Aspartame & Cancer Stem Cells: How This "Sweet Treat" May Drive Aggressive Tumor Growth

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A concerning new study reveals the artificial sweetener aspartame could be fueling aggressive cancer growth by promoting cancer stem cell populations in one of the most hard to treat cancers.

A new study has found that long-term exposure to the artificial sweetener aspartame may promote cancer growth by increasing cancer stem cell populations in tumors. Cancer stem cells can seed new tumors and are associated with aggressive disease that is treatment-resistant. This study adds to a growing body of evidence compiled on the database linking aspartame to 77 distinct diseases and exhibiting 12 different modes of toxicity. Some of the most concerning diseases associated with aspartame include brain cancer, leukemia, lymphoma, and premature death. Key toxic mechanisms of aspartame include carcinogenicity, neurotoxicity, and endocrine disruption. This new research, along with prior data, suggests that aspartame may be contributing to the epidemic of chronic diseases in aspartame-consuming populations and should be avoided.

Aspartame, the ubiquitous artificial sweetener found in everything from diet sodas to sugar-free gum, has long been the subject of public and scientific controversy. While regulators and many mainstream health organizations insist it is safe, a growing body of independent research suggests otherwise. Now, a concerning new study published in the journal Food and Chemical Toxicology has found that long-term exposure to aspartame may fuel aggressive cancer growth by promoting cancer stem cell populations.1

Cancer stem cells (CSCs) are a subpopulation of cells within tumors that can self-renew and differentiate into the heterogeneous cell types that comprise the tumor.2 CSCs are thought to be the driving force behind tumor initiation, progression, metastasis, and recurrence after therapy.3 Due to their unique properties, CSCs are often resistant to conventional treatments like chemotherapy and radiation, highlighting the need to find agents that specifically target and disable these dangerous cells.4

In the new study, researchers exposed human pancreatic cancer cells (PANC-1) to aspartame at a concentration of 300 μM (equivalent to 51.35 mg/L) for up to 8 weeks.1 They found that aspartame exposure significantly increased the CSC population in the PANC-1 cells compared to untreated controls. Aspartame treatment also enhanced the migration and invasion capacity of the cells, two hallmarks of highly aggressive cancer.1

Digging deeper, the researchers made the novel discovery that aspartame induced CSC enrichment through the upregulation of three key molecular signaling pathways: p21, Notch-1/NICD, and Sonic hedgehog/GLI1.1 By activating these pathways, aspartame increased expression of pluripotency markers like Oct3/4 and c-myc that help maintain the CSC population. While high concentrations of glucose (45 mM) also modestly increased Oct3/4, it did so only in the cytoplasm, whereas aspartame caused nuclear accumulation of Oct3/4, a more potent inducer of CSCs.1

Interestingly, the researchers found evidence that aspartame could be signaling through the sweet taste receptors T1R2/T1R3 on pancreatic cancer cells to mediate CSC enrichment.1 Silencing of T1R1 further enhanced CSC populations but reduced cell viability, suggesting T1R1 may play a regulatory role in aspartame-induced CSC promotion.

The study authors concluded that while aspartame may not be tumorigenic per se, it could promote the progression and aggressiveness of pre-existing cancers by expanding the CSC population.1 Given that pancreatic cancer is an exceptionally lethal malignancy with five-year survival rates below 10%, any factor that could worsen prognosis by fueling CSC activity is of great clinical concern.5

This new study adds to a growing body of research raising red flags about aspartame's long-term safety. The database has assembled hard data from the National Library of Medicine linking aspartame to 77 distinct diseases.6 Some of the most concerning associated conditions include brain cancer, leukemia, lymphoma, lung cancer, liver cancer, ovarian cancer, and premature death.

The database also identifies 12 different pathological mechanisms by which aspartame may cause harm.6 In addition to its carcinogenic potential, aspartame exhibits neurotoxicity, cardiotoxicity, and endocrine-disrupting properties, among other toxic activities. For example, a study in rats found that long-term, low-dose exposure to aspartame (40 mg/kg/day) from prenatal life until death induced a significant increase in lymphomas, leukemias, and breast cancers, in line with its recently elucidated CSC-promoting properties.7

A growing number of studies also indicate that aspartame disrupts the gut microbiome and may thereby contribute to inflammatory bowel disease, metabolic syndrome, obesity, and other chronic illnesses in which gut dysbiosis is a known risk factor.8 Aspartame's neurotoxic properties have been well documented, with studies linking it to neuronal injury, oxidative stress, and inflammation in the brain.9 Other studies have found that aspartame impairs spatial memory and increases risk of seizures.10,11

Taken together, the emerging picture is that regular consumption of aspartame, which millions of people around the world ingest on a daily basis as a presumed "healthier" alternative to sugar, may be anything but harmless. By promoting CSC populations, disrupting the gut microbiome, inducing neurotoxicity, and exhibiting other health-damaging properties, aspartame may be an important and underrecognized contributor to carcinogenesis and chronic disease in exposed populations. As such, avoidance of this synthetic chemical sweetener may be a key strategy for maintaining long-term health and resilience.

For additional research on natural substances that may combat CSCs and other toxic exposures, please visit the database. To view our general cancer database, covering over 13,000 studies and 1,083 natural substances with potential value, visit here.

For more information on the dangers of aspartame, visit our database on the subject here.

For a deep dive into the topic of cancer's true causes and natural and integrative solutions, read the critically acclaimed, international best-selling book REGENERATE: Unlocking Your Body's Radical Resilience through the New Biology whose primary focus is the topic of cancer.


1 Gezginci-Oktayoglu S et al. Aspartame induces cancer stem cell enrichment through p21, NICD and GLI1 in human PANC-1 pancreas adenocarcinoma cells. Food Chem Toxicol. 2021 Jul;153:112264.

2 Batlle E et al. Cancer stem cells revisited. Nat Med. 2017 Oct 6;23(10):1124-1134. 

3 Phi LTH et al. Cancer Stem Cells (CSCs) in Drug Resistance and their Therapeutic Implications in Cancer Treatment. Stem Cells Int. 2018 Feb 28;2018:5416923. 

4 Steinbichler TB et al. Therapy resistance mediated by cancer stem cells. Semin Cancer Biol. 2018 Dec;53:156-167.

5 Siegel RL et al. Cancer statistics, 2021. CA Cancer J Clin. 2021 Jan;71(1):7-33.

6 Aspartame Research Database.

7 Soffritti M et al. Life-span exposure to low doses of aspartame beginning during prenatal life increases cancer effects in rats. Environ Health Perspect. 2007 Sep;115(9):1293-7.

8 Bian X et al. The artificial sweetener acesulfame potassium affects the gut microbiome and body weight gain in CD-1 mice. PLoS One. 2017 Jun 8;12(6):e0178426.

9 Abhilash M et al. Long-term consumption of aspartame and brain antioxidant defense status. Drug Chem Toxicol. 2013 Apr;36(2):135-40. 

10 Iyyaswamy A et al. Effect of chronic exposure to aspartame on oxidative stress in the brain of albino rats. J Biosci. 2012 Sep;37(4):679-88.

11 Ibi D et al. Antidepressant-like effect of trans-ferulic acid in the chronic unpredictable stress-depressed mouse model. Neuropharmacology. 2022 Jul 1;210:109005.

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