~Amyotrophic Lateral Sclerosis (ALS), Part 3 - Diet and Supplements

  • Monosodium Glutamate
  • Aspartate
People suffering with ALS should avoid eating processed foods (foods with preservatives and artificial ingredients) and only eat fresh, natural foods. Fresh fruits and vegetables are good because they provide vitamins and antioxidant s substances. Meat, fish, eggs, and cheese, which contain protein s which is used to build muscle and should also be consumed. Nutrient-dense foods should be eaten. These are foods a person can eat much less of to get the adequate amount of nutrition ;. thus, the patient does not have to waste a lot of energy eating. Foods containing fiber are also good to eat because they prevent constipation.

Monosodium Glutamate. Dietary intake of glutamate is associated with an increased risk of ALS (Nelson et al. 2000). Glutamate is found in monosodium glutamate (MSG) which occurs naturally in many foods. The following foods should be avoided:

Monosodium Glutamate Content in Food
  • High (over 1000 mg/100 grams) - Roquefort cheese, parmesan cheese, soy sauce
  • Medium (100-1000 mg/100 grams) - Walnuts, fresh tomato juice, grape juice, peas, mushrooms, broccoli, tomatoes, oysters, corn, potatoes
  • Low (1-99 mg/100 grams) - Chicken, fish (mackerel), beef, eggs, cow's milk
Source: MSG Facts http://www.msginfo.com

Aspartate. Aspartate, another potent neurotoxin, should also be avoided in chronic neurologic disease. Aspart ic ate acid is found in artificial sweeteners such as aspartame (NutraSweet).

Nutritional Supplements
  • Protection Against Glutamate Toxicity
  • Methylcobalamin and SAMe
  • Antioxidants
  • Glutathione
  • Superoxide Dismutase
  • Zinc and Copper
  • N-acetyl-cysteine
  • Vitamin C
  • Vitamin E
  • Alpha-Lipoic Acid
Most of the research on nutritional supplements for ALS focuses on several areas:
  • Protection against glutamate toxicity with vitamin B12 (methylcobalamin) and S-adenosylmethionine (SAMe)
  • Antioxidants including N-acetyl-cysteine, vitamin C, vitamin E, tocotrienol (palm-oil derived), and alpha-lipoic acid
  • Protection and regeneration of neurons with methylcobalamin, the proper balance of omega-3 and omega-6 essential fatty acids, acetyl-L-carnitine, pregnenolone, and DHEA
  • Improving mitochondrial function with coenzyme Q10 and creatine
  • Growth stimulation with human growth hormone and testosterone
  • Mineral deficiencies of magnesium, calcium, and vitamin D
  • Miscellaneous supplements including ginseng, branched-chain amino acids, Hydergine, vinpocetine, and trimethylglycine(TMG)
Protection Against Glutamate Toxicity. One cause of brain cell death is glutamate toxicity. Brain cells use glutamate as a neurotransmitter, but unfortunately glutamate is a double-edged sword in that it can also kill aging brain cells. The release of glutamate from the synapses is the usual means by which neurons communicate with each other. Effective communication means controlled release of glutamate at the right time to the right cells. However, when glutamate is released in excessive amounts, intercellular communication ceases. It is like replacing radio signals with x-rays. The flood of glutamate onto the receiving neurons drives them into hyperactivity, and the excessive activity leads to cellular degradation.

Methylcobalamin and SAMe. It may be possible to protect brain cells against glutamate toxicity by taking methylcobalamin supplements. A study demonstrated that chronic exposure of rat cortical neurons to methylcobalamin protected against glutamate-, aspartate-, and nitroprusside-induced neurotoxicity. This study also showed that SAMe protected against neurotoxicity (Akaike et al. 1993).

In another study, a combination of methylcobalamin and SAMe was used to protect against retinal brain cell toxicity caused by glutamate and nitroprusside. The mechanism by which methylcobalamin protected against neurotoxicity was postulated by the researchers to be enhancement of brain cell methylation. The scientists who conducted these studies emphasized that chronic exposure of methylcobalamin was necessary to protect against neurotoxicity (Kikuchi et al. 1997).

Based on its unique mechanisms of action, methylcobalamin could be effective in slowing the progression of diseases such as ALS. Because methylcobalamin is not a drug, there is little economic incentive to conduct expensive clinical studies. It may be a long time before we know just how effective this vitamin B12 analog is in slowing the progression of ALS. This indicates that for methylcobalamin to be effective in protecting against neurological disease, daily supplementation may be required. An appropriate dose for an ALS patient to take would be 20-60 mg a day taken sublingually.

Antioxidants. Free radicals are molecules that have an unpaired electron, a highly unstable state. Most free radicals react with molecules that contain oxygen to form reactive oxygen species, such as nitric oxide (NO), superoxide (O2-), and hydroxyl ( OH- ). Free radical damage is associated with many degenerative conditions, including neurological disorders (Jenner 1994).

Antioxidants inhibit oxidation by free radicals. The term "oxidative stress" refers to the balance of free radicals to antioxidants. Antioxidants include detoxification enzymes, such as SOD; vitamins, including beta carotene and other carotenoids; vitamins C and E; and nutritional supplements such as coenzyme Q10, cysteine, glutathione, lipoic acid, and melatonin.

In a study by Oteiza et al. (1997), several parameters indicative of oxidative stress were evaluated in blood from individuals with the sporadic form of ALS and were compared to healthy controls. Plasma levels of 2-thiobarbituric-reactive substances (TBARS), products of lipid peroxidation, were significantly higher (p < 0.03) in the sporadic ALS patients compared to controls. The ratio TBARS/alpha-tocopherol was 47% higher in the sporadic ALS individuals than in controls.

Evidence suggests that free radicals in the brain may play a role in the development of age-related neuronal impairments. The increase in the concentration of the pro - inflammatory cytokine (cells which regulate immune responses), interleukin-1 beta (which can cause fever, induce synthesis of acute phase proteins, and initiate metabolic wasting) may also be a contributory factor in aged brain tissue. This study analyzed changes in enzymatic and nonenzymatic antioxidant levels, in parallel with interleukin-1 beta concentration, and in cortical brain tissue prepared from young and aged rats. Results showed an age-related increase in the activity of SOD. An age-related decrease in the concentrations of vitamins E and C was also shown. These observations, coupled with age-related increases in lipid peroxidation and interleukin-1 beta concentration, show a compromised antioxidant defense in cortex of aged rats. These negative changes were not observed in cortical tissue prepared from rats fed on a diet supplemented with vitamins E and C for 12 weeks (O'Donnell et al. 1998).

Glutathione. Glutathione, an antioxidant and molecule used to conjugate toxins in the body, may be beneficial for ALS. A decrease in total glutathione concentrations in the substantia nigra has been observed in preclinical stages, while at a time at which other biochemical changes are not yet detectable (Schulz et al. 2000).

One study showed that estradiol, a naturally occurring estrogen that has been produced semisynthetically, protects spinal motor neurons from excitotoxic insults in vitro and may have application as a treatment for ALS. The dose of estradiol required for motor neuron protection was greatly reduced by co - administration with glutathione (Nakamizo et al. 2000). A study of the role of estrogen in ALS, however, found that there was no difference in survival in those patients taking estrogen compared to those not on the medication (Rudnicki 1999).

Superoxide Dismutase (SOD). The genetic form of ALS is autosomal dominant with a defect on SOD1, the gene encoding SOD. Superoxide is an oxygen molecule with an extra electron. SOD is an antioxidant enzyme that adds hydrogen to the superoxide molecule to convert it into stable oxygen plus hydrogen peroxide (H2O2) (Robberecht 2000).

There is evidence that the point mutations in SOD, which are associated with ALS, may contribute to mitochondrial dysfunction (Beal 1999b). Another study showed that treatment with SOD improves neuromuscular dysfunction and morphological changes in wobbler mouse motor neuron disease (Ikeda et al. 1995).

SOD is under Phase I scientific investigation for its use in ALS (Kinoshita et al. 1998; Hurko et al. 2000).

Zinc and Copper. Zinc supplementation should be considered in addition to SOD. A study showed that the loss of zinc from SOD was sufficient to induce apoptosis (programmed cell death) in cultured motor neurons. When replete with zinc, SOD was not toxic. Both protected motor neurons from growth factor withdrawal (Estevez et al. 1999).

Mitochondrial SOD requires manganese, while the cytoplasmic (cellular) form requires copper and zinc. Patients with familial ALS possess a defective gene that decreases cytoplasmic SOD (Bowling et al. 1993; Brown et al. 1993; Ince et al. 1998).

N-acetyl-cysteine. N-acetyl-cysteine (NAC) is an antioxidant agent that reduces free radical damage.

In a study at Massachusetts General Hospital and Harvard Medical School, NAC was used as preventative treatment in transgenic mice with a SOD mutation. NAC supplementation resulted in significantly prolonged survival and delayed onset of motor impairment when compared to control mice. The authors encouraged further research and clinical trials for ALS treatment with NAC (Andreassen et al. 2000).

One study examined the effects of NAC on mice with mutation that caused lower motoneuron degeneration with associated skeletal muscle atrophy (wobbler mice). This mutation shares some of the clinical features of ALS. Litters of wobbler mice were given a 1% solution of the glutathione precursor NAC in their drinking water for a period of 9 weeks. Functional and neurological examination of these animals revealed that wobbler mice treated with NAC exhibited (1) a significant reduction in motor neuron loss and elevated glutathione peroxidase levels within the cervical spinal cord, (2) increased axon caliber in the medial facial nerve, (3) increased muscle mass and muscle fiber area in the triceps and flexor carpi ulnaris muscles, and (4) increased functional efficiency of the forelimbs, as compared with untreated wobbler littermates. These data suggest that reactive oxygen species may be involved in the degeneration of motor neurons in wobbler mice and demonstrate that oral administration of NAC effectively reduces the degree of motor degeneration in wobbler mice (Henderson et al. 1996).

Another study described how 36 patients with sporadic ALS were treated with an array of antioxidants in addition to their prescription medications. Their customary prescription sequence was NAC, vitamins C and E, N-acetyl methionine ( NAM ), and dithiothreitol (DTT) or its isomer dithioerythritol (DTE). Patients with a history of heavy exposure to metal were also given meso 2,3-dimercaptosuccinic acid (DMSA). NAC, NAM, DTT, and DTE were administered by subcutaneous injection, by mouth, or by both routes; the other vitamins and DMSA were by mouth alone. Comparison of survival in the treated group and in a cohort of untreated historical controls, disclosed a median survival of 3.4 years (95% confidence interval: 3.0-4.2 years) in the treated and of 2.8 (95% confidence interval 2.2-3.1 years) years in the control patients. This difference may be explained by self-selection of the highly motivated treated group and by its initial survival of diagnosis for an average of 8.5 months before onset of treatment (Vyth et al. 1996).

Vitamin C. A 1997 paper proposed that vitamin C deficiency may be the underlying mechanism for the development of ALS. Three mechanisms were proposed. First, superoxide radicals are a common substrate for both SOD and ascorbate. Second, brain-cell ascorbate release is coupled with glutamate uptake. Third, there is evidence supporting the vitamin C deficient (scurvy) guinea pig as a model for ALS (Kok 1997).

Vitamin C also plays an important role in the transmission of signals between neurons. Glutamate and ascorbate (vitamin C) are the two main excitatory neurotransmitters in the brain with glutamate being responsible for 75% of it. One possible hypothesis would be that excessive reliance on glutamate may be due to a deficiency of vitamin C (Ganong 1995).

To help protect against respiratory dysfunction, 600 mg of NAC and 1000 mg of vitamin C, 3 times a day, are suggested.

Vitamin E. Vitamin E is a potent antioxidant. Deficiency is associated with progressive neurologic deterioration. Several studies in the 1940s described improvement in ALS patients when supplemented with alpha-tocopherol (vitamin E) (Wechsler 1940; Rosenberger 1971; Werbach 1996).

A study reported remarkably low levels of alpha-tocopherol quinone in the cerebrospinal fluid of patients with sporadic ALS (Tohgi et al. 1996).

The authors of one paper on vitamin E stated that "dietary supplementation with vitamin E delays onset of clinical disease and slows progression in the transgenic mice model but does not prolong survival" (Gurney et al. 1996).

Another author notes that vitamin E is beneficial only for some patients with ALS and recommends further investigation (Reider et al. 1997).

Alpha-Lipoic Acid. Alpha-lipoic acid is a potent antioxidant that is especially effective in preventing diabetic neuropathy (Klein 1975; Ziegler et al. 1995; Reljanovic et al. 1999). Alpha-lipoic acid has been shown to stimulate nerve growth factor synthesis and secretion in mouse astroglial cells. Astrocytes are cells which support the structure of the nervous tissue (Murase et al. 1993).

Therefore, a dose of 250 mg 3 times a day of alpha-lipoic acid to protect the neurons affected by ALS is suggested.

Continued . . .

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