Autism Severity and Metabolic and Nutritional Status

Table 1. Characteristics of Participants
	Autism Group	Neurotypical Group
Total Participants	55	44
Male	49 (89%)	39 (89%)
Female	6 (11%)	5(11%)
Age (years)	10.0 +/- 3.1	11.0 +/- 3.1
Diagnosis	85% autism, 4% PDD/NOS, 11% Asperger's	In good mental and physical health
Medications	55% no medications 29% psycho-pharmaceuticals - primarily risperidone and clonidine; 9% on CNS stimulants (primarily Concerta); 4% on anti-convulsants 5% on GI medications; 7% on asthma/allergy medicine; 2% on insulin	89% no medications; 9% on anti-inflammatories (asthma/allergies); 2% on anti-incontinence medication
Special Diets	84% on regular diet; 3 gluten-free, casein-free diet; 1 gluten-free; 3 reduced dairy/gluten; 2 low sugar	1 child on dairy-free diet
Nutritional Supplements	1 on fish oil; 2 on melatonin	none
PDD-BI (modified autism composite)	-63 +/- 54	n/a
ATEC	64 +/- 25	n/a
SAS	4.9 +/- 2.4	n/a

Table 2. Symptoms of Autism Participants, per the ATEC Subscale on Health/Physical Behavior
Symptom	% with moderate or severe problem
bedwetting	20%
wets pants/diapers	16%
soils pants/diapers	20%
diarrhea	18%
constipation	41%
sleep problems	40%
eats too much/little	68%
limited diet	53%
hyperactive	40%
lethargic	17%
hits/injures self	18%
hits/injures others	24%
destructive	24%
sound sensitive	44%
anxious/fearful	27%
unhappy/crying	14%
seizures	4%
obsessive speech	33%
rigid routines	35%
shouts/screams	50%
demands sameness	43%
often agitated	41%
not sensitive to pain	30%
hooked or fixated on certain objects	63%
repetitive movements	38%

This section was rated on a scale of 0 (none), 1 (mild), 2 (moderate), 3 (severe). Below are listed the percentages with moderate or severe problems, as reported by parents.

Table 3. Analytical methods for some of the measurements
Analyte	Source	Methodology
Vitamin A	Plasma	Spectrophotometry [80]
Total Carotenes (alpha, beta, epsilon, gamma)	Plasma	Spectrophotometry [81]
Vitamin C (sum of reduced and oxidized forms)	Plasma	Spectrophotometry [82]
Vitamin D3 (25-hydroxy)	plasma	Measured in plasma by liquid chromatography - tandem mass spectroscopy (LC/MS/MS) [83]
Vitamin E (total tocopherols, including alpha, gamma1, gamma2)	serum	Spectrophotometry [84]
Vitamin K	plasma	Vitamin K was extracted from plasma by methylene chloride in a monophasic design, purified on a C-18 cartridge, separated on a reversed-phase column, and then detected fluorometrically [85]
Thiamine	Whole Blood	Microbiological Assay [86]
Riboflavin	Whole Blood	Microbiological Assay [87]
Niacin	Whole Blood	Microbiological Assay [88]
Pantothenic Acid	Whole Blood	Microbiological Assay [89]
P5P	RBC	Microbiological Assay [90]
Biotin	Whole Blood	Microbiological Assay [91]
Folic Acid	Serum	Microbiological Assay [92]
Vitamin B12	Plasma	Microbiological Assay [93]
Choline (Free and Total)	RBC	Microbiological Assay [94]
Alpha lipoic acid	Plasma	Microbiological Assay [95]
CoQ10	Plasma	Reverse-phase high-performance liquid chromatography (HPLC) using hexane extraction on a C-18 column (15 cm, 5 micron) with methanol:hexane (95:5) as the mobile phase and UV detection [96]
Adenosine, Inosine, Uridine	Plasma	HPLC with 254 adsorption [97]
Formimino-glutaric acid (FIGLU)	Urine	Spectrophotometrically [98] after adjustment of specific gravity at neutral pH [99]
Kryptopyrole	Urine	Spectrophotometrically [100] after adjustment of specific gravity at neutral pH [99]
Methylmalonic Acid	Urine	Liquid chromatography - tandem mass spectroscopy (LC-MS/MS) with electrospray ionization [101], expressed per gram creatinine
N-methylnicotinamide	Urine	HPLC, with ultraviolet diode array detection [102], and the results are expressed per gram creatinine
Serum Ferritin	Serum	Immunometric assay with Immunlite 2000 (Diagnostics Product Corp., Los Angeles, California)
S-adenosylmethionine (SAM) and S-adenyosylhomocysteine (SAH)	RBC	Extracted from RBC [103] and measured by LCMS [104]
Glutathione (GSH and GSSG)	Plasma	Fluorescence detector [105]
Nitrotyrosine	Plasma	LCMS [106]
ATP	Plasma	Luciferin-luciferase assay [107]
NADH, NADPH	RBC	Spectrophotometry [108]
Sulfate (Free and Total)	Plasma	Using indirect atomic absorption spectrometry [109]

Table 4. Correlations of autism severity scales
	Modified PDD-BI-Autism	ATEC	SAS
Modified PDD-BI-Autism Composite	1
ATEC	0.81	1
SAS	0.78	0.75	1

Table 5. Vitamins: The average levels of vitamins measured in the Autism and Neurotypical groups are reported below, along with their standard deviations
Vitamins	Units	Autism Group	Neuro-typical Group	% Difference	p-value	Neurotypical Reference Range (10^th and 90^th percentiles)	Autism Group % below RR	Autism Group % above RR	Tietz Reference Range [39]	NHANES1999–2002 Reference Range (6–11 yr and 12–19 yr) [38]	Sonora Quest
Vit. A (plasma)	μg/100 ml	54.3 +/- 10.7	54.9 +/- 12		n.s.	39–71	0%	9%	26–61 (7–19 yr)	26.0–51.2 30.8–70.6 (in serum)	26–49 (7–12 yr, in serum)
Total Carotenes (beta carotene and other carotenes, in plasma)	μg/100 ml	150 +/- 55	178 +/-53	-16%	0.01	111–251	29%	8%
Vit B1 Thiamine (WB)	μg/l	64 +/- 10	63 +/-9		n.s.	48–72	11%	20%	56 +/- 12 (children and young adults)^a		87–280 nmol.L (adult)
Vit B2 Riboflavin (WB)	μg/l	284 +/- 42	282 +/-52		n.s.	224–332	4%	15%
Vit B3 Niacin and Niacinamide (WB)	μg/l	7.00 +/- 1.1	7.07 +/-0.97		n.s.	5.9–8.2	16%	15%
Vit B5 Pantothenic Acid (WB)	μg/l	640 +/- 128	714 +/-180	-11%	0.02	504–965	11%	0%	200–1800 (adult)
Vit B6 (as P5P in RBC)	μg/l	17.9 +/- 16	15.2 +/-5.3		n.s.	8–21	13%	20%
Folic Acid (serum)	μg/l	17.7 +/- 7.2	18.7 +/-6.1		n.s.	12–28	20%	7%	3–20 (adult)	9.9–33.2 6.0–24.7	3.1–17.5 (adult)
Vit B12 (plasma)	ng/l	699 +/- 235	676 +/-215		n.s.	327–938	4%	18%	200–835 (adult)	369–1260 267–941 (in serum)	243–394 (adult, in serum)
Vit C (plasma)	mg/100 ml	1.57 +/- 0.61	1.33 +/-0.46	+18%	0.03	0.75–1.85	13%	29%	0.4–1.5 (adult)	0.2–1.7 (12–19 yr, in serum)^b	0.2–1.9 (adult)
Vit D3 (25-hydroxy in plasma)	μg/l	29.9 +/-8.4	28.6 +/-8.4		n.s.	19–44	9%	7%	14–60 (adult)	17–35 13–35	30–100
Total Vit E (serum)	mg/100 ml	0.78 +/- 0.18	0.90 +/-0.32	-14%	0.03	0.6–1.4	9%	0%	0.45–0.95 (1–19 yr)	0.55–1.13 0.53–1.14
Biotin (WB)	ng/l	394 +/-100	491 +/-164	-20%	0.001 *	257–709	7%	0%	200–500 (adult)
Vit K (plasma)	ng/l	294 +/- 158	295 +/- 189		n.s.	129–530	9%	7%	130–1190 (adult)		80–1160 (adult)
Vitamin-like substances
Free Choline (RBC)	mg/l	6.3 +/- 2.9	5.6 +/- 1.7		n.s.	4.0–7.6	22%	35%
Total Choline (RBC)	mg/l	363 +/- 66	310 +/- 51	+17%	< 0.0001 *	260–362	5%	53%
Lipoic Acid (plasma)	μg/l	2.56 +/- 1.5	2.85 +/- 1.2		n.s.	1.2–4.5	5%	16%
Biomarkers of functional need for vitamins
FIGLU	μg/l	1.99 +/- 0.92	1.62 +/- 0.72	+23 %	0.03	0.65–2.6	5%	27%
Methylmalonic Acid	mg/g-creatinine	9.0 +/- 7.3	7.5 +/- 5.0		n.s.	1.6–13.7	2%	13%
N-methyl-nicotinamide	mg/g-creatinine	5.0 +/- 4.4	3.6 +/- 2.3	+40%	0.04	1.2–7.1	13%	17%
Kryptopyroles	μg/dl	39.3 +/- 30.	35.8 +/- 15		n.s.	14–56	13%	11%

The p-value for a t-test comparison of the two groups is also reported. If the p-value is below 0.05, then the % difference between the groups is reported, and the result is highlighted.
The table also lists the reference range of the neurotypical group (10^th and 90^th percentiles), and the % of the Autism group who are above or below the reference ranges. Note that if the groups were identical, 10% would be above and 10% would be below. Percentages above 25% are highlighted. Reference Ranges from Tietz Textbook of Clinical Chemistry (Burtis and Ashwood 1999), the NHANES National Report, and Sonora Quest are given where available.
a) From Wyatt et al 1991 [110].
b) From Schleicher et al 2009 [111], based on NHANES data from 1999–2002 [38].
* Statistically significant difference between the two groups with 95% confidence per Bonferroni analysis.

Table 6. Essential Minerals and non-essential minerals measured in whole blood, RBC, serum, and urine
Essential Minerals + other minerals	Units	Autism Group	Neuro-typical Group	% Difference	p-value	Neurotypical Reference Range (10^th and 90^th percentiles)	Autism Group % below RR	Autism Group % above RR	Tietz Ref. Range [39]	NHANES1999–2002 Reference Range (6–11 yr and 12–19 yr) [38]	Sonora Quest Ref. Range
Calcium-WB	mg/dl	5.9 +/- 0.4	5.8 +/- 0.3		n.s.	5.45–6.20	11%	11%
Calcium-RBC	μg/g	19.3 +/-7	22.4 +/- 6	-14%	0.02	12.5–29.5	31%	7%
Calcium-Serum (total)	mg/dl	9.6 +/- 0.5	9.6 +/- 0.2		n.s.	9.25–9.9	13%	9%	8.8–10.8 (2–12 yr)		8.8–10.8 (2–12 yr)
Chromium-RBC	ng/g	0.91 +/-0.5	0.80 +/- 0.4		n.s.	0.3–14	9%	16%
Copper-WB	μg/dL	95 +/-11	89 +/- 14	+7%	0.02	70–108.5	0%	11%
Copper-RBC	μg/g	0.76 +/-0.08	0.72 +/- 0.09	+5%	0.03	0.61–0.86	2%	13%
Iodine-Urine	μg/mg-creatinine	0.24 +/- 0.2	0.26 +/- 0.3		n.s.	0.097–0.57	25%	4%		0.116–0.699 0.067–0.364
Iron-RBC	μg/g	891 +/-94	833 +/- 64	+7%	0.0005 *	764–922	2%	42%
Iron-Serum	μg/dl	83 +/- 34	87 +/- 35		n.s.	42–130	7%	7%	50–120 (child)	39–126 45–141	28–136 (6–14 yr)
Serum Ferritin	μg/l	39.1 +/- 22	36.9 +/- 17		n.s.	17–63	9%	16%	7–140 (1 - 15 yr)	11–74 8.0–115
Lithium-WB	μg/L	1.7 +/-0.8	3.6 +/- 6	-52%	0.006 W	1–5.0	11%	0%
Lithium-WB (without 3 highest neurotypical outliers #)	μg/L		2.2 +/- 1.1	-23%	0.006 W	3.25–3.90	13%	7%
Magnesium-WB	mg/dl	3.53 +/-0.31	3.64 +/- 0.26	-3%	0.02 W	42–54.5	18%	22%
Magnesium-RBC	μg/g	48.9 +/-6	47.5 +/- 5		n.s.	1.8–2.2	4%	2%			40–64 (adult)
Magnesium-Serum	mg/dl	1.95 +/- 0.14	2.03 +/- 0.15	-4%	0.02 W	8–16	13%	15%	1.7–2.1 (6–12 yr)		1.7–2.4 (adult)
Manganese-WB	μg/L	12.1 +/4	11.6 +/- 3		n.s.	0.012–0.025	11%	20%	7.7–12.1 (adult)
Manganese-RBC	μg/g	0.021 +/-0.007	0.018 +/- 0.005	+12%	0.07 W	1–1.8	6%	7%
Molybdenum-WB	μg/L	1.4 +/-0.4	1.4 +/- 0.3		n.s.	0.15–0.30	7%	13%	0.8–3.3 (adult)
Molybdenum-RBC	ng/g	0.93 +/- 0.3	0.98 +/- 0.2		n.s.	520–629	7%	33%
Phosphorus-RBC	μg/g	597 +/-59	567 +/- 43	+5%	0.004	3.85–5.35	6%	6%
Phosphorus-Serum	mg/dL	4.6 +/- 0.5	4.6 +/- 0.5		n.s.	73–83.5	9%	20%	4.5–5.5 (2–12 yr)		3.1–5.9 (4–12 yr)
Potassium -RBC	mEq/L	79 +/- 5.3	76.9 +/- 4.1	+3%	0.007 W	3.8–4.6	15%	9%
Potassium-Serum	mEq/L	4.1 +/- 0.3	4.2 +/- 0.3		n.s.	186–236	19%	9%	3.4–4.7 (child)		2.8–6.0 (child)
Selenium-WB	μg/L	207 +/-28	210 +/- 20		n.s.	0.20–0.27	9%	18%	58–234 (adult)
Selenium-RBC	μg/g	0.24 +/- 0.04	0.23 +/- 0.03		n.s.	136–139	9%	17%	0.07–0.24 (adult)
Sodium-Serum	mEq/l	138 +/- 2	137 +/- 1		n.s.	0.15–0.30	11%	2%	138–145 (child)		135–145 (adult)
Vanadium-RBC	ng/g	0.21 +/- 0.07	0.22 +/- 0.07		n.s.	465–657	7%	7%
Zinc-WB	μg/dL	551 +/-68	555 +/- 74		n.s.	6.8–10.8	2%	15%
Zinc-RBC	μg/g	9.2 +/-1.4	8.9 +/- 1.4		n.s.
Non-essential minerals
Boron-RBC	μg/g	0.029 +/-0.014	0.025 +/- 0.007	+16%	0.04	0.014–0.032	13%	36%
Strontium-WB	μg/L	25 +/-8	24 +/- 6		n.s	17–34	7%	6%

The average levels of minerals measured in the Autism and Neurotypical groups are reported below, along with their standard deviations. The p-value for a t-test comparison of the two groups is also reported. If the p-value is below 0.05, then the % difference between the groups is reported. For several tests the data was not normally distributed, and in those cases a non-parametric Wilcoxon test (also known as the Mann-Whitney test) was used instead of a t-test - those p-values are marked with a W.
The table also lists the reference range of the neurotypical group (10^th and 90^th percentiles), and the % of the Autism group who are above or below the reference ranges. Note that if the groups were identical, 10% would be above and 10% would be below. Percentages above 25% are highlighted. Reference Ranges from Tietz Textbook of Clinical Chemistry (Burtis and Ashwood 1999), the NHANES National Report, and Sonora Quest are given where available.
# Note that the lithium level for the neurotypical group is greatly increased by three siblings with very high lithium levels of 16, 16, and 35 mcg/L. A second value for lithium is given for the neurotypical group without those 3 siblings; the difference between the autism group and this revised neurotypical group is smaller but slightly more significant.
* Statistically significant difference between the two groups with 95% confidence per Bonferroni analysis.

Table 7. Correlations of essential minerals in different blood components
	Comparison	Autism Group	Neurotypical Group
Calcium	WB -RBC	0.00	0.14
	WB-Serum	0.40	0.33
	RBC-Serum	-0.30	-0.32
Magnesium	WB-RBC	0.52	0.65
	WB-Serum	0.41	0.34
	RBC-serum	0.37	0.13
Copper	WB-RBC	0.46	0.74
Zinc	WB-RBC	0.65	0.84
Manganese	WB-RBC	0.84	0.90
Selenium	WB-RBC	0.79	0.62
Molybdenum	WB-RBC	0.45	0.24
Potassium	RBC-Serum	-0.18	0.14
Phosphorus	RBC-Serum	0.11	0.28
Iron	RBC-Serum	-0.03	0.13
	RBC-serum ferritin	-0.09	0.13
	Serum- serum ferritin	-0.08	-0.24

Table 8. Metabolic Markers The average levels measured in the Autism and Neurotypical groups are reported below, along with their standard deviations
	Units	Autism Group	Neuro-typical Group	% Difference	p-value	Neurotypical Reference Range (10^th and 90^th percentiles)	Autism Group % below RR	Autism Group % above RR
Free Sulfate (plasma)	μmol/ g protein	1.44 +/- 0.51	4.09 +/- 2.28	-65%	< 0.00001 *	1.4–7.5	56%	0%
Total Sulfate (plasma)	μmol/ g-protein	1121 +/- 212	1566 +/- 384	-28%	< 0.0001 *	987–2070	36%	0%
SAM (RBC)	μmol/dl	214.5 +/- 15	228.4 +/- 12	-6%	< 0.0001 *	210–242	39%	4%
SAH (RBC)	μmol/dl	44.6 +/- 8.0	42.6 +/- 4.4		n.s.	40–52	27%	24%
SAM/SAH ratio		4.9 +/- 1.1	5.4 +/- 0.6	-10%	0.006	4.1–6.0	25%	13%
Uridine (plasma)	10⁻⁶ mol/l	15.3 +/- 7.5	7.9 +/- 2.7	+93%	< 0.00001 *	5.5–10.9	4%	60%
Adenosine (plasma)	10⁻⁸ mol/l	23.2 +/- 5.9	20.6 +/- 3.4	+12%	0.008	17–26	11%	33%
Inosine (plasma)	10⁻⁶ mol/l	3.56 +/- 0.91	3.83 +/- 0.93		n.s.	2.7–5.2	16%	5%
Reduced plasma glutathione (GSH)	nmol/ml	3.23 +/- 0.48	4.09 +/- 0.79	-21%	< 0.0001 *	3.1–5.1	53%	0%
Oxidized glutathione (GSSG)	nmol/ml	0.447 +/- 0.13	0.362 +/- 0.10	+24%	0.001 *	0.22–0.52	0%	30%
Ratio of oxidized to reduced plasma glutathione		0.14 +/- 0.05	0.093 +/- 0.04	+49%	< 0.0001 *	0.05–0.15	4%	42%
Plasma nitro-tyrosine	μg/l	16.6 +/- 7.8	7.4 +/- 5.1	+125%	< 0.0001 *	3.7–18	0%	44%

The p-value for a t-test comparison of the two groups is also reported. If the p-value is below 0.05, then the % difference between the groups is reported, and the result is highlighted.
The table also lists the reference range of the neurotypical group (10^th and 90^th percentiles), and the % of the Autism group who are above or below the reference ranges. Note that if the groups were identical, 10% would be above and 10% would be below. Percentages above 25% are highlighted.
* Statistically significant difference between the two groups with 95% confidence per Bonferroni analysis.

Table 9. ATP, NADH, NADPH, and CoQ10 The average levels measured in the Autism and Neurotypical groups are reported below, along with their standard deviations
	Units	Autism Group	Neuro-typical Group	% Difference	p-value	Neurotypical Reference Range (10^th and 90^th percentiles)	Autism Group % below RR	Autism Group % above RR
ATP (plasma)	nmol/l	14.5 +/- 4.2	18.5 +/- 4.8	-22%	< 0.0001 *	13.21	36%	4%
NADH (RBC)	nmol/ml	15.3 +/- 4.1	20.7 +/- 4.3	-26%	< 0.0001 *	16–25	51%	2%
NADPH (RBC)	nmol/ml	22.6 +/- 6.1	30.9 +/- 8.5	-27%	< 0.0001 *	20–40	37%	2%
CoQ10 (plasma)	μg/ml	0.55 +/- 0.15	0.60 +/- 0.16		n.s.	0.4–0.8	9%	2%

The p-value for a t-test comparison of the two groups is also reported. If the p-value is below 0.05, then the % difference between the groups is reported, and the result is highlighted.
The table also lists the reference range of the neurotypical group (10^th and 90^th percentiles), and the % of the Autism group who are above or below the reference ranges. Note that if the groups were identical, 10% would be above and 10% would be below. Percentages above 25% are highlighted.
* Statistically significant difference between the two groups with 95% confidence per Bonferroni analysis.

Table 10. Table of Primary Amino Acids in Plasma The average levels measured in the Autism and Neurotypical groups are reported below, in units of μmol/dl, along with their standard deviations
Amino Acids	Autism Group	Neuro-typical Group	% Difference	p-value	Neurotypical Reference Range (10^th and 90^th percentiles)	Autism Group % below RR	Autism Group % above RR	Tietz Ref. Range	Lepage et al Reference Range at 6 yr (top) and 16 yr (bottom)
Essential Amino Acids
Histidine	8.84 +/- 2.0	8.2 +/- 1.3		0.06	6.4–9.8	15%	36%		6.3–9.3 7.7–10.7
Isoleucine	5.26 +/- 1.0	5.8 +/- 1.6	-9%	0.05	4.1–8.3	16%	0%	3.8–9.5 (6–18 yr, serum)	4.0–6.9 4.7–7.4
Leucine	10.7 +/- 2.2	10.7 +/- 2.1		n.s.	8.2–13	13%	11%	7.9–17.4 (6–18 yr, serum)	8.6–13.6 10.1–15.9
Lysine	13.5 +/- 3.8	14.5 +/- 4.8		n.s.	8.7–22	11%	2%		9.6–18.1 15.7–24.2
Methionine	1.83 +/- 0.46	1.75 +/- 0.34		n.s.	1.4–2.3	16%	13%	1.6–3.7 (6–18 yr, serum)	1.4–2.5 2.0–3.4
Phenylalanine	4.45 +/- 0.62	4.83 +/- 0.83	-8%	0.01	3.9–6.0	20%	0%	4.8–10.9 (adult, serum)	4.0–6.1 4.7–7.4
Threonine	9.25 +/- 2.9	8.88 +/- 2.1		n.s.	6.7–11	18%	16%		6.5–12.5 10.4–18.8
Tryptophan	3.49 +/- 1.2	4.33 +/- 1.0	-19%	0.001 *	2.7–5.6	24%	4%		3.7–7.6 5.4–9.3
Valine	19.5 +/- 3.8	20.5 +/- 4.3		n.s.	16–27	16%	4%	15.6–28.8 (6–18 yr, serum)	16.5–23.4 17.8–27.5
Other Amino Acids
Alanine	36.4 +/-10.5	33.4 +/- 8.9		n.s.	24–45	7%	18%	19.3–54.5 (6–18 yr, serum)	18.2–31.9 24.0–48.2
Arginine	6.50 +/- 2.4	6.7 +/- 1.8		n.s	4–9.35	16%	9%		5.0–9.9 6.8–12.8
Asparagine	4.33 +/- 1.0	4.40 +/- 0.85		n.s.	3.6–5.7	30%	8%		3.1–6.7 3.7–8.1
Aspartate	0.71 +/-0.29	0.78 +/- 0.38		0.08	0.39–1.25	8%	6%		0.3–0.6 0.2–0.5
Cystine (oxidized form of cysteine)	3.22 +/- 0.82	3.48 +/- 0.74		n.s.	2.4–4.25	15%	11%
Glutamate	6.5 +/- 1.5	5.5 +/- 1.3	+18%	0.001 *	4.2–7.7	6%	26%		1.3–6.5 1.1–4.6
Glutamine	43.3 +/- 9.0	41.6 +/- 6.9		n.s.	34–52	16%	20%	36–74 (6–18 yr, serum)	49.3–72.4 55.1–79.7
Glycine	26.7 +/- 8.1	27.3 +/- 10.1		n.s.	16–39	4%	6%		14.4–28.2 18.3–32.2
Proline	15.7 +/- 5.5	15.8 +/- 4.9		n.s.	11.5–24	20%	7%		9.3–20.1 11.3–27.1
Serine	10.4 +/- 2.5	9.47 +/- 2.1	+10%	0.04	6.9–12	5%	15%		9.6–15.5 10.1–17.7
Tyrosine	5.51 +/- 1.2	6.1 +/- 1.6	-10%	0.03	4.8–8	31%	4%	4.4–7.2 (adult)	3.9–6.5 4.6–8.7

The p-value for a t-test comparison of the two groups is also reported. If the p-value is below 0.05, then the % difference between the groups is reported, and the result is highlighted.
The table also lists the reference range of the neurotypical group (10^th and 90^th percentiles), and the % of the Autism group who are above or below the reference ranges. Note that if the groups were identical, 10% would be above and 10% would be below. Percentages above 25% are highlighted. Reference Ranges from Tietz Textbook of Clinical Chemistry are given for serum amino acids where available. For Lepage et al, the reference ranges are the 10^th and 90^th percentiles for ages 6 yr and ages 16 yr.
* Statistically significant difference between the two groups with 95% confidence per Bonferroni analysis.

Table 11. Secondary Plasma Amino Acids and their metabolites, in units of μmol/dl
Amino Acids	Autism Group	Neuro-typical Group	% Difference	p-value	Neuro-typical Ref. Range (10^th and 90^th percentiles)	Autism Group % below RR	Autism Group % above RR
1-Methyl histidine	0.365 +/- 0.15	0.355 +/- 0.12		n.s.	0.19–0.52	11%	15%
3-Methyl histidine	0.74 +/- 0.68	0.68 +/- 0.52		n.s.	0.20–1.4	13%	20%
Alpha-amino adipate (33%/27% below dl)	0.079 +/- 0.32	0.088 +/- 0.044		n.s.	0.05–0.17	0%	0%
Alpha-amino-N-butyrate	1.78 +/- 0.66	1.82 +/- 0.72		n.s.	1.0–2.8	11%	7%
Anserine (85%/95% below dl)	0.058 +/- 0.027	0.051 +/- 0.006		0.06	0.32–1.0	11%	11%
Beta-alanine	0.60 +/- 0.28	0.62 +/- 0.31		n.s.	0.05–0.26	0%	15%
Beta-amino isobutyrate	0.191 +/- 0.89	0.138 +/- 0.088	+39%	0.004	2.45–3.75	25%	20%
Carnosine (76%/89% below dl)	0.061 +/- 0.031	0.054 +/- 0.015		n.s.	2.4–4.3	15%	11%
Citrulline	3.02 +/- 0.80	3.02 +/- 0.52		n.s.	0.31–1.55	9%	18%
Cystine + Cysteine	3.22 +/- 0.82	3.48 +/- 0.74		n.s.	1.3–3.6	5%	5%
Ethanolamine	1.07 +/- 0.75	0.94 +/- 0.63		n.s.	0.13–0.65	2%	9%
Gamma-amino butyrate (75%/84% below dl)	0.053 +/- 0.006	0.053 +/- 0.008		n.s.	3.9–8.3	9%	5%
Homocystine + Homocysteine (71%/89% below dl)	0.0094 +/- 0.010	0.0055 +/- 0.0016	+71%	0.006	0.87–2.2	25%	13%
Hydroxy proline	2.40 +/- 0.80	2.19 +/- 0.80		n.s.	0.0085–0.022	5%	33%
Methionine Sulfoxide	0.368 +/- 0.20	0.315 +/- 0.21		n.s.	0.4–1.35	13%	5%
Ornithine	5.9 +/- 1.6	5.98 +/- 1.7		n.s.	5.3–23.5	4%	4%
Phospho ethanol amine	1.34 +/- 0.73	1.55 +/- 0.59		n.s.	195–400	2%	3%
Phospho serine	0.045 +/- 0.078	0.024 +/- 0.044		n.s.
Sarcosine	0.80 +/- 0.32	0.893 +/- 0.36		n.s.
Taurine	13.9 +/- 5.8	16.8 +/- 5.8	-17%	0.02
Urea	299 +/- 94	309 +/- 87		n.s.

In some cases data was below the detectable limit -if this was greater than 20%, then we report the data as the % of the autism group and then the % of the neurotypical group below the detectable limit (dl).
The table also lists the reference range of the neurotypical group (10^th and 90^th percentiles), and the % of the Autism group who are above or below the reference ranges. Note that if the groups were identical, 10% would be above and 10% would be below. Percentages above 25% are highlighted.

Table 12. Correlation of Biomarkers with the modified PDD-BI Autism Composite, ATEC, and SAS, with the correlation coefficient followed by the p-value in parentheses
	PDDBI	ATEC	SAS
Plasma Free Sulfate	-0.19 (n.s.)	-0.25 (n.s.)	-0.38 (0.006)
RBC Iron	0.36 (0.009)	0.27 (0.05)	0.12 (n.s.)
Serum Phosphorus	0.38 (0.006)	0.11(n.s.)	0.12 (n.s.)
Plasma Phenylalanine	-0.22 (n.s.)	-0.29 (0.03)	-0.43 (0.002)

Only biomarkers with values of R = 0.34 or greater are listed, corresponding to a p-value of 0.01 or lower. Note that since many correlations were investigated, these results are not highly significant, and are at most possibly significant.

Table 13. Regression Analysis for Autism Severity vs. Vitamins (and related metabolites) and Minerals
	PDD-BI	ATEC	SAS
Vitamins
Adjusted R²	0.57	0.25	0.26
P-value	0.0008	0.005	0.02
Primary variables	Vit B6* Vit C* N-Methy-nicotinamide* Vit K Vit B2* Lipoic Acid * Kryptopyroles*	Vit C ** N-methyl-nicotinamide *	Vit C * Vit B6 N-methyl-nicotinamide ** Vit K *
Minerals
Adjusted R²	0.38	0.22	0.27
P-value	0.0007	0.007	0.003
Primary variables	Calcium (RBC) * Iron (RBC) Zinc (WB) Selenium (WB) Manganese (RBC) * Copper (WB) * Lithium (WB) * Zinc (RBC) *	Iron (RBC) * Calcium (RBC) Potassium (RBC) * Zinc (WB) *	Iron (RBC) * Calcium (RBC) Zinc (RBC) Potassium (RBC) Vanadium (RBC) *

* variable has a significance of p < 0.05
** variable has a significance of p < 0.01
*** variable has a significance of p < 0.001

Table 14. Regression analysis of autism severity and plasma amino acids
	PDD-BI	ATEC	SAS
Primary Plasma Amino Acids (20)
Adjusted R²	0.39	0.22	0.24
P-value	0.001	0.01	0.007
Primary variables	Proline Serine Leucine** Valine * Taurine *	Asparagine ** Tryptophan * Glutamic Acid * Glutamine * Phenylalanine *	Serine ** Asparagine * Proline *
Other Amino Acids
Adjusted R²	0.23	0.26	0.18
P-value	0.008	0.005	0.04
Primary variables	Beta-amino-isobutyrate ** Ethanolamine * Sarcosine *	Ethanolamine Sarcosine Beta-amino-isobutyrate ** 1-methyl-histidine *	Ethanolamine *

* variable has a significance of p < 0.05
** variable has a significance of p < 0.01
*** variable has a significance of p < 0.001

Table 15. Regression Analysis for Autism Severity vs. Sulfation/Methylation/Glutathione/Oxidative Stress, and vs. ATP/NADH/NADPH/CoQ10
	PDD-BI	ATEC	SAS
Sulfation, Methylation, Glutathione, Oxidative Stress
Adjusted R²	0.20	0.15	0.24
P-value	0.005	0.03	0.002
Primary variables	Free Sulfate ** SAM * Oxidized Glut. *	Free Sulfate ** SAM * Oxidized Glut. *	Free Sulfate ** Oxidized Glutat. * Adenosine *
ATP, NADH, NADPH, CoQ10
Adjusted R²		0.13
P-value	n.s.	0.01	n.s.
Primary variables		NADH ** ATP *

* variable has a significance of p < 0.05
** variable has a significance of p < 0.01
*** variable has a significance of p < 0.001

Table 16. Regression analysis of autism severity vs. highly significant biomarkers (defined as p < 0.01, in a previous regression analysis)
	PDD-BI	ATEC	SAS
Significant Biomarkers
Adjusted R²	0.56	0.24	0.42
P-value	0.000003	0.002	0.0002
Primary variables	Iron (RBC) * Methylmalonic Acid Glutamate Proline Serine	Sarcosine * Ethanolamine * Beta-amino-isobutyrate * Free Sulfate *	Potassium (RBC) Calcium (RBC) N-Methyl-nicotinamide Serine Phenylalanine ** Alanine *

* variable has a significance of p < 0.05
** variable has a significance of p < 0.01
*** variable has a significance of p < 0.001

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