Down Syndrome Abstract
of the Month:
Sept 1999
Effect of vitamin E on chromosomal aberrations in lymphocytes from patients with Down's syndrome.
Pincheira J, Navarrete MH, de la Torre C, Tapia G, Santos MJ
Clin Genet 1999 Mar;55(3):192-7
Departamento de Pediatria y Cirugia Infantil, Facultad de Medicina, Universidad de Chile, Santiago.
Abstract:
A possible protective effect of vitamin E (DL-alpha-tocopherol) on chromosomal damage was evaluated in lymphocytes from patients with Down's syndrome (DS) and from controls. This included the analysis of the basal and G2 chromosomal aberration frequencies in lymphocytes cultured with and without 100 microM vitamin E. The chromosomal damage in G2 was determined by scoring the number of chromosomal aberrations in lymphocyte cultures treated with 5 mM caffeine, 2 h before harvesting. Vitamin E treatment decreased the basal and G2 chromosomal aberrations both in control and DS lymphocytes. In DS cells, this protective effect, expressed as a decrease in the chromosomal damage, was greater (50%) than in controls (30%). These results suggest that the increment in basal and G2 aberrations yield in DS lymphocytes may be related to the increase in oxidative damage reported in these patients.
My comments:
First, some background. In the ongoing search for some signs that there is real oxidative damage from overexpression of the enzyme Superoxide Dismutase (SOD) in DS, these authors turn to the topic of chromosomal damage.The life cycle of a cell can be divided into mitosis and non-mitosis. The non-mitosis portion, or the "interphase," is the time during which growth of the cell occurs. This phase is split into three smaller parts, G1 (no DNA synthesis), S (DNA synthesis) and G2 (no DNA synthesis). G2 is followed by mitosis, and the whole thing starts again. During G2, if there is any DNA damage for whatever reason, the cell will attempt to repair the damage. Researchers have found that adding certain chemicals, like caffeine, to the culture media during G2 will inhibit normal DNA repair.
An earlier paper by these authors showed that when you add caffeine to white blood cells of subjects with DS, there is a smaller amount of repair than in control white blood cells. This indicated to the researchers that the level of endogenous DNA damage ("aberrations") may be higher in DS lymphocytes than in the controls. So they set out to see what adding vitamin E, which can protect DNA from oxidative damage, would do to the process.
The authors looked at white blood cells from 14 healthy people wDS, aged 1 to 5 years. Ten age-matched control subjects were used. All tests were done in vitro, meaning the vitamin E was added to the cells in a petri dish, not given orally to the children.
The end result of the experiment was that DS white blood cells treated first with vitamin E and then with caffeine showed that the number of chromosomal aberrations dropped in comparison to the number of aberrations in the DS white blood cells with caffeine alone. In 9 of the 14 cases, the number of aberrations reached the level of the average value of the control white blood cell DNA aberrations. This reversion effect of vitamin E was seen in all of the DS white blood cells so treated.
Assuming that vitamin E is a free radical scavenger, this study suggests that baseline chromosomal damage in DS may be due to oxidative stress, and also that vitamin E may be an effective agent against that stress. Further, vitamin E may improve the repair efficiency by the cells.
It's very important to note that this is an "in vitro" study and does not prove that oral vitamin E would do the same thing, or what doses would be required. However, this is an effective argument for the use of vitamin E in DS.
If this study makes you want to rush out and buy vitamin E for your child, you're probably going to wonder how much to give. Unfortunately, that's a problem. There's very limited data on what the appropriate dose would be for children. The RDA states about 3 to 10 IU per day, but that's a very low amount. And we're looking at treating a condition here, not just supplementing. And since no study has looked at whether or not oral vitamin E can stop in vivo peroxidation, let alone the dose that it would take, we're left without guidelines. The only information I can offer is that children with vitamin E deficiency are treated with 25 IU per kilogram body weight per day, up to a maximum of 400 IU per day of alpha-tocopherol polyethylene glycol succinate (TPGS), a water-soluble version. However, there has also been concern that the alpha-tocopherol version alone may not be enough, and some researchers have advocated using half alpha-tocopherol and half gamma-tocopherol, though a liquid form of such a preparation isn't available as far as I know.