Join Us | Latest Articles | Contact

Journal Home


Editorial Board


Recent Articles


Submit to this journal


Special Issues


Current issue

International Journal of Clinical Cardiology





DOI: 10.23937/2378-2951/1410006



Energy Drink Ingredients and their Effect on Endothelial Function: A Review

John P. Higgins* and Brandon L. Ortiz


Lyndon B. Johnson General Hospital, The University of Texas Health Science Center at Houston (UT Health) and Memorial Hermann Sports Medicine Institute, USA


*Corresponding author: John P. Higgins, Associate Professor of Medicine, The University of Texas Medical School at Houston, LBJ General Hospital, 5656 Kelley St, UT Annex-Room 104, Houston, TX 77026-1967, USA, Tel: 713-500-6836; Fax: 713-500-5912; E-mail: John.P.Higgins@uth.tmc.edu
Int J Clin Cardiol, IJCC-1-006, (Volume 1, Issue 1), Review Article; ISSN: 2378-2951
Received: October 13, 2014 | Accepted: October 29, 2014 | Published: October 31, 2014
Citation: Higgins JP, Ortiz BL. (2014) Energy Drink Ingredients and their Effect on Endothelial Function: A Review.Int J Clin Cardiol 1:006. 10.23937/2378-2951/1410006
Copyright: © 2014 Higgins JP, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.



Introduction

It is an age-old idea to try to boost one's performance in order to achieve an elusive goal or conquer an obstacle. Many energy products, especially energy drinks (ED) are now marketed to this need, and examples include Red Bulls' 'Gives You Wings,' as well as Monster Energy's 'Unleash the Beast' advertising campaigns [1,2].

In the light of ED consumption recently being associated with high risk behaviors, unhealthy habits, and some deaths in adolescents and young adults, especially when consumed while exercising, the Food and Drug Agency and the scientific community is now asking for more evidence as to whether these EDs work, what is in them, who should use them, and what if any is a safe dose [3-6].

Studies on the effects of EDs to improve ones physical or cognitive performance have yielded mixed results [7-12]. In a systematic review of the ED ingredients that examined them alone or in combination with caffeine to assess the claims of enhancing physical and cognitive performance, 32 articles found some evidence, albeit weak, to support the claims for glucose and guarana [13]. As for the other common ingredients of taurine, ginseng, B vitamins, glucuronolactone and others, there was an overwhelming lack of evidence for their enhancing physical and cognitive performance [13]. Clearly, more studies that are well designed to examine the effects of EDs and their components are needed to clarify their effects.

The consumption of EDs before or during exercise might be linked to an increased risk for myocardial ischemia in association with endothelial dysfunction [14]. A case report suggested that abnormal vascular function, specifically coronary artery spasm, may have been the result of the high levels of taurine and caffeine in the ED [15]. Several studies have noted reduced endothelial cell function (ECF) following ED consumption [14,16,17]; others have shown no difference [10]. In addition, caffeine, which is often present in high concentrations in EDs, has been associated with reduced myocardial blood flow during exercise [18].

It has been commonly accepted that ECF is closely related to cardiovascular risk, with impairment being involved in the pathogenesis of atherosclerosis and coronary artery disease (CAD) [19,20]. Impairment of ECF is also related to a decrease in the bioavailability of nitric oxide, a vasodilator and inhibitor of platelet aggregation, which also has anti-inflammatory and anti-proliferative properties [19]. ECF is commonly measured indirectly by flow-mediated dilatation (FMD) in the brachial artery, which is well validated, and serves as a strong predictor of cardiovascular events [19,20]. Due to the various uses of tracking ECF in the process of CAD and other diseases, it is important to determine what effects the various components of ED have on ECF alone or in combination as part of an ED. The goal of this review is to summarize the known effects of the individual ingredients of ED have on ECF.


Methods

A search of the English-language scientific literature was performed primarily by searching MEDLINE, PubMed, EMBASE, The Cochrane Library, CINAHL Plus, Google Scholar for the time period 1976 through September 2014. Keywords used in the search included the name of each ingredient e.g. 'L-carnitine' AND 'endothelial function'. The bibliographies of articles from the above searches were also explored for relevant articles, and links on websites containing published papers were searched for pertinent information. The final results were pared down to include only human trials and in vivo studies.


Results

L-carnitine: L-carnitine (LC) is synthesized in the body from lysine and methionine [21]. It serves as a carboxylic acid that plays a vital role in the transport of fatty acids into mitochondria for ß-oxidation, while also preventing accumulation of toxic acyl-CoA [13]. Currently there is no experimental evidence to support claims of improvement in physical or cognitive improvements from LC supplementation. One study investigated LC on vascular function in diabetes and heart disease by testing volunteer subjects after free fatty acid elevations both with and without LC supplementation [22]. They found that LC may in fact attenuate free fatty acid induced and obesity associated endothelial dysfunction. Limits of the study include that the delivery of LC was intravenous, the subjects were healthy, and effects of LC supplementation were examined in the short term only. Another study observed the effects of LC during three weeks of 2 g/day supplementation and observed the postprandial FMD after a high fat meal at baseline and after supplementation in healthy individuals [23]. They found a significant improvement in FMD after the healthy subjects were given a high fat meal, and determined the effects were probably independent of postprandial lipemic response.

Another review focused on carnitine, specifically the isomer Propionyl-L-carnitine (PLC), which exhibits high affinity for both skeletal and cardiac muscle, and is rapidly converted to LC when given exogenously [24]. They noted improvement of endothelial-dependent dilation in endothelial dysfunction when subjects were given PLC supplementation. Other effects included decreased body weight and abdominal adiposity, decreased vascular inflammation, triglycerides, low-density lipoprotein cholesterol, atherosclerotic lesions, lipid peroxidation, improved peripheral arterial disease symptoms, and possible improvement in myocardial function after ischemia. A further study also showed the benefit of PLC in improving ECF and pain management in critical limb ischemia in the end processes of peripheral arterial disease [25]. They suggested the beneficial effect of PLC on the arterial wall occurred through anti-proliferative, as well as pro-apoptotic effects on smooth muscle cells, leading to functional improvement in the peripheral arterial disease.

Guarana: Guarana (Paulliniacupana) is a plant from Brazil whose caffeine concentrations is 2-15% of its dry weight (about twice that of coffee beans), and it exhibits antioxidant effects and can decrease platelet aggregation [13,26]. There has been inconsistent evidence for its improvement in cognitive function due to the effects of the ingredients other than caffeine, and no experimental evidence for improvement in physical performance [3,27]. No studies showed any effect of guarana on ECF, whether alone or in conjugation with another substance.

Glucuronolactone: Glucuronolactone is a naturally occurring metabolite in liver derived from glucose that serves as a precursor for ascorbic acid synthesis, an antioxidant, and as a structural component of connective tissues [13]. One study evaluating glucuronolactone as a component of an ED showed reduced ECF and platelet function from the ED, but it did not specifically test the glucuronolactone component separately [16]. Though endothelial dysfunction and platelet impairment has been found to be associated with increased glucose levels, given glucuronolactone is a glucose metabolite, it may also result in detrimental effects on ECF and platelet function [13].

Taurine: Taurine is a non-essential amino acid that is found in high concentrations in the brain, heart, and skeletal muscle [13]. It is involved in the process of conjugating bile acids with chenodeoxycholic acid and cholic acid. In toxicology studies, there have been no adverse effects of taurine supplementation with levels up to 1,000 mg per kilogram of body weight when dosing. There has been mixed results regarding the benefits of use before and during exercise on improving physical performance; in addition, it is also unlikely that increased plasma taurine levels would alter brain levels and neurotransmitters in young adults [13].

A study of taurine and vitamin C supplementation in young smokers noted protective effects on ECF when exposed to pro-inflammatory insults [28]. The study found that taurine and vitamin C may restore the ECF in the young smokers by modifying monocyte-endothelial interactions and thus attenuating impairment of FMD. While vitamin C supplementation did improve FMD, its effect was not as great as taurine. The study also found no adverse effects of taurine supplementation, and that a taurine dose equivalent to 100g of fresh fish would likely reduce risk of coronary artery disease [28].

Taurine, by potentiating the effect of insulin and insulin receptors may benefit diabetic patient's blood glucose levels, which may then improve ECF [29]. In a study of males less than 30 years of age with type I diabetes mellitus, after two weeks supplementation with taurine, the FMD of the subjects improved. However, another study found large quantities of taurine as part of an ED resulted in detrimental effects on platelet function and ECF [16]. They also reported a significant increase in mean arterial pressure, a significant increase in platelet aggregation, and a significant decrease in ECF. Although taurine was found in high levels in platelets, its exact function on platelets remains unknown. Further, due to previously reported beneficial effects of taurine, the authors speculated that it was unlikely that the negative effects of ED on platelets and ECF were due to the taurine component [16]. However, they could not rule out some interaction effect from between taurine and the other components resulting in worsening of ECF.

Ginseng: There has been no experimental evidence to support any benefit in enhancing physical or cognitive performance from ginseng being added to an ED [13]. Ginseng is available in various forms and types: root, powdered form, Korean and American red ginseng. One study examined the effects of Korean Red Ginseng (KRG) and its metabolites on arterial stiffness in healthy individuals [30]. The augmentation index and blood pressures were measured at baseline and every hour for three hours after treatment with a 3 g KRG dose. An increase in the augmentation index is known to unfavorably affect ventricular after load and compromise coronary perfusion. It was found that the acute consumption of KRG resulted in significant reduction of the augmentation index and also it did indeed cause vasodilation via increases in nitric oxide levels in healthy individuals [30]. The authors suggested that the increase in vasodilation, as well as other effects including inhibition of platelet adhesion, and stimulation of nitric oxide release, were likely attributed to ginsenosides, a class of steroid glycosides, found exclusively in the plant genus Panax (ginseng).

KRG was also studied to determine its effect on arterial stiffness in those with hypertension. In contrast to the former study, after receiving a dose of 3 g per day for 3 months, KRG did not result in a significant decrease in blood pressure nor did it improve atherosclerosis [31]. In contrast, a study using American Red Ginseng (ARG) on arterial stiffness in those with type 2 diabetes mellitus with concomitant hypertension showed significant benefit [31]. They noted that ARG improved ECF and arterial stiffness in healthy, those with hypertension, and even type 2 diabetes mellitus by increasing nitric oxide bioavailability. ARG was found to have significantly lower radial augmentation index and systolic blood pressure. However, the true physiologic effects of ARG may not be known due to the many different marketed preparations; further, when whole ARG was tested, it only showed neutral effects on blood pressure and ECF both in the acute and long term setting. Further testing and stricter parameters need to be defined in relation to the exact preparations of ginseng, and evaluation in long-term studies before any recommendations for adjunct treatment can be made [32].

B Vitamins: Many manufacturers tout their complexes of B vitamins as a major contributor to the energy enhancing abilities of their EDs. This section will cover riboflavin (B2), niacin (B3), pyridoxine (B6), inositol (B8), folate (B9), and cobalamin (B12) in respect to ECF. As far as their effect in improving physical and cognitive performance, there has been no evidence supporting the addition of B vitamins to ED that explain improved effects beyond those of caffeine alone.

Riboflavin (Vitamin B2): Articles reviewed only addressed riboflavin's use in possible ophthalmological treatments in certain diseases of the cornea, or its effect in promoting lung cancer progression in high doses [33]. No papers addressed its effects on the vascular system.

Niacin (Vitamin B3): Niacin was studied in several different populations concerning its effects on vascular function. Niacin still serves as the most potent therapy to increase high-density lipoprotein cholesterol, and studies on statin-naive patients show improvement in ECF [34]. Extended release niacin given to metabolic syndrome patients was found to cause a regression in carotid intima-media thickness, improving high-density lipoprotein cholesterol, reducing low-density lipoprotein cholesterol and triglyceride levels, improving ECF, and decreasing vascular inflammation as measured by a decrease in C-reactive protein levels [35]. The improvement in ECF with niacin was consistent with previous studies that showed similar improvement after three months of treatment [35]. Another study evaluated the effect of niacin in coronary artery disease (CAD) patients and endothelial dysfunction and found an improvement in FMD, though only in patients with low high-density lipoprotein cholesterol at baseline [36]. However, no effect on glucose metabolism or inflammatory markers was found in this study [36].

Another study evaluating niacin therapy for twelve months also showed a significant decrease in carotid intima-media thickness as well as an improvement in ECF [37]. In patients with diabetes mellitus type 2 already on statin therapies, addition of niacin was also found to significantly improve brachial FMD and small artery compliance [38]. Niacin was studied to determine its effects on FMD in patients already on high dose statin therapy for CAD. After three months, niacin therapy was still able to significantly improve lipid profiles, but had no observed improvements in FMD [39]. The study further clarified that the low-density lipoprotein cholesterol levels in the subjects were significantly below target levels which may have influenced the effects shown on FMD with extended-release-niacin treatment.


Pyridoxine (Vitamin B6),Folate (Vitamin B9), and Cobalamin (Vitamin B12):

Studies usually group these vitamins so they will be discussed together.

One study evaluated the possible benefits of homocysteine (HCY) lowering treatment with pyridoxine and folate therapy, and found both improved HCY levels and ECF in those with hyperhomocysteinemia (HHC) [40]. Another study also examined pyridoxine and folate therapy on HHC patients after three months of treatment, but found only significant improvement in biomarkers of ECF after a pyridoxine load at baseline, not after the test period [41]. An additional study was done to investigate the effects of pyridoxine supplementation in cardiac transplant patients, as HHC is common and associated with transplant CAD that can be predicted by endothelial dysfunction [42]. Although no significant change in plasma HCY levels was seen, there was a significant association between pyridoxine and improved ECF. In addition, pyridoxine deficiency is linked to premature CAD and impaired oxidative defense mechanisms due to a reduction in the ratio of reduced to oxidized glutathione, as reduced glutathione itself improves ECF [42].

A two year trial looked at the effects of folate and pyridoxine treatment and determined the only significant associations were with lower systolic and diastolic pressures, but no effects could be demonstrated with the HCY lowering treatment on brachial FMD or carotid artery stiffness in healthy individuals [43]. One study evaluated the use of folate, pyridoxine and cobalamin administration on endothelial dysfunction induced by post-methionine load HHC finding a significant improvement of FMD with the short term vitamin administration [44]. Another similar combination study found significant decreases in HCY levels, improved endothelium dependent dilation, and improved exercise performance while decreasing exercise induced ischemia in patients with CAD and HHC [45]. Yet another group using the folate, pyridoxine and cobalamin showed no effect on the markers of ECF in healthy volunteers [46]. Two further studies using this combination in patients with recent myocardial infarctions or with previous TIAs or stroke found no benefits in markers of inflammation or ECF [47,48]. One additional study on stroke patients explored the effects of long term combination therapy on lowering HCY levels and on carotid intima-media thickness and FMD [49]. The subjects had a mean treatment period of four years and while the treatment group had significantly lowered its plasma HCY levels, and there was no significant difference in carotid intima-media thickness or FMD. They also conducted a meta-analysis as a part of their study that suggested combination treatment would actually decrease carotid intima-media thickness and increase FMD. While these effects were significant in the short term studies, over a long-term treatment period, combination therapy did not significantly improve FMD or carotid intima-media thickness in patients with a history of stroke [50].

Cobalamin and folate were studied in patients with CAD after eight weeks of treatment and showed improved FMD, significant lowered levels of total plasma HCY, protein bound HCY, and free HCY [50]. This research was unique in that it studied the different ways HCY levels can be measured and the subsequent effects of treatment with B vitamins have on them. It was found that the FMD correlated closely with reduction in free HCY, independent of protein bound HCY, folate or cobalamin levels. They postulated that the improved FMD in ECF of patients with CAD was mediated via this decrease in free HCY. After two months of treatment with folate and cobalamin, patients with metabolic syndrome were found to have significant decreases in HCY and insulin levels, while exhibiting significant improvements in ECF [51]. Another study examined the effects of cobalamin deficiency in subjects with a homozygous mutation, but with no symptoms of coronary, brain or peripheral artery disease and determined that these individuals had high HCY levels, severe forearm endothelial dysfunction and a high prevalence of cobalamin deficiency [52]. They noted that cobalamin therapy was able to normalize ECF.

Inositol (Vitamin B8): Inositol which is a component of phosphatidylinositol lipids, also serves as a second messenger, where it triggers release of calcium in cells and transmission of messages between neural cells, and facilitates transport of fat within cells [53]. Currently, there are no studies examining the effects of inositol on ECF alone, or even in conjugation with other compounds in either healthy or diseased states.

Glucose: Glucose has been found to extend endurance exercise as long as it is consumed at regular intervals in fluids at levels of 6-8% of content rather than the 11-12% that is commonly found in ED that can slow gastric emptying [13]. The combination of glucose and caffeine may enhance cognitive performance in sleep deprived individuals for 30-60 minutes post ingestion, though with inconsistent evidence causing improvements in physical or cognitive improvement on its own. A study exploring the relation of plasma glucose levels on ECF in those without diabetes found that FMD significantly decreased in those with impaired fasting glucose [54]. Thus hyperglycemia plays a significant role in the pathogenesis of vascular dysfunction at different stages of diabetes mellitus development, while also playing an important role in the development of atherosclerosis even in pre-diabetics. Children with type 1 diabetes mellitus also show endothelial dysfunction when compared to controls [55].

The effect of the glucose spike and peak during an oral glucose tolerance test was studied to verify the effect of spike compared to peak on ECF and the possible involvement of oxidative stress [56]. It was found that the incremental increase in glucose correlated with a decrease in ECF, that the glucose spike may be a stronger predictor of carotid intima-media thickness, and that oxidative stress works as an integral part in changes of ECF and can be mediated by vitamin C supplements. Another strategy to asses hyperglycemia effects on vascular function was to examine glycemic variability in those with metabolic syndrome and diabetes mellitus type 2 [57]. These researchers found that FMD decreased while carotid intima-media thickness increased across groups with increase glycemic variability. This increase in variability may precede established hyperglycemia and be associated with endothelial dysfunction. Another study of obese children and adolescents and the effect of postprandial hyperglycemia on ECF, inflammation and oxidative stress determined that an acute oral glucose load did not reduce ECF or increase levels of inflammation or oxidative stress [58]. Thus, the arteries may be able to retain their ability to regulate blood flow and dilatory capacity within a postprandial setting during childhood, even in the content of obesity [58].

Low versus high glycemic indices during hypocaloric diets were tested for three months in overweight and obese adults without diabetes, yet at increased risk for CAD, and showed improved ECF and glycemic variability in those relegated to a low glycemic index hypocaloric diet [4]. Post-prandial hyperglycemia was found to transiently decrease FMD responses in healthy individuals, while those with impaired glucose tolerance, or even overt diabetes mellitus had a more pronounced response [59]. Post-prandial hyperglycemia appears to impair vascular function in an oxidative stress dependent manner, likely from inducing peroxidation of lipids. In subjects with normal glucose tolerance, it was found that post-prandial hyperglycemia effects on ECF was associated with short term decreases in FMD; those with insulin resistance also showed short term impairment in ECF [60]. Improvement of the fasting FMD correlated with an improvement of insulin resistance [60].

Caffeine: Pure caffeine and its effect on ECF are different to those of caffeine when consumed as coffee or as part of an ED [18]. Indeed, coffee and EDs contains substances other than caffeine that are known to have antioxidative effects and may improve ECF [18].

When studied in healthy subjects who were regular non-heavy coffee drinkers, caffeinated coffee showed a decrease in FMD, whereas decaffeinated coffee showed no significant difference in FMD [61]. The unfavorable effects of coffee on ECF in healthy adults lasted up to an hour. When testing a load of 300 mg of oral caffeine, a significant increase was found in both diastolic and systolic blood pressures, but no alterations were found in heart rate or forearm blood flow in healthy subjects [62]. Though caffeine ingestion did not increase forearm blood flow directly, it did seem to increase forearm blood flow response to acetylcholine in a significant manner suggesting that caffeine augments endogenous nitric oxide production by agonist stimulation, even though simultaneously causing vasoconstrictive effects as an adenosine receptor antagonist [62].

A study that evaluated healthy and diabetic women showed those diabetics who had caffeinated coffee had decreased levels of inflammatory markers, while the healthy subjects had the same effect but with decaffeinated coffee [63]. Additionally, with either the caffeinated or decaffeinated coffee, no detrimental effects were observed on ECF. One study tried to address this discrepancy by trying to determine whether caffeine or the antioxidants in the coffee determined the type of change in FMD [64]. What was determined was that antioxidant levels were higher in the caffeinated coffee, and thus responsible for the increase in FMD. Though the detrimental effects of caffeine on FMD cannot be blunted solely by antioxidants, further studies are needed to evaluate the long term effects of coffee in relation to caffeine and antioxidant consumption. Another study with decaffeinated versus caffeinated coffee in healthy subjects showed a significant, acute progressive decrease in FMD after caffeinated, but no change with decaffeinated coffee [65]. A final study studied caffeine ingestion in patients with and without CAD noted that acute caffeine ingestion significantly increased FMD and decreased C-reactive protein in comparison to placebo group [66]. These results were seen in the CAD subjects and subjects without CAD after ingesting 200 mg of purified caffeine in a capsule instead of a drink. This was the first study to test caffeine this way, and the first to show improved brachial ECF and decreased inflammatory markers in patients with CAD [66].
Table 1 summarizes the effects of the various components of EDs on ECF.


Table 1: Effects of Energy Drink Ingredient of Endothelial Function.
Table 1: Effects of Energy Drink Ingredient of Endothelial Function. View Table 1


Discussion

While many ingredients in ED have the potential to effect ECF, more research is needed to determine their specific effects alone and in combination with other ingredients. Researchers have only begun research on guarana, inositol, glucuronolactone and riboflavin using strict protocols with enough power to produce recommendations for therapy if beneficial results are found. Most of the results with LC suggest the compound may provide some benefits in a diseased state.

Further research for taurine should be directed at elucidating its real function in platelets, and like LC, how it works in healthy individuals and what goals can be deemed acceptable for use in therapies. The next step for ginseng, is to determine the ideal preparation that can be used to garner positive effects in the healthy and diseased individuals, since its two most popular forms, KRG and ARG, have yielded mixed results.

Niacin is the only one of the ED ingredients that is used as pharmacologic therapy, with recent evidence supporting its benefits. Further studies will help clarify to what point niacin as an adjunct therapy will be beneficial to the patient, and if there is any benefit to using niacin for therapy alone or for possible disease prevention, especially with respect to improvement in ECF. Pyridoxine and cobalamin need further studies examining them without folate, to determine their effects not only in individuals with HHC, but if there is any added benefits to supplementation in healthy and/or those at increased risk for disease.

Abnormally high levels of glucose are generally detrimental to ECF [67]. More research on the types of glucose lowering treatment, and how much they improve ECF when preventing disease is needed.

Finally, caffeine may be the most controversial of all the ingredients since there are many studies with coffee exhibiting mixed results. The next step in research should focus on purified capsules of caffeine at different doses, and studying their effects on vascular function to determine recommendations on safe daily amounts of ingestion.


Conclusion

While some components of ED's may have been shown to improve ECF, some appear to be detrimental, while others have just not been studied. Further, the popular EDs mix together glucose, high levels of caffeine, glucose, B-vitamins, L-Carnitine, Guarana, Glucuronolactone, Taurine, Ginseng and other components as part of an energy blend. In order to better understand the effect of consumption of these drinks on ECF, it is likely that an approach will be required which evaluates each of the components of the EDs separately as well as their effect in combination, both at rest and during exercise. Specifically, we need to determine if there is an interaction between the ingredients of EDs that may result in an acute adverse effect on ECF, which could possibly result in adverse effects. In addition, more research is required to determine what, if any, are safe levels of consumption of EDs, and whether they are efficacious with respect to improving performance as their manufacturers claim i.e. safety and efficacy studies are needed. Given the associations between ED consumption and reported adverse events and deaths, it behooves us to study EDs further and if needed, regulate them appropriately to protect vulnerable populations from their adverse events.


References
  1. RedBull.com (2014) Red Bull Gives You Wings.

  2. Monsterenergy.com (2014) Monster Energy Unleash the Beast.

  3. Higgins JP, Tuttle TD, Higgins CL (2010) Energy beverages: content and safety. Mayo Clin Proc 85: 1033-1041.

  4. Goldfarb M, Tellier C2, Thanassoulis G2 (2014) Review of published cases of adverse cardiovascular events after ingestion of energy drinks. Am J Cardiol 113: 168-172.

  5. Thorlton J, Colby DA, Devine P (2014) Proposed actions for the US Food and Drug Administration to implement to minimize adverse effects associated with energy drink consumption. Am J Public Health 104: 1175-1180.

  6. Larson N, Dewolfe J, Story M, Neumark-Sztainer D (2014) Adolescent consumption of sports and energy drinks: linkages to higher physical activity, unhealthy beverage patterns, cigarette smoking, and screen media use. J Nutr Educ Behav 46: 181-187.

  7. Phillips MD, Rola KS, Christensen KV, Ross JW, Mitchell JB (2014) Preexercise energy drink consumption does not improve endurance cycling performance but increases lactate, monocyte, and interleukin-6 response. J Strength Cond Res 28: 1443-1453.

  8. Nelson MT, Biltz GR, Dengel DR (2014) Cardiovascular and ride time-to-exhaustion effects of an energy drink. J Int Soc Sports Nutr 11: 2.

  9. Lara B, Gonzalez-Millán C, Salinero JJ, Abian-Vicen J, Areces F, et al. (2014) Caffeine-containing energy drink improves physical performance in female soccer players. Amino Acids 46: 1385-1392.

  10. Grasser EK, Yepuri G, Dulloo AG, Montani JP (2014) Cardio- and cerebrovascular responses to the energy drink Red Bull in young adults: a randomized cross-over study. Eur J Nutr 53: 1561-1571.

  11. Del Coso J, Pérez-López A, Abian-Vicen J, Salinero JJ, Lara B, et al. (2014) Enhancing physical performance in male volleyball players with a caffeine-containing energy drink. Int J Sports Physiol Perform 9: 1013-1018.

  12. Abian-Vicen J, Puente C, Salinero JJ, González-Millán C, Areces F, et al. (2014) A caffeinated energy drink improves jump performance in adolescent basketball players. Amino Acids 46: 1333-1341.

  13. McLellan TM, Lieberman HR (2012) Do energy drinks contain active components other than caffeine? Nutr Rev 70: 730-744.

  14. Higgins JP (2013) Endothelial function acutely worse after drinking energy beverage. Int J Cardiol 168: e47-49.

  15. Berger AJ, Alford K (2009) Cardiac arrest in a young man following excess consumption of caffeinated "energy drinks". Med J Aust 190: 41-43.

  16. Worthley MI, Prabhu A, De Sciscio P, Schultz C, Sanders P, et al. (2010) Detrimental effects of energy drink consumption on platelet and endothelial function. Am J Med 123: 184-187.

  17. Higgins JP, Yang B, Ortiz B, Herrin N, Doolittle J, Kahlden K, et al. (2014) consumption of energy beverage is associated with an attenuation of arterial endothelial flow-mediated dilatation. Arterioscler Thromb Vasc Biol 34: A519.

  18. Higgins JP, Babu KM (2013) Caffeine reduces myocardial blood flow during exercise. Am J Med 126: 730.

  19. Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, et al. (2002) Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol 39: 257-265.

  20. Deanfield JE, Halcox JP, Rabelink TJ (2007) Endothelial function and dysfunction: testing and clinical relevance. Circulation 115: 1285-1295.

  21. Shang R, Sun Z, Li H (2014) Effective dosing of L-carnitine in the secondary prevention of cardiovascular disease: a systematic review and meta-analysis. BMC Cardiovasc Disord 14: 88.

  22. Shankar SS, Mirzamohammadi B, Walsh JP, Steinberg HO (2004) L-carnitine may attenuate free fatty acid-induced endothelial dysfunction. Ann N Y Acad Sci 1033: 189-197.

  23. Volek JS, Judelson DA, Silvestre R, Yamamoto LM, Spiering BA, et al. (2008) Effects of carnitine supplementation on flow-mediated dilation and vascular inflammatory responses to a high-fat meal in healthy young adults. Am J Cardiol 102: 1413-1417.

  24. Mingorance C, Rodriguez-Rodriguez R, Justo ML, Herrera MD, de Sotomayor MA (2011) Pharmacological effects and clinical applications of propionyl-L-carnitine. Nutr Rev 69: 279-290.

  25. De Marchi S, Zecchetto S, Rigoni A, Prior M, Fondrieschi L, et al. (2012) Propionyl-L-carnitine improves endothelial function, microcirculation and pain management in critical limb ischemia. Cardiovasc Drugs Ther 26: 401-408.

  26. Schimpl FC, Kiyota E1, Mayer JL2, Gonçalves JF3, da Silva JF4, et al. (2014) Molecular and biochemical characterization of caffeine synthase and purine alkaloid concentration in guarana fruit. Phytochemistry 105: 25-36.

  27. White DJ, Camfield DA, Maggini S, Pipingas A, Silberstein R, et al. (2014) The effect of a single dose of multivitamin and mineral combinations with and without guaraná on functional brain activity during a continuous performance task. Nutr Neurosci .

  28. Fennessy FM, Moneley DS, Wang JH, Kelly CJ, Bouchier-Hayes DJ (2003) Taurine and vitamin C modify monocyte and endothelial dysfunction in young smokers. Circulation 107: 410-415.

  29. Moloney MA, Casey RG, O'Donnell DH, Fitzgerald P, Thompson C, et al. (2010) Two weeks taurine supplementation reverses endothelial dysfunction in young male type 1 diabetics. Diab Vasc Dis Res 7: 300-310.

  30. Jovanovski E, Jenkins A, Dias AG, Peeva V, Sievenpiper J, et al. (2010) Effects of Korean red ginseng (Panax ginseng C.A. Mayer) and its isolated ginsenosides and polysaccharides on arterial stiffness in healthy individuals. Am J Hypertens 23: 469-472.

  31. Rhee MY, Kim YS, Bae JH, Nah DY, Kim YK, et al. (2011) Effect of Korean red ginseng on arterial stiffness in subjects with hypertension. J Altern Complement Med 17: 45-49.

  32. Mucalo I, Jovanovski E, Rahelic D, Božikov V, Romic Z, et al. (2013) Effect of American ginseng (Panax quinquefolius L.) on arterial stiffness in subjects with type-2 diabetes and concomitant hypertension. J Ethnopharmacol 150: 148-153.

  33. Yang HT, Chao PC, Yin MC (2013) Riboflavin at high doses enhances lung cancer cell proliferation, invasion, and migration. J Food Sci 78: H343-349.

  34. Villines TC, Kim AS, Gore RS, Taylor AJ (2012) Niacin: the evidence, clinical use, and future directions. Curr Atheroscler Rep 14: 49-59.

  35. Thoenes M, Oguchi A, Nagamia S, Vaccari CS, Hammoud R, et al. (2007) The effects of extended-release niacin on carotid intimal media thickness, endothelial function and inflammatory markers in patients with the metabolic syndrome. Int J Clin Pract 61: 1942-1948.

  36. Warnholtz A, Wild P, Ostad MA, Elsner V, Stieber F, et al. (2009) Effects of oral niacin on endothelial dysfunction in patients with coronary artery disease: results of the randomized, double-blind, placebo-controlled INEF study. Atherosclerosis 204: 216-221.

  37. Lee JM, Robson MD, Yu LM, Shirodaria CC, Cunnington C, et al. (2009) Effects of high-dose modified-release nicotinic acid on atherosclerosis and vascular function: a randomized, placebo-controlled, magnetic resonance imaging study. J Am Coll Cardiol 54: 1787-1794.

  38. Hamilton SJ, Chew GT, Davis TM, Watts GF (2010) Niacin improves small artery vasodilatory function and compliance in statin-treated type 2 diabetic patients. Diab Vasc Dis Res 7: 296-299.

  39. Philpott AC, Hubacek J, Sun YC, Hillard D, Anderson TJ (2013) Niacin improves lipid profile but not endothelial function in patients with coronary artery disease on high dose statin therapy. Atherosclerosis 226: 453-458.

  40. Van den Berg M, Boers GH, Franken DG, Blom HJ, Van Kamp GJ, et al. (1995) Hyperhomocysteinaemia and endothelial dysfunction in young patients with peripheral arterial occlusive disease. Eur J Clin Invest 25: 176-181.

  41. Constans J, Blann AD, Resplandy F, Parrot F, Renard M, et al. (1999) Three months supplementation of hyperhomocysteinaemic patients with folic acid and vitamin B6 improves biological markers of endothelial dysfunction. Br J Haematol 107: 776-778.

  42. Miner SE, Cole DE, Evrovski J, Forrest Q, Hutchison S, et al. (2001) Pyridoxine improves endothelial function in cardiac transplant recipients. J Heart Lung Transplant 20: 964-969.

  43. van Dijk RA, Rauwerda JA, Steyn M, Twisk JW, Stehouwer CD. (2001) Long-term homocysteine-lowering treatment with folic acid plus pyridoxine is associated with decreased blood pressure but not with improved brachial artery endothelium-dependent vasodilation or carotid artery stiffness: a 2-year, randomized, placebo-controlled trial. Arterioscler Thromb Vasc Biol 21: 2072-2079.

  44. Chao CL, Chien KL, Lee YT (1999) Effect of short-term vitamin (folic acid, vitamins B6 and B12) administration on endothelial dysfunction induced by post-methionine load hyperhomocysteinemia. Am J Cardiol 84: 1359-1361, A8.

  45. Dinckal MH, Aksoy N, Aksoy M, Davutoglu V, Soydinc S, et al. (2003) Effect of homocysteine-lowering therapy on vascular endothelial function and exercise performance in coronary patients with hyperhomocysteinaemia. Acta Cardiol 58: 389-396.

  46. Peeters AC, van der Molen EF, Blom HJ, den Heijer M (2004) The effect of homocysteine reduction by B-vitamin supplementation on markers of endothelial dysfunction. Thromb Haemost 92: 1086-1091.

  47. Chia S, Wilson R, Ludlam CA, Webb DJ, Flapan AD, et al. (2005) Endothelial dysfunction in patients with recent myocardial infarction and hyperhomocysteinaemia: effects of vitamin supplementation. Clin Sci (Lond) 108: 65-72.

  48. Dusitanond P, Eikelboom JW, Hankey GJ, Thom J, Gilmore G, et al. (2005) Homocysteine-lowering treatment with folic acid, cobalamin, and pyridoxine does not reduce blood markers of inflammation, endothelial dysfunction, or hypercoagulability in patients with previous transient ischemic attack or stroke: a randomized substudy of the VITATOPS trial. Stroke 36: 144-146.

  49. Potter K, Hankey GJ, Green DJ, Eikelboom J, Jamrozik K, et al. (2008) The effect of long-term homocysteine-lowering on carotid intima-media thickness and flow-mediated vasodilation in stroke patients: a randomized controlled trial and meta-analysis. BMC Cardiovasc Disord 8: 24.

  50. Chambers JC, Ueland PM, Obeid OA, Wrigley J, Refsum H, et al. (2000) Improved vascular endothelial function after oral B vitamins: An effect mediated through reduced concentrations of free plasma homocysteine. Circulation 102: 2479-2483.

  51. Setola E, Monti LD, Galluccio E, Palloshi A, Fragasso G, et al. (2004) Insulin resistance and endothelial function are improved after folate and vitamin B12 therapy in patients with metabolic syndrome: relationship between homocysteine levels and hyperinsulinemia. Eur J Endocrinol 151: 483-489.

  52. Zittan E, Preis M, Asmir I, Cassel A, Lindenfeld N, et al. (2007) High frequency of vitamin B12 deficiency in asymptomatic individuals homozygous to MTHFR C677T mutation is associated with endothelial dysfunction and homocysteinemia. Am J Physiol Heart Circ Physiol 293: H860-865.

  53. Wundenberg T, Mayr GW (2012) Synthesis and biological actions of diphosphoinositol phosphates (inositol pyrophosphates), regulators of cell homeostasis. Biol Chem 393: 979-998.

  54. Rodriguez CJ, Miyake Y, Grahame-Clarke C, Di Tullio MR, Sciacca RR, et al. (2005) Relation of plasma glucose and endothelial function in a population-based multiethnic sample of subjects without diabetes mellitus. Am J Cardiol 96: 1273-1277.

  55. Haller MJ, Stein J, Shuster J, Theriaque D, Silverstein J, et al. (2007) Peripheral artery tonometry demonstrates altered endothelial function in children with type 1 diabetes. Pediatr Diabetes 8: 193-198.

  56. Ceriello A, Esposito K, Piconi L, Ihnat M, Thorpe J, et al. (2008) Glucose "peak" and glucose "spike": Impact on endothelial function and oxidative stress. Diabetes Res Clin Pract 82: 262-267.

  57. Buscemi S, Re A, Batsis JA, Arnone M, Mattina A, et al. (2010) Glycaemic variability using continuous glucose monitoring and endothelial function in the metabolic syndrome and in Type 2 diabetes. Diabet Med 27: 872-878.

  58. Metzig AM, Schwarzenberg SJ, Fox CK, Deering MM, Nathan BM, et al. (2011) Postprandial endothelial function, inflammation, and oxidative stress in obese children and adolescents. Obesity (Silver Spring) 19: 1279-1283.

  59. Mah E, Bruno RS (2012) Postprandial hyperglycemia on vascular endothelial function: mechanisms and consequences. Nutr Res 32: 727-740.

  60. Suzuki K, Watanabe K, Futami-Suda S, Yano H, Motoyama M, et al. (2012) The effects of postprandial glucose and insulin levels on postprandial endothelial function in subjects with normal glucose tolerance. Cardiovasc Diabetol 11: 98.

  61. Papamichael CM, Aznaouridis KA, Karatzis EN, Karatzi KN, Stamatelopoulos KS, et al. (2005) Effect of coffee on endothelial function in healthy subjects: the role of caffeine. Clin Sci (Lond) 109: 55-60.

  62. Umemura T, Ueda K, Nishioka K, Hidaka T, Takemoto H, et al. (2006) Effects of acute administration of caffeine on vascular function. Am J Cardiol 98: 1538-1541.

  63. Lopez-Garcia E, van Dam RM, Qi L, Hu FB (2006) Coffee consumption and markers of inflammation and endothelial dysfunction in healthy and diabetic women. Am J Clin Nutr 84: 888-893.

  64. Buscemi S, Batsis JA, Arcoleo G, Verga S (2010) Coffee and endothelial function: a battle between caffeine and antioxidants? Eur J Clin Nutr 64: 1242-1243.

  65. Buscemi S, Verga S, Batsis JA, Donatelli M, Tranchina MR, et al. (2010) Acute effects of coffee on endothelial function in healthy subjects. Eur J Clin Nutr 64: 483-489.

  66. Shechter M, Shalmon G, Scheinowitz M, Koren-Morag N, Feinberg MS, et al. (2011) Impact of acute caffeine ingestion on endothelial function in subjects with and without coronary artery disease. Am J Cardiol 107: 1255-1261.

  67. Lee CH, Shieh YS, Hsiao FC, Kuo FC, Lin CY, et al. (2014) High glucose induces human endothelial dysfunction through an Axl-dependent mechanism. Cardiovasc Diabetol 13: 53.

International Journal of Anesthetics and Anesthesiology (ISSN: 2377-4630)
International Journal of Blood Research and Disorders   (ISSN: 2469-5696)
International Journal of Brain Disorders and Treatment (ISSN: 2469-5866)
International Journal of Cancer and Clinical Research (ISSN: 2378-3419)
International Journal of Clinical Cardiology (ISSN: 2469-5696)
Journal of Clinical Gastroenterology and Treatment (ISSN: 2469-584X)
Clinical Medical Reviews and Case Reports (ISSN: 2378-3656)
Journal of Dermatology Research and Therapy (ISSN: 2469-5750)
International Journal of Diabetes and Clinical Research (ISSN: 2377-3634)
Journal of Family Medicine and Disease Prevention (ISSN: 2469-5793)
Journal of Genetics and Genome Research (ISSN: 2378-3648)
Journal of Geriatric Medicine and Gerontology (ISSN: 2469-5858)
International Journal of Immunology and Immunotherapy (ISSN: 2378-3672)
International Journal of Medical Nano Research (ISSN: 2378-3664)
International Journal of Neurology and Neurotherapy (ISSN: 2378-3001)
International Archives of Nursing and Health Care (ISSN: 2469-5823)
International Journal of Ophthalmology and Clinical Research (ISSN: 2378-346X)
International Journal of Oral and Dental Health (ISSN: 2469-5734)
International Journal of Pathology and Clinical Research (ISSN: 2469-5807)
International Journal of Pediatric Research (ISSN: 2469-5769)
International Journal of Respiratory and Pulmonary Medicine (ISSN: 2378-3516)
Journal of Rheumatic Diseases and Treatment (ISSN: 2469-5726)
International Journal of Sports and Exercise Medicine (ISSN: 2469-5718)
International Journal of Stem Cell Research & Therapy (ISSN: 2469-570X)
International Journal of Surgery Research and Practice (ISSN: 2378-3397)
Trauma Cases and Reviews (ISSN: 2469-5777)
International Archives of Urology and Complications (ISSN: 2469-5742)
International Journal of Virology and AIDS (ISSN: 2469-567X)
More Journals

Contact Us

ClinMed International Library | Science Resource Online LLC
3511 Silverside Road, Suite 105, Wilmington, DE 19810, USA
Email: contact@clinmedlib.org
 

Feedback

Get Email alerts
 
Creative Commons License
Open Access
by ClinMed International Library is licensed under a Creative Commons Attribution 4.0 International License based on a work at https://clinmedjournals.org/.
Copyright © 2017 ClinMed International Library. All Rights Reserved.