Do Humans Have a “Sixth Taste” That Detects Calories?

Imagine this: You’re sipping on a diet soda, enjoying that sweet, sugary taste—without a single calorie in sight. Sounds like a dream, right? You get all the sweetness without the guilt. But here’s the catch: while your tongue might be fooled, your brain isn’t.

New research suggests that the human brain has its own built-in calorie detector independent of taste perception, one that artificial sweeteners can’t trick. This system allows the body to distinguish between energy-yielding sugars and non-nutritive artificial sweeteners, influencing metabolic and behavioural responses. But how does this system work, and what implications does it have for human nutrition and food science?

How the Tongue Detects Sweetness (T1R2/T1R3 Receptors)

The tongue is a highly specialised sensory organ responsible for detecting five basic tastes: sweet, salty, sour, bitter, and umami. The perception of sweetness is primarily mediated through the T1R2/T1R3 receptor complex, a G protein-coupled receptor (GPCR) found on taste buds (Fernstrom et al., 2012). When sugar or artificial sweeteners bind to this receptor, a signaling cascade is triggered, sending electrical impulses to the gustatory cortex—the brain region responsible for processing taste.

However, there is a crucial difference between real and artificial sweeteners: calories. 

While both activate the sweetness receptors on the tongue, only real sugar provides energy. Artificial sweeteners, despite mimicking the taste, fail to engage post-ingestive metabolic pathways—the body’s internal system for processing nutrients. This disconnect may disrupt appetite regulation, as the brain detects sweetness but receives no actual fuel. 

Neural Differences Between Sugar and Artificial Sweeteners:

Furthermore, the striatum, a key part of the brain’s reward system, plays a crucial role in distinguishing caloric sugars from artificial sweeteners. Research suggests that only real sugars trigger dopamine release in the striatum, reinforcing the body’s preference for energy-rich foods.

Deep within the brain, neurons in the striatum respond strongly when you consume real sugar. But when you ingest artificial sweeteners? The response is muted. It’s as if the brain is anticipating energy, and when it doesn’t arrive, the reward system remains unfulfilled, potentially leading to increased cravings and food intake.

A systematic review by Yeung and Wong (2020) analysed fMRI studies comparing brain responses to sugars and non-nutritive sweeteners. The review revealed that sugar consumption leads to stronger activation in the brain's hedonic pathways, including regions such as the anterior insula, frontal operculum, striatum, anterior cingulate cortex, ventral tegmental area, and amygdala, compared to artificial sweeteners. This suggests that the brain has a distinct mechanism for detecting caloric content, separate from taste perception alone.

Implications for Diet and Metabolism

Artificial sweeteners, despite mimicking the taste of sugar, may disrupt the brain’s natural hunger and satiety signals, potentially leading to increased food intake. Since real sugar activates metabolic and reward pathways linked to energy detection, the absence of caloric content in artificial sweeteners could create a mismatch between perceived sweetness and actual energy intake, causing the brain to signal for more food. This mechanism may play a role in obesity and metabolic disorders, as frequent artificial sweetener consumption could lead to dysregulated appetite control.

Researchers are now investigating whether caloric detection pathways can be consciously overridden or manipulated to support weight management. If scientists can better understand how the brain distinguishes between caloric and non-caloric sweeteners, they might develop low-calorie foods that provide a more satisfying and metabolically appropriate response, potentially revolutionising diet products.

However, many questions remain: Can we target these neural circuits to curb cravings? Could food scientists design artificial sweeteners that engage both taste and metabolic pathways? Ongoing research in neuroscience and food science aims to decode these mechanisms, paving the way for innovations in nutrition and metabolic health.

Reference list

Fernstrom, J.D., Munger, S.D., Sclafani, A., de Araujo, I.E., Roberts, A. and Molinary, S. (2012). Mechanisms for Sweetness. The Journal of Nutrition, 142(6), pp.1134S1141S. doi:https://doi.org/10.3945/jn.111.149567.

Health, Y. (2015). Your Brain Isn’t Fooled by Diet Sweeteners. [online] Yahoo Life. Available at: https://www.yahoo.com/lifestyle/your-brain-isnt-fooled-by-diet-sweeteners-121372934282.html [Accessed 17 Mar. 2025].

Myüz, H. and Hout, M.C. (2019). Trick or Treat? How Artificial Sweeteners Affect the Brain and Body. Frontiers for Young Minds, [online] 7. doi:https://doi.org/10.3389/frym.2019.00051.

Tellez, L.A., Ren, X., Han, W., Medina, S., Ferreira, J.G., Yeckel, C.W. and de Araujo, I.E. (2013). Glucose utilization rates regulate intake levels of artificial sweeteners. The Journal of Physiology, 591(22), pp.5727–5744. doi:https://doi.org/10.1113/jphysiol.2013.263103.

Vera, L.A. and Wooding, S.P. (2017). Taste: Links in the Chain from Tongue to Brain. Frontiers for Young Minds, 5. doi:https://doi.org/10.3389/frym.2017.00033.

Yeung, A.W.K. and Wong, N.S.M. (2020). How Does Our Brain Process Sugars and Non-Nutritive Sweeteners Differently: A Systematic Review on Functional Magnetic Resonance Imaging Studies. Nutrients, 12(10), p.3010. doi:https://doi.org/10.3390/nu12103010.