Onions, often seen as a kitchen staple, have recently gained attention for their impressive health benefits. Research shows that quercetin, a flavonoid found in onions, can be transformed by gut microbiota into a metabolite called DOPAC, which enhances immune responses and shows potential in cancer prevention. DOPAC boosts the activity of CD8+ T cells, making them more effective in targeting and eliminating tumor cells. Additionally, quercetin has been found to protect ovarian function, particularly against chemotherapy-induced damage, by reducing oxidative stress and improving hormone levels. These findings highlight onions as a powerful, natural ingredient with significant health-promoting properties.
"If you're willing to peel back its layers, you'll find it's truly a great thing!" Research shows that onions can boost immune cells to "reverse the odds" in the tumor microenvironment and can also improve ovarian function.
The familiar melody of “If you are willing to peel back my heart layer by layer, you'll be amazed…” might immediately bring to mind the humble kitchen staple—onions. As the song suggests, most people have a complicated relationship with onions, a mix of love and hate.
Those who love onions appreciate their caramelized sweetness when sautéed, their crisp spiciness when raw, and consider them a vital ingredient in salads, burgers, and grilled meats. On the other hand, those who dislike them avoid them due to their tear-jerking potency while chopping, and the lingering aftertaste that follows.
But if we can look past the “tearful” aspect and truly peel back the layers of this vegetable, we’ll discover that onions are a remarkably underrated health powerhouse, capable of surprising health benefits that may make you reconsider this everyday kitchen guest!
The “Anti-Cancer” Power of Onions
Recently, a research team from Shandong University published a paper in the renowned journal Cell Metabolism, titled “Quercetin-derived microbial metabolite DOPAC potentiates CD8+ T cell anti-tumor immunity via NRF2-mediated mitophagy.” The study revealed that quercetin, a flavonoid compound found in onions, when processed by gut microbiota, produces a key metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), which can inhibit tumor growth and significantly enhance anti-tumor effects. This offers a promising candidate molecule for cancer immunotherapy.
Doi: 10.1016/j.cmet.2025.09.010
Quercetin (QR) is a natural flavonoid compound found in foods like apples, grapes, tomatoes, onions, tea, and herbs like honeysuckle, ginkgo, forsythia, and turmeric. Modern pharmacology has shown that quercetin and its derivatives possess antioxidant, anti-inflammatory, antimicrobial, antifibrotic, and anti-apoptotic properties. They have potential applications in treating conditions like diabetes, hypertension, infections, and aging.
Earlier research confirmed that quercetin could suppress tumor metastasis, angiogenesis, and cell proliferation. However, its mechanism in regulating immune cells, particularly CD8+ T cells in the tumor microenvironment (TME), was not fully understood.
This study combined animal models (melanoma, liver cancer, and colon cancer mouse models), cell experiments, and multi-omics analyses to investigate the key mediators through which quercetin exerts anti-tumor effects.
They found that quercetin in onions doesn't directly fight cancer but is processed by the gut microbiota into DOPAC, which can then have anti-cancer effects. In animal experiments, oral quercetin inhibited tumor growth. However, when antibiotics were used to eliminate the gut microbiota, quercetin's anti-cancer effect disappeared, demonstrating that the gut microbiota is essential for quercetin’s cancer-fighting benefits.
Further studies showed that DOPAC doesn't directly kill cancer cells but enhances the function of CD8+ T cells, which are critical "killers" in the immune system. DOPAC significantly increased both the number and activity of CD8+ T cells in the tumor, enabling them to better recognize and attack cancer cells.
Figure: Dietary quercetin-derived 3,4-dihydroxyphenylacetic acid (DOPAC) inhibits tumor growth.
CD8+ T cells often become “exhausted” and lose function in the tumor microenvironment. So, how does DOPAC make T cells "stronger"?
Researchers found that DOPAC boosts T cell mitochondrial quality, giving them more energy to fight cancer for longer periods. DOPAC inhibits the KEAP1 protein, preventing it from degrading NRF2. This leads to NRF2 accumulation, which stimulates the expression of the BNIP3 gene, promoting mitophagy (the process of clearing damaged mitochondria), improving overall mitochondrial function.
This process doesn't just enhance immunity—it also changes the epigenetics of the cells. For example, DOPAC improves CD8+ T cell metabolism and, by lowering the repressive H3K27me3 modification, activates genes related to T cell activation and function. This means DOPAC works on both metabolic and epigenetic levels to boost T cell “fighting power.”
The researchers also found that DOPAC has a synergistic effect with immune checkpoint blockade (ICB) therapy. DOPAC upregulates PD-1 and Tim-3 expression on tumor-infiltrating CD8+ T cells, providing targets for ICB treatment. When DOPAC was combined with anti-PD-1 antibodies, the tumor-suppressing effect was significantly stronger than with either treatment alone, also increasing CD8+ T cell infiltration and the expression of effector molecules.
Figure: DOPAC promotes response to immune checkpoint blockade (ICB) therapy and is associated with cancer progression.
This suggests that quercetin in onions, when transformed by gut microbiota into DOPAC, can have significant anti-cancer potential and offers promising clinical applications.
Onions and Liver Cancer Prevention
Earlier, we shared research from Shanghai Jiao Tong University, which analyzed the dietary habits of the Chinese population and their links to liver cancer risk. Among 142 foods and nutrients studied, onions, along with retinol and manganese, showed significant associations with liver cancer risk. Higher intake of onions and manganese was linked to a lower risk of liver cancer, further supporting the idea that onions contribute to liver health and cancer prevention.
Onions: A Guardian for Ovarian Health
But onions' health benefits don't stop at cancer prevention. Recent research from Anhui University of Traditional Chinese Medicine and other institutions has revealed that quercetin can also protect ovarian function, particularly against chemotherapy-induced ovarian damage.
In a study titled Modulatory effect of quercetin on premature ovarian insufficiency induced by cyclophosphamide via the PARP1 and GSK3β, researchers found that quercetin could improve ovarian function by inhibiting the expression of PARP1 and the activity of GSK3β, reducing oxidative stress, and combating cell aging. This makes quercetin a potential protector against premature ovarian insufficiency (POI), a common side effect of chemotherapy drugs like cyclophosphamide.
Doi: 10.1038/s41598-025-21397-5
The study demonstrated that quercetin can significantly improve ovarian tissue morphology, regulate hormone levels (increasing AMH and E2, and decreasing FSH and LH), enhance antioxidant capacity (boosting SOD and GSH-PX, and lowering MDA), and reduce granulosa cell apoptosis (lowering Bax and Caspase-3, while increasing Bcl-2).
By inhibiting key proteins like PARP1 and GSK3β, quercetin alleviated ovarian damage caused by chemotherapy, offering a potential treatment for POI. This discovery highlights quercetin's broad potential in improving female reproductive health, especially in women undergoing cancer treatments.
Conclusion
So, next time you're in the kitchen, don't underestimate the power of onions! Adding a few slices to your meal not only enhances the flavor but also supports your health in ways you might not have expected. Small dietary habits like this could help maintain a youthful and healthy body, making it an easy and effective strategy for wellness. Keep the humble onion in your diet—it could be a key player in preserving your health!
References:
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Han P, Chu S, Shen J, et al. Quercetin-derived microbial metabolite DOPAC potentiates CD8+ T cell anti-tumor immunity via NRF2-mediated mitophagy. Cell Metab. 2025 Oct 24:S1550-4131(25)00395-X.
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Tuo JY, Li ZY, Shen QM, et al. A diet-wide association study for liver cancer risk: findings from a prospective cohort study in Chinese men. Eur J Epidemiol. Published online January 10, 2024.
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Wang Y, Chen M, Deng T, et al. Modulatory effect of quercetin on premature ovarian insufficiency induced by cyclophosphamide via the PARP1 and GSK3β. Sci Rep. 2025 Oct 28;15(1):37610.