Introduction
This study, conducted by Kern et al., investigates the effects of oral and transdermal glutathione supplementation in children diagnosed with autism spectrum disorders (ASD). Previous research has shown that children with ASD exhibit lower levels of reduced glutathione and abnormalities in transsulfuration metabolites, which are crucial for detoxification, antioxidant defense, and immune function.
The primary goal of the study was to assess whether these supplementation methods could significantly raise glutathione levels and improve related biochemical markers, thereby providing a potential therapeutic avenue for managing ASD symptoms.
Study Design and Participants
The research was an 8-week, open-label clinical trial involving children aged 3 to 13 years diagnosed with ASD. A total of 39 children were recruited, and after exclusions, 33 were randomized into two treatment groups:
- Oral glutathione (n=13)
- Transdermal glutathione (n=13)
A total of 26 children completed the study; 7 dropped out due to side effects or loss to follow-up. The interventions involved titrated doses of glutathione over time, with full doses reached by week three, depending on individual tolerance.
Measures and Assessments
The following laboratory markers were analyzed before and after treatment:
- Plasma reduced glutathione
- Plasma oxidized glutathione
- Whole-blood glutathione
- Plasma cysteine
- Plasma taurine
- Plasma sulfate (total and free)
All samples were collected under fasting conditions and analyzed at CLIA-certified labs.
Behavioral severity was measured using the Childhood Autism Rating Scale (CARS), and adherence to treatment was tracked using parent-reported measures. Side effects were rated using standardized tools such as the FISER/GRSEB/PRISE scales.
Key Results
1. Plasma Reduced Glutathione
- Oral group: Significant increase from 3.22 ± 0.54 µmol/L to 3.83 ± 0.63 µmol/L (p < 0.05), a 16% rise.
- Transdermal group: Increased from 3.06 ± 0.57 to 3.43 ± 0.4 µmol/L, an 11% increase, but not statistically significant.
2. Whole-Blood Glutathione
- Increased in both groups:
- Transdermal: 9% (977 ± 275 to 1,075 ± 336 µmol/L)
- Oral: 12% (984 ± 371 to 1,106 ± 317 µmol/L)
- Neither change reached statistical significance (NS).
3. Other Transsulfuration Metabolites
- Cysteine:
- Oral: 17.6 ± 8.5 to 24 ± 10.6 µmol/L, 27% increase, p < 0.05
- Transdermal: 19.4 ± 11.2 to 24.7 ± 12.9 µmol/L, 21% increase, p < 0.05
- Taurine:
- Oral: 45.8 ± 12.7 to 56.6 ± 13.6 µmol/L, 19% increase, p < 0.05
- Transdermal: 51.4 ± 21 to 68.1 ± 32.2 µmol/L, 25% increase, p < 0.05
- Total Plasma Sulfate:
- Oral: 863 ± 291 to 1,087 ± 188 µmol/g P, 21% increase, p < 0.01
- Transdermal: 950 ± 186 to 1,095 ± 231 µmol/g P, 13% increase, p < 0.01
- Plasma Free Sulfate: Slight increases in both groups but not statistically significant.
- Plasma Oxidized Glutathione: Showed no significant changes in either group.
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Side Effects and Compliance
Out of the 33 participants:
- 17 children (51.5%) had none or minimal side effects.
- 10 children (30.3%) experienced mild side effects.
- 1 child (3%) experienced moderate side effects.
- 5 children (15.1%) had intolerable side effects and were withdrawn.
Notably:
- 2 cases of rash occurred in the transdermal group.
- 3 cases of irritability (2 from transdermal, 1 from both treatments) led to withdrawal.
Compliance was high, with most participants missing fewer than two doses over the 8-week period.
Interpretation and Implications
The study demonstrated that both oral and transdermal glutathione supplementation significantly increased levels of cysteine, taurine, and plasma sulfate, which are crucial intermediates in the transsulfuration pathway. However, only oral supplementation significantly raised plasma reduced glutathione levels, which may suggest better systemic absorption through the liposomal formulation.
The changes observed in cysteine and glutathione were of a magnitude comparable to differences previously observed between autistic and neurotypical children, implying potential biological relevance. However, the lack of significant improvement in whole-blood glutathione raises concerns about whether glutathione is being effectively absorbed at the intracellular level, where it is most needed.
The results may also reflect glutathione breakdown products rather than direct enhancement of the transsulfuration pathway. Prior studies, such as those by Fukagawa et al., found that cysteine levels rose following glutathione infusion due to its degradation rather than synthesis.
Conclusions
This study provides preliminary evidence that oral and transdermal glutathione supplementation can improve certain biochemical markers related to oxidative stress and detoxification in children with ASD. However, clinical significance remains uncertain, particularly in light of the modest effect size and side-effect burden in a minority of participants.
- Oral glutathione showed more favorable outcomes than transdermal, particularly for increasing plasma reduced glutathione.
- Neither method significantly improved intracellular (whole-blood) glutathione levels, suggesting a need for alternative strategies or precursors for optimal efficacy.
- Future research should focus on larger samples, alternative administration method (such as IV therapy), longer durations, and explore precursor-based therapies like N-acetylcysteine (NAC) that may support intracellular synthesis.
For full details, refer to the original article: https://pmc.ncbi.nlm.nih.gov/articles/PMC3628138/
