vrijdag 13 januari 2012

Kan de toename in autisme in verband staan met het gebruik van progestagenen

Urgent need for progress in autism Could the increase in autism relate to use of progestin contraceptives, as well as to other environmental factors?

  • Ellen CG Grant, Physician and Medical Gynaecologist
Kingston-upon-Thames, KT2 7JU
The prevalence of autism increased by 300% between 1987 and 1998 in California but the increase in the prevalence of cerebral palsy, epilepsy and mental retardation was only 3%. In the UK about one in 87 children are now autistic.1
What has changed over the past decade apart from a large increase in childhood vaccinations? We now have up to 3 successive generations of women who have used hormonal contraceptives with increasingly longer use from younger ages before first full time pregnancies (which increases breast cancer risks).
Such hormone use lowers white cell zinc and raises copper levels leading to impaired superoxide dismutase (SOD) function and reduced ability to deal with oxidative stress. Adequate zinc levels are needed for DNA repair. Vitamin B6 , B12 and folic acid levels and omega-3 and omega-6 essential fatty acid (EFA) deficiencies are common. I have routinely investigated the biochemistry of hundreds of women with histories of unexplained infertility and recurrent miscarriages. Most preconception patients are past hormone takers, with 50% longer takers for 5 years, and most have mineral deficiencies and poor SOD activity.
McLaren-Howard has presented data showing that women who ever took hormones had more DNA adducts than never takers. Of 356 women who had used oral contraceptives or HRT, 12.4% had adducts to nickel and 8.7% to Lindane compared with 7.1% and 3.8% of 182 never takers.2 He also compared 27 patients with cancer with 27 age and sex matched controls. 18.5% of cancer patients had DNA adducts to malondialdehyde (from lipid oxidation) and 18.5% had adducts to nickel compared with 0% and 3.7% of controls respectively.2
McLaren-Howard's routine analyses of blood from 61 autistic children found deficiencies of zinc, magnesium, chromium, selenium, manganese, molybdenum, and/or B vitamins. Such deficiencies can impair EFA pathways. In addition, 26% (16) of the children had DNA-adducts to malondialdehyde in their leucocytes, 20% (12) to cadmium, 15% (9) to nickel and one child had DNA-adducts to lead.3 A simple non-invasive sweat test shows that children with learning problems usually suffer from zinc deficiency and have higher levels of common toxic metals. Zinc deficiency increases food and chemical allergies and decreases food absorption.
Experimentally, higher doses of chlormadione and megestrol (progestins without oestrogenic or androgenic activity) increased sister chromatid exchanges and chromosomal aberrations. In vitro studies show the generation of free oxygen radicals by progestins to be responsible for genotoxic damage.4
Could longer progestin use cause more maternal genotoxic damage which in turn increases the susceptibility of children to develop autism? In a 2010 exploratory study children with autism were more likely to have mitochondrial dysfunction, mitochondrial DNA over-replication, and mitochondrial DNA deletions than typically developing children.5
Children who are susceptible to becoming autistic, or who seem apparently healthy but die from common infections, are not easily identified by epidemiological means. Perturbations of basic cell chemistry in mothers and children should be investigated and treated. Brain function is particularly vulnerable to damage by toxins and by deficiencies of zinc and essential fatty acids.

1 Downing D. Autism: are we entering the final straight? In memory of Bernard Rimland. JNEM 2007;16:3,173-180.
2 McLaren Howard J. The Detection of DNA Adducts (Risk Factors for DNA Damage). A Method for Genomic DNA, the Results and Some Effects of Nutritional Intervention. J. Nutr. & Env. Medicine. 2002; 12: 19-31. Also Essential nutrients, anti-nutrients, oestrogenic pesticides, toxic metals and DNA-adducts. Further results presented at the British Society for Ecological Medicine conference Progesterone and Breast Cancer. London November 2006
3 Grant ECG. McLaren-Howard J. Re: The effects of toxic metals in autistic children. http://bmj.com/cgi/eletters/329/7466/588-b#74117, 13 Sep 2004
4 Siddique YH, Beg T, Afzal M. Antigenotoxic effects of ascorbic acid against megestrol acetate-induced genotoxicity in mice. Hum Exp Toxicol. 2005 Mar;24(3):121-7.
5 Giulivi C, Zhang YF, Omanska-Klusek A, Ross-Inta C, Wong S, Hertz- Picciotto I, Tassone F, Pessah IN. Mitochondrial dysfunction in autism. JAMA 2010 Dec 1;304(21):2389-96.
Competing interests: None declared

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