Smart Drugs & Down’s Syndrome: Part 3

Nutritional Intervention
in Down’s Syndrome

The previous article of this series (Part 2) discussed genetic overexpression and the antioxidant disturbances associated with the superoxide dismutase (SOD) gene. This article will cover additional metabolic disturbances, and nutritional interventions targeted to ameliorate those disturbances.

Methylation Pathways

Down’s syndrome individuals exhibit significant disturbances in methylation pathways (see Figure 1). The over-expression of cystathionine beta-synthase (located on the 21st chromosome) causes homocysteine to be converted into cysteine (reaction 2) at an accelerated rate [Chadefaux, 1985]. This conversion requires serine. One of the signs of increased cystathionine beta-synthase enzyme activity is a systemic depletion of serine reserves. Indeed, the vast majority of untreated Down’s individuals show serum serine levels at the low end or below the low end of the normal range.

Serine is also used to fuel the folic acid cycle (Figure 1, cycle B). The shortage of serine impairs the production of methyl tetrahydrofolate (Me-THF), which is required to recycle homocysteine to methionine (reaction 1). With an insufficiency of Me-THF, more homocysteine goes down the cystathionine pathway to be converted into cysteine instead of being recycled into methionine. This undercuts methylation metabolism.

Methionine is required for the production of S-adenosylmethionine (SAM), the “active methyl donor” that is a vital part of countless metabolic reactions throughout the body. The under-activity of the folate cycle coupled with overactivity of the cystathionine pathway diverts the homocysteine from the SAM cycle (see Figure 2). In other words, the almost-closed cycle is opened and homocysteine drains into the cysteine pool.

Many parents have reported cognitive and behavioral improvements after supplementation with methyl donors (DMAE, choline, DMG and betaine) and methylation catalysts (folic acid and vitamins B-6 and B-12). SAM itself has also been used to treat children with attention-deficit disorders.

Although methylation pathways are usually deficient in Down’s syndrome, some degree of moderation is required not to overdrive the folic acid cycle (Figure 1, Cycle B). In Dr. Peters study of folic acid in Down’s syndrome, approximately ten percent of the children exhibited excessive hyperactivity and/or irritability when given 20 mg folic acid (50 times the adult RDA). In a recent version of MSB Plus compounded by Nutrichem Pharmacy... (end of full-text presentation)

Begin Summary of Remaining Contents...

Section: Collagen Expression: “Collagen is a major constituent of connective tissue, skin, cartilage, tendon and bone. It comprises approximately 30% of all the protein...”

Section: Tryptophan, Serotonin, Melatonin: “Down’s syndrome individuals frequently show low serum tryptophan levels. Whether this deficiency is primary (poor tryptophan absorption) or secondary (increased tryptophan catabolism) is...”

Section: Ammonia Detoxification: “Ammonia is a byproduct of many metabolic reactions. When protein is burned for energy, ammonia is released...”

Section: Glutamine and Arginine: “One of the key ammonia-carrying molecules in the brain is glutamine, an amino acid which tends to accumulate in...”

Section: Testing and Customization: “Although antioxidant disturbances, and serine and tryptophan deficiencies, are almost universal concomitants of Down’s syndrome...”

Section: Nutritional Assessment: “In the last decade, several new testing technologies have been developed for assessing nutritional requirements. The use of these...”

Section: References: Ten references are provided.