Diseases affecting motor neurons, such
as amyotrophic lateral sclerosis (Lou Gerhig's disease), hereditary
spastic paraplegia, and spinal bulbar muscular atrophy (Kennedy's disease)
are a group of chronic progressive diseases among
the most puzzling yet untreatable illnesses. Identification of mutations in genes predisposing to these disorders has
provided the means to better understand their pathogenesis. The discovery
years ago of
superoxide dismutase SOD1 mutations linked to ALS, which account for less
than 2% of total cases, had a major impact in the field. However, despite
intensive research effort, the pathways leading to the specific motor
neurons degeneration in the presence of SOD1 mutations have not been fully
identified. Cases of amyotrophic lateral sclerosis or ALS-like conditions
have arisen in apparent association with HMG-CoA reductase inhibitors (statin
drugs) and/or other lipid-lowering drugs.
Compared to years past, people who come down with amyotrophic lateral sclerosis nowadays seem to have slower disease progression and to live long. Nonetheless, amyotrophic lateral sclerosis is still always fatal, ultimately. A history of head injury is associated with an increased risk of developing amyotrophic lateral sclerosis.
Diet and ALS, the role of inflammation
A diet high in polyunsaturated fat and vitamin E is associated with a decreased likelihood of developing Lou Gehrig disease. The findings are based on a comparison of dietary intake for patients with amyotrophic lateral sclerosis (before the disease set in) and healthy controls. High levels of polyunsaturated fatty acids or vitamin E seemed to decrease the risk of amyotrophic lateral sclerosis, while a high intake of both nutrients cut the risk even further, suggesting a synergistic effect. Specifically, a diet high in polyunsaturated fatty acids and vitamin E decreased the risk of developing amyotrophic lateral sclerosis ALS by 50 percent to 60 percent. By contrast, the researchers found no apparent anti- ALS effect for lycopene, flavonols, vitamin C, vitamin B2, glutamate, calcium, or plant-derived estrogens. Journal of Neurology, Neurosurgery, and Psychiatry, 2006.
A diet rich in omega-3 fatty acids may help cut your risk for the fatal neurodegenerative disease amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. These fatty acids -- found most commonly in certain fish -- are known to help reduce inflammation and oxidative stress on cells. Both of those processes can damage nerve tissue. Kathryn Fitzgerald, M.Sc., Harvard School of Public Health, Boston; Michael Swash, M.D., neurologist, Royal London Hospital, United Kingdom; July 14, 2014, JAMA Neurology, online.
Fruit and vegetable intake
Fruit and Vegetable Intake and Risk of Amyotrophic Lateral Sclerosis in Japan.
Neuroepidemiology. 2009. Okamoto K, Kihira T, Kobashi G, Washio M. Department of Public Health, Aichi Prefectural College of Nursing and Health, Nagoya, Japan.
There has been little interest in the role of nutrition in the prevention of amyotrophic lateral sclerosis. We investigated the relationship between dietary intake of vegetables, fruit, and antioxidants and the risk of amyotrophic lateral sclerosis in Japan. Between 2000 and 2004, we recruited 153 amyotrophic lateral sclerosis patients aged 18-81 years with disease duration of 3 years within the study period in accordance with El Escorial World Federation of Neurology criteria. Three hundred and six gender- and age-matched controls were randomly selected from the general population. A higher consumption of all fruits and vegetables and fruit alone in the highest quartiles was associated with a statistically significantly reduced risk of amyotrophic lateral sclerosis. Although not statistically significant, a beneficial association between intake of all vegetables, green and yellow vegetables and other vegetables and amyotrophic lateral sclerosis was found. No statistically significant dose-response relationship was observed between intake of beta-carotene, vitamin C and vitamin E and the risk of amyotrophic lateral sclerosis. Our findings suggest that higher intake of food rich in antioxidants such as fruit and vegetables confer protection against the development of ALS.
Role of nutrition and exercise
Nutritional and exercise-based interventions in the treatment of amyotrophic lateral sclerosis.
Clin Nutr. 2009. School of Kinesiology and Health Science, York University, Toronto, Ontario; Muscle Health Research Centre, York University, Toronto, Ontario, Canada.
Disease pathogenesis in amyotrophic lateral sclerosis involves a number of interconnected mechanisms all resulting in the rapid deterioration of motor neurons. The main mechanisms include enhanced free radical production, protein misfolding, aberrant protein aggregation, excitotoxicity, mitochondrial dysfunction, neuroinflammation and apoptosis. The aim of this review is to assess the efficacy of using nutrition and exercise-related interventions to improve disease outcomes in ALS. Studies involving nutrition or exercise in human and animal models of ALS were reviewed. Treatments conducted in animal models of ALS have not consistently translated into beneficial results in clinical trials due to poor design, lack of power and short study duration, as well as differences in the genetic backgrounds, treatment dosages and disease pathology between animals and humans. However, vitamin E, folic acid, alpha lipoic acid, lyophilized red wine, coenzyme Q10, epigallocatechin gallate EGCG, Ginkgo biloba, melatonin, Copper chelators, and regular low and moderate intensity exercise, as well as treatments with catalase and l-carnitine, hold promise to mitigating the effects of ALS, whereas caloric restriction, malnutrition and high-intensity exercise are contraindicated in this disease model.
CNS Neurosci Ther. Feb 2014. Vitamin d as a potential therapy in amyotrophic lateral sclerosis. Vitamin D has been demonstrated to influence multiple aspects of amyotrophic lateral sclerosis (ALS) pathology. Both human and rodent central nervous systems express the vitamin D receptor (VDR) and/or its enzymatic machinery needed to fully activate the hormone. Clinical research suggests that vitamin D treatment can improve compromised human muscular ability and increase muscle size, supported by loss of motor function and muscle mass in animals following VDR knockout, as well as increased muscle protein synthesis and ATP production following vitamin D supplementation. Vitamin D has also been shown to reduce the expression of biomarkers associated with oxidative stress and inflammation in patients with multiple sclerosis, rheumatoid arthritis, congestive heart failure, Parkinson's disease and Alzheimer's disease; diseases that share common pathophysiologies with ALS. Furthermore, vitamin D treatment greatly attenuates hypoxic brain damage in vivo and reduces neuronal lethality of glutamate insult in vitro; a hallmark trait of ALS glutamate excitotoxicity. We have recently shown that high-dose vitamin D3 supplementation improved, whereas vitamin D3 restriction worsened, functional capacity in the G93A mouse model of ALS. In sum, evidence demonstrates that vitamin D, unlike the antiglutamatergic agent Riluzole, affects multiple aspects of ALS pathophysiology and could provide a greater cumulative effect.
Amyotroph Lateral Scler Frontotemporal Degener. 2013. Vitamin E serum levels and controlled supplementation and risk of amyotrophic lateral sclerosis. Results are consistent with a hypothesized protective effect of α-tocopherol on ALS risk.
AAKG, Deana protocol
PLoS One. 2014. Metabolic therapy with Deanna Protocol supplementation delays disease progression and extends survival in amyotrophic lateral sclerosis (ALS) mouse model. Besides motor neuron degeneration, ALS is associated with impaired energy metabolism, which is linked to mitochondrial dysfunction and glutamate excitotoxicity. The Deanna Protocol (DP) is a metabolic therapy that has been reported to alleviate symptoms in patients with ALS. In this study we hypothesized that alternative fuels in the form of TCA cycle intermediates, specifically arginine-alpha-ketoglutarate (AAKG), the main ingredient of the DP, and the ketogenic diet (KD), would increase motor function and survival in a mouse model. ALS mice were fed standard rodent diet (SD), KD, or either diets containing a metabolic therapy of the primary ingredients of the DP consisting of AAKG, gamma-aminobutyric acid, Coenzyme Q10, and medium chain triglyceride high in caprylic triglyceride. Targeting energy metabolism with metabolic therapy produces a therapeutic effect in ALS mice which may prolong survival and quality of life in ALS patients.
We evaluated the efficacy of oral supplementation with milk whey proteins and modified starch (70%WPI:30%MS), on nutritional and functional parameters of patients with ALS. A prospective randomized double-blind study was performed with 16 ALS patients, divided in two groups, the treatment group received (70%WPI:30%MS) and the control group received (maltodextrin). They underwent prospective nutritional and functional assessment for 4 months. Patients in the treatment group presented weight gain, increased body mass index (BMI), increased arm muscle area and circumference, higher albumin, white blood cell and total lymphocyte counts, and reduced creatine-kinase, aspartate aminotransferase and alanine aminotransferase. In the control group, biochemical parameters did not change, but weight and BMI declined. Our results indicate that the agglomerate 70%WPI:30%MS may be useful in the nutritional therapy of patients with ALS. Arq Neuropsiquiatr. 2010. Effect of nutritional supplementation with milk whey proteins in amyotrophic lateral sclerosis patients. Silva LB, Mourão LF, Silva AA, Nucci A, Amaya-Farfán J. Federal University of Alfenas, MG, Campinas SP, Brazil.
Creatine for improved survival
Our objective was to determine the effect of creatine monohydrate on disease progression in patients with amyotrophic lateral sclerosis (ALS). One hundred and seven patients with the diagnosis of probable or definite ALS, of less than five years duration from symptom onset, were randomized to either treatment with daily creatine monohydrate (5 g/d) or placebo. In this multicenter, double-blinded study we followed changes in disease progression: using quantitative measures of strength via maximal isometric voluntary contraction, forced vital capacity, ALSFRS, quality of life, fatigue and survival. Patients were followed for nine months. The results showed that creatine monohydrate did not significantly improve motor, respiratory or functional capacity in this patient population. The drug was well tolerated and the study groups well balanced, especially considering the absence of forced vital capacity criteria for entrance into the study. There was a trend toward improved survival in patients taking daily creatine monohydrate and this was identical to the trend seen in another recently published report of creatine in ALS patients 1. In conclusion, creatine monohydrate (5 g/d) did not have an obvious benefit on the multiple markers of disease progression measured over nine months. We measured fatigue during isometric contraction and found no significant improvement despite anecdotal patient reports prior to and during the study. The trend toward improved survival was also found in another recently completed blinded trial using creatine monohydrate. Further investigation on the possible survival benefit of creatine in this patient population is ongoing. Amyotroph Lateral Scler. 2008. Creatine monohydrate in ALS: effects on strength, fatigue, respiratory status and ALSFRS. Rosenfeld J, Jackson CE, Chapin J, Gelinas DF, Lou JS. The Carolinas Neuromuscular/ALS Center, Charlotte North Carolina, Carolinas Medical Center, USA.
Do you think lipoic acid would be helpful in preventing amyotrophic lateral sclerosis?
It's an interesting question, but I don't know.
Lead as one cause? Environmental pollutants?
Dr. Freya Kamel, a staff scientist at the U.S. National Institute of Environmental Health Sciences, in Research Triangle Park, North Carolina found blood lead levels to be associated with ALS risk. The study involved 184 U.S. male veterans with ALS and 194 vets without the disease. All of the men were white and the average age in each group was 63 and 64, respectively. Analyzing blood samples from the men, Dr. Freya Kamel found that a doubling in the blood lead level was associated with a doubling in the risk of ALS. American Journal of Epidemiology, 2010.
Environ Pollut. 2014 Dec 23. Exposure to hazardous air pollutants and the risk of amyotrophic lateral sclerosis. ALS is a serious and rapidly fatal neurodegenerative disorder with an annual incidence of 1-2.6/100,000 persons. Few known risk factors exist although gene-environment interaction is suspected. We investigated the relationship between suspected neurotoxicant hazardous air pollutants (HAPs) exposure and ALS. Metals, pesticides, and other HAPs were not associated with ALS. A potential relationship is suggested between residential ambient air aromatic solvent exposure and risk of ALS in this study.
Male funeral directors who routinely work with embalming fluid might be at increased risk of developing amyotrophic lateral sclerosis.
Military service, particularly in the Gulf War, may be linked to development of amyotrophic lateral sclerosis. The evidence, however, is limited and inconsistent.
Amyotrophic Lateral Sclerosis
symptom and sign
Symptoms of ALS include progressive muscle weakness and wasting. Spontaneous tiny local areas of muscle twitching, called fasciculations, are characteristic in the majority of those afflicted with the disease. These may be sensed by the patient as muscle cramping. Lower extremity muscle wasting (atrophy) and weakness generally follows wasting of the arms, hands, and shoulders. Spastic muscles can be present.
Four out of every 100,000 American has amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis
ALS is an invariably fatal disease in which the nerve cells that control movement progressively degenerate, leading to paralysis and death from respiratory failure. It is diagnosed in about 5,000 Americans each year. Up to 10 percent of ALS cases are an inherited form of the disease. In most cases, though, ALS occurs for no known reason. Researchers have identified three proteins found in significantly lower concentrations in the cerebrospinal fluid (CSF) of amyotrophic lateral sclerosis ALS patients than in healthy controls or patients with other neurologic diseases. At present, the diagnosis of amyotrophic lateral sclerosis is made by ruling out all treatable illnesses that may mimic amyotrophic lateral sclerosis, and waiting over time to see if it progresses. It can take up to 3 years to diagnose, and even then it is easily misdiagnosed. As a result, patients are left with a lot of uncertainty and anxiety as they watch themselves waste away. Three proteins are significantly reduced in the CSF of amyotrophic lateral sclerosis patients: a protein that is a proteolytic fragment of the neuroendocrine specific protein VGF; a protein identified as cystatin c; and a 6.7-kDa unidentified protein.
Other muscles diseases are considered in the evaluation. Blood testing and muscle electrical testing with electromyography (EMG) and nerve conduction velocities (NCV) can be helpful for a diagnosis.
Ann Neurol. 2013. Amyotrophic lateral sclerosis: Problems and prospects. ALS is a lethal degenerative disorder of motoneurons, which may occur concurrently with frontotemporal dementia. Genetic analyses of the 10% of ALS cases that are dominantly inherited provide insight into ALS pathobiology. Two broad themes are evident. One, prompted by investigations of the SOD1 gene, is that conformational instability of proteins triggers downstream neurotoxic processes. The second, from studies of the TDP43, FUS, and C9orf72 genes, is that perturbations of RNA processing can be highly adverse in motoneurons. Several investigations support the concept that non-neuronal cells (microglia, astroglia, oligodendroglia) participate in the degenerative process in ALS. Recent data also emphasize the importance of molecular events in the axon and distal motoneuron terminals. Only 1 compound, riluzole, is approved by the US Food and Drug Administration for ALS; several therapies are in clinical trials, including 2 mesenchymal stem cell trials. The challenges and unmet needs in ALS emphasize the importance of new research directions: high-throughput sequencing of large DNA sets of familial and sporadic ALS, which will define scores of candidate ALS genes and pathways and facilitate studies of epistasis and epigenetics; infrastructures for candidate gene validation, including in vitro and in vivo modeling; valid biomarkers that elucidate causative molecular events and accelerate clinical trials; and in the long term, methods to identify environmental toxins. The unprecedented intensity of research in ALS and the advent of extraordinary technologies (rapid, inexpensive DNA sequencing; stem cell production from skin-derived fibroblasts; silencing of miscreant mutant genes) bode well for discovery of innovative ALS therapies.
Q. My mother has Amyotrophic lateral sclerosis. I stopped progression of her disease two years ago with alternative natural treatment and mildly improve her health condition. Her health condition is stable for 2 years. But her legs are not function and hands are very weak and also she dont speak. She can not go to clinic because she can not walk and she is on bed. Please advice me which supplements,products, therapies are effective for repair and restore her damaged and destroyed motor neurons in brain and repair and restore her motor neurons signals to nerves and muscles. Which supplements, products, therapies are effective for restore her voice and speech. And which supplements, products, therapies are effective for rebuild muscles and strenghten muscles of her legs and hands.