Autism and Schizophrenia subgroup related to blockage by toxic exposures             of enzymes processing gluten and casein, 

         B.Windham (Ed), 2008        


(affects at least 65% of autistic children (100) ) (overlaps with other mechanisms documented in (110) )

I.    Enzymatic Inhibitation by mercury (and other toxic metals)

A direct mechanism involving mercury’s inhibition of cellular enzymatic processes by binding with the hydroxyl radical(SH) in amino acids appears to be a major part of the connection to allergic/immune reactive conditions(15-23,28,36,47,51,98). For example mercury has been found to strongly inhibit the activity of xanthine oxidase(16) and dipeptyl peptidase (DPP IV) which are required in the digestion of the wheat protein gluten or the milk protein casein (15,17,19,20,22a,24,-26,31,98, 105) - the same protein that is cluster differentiation antigen 26  (CD26) which helps T lymphocyte activation. CD26 or DPPIV is a cell surface glycoprotein that is very susceptible to inactivation by mercury binding to its cysteinyl domain. Mercury and other toxic metals also inhibit binding of opioid receptor agonists to opioid receptors, while magnesium stimulates binding to opioid receptors(15). Studies involving a large sample of  patients with autism, schizophrenia, or mania found that over 90 % of those tested had high levels of the milk protein beta-casomorphine-7 in their blood and urine and defective enzymatic processes for digesting milk protein(24,25,27), and similarly for the corresponding enzyme needed to digest wheat gluten (24,26). Like casein, gluten breaks down into molecules with opioid traits, called gluteomorphine. As with caseomorphin, it too can retain biological activity if the enzymes needed to digest it are not functioning properly.

Proteins in bovine milk are a common source of bioactive peptides. The peptides are released by the digestion of caseins and whey proteins (105).  In vitro the bioactive peptide beta-casomorphin 7 (BCM-7) is yielded by the successive gastrointestinal proteolytic digestion of bovine beta-casein variants A1 and B, but this was not seen in variant A2 or in goats milk. In hydrolysed milk with variant A1 of beta-casein, BCM-7 level is 4-fold higher than in A2 milk.  Variants A1 and A2 of beta-casein are common among many dairy cattle breeds. A1 is the most frequent in Holstein-Friesian (0.310–0.660), Ayrshire (0.432–0.720) and Red (0.710) cattle. In contrast, a high frequency of A2 is observed in Guernsey (0.880–0.970) and Jersey (0.490–0.721) cattle(105). In children with autism, most of whom have been found to have been exposed to high levels of toxic metals through vaccines, mother’s dental amalgams, or other sources;   higher levels of BCM-7 is found in the blood(24-26).  

BCM-7 appears to play a significant role in the aetiology of human diseases including diabetes, immune, neurological, and cardiovascular(105,106). Epidemiological evidence from New Zealand claims that consumption of beta-casein A1 is associated with higher national mortality rates from ischaemic heart disease. It appears that the populations that consume milk containing high levels of beta-casein A2 have a lower incidence of cardiovascular disease and type 1 diabetes. Beta-casomorphin-7 has opioid properties including immunosuppression, which  account for the specificity of the relation between the consumption of some but not all beta-casein variants and diabetes incidence.  BCM-7 has also been suggested as a possible cause of sudden infant death syndrome (SIDS). In addition, neurological disorders, such as autism and schizophrenia, appear to be associated with milk consumption and a higher level of BCM-7 (105,106).


The studies also found high levels of Ig A antigen specific antibodies for casein, lactalbumin and beta-lactoglobulin and IgG and IgM for casein.   Beta-casomorphine-7  is a morphine like compound that results in neural disfunction (24,25), as well as being a direct histamine releaser in humans and inducing skin reactions (14,21,25c).  Similarly many also had a corresponding form of  gluten protein with similar effects(24,26).   Elimination of milk and wheat products and sulfur foods from the diet has been found to improve the condition of ASD children (100,28,etc.).  A double blind study using a potent opiate antagonist, naltrexone(NAL), produced significant reduction in autistic symptomology among the 56% most responsive to opioid effects(28).  The behavioral improvements was accompanied by alterations in the distribution of the major lymphocyte subsets, with a significant increase in the T-helper-inducers and a significant reduction of the T-cytotoxic-suppressors and a normalization of the CD4/CD8 ratio.   Studies have found mercury causes increased levels of the CD8 T-cytotoxic-suppressors(29).   As noted previously, such populations of patients have also been found to have high levels of mercury and to recover after mercury detoxification (23,11,22a,30,40,96,100).  As mercury levels are reduced the protein binding is reduced and improvement in the enzymatic process occurs(22a,11,96).

II.  Lactose Intolerance

Lactose (milk sugar), which is a major component of milk, is a disaccharide sugar made up of the simple sugars glucose and galactose(5).  Lactase is an enzyme which facilitates digestion of lactose.  Over 50% of non-Caucasians are lactose intolerant, to a significant degree and about 20% of Caucasians. Infants are most lactose tolerant but lactase activity declines dramatically over time so that by adulthood to about 5 to 10 % of the level of infants. Only a relatively small percentage of people retain enough lactase activity to absorb significant amounts of lactose throughout their adult life (5). Lactose intolerance results in undigested lactose in the intestines which often causes gas, bloating, abdominal discomfort, and proliferation of bacteria in the intestines. In addition to inhibiting the enzymes required to digest milk casein and whey, chronic mercury exposure in animals has also been found to inhibit lactase and glucose-6-phosphatase needed to digest lactose and other polysaccharides (31). Thus chronic exposure to mercury and toxic metals also increases lactose intolerance and digestion problems of carbohydrates in general.  Digestive problems have been found to commonly be improved by reducing chronic mercury and toxic metal exposures.

Lactose intolerance can also be alleviated to some degree by supplemental enzymes, using fermented milk products such as yogurt or kefir, or using only small amounts of milk products spread throughout the day(5).

    A new study has found that there has been a significant increase in another gluten related condition in the last 50 years –celiac disease (32). The researchers showed that the presence of undiagnosed celiac disease was 4 to 4.5-fold greater in the more recent subject group compared to an earlier Warren Air Force Base group.  This study indicates that the rise in the prevalence of celiac disease over the last 50 years is not simply due to increased awareness and better diagnostic tests for this condition. Additionally, the fact that the mortality rate of undiagnosed celiac disease is almost 4-fold higher than for those without the condition suggests that screening for celiac disease instead of waiting for a patient to complain of symptoms may be warranted. A positive test result should be confirmed before undergoing a gluten-free diet. The study authors concluded, “During 45 years of follow-up, undiagnosed celiac disease was associated with a nearly 4-fold increased risk of death. The prevalence of undiagnosed celiac disease seems to have increased dramatically in the United States during the past 50 years.”   Studies have also found that untreated celiac disease can result in infertility, spontaneous abortions, and birth defects, along with other reproductive system problems (10).



(5) Understanding Nutrition, 11th Edition; E. Whitney, S.R. Rolfes, Wadsworth Cengage Learning, 2008, p 110,111, etc. 

(10) Dr. Sheila Crowe,   Division of gastroenterology and hepatology in the department of medicine at the University of Virginia, New York Times February 3, 2010


(11) V.D.M.Stejskal, Dept. Of Clinical Chemistry, Karolinska Institute, Stockholm, Sweden    LYMPHOCYTE    IMMUNO‑STIMULATION ASSAY ‑MELISA”,  paper presented at international autism conference &

  & “Mercury-specific Lymphocytes: an indication of  mercury allergy in man”, J. Of Clinical Immunology, 1996, Vol 16(1);31-40;     see:       

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(19)  Shibuya-Saruta H, Kasahara Y, Hashimoto Y. Human serum dipeptidyl peptidase IV (DPPIV) and its unique properties.  J Clin Lab Anal. 1996;10(6):435-40; & Blais A, Morvan-Baleynaud J, Friedlander G, Le Grimellec C. Primary culture of rabbit proximal tubules as a cellular model to study nephrotoxicity of xenobiotics. Kidney Int. 1993 Jul;44(1):13-8; & Puschel G, Mentlein R, Heymann E, 'Isolation and characterization of dipeptidyl peptidase IV from human placenta', Eur J Biochem 1982 Aug;126(2):359-65; & Kar NC, Pearson CM.  Dipeptyl Peptidases in human muscle disease.  Clin Chim Acta 1978; 82(1-2): 185-92; & Seroussi K, Autism and Pervasive Developmental Disorders , 1998, p174,etc.,

(20) Stefanovic V. et al, Kidney ectopeptidases in mercuric chloride-induced renal failure.  Cell Physiol Biochem        1998; 8(5): 278-84.

(21) Crinnion WJ.   Environmental toxins and their common health effects.  Altern Med Rev 2000, 5(1):52-63.

(22) Windham, B. Annotated Bibliography: Adverse health effects related to mercury and amalgam fillings and clinically documented recoveries after amalgam replacement. (over 3000 peer-reviewed references);

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(24) J.R. Cade et al,  Autism and schizophrenia linked to malfunctioning enzyme for milk protein digestion.  Autism, Mar 1999. ;& Autism and Schizophrenia: Intestinal Disorders, Cade R et al. Nutritional Neuroscience, March 2000.   & ; & "Beta-casomorphin induces Fos-like immunoreactivity in discrete brain regions relevant to schizophrenia and autism" Autism March 1999 vol 3(1) 67-83; Sun, ZJ, Cade JR, et al ;    &  A Peptide Found in Schizophrenia and Autism Causes Behavioral Changes in Rats, J.R. Cade, Z. Sun , Univ of Florida, USA , Autism, Vol. 3, No. 1, 85-95 (1999)  DOI: 10.1177/1362361399003001007  © 1999 The National Autistic Society, SAGE Publications ; & Opiate hypothesis in infantile autism? Therapeutic trials with naltrexone, Leboyer M, et al., Encephale 1993 Mar-Apr;19(2):95-102; & Food allergy and infantile autism. Lucarelli S, et al., Panminerva Med 1995 Sep;37(3):137-41; ; & Peptides from Casomorphin & Gliadorphin, The Great Plains Laboratory, ; & Why Use the Gluten-Free and Casein-Free Diet in Autism and What the Results have Shown so Far, Peptides and Autism, Karl Reichelt, MD, PhD1 and A. M. Knivsberg PhD, Fall Defeat Autism Now!TM 2003 Conference  *** Portland, Oregon *** October 3-5, 2003,         &

Milk Linked to Autism, Schizophrenia


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(26) Huebner FR, Lieberman KW, Rubino RP, Wall JS.  Demonstration of high opioid-like activity in isolated peptides from     wheat gluten hydrolysates.  Peptides 1984; 5(6):1139-47; & Wheat gluten as a pathogenic factor in schizophrenia. Singh MM, Kay SR, Science 1976 Jan 30;191(4225):401-2; & Demonstration of high opioid-like activity in isolated peptides from wheat gluten hydrolysates.  Huebner FR, Lieberman KW, Rubino RP, Wall JS.   Peptides. 1984 Nov-Dec;5(6):1139-47; & Naloxone antagonises effect of alpha-gliadin on leucocyte migration in patients with coeliac disease. Horváth K, Gráf L, Walcz E, Bodánszky H, Schuler D. Lancet. 1985 Jul 27;2(8448):184-5

(27) Willemsen-Swinkels SH, Buitelaar JK, Weijnen FG, Thisjssen JH, Van Engeland H.  Plasma beta-endorphin         concentrations in people with learning disability and self-injurious and/or autistic behavior.  Br J Psychiary 1996; 168(1):    105-9; & Leboyer M, Launay JM et al.   Difference between plasma N- and C-terminally directed beta-endorphin immunoreactivity in infantile autism.  Am J Psychiatry 1994; 151(12): 1797-1801.

(28) Scifo R, Marchetti B, et al.  Opioid-immune interactions in autism: behavioral and immunological assessment during a double-blind treatment with naltexone.  Ann Ist Super Sanita 1996; 32(3): 351-9.

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(31) Changes in the activities of some digestive enzymes , exposed chronically to mercuric

chloride; Sastry KV, Gupta PK.  J Environ Sci Health B. 1980;15(1):109-19

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(98) Infections, toxic chemicals and dietary peptides binding to lymphocyte receptors and tissue enzymes are major instigators of autoimmunity in autism.  Vojdani A, Pangborn JB, et al,  Int J Immunopathol Pharmacol. 2003 Sep-Dec;16(3):189-99.

 (100) Results of treatment survey of 25,000 parents of autistic children, Autism Research Institute,

(105) Polymorphism of bovine beta-casein and its potential effect on human health, J

Appl Genet 48(3), 2007, pp. 189–198, Stanis³aw Kamiñski1, Anna Cieoeliñska1, El¿bieta Kostyra2; & Type I (insulin-dependent) diabetes mellitus and cow milk: casein variant consumption.  Diabetologia 1999 Aug;42(8):1032; Elliott RB, Harris DP, Hill JP, Bibby NJ, Wasmuth HE;  &(c) Sokolov OIu, Kost NV et al, [Regulatory peptides and psychomotor development in infants], Vestn Ross Akad Med Nauk. 2007;(3):33-9 & Influence of human B-casomorphin-7 on specific binding of 3H-spiperone to the 5-HT2-receptors of rat brain frontal cortex;  Protein Pept Lett. 2006;13(2):169-70; &(d) Dubynin VA, Malinovskaia IV, et al; Delayed effect of exorphins on learning of albino rat pups], [Article in Russian]  Izv Akad Nauk Ser Biol. 2008 Jan-Feb;(1):53-60; & (e) Findings in normal rats following administration of gliadorphin-7 (GD-7), Sun Z, Cade R.  Peptides. 2003 Feb;24(2):321-3


(106)  Devil in the Milk Illness, Health, and the Politics of A1 and A2 Milk , Keith Woodford & Thomas Cowan, MD, Chelsea Green Publishing, 2009  &


& rest in (110)