Subchronic Tolerance Trials of Graded Oral Supplementation with Phenylalanine or Serine in Healthy Adults
Abstract
:1. Introduction
2. Materials and Methods
2.1. Subjects
2.2. Supplementation
2.3. Study Intervention, Sample Collection and Analysis
2.4. Statistical Analyses
3. Results
3.1. Subjects in the Per-Protocol Set
3.2. Blood Biochemistry
3.3. Adverse Effects
3.4. Sleep Quality, Mental Fatigue, Macronutrient and Caloric Intakes, Body Weight Changes
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Blood Parameter | Trial | Phenylalanine (n = 23) | Serine (n = 30) |
---|---|---|---|
Total bilirubin (mg/L) Ref. value: 2–12 | Baseline | 9.1 ± 0.5 | 0.6 |
3 g/day | 9.7 ± 0.6 | 0.7 | |
6 g/day | 0.5 | 0.5 | |
9 g/day | 0.7 | 0.7 | |
12 g/day | 0.5 | 0.7 | |
Glutamic oxaloacetic transaminase (U/L) Ref. value: 10–40 | Baseline | 0.8 | 0.9 |
3 g/day | 1.0 | 1.3 | |
6 g/day | 0.7 | 0.7 | |
9 g/day | 2.1 | 1.1 | |
12 g/day | 1.2 | 0.9 | |
Glutamic pyruvic transaminase (U/L) Ref. value: 5–45 | Baseline | 0.8 | 2.0 |
3 g/day | 2.0 | 1.9 | |
6 g/day | 1.7 | 1.6 | |
9 g/day | 1.7 | 1.9 | |
12 g/day | 1.7 | 1.8 | |
Alkaline phosphatase (U/L) Ref. value: 100–325 | Baseline | 9.8 | 11.4 |
3 g/day | 8.8 | 0.2 | |
6 g/day | 10.1 | 10.1 | |
9 g/day | 9.0 | 9.0 | |
12 g/day | 9.0 | 9.0 | |
Lactate dehydrogenase (U/L) Ref. value: 120–240 | Baseline | 4.7 | 3.4 |
3 g/day | 4.7 | 7.0 | |
6 g/day | 4.2 | 3.7 | |
9 g/day | 8.7 | 4.1 | |
12 g/day | 4.9 | 3.1 | |
Gamma-glutamyltransferase (U/L) Ref. value: ≤80 | Baseline | 2.1 | 3.6 |
3 g/day | 2.7 | 3.0 | |
6 g/day | 2.7 | 2.0 | |
9 g/day | 2.9 | 3.8 | |
12 g/day | 2.5 | 3.8 | |
Creatine kinase (U/L) Ref. value: 60–270 | Baseline | 12.8 | 8.2 |
3 g/day | 18.2 | 12.9 | |
6 g/day | 13.4 | 10.9 | |
9 g/day | 169.0 | 5.9 | |
12 g/day | 33.6 | 17.6 | |
Total protein (g/L) Ref. value: 67–83 | Baseline | 0.6 | 0.7 |
3 g/day | 0.7 | ||
6 g/day | 0.6 | 0.6 | |
9 g/day | 0.6 | 0.7 | |
12 g/day | 0.8 | 0.6 | |
Creatine (mg/L) Ref. value: 6.1–10.4 | Baseline | 0.2 | 0.2 |
3 g/day | 0.2 | 0.2 | |
6 g/day | 0.2 | 0.2 | |
9 g/day | 0.2 | 0.2 | |
12 g/day | 0.2 | 0.2 | |
Blood urea nitrogen (mg/L) Ref. value: 80–200 | Baseline | 6.0 | 6.3 |
3 g/day | 5.5 | 7.4 | |
6 g/day | 6.5 | 6.3 | |
9 g/day | 6.9 | 7.3 | |
12 g/day | 5.2 | 5.9 | |
Uric acid (mg/L) Ref. value: 38–70 | Baseline | 2.2 | 1.9 |
3 g/day | 2.1 | 2.0 | |
6 g/day | 1.9 | 1.9 | |
9 g/day | 2.5 | 2.0 | |
12 g/day | 1.8 | 1.9 | |
Total cholesterol (mg/L) Ref. value: 2100–2190 | Baseline | 74 | 47 |
3 g/day | 73 | 53 | |
6 g/day | 68 | ||
9 g/day | 71 | 56 | |
12 g/day | 59 | 57 | |
Triglycerides (mg/dL) Ref. value: less than 147 | Baseline | 9.2 | 8.2 |
3 g/day | 7.8 | 9.3 | |
6 g/day | 17.8 | 6.3 | |
9 g/day | 10.1 | 12.1 | |
12 g/day | 7.8 | 11.4 | |
Sodium (mmol/L) Ref. value: 137–147 | Baseline | 0.3 | 0.2 |
3 g/day | 0.3 | 0.3 | |
6 g/day | 0.3 * | 0.4 $ | |
9 g/day | 0.4 | 0.3 | |
12 g/day | 0.2 | 0.3 | |
Potassium (mmol/L) Ref. value: 3.5–5.0 | Baseline | 0.04 | 0.05 |
3 g/day | 0.05 | 0.03 | |
6 g/day | 0.04 | 0.04 | |
9 g/day | 0.05 | 0.05 | |
12 g/day | 0.05 | 0.04 | |
Chloride (mmol/L) Ref. value: 97–107 | Baseline | 0.3 | 0.3 |
3 g/day | 0.3 * | 0.4 * | |
6 g/day | 0.3 * | * | |
9 g/day | 0.4 * | 0.3 * | |
12 g/day | 0.3 * | 0.3 | |
Calcium (mEq/L) Ref. value: 8.4–10.4 | Baseline | 0.07 | 0.05 |
3 g/day | 0.07 | 0.05 | |
6 g/day | 0.05 | 0.05 | |
9 g/day | 0.04 | 0.05 | |
12 g/day | 0.06 | 0.06 | |
HDL cholesterol (mg/dL) Ref. value: 40–85 | Baseline | 2.3 | 2.9 |
3 g/day | 2.0 | 3.0 | |
6 g/day | 2.1 | 2.8 | |
9 g/day | 1.9 | 3.0 | |
12 g/day | 1.7 | 3.4 | |
LDL cholesterol (mg/dL) Ref. value: 65–139 | Baseline | 6.1 | 4.8 |
3 g/day | 5.8 | 4.6 | |
6 g/day | 5.5 | 4.9 | |
9 g/day | 5.9 | 5.1 | |
12 g/day | 5.1 | 5.0 | |
Albumin (g/L) Ref. value: 38–52 | Baseline | 0.7 | 0.4 |
3 g/day | 0.5 | 0.4 | |
6 g/day | 0.6 | 0.4 | |
9 g/day | 0.6 | 0.3 | |
12 g/day | 0.7 | 0.4 | |
White blood cells (/mL) Ref. value: 3300–9900 | Baseline | 201 | 223 |
3 g/day | 221 | ||
6 g/day | 274 | 208 | |
9 g/day | 241 | 255 | |
12 g/day | 386 | 196 | |
Red blood cells (×104/mL) Ref. value: 430–580 | Baseline | 5.4 | 5.6 |
3 g/day | 5.3 | 5.1 | |
6 g/day | 6.5 | 5.3 | |
9 g/day | 5.2 | 5.2 | |
12 g/day | 6.9 | 5.1 | |
Hemoglobin (g/dL) Ref. value: 13.5–17.5 | Baseline | 0.21 | 0.21 |
3 g/day | 0.21 | 0.17 | |
6 g/day | 0.23 | 0.20 | |
9 g/day | 0.22 | 0.20 | |
12 g/day | 0.26 | 0.16 | |
Hematocrit (%) Ref. value: 39.7–52.4 | Baseline | 0.50 | 0.50 |
3 g/day | 0.52 | 0.45 | |
6 g/day | 0.69 | 0.54 | |
9 g/day | 0.55 | 0.53 | |
12 g/day | 0.58 | 0.41 | |
Platelet (×104/mL) Ref. value: 14–34 | Baseline | 0.84 | 0.75 |
3 g/day | 0.85 | 0.81 | |
6 g/day | 0.79 | 0.86 | |
9 g/day | 0.78 | 0.77 | |
12 g/day | 0.87 | 0.70 | |
Glucose (mg/dL) Ref. value: 70–109 | Baseline | 1.5 | 1.4 |
3 g/day | 1.5 | 1.0 | |
6 g/day | 1.5 | 1.9 | |
9 g/day | 1.6 | 1.4 | |
12 g/day | 1.3 | 2.0 |
Essential Amino Acids (mmol/L) | Trial | Phenylalanine (n = 23) | Serine (n = 30) |
---|---|---|---|
Histidine | Baseline | 1.6 | 1.4 |
3 g/day | 1.6 | 1.9 | |
6 g/day | 1.4 | 1.6 | |
9 g/day | 1.1 | 1.6 | |
12 g/day | 1.7 | 1.6 | |
Isoleucine | Baseline | 2.1 | 3.9 |
3 g/day | 2.5 | 3.9 | |
6 g/day | 5.0 | 3.0 | |
9 g/day | 3.1 | 4.5 | |
12 g/day | 2.7 | 3.6 | |
Leucine | Baseline | 3.8 | 6.8 |
3 g/day | 3.6 | 6.9 | |
6 g/day | 5.8 | 3.9 | |
9 g/day | 4.9 | 7.2 | |
12 g/day | 4.3 | 5.5 | |
Lysine | Baseline | 4.5 | 8.4 |
3 g/day | 5.1 | 5.6 | |
6 g/day | 5.7 | 4.9 | |
9 g/day | 5.7 | 5.5 | |
12 g/day | 6.0 | 6.5 | |
Methionine | Baseline | 0.9 | 1.1 |
3 g/day | 0.8 | 0.9 | |
6 g/day | .3 | 0.7 | |
9 g/day | 1.1 | 0.9 | |
12 g/day | 0.6 | 1.1 | |
Phenylalanine | Baseline | 1.7 | 1.5 |
3 g/day | 2.7 | 1.5 | |
6 g/day | 5.2 | 1.3 | |
9 g/day | 3.7 | 1.8 | |
12 g/day | 3.8 | 1.3 | |
Threonine | Baseline | 4.4 | 5.2 |
3 g/day | 4.0 | 4.7 | |
6 g/day | 5.0 | 3.5 | |
9 g/day | 5.0 | 3.8 | |
12 g/day | 3.7 | 4.6 | |
Tryptophan | Baseline | 1.2 | 2.1 |
3 g/day | 1.3 | 2.7 | |
6 g/day | 1.4 | 1.6 | |
9 g/day | 1.6 | 2.1 | |
12 g/day | 1.3 | 2.0 | |
Valine | Baseline | 5.7 | 10.1 |
3 g/day | 5.9 | 11.1 | |
6 g/day | 8.4 | 7.9 | |
9 g/day | 8.0 | 10.6 | |
12 g/day | 7.5 | 8.3 | |
Non-Essential Amino Acids, Cystine and Homocysteine (mmol/L) | Trial | Phenylalanine (n = 23) | Serine (n = 30) |
Alanine | Baseline | 17.9 | 14.8 |
3 g/day | 15.6 | 17.9 | |
6 g/day | 20.0 | 17.3 | |
9 g/day | 18.2 | 16.0 | |
12 g/day | 15.4 | 16.5 | |
Arginine | Baseline | 2.6 | 3.3 |
3 g/day | 3.1 | 2.7 | |
6 g/day | 3.1 | 2.7 | |
9 g/day | 2.7 | 3.4 | |
12 g/day | 2.4 | 3.6 | |
Aspartic acid | Baseline | 0.2 | 0.3 |
3 g/day | 0.3 | 0.2 | |
6 g/day | 0.2 | 0.2 | |
9 g/day | 0.2 $ | 0.2 | |
12 g/day | 0.3 | 0.3 | |
Asparagine | Baseline | 1.3 | 1.9 |
3 g/day | 1.4 | 1.8 | |
6 g/day | 2.3 | 2.0 | |
9 g/day | 1.9 | 1.9 | |
12 g/day | 1.4 | 1.9 | |
Cystine | Baseline | 1.5 | 1.6 |
3 g/day | 1.6 | 1.5 | |
6 g/day | 1.5 | 1.4 | |
9 g/day | 1.4 | 1.6 | |
12 g/day | 1.4 | 1.4 | |
Glutamic acid | Baseline | 1.7 | 2.2 |
3 g/day | 2.2 | 2.0 | |
6 g/day | 2.6 | 1.8 | |
9 g/day | 2.4 | 2.0 | |
12 g/day | 2.3 | 2.5 | |
Glutamine | Baseline | 10.5 | 8.6 |
3 g/day | 10.9 | 9.6 # | |
6 g/day | 12.4 | 9.5 | |
9 g/day | 9.4 *,# | 9.6 | |
12 g/day | 10.5 | 10.2 | |
Glycine | Baseline | 8.5 | 12.4 |
3 g/day | 8.5 | 11.3 | |
6 g/day | 10.0 | 13.6 | |
9 g/day | 9.1 | 12.0 | |
12 g/day | 7.4 | 13.0 | |
Proline | Baseline | 6.8 | 8.5 |
3 g/day | 6.7 | 9.2 | |
6 g/day | 10.0 | 8.2 | |
9 g/day | 6.2 | 11.0 | |
12 g/day | 5.6 | 9.5 | |
Serine | Baseline | 3.4 | 4.0 |
3 g/day | .9 | 3.6 | |
6 g/day | 4.4 | 5.6 | |
9 g/day | 3.5 | 7.2 ** | |
12 g/day | 3.5 | 12.7 ** | |
Tyrosine | Baseline | 1.8 | 2.1 |
3 g/day | 2.2 | 2.5 | |
6 g/day | 3.6 | ||
9 g/day | 3.7 | 2.8 | |
12 g/day | 4.2 * | 2.4 | |
Homocysteine | Baseline | 0.6 | |
3 g/day | 1.4 | ||
6 g/day | 2.0 | ||
9 g/day | 2.2 | ||
12 g/day | 2.0 |
Sleep Quality | Phenylalanine (n = 23) | Serine (n = 30) |
---|---|---|
Baseline (7 days) | 0.0769 | 0.1300 |
3 g/day (28 days) | .0812 | 0.1442 |
Wash-out period (14 days) | 0.1012 | 0.1271 |
6 g/day (28 days) | 0.1069 | 0.1335 |
Wash-out period (14 days) | 0.0718 | 0.1168 |
9 g/day (28 days) | 0.0577 | 0.1815 |
Wash-out period (14 days) | .0181 | 0.1840 |
12 g/day (28 days) | 0.0615 | 0.1848 |
Mental fatigue | Phenylalanine (n = 23) | Serine (n = 30) |
Baseline (7 days) | 0.0513 | 0.1428 |
3 g/day (28 days) | 0.0887 | 0.1310 |
Wash-out period (14 days) | 0.1066 | 0.1236 |
6 g/day (28 days) | 0.1007 | 0.1212 |
Wash-out period (14 days) | 0.0657 | 0.1275 |
9 g/day (28 days) | 0.0706 | 0.1829 |
Wash-out period (14 days) | 0.0308 | 0.1800 |
12 g/day (28 days) | 0.0457 | 0.1856 |
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Miura, N.; Matsumoto, H.; Cynober, L.; Stover, P.J.; Elango, R.; Kadowaki, M.; Bier, D.M.; Smriga, M. Subchronic Tolerance Trials of Graded Oral Supplementation with Phenylalanine or Serine in Healthy Adults. Nutrients 2021, 13, 1976. https://doi.org/10.3390/nu13061976
Miura N, Matsumoto H, Cynober L, Stover PJ, Elango R, Kadowaki M, Bier DM, Smriga M. Subchronic Tolerance Trials of Graded Oral Supplementation with Phenylalanine or Serine in Healthy Adults. Nutrients. 2021; 13(6):1976. https://doi.org/10.3390/nu13061976
Chicago/Turabian StyleMiura, Naoki, Hideki Matsumoto, Luc Cynober, Patrick J. Stover, Rajavel Elango, Motoni Kadowaki, Dennis M. Bier, and Miro Smriga. 2021. "Subchronic Tolerance Trials of Graded Oral Supplementation with Phenylalanine or Serine in Healthy Adults" Nutrients 13, no. 6: 1976. https://doi.org/10.3390/nu13061976