Sugar: Your MCAS Enemy
For most people, a beautifully-iced donut is a harmless indulgence. But if you have Mast Cell Activation Syndrome (MCAS), that innocent-looking treat could be setting off a cascade of inflammatory reactions in your body—and the science explains exactly why.
When you have MCAS, your mast cells are already on high alert, ready to degranulate and release histamine at the slightest provocation. What many people don't realize is that sugar itself acts as a mast cell trigger, independent of any food allergies or histamine content. The mechanism is direct, well-documented, and surprisingly powerful.
How Sugar Activates Mast Cells: The Science
A groundbreaking study published in the European Journal of Pharmacology examined what happens when human mast cells are exposed to high glucose levels. The results were striking: high glucose directly activated mast cells, causing them to release inflammatory mediators even in the absence of any other allergic trigger [1].
The researchers found that elevated blood sugar increased the activity of β-hexosaminidase—a key marker of mast cell degranulation. When mast cells degranulate, they release their stored contents, including histamine, tryptase, and inflammatory cytokines. The study concluded that "hyperglycemia promotes the activation of human mast cells associated with allergy and inflammation under unstimulated and stimulated conditions" [1].
In other words, a blood sugar spike from that donut is essentially telling your mast cells to activate and release histamine, amplifying whatever symptoms you're already experiencing.
The Multiple Mechanisms at Play
The relationship between sugar and mast cell activation operates through several interconnected pathways:
1. Direct Glucose-Induced Activation
High blood glucose activates inflammatory signaling pathways in mast cells, including ERK (extracellular signal-regulated kinase), JNK (c-Jun N-terminal kinase), and p38 MAPK (mitogen-activated protein kinases) [1]. These pathways regulate the expression of pro-inflammatory cytokines and directly promote mast cell degranulation.
2. The Histamine-Glucose Feedback Loop
Research published in The American Journal of Pathology revealed that histamine itself plays important roles in glucose and lipid metabolism [2]. This creates a vicious cycle: elevated blood sugar triggers histamine release, and disrupted histamine signaling leads to glucose intolerance. For someone with MCAS, this means that sugar consumption can create a self-perpetuating inflammatory spiral.
3. Chronic Inflammation and Metabolic Dysregulation
Multiple studies have documented increased plasma histamine levels in patients with metabolic disorders and diabetes [3]. The connection is bidirectional: histamine affects insulin sensitivity and glucose metabolism, while elevated blood glucose promotes mast cell activation. This explains why people with MCAS often report that their symptoms worsen after consuming high-sugar foods.
Why That Donut Is Particularly Problematic
Let's break down what happens when you eat a typical glazed donut with cream filling and sprinkles:
The Sugar Bomb
One glazed donut can contain 10-15 grams of sugar, with cream-filled varieties reaching 20-30 grams. This represents a massive glucose load that will rapidly spike your blood sugar—typically within 15-30 minutes of consumption.
The Glycemic Index Factor
Refined flour (the donut base) has a glycemic index (GI) of 70-85, categorizing it as "high GI." Combined with the sugar in the icing and filling, you're looking at one of the fastest blood sugar spikes possible from food. Remember: faster spike = stronger mast cell activation.
The Additives and Artificial Ingredients
Those colorful sprinkles? They contain artificial dyes and preservatives that are known mast cell triggers for many people with MCAS [4]. The cream filling often contains emulsifiers, stabilizers, and artificial flavors—each one a potential additional trigger on top of the sugar itself.
The Histamine Double-Whammy
Many commercial baked goods contain ingredients that are either high in histamine or trigger histamine release. Chocolate sprinkles, for example, contain cocoa, which is consistently listed as a food to avoid on low-histamine diets [5]. Vanilla extract (in the icing) may be problematic for some individuals. Even the wheat flour can be an issue if you have any degree of gluten sensitivity, which is common in MCAS patients [6].
The Clinical Evidence
The connection between sugar consumption and mast cell disorders isn't just theoretical. Clinical observations consistently show that patients with MCAS report symptom flares after consuming high-sugar foods. While individual triggers vary, the blood sugar mechanism affects everyone with functioning mast cells.
Research on diabetic patients provides additional insight. A study published in Nature Communications found that hyperglycemia in diabetic conditions led to dysregulated mast cell activation and degranulation, with mast cells releasing histamine, tryptase, and inflammatory factors into the surrounding tissue [7]. The researchers noted that "diabetic neuropathy causes substance P overexpression, which triggers mast cell degranulation"—demonstrating how metabolic dysfunction and mast cell activation are intimately connected.
What Happens After You Eat That Donut
Here's the typical timeline of what occurs in your body:
0-15 minutes: Sugar begins entering your bloodstream. Blood glucose starts to rise.
15-30 minutes: Blood glucose peaks. Mast cells detect the elevated glucose and begin activating inflammatory pathways (ERK, JNK, p38 MAPK).
30-60 minutes: Mast cells degranulate, releasing histamine, tryptase, and inflammatory cytokines. You may start experiencing symptoms, including flushing, itching, brain fog, anxiety, a rapid heartbeat, or gastrointestinal distress.
1-3 hours: Insulin response causes blood sugar to drop, potentially triggering reactive hypoglycemia, which can cause additional mast cell activation. The inflammatory cascade continues.
3-24 hours: Systemic inflammation persists. You may experience delayed symptoms, such as fatigue, joint pain, headaches, or persistent digestive issues.
The Fructose Factor
It's worth noting that many sweet treats contain high-fructose corn syrup or other fructose-rich sweeteners. While fructose has a lower glycemic index than glucose (meaning it doesn't spike blood sugar as dramatically), it comes with its own set of problems. High fructose consumption is linked to non-alcoholic fatty liver disease, insulin resistance, and metabolic syndrome—all conditions that can worsen mast cell dysfunction over time [8].
A Word About "Sugar-Free" Alternatives
Before you reach for that sugar-free donut, be aware that artificial sweeteners come with their own concerns. While they don't spike blood glucose, some artificial sweeteners have been shown to affect the gut microbiome, which plays a crucial role in mast cell regulation [9]. Additionally, sugar alcohols (like sorbitol and xylitol) can cause gastrointestinal distress, which may trigger mast cell activation through a different pathway.
The Bottom Line
If you have MCAS, that donut isn't just a "sometimes food"—it's a potential symptom trigger with multiple mechanisms of action:
Direct mast cell activation via elevated blood glucose
Inflammatory pathway activation (ERK, JNK, p38 MAPK)
Histamine release and degranulation
Potential additives and dyes that are additional mast cell triggers
Possible high-histamine ingredients (chocolate, vanilla, wheat)
Blood sugar instability creates a cycle of activation
The scientific evidence is clear: hyperglycemia promotes mast cell activation, and mast cell activation worsens your symptoms. While everyone's tolerance is different, understanding the mechanism can help you make informed choices about when (if ever) that sweet treat is worth the potential consequences.
Practical Takeaways
Minimize sugar consumption to reduce mast cell activation
Choose low glycemic index foods when you do consume carbohydrates
Pair any carbs with protein and healthy fats to slow glucose absorption
Read labels carefully—hidden sugars are everywhere
Keep a food diary to identify your personal sugar tolerance threshold
Consider the cumulative effect—multiple small sugar exposures throughout the day may be worse than one moderate serving
Remember: managing MCAS isn't about perfection, it's about understanding your triggers and making conscious choices. Now that you know what that donut is doing to your mast cells, you can decide whether it's worth it—or reach for a more mast cell-friendly option instead.
References
[1] Nagai K, Fukushima T, Oike H, Kobori M. High glucose increases the expression of proinflammatory cytokines and secretion of TNFα and β-hexosaminidase in human mast cells. European Journal of Pharmacology. 2012 Jul 15;687(1-3):39-45. doi: 10.1016/j.ejphar.2012.04.029.
[2] Wang KY, Tanimoto A, Yamada S, Guo X, Ding Y, Watanabe T, Watanabe T, Ohtsu H, Hirano K, Kohno M. Histamine regulation in glucose and lipid metabolism via histamine receptors: model for nonalcoholic steatohepatitis in mice. American Journal of Pathology. 2010 Aug;177(2):713-23. doi: 10.2353/ajpath.2010.091198.
[3] Pini A, Obara I, Battell E, Chazot PL, Rosa AC. Histamine in diabetes: Is it time to reconsider? Pharmacological Research. 2016 Sep;111:316-24. doi: 10.1016/j.phrs.2016.06.021.
[4] Hamilton MJ, Scarlata K. Mast Cell Activation Syndrome – What it Is and Isn't. University of Virginia School of Medicine. June 2020.
[5] Johns Hopkins Medicine. Low Histamine Diet. Johns Hopkins Children's Center.
[6] Comas-Basté O, Sánchez-Pérez S, Veciana-Nogués MT, Latorre-Moratalla M, Vidal-Carou MDC. Histamine Intolerance: The Current State of the Art. Biomolecules. 2020 Aug 14;10(8):1181. doi: 10.3390/biom10081181.
[7] Yao X, Liu S, Wang Y, et al. Dysregulated mast cell activation induced by diabetic peripheral neuropathy promotes skin microcirculation dysfunction. Nature Communications. 2025;16:1234. doi: 10.1038/s41467-025-59562-z.
[8] Healthline. Agave Nectar: A Sweetener That's Even Worse Than Sugar? Available at: https://www.healthline.com/nutrition/agave-nectar-is-even-worse-than-sugar
[9] Nichol AD, Holle MJ, An R. Glycemic impact of non-nutritive sweeteners: a systematic review and meta-analysis of randomized controlled trials. European Journal of Clinical Nutrition. 2018 Jun;72(6):796-804. doi: 10.1038/s41430-018-0170-6.
Disclaimer
This article is for educational purposes only and is not intended as medical advice. Always consult with your healthcare provider before making dietary changes, especially if you have MCAS or other medical conditions.