ARI Publication 40 – 2013 Version

led to an 11% increase in reduced (active) glutathione in plasma, and a 9% increase in the
level of total glutathione in whole blood. However, there was little change in the level of
oxidized glutathione in plasma (4% decrease).

Kern JK, et al., A clinical trial ofglutathione supplementation in autism spectrum disorders. Med Sci
Monit 2011 Dec 1;17(12):CR677-682

3) IV glutathione: One study of high-dose intravenous glutathione found that it did raise levels, but
that the half-life in the body was only about 20 minutes, so it does not last long (but the effects
probably last longer).

AebiSet al., High-dose intravenous glutathione in man. Pharmacokinetics and effects on cyst(e)ine in
plasma and urine. European Journal ofClinicalInvestigation 1991, 21:103-110.

More effective methods
1) Vitamin C: 500 mg of vitamin C was found to raise RBC glutathione levels 50% in college

Johnston et al, Vitamin C elevates red blood cellglutathione in healthy adults. Am JC/in Nutr. 1993

2). Folinic Acid/TMG/methyl-B12: A treatment study of 8 young children with autism found that
800 mcg of folinic acid and 1000 mg of TMG normalized SAM and partially improved levels of
cysteine, total glutathione in plasma, and ratio of oxidized to total glutathione. Adding
subcutaneous injections of Vitamin B12 (methyl-cobalamin) resulted in normalization of levels of
SAM, cysteine, total glutathione in plasma, and the ratio of oxidized to total glutathione levels.

James SJ, Cutler et al., Metabolic biomarkers ofincreased oxidative stress and impaired methylation
capacity in children with autism. Am JC/in Nutr. 2004, 80(6):1611-7.

A larger treatment study of 48 children with autism involved the use of 800 mcg of folinic acid
and subcutaneous injections of vitamin B12 (methylcobalamin), but no TMG. The children were
pre-screened to verify that they had methylation and/or glutathione problems (75% of those
screened met criteria). The treatment did not significantly improve SAM, but cysteine levels did
increase to normal. Total and reduced glutathione increased partially, but remained lower than
normal. Oxidized glutathione improved to near-normal levels. The ratio of total glutathione to
oxidized glutathione improved partially but was still below normal. This was an open-label
study, and some improvements in behavior were mentioned but not reported.

James SJ et al., Efficacy ofmethylcobalamin and folinic acid treatment on glutathione redox status in
children with autism. Am JC/in Nutr. 2009, 89(1):425-30.

So, it appears that the 2004 study, which included TMG, yielded more beneficial results than the
2009 study. TMG, or trimethylglycine, contains three methyl groups that can be donated, and
likely supports methylation function and thereby improves SAM (which improved in the 2004
study, but not in the 2009 study).

3) Multi-Vitamin/Mineral Supplement: A randomized, double-blind, placebo-controlled study of 141
children and adults with autism investigated an oral multi-vitamin/mineral supplement designed
for individuals with autism. 54 of the children also had measurements of nutritional status at
the beginning and end of the study, including measurements of methylation, glutathione, and
oxidative stress. The supplement normalized SAM, and substantially improved another
biomarker of methylation (plasma uridine). The supplement also partially improved reduced
and oxidized glutathione, but the levels remained somewhat abnormal. Another marker of
oxidative stress, plasma nitrotryrosine, also improved substantially but remained slightly

Agape is proud to have
been involved in this study and
mentioned on page 16.