Peptides’ role in autism with emphasis on exorphins

Figures & data

Table 1. Some known exorphins are listed (one letter code)

Glumorphin
A5	G-Y-Y-P-T; A4:G-Y-Y-P
B5	Y-G-G-W-L; B4:Y-G-G-W
C	Y-P-I-S-L
From alpha-casein	R-Y-L-G-Y-L-(E)
	Y-V-P-F-P (and amide)
From beta-casein	Y-P-F-P-G-P-I-P
Short forms down to	Y-P (amide)
Casorphin	Y-P-S-F (amide)
Alpha-lactorphin	Y-G-L-F (amide)
Beta-lactophin	Y-L-L-F (amide)
Gliadinomorphin	Y-P-Q-P-Q-P-F
β-Casomorphin (h)	Y-P-F-V-E-P-I

Note: The bovine form of casomorphins are shown. The human (h) is different in sequence.

Table 2. Area under the 215 nm curve eluting after hippuric acid. Arbitrary units

	Italy	Serbia	Slovenia	Control
Mean	403	584	564	289
SD	307	504	523	84
N	145	139	51	181
95% CI	343	500	416	277
	453	667	711	302
P	<0.0001	<0.0001	0.0005

Fig. 1.  The HPLC pattern of a normal urine equivalent to 250 nanomoles creatinin.

Fig. 2.  The HPLC pattern of a boy with infantile autism.

Fig. 3.  Bottom trace amino acid analysis before hydrolysis, and top trace after hydrolysis in 6 M HCl in closed vials at 1108C for 16 hours. The late eluting (to the right) large peak is ammonia.

Fig. 4.  Demonstration of glumorphin A-5 by MS/MS (fragmentation). Top trace is synthetic standard, and bottom trace Glumorphin A5 isolated from regressive autistic children's urine. Declustering potential was set at 20 and collision energy at 30. The X axis has been extended in bottom trace to secure against hidden ion peaks.

Fig. 5.  Casomorphin 1–7. The casomorphin 1–7 standard is the top trace, from CPDD bottom trace. The peak appearing after the intact ion could be removed by increasing the declustering potential. It is shown here to illustrate the strong propensity for peptides to form aggregates and adducts. Declustering here is 20 and collision potential is 70.

Table 3. Year open study of dietary intervention in 15 patients

Test	Initial score	1-year change	4-year gain	No	p-Value
C-Raven	6.8±2.8	+8.6±2.8	+8.6±3.2	12	0.005
ITPA	25.7±5.5	+2.7±2.5	+6.1±2.8	10	0.005
DIPAB test
Social isolation	8.5±3.3	−6.1±2.7		14	0.005
Bizarre traits	5.3±2.2	−5.3±1.22		14	0.005

DIPAB, Diagnosticering af psykotisk Adfærd hos barn (Diagnosis of Psychotic behaviour in children); ITPA, Illinois test of psycholinguistic ability.ITPA, Illinois test of psycholinguistic ability.

The scores are the mean±standard deviation. Mann–Whitney U-test, two-tailed used throughout.

Five children had to be dropped from the ITPA test since the test has age limitations, and they were too old after 4 years. One of the 15 only participated for 6 months when he was convinced to quit by his GP.

Table 4. GF/Cf diet with control group for pair wise matched and randomly assigned autistic children 52

Group	Diet	Diet	Control	Control	Diet compared with controls
Period	Start	12 m	Start	12 m
Mean	12.5	5.6	11.5	11.2
SD	2.2	2.4	3.9	5.0
Significance		0.005*		0.798	0.001

Diet group N=10 and control group also 10. Mann Whitney U test two tailed was used.

Fig. 6.  Overloading normal person with gluten and gliadin for three days resulted in a demonstrable glumorphin B 5. Topp trace is spiked with standard peptide, bottom trace urine pattern after three days excessive gluten exposure.

Knivsberg A-M. Reichelt KL. Høien T. Nødland M. A randomized, controlled study of dietary intervention in Autistic syndromes. Nutrit. Neurosci. 2002; 5: 251–61. 10.3402/mehd.v23i0.18958.

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