Loved by some for their caramelized sweetness when sautéed and crisp pungency when eaten raw, and avoided by others for their tear-inducing nature and lingering odor, onions are a polarizing yet indispensable ingredient in global cuisines. Beyond their culinary appeal, emerging scientific evidence reveals that onions are a remarkably underestimated multifunctional health food. Recent high-impact studies demonstrate that quercetin, a flavonoid abundantly found in onions, can be metabolized by gut microbiota into bioactive compounds with potent anti-tumor immunomodulatory effects, while also exerting protective actions on ovarian function under chemotherapeutic stress. This article systematically reviews and translates recent mechanistic findings from animal models, multi-omics analyses, and epidemiological studies, highlighting how dietary onions may contribute to cancer prevention, immune enhancement, liver health, and female reproductive protection. These discoveries invite a renewed scientific appreciation of this humble vegetable as a meaningful contributor to long-term health maintenance.
People who love onions are captivated by their caramelized sweetness after sautéing, enjoy their crisp and pungent bite when eaten raw, and consider them an indispensable finishing touch in salads, hamburgers, and grilled meats. Those who dislike them, however, tend to avoid the tear-inducing irritation during preparation and the persistent odor that lingers after meals.
When we set aside our resistance to their “tear-provoking” nature and truly peel back their many layers, we discover that onions are, in fact, a severely underestimated “multifunctional health powerhouse.” The health benefits they offer are compelling enough to prompt a complete reassessment of this familiar kitchen staple.
A Small Onion with Remarkable Anti-Cancer Potential
Recently, a research team from Shandong University published a study in the prestigious journal Cell Metabolism entitled “Quercetin-derived microbial metabolite DOPAC potentiates CD8⁺ T cell anti-tumor immunity via NRF2-mediated mitophagy.” The study revealed that a key metabolite produced from quercetin—a dietary flavonoid abundant in onions—by the gut microbiota, namely 3,4-dihydroxyphenylacetic acid (DOPAC), can suppress tumor growth in a CD8⁺ T cell–dependent manner. This metabolite significantly enhances anti-tumor immune responses and represents a promising new candidate molecule for cancer immunotherapy.
DOI: 10.1016/j.cmet.2025.09.010
Quercetin (QR) is a naturally occurring flavonoid widely present in apples, grapes, tomatoes, onions, and tea, as well as in traditional Chinese medicinal herbs such as honeysuckle, ginkgo biloba, forsythia, and turmeric. Modern pharmacological studies have demonstrated that quercetin and its derivatives possess antioxidant, anti-inflammatory, antibacterial, anti-fibrotic, and anti-apoptotic properties, and may be applied in the management of diabetes, hypertension, microbial infections, aging-related conditions, and other pathological processes.
Previous studies have confirmed that quercetin has the potential to inhibit tumor metastasis, angiogenesis, and cellular proliferation. However, its regulatory effects on immune cells—particularly CD8⁺ T cells—within the tumor microenvironment (TME) had remained unclear.
To address this gap, the present study employed a combination of in vivo animal models (including mouse models of melanoma, hepatocellular carcinoma, and colorectal cancer), in vitro cellular experiments, and multi-omics analyses to identify the key mediators responsible for quercetin’s anti-tumor activity in vivo.
The researchers found that quercetin itself does not directly exert anti-cancer effects. Instead, it must first be metabolized by the gut microbiota into DOPAC in order to become biologically effective. In animal experiments, oral administration of quercetin significantly inhibited tumor growth. However, when antibiotics were used simultaneously to eliminate gut microbiota, the anti-tumor effects of quercetin were completely abolished. This clearly indicates that the gut microbiota is an indispensable partner in quercetin-mediated anti-cancer activity.
Dietary quercetin-derived 3,4-dihydroxyphenylacetic acid (DOPAC) suppresses tumor growth.
Further investigation revealed that DOPAC does not directly kill tumor cells. Instead, it suppresses tumor growth indirectly by enhancing the function of CD8⁺ T cells—the most critical “killer” cells of the immune system. Experimental results showed that DOPAC significantly increased both the number and activity of CD8⁺ T cells within tumor tissues, enabling them to more effectively recognize and attack cancer cells.
It is well established that CD8⁺ T cells often become “exhausted” within the tumor microenvironment, leading to functional decline. This raised an important question: how does DOPAC enhance T cell strength?
The researchers discovered that DOPAC improves mitochondrial quality within T cells, allowing them to generate more energy and sustain prolonged anti-tumor activity. Mechanistically, DOPAC binds to and inhibits the KEAP1 protein, preventing it from degrading NRF2. The accumulation of NRF2 subsequently promotes BNIP3 gene expression, which enhances mitophagy—the selective removal of damaged mitochondria—thereby improving overall mitochondrial function.
DOPAC enhances responses to immune checkpoint blockade (ICB) therapy and is associated with cancer progression.
Notably, this process not only strengthens immune function but also induces epigenetic changes. DOPAC improves the metabolic state of CD8⁺ T cells and simultaneously reduces the repressive histone modification H3K27me3, further activating genes associated with T cell activation and effector functions. This indicates that DOPAC enhances T cell “combat capacity” through coordinated metabolic and epigenetic regulation.
The researchers also found that DOPAC exhibits synergistic effects with immune checkpoint blockade (ICB) therapy. DOPAC upregulates the expression of PD-1 and Tim-3 on tumor-infiltrating CD8⁺ T cells, providing a molecular basis for ICB targeting. When DOPAC was combined with anti–PD-1 antibodies, tumor suppression was significantly greater than with either treatment alone, accompanied by increased CD8⁺ T cell infiltration and effector molecule expression.
These findings demonstrate that quercetin from onions—seemingly ordinary at first glance—can be transformed by the gut microbiota into DOPAC, a metabolite with substantial anti-cancer potential and promising clinical application prospects.
Beyond Cancer: Onion Intake and Ovarian Protection
Interestingly, earlier we also published an interpretation of a landmark study in the European Journal of Epidemiology. In this study, a research team from Shanghai Jiao Tong University conducted a comprehensive “diet-wide association study” evaluating the relationships between 142 foods and nutrients and liver cancer risk in a Chinese population, providing valuable population-specific data on diet and liver health.
The results further reinforced the idea that onions are a nutritional treasure. Among all analyzed foods and nutrients, onion intake, retinol, and manganese showed particularly strong associations with liver cancer risk. Higher retinol intake was significantly associated with increased liver cancer risk in men. In contrast, higher intake of onions and manganese was associated with a lower risk of liver cancer. This finding not only offers new directions for dietary prevention of liver cancer, but also provides additional scientific evidence supporting the hepatoprotective and anti-cancer value of onions.
At this point, it is difficult to underestimate onions. Yet their benefits extend even further—unexpectedly offering protection for female ovarian function.
Recently, a research team from Anhui University of Chinese Medicine and collaborating institutions published a study entitled “Modulatory effect of quercetin on premature ovarian insufficiency induced by cyclophosphamide via the PARP1 and GSK3β”. The study demonstrated that quercetin can improve ovarian function and alleviate oxidative stress and cellular senescence by inhibiting PARP1 expression and GSK3β activity, thereby exerting protective effects against cyclophosphamide (CTX)-induced premature ovarian insufficiency (POI).
This study explored the protective effects and mechanisms of quercetin against cyclophosphamide-induced POI. In simple terms, chemotherapy drug cyclophosphamide can inadvertently damage the ovaries, causing them to lose function prematurely—a condition known as POI. Quercetin, widely present in onions and apples, acts like a natural “ovarian guardian.”
Using network pharmacology and molecular docking approaches, the researchers predicted and validated that quercetin may exert its effects by targeting key molecules such as PARP1 and GSK3β, which are involved in oxidative stress, apoptosis, and cellular aging.
Subsequent animal experiments confirmed that quercetin significantly improved ovarian tissue morphology, regulated hormone levels (including increased AMH and estradiol, and reduced FSH and LH), enhanced antioxidant capacity (increased SOD and GSH-PX, reduced MDA), and inhibited granulosa cell apoptosis (decreased Bax and Caspase-3, increased Bcl-2).
Visualization of predicted target networks of quercetin (QR).
The results indicate that quercetin mitigates cyclophosphamide-induced ovarian damage by suppressing PARP1 expression and GSK3β activity, thereby protecting ovarian function at multiple levels. This discovery not only highlights quercetin’s potential application in preventing chemotherapy-induced ovarian failure, but also provides a theoretical basis for the development of related functional foods or therapeutic agents.
In summary, incorporating onions into daily meals offers far more than enhanced flavor—it represents a simple yet meaningful investment in long-term health. Small dietary habits, when maintained consistently, may help preserve a more youthful physiological state. Such an affordable and effective health strategy is certainly worth embracing.
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.