Methodological and metabolic considerations in the study of caffeine-containing energy drinks

Introduction

Caffeine-containing energy drinks are beverages that typically contain mixtures of simple sugars and caffeine, and may additionally contain vitamin, mineral, and/or herbal preparations.¹ Caffeine can be added in its purified form, or be derived from plants such as guarana (Paullinia cupana) and yerba maté (Ilex paraguariensis).^2,3 Marketed to boost energy, increase alertness, and reduce fatigue, there has been an exponential increase in sales of these products worldwide.⁴ Indeed, caffeine-containing energy drinks fit a growing category of supplements that are perceived to have multifunctional, physiological benefit beyond normal nutritional value. The purpose of this review is twofold. First, it highlights some important methodological considerations in the study of caffeine-containing energy drinks. Being of variable composition and with some products marketed as beverages and others as dietary supplements, these products are challenging to study.⁵ In particular, the scientific work performed to date suffers from the same methodological shortcomings observed with many nutritional supplements, including the proposition of value-added claims that are not necessarily based on a substantial body of clinical, epidemiological, or pharmacological knowledge. Complicating matters, many of the studies that have been performed on caffeine-containing energy drinks lack appropriate controls, scientific rigor, and reproducibility. As a result, the nutritional default has been to collect data on individual components. Such a reductionist analysis, however, cannot address potential interactions of ingredients.

Second, this review summarizes the latest data on the effects that caffeine-containing energy drinks have on the gastrointestinal (GI) system, liver, and metabolic health. The GI system is important as it experiences the ingredients of energy drinks at the highest concentration and initiates a chain of events to communicate with peripheral tissues. From a metabolic perspective, the two most critical ingredients are simple sugars and caffeine. Caffeine-containing energy drinks typically contain anywhere from 25 to 250 mg of caffeine per serving along with 6–29 g of sugar in the form of glucose, fructose, and/or sucrose.⁴ As an alternative, many companies have also launched zero- or low-calorie artificially sweetened products. Currently, the caffeine content in caffeine-containing energy drinks varies widely; regulation by the US Food and Drug Administration depends on product category, and is described elsewhere in this issue. Thus, some caffeine-containing energy drinks contain greater than 300% of the caffeine allowed in typical carbonated cola beverages. Within the product category of caffeine-containing energy drinks are energy “shots,” smaller-format products that tend to contain very high doses of caffeine in small volumes. This review considers both types of products as caffeine-containing energy drinks.

Methodological and Metabolic Considerations in the Study of Caffeine-Containing Energy Drinks

Consumption of caffeine-containing energy drinks results in multiple, systemic effects on the body. These effects are diverse and often tissue-specific. While there is an abundance of data on the effects these beverages have on certain tissues (e.g., skeletal muscle), there is very little on others (e.g., GI system). Throughout this review, attempts have been made to highlight knowledge gaps and methodological considerations in the study of caffeine-containing energy drinks. The primary methodological considerations are as follows.

Effect of ingredient mixtures

As noted above, caffeine-containing energy drinks contain a myriad of ingredients in varying concentrations and forms. While these beverages contain far more than simply glucose and caffeine, those two ingredients drive the majority of the metabolic effects associated with consumption. It needs to be kept in mind that studying these ingredients in isolation does not necessarily reflect their effects when given in combination. This complication extends even to a single ingredient such as caffeine. Caffeine can be directly added in its purified caffeine form, or as a plant extract. These various sources all provide caffeine and while their metabolic actions are likely similar, it should not be assumed that they are equivalent. Take, for example, purified caffeine versus coffee-derived caffeine. Both are associated with performance-enhancing effects during exercise, as well as impairments in whole-body insulin sensitivity.^6,7 However, the degree of enhancement or impairment is generally less when caffeine is consumed as coffee.

To examine the difference between purified caffeine and coffee-derived caffeine and its effects on performance, Graham et al.⁸ exercised subjects to volitional exhaustion on a treadmill. Results showed purified caffeine to have an ergogenic effect; however, the same amount of caffeine consumed as coffee increased performance only slightly, resulting in no significant difference between placebo and coffee trials. Likewise, Battram et al.⁹ administered equivalent doses of caffeine (4.45 mg/kg), either as purified caffeine or as coffee, 1 hour prior to an oral glucose tolerance test in humans. Purified caffeine resulted in a decrease in the insulin sensitivity index (ISI)¹⁰ from 8.7 (placebo) to 7.6, reflecting a decline in whole-body glucose disposal. The same amount of coffee-derived caffeine resulted in an identical concentration of circulating caffeine metabolites, but a nonsignificant decline in ISI to 8.2. Moreover, decaffeinated coffee improved ISI to 9.0. This demonstrates that other components of coffee are biologically active⁷,^11,12 highlighting the complex nature of caffeine-containing energy drinks and the importance of examining their ingredient mixtures as opposed to individual ingredients. Although the study of individual ingredients may play a critical role in elucidating the mechanisms underlying the effects of caffeine-containing energy drinks, the activity of an ingredient in isolation may differ from its effects in the context of these beverages.

Variable responses according to dose and repeat exposure

In determining the impact of a caffeine-containing energy drink or an isolated ingredient, most studies examine acute dosing; that is, consuming either one or multiple servings over a short duration. While these studies are informative, caution is warranted in applying these findings to chronic consumption of caffeine-containing energy drinks, i.e., over weeks to years. While chronic consumption of most ingredients has not been investigated, it is known that a dampening of some, but not all, of the physiological responses to caffeine occurs. The primary action of physiological concentrations of caffeine and its related methylxanthines is the antagonism of adenosine receptors.^13,14 Acute caffeine consumption in naive individuals results in elevations in blood pressure, heart rate, catecholamines, and renin.¹⁵ However, prolonged caffeine exposure results in near tolerance to these effects.¹⁵ Likewise, resistance to the behavioral and electrophysiological effects of caffeine have been noted and occur, in part, due to the upregulation of adenosine receptors.¹³,¹⁶ In contrast, other effects of caffeine, such as its performance-enhancing benefits and negative impacts on glucose tolerance, remain unchanged with repeated exposure.^17,–19 Therefore, caution is needed when extrapolating the acute effects of caffeine-containing energy drink consumption to longer-term exposure.

In the past, it was assumed that caffeine was detrimental to health.²⁰ However, for many metabolic disease states, associations between caffeine consumption and disease risk are weak to nonexistent.^21,–23 For example, it is known that acute coffee consumption is metabolically deleterious and causes insulin resistance in the sedentary state.^24,–26 Intuitively, one would expect that caffeine-induced insulin resistance, over the course of a lifetime, would result in weight gain and an increased risk of the metabolic syndrome, type 2 diabetes, and cardiovascular disease.^27,–30 However, there is currently no evidence to support such a conclusion and, in fact, coffee consumption is associated with not increased, but reduced, incidence of type 2 diabetes in epidemiological studies.^31,–33 This result has been attributed to ingredients such as polyphenols and related compounds derived from coffee; thus, the energy drinks that use caffeine extracted from botanical sources could also contain such beneficial compounds.³,⁷ The chronic impacts of a caffeine-containing energy drink could consequently vary depending on the specific chemical composition. In other words, the effect would be different if whole guarana or yerba maté extract were used instead of purified caffeine, with the critical difference being not the source of the caffeine, but what else is added along with it and if it is added as part of a more complex product.

Tissue-specific responses

When considering the impact of caffeine-containing energy drinks on the GI system, it is important to acknowledge that not all organs experience the same concentration of active ingredients. Upon ingestion of a beverage, the GI tract comes into contact with a greater concentration of ingredients compared to the systemic circulation and other peripheral systems (Figure 1). Similarly, the reaction of individual tissues to a specific ingredient may differ. For example, caffeine is known to cause an increase in net glucose uptake in the liver,³⁴ while impairing glucose uptake in skeletal muscle.²⁶,³⁵ Tissues express different adenosine receptor subtypes in varied ratios.³⁶ In addition, the liver experiences a very different exposure to nutrients during food assimilation due to its portal circulation from the GI tract. Although metabolic responses can be tissue-specific, they do not occur in isolation. The body has redundant and well-developed systems for communicating between tissues, which is a concept that will become evident in the following discussion on incretin hormones.^37,38

Individual differences in metabolism

Physiologic and metabolic responses to caffeine-containing energy drinks are likely dependent on age and genetics as well as the health status of an individual. For example, these drinks have been indicated as potentially hazardous to children and to adolescent populations,³⁹ because the smaller weight of these individuals results in a greater exposure to active ingredients on a per kilogram basis. These concerns have warranted a warning label on caffeine-containing energy drinks sold in Canada, which state that the beverages are not recommended for children.⁴⁰ Concerns about potential effects in pediatric populations not only extend to caffeine; they also apply to other active ingredients.³⁹

The majority of studies on caffeine-containing energy drinks have been conducted in healthy adults. It is well documented that an individual's preference for, sensitivity to, and metabolism of caffeine are determined, in part, by genetics.^41,–43 Ethnicity, sex, diet, prior caffeine exposure, and other lifestyle habits, such as smoking, can influence caffeine metabolism and result in an up to 40-fold difference in caffeine clearance among individuals.^44,–47 Studies of identical twins show that the heritability of caffeine-related traits, including consumption and tolerance, ranges between 0.30 and 0.60,^48,49 with 0 being not inherited and 1 being completely explained by genetic influences. Furthermore, this high level of heritability has been found to be relatively stable over the lifetime of individuals.⁴⁸ To date, the primary genes driving this association appear to be those associated with adenosine, dopamine, and the liver cytochrome P450 system.⁴²,^50,51 Investigations of caffeine metabolism need to ensure that they are adequately powered to account for “responders” and “nonresponders.”⁵² Caution also needs to be exercised in extrapolating research on the effects of any health product or supplement in healthy individuals to those with poor health. For example, it is accepted that particular ingredients of some caffeine-containing energy drinks, such as taurine, have little to no metabolic benefit in the healthy state. However, taurine supplementation is proving to have therapeutic benefit in specific clinical cases, including patients with liver dysfunction, diabetes, and cardiovascular disease.^53,–58 This raises the issue of “personalized diets,” and it is intriguing to think that caffeine-containing energy drinks may one day be customized to such populations.

Understanding the Effects of Caffeine-containing Energy Drinks on the Gastrointestinal System and Liver

Gastrointestinal system

Consideration of the GI system in relation to caffeine-containing energy drinks requires examination of gastric emptying, intestinal permeability, intestinal transport, rate of absorption, and orocecal transit time. The possible impact of a caffeine-containing energy drink on gastrointestinal hormones and the composition of gut microbiota may be even more important.

In the mouth, caffeine contained in energy drinks transiently stimulates salivary secretions. According to Fredholm,³⁶ this effect has very limited clinical significance to humans. Subsequently, high doses of caffeine relax the lower esophageal sphincter and increase gastric acid secretion. Anecdotally, caffeine has been thought to cause gastroesophageal reflux and gastric ulcers. However, no definitive associations between caffeine and gastric ulcer, duodenal ulcer, reflux esophagitis, and non-erosive reflux disease exist. Analysis of 9,517 adults with confirmed upper GI disease found no association between coffee consumption and the incidence of disease when corrected for age, gender, body mass index, Helicobacter pylori infection status, pepsinogen I/II ratio, smoking, and alcohol use.⁵⁹ This study concluded there was little evidence for an association of coffee with the four aforementioned major acid-related upper GI disorders.⁵⁹ Likewise, analysis of duodenal ulcers in a prospective cohort of 47,806 male health professionals revealed no association between caffeine, caffeine-containing beverages, or decaffeinated coffee and duodenal ulcer risk.⁶⁰ Thus, there is no evidence to show that caffeine-containing beverages cause gastrointestinal dysfunction, although they may worsen existing symptoms. To date, the majority of work has focused on coffee, with little to no data existing on the impact of caffeine-containing energy drinks. A single study has examined self-reported adverse events associated with consumption of energy drinks based on emergency room visits. Of 1,298 individuals completing the survey, 82 (∼6%) reported GI upset.⁶¹ It is clear that more research examining any potential association between these beverage products and GI upset is warranted.

Caffeine-containing energy drinks would be expected to have two main effects on the stomach, based on their ingredients. First, the glucose load should act to increase the postprandial muscle activity of the stomach and act to delay gastric emptying in the following manner: the greater the concentration of glucose, the slower the rate of gastric emptying.⁶² This would be suboptimal in conditions such as prolonged exercise or hot, humid conditions where hydration status is important.⁶² Upon exiting the stomach, the ingredients come into direct contact with the small intestine. Predicting the impact of caffeine-containing energy drinks on intestinal absorption differs by the intestinal segment studied and the composition of the beverage. Transit throughout the intestine is also dependent on the beverage's osmolality, the type and concentration of carbohydrates, and the presence of other active ingredients.^63,64 Generally speaking, the greater the concentration of carbohydrates in a caffeine-containing energy drink, the slower the rate of water absorption. Rates of water absorption also depend on the hydration status of the individual and their physiological condition. For example, water absorption from the intestine is enhanced during exercise.⁶⁵ Individual ingredients other than caffeine, as well as fluid volume, may also act on the intestine.⁶⁶ Chlorogenic acids, found in both coffee and yerba maté, are known to have an inhibitory effect on sodium-dependent glucose transport across the brush-border of intestinal membranes.^63,64,⁶⁷ These inhibitory effects on glucose transport may contribute to the benefits of chlorogenic acid in diet-induced obesity and diabetes.⁶⁶,^68,69

While in the gut, the contents of caffeine-containing energy drinks also interact with specialized gastrointestinal cells in the intestine known to secrete incretins, which are peptide hormones that are released into the circulatory system in response to nutrient ingestion. Collectively, these hormones are responsible for 50–70% of insulin secretion following a meal. Although many incretin hormones have been identified, this review highlights the two most commonly studied, gastric inhibitory peptide (GIP) and glucose-dependent insulinotropic polypeptide (GLP-1). GIP is released from K cells in the small intestine, while GLP-1 is released from intestinal L cells. In response to a glucose load from a caffeine-containing energy drink, both GLP-1 and GIP are released into the circulation to signal insulin release and satiety.^70,71 It is now known that GLP-1 secretion is blunted in obese and insulin-resistant individuals; as a result, the maintenance of GLP-1 levels has become a key pharmaceutical target for type 2 diabetes.^72,73 Many phytochemicals are known to independently stimulate GLP-1, as does coffee⁷⁴; however, this appears to occur independently of caffeine. Thus, other plant-based compounds in caffeine-containing energy drinks may also have a stimulatory impact on GLP-1 and GIP. For example, chronic ingestion of high concentrations of yerba maté leaf for 3 weeks by mice with diet-induced obesity resulted in elevated GLP-1 levels and was associated with reductions in body mass, food intake, and liver triglycerides.⁷⁵ The physiological effects of yerba maté in humans are not well understood.

Upon passing through the small intestine, some components of caffeine-containing energy drinks (e.g., caffeine) are completely absorbed, while others will come into contact with the large intestine and colon. The gut microbiome (trillions of bacteria and other microorganisms that live in symbiosis with humans in the GI tract⁷⁶) has been shown to play important roles in health. It is estimated that these bacteria contribute 10–15% of human energy requirements through the fermentation of nondigestible carbohydrates.⁷⁷ Alterations in the diet can change the composition of the microbiome, resulting in downstream changes in immune function, and in metabolism, including increases in fat deposition in the host.⁷⁶,⁷⁸ While there are over 50 different phyla in the gut microbiome, Bacteroidetes and Firmicutes make up the vast majority of the bacteria in humans, rats, and mice.^79,80 Current research suggests that obesity and type 2 diabetes are associated with an altered gut microbiota profile or phylotype.⁷⁸,⁸¹ Although not all reports are consistent, numerous studies have demonstrated that obesity and high-fat feeding are associated with an increased abundance of Firmicutes and a lower abundance of Bacteroidetes when compared to lean individuals⁷⁸,^81,82; this obese phylotype has been shown to be more efficient at energy extraction. Generally speaking, artificial sweeteners and certain plant-derived components (including caffeinated coffee) are known to affect the balance of microbiota in the gut.^83,–85 Likewise, chronic consumption of simple sugars (such as those contained in caffeine-containing energy drinks) as part of a Western diet, results in reduced bacterial gut diversity, activity, and gene expression, which may promote obesity and metabolic dysfunction.⁸¹,^86,87 A review by Payne et al⁸⁴ concluded that continuous exposure to both fructose and sugar substitutes alter gut microbiota in a negative manner. While it is highly unlikely that anyone would consume enough caffeine-containing energy drinks to result in these changes and consequences, regular consumption of such beverages would likely add to the insult on gut microflora imposed by the Western diet.

Caffeine-containing energy drinks and the liver

The components of caffeine-containing energy drinks that are assimilated will go to the liver via the portal circulation, while any nonabsorbed components will pass into the large intestine. The hepatic portal circulation exposes the liver to relatively high concentrations of energy drink components compared to those found in the systemic circulation. Pencek et al.³⁴ injected caffeine directly into the portal circulation of conscious dogs. Of the caffeine infused into the portal circulation, only 75% appeared in the hepatic venous circulation. From there, caffeine was dispersed into the systemic circulation, where arterial levels of caffeine were only 35% of what was initially infused. As such, it is very likely that the liver is the key site of extraction and metabolic processing of many of the individual components of caffeine-containing energy drinks.

It is also important to note that the liver is largely responsible for maintaining whole-body glucose homeostasis.⁸⁸ Consumption of sugar-sweetened caffeine-containing energy drinks will result in a rapid spike in blood glucose from sucrose, fructose, glucose, or any combination of these sugars. The liver will take up this glucose load and store some as glycogen while releasing the rest into the systemic circulation where most will be stored in muscle. High-fructose corn syrup can have detrimental health effects relative to other sugars, in part because it is preferentially metabolized by the liver and causes an increase in the rate of hepatic de novo lipogenesis compared to glucose.^89,90 Whether fructose itself is also more detrimental to metabolic health compared to other sugars remains a topic of intense debate.^91,92

In addition to caffeine's ability to increase hepatic glucose uptake, recent work by Sinha et al.⁹³ shows that caffeine induces fatty acid oxidation by increasing the rate of autophagy of intracellular lipids in the liver. This ability to selectively catabolize lipid droplets has been termed lipophagy. Lipophagy results in elevated rates of mitochondrial fatty acid oxidation.⁹⁴ This finding may explain why regular coffee consumption results in a lower incidence of type 2 diabetes and fatty liver disease.³³,^95,96 At present, the dosage required to elicit lipophagy in the liver is not known. However, the possibility exists that caffeine-containing energy drinks may be beneficial for promoting the clearance and turnover of hepatic lipids.^97,98

Caffeine in energy drinks is metabolized by the cytochrome P450 system into dimethylxanthines (paraxanthine, theobromine, theophylline). The primary and rate-limiting enzyme is P450 1A2, coded by the gene CYP1A2.⁹⁹ Recent work has revealed that polymorphisms in this gene can affect the rate of caffeine clearance.^41,–43 A primary hepatic metabolic action of caffeine is to increase net hepatic glucose uptake. Increased uptake of glucose by the liver would be expected to improve whole-body insulin sensitivity. However, it is well documented that, overall, caffeine causes a reduction in whole-body glucose disposal by approximately 30%.^100,–104 This level of impairment is known to occur in a dose-dependent fashion. The ingestion of 1 mg/kg body weight is sufficient to impair glucose tolerance, with every additional milligram causing a 5.8% increase in the rise in insulin needed to dispose of circulating glucose.¹⁰⁰ The primary tissue responsible for caffeine-induced insulin resistance is skeletal muscle, which disposes of the majority of ingested glucose.³⁵

The liver is also confronted with taurine, ginseng, and carnitine through consumption of some caffeine-containing energy drinks. For example, taurine is found in many of these beverages at levels ranging from 700 to 1,000 mg per serving.¹ Upon ingestion, taurine is well absorbed by taurine transporters in the intestinal epithelium, with circulating levels peaking at 1–2 h post-ingestion.^105,106 Taurine has been described as the “most abundant free amino acid in animal tissues.”¹⁰⁷ Despite its relatively high tissue concentrations (25% and 50% of the free amino acid pool in liver and kidney, respectively), this amino acid accounts for only 3% of the free amino acid pool in plasma.¹⁰⁷ Generally, this amino acid does not equilibrate with the body's exchangeable amino acid pool, meaning that acute consumption results in relatively minor transient increases in total-body taurine in healthy individuals.^108,109 Recently, van Stijn¹¹⁰ showed relatively stable levels of taurine in arterial, portal venous, hepatic venous, and renal venous plasma, suggesting minimal hepatic extraction. However, taurine is a major constituent of bile. Supplementation with taurine increases the flow, volume, and proportion of taurine-conjugated bile acids.^111,112 Beyond bile acid production, taurine has also been described as having antioxidant properties.¹¹³ While taurine consumption is relatively inert in healthy individuals, it may have some benefit in people with established metabolic disease.⁵⁴,^56,–58

A number of caffeine-containing energy drinks also contain ginseng and carnitine. Ginseng is a plant and popular herbal remedy that is used in some caffeine-containing energy drinks at levels ranging from 20 to 200 mg per serving.¹ The most noted active ingredients in ginseng are ginsenosides¹ and their amount in the typical dose range is considered safe for consumption.¹¹⁴ Generally, ginsenosides are thought to be poorly absorbed, so significant amounts reach the colon.¹¹⁵ Ginsenosides have also been found to stimulate GLP-1 and may, therefore, be of benefit in stimulating insulin secretion.¹¹⁶ The amount of carnitine in caffeine-containing energy drinks ranges from 20 to 50 mg per serving. Carnitine is a generic term for a number of compounds that include L-carnitine, acetyl-L-carnitine, and propionyl-L-carnitine that play a role in energy production from fatty acids.¹¹⁷ Carnitine is biosynthesized in humans at a rate of 1 to 2 μmoL/kg/day from lysine and methionine^118,119 and is readily absorbed from the gut by diffusion,¹²⁰ although it is not an essential nutrient.¹²⁰ Carnitine is quickly dissipated following ingestion, with clearance by the liver and excretion in the urine. Unabsorbed carnitine reaches the large intestine, where it is acted upon by the gut microbiota. The kidneys are extremely efficient at carnitine reabsorption; thus, it is highly unlikely that habitual supplementation in healthy individuals has any major physiological effect.¹²⁰ Indeed, a recent review of ingredients in caffeine-containing energy drinks by McLellan and Lieberman¹ concluded there was no experimental evidence showing improvements in physical and cognitive performance with ginseng or carnitine.¹

Potential Impacts of Caffeine-containing Energy Drinks on Metabolic Health

To date, little to no information on the metabolic impact of caffeine-containing energy drink consumption exists. The most relevant data examines the effects of sugar-sweetened beverages on metabolic function, weight management, and disease risk.¹²¹ There has been a steady rise in the consumption of sugar-sweetened beverages that has coincided with a rise in the prevalence of obesity and type 2 diabetes.^122,–124 The majority of studies,^125,–128 but not all,^129,130 have found evidence supporting an association between weight gain and consumption of sugar-sweetened beverages. Given that one in three North American adults are overweight or obese^131,132 and one in five children between the ages of 6 and 19 years are clinically obese,^133,134 it can be hypothesized that regular consumption of caffeine-containing energy drinks would contribute to this epidemic, since these beverages generally have high levels of simple sugars and very low nutritive value. However, the contribution would be very modest unless daily consumption occurred.

A recent meta-analysis of sugar-sweetened beverages by Milik et al.¹³⁵ included 32 studies (20 of which examined children) containing 200,000 subjects. They found that consumption of one sugar-sweetened beverage serving daily (standard serving size being 12 oz or 350 mL) resulted in an additional weight gain of 0.12 to 0.22 kg per year in adults. In children, a positive association with body mass index (BMI) was also found, suggesting that a daily serving of a sugar-sweetened beverage resulted in a 0.06 unit increase in BMI/year. (It is worth noting that assessing BMI in children is difficult, in part due to the variation that occurs with normal maturation). Relevant to the examination of caffeine-containing energy drinks, Bhupathiraju et al.¹³⁶ retrospectively examined the relationship between either caffeinated or caffeine-free sugar-sweetened beverages and the risk for type 2 diabetes in 75,500 subjects. Intake of sugar-sweetened beverages increased the relative risk for type 2 diabetes independent of caffeine intake, with the caffeinated beverages increasing risk by 16% and caffeine-free beverages increasing risk by 23%.

One major reason for consuming caffeine-containing energy drinks is to maintain wakefulness and alertness, as required by shift workers. It is well documented that shift workers have a greater predisposition to obesity and metabolic diseases compared to individuals who have a regular, daytime work schedule.^137,138 Indeed, food intake and metabolism are regulated by circadian rhythm.^139,140 Shift workers have increased caloric intake, lower insulin sensitivity, hyperlipidemia, and greater levels of stress-related hormones.¹⁴¹ They also display differential incretin responses to a meal.¹⁴² While it is known that consumption of caffeine-containing energy drinks by shift workers results in reduced sleep time and efficiency,¹⁴³ the interaction of caffeine-containing energy drinks and weight management in this population has not been well characterized.

Conclusion

Consumption of caffeine-containing energy drinks is increasing rapidly and relatively little is known about the potential impact of these beverages on metabolic health. In this review, two aspects of caffeine-containing energy drinks have been considered: 1) the methodological considerations in their study, and 2) the impact of their consumption on the gastrointestinal system, liver, and overall metabolic health. Individual components of caffeine-containing energy drinks should not be studied in isolation, but rather as mixtures. Likewise, the impact of acute and long-term consumption needs to be considered in different populations. It is highly likely that individual responses to caffeine-containing energy drinks exist, as this is true for caffeine, which is the major active ingredient. These are important factors to consider in the design and evaluation of future studies.

Another consideration is that the gastrointestinal tract and liver are “gateway tissues” and, as such, are exposed to a much greater concentration of the components of caffeine-containing energy drinks than the periphery. These tissues are also key players in initiating metabolic events (e.g., incretin release) that will affect the processing of simple sugars and other beverage ingredients. Given this and the highly metabolic nature of the liver, it is critical that future investigations focus on these highly complex systems.

The authors thank Virginia L. Johnsen for her assistance in editing the document. The editing and motivation of Dr. Terry Graham were also greatly appreciated

Funding

This work was supported by the National Science and Engineering Research Council of Canada. JS holds a salary support award from Alberta Innovates Health Solutions.

Declaration of interest

The authors have no relevant interests to declare.

References