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Magnesium and glycine play an important role in NMDA (N-methyl-D-aspartate) receptors, which is a type of glutamate receptor. NMDA receptors permit passage of relatively large amounts of calcium ions. First, glycine binds to it to facilitate its function. Second, the channel is blocked (closed) by a magnesium ion. The channel becomes unblocked when the membrane becomes partially depolarized. [3]
Two studies have shown a deficiency of vitamin D in patients with ALS along with decreased intestinal absorption of calcium and a reduction in bone mass (osteopenia). [120] [121]
Growth hormone has multiple functions in the body, including maintenance of lean body mass, mobilization of fat, counteracting insulin, enhancing immunity, lowering blood pressure and improving cholesterol levels, increasing energy, and even improving vision. [122]
Growth hormone received the Food and Drug Administration's imprimatur in 1996 for use in adults with GH deficiency due to pituitary or hypothalamic disease, injury, surgery or radiation therapy. This now allows doctors to prescribe growth hormone as an anti-aging treatment for adults with low levels of IGF-1, which indicates a failure of the pituitary gland to produce adequate amounts of growth hormone.
Innovative drug therapies for ALS also might include 10 to 20 mg a day of Hydergine, 40 mg a day of vinpocetine, and testosterone and human growth hormone replacement therapy.
The link between testosterone and ALS has been proposed, but discounted in research conducted in the 1980s. Testosterone was explored because of the male-to-female ratio of the disease, the age of onset, and the sparing of neurons of cranial nerves III, IV, and VI that coincidentally lack androgen receptors. The hypothesis is that ALS may be due to a loss of androgen receptors that results in an inability to respond to a variety of insults including axonal damage. [123] The hypothesis was discounted by a study in which four men with ALS were treated with 200 mg of testosterone weekly. Lab tests indicated the expected degree of suppression of pituitary luteinizing hormone and follicle-stimulating hormone production. These data suggest that testosterone's (androgen) interaction with its receptors in the hypothalamic-pituitary axis is normal in patients with ALS. [124]
Testosterone is an anabolic steroid. It stimulates the body to grow. Testosterone is responsible for the development of masculine characteristics. The role of testosterone in amyotrophic lateral sclerosis is unclear, but the evidence presented clearly indicates that it may have a role in some patients.
Several studies have proposed that a deficiency of thiamin (Vitamin B1) may be associated with amyotrophic lateral sclerosis. Thiamin and its esters are present in axonal membranes, and electrical stimulation of nerves effects the hydrolysis and release of thiamin diphosphate and triphosphate. Thiamin deficiency causes dry beriberi, a neurologic disease characterized by “burning” feet, peripheral neuropathy, and Wernicke-Korsakoff syndrome that causes the neurological problems common in alcoholism (staggering gait, confusion, problems with coordination, etc). The histological lesion of thiamin deficiency is a non-inflammatory degeneration of myelin sheaths.
A study published in the journal Archive Neurology measured free thiamin and thiamin monophosphate levels in plasma and cerebral spinal fluid of patients with amyotrophic lateral sclerosis (ALS), alcoholics, and controls. In plasma of patients with ALS as well as in plasma and CSF of alcoholics, both thiamin and thiamin monophosphate concentrations were decreased. In CSF of patients with ALS, however, thiamin monophosphate values decreased much more than thiamin levels. The selective impairment of thiamin monophosphate production by nerve cells is likely to result from the reduction of the activity of thiamin pyrophosphatase, an enzyme synthesized and highly concentrated in the Golgi complex, a component of the cell where complex molecules such as proteins are synthesized and packaged for use in the body. Thiamin pyrophosphatase is known to diminish in ALS as well as in experimental motor neuronal degeneration or axotomy. Thus, the Thiamin to Thiamin monophosphate ratio could be taken as an index of the impairment of neuronal protein synthesis in ALS.[125]
In a follow-up study, thiamine and thiamine monophosphate levels were measured in the CSF of patients with typical sporadic ALS (50 cases), in other motor neuron diseases (MND) (14 cases) and in patients with upper and/or lower motor neuron lesions of varying origin (disseminated sclerosis, polyneuropathy, spondylotic myelopathy). The Thiamin to Thiamin monophosphate ratio was greater than or equal to 1 in a high percentage of patients with typical sporadic ALS (94%), in 35.7% of cases with other MND, while it was below 1 in the all other patients. The decrease of Thiamin monophosphate with the inversion of the Thiamin to Thiamin monophosphate ratio is a finding highly specific to typical sporadic ALS. [126]
More recent research measured the enzymes involved in thiamin synthesis: thiamin-pyrophosphatase (TPPase) and thiamin-monophosphatase (TMPase) in brain tissue obtained at autopsy from amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia (PD) patients from Guam and from Guamanian patients who died from other diseases (controls). TPPase content, chemically determined at pH 9.0, was found to be significantly reduced in the frontal cortex of ALS and PD patients compared to controls. TMPase content, on the contrary, was unchanged. [127]
Ginseng (Panax quinquefolium) was given to transgenic mice with a defect in SOD1-G93A. Compared to controls there was a prolongation in onset of signs of motor impairment and survival. These experiments lend support to the use of ginseng root in ALS. [128]
Nutritional supplements called branched-chain amino acids can slow weight loss and muscle decline. There is, however, controversy in using branched-chain amino acids with ALS patients. One research group, however, reported higher than usual normal mortality rates, which caused the cessation of the clinical trial. [129]
Hydergine is a drug approved by the FDA for persons “over sixty who manifest signs and symptoms of an idiopathic decline in mental capacity.” Studies have shown that it increases stores of the universal energy molecule, adenosine triphosphate (ATP), stabilizes the intracellular messenger molecule cyclic adenosine monophosphate (cAMP) content of nerve cells, improves utilization of glucose in the brain, and enhances cerebral microcirculation. [130]
A recent study published in European Neuropsychopharmacology, showed that Hydergine causes an increase of superoxide dismutase (SOD) and catalase in the brain. SOD and catalase are the body’s natural antioxidants and are among the most effective free radical scavengers. [131]
What was interesting about this study is that Hydergine was administered for only 20 days, but its effects in the brains of the lab rats were dramatic. Hydergine specifically increased catalase levels in the brain, as well as SOD in the hippocampus and in the corpus striatum regions. Those regions of the brain suffer severe oxidative damage from hydrogen peroxide and other free-radical generating agents. Orally ingested SOD and catalase have not proven efficacious because these antioxidant enzymes are broken down in the stomach, so scientists have concentrated on ways of prompting the body to produce its own cellular SOD and catalase. This study showed that Hydergine could increase brain levels of SOD and catalase after only short-term administration. [132]
Vinpocetine is produced by slightly altering the Vincamine molecule, an alkaloid extracted from the Periwinkle plant, Vinca minor. Vinpocetine has been shown to enhance cerebral metabolism and selectively vasodilate cerebral arteries. Vinpocetine has also been shown to enhance oxygen and glucose uptake from blood by brain neurons, and to increase neuronal ATP bio-energy production, even under hypoxic (low oxygen) conditions. [133] [134] [135] [136]
Recent studies demonstrate that vinpocetine offers significant and direct protection against neurological damage caused by aging. The molecular evidence indicates that the neuroprotective action of vinpocetine is related to its ability to maintain brain cell electrical conductivity and to protect against damage caused by excessive intracellular release of calcium. Vinpocetine also has been documented to partially protect against excitotoxicity induced by a wide range of glutamate-related neurotoxins. [137]
Re-methylation nutrients such as folic acid and TMG (trimethylglycine) are being studied as possible therapies to treat Alzheimer’s disease, and the same mechanism of action might have a beneficial effect against ALS.
Sphingolin, from Ecological Formulas, is an extract of bovine myelin sheath and is a rich source of myelin protective proteins. Use of this product may benefit those with myelin diseases such as multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS - Lou Gehrig's Disease)
Continue to Part 8 of the ALS Article
© 2002