Amino-acid studies raise hopes: Nutrients may reduce ALS problems

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Symptomatic improvements in some patients with amyotrophic lateral sclerosis (ALS) have been confirmed in new studies conducted by Bernard M. Patten, M.D., F.A.C.P., Baylor College of Medicine, Houston, Texas.

In the ten-month study, Dr. Patten gave 15 ALS patients L-threonine, an amino acid, doses from 2 to 4 grams daily with no ill effects. Some patients noted improvement within 48 hours including better voice, swallowing, less drooling, increased energy and improved spasticity. The changes occurred more dramatically with those most severely affected.

Substitutions of amino acid leucine or isoleucine as placebos caused the patients to revert to their previous status. A return to L-threonine caused improvements in some of the physical manifestations of ALS.

In summary, of the 15 patients, seven made a definite improvement, three had minor improvement, and the remaining five experienced no change at all.

Mt. Sinai Medical Center in New York City is also conducting a clinical trial of a combination of three amino acids -- protein building blocks -- in an attempt to treat ALS. This study will involve some 100 volunteer patients over 3 years.

The experimental treatment involves "branched-chain amino acids," a combination of L-valine, L-leucine, and L-isoleucine, three of the twenty amino acids that naturally occur in all plants and animals and are the main components of all proteins.

In a small-scale preliminary trial, the Mt. Sinai investigative team, headed by Andreas Plaitakis, M.D., obtained evidence suggesting that the treatment may slow the progression of muscle weakness in ALS.

The branched-chain amino acid treatment is designed to help correct a suspected underlying abnormality in the way nerve cells use glutamate --a related amino acid believed to be involved in the transmission of nerve signals.

Evidence for such an abnormality was reported by investigators in the Annals of Neurology (11/87).

L-Threonine is a large, neutral naturally occurring amino acid, one of those essential for human metabolism. It serves as a precursor of glycine, a nonessential amino acid functioning as an inhibitory neurotransmitter in the central nervous system.

The rationale for using k-threonine in ALS is based on several factors:

1. Excitatory amino acids cause the death of neurons with toxicity, introduced via the aspartate receptor (aspartate is an excitatory amino acid). (Spencer, 1985)
2. Aspartate levels in ALS patients correspond directly with the rate of progression of the disease. (Patten, 1978)
3. Infusions of amino acids containing aspartate produced sudden worsening of ALS (Festoff, 1978)
4. Glutamate metabolism is abnormal in ALS (glutamate is an excitatory amino acid) (Plaitakis and Caroscio, 1985)

Therefore, ALS may relate to excess excitatory amino acids. L-threonine, which increases the inhibitory amino acid glycine in the cerebral spinal fluid, is used to neutralize the excess excitatory amino acid, which may help to modify the signs and symptoms of ALS.

Experience to date with 15 patients treated 2 to 10 months with 2-4 grams of L-threonine daily showed definite improvements in seven, minor improvements in three, and no change in five. There is currently a double-blind study under way at Brigham and Women's Hospital at Harvard.

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