ARI Publication 40 – 2013 Version

Behavioral changes were investigated for all participants, and the treatment group
improved significantly more than the placebo group as evaluated by the Parent Global
Impressions-Revised, including modest but statistically significant improvements in the Average
Change of all symptoms on the Parent Global Impressions-Revised, and significant
improvements in subscores in expressive language, tantrumming, hyperactivity, and overall
symptoms.
This study also reported that children with autism compared to neurotypical children had
significantly lower levels of NADH, the active form of vitamin B3, which is needed to recycle
oxidized glutathione to reduced (active) glutathione. The vitamin/mineral supplement
normalized levels of NADH, and this at least partially explains the improvement in the ratio of
oxidized to reduced glutathione, and improvements in overall oxidative stress

Adams JB et al, Effect ofa Vitamin/Mineral Supplement on Children with Autism, BMCPecliatrics 2011,
11:111

4) NADH: NADH is the active form of vitamin B3, and is an important co-factor for many
enzymatic reactions in the body. One study found that children with autism had normal levels
of vitamin B3, but significantly low levels of NADH (Adams et al 2011). One small treatment
study of 8 children with autism investigated the effect of 2 weeks of supplementation with 5-10
mg/day NADH (the active form of vitamin B3). It resulted in significant improvements in SAM to
near-normal levels. It significantly improved levels of reduced glutathione, but did not
significantly improve levels of oxidized glutathione.

Freedenfeld Set al, Biochemical Effects ofRibose and NADH Therapy in Children with Autism, Autism
Insights, 2011:3 3-13

5) Ribose: D-ribose is a naturally occurring sugar that is a key structural component of DNA, RNA,
NADH, NADPH, and many other important molecules in the body. It is a commonly used
nutritional supplement. One small treatment study of 8 children with autism investigated the
effect of 2 weeks of supplementation with 5 g/day ribose. It resulted in significant
improvements in SAM, but levels were still somewhat low. It slightly improved levels of reduced
glutathione, but did not significantly improve levels of oxidized glutathione.
Overall, the effects of NADH supplementation were similar to the effects of ribose
supplementation. Both treatments increased levels of NADH (by 22% and 18%, respectively)
and greatly increased levels of ribose (173% and 222%, respectively).

Freedenfeld Set al, Biochemical Effects ofRibose and NADH Therapy in Children with Autism, Autism
Insights, 2011:3 3-13

6) DMSA: Toxic metals such as mercury can greatly decrease the body’s ability to make
glutathione, and removing toxic metals seems to normalize glutathione levels. One study
investigated treatment with oral DMSA, a medication that is FDA-approved for treating lead
poisoning in infants and children. Phase 1 of the study involved giving 3 doses of oral DMSA
each day for 3 days (10 mg/kg bodyweight per dose). Levels of glutathione in RBC were
measured previous to treatment, and 1-2 months after treatment. Initially, many children with
autism had levels that were much below or much above that of the adult reference range, but
after treatment they had levels that were almost all within the adult reference range; i.e., those
with initially low levels increased towards normal, and those with high levels decreased towards
normal. It appeared that high levels of RBC glutathione were associated with high levels of
toxic metals (perhaps the body made more glutathione to respond?) and low levels of
glutathione were associated with mercury (which inhibits production and decreases levels of
glutathione). This treatment was safe and effective, and seemed to improve behavior.

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

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