Background and Significance
Methodology
Participants
Enrollment criteria
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 |
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% |
Study Protocol
Lab 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 | |
Kryptopyrole | Urine | |
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 | |
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] |
Amino Acids
Assessing Autistic Symptoms and Severity
Statistical Analysis
Results
Correlation Of Autism Severity Scales
Comparison of Neurotypical and Autism Groups with Published Reference Ranges
Vitamins | Units | Autism Group | Neuro-typical Group | % Difference | p-value | Neurotypical Reference Range (10th and 90th 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% |
Essential Minerals + other minerals | Units | Autism Group | Neuro-typical Group | % Difference | p-value | Neurotypical Reference Range (10th and 90th 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% |
Comparisons of biomarkers between autistic and neurotypical groups
Vitamins
Essential Minerals
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 |
Sulfation, Methylation, Glutathione, Oxidative Stress
Units | Autism Group | Neuro-typical Group | % Difference | p-value | Neurotypical Reference Range (10th and 90th 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%
|
ATP, NADH, NADPH, CoQ10
Units | Autism Group | Neuro-typical Group | % Difference | p-value | Neurotypical Reference Range (10th and 90th 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% |
Plasma Amino Acids: Primary
Amino Acids | Autism Group | Neuro-typical Group | % Difference | p-value | Neurotypical Reference Range (10th and 90th 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 |
Plasma Amino Acids: Secondary
Amino Acids | Autism Group | Neuro-typical Group | % Difference | p-value | Neuro-typical Ref. Range (10th and 90th 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. |
Medication Effects
Correlations with Autism Severity
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)
|
Regression Analyses
Vitamins
Minerals
Sulfation, Methylation, Glutathione, Oxidative Stress
ATP, NADH, NADPH, CoQ10
Primary Amino Acids
Secondary Amino Acids
Overall Analysis
Discussion
Overview
Sulfation and ATP
Methylation and ATP
Oxidative Stress
Vitamins
Functional tests
Minerals
Sulfation, Methylation, Glutathione and Oxidative Stress
ATP, NADH, NADPH, CoQ10
Primary Amino Acids
Secondary Amino Acids
Potential Confounding Factors: Medication, Gastrointestinal and Dietary Issues
Correlation Analysis
Regression Analysis
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) * |
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 * |
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 * |
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 * |