May 2024 Issue

CPE Monthly: Nutrition Guidance for People With ALS
By Alexandria Hardy, RDN, LDN
Today’s Dietitian
Vol. 26 No. 5 P. 32

Take this course and earn 2 CEUs on our Continuing Education Learning Library

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is a fatal disease in which motor neurons in the brain and spinal cord degenerate as the disease advances.1-4 Neurons are transmitter cells that depend on glucose; in the absence of sufficient energy sources, glucose hypometabolism can occur in the brain.2,5 Physically, this translates into a loss of gross and fine motor skills with eventual paralysis and an impaired respiratory system.2

This continuing education course will examine nutrition interventions to support people diagnosed with ALS. Lifestyle and dietary challenges will be explored with the goals of preventing malnutrition, maintaining muscle tone and strength, and identifying therapeutic practices to promote quality of life.

The Science of ALS
ALS is the most prevalent motor neuron disease globally and affects roughly five to six people per every 100,000.6 In 2017, the National ALS Registry, a program developed through the CDC, estimated that there were around 31,843 people with ALS (PALS) in the United States.2 This estimate shows a steady incline from the establishment of the registry in 2010.7 Most PALS live two to five years postdiagnosis, with the main cause of death attributed to respiratory failure due to paralysis.3,4,8 ALS typically manifests between the ages of 50 and 69 and is more commonly seen in Western countries (European countries, the United States) than Eastern countries like China or South Korea, possibly due to enhanced screening and testing in Western countries.7,9 ALS is more likely to occur in white populations than in Asian, Hispanic, and African populations.9 As the global population ages, ALS cases may increase by 69% from 2015 to 2040.10

Symptoms and Diagnosis
On average, it takes more than 12 months from the presentation of symptoms to a clinical diagnosis.11 Early symptoms typically present as muscle twitching and weakness or difficulties when speaking or swallowing.12 ALS tends to manifest either in the limbs, which slows gross and motor movement, or the bulbar region, which mainly affects the face and neck.1 Spinal or limb onset ALS is more common and has a longer disease progression and expresses itself through lower motor neuron symptoms, such as weakness or lack of muscle control in the limbs.13,14 Bulbar onset ALS primarily impacts upper motor neurons and may affect speech, language, and swallowing.13,14 Bulbar onset ALS may require early intervention from a speech and language pathologist, a respiratory therapist, and a dietitian, whereas individuals with limb onset ALS initially may need more support from an occupational therapist and an assistive technology specialist.1

ALS Classifications and Risk Factors
There are two types of ALS—sporadic ALS (sALS) and familial ALS (fALS). Most PALS fall into the sporadic category, with only 5% to 10% of individuals identifying a family history before diagnosis.8 sALS is influenced by many factors, including age, lifestyle, environment, diet, and sex.4 Men are more than 60% more likely to be affected than women, though women are more likely than men to develop ALS as they age and pass through menopause, especially if they’re underweight.4 Women are prone to experience bulbar onset ALS, which may impact their emotional expression and cognitive abilities.14 People with sALS are more likely to be older than those with fALS, who tend to display characteristics of the disease earlier in life.15 More research is needed to understand how and why age and sex hormones seem to affect prevalence and development.4

Environmental factors also can impact disease development. This is evident in areas with landfills, where cyanobacteria blooms, and where heavy metals and organic chemicals are prevalent.13,16,17 These sites are concentrated sources of environmental toxins, which can lead to an accumulation of beta-N-Methylamino-L-alanine, a nonproteinogenic amino acid associated with the development of neurodegenerative disease.16,18 Research isn’t yet clear whether the presence of beta-N-Methylamino-L-alanine in the brain tissue is the cause of disease development or if its presence advances a disease already developing.18

Lifestyle factors also may play a role in ALS development, though research is inconclusive as to the reason.13 A study published in Aging and Disease found that compared with a control group, PALS were more likely to live in rural areas and have completed college, though agricultural work was ruled out as a contributing cause.13 Some research indicates that military veterans are up to two times more likely to develop ALS—specifically sALS—than someone who hasn’t served.1,19 Neither length nor branch of service affects the rate of development, though more research is needed to better understand the link between military service and motor neuron degeneration.1

Dietary factors are less conclusive, but it appears certain foods, nutrients, and eating patterns may decrease or increase ALS risk. Consuming a higher fat diet may decrease the risk of developing ALS by 34%, even when fasting triglycerides and total cholesterol levels are higher than normal.4 Conversely, there may be a positive association between high LDL cholesterol, coronary heart disease, and the development of ALS.4,20 In a 2019 study published in the Annals of Neurology, Bandres-Ciga and colleagues concluded that this was likely due to a linear association.20 A 2022 two-sample randomized study published in Nutrients noted an association between elevated levels of linoleic acid and an increased risk of developing ALS.21 The same study also found that high levels of vitamins D and E are protective against its development.21 This may suggest that lipid metabolism plays a role in the development of ALS.21 The authors concluded that supplementation of essential fatty acids and minerals wasn’t likely to prevent ALS but that monitoring these levels may be appropriate for early intervention.21

Moreover, high levels of glutamate, a neurotransmitter that aids in message transmission, are sometimes seen in PALS.9,22,23 This occurs due to a decreased quantity of EAAT2/Glt-1 transporters, which are responsible for glutamate removal.24 As a result, excessive extracellular glutamate leads to protein and lipid degradation and a convergence of calcium ions, and, ultimately, neuron degeneration and apoptosis.23,24 Dietary glutamate primarily is found in mushrooms, grains, dairy products, fish, poultry, and red meats.25

Health Care Team Support for PALS
Due to the debilitating nature of ALS and the many body systems it impacts as the disease progresses, a multidisciplinary team is critical for supporting PALS. A wide range of specialties may be included in the PALS care team.26 A typical multidisciplinary team in an ALS clinic may include an RD, dentist, mental health therapist, pulmonologist, endocrinologist, social worker, speech language pathologist, gastroenterologist, palliative care physician, assistive technology specialists, neurologist, occupational and respiratory therapists, and nurses.1,27

The effectiveness of the multidisciplinary team interventions is most impactful when the team is involved early in diagnosis.21 The goals of the multidisciplinary team are to maintain basic body functionality as the disease develops.1 This includes preserving and maintaining muscle tone and strength, which can be measured using grip strength assessment, and monitoring weight to determine if muscle and fat stores are changing due to wasting, edema, or malnutrition.1 Grip strength assessment typically is conducted by an occupational or physical therapist and requires the patient to squeeze a dynamometer as hard as possible three times. It can be used to help assess ALS progression as the results correlate with a patient’s motor function and reflexes.

As weakness advances, estimates are that 85% of PALS will need a mechanically altered diet at some point in disease progression. It’s common for the strength of the oropharyngeal muscles to wane, leading to dysphagia and increased risk of choking.1 This often is complicated by the development of sialorrhea, or excessive saliva, which is less able to be swallowed and may lead to dehydration.1 Due to these changes, malnutrition is one of the most complex and concerning side effects of ALS and requires the cooperation of the RD and speech language pathologist to coordinate feeds and best practices for patients.1 Using a speech language pathologist to evaluate swallow strength and dysphagia risk could help the multidisciplinary team more accurately assess potential future nutrition deficiencies.28

Currently, there are more than 150 multidisciplinary clinics in the United States funded by The ALS Association, and research has shown that receiving multidisciplinary care may extend survival rates by six to 10 months and positively impact quality of life.1,19,26,29,30 The benefits to PALS aren’t just physical but also can have emotional and mental payoffs. Postdiagnosis, the mental health therapist may choose to introduce relaxation or meditation practices and work to help PALS reframe their diagnosis.23 These practices may seem trivial, but some studies have linked an increase in patient morale and positivity to a longer lifespan or slower disease progression.23

Nutrition Concerns for PALS
Feeding and caring for an individual with ALS necessitates the support and cooperation of the patient, multidisciplinary team, and caregivers. PALS face many dietary and nutrient challenges that require a flexible approach as the disease progresses, and energy needs may be more difficult to meet. The most significant of these concerns is a change in metabolism, which can lead to malnutrition, both of which impact quality of life.

Altered Metabolism
PALS are more likely to experience hypermetabolism, which can lead to unintentional weight loss.4,31 In PALS, hypermetabolism is defined as a measured resting energy that’s ≥120% of predicted resting energy expenditure (REE).31 This occurs 25% to 67% of the time in people with sALS and in all people with fALS.31 It’s essential for the multidisciplinary team to proactively work to prevent hypermetabolism, as it can lead to a rapid decline in body functionality; specifically, an increase in lower motor neuron involvement, which can cause atrophy or weakness, and a lower survival rate.31

The degree of hypermetabolism can be difficult to predict accurately because traditional REE calculations don’t account for the muscle atrophy experienced by PALS, whose REE is affected by their fat-free mass.31 This energy discrepancy can be as large as 19.7+/-6.4% higher than REE calculated by the Harris-Benedict equation.1 To offset these energy losses, it’s recommended that a higher energy diet of 30 to 35 kcal/kg/day be introduced in an effort to prolong quality of life.1,31

Malnutrition
Malnutrition is found in 16% to 55% of PALS and, along with hypermetabolism, is linked to shorter life expectancy.1 The Alliance to Advance Patient Nutrition found that collaborating and using a multidisciplinary team to assess the many layers of malnutrition treatment can yield better results than a sole practitioner in providing quality care.32

Upon diagnosis, malnutrition status may be the single best gauge to determine the survival rate and disease progression of ALS, followed closely by BMI. BMI can serve as a protective factor when above the normal range at diagnosis and as a risk factor when an individual falls into the underweight category.17 Weight loss during disease progression can be particularly detrimental, as each lost BMI unit may impact survival by up to 20%.17 More research is needed to determine why a BMI of 30 to 35 kg/m2 is the most protective.1,17

Identifying malnutrition using standard metrics is challenging thanks to the complex nature of ALS.1 Dietary recalls may reflect no notable change, yet unintended weight loss can still occur as a result of muscle loss from muscle degeneration.1 Despite concentrated caloric efforts on the part of the multidisciplinary team and PALS, most PALS can consume only 84% of their caloric needs daily.1 This is due to a variety of causes, including hypermetabolism, dysphagia, sialorrhea, constipation, various mood disorders, and disease progression, which may result in the need for nutrition support.1

Protein Needs
While increasing protein intake for PALS may seem warranted with the high risk of malnutrition, protein needs are largely unknown for PALS, with little evidence that a protein-rich diet will reverse lean muscle loss.1 In one Italian study, published in Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 212 newly diagnosed PALS were matched with a control subject to assess foods as potentially protective or damaging.33 All subjects were interviewed per a food frequency questionnaire, and their information was input into a database to determine macro and micronutrient values, total calories consumed, and fatty acid intake.33 The researchers found that red meat, pork, processed meat, and total protein intake were all associated with an increased risk of developing ALS.33 Dietitians therefore are encouraged to recommend moderate protein intake, using 0.6 to 1.5 g/kg/day when calculating adequate protein intake for PALS, per the “Nutritional Care of the Patient With Amyotrophic Lateral Sclerosis” published in Nutrition Issues in Gastroenterology.1

ALS and the Gut
The risk of altered gastrointestinal function is another concern for PALS that may impact appetite and quality of life. Rates of self-reported constipation increase significantly postdiagnosis, especially as fiber-rich foods, stool softeners, and physical activity may not be well tolerated in PALS. Depending on intake and swallowing abilities as the disease progresses, a modified diet may need to be considered in addition to other strategies to reduce or alleviate the potential negative impacts of constipation.1,34 Dietitians can lay the groundwork for additional nutrition support, particularly enteral nutrition (EN), as a means to maintain weight and prevent loss.12 This topic may be helpful to address shortly after diagnosis so PALS and their caregivers have time to think critically and ask questions about EN before it may be needed.1

Probiotics also may prove useful in decreasing the severity of PALS and supporting the changing microbiome if EN is needed as the disease progresses.35 A systematic review published in The Journal of Internal Medicine yielded a handful of small cross-sectional studies that examined ALS and the microbiome in humans.36 Results were mixed. Larger studies are needed to determine if PALS have a different microbial composition and if and how it changes as the disease progresses.36 While research is currently in the beginning stages, it may prove fertile ground for therapeutic treatments in the future.36 More research is needed to determine if probiotics can help rebalance the gut microbiome and improve symptomology in ALS patients.1,35,37

Diet Considerations for PALS
While consuming a balanced diet with adequate calories is the most important focus area for PALS, there are a couple of dietary approaches to note that may be helpful in combating malnutrition and preserving quality of life. These include specific dietary patterns, like the ketogenic Mediterranean diet (MDiet) and the consideration of EN support.

The Ketogenic MDiet
Researchers theorize that ALS shares many neural pathways with age-related diseases and that applying research that has proven efficacious in combating these diseases also may be beneficial for PALS.23 One of these dietary patterns is the ketogenic MDiet, which is a blend of the established ketogenic and Mediterranean dietary patterns. This eating plan emphasizes very low carbohydrate, high fat, and moderate protein intake with a focus on unprocessed foods and healthful fats, primarily omega-3 fatty acids. The combination of these two dietary patterns may help PALS achieve ketogenesis while increasing their antioxidant intake, both of which may be neuroprotective.2

Specifically, inclusion of ketogenic principles is thought to be neuroprotective by improving mitochondrial dysfunction, a pathology that is seen in both aging brains and neurodegenerative disorders. The production of ketone bodies, which include acetoacetate, beta-hydroxybutyrate, and acetone, appears to improve mitochondrial function.2,3 The efficaciousness of ketone bodies as fuel varies depending on the specific neurodegenerative disease, so more research is needed to determine a specific recommendation, though a diet composed of <30 g of carbohydrate per day may provide adequate ketone bodies.2,3

In 2020, Food Science & Nutrition studied the effects of a ketogenic MDiet on oxidative stress and ALS, theorizing that both the antioxidant profile of the MDiet and the ketone bodies of the ketogenic diet may be neuroprotective.2 The researchers noted that many of the foods that feature prominently in the MDiet (eg, nonstarchy vegetables, nuts, seeds, deeply pigmented fruits, olive oil, eggs, wine, and fish) also fit well within a ketogenic framework. 2 The MDiet approach incorporates medium-chain triglycerides, like coconut oil and goat’s milk, which are common in the ketogenic diet and may decrease inflammation.2 The MDiet also boasts an array of polyphenols; phenols; carotenoids; curcumin; coenzyme Q10; vitamins E, A, and C; and minerals that may decrease oxidative stress.2,9,22 After a thorough review of the existing research, researchers concluded that a ketogenic MDiet might serve as a therapeutic approach for slowing ALS progression, especially through improved motor function.2,38

Long-term adherence to this type of diet may be challenging for individuals and their caregivers, as low-carbohydrate, higher fat foods may be less tolerable as ALS progresses.3 To compensate for this challenge, dietitians may want to encourage a week on/week off approach to the ketogenic MDiet to support patient satiety and maintain neuroprotective benefits.3

EN
As ALS progresses, receiving adequate nutrients through the diet becomes more and more difficult. Some PALS and their caregivers choose to pursue EN as a means to safely and consistently meet hydration, medication, and nutrition goals.1 Members of the multidisciplinary team (typically the neurologist, palliative care physician, RD, respiratory therapist, and speech language pathologist) may recommend EN if meals take PALS longer than 45 minutes to consume or if fatigue and dysphagia are present and preventing adequate nutrient intake.1 Depending on the patient’s preference and abilities, this could look like bolus, intermittent, or cyclic feeds, though none has a definitive effect on quality of life or survival.1,39,40 Regardless of EN strategy, some PALS still may choose to consume food orally at times to boost quality of life, though appetite loss is common as the disease progresses.1,21

A study published in the American Journal of Translational Research in 2022 evaluated the efficacy of complete high caloric nutrition in PALS with gastrostomy tubes.41 Forty PALS were divided into two equal groups, one of which received Ensure along with a conventional diet, while the other served as a control group and received only the conventional diet.41 The survival rates for the Ensure group were 20% to 30% higher than the control at three, six, and 12 months after gastrostomy, and cholesterol and BMI didn’t change significantly.41

Early placement of a percutaneous endoscopic gastronomy tube also may help slightly prolong survival time. An observational study published in Nutricion Hospitalaria explored percutaneous endoscopic gastronomy tube placement in 37 PALS with an average age of 69. This group, which couldn’t consume any food orally due to dysphagia, tolerated the endoscopic gastrostomy without major complications within the first year of diagnosis. The average survival rate was 11.2 months postplacement; PALS with the highest BMI at baseline had the best results.42

Micronutrient Status and Dietary Supplementation
Nutrient absorption in PALS may be affected by the possible changes in feeding abilities and appetite, especially as the disease progresses; therefore, many PALS take supplements as an alternative therapeutic treatment.21 Vitamin and mineral supplementation isn’t a cure but may assist PALS with maintaining or improving quality of life.23

Micronutrients aid in metabolism and tissue functionality, both of which are negatively impacted by ALS.23 Studies on vitamin deficiency and supplementation vary, but fat-soluble vitamins, such as A and E, have been found in higher concentrations in PALS, while water-soluble vitamins, including B2, B9, and C, have been found in lower concentrations.21,43

Researchers have theorized that elevated concentrations of fat-soluble vitamins suggest a neuroprotective effect against the development and rapid progression of ALS.21 This further highlights the important role of lipid metabolism related to nutrient status in PALS. Many nutrients deemed essential for PALS, namely alpha-linolenic acid, DHA, linoleic acid, copper, calcium, magnesium, iron, phosphorus, and vitamins A, B, C, D, and E, among others, may be at their most potent in the presence of polyunsaturated fatty acids and other fat-soluble vitamins.21

While researchers have looked at many of these nutrients and the possible role of supplementation in PALS, results have been mostly inconclusive. However, a few have shown some benefit, mainly in the role of reducing oxidative stress. Overall, supplementing PALS with 25,000 IU of vitamin A daily, 400 IU of vitamin E daily, and 1 g of vitamin C three times per day are common practices to boost antioxidant intake and potentially slow disease progress.12 All supplements should be reviewed and discussed with the multidisciplinary team before use to ensure there are no complications or interactions with other medications.9

Areas of Future Research
At present, there’s a dearth of regional epidemiologic data in the United States, and most of it stems from the National ALS Registry.19 The registry shows that the largest number of self-reported cases come from the Midwest, though survival data isn’t available.19 Developing a screening tool that can assess the prevalence of ALS in different geographic locations and populations may help clinicians target their therapeutic efforts.8 This type of tool also may indicate trends in disease development and treatment.8

Other areas of future research include developing a better working knowledge of the molecular pathways that impact ALS; some of this work has begun in various animal and in vivo models.4,44,45 Epigenetic research may provide valuable insight into the impact of environmental factors on gene expression, which directly impacts the development and potential delay or prevention of disease in fALS.11 More research regarding therapeutic approaches is needed, particularly largescale randomized clinical trials.3 This is especially true when investigating therapeutic approaches like supplementation, the microbiome, dietary patterns, and multidisciplinary team interventions.

Putting It Into Practice
ALS is a fatal disease, but there are many dietary interventions that may improve quality of life, maintain muscle mass, improve handgrip strength, and slightly extend the lifespan. After an individual is diagnosed with ALS, the best indicator of survival is nutrition status.1,28 Dietitians are primed to play a role in evaluating nutrition status and risk by assessing the patient’s medical history, determining ability to prepare meals and feed oneself, appraising appetite and ability to chew and swallow, and reviewing dietary supplements.1,27 Upon collecting this data, RDs can determine hydration and macro- and micronutrient needs and review dietary patterns and potential supplement needs with patients.1

Moreover, the multidisciplinary team is an important tool for PALS and their personal support team/caregivers, as they can help with the dietary and physical challenges that accompany disease onset and progression. They also may be able to positively impact the length of hospital stays and the mental health of PALS.12

Though ALS has been studied for more than 100 years, there’s still much to learn regarding its etiology and best practices for treatment.24 However, progress is being made. Over the past two decades, ALS research has quadrupled globally in terms of published studies.6 By expanding the quantity of published evidence and the number of countries that undertake this research, a more diverse and accurate picture of the trends and lifestyle, and environmental and dietary factors influencing ALS can be better understood and applied for optimal patient care.

— Alexandria Hardy, RDN, LDN, is a freelance food and nutrition writer based in Pennsylvania.

Learning Objectives
After completing this continuing education course, nutrition professionals should be better able to:
1. Counsel patients on three ways to improve energy intake and slow weight loss.
2. Determine when additional nutrition support is recommended and the best options to consider.
3. Analyze strategies the multidisciplinary team can use to support improved patient quality of life.

Examination
1. What factor is the best predictor of the survival rate and disease progression of amyotrophic lateral sclerosis (ALS)?
a. Malnutrition
b. Cholesterol level
c. Grip strength
d. Swallowing ability

2. Which type of supplement is more likely to exert a neuroprotective effect against the development and rapid progression of ALS?
a. Water-soluble vitamins
b. Mineral-based vitamins
c. Fat-soluble vitamins
d. Botanical compounds

3. As the global population ages, ALS cases may increase by how much from 2015 to 2040?
a. 39%
b. 49%
c. 59%
d. 69%

4. For people with ALS, what is one of the biggest benefits of receiving multidisciplinary care postdiagnosis?
a. Lower cost of care
b. Extended survival rates by six to 10 months
c. Access to supplements
d. Clinical trial enrollment

5. Adding an enteral nutrition supplement to an oral diet via a gastrostomy tube may improve which of the following metrics?
a. BMI
b. Weight
c. Survival rate
d. Cholesterol

6. What is the main cause of death for the majority of people with ALS?
a. Respiratory failure due to paralysis
b. Unintended weight loss
c. Muscle catabolism
d. Inadequate hydration status

7. If a person with ALS was interested in adopting a ketogenic Mediterranean diet, what would be an appropriate daily amount of carbohydrate to recommend?
a. <10 g
b. <20 g
c. <30 g
d. <40 g

8. If a person with ALS has excessive extracellular glutamate, what can happen?
a. Decrease of sodium in cells
b. Neuron degeneration
c. Decrease of calcium in cells
d. Neuron regeneration

9. What is the appropriate energy recommendation to prevent unwanted weight loss due to hypermetabolism?
a. 20 to 25 kcal/kg/day
b. 25 to 30 kcal/kg/day
c. 30 to 35 kcal/kg/day
d. 35 to 40 kcal/kg/day

10. Which type of ALS is seen in 90% to 95% of diagnosed individuals?
a. Limb onset
b. Familial
c. Bulbar onset
d. Sporadic

References
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39. Ichimaru S. Methods of enteral nutrition administration in critically ill patients: continuous, cyclic, intermittent, and bolus feeding. Nutr Clin Pract. 2018;33(6):790-795.

40. Kak M, Issa NP, Roos RP, et al. Gastrostomy tube placement is safe in advanced amyotrophic lateral sclerosis. Neurol Res. 2017;39(1):16-22.

41. Wang S, Yuan T, Yang H, Zhou X, Cao J. Effect of complete high-caloric nutrition on the nutritional status and survival rate of amyotrophic lateral sclerosis patients after gastrostomy. Am J Transl Res. 2022;14(11):7842-7851.

42. Nunes G, Santos CA, Grunho M, Fonseca J. Enteral feeding through endoscopic gastrostomy in amyotrophic lateral sclerosis patients. Nutr Hosp. 2016;33(5):561.

43. Wang M, Liu Z, Sun W. Association between vitamins and amyotrophic lateral sclerosis: a center-based survey in Mainland China. Front Neurol. 2020;11:488.

44. La Gall L, Angkor E, Connolly O, Vijayakumar UG, Duddy WJ, Duguez S. Molecular and cellular mechanisms affected in ALS. J Pers Med. 2020;10(3):101.

45. Amin A, Perera ND, Beart PM, Turner BJ, Shabanpoor F. Amyotrophic lateral sclerosis and autophagy: dysfunction and therapeutic targeting. Cells. 2020;9(11):2413.