Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting nerve cells in the brain and spinal cord. Once ALS starts, it almost always progresses, eventually destroying a person’s ability to complete daily functions before progressing to death. Around 5,000 people in the U.S. are diagnosed with ALS annually, but it occurs worldwide with no racial, ethnic, or socioeconomic boundaries.
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Despite extensive research, the exact cause of ALS remains unknown, and no cure exists. With a short life expectancy after diagnosis, the search for effective treatment or prevention measures is pressing. Among the contenders, research is pointing toward diet as a possible tactic to moderate ALS risk and disease progression.
What are the ALS Symptoms and Risk factors?
ALS leads to the progressive neurodegeneration of motor neurons, eventually preventing the brain from initiating and controlling voluntary and involuntary movement of the body. Symptoms of ALS vary from person to person and will depend on which nerve cells are affected.
According to the National Institute of Neurological Disorders and Stroke (NIH), early symptoms may include muscle twitches and cramps, tight or stiff muscles (spasticity), slurred speech, or difficulty chewing or swallowing. As the disease progresses, a person may lose their ability to stand or walk on their own, chew or swallow (dysphagia), speak or form words (dysarthria), or breathe (dyspnea).
About 90% of ALS cases that occur are considered sporadic, meaning the disease seems to occur at random with no associated risk factors or family history of the disease, while the remaining 10% are inherited through genetic mutation. Although the cause of most cases of ALS is unknown, there are some established risk factors, including:
- Age – symptoms most commonly develop between ages 55-75
- Sex – males are more likely to develop ALS than women
- Race and ethnicity – Caucasians are most likely to develop the disease
- Military service – veterans are approximately twice as likely to develop ALS
- Family history – although only 10% of all ALS cases are familial, having a parent with ALS does increase the risk
Treating ALS
There is no treatment to cure ALS or reverse damage done to motor neurons caused by ALS. Therefore, most treatments focus on keeping people mobile, comfortable, and independent after diagnosis.
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Strategies are typically individualized and include multidisciplinary care, and incorporate pharmacological and lifestyle interventions. Several medications have been approved by the U.S. Food and Drug Administration (FDA) to support a treatment plan for ALS. The medicines are believed to moderate damage to motor neurons, slow exacerbation of symptoms, and prolong survival by a few months. Other medications may be prescribed to help manage symptoms, including muscle cramps or stiffness, excess saliva and phlegm, sleep disturbances, and alterations in gut function.
In addition to pharmacological support, interventions may also include assistance from physical and occupational therapists to help individuals maintain mobility and independence as long as possible. Speech therapy and pulmonary specialists may also provide strategies and equipment for prolonged communication and breathing support as the disease progresses. Finally, registered dietitians may provide nutrition strategies to maintain adequate calories, fiber, and fluids. However, emerging evidence suggests that diet may play a larger role in ALS outcomes than previously believed.
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The Relationship Between Omega-3s and ALS
Polyunsaturated fatty acids (PUFAs) are incorporated into and play roles in neuron survival, neuroinflammation, and the structural and functional regulation of neurons, all of which are relevant to the etiology of ALS. Of the many PUFAs, omega-3 fatty acids, in particular, have exhibited neuroprotective properties. Therefore, it’s little surprise that multiple studies have uncovered associations between omega-3 intake and ALS risk.
A 2014 study conducted a pooled analysis of nearly 1,000 cases of ALS occurring in 5 extensive prospective cohort studies to examine the association between omega-6 and omega-3 PUFA consumption and ALS risk. The researchers found that individuals with higher dietary intakes of omega-3 PUFAs had markedly reduced risk of ALS. They found that total omega-3 PUFA intake was associated with a 34% reduced risk of ALS when comparing the highest to the lowest quintile and that intakes of alpha-linolenic acid (ALA) and marine omega-3 PUFAs were individually associated with lower ALS risk.
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Similarly, a 2007 study that used a food frequency questionnaire to assess dietary intake patterns and associated risk of developing ALS found that high intake of PUFAs and vitamin E was associated with a 50-60% decreased risk of developing ALS and that the nutrients appeared to act synergistically. However, not every study has confirmed these findings, and some evidence has found no association between PUFAs and ALS risk. Furthermore, most of the literature assesses ALS risk, and data on disease progression in ALS patients has been limited.
New Evidence: ALA is Associated with Longer Survival and Slower Functional Decline of ALS
A new study published in June 2023 investigated whether plasma levels of ALA and other fatty acids were associated with ALS disease progression, specifically survival time and functional decline during follow-up. The study population included 449 individuals with ALS who participated in the EMPOWER clinical trial, described in detail here.
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Blood samples were collected from all participants at the time of randomization and assessed to determine the concentration of individual fatty acids, expressed as a percentage of total fatty acids measured. The endpoints included were (1) death and (2) a joint-rank test that considers functional decline as a change from baseline, the ALF Functional Rating Scale-Revised (ALSFRS-R) score. Participants who died during follow-up were ranked according to time of death, while those who survived until 12 months were ranked according to change in ALFFRS-R scores.
The researchers found that higher plasma levels of ALA measured at the time of randomization in the EMPOWER trial were associated with longer survival and slower functional decline during follow-up. Furthermore, they found that higher levels of omega-3 fatty acid, eicosapentaenoic acid (EPA), and omega-6 fatty acid, linoleic acid (LA), were also associated with a lower risk of death, and LA was associated with slower functional decline. Therefore, the authors concluded that specific PUFAs, particularly ALA, may benefit ALS patients and slow disease progression.
Dietary Sources of PUFAs for ALS Patients
As the evidence indicates, the two major classes of PUFAs that may benefit patients with ALS or ALS risk are omega-3s and omega-6s. Omega-3 fatty acids ALA, EPA, and DHA are considered “essential” since the body cannot synthesize them in adequate amounts to maintain health, so they must be obtained from our diet.
ALA can be found in plants and plant oils such as flaxseed, soybean, and canola oils. While ALA can be converted into EPA and DHA, conversion rates are reported to be less than 15%. Therefore, consuming EPA and DHA directly is highly recommended. DHA and EPA are present in fish, fish oil, krill oil, and microalgae oils. While ALA requirements may be met relatively easily through plants and plant-based oils, meeting recommendations for EPA and DHA through food alone is much more challenging. DHA/EPA supplementation may be required to obtain health benefits if fish or seafood consumption is not routine.
The omega-6 fatty acid LA is the most highly consumed PUFA in the human diet. Also, an “essential” fatty acid deficiency, although extremely rare, can result in adverse health outcomes such as skin lesions and growth retardation. LA can be found in vegetable oils, nuts, seeds, meats, and eggs. Manufactured foods containing soybean oil as a primary ingredient will be rich in LA, and currently, soybean oil accounts for ~45% of dietary LA in the U.S. diet. Since LA is so prevalent among standard Western diets, most people are likely to be meeting or exceeding basic needs and will not have to make any changes in intake to meet recommendations.
Summary
ALS is a progressive adult-onset neurodegenerative disease with unknown etiology and no effective treatment options or cure. Once ALS starts, it almost always progresses, eventually leading to the loss of muscle control and the inability to walk, dress, speak, swallow, and breathe. The average life expectancy of a person with ALS averages 2-5 years from the time of diagnosis, and the search for prophylactic and treatment strategies are imperative.
Large prospective studies have documented an inverse association between omega-3 PUFA intake, particularly ALA, and ALS risk, where higher prediagnostic plasma ALA levels were associated with a lower risk of ALS. Moreover, a brand-new study published in the American Academy of Neurology medical journal found that higher levels of ALA were also associated with longer survival and slower functional decline in patients with ALS.
The most recent evidence concluded that PUFAs, especially ALA, EPA, and LA, were all associated with better disease outcomes. More research on ALS is needed to better understand the disease’s etiology and treatment options. For more information about ALS, be sure to check out the ALS Association.
