The Hidden Link Between Parkinsons and Autism

The Hidden Link Between Parkinsons and Autism...

The Hidden Link Between Parkinson’s and Autism

Nieske Zabriskie, ND

Autism and Parkinson’s disease are two seemingly unrelated conditions. Yet, they are tied together by a common denominator—glutathione deficiency.

Glutathione deficiency has been associated with several neurological and degenerative diseases. Glutathione is a potent antioxidant that has been shown to decrease with age, and these diminished levels manifest in increased oxidative stress associated with neurological conditions such as Alzheimer’s disease, Parkinson’s disease, autism and Lou Gehrig’s disease (ALS).1

Glutathione is a molecule synthesized by the liver comprised of the amino acids glycine, cysteine and glutamate. Glutathione provides antioxidant activity protecting DNA and cell membranes from free radical damage, detoxifies external substances such as pharmaceuticals and environmental pollutants, and enhances immune function. Glutathione exists in the body in 2 forms: the reduced state and the oxidized, disulfide forms. Reduced glutathione reacts with and neutralizes free radicals, and in the process is converted into the oxidized form, which is no longer functional. Thus, sufficient levels of reduced glutathione are imperative to inhibit free radical damage.

The brain has very high levels of fats yet has relatively low levels of antioxidants. This creates a situation in which the brain is extremely vulnerable to fatty acid oxidation, called lipid peroxidation.2 Many degenerative diseases of the brain can be traced back to lipid peroxidation.


Autism is one condition of particular interest that has been associated with decreased levels of glutathione. Autism is classified as a Pervasive Developmental Disorder (PDD), along with similar conditions such as Asperger disorder, disintegrative disorder, atypical autism, and Rett disorder. Autism, the classical presentation of autistic spectrum disorders (ASD), has increased in pediatric prevalence by an astounding 556 percent between 1991 and 1997.3 Data estimates that 1 in 100 children have ASD.4 It is estimated that 673,000 US children have ASD,4 and males are four times more likely to have ASD than females.5

Autism is characterized by impaired social interaction. Children with autism also exhibit impaired communication, imaginative play, and range of interests and activities. Individuals with ASD also have difficulty with reciprocal social interaction and non-verbal cues such as facial expression, body posture, and eye-to-eye gaze. They often exhibit repetitive stereotyped behavior, repetitive motor mannerisms and require strict routines or rituals. As parents, teachers and family members know, each child with autism presents uniquely as an individual relative to symptoms and severity.

Research is showing that both genetic and environmental factors play a role in the development of autism, although the exact cause of the disease is unknown. Research has shown that monozygotic (identical) twins have a concordance of greater than 60 percent, meaning that if one twin has the disease, the other twin has the same disease 60 percent of the time. When the researchers looked at the concordance rate for monozygotic twins and all PDD’s, they found a 92 percent concordance rate and 10 percent concordance rate for dizigotic (fraternal) twins. In addition, siblings of autistic children have a reoccurrence rate ranging from 2-8 percent, which is much higher than the general population.3

Studies have shown that children with autism have significantly decreased plasma total glutathione levels compared to healthy children.6 Furthermore, research has shown that the reduced glutathione (GSH) to oxidized glutathione (GSSG) redox ratio was decreased and the percentage of oxidized glutathione is increased in lymphoblastoid cells (LCLs) derived from autistic children compared to unaffected controls. Additionally, this study showed that exposure to oxidative stress via thimerosal, a mercury-containing compound found in some vaccinations, resulted in a greater decrease in the GSH/GSSG ratio and increase in free radical generation in autism compared to cells from unaffected children. The study authors stated, “These results suggest that the autism LCLs exhibit a reduced glutathione reserve capacity in both cytosol and mitochondria that may compromise antioxidant defense and detoxification capacity under pro-oxidant conditions.”7 Similarly, another study showed that children with autism have significantly decreased plasma levels of reduced glutathione and significantly increased plasma oxidized glutathione compared to healthy children. This study also found that subjects with severe ASDs had significantly increased mercury intoxication-associated urinary porphyrins, which correlated to oxidized glutathione levels. These results suggest that mercury intoxication is significantly associated with autistic symptoms, and ASD is associated with increased oxidative stress and decreased detoxification capacity.8

Additional research has shown that lipid peroxidation is significantly higher and glutathione and vitamin E levels are significantly lower in children with autism compared to healthy children. Also, the antioxidant enzymes glutathione peroxidase and superoxide dismutase were significantly upregulated in autistic children compared to the control group. These researchers concluded that this study suggested the possibility of antioxidant supplementation for the early intervention with autistic children.9 Another study found that 45 percent of children with autism have decreased natural killer (NK) cell activity, which is a white blood cell important for fighting infections, and that the decrease in NK activity correlated with decreased intracellular level of glutathione. Cells from the affected children were treated with cellular mediators and glutathione, which restores NK cell activity.10

Parkinson’s Disease

Parkinson’s disease is another neurological condition associated with glutathione deficiency. Parkinson’s disease is a progressive neurodegenerative disorder associated with a loss of the production of the neurotransmitter dopamine in the brain. It is estimated that over 500,000 individuals in the U.S. have Parkinson’s disease, and approximately 50,000 new cases are reported annually. The average age of onset is approximately 60, and it is slightly more common in men than women.11

Parkinson’s disease is characterized by a resting tremor, including trembling in hands, arms, legs, jaw, and face; rigidity or stiffness of the limbs and trunk; bradykinesia or akinesia, which is slow movements or the inability to move: and impaired balance and coordination. Other symptoms may include depression and other emotional changes; sleep disruption; difficulty in swallowing, chewing, and speaking; and problems with urination, constipation, or the skin. As the condition progresses, individuals may have difficulty walking, talking or completing other simple tasks.

Parkinson’s disease occurs from the loss of sufficient dopamine production in the portion of the brain called the substantia nigra. The substantia nigra is an area within the basal ganglia that contains dopaminergic (dopamine-producing) cells located at the base of the cerebral cortex, which helps control coordination and movement. Dopamine is a neurotransmitter responsible for controlling voluntary movement and coordination, and death of dopaminergic cells causes loss of coordination and voluntary movement.

The cause of Parkinson’s disease is unclear; it is likely to have both genetic and environmental factors. The development of Parkinson’s disease is strongly associated with exposure to environmental toxins. Studies have shown that the degree of hydrocarbon solvent exposure during a person’s lifetime is a major risk factor for Parkinson’s disease development.12 Hydrocarbon solvents cause damage to cells in the brain by lipid peroxidation. Oxidative stress has been implicated to play a major role in the neuronal cell death associated with Parkinson’s disease.

One of the earliest biochemical changes seen in Parkinson’s disease is a reduction in the levels of total glutathione. This decrease in glutathione levels was believed to be due to increased oxidative stress, a process heavily implicated in the pathology of this disease. However, recent evidence now suggests that glutathione depletion may itself play an active role in causing Parkinson’s disease.13 In fact, data indicates that there is a 40-50 percent deficit in total glutathione levels in the substantia nigra in individuals with Parkinson’s disease.14 In addition, research has shown a decrease in systemic antioxidants, including the enzyme glutathione peroxidase in red blood cells and plasma vitamin E levels, with an increase in markers of oxidative stress such as plasma malondialdehyde.15 A similar study showed that subjects with Parkinson’s disease have a reduction in antioxidant enzyme activity in red blood cells including glutathione peroxidase, superoxide dismutase, catalase, and glucose-6-phosphate dehydrogenase, which was directly correlated to the severity of the disease.16 In a recently published study, glutathione was given to subjects with Parkinson’s disease who had motor symptoms not adequately controlled by medication. Subjects received 1,400 mg of intravenous glutathione or placebo three times per week for 4 weeks. The results showed that Unified Parkinson’s Disease Rating Scale activity of daily living and motor scores improved by a mean of 2.8 units more in the glutathione group compared to the placebo group. Also, the subject’s symptoms returned after discontinuing the glutathione.17

Liposomal Glutathione

Liposomal glutathione is a highly absorbable form of glutathione, and can be supplemented to increase glutathione levels, fight free radical damage, and promote detoxification. Liposomes are a fat-soluble “bubble” that allows for increased absorption and protects the glutathione so it remains in the reduced state, which is the physiologically functional form. Recent developments with a liposomal form of glutathione suggest that wrapping glutathione in a liposome is an excellent way to keep glutathione stable and make it available for use in cells.18


A hallmark of numerous neurological diseases is a reduction in antioxidants, including glutathione. In both autism and Parkinson’s disease, numerous studies indicate that deficient glutathione may play a role in the development and progression of these conditions. Supplementation with glutathione may help fight the oxidative stress and free radical damage associated with these diseases.


1. Bains JS, Shaw CA. Neurodegenerative disorders in humans: the role of glutathione in oxidative stress-mediated neuronal death. Brain Res Brain Res Rev. 1997 Dec;25(3):335-58.

2. Volchegorskii IA, Malinovskaya NV, Shumelyova OV, et al. Dynamics of LPO products and oxidative modification of proteins in human brain during postnatal development. Bull Exp Biol Med. 2007 Aug; 144(2):192-9.

3. Muhle R, Trentacoste SV, Rapin I. The genetics of autism. Pediatrics. 2004 May;113(5):e472-86.

4. Kogan MD, Blumberg SJ, Schieve LA, Boyle CA, Perrin JM, Ghandour RM, Singh GK, Strickland BB, Trevathan E, van Dyck PC. Prevalence of Parent-Reported Diagnosis of Autism Spectrum Disorder Among Children in the US, 2007. Pediatrics. Published online October 5, 2009.

5. Center for Disease Control and Prevention, Autism Information Center. Available at: . Accessed on: 12-13-09.

6. James SJ, Cutler P, Melnyk S, et al. Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. Am J Clin Nutr. 2004 Dec;80(6):1611-7.

7. James SJ, Rose S, Melnyk S, et al. Cellular and mitochondrial glutathione redox imbalance in lymphoblastoid cells derived from children with autism. FASEB J. 2009 Aug;23(8):2374-83.

8. Geier DA, Kern JK, Garver CR, et al. Biomarkers of environmental toxicity and susceptibility in autism. J Neurol Sci. 2009 May 15;280(1-2):101-8.

9. Al-Gadani Y, El-Ansary A, Attas O, et al. Metabolic biomarkers related to oxidative stress and antioxidant status in Saudi autistic children. Clin Biochem. 2009 Jul;42(10-11):1032-40.

10. Vojdani A, Mumper E, Granpeesheh D, et al. Low natural killer cell cytotoxic activity in autism: the role of glutathione, IL-2 and IL-15. J Neuroimmunol. 2008 Dec 15;205(1-2):148-54.

11. National Institute of Neurological Disorders and Stroke. Parkinson’s Disease Backgrounder. Available at: . Accessed on: 12-10-09.

12. Jenner P. Oxidative mechanisms in nigral cell death in Parkinson’s disease. Mov Disord 1998;13 Suppl 1:24-34.

13. Martin HL, Teismann P. Glutathione–a review on its role and significance in Parkinson’s disease. FASEB J. 2009 Oct;23(10):3263-72. Epub 2009 Jun 19.

14. Zeevalk GD, Razmpour R, Bernard LP. Glutathione and Parkinson’s disease: is this the elephant in the room? Biomed Pharmacother. 2008 Apr-May;62(4):236-49.

15. Chen CM, Liu JL, Wu YR, et al. Increased oxidative damage in peripheral blood correlates with severity of Parkinson’s disease. Neurobiol Dis. 2009 Mar;33(3):429-35.

16. Abraham S, Soundararajan CC, Vivekanandhan S, et al. Erythrocyte antioxidant enzymes in Parkinson’s disease. Indian J Med Res. 2005 Feb;121(2):111-5.

17. Hauser RA, Lyons KE, McClain T, et al. Randomized, double-blind, pilot evaluation of intravenous glutathione in Parkinson’s disease. Mov Disord. 2009 May 15;24(7):979-83.

18. eevalk G, Guilford F, Bernard L. Liposomal glutathione for replenishment and maintenance of intracellular glutathione in mesencephalic cultures. Abstract Neuroscience 2009: Soc. for Neuroscience 2009.

Join Thousands of People & Receive - Advanced Health & Wellness Monthly Newsletter
Join Our Wellness Newsletter!