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From Sip to Synapse

by Advika Ramesh

art by Ariel Brown-Ogha


In the effervescent world of soft drinks, Diet Coke, amongst its many flashy diet counterparts, stands as a seemingly immortal icon, having found its way into the hearts and habits of millions globally. Yet, beneath the surface of its carbonated success, lies the intricate web of media influence, a potent force that has shaped the trajectory of this zero calorie beverage in society. Media and advertising have deftly crafted stories of diet sodas as an unspoken, yet prominently featured, character in our culture. Celebrity endorsements, for instance, have further perpetuated the narrative that diet drinks are the solution to body image issues. Kate Moss, a slim model who was famously quoted saying “nothing tastes as good as skinny feels,” is now tethered to the Diet Coke advertising campaigns. Lana Del Rey, an artist who has brought on a new revolution of svelte, girlish young women, has a song cooing about Diet Mountain Dew as a nod to diet culture. As various stars sip away at the calorie-free beverage, an aspirational image attached to success, beauty, and desirability is created. The insinuation is clear: to sip on Diet Coke is to sip on a potion of modern, guilt-free luxury. Laced with the notable artificial sweetener, aspartame, the beverage promises indulgence with little, if any, of the caloric cost. However, the media’s perspective on aspartame is not just an anthem of praise and aspiration.

Aspartame, an artificial sweetener that is approximately 200 times sweeter than table sugar, is ubiquitously employed in a myriad of food and beverage products [1]. It was invented in 1965 through a work safety violation, and during the 1970s, the FDA began to thoroughly review and evaluate the safety of aspartame [1, 2]. Since the initial research on aspartame seemed to be veering towards the optimistic end, stating that aspartame is safe for consumption within acceptable daily intake, consumers began to trade in their regular soda for diet [2]. However, new research reveals a landscape that serves as a battleground, where the health implications of diet sodas’ artificial sweeteners, especially aspartame, are hotly debated. It has spotlighted concerns and research regarding aspartame’s potential health risks, especially towards the brain, sparking dialogues that shift aspartame’s image from a healthy sugar alternative to a neurologically damaging, potential carcinogen that may not deliver on all it promises.

Diet Coke has found its niche in the realm where health consciousness converges with the unyielding human craving for sweetness, which is intricately linked to various neurological processes. The consumption of sugar not only activates sweet-taste receptors in the tongue, which send signals to the brain, but also stimulates nerve cells in the gut [3]. This dual stimulation leads to the activation of a neurological pathway that begins in the gut, where signals of sugar ingestion travel to the brain, thereby increasing the appetite for more sweet foods​​​​ [3]. When you bite into a sugary treat, it's not just your taste buds that light up. Sugar sets off a fireworks display in your brain's reward center, releasing feel-good chemicals like dopamine [4]. This neurological tango is why we often find ourselves craving another piece of chocolate or an extra scoop of ice cream — our brains are literally wired to find sugar irresistible. Aspartame acts in the same way as sugar, but at a lower rate [5]. This leaves us wanting more, as we are only halfway satisfied.

Aspartame is marketed as “sugar-free” or “diet” under the premise of offering a potently sweet low/no calorie alternative that had, in its initial rollout, conferred great benefits to the public, particularly diabetics and those striving to manage their weight, by providing a sweet-tasting option without the related surge in blood sugar levels or caloric intake [1]. The initial defense of aspartame was rooted in numerous studies that underscored its safety and efficacy as a sugar substitute [6]. Regulatory agencies, including the U.S. Food and Drug Administration (FDA) and the European Food Safety Authority (EFSA), reviewed the scientific evidence and affirmed the safety of aspartame for human consumption. They underlined that the research given by the opposition does not directly link aspartame to any detrimental effects and posed no significant threat to human health when consumed within established acceptable daily intake levels of 40-50 milligrams per kilogram a day, about 9-14 Diet Cokes a day for the average American (though its impact on the reward system, as discussed earlier, may make it harder for some to stay under the limit) [6–8]. Even after the International Agency for Research on Cancer (IARC) and the World Health Organization (WHO) spoke out against aspartame, the FDA released a statement doubling down on its belief that aspartame is safe within normal use, citing that Health Canada and EFSA continue to support aspartame as an alternative as well [8]. Despite ongoing debates and emerging studies exploring all facets of its health impacts, its defenders continue to tout that aspartame remains one of the most rigorously tested and globally approved food additives in the market.

However, this sweet tale is far from over. The assertions of the FDA, EFSA, and the many corporations mongering aspartame products has been challenged in scientific studies regarding its neurological impacts since around 2005 [2]. Aspartame is known to break down into phenylalanine and aspartic acid, two amino acids, and methanol, an organic alcohol, in the body. Phenylalanine has a unique property to cross the blood-brain barrier––a protective boundary that filters potentially harmful substances from entering the brain––which may limit the entrance of larger amino acids [9]. Phenylalanine is a precursor to the amino acid tyrosine. Tyrosine, in turn, is used by the body to synthesize several important neurotransmitters, including dopamine, norepinephrine, and epinephrine, which are each uniquely involved in facets of mood regulation, alertness, and the body's stress response [10]. Disruptions in the levels of phenylalanine and tyrosine, occurring because of excess phenylalanine consumption, can potentially impact the synthesis of these neurotransmitters and influence various neurological and psychological processes due to over synthesis [11]. Conditions like tyrosinemia, excess levels of tyrosine, inhibit essential metabolic enzymes in the brain, which can lead to oxidative stress––an imbalance between extremely reactive molecules and the body's ability to counteract or detoxify their harmful effects through neutralization by antioxidants––and cognitive impairments [12] . Some studies and anecdotal evidence have also suggested that aspartame may lower the seizure threshold because of this increase in neurotransmitters, making individuals more susceptible to epileptic episodes [13]. A more unique challenge is faced by people with phenylketonuria (PKU), a genetic defect occurring in about 1 in 10000 people that results in the inability to properly metabolize phenylalanine. If levels of phenylalanine become too high, it can lead to brain damage, with research specifically showing impaired cognition, making strict dietary control especially important for these individuals [14, 15].

These potential negative effects of aspartame may also imply that sipping on diet soda may be fizzling out your memory spanning generations! A study on mice has shown that, after aspartame exposure, mice exhibited decreased spatial memory due to a reduction of glutathione [16]. Glutathione plays a key role in detoxifying oxygen-containing species in the body to keep cells healthy and functional. A reduction in glutathione results in increased susceptibility to oxidative damage, which consequently impairs short term memory, memory held in your brain for about 20 to 30 seconds before it's either forgotten or transferred to long-term memory. This study investigated the effects of repeated aspartame administration on mice's memory and brain health. Results showed that only the highest dose of aspartame, a level seen in chronic users, significantly impaired the mice's ability in the water maze test, a behavioral experiment used in neuroscience to assess spatial learning and memory in rodents by measuring their ability to locate a hidden platform in a circular pool of water. Additionally, aspartame increased oxidative stress in the brain, reduced glucose availability, and inhibited certain neurotransmitters like dopamine, epinephrine, and serotonin, linking aspartame to impaired memory performance and increased oxidative stress in the brain [16]. In another study, male mice were given water containing aspartame at levels found in about 2-4 small cans of diet soda daily [17]. Over a 16-week period, these mice had noticeable troubles with their spatial memory and learning abilities. Interestingly, these memory issues started showing as early as 4 weeks into the experiment and persisted for up to 12 weeks. What is even more surprising is that these memory problems were passed down to their children, leading to two generations of spatial working memory and spatial learning deficits. However, the next generation––their grandchildren––didn't seem to inherit these issues. This study aimed to replicate the effects of long-term human consumption but at only 7-15% of the daily amount the FDA recommends as safe, replicating an amount closer to the average daily drinker of aspartame. These findings suggest that aspartame may not only impact our memory and learning abilities, but also that these effects could be passed down to our children.

Aspartame’s hit on memory is not limited to the short-term. Recent research from a community-based study has found a link between drinking artificially-sweetened sodas and an increased risk of stroke and dementia [18]. Interestingly, this risk wasn't found with naturally sugary drinks! The study dove deep into the dietary habits of thousands of men and women for over 10 years. It is also worth noting a confounding variable: people with diabetes, a known risk factor for dementia, are likely more frequent consumers of artificially-sweetened drinks because of their dietary restrictions. Although, it is still uncertain whether these drinks increase the risk of diabetes or if those with diabetes just tend to drink more of them [18].

For many people, the idealized image of becoming more slender is what keeps them drawn to diet sodas, but recent findings indicate that consuming aspartame and other artificial sweeteners over an extended period might contribute to an increase in fat deposits in the body and a heightened risk of obesity [19]. Surprisingly, these effects seem to persist regardless of the overall quality of one's diet or the total calories consumed [19]. This study challenges the common advice to swap out regular sugar for artificial sweeteners as a healthier choice.

Aspartame’s most recent negative attention has come because of its potential cancer-causing properties. Imagine sipping on your favorite low-calorie beverage, believing it's a healthier choice, only to discover that it might be similar to smoking a cigarette. One study discovered that rats and mice exposed to aspartame at the acceptable daily limit developed malignant tumors in various organs [20]. Shockingly, even minimal exposure levels, close to the acceptable daily intake, showed an increased cancer risk. It is increasingly alarming that unborn animals exposed to aspartame were more prone to developing cancer than adults [20]. Given that the brain is a primary organ affected by dietary intake and metabolic processes, the potential carcinogenic effects of aspartame at a neural level warrant further investigation, particularly considering the heightened vulnerability of unborn animals in these studies. This underscores the importance of reevaluating aspartame's safety, not just in terms of general health but also concerning its specific impact on neurological health and development, especially in sensitive groups such as pregnant women and children. In 2023, the International Agency for Research on Cancer (IARC), the World Health Organization (WHO), and the Food and Agriculture Organization (FAO) Joint Expert Committee on Food Additives (JECFA) classified aspartame as a class 2B carcinogen, which states that aspartame is potentially carcinogenic, though they denied a necessity to change the acceptable daily intake of 40 mg/kg body weight due to a lack of evidence of its effects in humans [21]. This statement may lead to increased research into aspartame's health effects, influence consumer choices, and potentially prompt revisions of food labeling and safety regulations, while underscoring the need for ongoing research and evaluation.

Phenylalanine and aspartic acid, the byproducts of aspartame ingestion that were mentioned earlier, are also involved in neurotransmitter regulation and modulate mood and cognitive functions, such as anxiety, fear, pleasure, and reward. One study shows there is a significant decline in dopamine, serotonin, and GABA reuptake once aspartame is ingested; making emotional regulation dependent on one’s aspartame intake if they regularly consume it [22]. The subjective experience of enhanced mood or satisfaction following the consumption of aspartame-sweetened products might reinforce a repeat of the consumption behavior, which may invoke a cycle that outwardly resembles addiction. A sweet taste, irrespective of the source, triggers reward pathways in the brain, a mechanism fundamental to addictive behaviors [23]. Sweetness stimulates the release of dopamine, a neurotransmitter linked with the brain’s reward system, creating a pathway through which repeated engagement with sweet substances, like aspartame, might be perpetuated [23].

Anecdotal reports from aspartame users propose a scenario where individuals experience cravings and a habitual “pull” towards products containing aspartame. Thirty-three (5.6%) of 540 aspartame users in a study found it difficult, or impossible, to discontinue aspartame due to severe withdrawal effects [24]. They described several physical manifestations that are typically associated with withdrawal effects, like severe depression (23%), tremors (8%), thirst (10%) and urinary troubles (11%) [24]. These findings, suggesting that aspartame can induce cravings and withdrawal symptoms similar to addictive substances, highlight the need for a deeper understanding of its impact on human behavior and physiology, especially considering its widespread use in food products.

Aspartame addiction has been subject to scrutiny and skepticism in some scientific circles, citing doubt in the physiological pathways that characterize substance addiction. However, a study found that when given a choice between water sweetened with saccharin (a calorie-free sweetener far less sweet than aspartame) and intravenous cocaine, 94% of rats preferred the sweetened water [25]. This preference was also observed with natural sugar and not diminished by increased cocaine doses. This suggests that intense sweetness can be more rewarding than cocaine, leading to the possibility of sugar addiction in modern sugar-rich diets. This same study posits that because the amount of sugar and sugar-like substances humans consume today are far beyond our ancestors, our bodies have not yet adapted to this new, highly potent diet that sweeteners cause [25].

When it comes to addressing the controversies and health concerns swirling around aspartame, a range of potential solutions are being considered. One viewpoint suggests improving labeling and consumer education to ensure that individuals are well-informed about what they consume and can then make choices that align with their health needs and preferences [26]. Other groups of scientists and health experts propose rigorous, additional research to conclusively determine the impact of aspartame on human health, calling for studies that are transparent, comprehensive, and replicable to ensure unbiased and reliable results, considering many of these initial positive studies may have been conducted with an ulterior capitalist motive, like researchers who’d initially pioneered research having ties to PepsiCo, a company peddling aspartame products [27] . Still there are proponents for alternative sweeteners derived from natural sources, which might provide the sweetness desired without the potential health risks. Stevia, made with steviol glycosides, is a natural sweetener that's not just zero-calorie but also packs a punch with some surprising health benefits. Perfect for those with diabetes or the rare condition phenylketonuria (PKU), steviol glycosides have impacts beyond just sweetening your morning coffee because it has properties that may help with everything from inflammation and high blood pressure to even potentially fending off cancer [8, 28], which may suggest that steviol glycosides might be a safer choice than aspartame. Research indicates that also miracle fruit can be used as a natural flavor booster and sugar replacement in many sour foods and drinks. Miracle fruit not only has antioxidant properties, but also helps control high blood sugar, especially in large amounts. It appears to be a healthier sweetener choice compared to artificial ones like aspartame, particularly since miracle fruit protects the liver [8, 29].


It is evident that aspartame wields a double-edged sword; offering advantages while also stirring persistent concerns. On one hand, aspartame has enabled countless individuals to enjoy sweet flavors without the caloric and metabolic ramifications of sugar, supporting dietary management and providing options for diabetics. Conversely, the skepticism regarding its safety, spurred by various scientific studies and anecdotal evidence of adverse effects, cannot be dismissed lightly. Striking a meticulous balance between advocating for healthier, low-calorie alternatives and ensuring public safety necessitates ongoing, rigorous research that seeks to illuminate, with unassailable clarity, the long-term impacts of aspartame consumption. Consequently, while aspartame remains a pivotal player in the global food and beverage industry, it is imperative that its utilization is continually appraised through the lens of emerging scientific evidence, ensuring that its benefits genuinely outweigh any potential detriments to public health.

While diet sodas might be a tempting low-calorie option, it's essential to pause and ponder before popping that can open. The potential risks that lurk within the confines of aspartame, the sweetest secret, warrants a moment of contemplation. So, the next time you reach for that Diet Coke, consider if it's truly a healthier choice or just a bubbly illusion.


REFERENCES:

1. Czarnecka, K., Pilarz, A., Rogut, A., Maj, P., Szymańska, J., Olejnik, Ł., & Szymański, P. (2021). Aspartame-True or False? Narrative Review of Safety Analysis of General Use in Products. Nutrients, 13(6), 1957. https://doi.org/10.3390/nu13061957

2. Nutrition, C. for F. S. and A. (2023). Timeline of Selected FDA Activities and Significant Events Addressing Aspartame. FDA. Retrieved from https://www.fda.gov/food/food-additives-petitions/timeline-selected-fda-activities-and-significant-events-addressing-aspartame

3. Tan, H.-E., Sisti, A. C., Jin, H., Vignovich, M., Villavicencio, M., Tsang, K. S., … Zuker, C. S. (2020). The gut–brain axis mediates sugar preference. Nature, 580(7804), 511–516. https://doi.org/10.1038/s41586-020-2199-7

4. Freeman, C. R., Zehra, A., Ramirez, V., Wiers, C. E., Volkow, N. D., & Wang, G.-J. (2018). Impact of sugar on the body, brain, and behavior. Frontiers in Bioscience (Landmark Edition), 23(12), 2255–2266. https://doi.org/10.2741/4704

5. Yang, Q. (2010). Gain weight by “going diet?” Artificial sweeteners and the neurobiology of sugar cravings: Neuroscience 2010. The Yale Journal of Biology and Medicine, 83(2), 101–108.

6. Butchko, H. H., Stargel, W. W., Comer, C. P., Mayhew, D. A., Benninger, C., Blackburn, G. L., … Trefz, F. K. (2002). Aspartame: Review of Safety. Regulatory Toxicology and Pharmacology, 35(2), S1–S93. https://doi.org/10.1006/rtph.2002.1542

7. EFSA completes full risk assessment on aspartame and concludes it is safe at current levels of exposure | EFSA. (2013, December 10). Retrieved November 30, 2023, from https://www.efsa.europa.eu/en/press/news/131210

8. Nutrition, C. for F. S. and A. (2023). Aspartame and Other Sweeteners in Food. FDA. Retrieved from https://www.fda.gov/food/food-additives-petitions/aspartame-and-other-sweeteners-food

9. Choi, T. B., & Pardridge, W. M. (1986). Phenylalanine transport at the human blood-brain barrier. Studies with isolated human brain capillaries. Journal of Biological Chemistry, 261(14), 6536–6541. https://doi.org/10.1016/S0021-9258(19)84595-7

10. Paravati, S., Rosani, A., & Warrington, S. J. (2023). Physiology, Catecholamines. In StatPearls. Treasure Island (FL): StatPearls Publishing. Retrieved from http://www.ncbi.nlm.nih.gov/books/NBK507716/

11. Matthews, D. E. (2007). An Overview of Phenylalanine and Tyrosine Kinetics in Humans. The Journal of Nutrition, 137(6), 1549S-1555S. https://doi.org/10.1093/jn/137.6.1549S

12. de Oliveira, J., Farias, H. R., & Streck, E. L. (2021). Experimental evidence of tyrosine neurotoxicity: focus on mitochondrial dysfunction. Metabolic Brain Disease, 36(7), 1673–1685. https://doi.org/10.1007/s11011-021-00781-w

13. Choudhary, A. K., & Lee, Y. Y. (2018). The debate over neurotransmitter interaction in aspartame usage. Journal of Clinical Neuroscience, 56, 7–15. https://doi.org/10.1016/j.jocn.2018.06.043

14. De Groot, M. J., Hoeksma, M., Reijngoud, D.-J., De Valk, H. W., Paans, A. M., Sauer, P. J., & Van Spronsen, F. J. (2013). Phenylketonuria: reduced tyrosine brain influx relates to reduced cerebral protein synthesis. Orphanet Journal of Rare Diseases, 8(1), 133. https://doi.org/10.1186/1750-1172-8-133

15. Trepp, R., Muri, R., Abgottspon, S., Bosanska, L., Hochuli, M., Slotboom, J., … Everts, R. (2020). Impact of phenylalanine on cognitive, cerebral, and neurometabolic parameters in adult patients with phenylketonuria (the PICO study): a randomized, placebo-controlled, crossover, noninferiority trial. Trials, 21, 178. https://doi.org/10.1186/s13063-019-4022-z

16. Abdel-Salam, O. M. E., Salem, N. A., El-Shamarka, M. E. S., Hussein, J. S., Ahmed, N. a. S., & El-Nagar, M. E. S. (2012). Studies on the effects of aspartame on memory and oxidative stress in brain of mice. European Review for Medical and Pharmacological Sciences, 16(15), 2092–2101.

17. Jones, S. K., McCarthy, D. M., Stanwood, G. D., Schatschneider, C., & Bhide, P. G. (2023). Learning and memory deficits produced by aspartame are heritable via the paternal lineage. Scientific Reports, 13(1), 14326. https://doi.org/10.1038/s41598-023-41213-2

18. Pase, M. P., Himali, J. J., Beiser, A. S., Aparicio, H. J., Satizabal, C. L., Vasan, R. S., … Jacques, P. F. (2017). Sugar- and Artificially Sweetened Beverages and the Risks of Incident Stroke and Dementia: A Prospective Cohort Study. Stroke, 48(5), 1139–1146. https://doi.org/10.1161/STROKEAHA.116.016027

19. Steffen, B. T., Jacobs, D. R., Yi, S.-Y., Lees, S. J., Shikany, J. M., Terry, J. G., … Steffen, L. M. (2023). Long-term aspartame and saccharin intakes are related to greater volumes of visceral, intermuscular, and subcutaneous adipose tissue: the CARDIA study. International Journal of Obesity, 47(10), 939–947. https://doi.org/10.1038/s41366-023-01336-y

20. Landrigan, P. J., & Straif, K. (2021). Aspartame and cancer – new evidence for causation. Environmental Health, 20(1), 42. https://doi.org/10.1186/s12940-021-00725-y

21. Aspartame hazard and risk assessment results released. (n.d.). Retrieved November 30, 2023, from https://www.who.int/news/item/14-07-2023-aspartame-hazard-and-risk-assessment-results-released

22. Li, X., Dong, G., Han, G., Du, L., & Li, M. (2021). Zebrafish Behavioral Phenomics Links Artificial Sweetener Aspartame to Behavioral Toxicity and Neurotransmitter Homeostasis. Journal of Agricultural and Food Chemistry, 69(50), 15393–15402. https://doi.org/10.1021/acs.jafc.1c06077

23. De Silva, P. N. (2020). Are sweetened drinks a gateway to alcohol, opiate and stimulant addiction? Summary of evidence and therapeutic strategies. Medical Hypotheses, 135, 109469. https://doi.org/10.1016/j.mehy.2019.109469

24. Authority (EFSA), E. F. S. (2010). Report of the meeting on Aspartame with National Experts. EFSA Supporting Publications, 7(5), 1641. https://doi.org/10.2903/sp.efsa.2010.ZN-002

25. Lenoir, M., Serre, F., Cantin, L., & Ahmed, S. H. (2007). Intense sweetness surpasses cocaine reward. PloS One, 2(8), e698. https://doi.org/10.1371/journal.pone.0000698

26. Farhat, G., Dewison, F., & Stevenson, L. (2021). Knowledge and Perceptions of Non-Nutritive Sweeteners Within the UK Adult Population. Nutrients, 13(2), 444. https://doi.org/10.3390/nu13020444

27. Ahmad, S. Y., Friel, J., & Mackay, D. (2020). The Effects of Non-Nutritive Artificial Sweeteners, Aspartame and Sucralose, on the Gut Microbiome in Healthy Adults: Secondary Outcomes of a Randomized Double-Blinded Crossover Clinical Trial. Nutrients, 12(11), 3408. https://doi.org/10.3390/nu12113408

28. Saad, A., Khan, F. A., Hayee, A., & Nazir, M. S. (2014). A Review on Potential Toxicity of Artificial Sweetners vs Safety of Stevia: A Natural Bio-Sweetner. Journal of Biology.

29. Haddad, S. G., Mohammad, M., Raafat, K., & Saleh, F. A. (2020). Antihyperglycemic and hepatoprotective properties of miracle fruit (Synsepalum dulcificum) compared to aspartame in alloxan-induced diabetic mice. Journal of Integrative Medicine, 18(6), 514–521. https://doi.org/10.1016/j.joim.2020.09.001

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