In addition to how it can help a person feel more awake and alert, guarana benefits may include anti-inflammatory and pain relief effects. Guarana side effects are similar to those resulting from caffeine.

It may be safe for people without medical conditions to take guarana daily as long as they monitor their overall caffeine intake. Some studies have shown that caffeine can benefit overall health.

However, others suggest that it may be harmful in excess. Read more to find out…. Some people may have caffeine sensitivity, meaning that they are more likely to experience side effects when consuming the substance. Learn more here. Matcha contains caffeine. In fact, it contains more caffeine than most other types of tea, as it consists of whole powdered tea leaves.

Evidence suggests that sauerkraut may provide various health benefits, including supporting gut health. While guarana does contain more caffeine than coffee, both have potential benefits when consumed in moderation. Learn more. My podcast changed me Can 'biological race' explain disparities in health?

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Medical News Today. Health Conditions Health Products Discover Tools Connect. What are the benefits of guarana, and are there any side effects? Medically reviewed by Dominique Fontaine, BSN, RN, HNB-BC, HWNC-BC — By Nancy Lovering on September 7, Increase energy Enhance cognition Reduce inflammation Antioxidants Anti-aging Wound healing Weight loss Pain relief Reduce cholesterol Anti-cancer properties anti-microbial effects Eye health Risks Safety Summary Guarana is a plant extract present in many energy drinks.

May increase energy. May enhance cognition. May reduce inflammation. May have antioxidant properties. May have anti-aging effects.

May promote wound healing. May help with weight loss. May provide pain relief. May reduce cholesterol. May have anticancer properties. May have antimicrobial effects. May protect eye health. Risks and side effects. Planarian motility was monitored after the worms were placed in a Petri dish containing the appropriate concentration of guarana seed extract following the tested habituation period.

The Petri dishes were placed over graph paper and the number of grid-lines crossed was monitored for three minutes. The white bar represents the normalized control pLmV, while the black bars indicate relative to control test pLmV values.

Due to the fact that our results indicated that guarana does provide for significantly greater stimulation of planarian motility, we went on to test the effect of purified caffeine on pLmV. Since other investigators determined that caffeine does not provide a significant stimulation of planarian motility we aimed to use the system to assess whether guarana provides an added stimulus over caffeine alone [ 47 , 50 ].

It was necessary, however, to determine if our system and choice of planarian species offered a comparable backdrop to these published reports. Again, we began by testing the planarian motility using a range of caffeine concentrations 0. Although planarian motility was slightly elevated at concentrations between 0.

However, because the calculated p-value for the pLmV using 0. To this end, we examined the effect of both 0. As with the guarana extract, 10 mM caffeine was inhibitory to planarian motility Fig 2A and resulted in sustained contractions during the assay period.

These results were compared with a one-hour incubation time Fig 2B. Just as with the guarana extract we examined 0. These results confirmed that purified caffeine provides for a noticeable, albeit insignificant stimulation in planarian locomotion at the concentrations tested.

Shown are selected pLmV data relative to water-only controls for Dugesia tigrina exposed to varying concentrations of caffeine. Planarian motility was monitored after the worms were placed in a Petri dish containing the appropriate concentration of caffeine following the tested habituation period.

To determine if an additional stimulant effect might be achievable by combining caffeine and guarana, we used solutions containing both low end and high end concentrations of caffeine and guarana seed extract and assessed planarian activity after exposure times lasting either two minutes or one hour Fig 3.

A caffeine concentration of 0. A combination of 0. Using a higher concentration of 0. The average relative pLmV using the combined solution after the two-minute exposure was slightly higher than that observed for guarana extract alone, 1. These two data sets were significantly different from each other with a p-value of 0.

Our findings suggested that guarana provides an additional level of stimulation above that provided by caffeine alone. Shown are pLmV data relative to water-only controls for Dugesia tigrina exposed a combination of 0.

Planarians were habituated in their respective conditions for either 2 minutes or 1 hour as indicated, before their pLmV activity was monitored. Planarian motility was monitored after the worms were placed in a Petri dish containing the appropriate concentrations of guarana seed extract and caffeine following the tested habituation period.

Since sugars are also a main ingredient in most energy drinks we next assessed how glucose influences guarana and caffeine stimulation. To begin, we determined how much sugar is present in these beverages by studying the ingredient list on the containers.

Further, if the type of sugar was listed, there were often different amounts reported for each—sucrose, fructose and glucose.

We also assessed concentration ranges using online resources [ 55 , 57 ]. We elected to use glucose as our sugar standard because it is the most easily metabolized sugar, and determined that sugar concentrations ranged from to mM.

We then calculated the average sugar concentration listed on the beverage containers to be mM, which we assumed to be glucose. We used that Fig. to prepare our standard stock solution. As with guarana and caffeine we conducted a pLmV study using glucose alone following exposure times of two minutes and one hour Fig 4.

The mM concentration proved inhibitory to planarian locomotion as determined by repeated coiling behavior, and as such, we conducted our experiments with a series of glucose concentrations below that value 0.

We did not detect any significant increase in pLmV using any of these concentrations after either a two-minute or one-hour exposure period. We did, however, detect a peak average relative stimulation of 1. This was significantly different from the average relative pLmV of 0.

In contrast, the average relative locomotor velocities for the glucose concentrations tested after a one-hour exposure to glucose Fig 4B , did not result in any notable stimulation peaks above the water control despite a significant difference between 0. Shown are selected pLmV data relative to water-only controls for Dugesia tigrina exposed to varying concentrations of glucose.

Planarian motility was monitored after the worms were placed in a Petri dish containing the appropriate concentration of glucose following the tested habituation period. We then assessed how the combination of guarana with glucose affected pLmV using low and high-end concentrations after two-minute and one-hour exposure times Fig 5.

At the low end, with a concentration of 0. Importantly, neither the guarana extract, nor glucose alone provided a significant stimulation at this time point at 0. This suggests that at low concentrations, glucose does provide a supportive effect to guarana stimulation over longer periods.

In contrast, this effect was not apparent using a combined high-end concentration consisting of 0. It is notable that guarana did provide stimulation as a single reagent after two minutes at 0.

Statistical analysis indicated that the two-minute guarana single data at 0. Planarian motility was monitored after the worms were placed in a Petri dish containing the appropriate concentrations of guarana extract and glucose following the tested habituation period.

In contrast, following with a complementary assessment of caffeine and glucose Fig 6 we did not observe an increase in planarian locomotor velocity at either low or high-end concentration combinations for incubation periods of two minutes and one hour.

These findings again highlighted a potential difference between guarana and caffeine in that the response to glucose was different between the two stimulants. Planarian motility was monitored after the worms were placed in a Petri dish containing the appropriate concentrations of caffeine and glucose following the tested habituation period.

Upon an assessment of locomotor velocity using guarana seed extract together with caffeine and glucose Fig 7 we observed a slightly significant increase using low concentrations 0.

Importantly, we did not detect a low-concentration stimulation after two minutes with the double combinations of guarana seed extract and caffeine, guarana seed extract and glucose, or caffeine and glucose Figs 3 , 5 and 6 , respectively. This suggests that some stimulant benefit is achievable through the combination of all three substances that might not be apparent otherwise at lower concentrations of any of the three substances alone, or in pairs, for the short-term.

The significant low-concentration stimulus was maintained at one hour albeit at a lower level, with an average relative stimulation of 1. But, we also observed a low-concentration average relative stimulus with guarana extract at 0. Shown are pLmV data relative to water-only controls for Dugesia tigrina exposed to a combination of 0.

Planarian motility was monitored after the worms were placed in a Petri dish containing the appropriate concentrations of guarana extract, caffeine and glucose following the tested habituation period. In contrast, despite observing an improved pLmV relative to controls when planarians were exposed to a combination of guarana seed extract and caffeine at higher concentrations 0.

These data suggest that a short-term benefit is achieved with guarana, caffeine and glucose, but when combined at lower concentrations. Energy drinks typically contain caffeine and sugars as their principal active ingredients.

But many popular brands also contain blends of other substances that purportedly provide an added stimulus. One of these increasingly common additives is guarana.

For this study we asked whether guarana had the potential to provide an added stimulant effect over caffeine alone using the planarian locomotor activity pLmV assay [ 42 , 43 ].

Reports suggesting that planarian activity is not significantly affected by caffeine supported our choice of model system in that it allowed us to detect the tonic effects of guarana seed constituents separate from those provided by caffeine [ 47 , 50 ].

Owing to the fact that caffeine is typically considered responsible for the stimulant properties of guarana, we used the reported five percent caffeine content of guarana seeds, and the typical range of caffeine concentrations reported for most energy drink formulations, as a starting point for our working guarana concentrations [ 19 , 30 , 55 , 56 ].

When comparing a gauntlet of caffeine and guarana concentrations on planarian motility, it was indeed apparent that caffeine did not significantly increase pLmV at any concentration tested, while guarana had a positive effect at concentrations ranging from 0.

Notably, while not significantly different from the water controls, the average relative pLmV for each of the concentrations of caffeine above 0. This contrasted to the results for the guarana extract alone after two minutes, where we observed a peak stimulation using a concentration of 0.

Had we chosen a less conservative caffeine content for our guarana seed powder, such as a high end estimate of 10 percent caffeine content—double our estimate—our high end concentration of 1.

Therefore, since the data for caffeine and the guarana extract do not follow the same overall pattern of activity, it further suggests that guarana provides another stimulant value separate from that of caffeine alone.

Inspecting the pLmV data collected after a one-hour habituation in caffeine alone there was no evidence of stimulation at any concentration tested indicating that even the trend for a low-level stimulus, while not significantly greater than the water control, was a short-term effect Fig 2B.

In contrast, the post one-hour data collected for guarana seed extract-exposed pLmV showed a significant stimulus at 0. These guarana findings suggested that a longer-term stimulus could be maintained at lower concentrations, providing further evidence in support of a difference between guarana and caffeine stimulation.

In general, however, we suggest that the one-hour data for both caffeine and guarana indicate that a tolerance-type of response occurs with length of exposure to higher concentrations of these stimulants.

Importantly, others have observed that planarians respond best to stimulants within the first five minutes of exposure, which is reflected in our findings as well [ 50 ]. Our locomotor data combining selected low and high concentrations of guarana seed extract and caffeine Fig 3 suggested that guarana provides an additional stimulation above that provided by caffeine alone.

Neither guarana seed extract nor caffeine alone provided a detectable increase in pLmV as a single stimulant at the low concentration examined 0. But, when the higher concentrations of 0. This average relative pLmV was augmented over that observed for guarana extract alone pointing to an additional short-term stimulation through the combination of higher concentrations of guarana and caffeine.

Furthermore, since such an additive effect was not observed by simply increasing the concentration of caffeine Fig 2 , the additional stimulation provided by guarana seed extract might be provided by some other water soluble ingredient in the seeds that functions using a metabolic pathway separate from that used by caffeine.

Significantly, another group examining the effects of guarana on mice also observed increases in activity that likely operated using a different mechanism than that used by caffeine [ 20 ]. While supporting our hypothesis that guarana contains stimulant properties independent of caffeine, this corroborating result also supports the use of the planarian for studies implicating stimulant effects in mammalian systems.

The stimulant effect of caffeine is suggested to be mediated by a number of mechanisms including the intracellular mobilization of calcium, the inhibition of phosphodiesterases, the binding of caffeine to benzodiazepine receptors, and antagonism at the level of adenosine receptors [ 58 , 59 ].

While the caffeine in guarana likely works by these mechanisms, other constituents possibly function using different pathways. In addition to caffeine, guarana seeds are known to harbor a number of other possible stimulants such as catachins, tannins and other alkaloids such as theophylline and theobromine [ 19 , 22 , 30 , 60 ].

At present, little information is available favoring one of these ingredients over the others. We expanded our work to consider the effect of sugar on pLmV in conjunction with both caffeine and our guarana seed extract. The specific sugars in energy drink varieties vary, and as such we chose to work with D-glucose, or dextrose in our study.

Not all producers of energy drinks disclose complete concentrations of sugars in their formulations, so we calculated an average concentration to use in our experiments. We arrived at this value by averaging the amount of sugar disclosed on the few containers that gave some details of the total sugars they contained.

We compared this amount with those of estimates of total sugars in energy drinks discovered online, which were reflected in our chosen stock concentration [ 55 , 57 ].

While we observed that glucose alone did not offer an apparent stimulation of planarian motility Fig 4 , it did support guarana stimulation at low-end concentrations for a longer time Fig 5.

This was particularly interesting in that neither glucose alone Fig 4B nor guarana seed extract alone Fig 1B resulted in an increased pLmV after the one-hour habituation at these concentrations.

We also observed a significant short-term relative average stimulation with the combined high-end concentrations of glucose and guarana seed extract Fig 5 , but since the guarana seed extract alone resulted in a significantly augmented pLmV Fig 1 after the same time period, it was not possible to determine if glucose further intensified this effect using our system.

But, our data do suggest that at low concentrations, glucose does provide a supportive effect to guarana stimulation over longer periods. These data are in line with published reports suggesting that glucose can support the effect of stimulants in the planarian model [ 48 ].

Conversely, our combinations of glucose and caffeine did not result in an increase of planarian motility at either time-point examined Fig 6 providing further evidence of stimulant properties in guarana that are indeed different from those of caffeine. Exposing planarians to guarana seed extract, caffeine and glucose together resulted in augmented planarian motility after both short and long-term stimulation, but only with our low concentration combination Fig 7.

However, since our low concentration of guarana seed extract coupled with our low concentration of glucose also offered a sustained significant stimulation after the one-hour incubation, we cannot conclude that caffeine had an additional effect in this situation. On the other hand, the triple combination was the only one tested that resulted an increased pLmV after only two minutes of stimulant exposure.

Significantly, these data provide evidence that low concentrations of guarana, caffeine and glucose in combination are sufficient to provide a short-term stimulus. We reiterate that since both caffeine and glucose provide only a low level of stimulation in the planarian model, we were able to detect the possibility of other stimulating substances within a guarana seed extract and assess whether caffeine and glucose can augment those effects.

Future studies will be required to identify the actual additional stimulant contained in guarana [ 19 ]. But, our overall impression from this work is that guarana does offer supplementary stimulation over caffeine, and that both caffeine and glucose can change the nature of this stimulation.

It is apparent that in order to fully appreciate how energy drinks affect physiology, it is important to consider the combination of the substituents they contain in that these substances may behave differently when mixed together in the same formulation.

Indeed, others have also put forward the idea of studying energy drink components in combination using human models [ 9 , 18 , 25 , 61 ], but given the complexities in controlling human dietary habits, particularly when caffeine is involved, we suggest that the planarian system offers a straightforward first approach to examine these complex interactions.

Further research is required, but our preliminary findings using the planarian model suggest that lower doses of stimulants can work together to provide a short-term stimulant effect, and that combining greater amounts of these ingredients might not provide a long-term benefit. We would like to thank John G.

Golfinos Department of Neurosurgery, New York University Langone Medical Center and Madeline Micceri Mignone Department of Math and Science, Dominican College , for helpful discussions, support and encouragement. We also thank Adam F. Green and Mala Misra Department of Biology, Colgate University , and Colleen A.

Evans Department of Math and Science, Dominican College for comments on the manuscript. We are also grateful to Dominican College for their support of undergraduate research in the Department of Math and Science, and Colgate University for providing a publication grant to support this work.

Conceived and designed the experiments: DM EBV. This allows tannins to waterproof the walls of your digestive tract, restricting how much water is secreted into your bowels On the other hand, guarana is rich in caffeine, which may act as a natural laxative.

Caffeine stimulates peristalsis, a process that activates contractions in the muscles of your intestines and colon. This may relieve constipation by pushing contents to the rectum Low doses of guarana do not provide much caffeine, so they are more likely to have an anti-diarrhea effect.

High doses provide more caffeine and may have laxative effects. The tannins in guarana may relieve diarrhea by preventing water loss. Meanwhile, the caffeine in guarana may relieve constipation by stimulating contractions in your intestines and colon that push contents toward the rectum.

Heart disease is responsible for one in four deaths in America First, the antioxidants in guarana appear to aid blood flow and may prevent blood clots Oxidized LDL cholesterol can contribute to plaque build-up in your arteries. However, most research on the connection between heart health and guarana comes from test-tube studies.

More human-based studies are needed before recommendations can be made. Guarana may aid heart health by improving blood flow and preventing blood clots. Two of these receptors — A1 and A2a — are involved in stimulating feelings of pain This is one reason why caffeine is commonly found in many over-the-counter pain relief medications.

Studies have shown it can significantly enhance their effects The caffeine in guarana may provide pain relief by blocking adenosine receptors, which are involved in stimulating feelings of pain. Due to its strong antioxidant and antimicrobial properties, guarana is popular in the cosmetics industry as an ingredient in anti-aging creams, lotions, soaps and hair products.

Moreover, its caffeine content aids blood flow to the skin Test-tube studies have shown that the antioxidants in guarana may significantly reduce age-related skin damage 9. Guarana has antioxidant and antimicrobial properties, making it a common additive in cosmetic products.

It may aid blood flow to your skin, reduce damage linked to aging and minimize undesirable features, such as saggy skin and wrinkles. Animal and test-tube studies suggest that guarana may protect against DNA damage, suppress cancer cell growth and even trigger cancer cell death 34 , 35 , Another test-tube study found that guarana suppressed the growth of cancer cells in the colon, as well as stimulated their death Scientists believe that the potential anti-cancer properties of guarana stem from its content of xanthines, which are compounds that are similar to caffeine and theobromine.

That said, though the results of test-tube and animal studies are promising, more human-based research is needed. Animal and test-tube studies have found that guarana may have anti-cancer properties. However, human-based research is required before recommending guarana for treatment.

One of these bacteria is Escherichia coli E. coli , which lives in the intestines of humans and animals. Most E. coli bacteria are harmless, but some can cause diarrhea or illness 38 , Studies have also found that guarana can suppress the growth of Streptococcus mutans S.

mutans , a bacteria that can cause dental plaques and tooth decay 40 , Guarana contains compounds that may inhibit or kill harmful bacteria, such as E. coli and Streptococcus mutans. Things like sunlight, poor diet and certain lifestyle choices like smoking can wear down your eyes over time and increase your risk of eye-related disorders Guarana contains compounds that fight oxidative stress, a major risk factor for age-related eye disorders like macular degeneration, cataracts and glaucoma One study found that people who consumed guarana regularly had better self-reported vision than people who consumed it sparingly or not at all In the same study, scientists performed test-tube experiments to discover if guarana could protect eye cells against compounds that create oxidative stress.

Guarana significantly reduced the amount of DNA damage and eye cell death, compared to a placebo That said, there is limited research in the area of guarana and age-related eye disorders. Test-tube studies have found that guarana may combat oxidative stress, which is linked to age-related eye disorders.

However, this area of research is limited, so more human-based studies are needed before providing recommendations.

It has also been linked to better heart health, weight loss, pain relief, healthier skin, lower cancer risk and a decreased risk of age-related eye diseases. Most research shows that doses between 50—75 mg of guarana are sufficient to provide you with health benefits, though there is no official dosage recommendation.

Whether you want to boost your energy levels or simply improve your overall health, guarana may be worth a try. Our experts continually monitor the health and wellness space, and we update our articles when new information becomes available. Caffeine can have impressive health benefits, but high doses can also lead to unpleasant side effects.

Here are 9 side effects of too much caffeine. For centuries, ginseng has been used in traditional Chinese medicine. Here are 7 proven benefits of ginseng. Caffeine is a natural stimulant consumed throughout the world. This article reviews caffeine and its health effects, both good and bad.

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A Quiz for Teens Are You a Workaholic? How Well Do You Sleep? Health Conditions Discover Plan Connect. Nutrition Evidence Based 12 Benefits of Guarana Plus Side Effects. By Ryan Raman, MS, RD — Updated on June 13, Share on Pinterest. Rich in Antioxidants. Can Reduce Fatigue and Improve Focus. May Help You Learn Better.

May Promote Weight Loss. May Relieve Chronic Diarrhea and Treat Constipation. May Boost Heart Health. May Provide Pain Relief. May Improve Skin Appearance. May Have Anti-Cancer Properties. Has Antibacterial Properties.

May Protect Against Age-Related Eye Disorders. Safe With Few Side Effects. The Bottom Line. How we reviewed this article: History.

Jun 13, Written By Ryan Raman. Share this article. Read this next. What Is Caffeine, and Is It Good or Bad for Health? By Alina Petre, MS, RD NL. Medically reviewed by Daniel Bubnis, M. The fruit contains black seeds that are covered by white arils, giving them a unique appearance that closely resembles an eye.

The seeds are very high in caffeine. They are often used as an additive in energy drinks or guarana soda brands like Guarana Antarctica.

Because of the guarana seed caffeine content, the seeds may come with other health benefits besides boosting energy levels. In fact, studies show that guarana could do everything from enhance skin health to increase weight loss and more. The fruit has a long history. It is deeply rooted in the mythology and culture of several indigenous South American groups.

According to legend, the cultivation of this plant began after a deity killed one of the children from the village. In an effort to console the people, the deity then plucked out the left eye of the child and planted it in the forest.

This is where wild guarana is believed to have first originated. Studies show that guarana can have a powerful impact on focus and memory. In fact, one study out of the Human Cognitive Neuroscience Unit at Northumbria University in the U.

showed that low doses were able to improve both memory performance and alertness compared to a control group. Similarly, another study conducted at Northumbria University compared the effects of guarana and ginseng and reported that guarana seed extract was able to significantly enhance task performance and attention to a greater extent than ginseng.

Guarana fruit contains a wide range of potent antioxidants, including caffeine, tannins, saponins, theobromine and catechins. Antioxidants are beneficial compounds that can help fight free radical formation and prevent oxidative damage to cells.

Not only that, but some research suggests that antioxidants can even protect against chronic conditions like heart disease, cancer and diabetes. Guarana is loaded with caffeine, with the seeds packing in a higher concentration of caffeine than even coffee beans.

Caffeine acts as a stimulant and affects the activity of certain neurotransmitters in your brain to amp up energy levels. This is why beverages like coffee and energy drinks are often used as a quick fix for low energy and fatigue.

In addition to fighting physical fatigue, some research indicates that guarana can help reduce mental fatigue as well. One study published in the journal Appetite showed that taking it was able to decrease mental fatigue associated with sustained mental effort in participants.

Guarana has long been used as a natural remedy for both constipation and diarrhea. It helps promote regularity and soothe digestive distress. Tannins are plant compounds that can prevent excess water from being excreted into the bowels to stop diarrhea fast.

Research shows that the guarana seed benefits heart health in several different ways. It can help prevent blood clots to reduce the risk of heart attacks and stroke, according to research out of the University of Cincinnati Medical Center.

Not only that, but it can also decrease the oxidation of LDL cholesterol in the blood. This can control the buildup of plaque in the arteries to prevent atherosclerosis.

Guarana makes a great addition to any natural skin care routine thanks to its content of both caffeine and antioxidants. Caffeine helps protect the skin against UV radiation. It also slows down photoaging of the skin and promotes circulation and blood flow.

One study published in the Journal of Cosmetic Dermatology showed that cosmetics containing guarana helped reduce skin sagging and minimized wrinkles underneath and around the eyes. Although current research is mostly limited to in vitro studies and animal models, preliminary evidence suggests that guarana could help effectively reduce the growth and spread of certain types of cancer cells.

For instance, one animal study showed that administering it to mice reduced liver cancer proliferation by 58 percent and increased cancer cell death by nearly fivefold.

Other studies have had similar findings. to prepare our standard stock solution. As with guarana and caffeine we conducted a pLmV study using glucose alone following exposure times of two minutes and one hour Fig 4.

The mM concentration proved inhibitory to planarian locomotion as determined by repeated coiling behavior, and as such, we conducted our experiments with a series of glucose concentrations below that value 0. We did not detect any significant increase in pLmV using any of these concentrations after either a two-minute or one-hour exposure period.

We did, however, detect a peak average relative stimulation of 1. This was significantly different from the average relative pLmV of 0. In contrast, the average relative locomotor velocities for the glucose concentrations tested after a one-hour exposure to glucose Fig 4B , did not result in any notable stimulation peaks above the water control despite a significant difference between 0.

Shown are selected pLmV data relative to water-only controls for Dugesia tigrina exposed to varying concentrations of glucose. Planarian motility was monitored after the worms were placed in a Petri dish containing the appropriate concentration of glucose following the tested habituation period.

We then assessed how the combination of guarana with glucose affected pLmV using low and high-end concentrations after two-minute and one-hour exposure times Fig 5. At the low end, with a concentration of 0. Importantly, neither the guarana extract, nor glucose alone provided a significant stimulation at this time point at 0.

This suggests that at low concentrations, glucose does provide a supportive effect to guarana stimulation over longer periods. In contrast, this effect was not apparent using a combined high-end concentration consisting of 0. It is notable that guarana did provide stimulation as a single reagent after two minutes at 0.

Statistical analysis indicated that the two-minute guarana single data at 0. Planarian motility was monitored after the worms were placed in a Petri dish containing the appropriate concentrations of guarana extract and glucose following the tested habituation period.

In contrast, following with a complementary assessment of caffeine and glucose Fig 6 we did not observe an increase in planarian locomotor velocity at either low or high-end concentration combinations for incubation periods of two minutes and one hour.

These findings again highlighted a potential difference between guarana and caffeine in that the response to glucose was different between the two stimulants. Planarian motility was monitored after the worms were placed in a Petri dish containing the appropriate concentrations of caffeine and glucose following the tested habituation period.

Upon an assessment of locomotor velocity using guarana seed extract together with caffeine and glucose Fig 7 we observed a slightly significant increase using low concentrations 0. Importantly, we did not detect a low-concentration stimulation after two minutes with the double combinations of guarana seed extract and caffeine, guarana seed extract and glucose, or caffeine and glucose Figs 3 , 5 and 6 , respectively.

This suggests that some stimulant benefit is achievable through the combination of all three substances that might not be apparent otherwise at lower concentrations of any of the three substances alone, or in pairs, for the short-term. The significant low-concentration stimulus was maintained at one hour albeit at a lower level, with an average relative stimulation of 1.

But, we also observed a low-concentration average relative stimulus with guarana extract at 0. Shown are pLmV data relative to water-only controls for Dugesia tigrina exposed to a combination of 0.

Planarian motility was monitored after the worms were placed in a Petri dish containing the appropriate concentrations of guarana extract, caffeine and glucose following the tested habituation period. In contrast, despite observing an improved pLmV relative to controls when planarians were exposed to a combination of guarana seed extract and caffeine at higher concentrations 0.

These data suggest that a short-term benefit is achieved with guarana, caffeine and glucose, but when combined at lower concentrations.

Energy drinks typically contain caffeine and sugars as their principal active ingredients. But many popular brands also contain blends of other substances that purportedly provide an added stimulus. One of these increasingly common additives is guarana. For this study we asked whether guarana had the potential to provide an added stimulant effect over caffeine alone using the planarian locomotor activity pLmV assay [ 42 , 43 ].

Reports suggesting that planarian activity is not significantly affected by caffeine supported our choice of model system in that it allowed us to detect the tonic effects of guarana seed constituents separate from those provided by caffeine [ 47 , 50 ]. Owing to the fact that caffeine is typically considered responsible for the stimulant properties of guarana, we used the reported five percent caffeine content of guarana seeds, and the typical range of caffeine concentrations reported for most energy drink formulations, as a starting point for our working guarana concentrations [ 19 , 30 , 55 , 56 ].

When comparing a gauntlet of caffeine and guarana concentrations on planarian motility, it was indeed apparent that caffeine did not significantly increase pLmV at any concentration tested, while guarana had a positive effect at concentrations ranging from 0.

Notably, while not significantly different from the water controls, the average relative pLmV for each of the concentrations of caffeine above 0. This contrasted to the results for the guarana extract alone after two minutes, where we observed a peak stimulation using a concentration of 0.

Had we chosen a less conservative caffeine content for our guarana seed powder, such as a high end estimate of 10 percent caffeine content—double our estimate—our high end concentration of 1. Therefore, since the data for caffeine and the guarana extract do not follow the same overall pattern of activity, it further suggests that guarana provides another stimulant value separate from that of caffeine alone.

Inspecting the pLmV data collected after a one-hour habituation in caffeine alone there was no evidence of stimulation at any concentration tested indicating that even the trend for a low-level stimulus, while not significantly greater than the water control, was a short-term effect Fig 2B.

In contrast, the post one-hour data collected for guarana seed extract-exposed pLmV showed a significant stimulus at 0.

These guarana findings suggested that a longer-term stimulus could be maintained at lower concentrations, providing further evidence in support of a difference between guarana and caffeine stimulation.

In general, however, we suggest that the one-hour data for both caffeine and guarana indicate that a tolerance-type of response occurs with length of exposure to higher concentrations of these stimulants.

Importantly, others have observed that planarians respond best to stimulants within the first five minutes of exposure, which is reflected in our findings as well [ 50 ].

Our locomotor data combining selected low and high concentrations of guarana seed extract and caffeine Fig 3 suggested that guarana provides an additional stimulation above that provided by caffeine alone.

Neither guarana seed extract nor caffeine alone provided a detectable increase in pLmV as a single stimulant at the low concentration examined 0. But, when the higher concentrations of 0. This average relative pLmV was augmented over that observed for guarana extract alone pointing to an additional short-term stimulation through the combination of higher concentrations of guarana and caffeine.

Furthermore, since such an additive effect was not observed by simply increasing the concentration of caffeine Fig 2 , the additional stimulation provided by guarana seed extract might be provided by some other water soluble ingredient in the seeds that functions using a metabolic pathway separate from that used by caffeine.

Significantly, another group examining the effects of guarana on mice also observed increases in activity that likely operated using a different mechanism than that used by caffeine [ 20 ].

While supporting our hypothesis that guarana contains stimulant properties independent of caffeine, this corroborating result also supports the use of the planarian for studies implicating stimulant effects in mammalian systems.

The stimulant effect of caffeine is suggested to be mediated by a number of mechanisms including the intracellular mobilization of calcium, the inhibition of phosphodiesterases, the binding of caffeine to benzodiazepine receptors, and antagonism at the level of adenosine receptors [ 58 , 59 ].

While the caffeine in guarana likely works by these mechanisms, other constituents possibly function using different pathways.

In addition to caffeine, guarana seeds are known to harbor a number of other possible stimulants such as catachins, tannins and other alkaloids such as theophylline and theobromine [ 19 , 22 , 30 , 60 ].

At present, little information is available favoring one of these ingredients over the others. We expanded our work to consider the effect of sugar on pLmV in conjunction with both caffeine and our guarana seed extract. The specific sugars in energy drink varieties vary, and as such we chose to work with D-glucose, or dextrose in our study.

Not all producers of energy drinks disclose complete concentrations of sugars in their formulations, so we calculated an average concentration to use in our experiments. We arrived at this value by averaging the amount of sugar disclosed on the few containers that gave some details of the total sugars they contained.

We compared this amount with those of estimates of total sugars in energy drinks discovered online, which were reflected in our chosen stock concentration [ 55 , 57 ]. While we observed that glucose alone did not offer an apparent stimulation of planarian motility Fig 4 , it did support guarana stimulation at low-end concentrations for a longer time Fig 5.

This was particularly interesting in that neither glucose alone Fig 4B nor guarana seed extract alone Fig 1B resulted in an increased pLmV after the one-hour habituation at these concentrations.

We also observed a significant short-term relative average stimulation with the combined high-end concentrations of glucose and guarana seed extract Fig 5 , but since the guarana seed extract alone resulted in a significantly augmented pLmV Fig 1 after the same time period, it was not possible to determine if glucose further intensified this effect using our system.

But, our data do suggest that at low concentrations, glucose does provide a supportive effect to guarana stimulation over longer periods.

These data are in line with published reports suggesting that glucose can support the effect of stimulants in the planarian model [ 48 ]. Conversely, our combinations of glucose and caffeine did not result in an increase of planarian motility at either time-point examined Fig 6 providing further evidence of stimulant properties in guarana that are indeed different from those of caffeine.

Exposing planarians to guarana seed extract, caffeine and glucose together resulted in augmented planarian motility after both short and long-term stimulation, but only with our low concentration combination Fig 7.

However, since our low concentration of guarana seed extract coupled with our low concentration of glucose also offered a sustained significant stimulation after the one-hour incubation, we cannot conclude that caffeine had an additional effect in this situation.

On the other hand, the triple combination was the only one tested that resulted an increased pLmV after only two minutes of stimulant exposure. Significantly, these data provide evidence that low concentrations of guarana, caffeine and glucose in combination are sufficient to provide a short-term stimulus.

We reiterate that since both caffeine and glucose provide only a low level of stimulation in the planarian model, we were able to detect the possibility of other stimulating substances within a guarana seed extract and assess whether caffeine and glucose can augment those effects.

Future studies will be required to identify the actual additional stimulant contained in guarana [ 19 ]. But, our overall impression from this work is that guarana does offer supplementary stimulation over caffeine, and that both caffeine and glucose can change the nature of this stimulation.

It is apparent that in order to fully appreciate how energy drinks affect physiology, it is important to consider the combination of the substituents they contain in that these substances may behave differently when mixed together in the same formulation.

Indeed, others have also put forward the idea of studying energy drink components in combination using human models [ 9 , 18 , 25 , 61 ], but given the complexities in controlling human dietary habits, particularly when caffeine is involved, we suggest that the planarian system offers a straightforward first approach to examine these complex interactions.

Further research is required, but our preliminary findings using the planarian model suggest that lower doses of stimulants can work together to provide a short-term stimulant effect, and that combining greater amounts of these ingredients might not provide a long-term benefit.

We would like to thank John G. Golfinos Department of Neurosurgery, New York University Langone Medical Center and Madeline Micceri Mignone Department of Math and Science, Dominican College , for helpful discussions, support and encouragement.

We also thank Adam F. Green and Mala Misra Department of Biology, Colgate University , and Colleen A. Evans Department of Math and Science, Dominican College for comments on the manuscript.

We are also grateful to Dominican College for their support of undergraduate research in the Department of Math and Science, and Colgate University for providing a publication grant to support this work. Conceived and designed the experiments: DM EBV.

Performed the experiments: DM MM BRR EBV MAC. Analyzed the data: EBV MEM DM. Wrote the paper: EBV. Browse Subject Areas? Click through the PLOS taxonomy to find articles in your field.

Article Authors Metrics Comments Media Coverage Reader Comments Figures. Abstract The stimulant effect of energy drinks is primarily attributed to the caffeine they contain. 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 Data Availability: All relevant data are within the paper.

Funding: The authors have no support or funding to report. Introduction Caffeine is considered the major stimulatory constituent of energy drinks while sugars and other substances such as guarana, taurine, and ginseng are added, often with combinations of vitamins, to formulate different blends [ 1 , 2 ].

Materials and Methods Planarian Husbandry Planarians Dugesia tigrina were purchased from Carolina Biological Supply Company ; Burlington, NC.

Planarian Locomotor Velocity pLmV Test The planarian locomotor velocity pLmV test as established by R.

Stock Solutions All solutions were prepared using distilled water. Results Guarana Provides Additional Short-Term Stimulation over Caffeine Alone The actual concentration of guarana present in energy drinks is typically not reported, but caffeine is considered the main stimulant present in the seeds [ 19 ].

Download: PPT. Fig 1. Planarian locomotor velocity pLmV increases in response to guarana alone. Fig 2. Caffeine alone does not support a significant increase in planarian locomotor velocity pLmV. Fig 3. Guarana supports an additional short-term stimulation of planarian locomotor velocity pLmV over caffeine alone.

Low Glucose Concentrations Support Long-Term Guarana Stimulation Since sugars are also a main ingredient in most energy drinks we next assessed how glucose influences guarana and caffeine stimulation.

Fig 4. Glucose alone does not support a significant increase in planarian locomotor velocity pLmV. Fig 5. Glucose supports guarana stimulation of planarian locomotor velocity pLmV. Fig 6. Glucose does not increase the effect of caffeine on planarian locomotor velocity pLmV. Guarana in Combination with Glucose and Caffeine Provides a Short-Term Stimulus at Low Concentrations Upon an assessment of locomotor velocity using guarana seed extract together with caffeine and glucose Fig 7 we observed a slightly significant increase using low concentrations 0.

Fig 7. Guarana with glucose and caffeine supports planarian locomotor velocity pLmV at low-end concentrations. Discussion Energy drinks typically contain caffeine and sugars as their principal active ingredients. Acknowledgments We would like to thank John G.