ASEA Metabolomics Results. Nieman DC. Human Performance Laboratory, North Carolina Research Campus and Appalachian State University

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1 Metabolomics Results Nieman DC., North Carolina Research Campus and Appalachian State University

2 Metabolomics Laboratory, North Carolina Research Campus, David H. Murdock Research Institute Slide 1

3 Blood/urine : PreEx Post Ex 1h Blood/urine : PreEx Post Ex 1h BASELINE TESTING for VO 2max, body composition (N=2 subjects) 1week 1 week 75km cycling 75km cycling 3week washout Crossover 1week 1week 75km cycling 75km cycling Metabolomics: Goal is to measure the influence of on small molecules (metabolites) that shift in response to supplementation. The shift in metabolites, depending on the nutritional product, may represent effects on inflammation, oxidative stress, and physiologic stress. Slide 2

4 Working Summary Slide 3 Seven days ingestion of (relative to placebo) caused an extensive mobilization of free fatty acids from adipose tissue in male cyclists. Athletes on for 7days started the 75km cycling trial with high blood free fatty acids leading to increased fat oxidation and a sparing of amino acids (and potentially muscle glycogen). intake was associated with a large increase in serum ascorbic acid levels (probably from the adrenal cortex). Serum creatinine and urea also increased postexercise.

5 Finding 1: Ingestion of beverage for one week strongly increased serum fatty acids levels (most likely from adipose tissue). 1) Chronic Effect: Higher fatty acid levels preexercise (several types of fatty acids see slides). 2, 1,5 1, 5 Myristic acid 14C Saturated Fatty Acid FDR=6.49E32 2) Acute Effect: Increased fatty acid oxidation and mobilization during exercise (placebo condition was linked to a late mobilization). Triglyceride Mobilization: corresponding with the increase in free fatty acids, glycerol was higher at baseline (indicative of extensive adipose triglyceride hydrolysis). 2, 1,5 1, 5 Myristic acid 14C Saturated Fatty Acid FDR=2.61E2 TG Hydrolysis FFAs + Glycerol with Slide 4

6 Post 7day Ingestion: Fatty Acids Higher in vs. Myristic acid 14C Saturated Fatty Acid FDR=6.49E32 Palmitic Acid 16C Saturated Fatty Acid FDR=1.86E25 2, 1,8 1,6 1,4 1,2 1, , 2, 15, 1, 5, Oleic Acid 18C Monounsaturated n9 Fatty Acid FDR=5.21E18 Stearic Acid 18C Saturated Fatty Acid FDR=3.22E Slide 5

7 7days Ingestion of Fatty Acids and Glycerol Backbone: Higher in vs. 1,2 1, Palmitelaidic Acid 16C Trans Fatty Acid FDR=1.13E Capric Acid 1C Saturated Fatty Acid FDR=5.39E7 Glycerol Backbone of Triglycerides FDR=9.49E Slide 6

8 Serum Fatty Acids During Exercise 2, 1,5 1, 5 Myristic acid 14C Saturated Fatty Acid FDR=2.61E2 25, 2, 15, 1, 5, Palmitic Acid 16C Saturated Fatty Acid FDR=1.56E2 1,2 1, Palmitelaidic Acid 16C Trans Fatty Acid FDR=1.66E16 2, 15, 1, 5, Oleic Acid 18C Monunsaturated n9 Fatty Acid FDR = 7.96E1 Slide 7

9 Serum Fatty Acids During Exercise 12, 1, 8, 6, 4, 2, Stearic Acid 18C Saturated Fatty Acids FDR=1.33E Capric Acid 1C Saturated Fatty Acids FDR=.59 1,2 1, Lauric Acid 12C Saturated Fatty Acids FDR= Glyercol Monosterate FDR =.6 Slide 8

10 Serum Aspartate FDR=.75 Serum Serine FDR=.273 Serum Glycine FDR=.162 Pyruvate In urea cycle Serum Fumarate FDR=1.6E6 Oxaloacetate Acetyl CoA Citrate Serum Citrate FDR =.37 Serum Threonine FDR=.18 Serum Malate FDR=.4 Malate Graph Key Isocitrate Fumarate alpha Ketoglutarate Via Beta Oxidation Serum Leucine FDR=.4 Succinate Succinyl CoA Finding 2: High levels of blood free fatty acids were linked to a sparing of amino acid catabolism, and increased Krebs Cycle intermediates, postexercise Slide 9 Via Odd Chain Beta Oxidation Serum Valine FDR=.89 Pre Via Glutamate Serum Proline FDR=.66 Post 1H Post

11 Serum Amino Acids at Pre, Post, and 1H PostExercise Sparing of Amino Acids with Leucine Krebs Entry: alpha Ketoglutarate FDR =.4 Proline Krebs Entry: alpha Ketoglutarate FDR =.66 3, 25, 2, 15, 1, 5, Lesat Square Mean Area 5, 4, 3, 2, 1, Aspartate Krebs Entry: Oxaloacetate FDR =.74 Valine Krebs Entry: Succinyl CoA FDR =.89 Lesat Square Mean Area Lesat Square Mean Area 5, 4, 3, 2, 1, Slide 1

12 Serum Amino Acids at Pre, Post, and 1H PostExericse Sparing of Amino Acids with Threonine Krebs Entry: Pyruvate FDR=.18 Serine Krebs Entry: Pyruvate FDR=.273 Lesat Square Mean Area 7, 6, 5, 4, 3, 2, 1, Lesat Square Mean Area 12, 1, 8, 6, 4, 2, Glycine Krebs Entry: Pyruvate FDR=.162 Lesat Square Mean Area Slide 11 Graph Key

13 Serum Krebs Intermediate at Pre, Post, and 1H PostExercise Higher Levels with Fumarate FDR = 1.6E6 Malate FDR=.4 Lesat Square Mean Area Lesat Square Mean Area Citrate FDR = Least Squre Mean Area Slide 12 Graph Key

14 3) Ascorbic Acid Metabolism: supplementation appears to be affecting ascorbic acid both acutely and chronically. Chronic Differences: group has lower baseline levels of fructose and lower levels of threonic acid. Fructose is broken down into ascorbic acid which is further metabolized into threonic acid. This could be suggestive of higher ascorbic acid production but no differences in groups were detected at baseline. Least Square Mean Area Fructose FDR=1.12E5 Least Square Mean Area Threonic Acid FDR=1.46E98 Acute Differences: group has higher levels of ascorbic acid, an antioxidant, and lower levels of both fructose and threonic acid. Least Square Mean Area 1,5 1, 5 Ascorbic Acid FDR = 5.6E6 Least Square Mean Area 1,5 1, 5 Fructose FDR =.2 Least Square Mean Area Threonic Acid FDR=.31 Slide 13 Graph Key

15 4) Other Changes. Some other changes were found both acutely and chronically that require further investigation into implications. Least Squre Mean Area Aminomalonic Acid FDR = 1.13E Serum Creatinine FDR=2.55 E6 Plays role in binding calcium to protein Breakdown product of creatine Urea FDR =.18 Graph Key Slide Formed in liver; Removal of nitrogen and ammonia

16 25 Blood Urinary Nitrogen (BUN) Normal Range: 82 mg/dl 2 mg/dl Pre Post 1H BUN levels did not differ between treatment (treatment x time pvalue=.9743) Slide 15

17 mg/dl Creatinine Normal Range:.71.2 mg/dl Pre Post 1H Creatinine levels did not differ between treatment (treatment x time pvalue=.7717) Slide 16

18 1 Bilirubin Normal Range:.31.2 mg/dl.8 mg/dl Pre Post 1H Bilirubin levels did not differ between treatment (treatment x time pvalue=.9971) Slide 17

19 68 Alkaline Phosphatase Normal Range: IU/L IU/L Pre Post 1H Alkaline Phosphatase levels did not differ between treatment (treatment x time pvalue=.8819) Slide 18

20 IU/L AST Normal Range: 1541 IU/L Pre Post 1H AST levels did not differ between treatment (treatment x time pvalue=.9546) Slide 19

21 IU/L ALT Normal Range: 1763 IU/L Pre Post 1H ALT levels did not differ between treatment (treatment x time pvalue=.9739) Slide 2