ARI Publication 40 – 2013 Version

One large study by Horvath, et al (1999) evaluated disaccharidase (sugar) activity from endoscopic
biopsies in 90 children with autism. They found that 49% had at least one deficient enzyme
activity, and 20% had deficiencies in two or more disaccharidase enzymes. “Lactase and maltase
deficiencies were the most frequent, followed by low activity of sucrase, palatinase, and
glucoamylase. All of the children with low enzyme activity had loose stools and/or gaseousness.”

Horvath Ket at Gastrointestinal abnormalities in children with autistic disorder,”J. Pediatrics 135no. 5
(1999) 559-563.
Horvath Kand Perman JA ”Autistic disorder andgastrointestinal disease,”Curr. Opinion in Pediatrics, 14

A small study by Williams et al 2011 also found substantial decreases in disaccharidases, resulting in
abnormal gut bacteria.

Williams BL et al., Impaired carbohydrate digestion and transport and mucosa/ dysbiosis in the intestines
ofchildren with autism andgastrointestinal disturbances. PLoS One. 2011;6(9):e24585. Epub 2011 Sep

A new large study at Harvard Medical School (Kushak et al 2011) involving intestinal biopsy samples
of 199 children and adults with autism (ages 22 months to 28 years) found that many had
deficiencies in disaccharidases (enzymes for digesting simple sugars). Specifically, they found that
62% had deficiencies in lactase, 16% were deficient in sucrase, and 10% were deficient in maltase.
The problems seemed to be equally common in children and adults, suggesting that these problems
are lifelong.

KushakRIetal, Intestinaldisaatlaridase activityin patients with autism: effectofage, gender, andintestinal
inflammation. Autism~ 2011 May;15(3):285-94. Epub 2011 Mar17.

Treatment Studies
One open-label treatment study involved a 12-week trial of a digestive enzyme. The digestive
enzyme included enzymes for proteins, peptides, casein, and phytic acid. 46 participants started the
study, and 17 dropped out, including 6 who stated adverse effects and others for various reasons
including lack of benefit. This was a rather high drop-out rate. The 29 who finished the study
reported improvements in many areas, especially socialization and hyperactivity, and half reported
improvements in digestion.

Brudnak MA et al. Enzyme-based therapy for autism spectrum disorders is it worth another look? Med
Hypotheses. 2002 May;58(5):422-8.

However, another digestive enzyme treatment study found no benefit. This was a more rigorous
randomized, double-blind, placebo-controlled, cross-over study lasting 6 months and involving 43
It involved a digestive enzyme designed to digest proteins and peptides (small
proteins), not carbohydrates or sugars. The digestive enzymes were well tolerated, but there were
no statistically significant clinical improvements on any symptoms.

Munasinghe et al., Digestive Enzyme Supplementation for Autism Spectrum Disorders: A Double-Blind
Randomized Controlled TrialJ Autism Dev Disord (2010) 40:1131-1138

The two studies listed above were for digestive enzymes focused on proteins, not sugars and
carbohydrates. According to three studies by Horvath et al 1999, Williams et al 2011, and Kushak
et al 2011, children with autism have a problem digesting sugars and carbohydrates, and especially
milk sugar (lactose). So, there is a need for a treatment study to investigate digestive enzymes
designed to digest sugars and carbohydrates, especially lactase.

Finally, the ARI survey data (which involves many different brands of digestive enzymes) suggests
that digestive enzymes can be helpful and are generally well-tolerated. The Specific Carbohydrate
Diet (which includes avoidance of most sugars and all carbohydrates except for monosaccharides)

also seems likely to be beneficial for people lacking digestive enzymes for those foods, but there are
no formal research studies on it yet (see ARI survey data below).



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

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