Lasting energy with sustained release caffeine

Caffeine is synonymous with energy, and is among the highest selling functional ingredients on the market. According to data from SPINS, based on the 52 weeks ending October 6, 2024, caffeine ranked 13 in the top 25 best-selling functional ingredients in the mainstream multioutlet channel, with $435 million in sales. Most people consumer caffeine from beverages, particularly coffee. A recently published study¹ based on a 2022 beverage survey of 49,700 American consumers over the age of two years found that about 69% of respondents consumed at least one caffeinated beverage per day with an average caffeine intake of 210±1.5 mg per day. The highest consumption of caffeine was among respondents between the ages of 50 and 64, with an average of 246±4.5 mg per day.At the 90th percentile, this intake went as high as 520 mg per day for all ages combined, while the U.S. Food and Drug Administration (FDA) recommends a limit of 400 mg of caffeine per day to avoid negative effects, or about two to three 12 fluid-ounce cups of coffee.² As far as the source of caffeine, coffee was the largest contributor of caffeine intake with 69%.

Overconsumption of caffeine can have some potential side effects. These include increases in blood pressure, heart rate, and heart palpitations, which can be risky for people with pre-existing heart conditions, as well as jitters, insomnia, and anxiety. Some people could even get headaches, upset stomach, or nausea from overconsumption. This can vary from person to person, with genetics playing a role in how caffeine is absorbed and processed by the body.³ A potential solution to problems of overconsumption and their side effects is sustained-release caffeine.

“Research has shown that after drinking caffeine-containing beverages, the effects are felt after only 10 to 15 minutes and the peak caffeine amount in the blood occurs after approximately 60 minutes; caffeine in tablet form will peak in the blood after an hour to 75 minutes,” says Rajat Shah, co-founder of Nutriventia (Mumbai, India), which offers a sustained release caffeine ingredient called CaffXtend. “While this may be beneficial in a pre-workout situation, the effect of conventional caffeine is often short-lived, providing a quick burst of energy that fades soon after exercise.”

By contrast, “sustained release provides longer-lasting energy and focus, while helping to minimize the side effects typically associated with a single high dose,” says Pawas Soni, global category manager of OmniActive Health Technologies (Bridgewater, NJ), which supplies a sustained-release caffeine ingredient called Xtenergy. “For the user, this means smooth, consistent alertness and mental clarity throughout the day, limiting the spikes and crashes.”

While caffeine is associated with energy, it is very much a nootropic ingredient as it works by binding to adenosine receptors in the central and peripheral nervous systems. Adenosine is a molecule that can fuel cells (in the form of adenosine triphosphate) and acts as a neuromodulator that can promotes sleep as well as affect memory and learning.⁴This is why both Nutriventia and OmniActive Health Technologies emphasizes the cognitive health effects of their products, particularly as they relate to focus and alertness.

“The dual benefit of steady stimulation and reduced crash makes it ideal for products supporting focus, attention, and executive function across a broad user base, from students and professionals to older adults and active consumers,” explains Soni. “It’s also an excellent fit in pre-workouts, energy shots, and RTD beverages, where lasting energy without overstimulation is desirable.”

Pharmacokinetic studies show impressive results for both these ingredients. Xtenergy at a dose of 200 mg per day was found to have time-to-peak concentration that was 325.53% higher than immediate-release caffeine, and a 21.34% longer half-life.⁵ Similarly, at a dose of 200 mg per day, CaffXtend was found in a study to have a 391.57% longer time-to-peak concentration and a 22.32% longer half life.⁶ Another sustained-released caffeine ingredient on the market, called zümXR, distributed by PLT Health Solutions (Morristown, NJ), was found in a pharmacokinetic study to have a 300% longer time-to-peak concentration and 64.6% longer half-life at a dose of 250 mg per day.⁷

When it comes to the cognitive health impacts, the studies showed that participants taking Xtenergy and CaffXtend had significantly higher alertness scores between four and 12 hours, compared to conventional caffeine, significantly lower tired scores overs the course of 12 hours, as well as significantly lower jittery scores. Consumption of sustained-release caffeine also resulted in significantly better overall mood over the course of 12 hours.

Caffeine Sources

Caffeine can come from natural sources such as green tea and coffee, or it can be synthesized. While functionally the same, the connotation of natural sources is often more positive. CaffXtend, for example, is sourced from Coffee Robusta beans. “The natural caffeine we use is a cleaner alternative, with a lower likelihood of chemical impurities or residues that can result from synthetic production processes,” explains Shah. “While it is 99% pure caffeine and chemically identical to synthetic caffeine, its natural origin offers added reassurance for those seeking a cleaner label and greater peace of mind.”

Soni agrees that natural sources allow for clean-label positioning, adding that “natural sources may also provide phytonutrients, such as antioxidants from green tea or polyphenols from coffee, offering potential added health benefits.”

Xtenergy is sourced from green coffee beans which Soni says naturally retain more caffeine compared to roasted coffee beans.

Paraxanthine

As mentioned previously, genetics can influence how caffeine is metabolized. To start, caffeine is metabolized in the liver by the isozyme, CYP1A2, and there are three major metabolites that caffeine is broken down into: paraxanthine, theobromine, and theophylline. Paraxanthine is the primary metabolite, accounting for 80% of caffeine biotransformation, while theobromine and theophylline account for 11% and 5%, respectively.⁸

Genetics influence the activity of CYP1A2, with some people having lower activity, and therefore slower metabolism of caffeine. That means it takes longer for it to leave their bodies, resulting in negative side effects, particularly if they consume caffeine in excess. Because the downstream metabolites are staying in the body for longer, slow metabolizers are more susceptible to some of their negative effects. Metabolites such as theophylline, for example, have been associated with negative side effects like nausea, diarrhea, and tachycardia.⁹

On the other hand, the metabolite paraxanthine has been shown to have less toxicity and anxiogenic effects than caffeine. Therefore, as a supplement, paraxanthine is being touted as a “clean energy” alternative to caffeine. One brand of paraxanthine that is currently on the market is called enfinity, which is being distributed by TSI Group (Missoula, MT).

According to Shawn Baier, MS, MBA, vice president of business development at TSI Group, the ingredient works well because it removes the need for metabolic conversion altogether. “By delivering paraxanthine directly, we eliminate this variability [of caffeine metabolites] and provide a more consistent, predictable response,” he explains. “This bypasses the potentially undesirable effects associated with caffeine’s other metabolites, allowing users to experience the primary benefits of caffeine—energy, focus, and alertness—without relying on individual metabolic efficiency.”

Baier says that because paraxanthine is the most efficacious metabolite of caffeine, supplementing with paraxanthine may have some advantages over caffeine itself. A recent study compared the cognitive health effects of paraxanthine to caffeine in trained runners following a 10 km run.¹⁰ Results showed that those taking paraxanthine had fewer errors in a Berg-Wisconsin Card Sorting Test (BCST) compared to placebo and caffeine. Researchers concluded that paraxanthine consumption improved “prefrontal cortex function, attenuates attentional decline, mitigates cognitive fatigue, and improves reaction time and vigilance.”

“Additionally, paraxanthine exhibits mechanistic differences: it supports dopaminergic signaling, nitric oxide production, and inhibits PDE9, which may contribute to improved cerebral blood flow and neuroprotection,” says Baier. “Preclinical studies also show increased BDNF expression, associated with enhanced neuroplasticity and long-term cognitive resilience.”

Formulation

Ease of formulation is an important factor to consider if you hope to combine an ingredient with other complementary ingredients or use in an alternative dosage format such as gummies. According to Soni and Shah, Xtenergy and CaffXtend both work well with other ingredients and are flexible to formulate with. This is an advantage considering the growth of alternative dosage formats.

“Capsules and tablets remain popular in cognitive and general energy supplements, while stick packs, RTD beverages, shots, and powdered drink mixes are preferred in sports and active lifestyle products,” says Soni. “The format often depends on the end use. Capsules for daily focus, pre-workout powders for fitness performance, and shots or gummies for convenient, on-the-go energy.”

Baier says the TSI’s enfinity paraxanthine is also versatile as it is 22% less bitter than caffeine and water soluble, making it ideal for a range of formats that include powders, liquids, gummies, and capsules.

Caffeine is here to stay, and the innovation of sustained-release caffeine, and caffeine derivatives only renews the ingredient’s staying power in the world of energy.

References

1. Mitchell, DC.; Trout, M.; Smith, R.; Teplansky, R.; Lieberman, HR. An update on beverage consumption patterns and caffeine intakes in a representative sample of the US population. Food and Chemical Toxicology. 2025. DOI:10.1016/j.fct.2025.115237. (accessed 2025-01-09). 
2. Spilling the Beans: How Much Caffeine is Too Much? U.S. Food and Drug Administration. August 28, 2024. https://www.fda.gov/consumers/consumer-updates/spilling-beans-how-much-caffeine-too-much#Footnote (accessed 2025-05-20). 
3. Wikoff, D.; Welsh, B.T.; Henderson, R.; Brorby, G.P.; Britt, J.; Myers, EE.; Goldberger, J.; Lieberman, H.R.; et al.Systematic review of the potential adverse effects of caffeine consumption in healthy adults, pregnant women, adolescents, and children. Food and Chemical Toxicology. 2017, 109 (1), 585-648. DOI:10.1016/j.fct.2017.04.002
4. Temple, J.L.; Bernard, C.; Lipschultz, S.E.; Czachor, J.D.; Westphal, J.A.; Mestre, M.A.The Safety of Ingested Caffeine: A Comprehensive Review. Front Psychiatry. 2017, 8, 80. DOI:10.3389/fpsyt.2017.00080 
5. Morde, A.; Sudhakar, K.; Rambabu, M.; Shankar, A.; Rai, D.; Pawar, K.; Acharya, M.; Bakan, M.; et al. Pharmacokinetic profile of a novel sustained-release caffeine with extended benefits on alertness and mood: A randomized, double-blind, single-dose, active-controlled, crossover study. Current Research in Behavioral Sciences. 2021, 2, 100036. DOI: 10.1016/j.crbeha.2021.100036
6. Thanawala, S.; Shah, R.; Abiraamasundari, R.; Senthurselvi, R.; Desomayanandam, P.Comparative Bioavailability and Benefits on Mental Functions of Novel Extended-Release Caffeine Capsules against Immediate-Release Caffeine Capsules: An Open-Label, Randomized, Cross-over, Single-Dose Two-Way Crossover Study. Journal of Dietary Supplements. 2023, 21 (1), 13-27. DOI:10.1080/19390211.2022.2160529
7. Kalman, D.; Hewlings, S.; Lee, R.; Foster, R.; Morton, K.A24 A comparative pharmacokinetic evaluation of caffeine in two different delivery vehicles in healthy adults. J Int Soc Sports Nutr. 2018, 15 (Suppl 1), 1-37. DOI:10.1186/s12970-018-0256-5 
8. Willson, C. The clinical toxicology of caffeine: A review and case study. Toxicol Rep. 2018, 5, 1140-1152. DOI: 10.1016/j.toxrep.2018.11.002 
9. Okuro, M.; Fujiki, N.; Kotorii, N.; Ishimaru, Y.; Sokoloff, P.; Nishino, S. Effects of Paraxanthine and Caffeine on Sleep, Locomotor Activity, and Body Temperature in Orexin/Ataxin-3 Transgenic Narcoleptic Mice. Sleep. 2010, 33 (7), 930-942. DOI:10.1093/sleep/33.7.930 
10. Yoo, C.; Xing, D.; Gonzalez, D.E.; Jenkins, V.; Nottingham, K.; Dickerson, B.; Leonard, M.; Ko, J.; et al. Paraxanthine provides greater improvement in cognitive function than caffeine after performing a 10-km run. J Int Soc Sports Nutr. 2024, 21(1), 2352779. DOI:10.1080/15502783.2024.2352779