Top

Nutrition & Metabolism

Published in:

Open Access 01-12-2009 | Research

Effect of oral acetyl L-carnitine arginate on resting and postprandial blood biomarkers in pre-diabetics

Authors: Richard J Bloomer, Kelsey H Fisher-Wellman, Patrick S Tucker

Published in: Nutrition & Metabolism | Issue 1/2009

Abstract

Background

Resting and postprandial oxidative stress is elevated in those with metabolic disorders such as diabetes. Antioxidant supplementation may attenuate the rise in oxidative stress following feeding. Therefore we sought to determine the effects of acetyl L-carnitine arginate (ALCA) on resting and postprandial biomarkers of glucose and lipid metabolism, as well as oxidative stress.

Methods

Twenty-nine pre-diabetic men and women were randomly assigned to either 3 g·day^-1 of ALCA (n = 14; 31 ± 3 yrs) or placebo (n = 15; 35 ± 3 yrs) in a double-blind design, to consume for eight weeks. Fasting blood samples were taken from subjects both pre and post intervention. After each fasting sample was obtained, subjects consumed a high fat, high carbohydrate meal and additional blood samples were taken at 1, 2, 4, and 6 hours post meal. Samples were analyzed for a variety of metabolic variables (e.g., glucose, HbA1c, lipid panel, C-reactive protein, nitrate/nitrite, and several markers of oxidative stress). Area under the curve (AUC) was calculated for each variable measured post meal, both pre and post intervention.

Results

ALCA, but not placebo, resulted in an increase in nitrate/nitrite (25.4 ± 1.9 to 30.1 ± 2.8 μmol·L^-1) from pre to post intervention, with post intervention values greater compared to placebo (p = 0.01). No other changes of statistical significance were noted (p > 0.05), although ALCA resulted in slight improvements in glucose (109 ± 5 to 103 ± 5 mg·dL^-1), HbA1c (6.6 ± 1.1 to 6.2 ± 1.2%), and HOMA-IR (3.3 ± 1.3 to 2.9 ± 1.2). AUC postprandial data were not statistically different between ALCA and placebo for any variable (p > 0.05). However, nitrate/nitrite demonstrated a moderate effect size (r = 0.35) for increase from pre (139.50 ± 18.35 μmol·L^-1·6 hr^-1) to post (172.40 ± 21.75 μmol·L^-1·6 hr^-1) intervention with ALCA, and the magnitude of decrease following feeding was not as pronounced as with placebo.

Conclusion

Supplementation with ALCA results in an increase in resting nitrate/nitrite in pre-diabetics, without any statistically significant change in other metabolic or oxidative stress variables measured at rest or post meal.

Available only for authorised users

Rosamond W, Flegal K, Friday G, Furie K, Go A, Greenlund K, Haase N, Ho M, Howard V, Kissela B, Kittner S, Lloyd-Jones D, McDermott M, Meigs J, Moy C, Nichol G, O'Donnell CJ, Roger V, Rumsfeld J, Sorlie P, Steinberger J, Thom T, Wasserthiel-Smoller S, Hong Y, American Heart Association Statistics Committee and Stroke Statistics Subcommittee: Heart disease and stroke statistics – 2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2007, 115 (5): e69-171. 10.1161/CIRCULATIONAHA.106.179918.

American Diabetes Association: Diagnosis and classification of diabetes mellitus. Diabetes Care. 2005, 28 (Suppl 1): S37-42. 10.2337/diacare.28.suppl_1.S37.

O'Keefe JH, Bell DS: Postprandial hyperglycemia/hyperlipidemia (postprandial dysmetabolism) is a cardiovascular risk factor. Am J Cardiol. 2007, 100 (5): 899-904. 10.1016/j.amjcard.2007.03.107.

Ceriello A, Motz E: Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? The common soil hypothesis revisited. Arterioscler Thromb Vasc Biol. 2004, 24 (5): 816-823. 10.1161/01.ATV.0000122852.22604.78.

Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J: Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol. 2007, 39 (1): 44-84. 10.1016/j.biocel.2006.07.001.

Dalle-Donne I, Rossi R, Colombo R, Giustarini D, Milzani A: Biomarkers of oxidative damage in human disease. Clin Chem. 2006, 52 (4): 601-623. 10.1373/clinchem.2005.061408.

Yung LM, Leung FP, Yao X, Chen ZY, Huang Y: Reactive oxygen species in vascular wall. Cardiovasc Hematol Disord Drug Targets. 2006, 6 (1): 1-19.

Cai H, Harrison DG: Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res. 2000, 87 (10): 840-844.

Tushuizen ME, Nieuwland R, Scheffer PG, Sturk A, Heine RJ, Diamant M: Two consecutive high-fat meals affect endothelial-dependent vasodilation, oxidative stress and cellular microparticles in healthy men. J Thromb Haemost. 2006, 4 (5): 1003-1010. 10.1111/j.1538-7836.2006.01914.x.

10.

Tsai WC, Li YH, Lin CC, Chao TH, Chen JH: Effects of oxidative stress on endothelial function after a high-fat meal. Clin Sci (Lond). 2004, 106 (3): 315-319.

11.

Pastromas S, Terzi AB, Tousoulis D, Koulouris S: Postprandial lipemia: An under-recognized atherogenic factor in patients with diabetes mellitus. Int J Cardiol. 2008, 7;126 (1): 3-12. 10.1016/j.ijcard.2007.04.172.

12.

Miyazaki Y, Kawano H, Yoshida T, Miyamoto S, Hokamaki J, Nagayoshi Y, Yamabe H, Nakamura H, Yodoi J, Ogawa H: Pancreatic B-cell function is altered by oxidative stress induced by acute hyperglycaemia. Diabet Med. 2007, 24 (2): 154-160. 10.1111/j.1464-5491.2007.02058.x.

13.

Serin O, Konukoglu D, Firtina S, Mavis O: Serum oxidized low density lipoprotein, paraoxonase 1 and lipid peroxidation levels during oral glucose tolerance test. Horm Metab Res. 2007, 39: 207-211. 10.1055/s-2007-970419.

14.

Schindhelm RK, Alssema M, Scheffer PG, Diamant M, Dekker JM, Barto R, Nijpels G, Kostense PJ, Heine RJ, Schalkwijk CG, Teerlink T: Fasting and postprandial glycoxidative and lipoxidative stress are increased in women with type 2 diabetes. Diabetes Care. 2007, 30 (7): 1789-1794. 10.2337/dc06-2585.

15.

Ceriello A, Taboga C, Tonutti L, Quagliaro L, Piconi L, Bais B, Da Ros R, Motz E: Evidence for an independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on endothelial dysfunction and oxidative stress generation: effects of short- and long-term simvastatin treatment. Circulation. 2002, 106 (10): 1211-1218. 10.1161/01.CIR.0000027569.76671.A8.

16.

Nappo F, Esposito K, Cioffi M, Giugliano G, Molinari AM, Paolisso G, Marfella R, Giugliano D: Postprandial endothelial activation in healthy subjects and in type 2 diabetic patients: role of fat and carbohydrate meals. J Am Coll Cardiol. 2002, 39 (7): 1145-1150. 10.1016/S0735-1097(02)01741-2.

17.

Bae JH, Bassenge E, Kim KB, Kim YN, Kim KS, Lee HJ, Moon KC, Lee MS, Park KY, Schwemmer M: Postprandial hypertriglyceridemia impairs endothelial function by enhanced oxidant stress. Atherosclerosis. 2001, 155 (2): 517-523. 10.1016/S0021-9150(00)00601-8.

18.

Halliwell B: Oxygen radicals: a commonsense look at their nature and medical importance. Med Biol. 1984, 62 (2): 71-77.

19.

Bogani P, Galli C, Villa M, Visioli F: Postprandial anti-inflammatory and antioxidant effects of extra virgin olive oil. Atherosclerosis. 2007, 190 (1): 181-186. 10.1016/j.atherosclerosis.2006.01.011.

20.

Jenkins DJ, Kendall CW, Josse AR, Salvatore S, Brighenti F, Augustin LS, Ellis PR, Vidgen E, Rao AV: Almonds decrease postprandial glycemia, insulinemia, and oxidative damage in healthy individuals. J Nutr. 2006, 136 (12): 2987-2992.

21.

Ventura P, Bini A, Panini R, Marri L, Tomasi A, Salvioli G: Red wine consumption prevents vascular oxidative stress induced by a high-fat meal in healthy volunteers. Int J Vitam Nutr Res. 2004, 74 (2): 137-143. 10.1024/0300-9831.74.2.137.

22.

Neri S, Signorelli SS, Torrisi B, Pulvirenti D, Mauceri B, Abate G, Ignaccolo L, Bordonaro F, Cilio D, Calvagno S, Leotta C: Effects of antioxidant supplementation on postprandial oxidative stress and endothelial dysfunction: a single-blind, 15-day clinical trial in patients with untreated type 2 diabetes, subjects with impaired glucose tolerance, and healthy controls. Clin Ther. 2005, 27 (11): 1764-1773. 10.1016/j.clinthera.2005.11.006.

23.

Anderson RA, Evans LM, Ellis GR, Khan N, Morris K, Jackson SK, Rees A, Lewis MJ, Frenneaux MP: Prolonged deterioration of endothelial dysfunction in response to postprandial lipaemia is attenuated by vitamin C in Type 2 diabetes. Diabet Med. 2006, 23 (3): 258-264. 10.1111/j.1464-5491.2005.01767.x.

24.

Denniss SG, Haffner TD, Kroetsch JT, Davidson SR, Rush JW, Hughson RL: Effect of short-term lycopene supplementation and postprandial dyslipidemia on plasma antioxidants and biomarkers of endothelial health in young, healthy individuals. Vasc Health Risk Manag. 2008, 4 (1): 213-222. 10.2147/vhrm.2008.04.01.213.

25.

Calo LA, Pagnin E, Davis PA, Semplicini A, Nicolai R, Calvani M, Pessina AC: Antioxidant effect of L-carnitine and its short chain esters: relevance for the protection from oxidative stress related cardiovascular damage. Int J Cardiol. 2006, 107 (1): 54-60. 10.1016/j.ijcard.2005.02.053.

26.

Dokmeci D: Oxidative stress, male infertility and the role of carnitines. Folia Med (Plovdiv). 2005, 47 (1): 26-30.

27.

Di Giacomo C, Latteri F, Fichera C, Sorrenti V, Campisi A, Castorina C, Russo A, Pinturo R, Vanella A: Effect of acetyl-L-carnitine on lipid peroxidation and xanthine oxidase activity in rat skeletal muscle. Neurochem Res. 1993, 18 (11): 1157-1162. 10.1007/BF00978367.

28.

Vanella A, Russo A, Acquaviva R, Campisi A, Di Giacomo C, Sorrenti V, Barcellona ML: L -propionyl-carnitine as superoxide scavenger, antioxidant, and DNA cleavage protector. Cell Biol Toxicol. 2000, 16 (2): 99-104. 10.1023/A:1007638025856.

29.

Volek JS, Judelson DA, Silvestre R, Yamamoto LM, Spiering BA, Hatfield DL, Vingren JL, Quann EE, Anderson JM, Maresh CM, Kraemer WJ: Effects of carnitine supplementation on flow-mediated dilation and vascular inflammatory responses to a high-fat meal in healthy young adults. Am J Cardiol. 2008, 102 (10): 1413-1417. 10.1016/j.amjcard.2008.07.022.

30.

Bian K, Doursout MF, Murad F: Vascular system: role of nitric oxide in cardiovascular diseases. J Clin Hypertens (Greenwich). 2008, 10 (4): 304-310. 10.1111/j.1751-7176.2008.06632.x.

31.

Loffredo L, Marcoccia A, Pignatelli P, Andreozzi P, Borgia MC, Cangemi R, Chiarotti F, Violi F: Oxidative-stress-mediated arterial dysfunction in patients with peripheral arterial disease. Eur Heart J. 2007, 28 (5): 608-612. 10.1093/eurheartj/ehl533.

32.

Bloomer RJ, Smith WA, Fisher-Wellman KH: Oxidative stress in response to forearm ischemia-reperfusion with and without carnitine administration. Int J Vitam Nutr Res. 2009,

33.

Bloomer RJ, Smith WA, Fisher-Wellman KH: Glycine propionyl-L-carnitine increases plasma nitrate/nitrite in resistance trained men. J Int Soc Sports Nutr. 2007, 4: 22-10.1186/1550-2783-4-22.

34.

Collier J, Vallance P: Physiological importance of nitric oxide. BMJ. 1991, 302 (6788): 1289-1290. 10.1136/bmj.302.6788.1289.

35.

Weiss EP, Park JJ, McKenzie JA, Park JY, Kulaputana O, Brown MD, Phares DA, Hagberg JM: Plasma nitrate/nitrite response to an oral glucose load and the effect of endurance training. Metabolism. 2004, 53 (5): 673-679. 10.1016/j.metabol.2003.12.017.

36.

Ceriello A: New insights on oxidative stress and diabetic complications may lead to a "causal" antioxidant therapy. Diabetes Care. 2003, 26 (5): 1589-1596. 10.2337/diacare.26.5.1589.

37.

Jackson AS, Pollock ML: Generalized equations for predicting body density of men. Br J Nutr. 1978, 40 (3): 497-504. 10.1079/BJN19780152.

38.

Siri WE: Body composition from fluid spaces and density – analysis of methods. Techniques for measuring body composition. Edited by: Brozek J, Henschel A. 1961, Washington, DC: National Academy of Sciences, 223-244.

39.

Bode-Boger SM, Boger RH, Creutzig A, Tsikas D, Gutzki FM, Alexander K, Frolich JC: L-arginine infusion decreases peripheral arterial resistance and inhibits platelet aggregation in healthy subjects. Clin Sci (Lond). 1994, 87 (3): 303-310.

40.

Giugliano D, Marfella R, Verrazzo G, Acampora R, Coppola L, Cozzolino D, D'Onofrio F: The vascular effects of L-Arginine in humans. The role of endogenous insulin. J Clin Invest. 1997, 99 (3): 433-438. 10.1172/JCI119177.

41.

Lin CC, Tsai WC, Chen JY, Li YH, Lin LJ, Chen JH: Supplements of L-arginine attenuate the effects of high-fat meal on endothelial function and oxidative stress. Int J Cardiol. 2008, 127 (3): 337-341. 10.1016/j.ijcard.2007.06.013.

42.

Bloomer RJ, Cole BJ, Fisher-Wellman KH: Racial differences in postprandial oxidative stress with and without acute exercise. Int J Sport Nutr Exerc Metab. 2009,

43.

Bloomer RJ, Ferebee DE, Fisher-Wellman KH, Quindry JC, Schilling BK: Postprandial oxidative stress: Influence of gender and exercise training status. Med Sci Sports Exerc. 2009,

44.

Melton CE, Tucker PS, Fisher-Wellman KH, Bloomer RJ: Acute exercise does not attenuate postprandial oxidative stress in pre-diabetic women. The Physician and Sportsmedicine. 2009,

45.

Bloomer RJ, Fisher-Wellman KH: Systemic oxidative stress is increased to a greater degree in young, obese women following consumption of a high fat meal. Medicine and Cellular Longevity. 2009, 2 (1): 1-7.

46.

Bloomer RJ, Fisher-Wellman KH: Postprandial oxidative stress in exercise trained and untrained cigarette smokers. International Journal of Environmental Research and Public Health. 2009, 6: 579-591. 10.3390/ijerph6020579.

47.

Bloomer RJ, Solis AD, Fisher-Wellman KH, Smith WA: Postprandial oxidative stress is exacerbated in cigarette smokers. Br J Nutr. 2008, 99 (5): 1055-1060. 10.1017/S0007114507844370.

48.

Jentzsch AM, Bachmann H, Furst P, Biesalski HK: Improved analysis of malondialdehyde in human body fluids. Free Radic Biol Med. 1996, 20 (2): 251-256. 10.1016/0891-5849(95)02043-8.

49.

Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC: Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985, 28 (7): 412-419. 10.1007/BF00280883.

50.

Katsanos CS, Moffatt RJ: Acute effects of premeal versus postmeal exercise on postprandial hypertriglyceridemia. Clin J Sport Med. 2004, 14 (1): 33-39. 10.1097/00042752-200401000-00006.

51.

Zhu W, Zhong C, Yu Y, Li K: Acute effects of hyperglycaemia with and without exercise on endothelial function in healthy young men. Eur J Appl Physiol. 2007, 99 (6): 585-591. 10.1007/s00421-006-0378-3.

52.

Mc Clean CM, Mc Laughlin J, Burke G, Murphy MH, Trinick T, Duly E, Davison GW: The effect of acute aerobic exercise on pulse wave velocity and oxidative stress following postprandial hypertriglyceridemia in healthy men. Eur J Appl Physiol. 2007, 100 (2): 225-234. 10.1007/s00421-007-0422-y.

53.

Pruessner JC, Kirschbaum C, Meinlschmid G, Hellhammer DH: Two formulas for computation of the area under the curve represent measures of total hormone concentration versus time-dependent change. Psychoneuroendocrinology. 2003, 28 (7): 916-931. 10.1016/S0306-4530(02)00108-7.

54.

Edwards DG, Schofield RS, Lennon SL, Pierce GL, Nichols WW, Braith RW: Effect of exercise training on endothelial function in men with coronary artery disease. Am J Cardiol. 2004, 93 (5): 617-620. 10.1016/j.amjcard.2003.11.032.

55.

Tordi N, Colin E, Mourot L, Bouhaddi M, Regnard J, Laurant P: Effects of resuming endurance training on arterial stiffness and nitric oxide production during exercise in elite cyclists. Appl Physiol Nutr Metab. 2006, 31 (3): 244-249. 10.1139/H05-033.

56.

Poveda JJ, Riestra A, Salas E, Cagigas ML, Lopez-Somoza C, Amado JA, Berrazueta JR: Contribution of nitric oxide to exercise-induced changes in healthy volunteers: effects of acute exercise and long-term physical training. Eur J Clin Invest. 1997, 27 (11): 967-971. 10.1046/j.1365-2362.1997.2220763.x.

57.

Beckman JS, Koppenol WH: Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am J Physiol. 1996, 271 (5 Pt 1): C1424-37.

58.

Gulcin I: Antioxidant and antiradical activities of L-carnitine. Life Sci. 2006, 78 (8): 803-811. 10.1016/j.lfs.2005.05.103.

59.

Corbucci GG, Montanari G, Mancinelli G, D'Iddio S: Metabolic effects induced by L-carnitine and propionyl-L-carnitine in human hypoxic muscle tissue during exercise. Int J Clin Pharmacol Res. 1990, 10 (3): 197-202.

60.

Sachan DS, Hongu N, Johnsen M: Decreasing oxidative stress with choline and carnitine in women. J Am Coll Nutr. 2005, 24 (3): 172-176.

61.

Rauchova H, Koudelova J, Drahota Z, Mourek J: Hypoxia-induced lipid peroxidation in rat brain and protective effect of carnitine and phosphocreatine. Neurochem Res. 2002, 27 (9): 899-904. 10.1023/A:1020339530924.

62.

Rajasekar P, Viswanathan P, Anuradha CV: Renoprotective action of L-carnitine in fructose-induced metabolic syndrome. Diabetes Obes Metab. 2008, 10 (2): 171-180.

63.

Murphy MC, Isherwood SG, Sethi S, Gould BJ, Wright JW, Knapper JA, Williams CM: Postprandial lipid and hormone responses to meals of varying fat contents: modulatory role of lipoprotein lipase?. Eur J Clin Nutr. 1995, 49 (8): 578-588.

64.

Dubois C, Beaumier G, Juhel C, Armand M, Portugal H, Pauli AM, Borel P, Latge C, Lairon D: Effects of graded amounts (0–50 g) of dietary fat on postprandial lipemia and lipoproteins in normolipidemic adults. Am J Clin Nutr. 1998, 67 (1): 31-38.

65.

Cohen JC, Noakes TD, Benade AJ: Serum triglyceride responses to fatty meals: effects of meal fat content. Am J Clin Nutr. 1988, 47 (5): 825-827.

66.

Blendea MC, Bard M, Sowers JR, Winer N: High-fat meal impairs vascular compliance in a subgroup of young healthy subjects. Metabolism. 2005, 54 (10): 1337-1344. 10.1016/j.metabol.2005.04.023.

67.

Mohanty P, Ghanim H, Hamouda W, Aljada A, Garg R, Dandona P: Both lipid and protein intakes stimulate increased generation of reactive oxygen species by polymorphonuclear leukocytes and mononuclear cells. Am J Clin Nutr. 2002, 75 (4): 767-772.

68.

69.

van Oostrom AJ, Sijmonsma TP, Verseyden C, Jansen EH, de Koning EJ, Rabelink TJ, Castro Cabezas M: Postprandial recruitment of neutrophils may contribute to endothelial dysfunction. J Lipid Res. 2003, 44 (3): 576-583. 10.1194/jlr.M200419-JLR200.

70.

Du X, Edelstein D, Obici S, Higham N, Zou MH, Brownlee M: Insulin resistance reduces arterial prostacyclin synthase and eNOS activities by increasing endothelial fatty acid oxidation. J Clin Invest. 2006, 116 (4): 1071-1080. 10.1172/JCI23354.

71.

Vincent HK, Innes KE, Vincent KR: Oxidative stress and potential interventions to reduce oxidative stress in overweight and obesity. Diabetes Obes Metab. 2007, 9 (6): 813-839. 10.1111/j.1463-1326.2007.00692.x.

72.

Calisti L, Tognetti S: Measure of glycosylated hemoglobin. Acta Biomed. 2005, 76 (Suppl 3): 59-62.

Title: Effect of oral acetyl L-carnitine arginate on resting and postprandial blood biomarkers in pre-diabetics
Authors: Richard J Bloomer
Kelsey H Fisher-Wellman
Patrick S Tucker
Publication date: 01-12-2009
Publisher: BioMed Central
Published in: Nutrition & Metabolism / Issue 1/2009
Electronic ISSN: 1743-7075
DOI: https://doi.org/10.1186/1743-7075-6-25

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2009

Erratum to: Physiological models of body composition and human obesity

Suppressive response of confections containing the extractive from leaves of Morus Alba on postprandial blood glucose and insulin in healthy human subjects

Plasma PLTP activity is inversely associated with HDL-C levels

Erratum to: Effects of alpha-linolenic acid vs. docosahexaenoic acid supply on the distribution of fatty acids among the rat cardiac subcellular membranes after a short- or long-term dietary exposure

Quantitation of alpha-linolenic acid elongation to eicosapentaenoic and docosahexaenoic acid as affected by the ratio of n6/n3 fatty acids

Effect of high amylose maize starches on colonic fermentation and apoptotic response to DNA-damage in the colon of rats

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials