitive disabilities. Current treatment relies on the restriction of galactose (and its precursors such as lactose) from the diet. This is imperfect and often slows, rather than prevents, the development of symptoms. Potential new treatment approaches include enzyme replacement therapy (ERT), inhibition of galactokinase, antioxidants, phosphate supplementation, and pharmacological chaperones. ERT has been successfully applied in other diseases, but it is likely that the proteins would need to be delivered to the brain to be fully effective. This would present problems with currently available technologies. Antioxidant therapy and phosphate supplementation would treat downstream effects of the disease and not the fundamental causes. They may be useful in conjunction with galactose restriction but are unlikely to provide a complete solution for the most severely affected patients. Galactokinase inhibition has the most underpinning research with several promising compounds identified. It has yet to be tested in clinical trials. Pharmacological chaperone therapy offers the opportunity to correct protein folding and restore activity. Challenges include development of suitable assays, potential for long-term toxicity of drugs that may be taken for a lifetime, and identifying compounds that work with different disease-associated variants.
Complementary and Alternative Therapies in Amyotrophic Lateral Sclerosis
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Citation Excerpt :
Although most of the supplements have little or no supporting scientific evidence to back their use, patients will take them. Rosenthal and Ellis,38 in their review of nutrition and dietary supplements for motor neuron disease, suggest that it is the responsibility of the practitioner to remain aware of known adverse effects and “offer advice or caution as our patients explore their own therapeutic combinations.”38 The Deanna Protocol is a supplement regimen that many PALS currently ask about.
Gastrostomy in patients with amyotrophic lateral sclerosis (ProGas): A prospective cohort study
2015, The Lancet Neurology
Citation Excerpt :
Three main methods of gastrostomy insertion are currently used in patients with amyotrophic lateral sclerosis: percutaneous endoscopic gastrostomy, radiologically inserted gastrostomy, and per-oral image-guided gastrostomy.8 However, with little evidence available,9,10 current practice in relation to choice of method and timing of gastrostomy insertion is largely based on consensus and expert opinion.8 Gastrostomy could be beneficial for the survival, quality of life, and nutritional outcome of patients with this disease, but there is a paucity of high-quality evidence relating to these aspects of the intervention.9,11–13
Gastrostomy feeding is commonly used to support patients with amyotrophic lateral sclerosis who develop severe dysphagia. Although recommended by both the American Academy of Neurology and the European Federation of Neurological Societies, currently little evidence indicates the optimum method and timing for gastrostomy insertion. We aimed to compare gastrostomy insertion approaches in terms of safety and clinical outcomes.
In this large, longitudinal, prospective cohort study (ProGas), we enrolled patients with a diagnosis of definite, probable, laboratory supported, or possible amyotrophic lateral sclerosis who had agreed with their treating clinicians to undergo gastrostomy at 24 motor neuron disease care centres or clinics in the UK. The primary outcome was 30-day mortality after gastrostomy. This study was registered on the UK Clinical Research Network database, identification number 9923.
Between Nov 2, 2010, and Jan 31, 2014, 345 patients were recruited of whom 330 had gastrostomy. 163 (49%) patients underwent percutaneous endoscopic gastrostomy, 121 (37%) underwent radiologically inserted gastrostomy, 43 (13%) underwent per-oral image-guided gastrostomy, and three (1%) underwent surgical gastrostomy. 12 patients (4%, 95% CI 2·1–6·2) died within the first 30 days after gastrostomy: five (3%) of 163 after percutaneous endoscopic gastrostomy, four (3%) of 121 after radiologically inserted gastrostomy, and three (7%) of 43 after per-oral image-guided gastrostomy (p=0·46). Including repeat attempts in 14 patients, 21 (6%) of 344 gastrostomy procedures could not be completed: 11 (6%) of 171 percutaneous endoscopic gastrostomies, seven (6%) of 121 radiologically inserted gastrostomies, and three (6%) of 45 per-oral image-guided gastrostomies (p=0·947).
The three methods of gastrostomy seemed to be as safe as each other in relation to survival and procedural complications. In the absence of data from randomised trials, our findings could inform clinicians and patients in reaching decisions about gastrostomy and will stimulate further research into the nutritional management in patients with amyotrophic lateral sclerosis.
Motor Neurone Disease Association of Great Britain and Northern Ireland (MNDA) and the Sheffield Institute for Translational Neuroscience (SITraN).

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Nutrition and Dietary Supplements in Motor Neuron Disease

Section snippets

The role of nutrition in motor neuron disease

Nutrition and survival

Nutraceuticals, functional foods, and dietary supplements

Oxidative injury

Vitamin E

Summary

Am J Clin Nutr

Neuromuscul Disord

Am J Clin Nutr

J Neurol Sci

Neurobiol Aging

Free Radic Biol Med

J Neurol Sci

Pharmacol Ther

Neurochem Int

J Neurol Sci

Brain Res Brain Res Rev

Mol Aspects Med

Nutrition

J Neurol Sci

J Biol Chem

Biochem Biophys Res Commun

Neurosci Lett

Neurosci Lett

Neurobiol Dis

Neuroscience

Mitochondrion

J Neurol Sci

Exp Neurol

Brain Res

J Neurol Sci

Neurosci Lett

Symptomatic treatment of respiratory and nutritional failure in amyotrophic lateral sclerosis

J Neurol

Nutritional status is a prognostic factor for survival in ALS patients

Neurology

Percutaneous endoscopic gastrostomy and enteral nutrition in amyotrophic lateral sclerosis

J Neurol

Hypermetabolism in ALS: correlations with clinical and paraclinical parameters

Neurodegener Dis

Standard equations are not accurate in assessing resting energy expenditure in patients with amyotrophic lateral sclerosis

JPEN J Parenter Enteral Nutr

Nutritional management in MND/ALS patients: an evidence based review

Amyotroph Lateral Scler Other Motor Neuron Disord

Practice parameter: the care of the patient with amyotrophic lateral sclerosis (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology: ALS Practice Parameters Task Force

Neurology

Complications and survival following radiologically and endoscopically-guided gastrostomy in patients with amyotrophic lateral sclerosis

Amyotroph Lateral Scler Other Motor Neuron Disord

Nutritional factors in the pathogenesis and therapy of respiratory insufficiency in neuromuscular diseases

Monaldi Arch Chest Dis

Nutritional issues and supplements in amyotrophic lateral sclerosis and other neurodegenerative disorders

Curr Opin Clin Nutr Metab Care

Safety and factors related to survival after percutaneous endoscopic gastrostomy in ALS. ALS Percutaneous Endoscopic Gastrostomy Study Group

Neurology

Percutaneous radiological gastrostomy: a safe and effective method of nutritional tube placement in advanced ALS

J Neurol Neurosurg Psychiatry

Nutritional assessment and survival in ALS patients

Amyotroph Lateral Scler Other Motor Neuron Disord

Percutaneous endoscopic gastrostomy (PEG) in patients with ALS and bulbar dysfunction

Amyotroph Lateral Scler Other Motor Neuron Disord

Early symptom progression rate is related to ALS outcome: a prospective population-based study

Neurology

Survival of patients with ALS following institution of enteral feeding is related to pre-procedure oximetry: a retrospective review of 98 patients in a single centre

Amyotroph Lateral Scler

In the midst of confusion lies opportunity: fostering quality science in dietary supplement research

J Am Coll Nutr

Changes in the management of ALS since the publication of the AAN ALS practice parameter 1999

Amyotroph Lateral Scler Other Motor Neuron Disord

Molecular biology of amyotrophic lateral sclerosis: insights from genetics

Nat Rev Neurosci

Amyotrophic lateral sclerosis: a review of current concepts

Amyotroph Lateral Scler Other Motor Neuron Disord