The Melanoma Diet: What the Evidence Says About Fats, Antioxidants, and Gut Microbiota

Nutrients has published a comprehensive review that brings together dozens of studies on how diet can affect the risk, course, and therapeutic response to melanoma. The authors examine the roles of fats (especially omega-3 and omega-6 PUFAs), vitamins and antioxidants, plant bioactive compounds, and — a separate block — the intestinal microbiota, which is associated with both tumor aggressiveness and the effectiveness of immunotherapy. The main idea: ultraviolet light remains factor No. 1, but dietary patterns are capable of modifying oxidative stress, inflammation, and the immune response, and therefore, theoretically, affect melanoma outcomes. There is not enough evidence yet for strict recommendations, but directions have already been outlined.

Background of the study

Melanoma remains one of the most aggressive skin tumors: the key risk driver is considered to be ultraviolet radiation (especially episodic burns in childhood and adolescence) against the background of genetic vulnerability - fair skin/hair, multiple nevi, family history, mutations in the MAPK pathway (BRAF/NRAS). But in addition to UV, the role of systemic environmental factors - chronic inflammation, metabolic shifts and immune surveillance - which are significantly affected by daily nutrition, has been discussed for several years. This shifts the conversation from the "local" effect of light to the general tone of the body, in which tumors are easier to grow or, conversely, more difficult to gain a foothold.

From a nutritional biology perspective, two major circuits are critical. The first is oxidative stress and inflammation. Excess saturated fats and omega-6 PUFAs (typical of the “Western” diet) support the production of eicosanoids such as PGE₂, which are associated with immunosuppression and tumor growth, while omega-3 (EPA/DHA) and plant polyphenols shift the balance toward anti-inflammatory mediators and enhance antioxidant defense. The second is the gut microbiota: adequate dietary fiber intake supports bacteria producing short-chain fatty acids (primarily butyrate), which strengthen the barrier, regulate T-cell responses, and, according to clinical series in melanoma patients, are associated with a better response to immunotherapy with checkpoint inhibitors.

Observational studies increasingly paint a consistent picture: a plant-based, anti-inflammatory dietary pattern (vegetables, fruits, whole grains, nuts/seeds, fish, olive oil) is associated with more favorable immune-inflammatory profiles and a “healthy” microbiome. In contrast, ultra-processed foods with excess sugars, omega-6-loaded fats, and food additives are associated with dysbiosis and chronic low-grade inflammation. However, the evidence for antioxidant supplements in capsules remains mixed, with both neutral and potentially adverse effects reported for a number of high doses, hence the shift in focus of reviews to whole foods over individual pills.

The clinical evidence is still fragmented: causal inferences are limited, and intervention trials are small and heterogeneous in design. However, a logical “axis” is emerging: diet → microbiota/metabolites → inflammation and immune surveillance → melanoma risk/behavior and response to therapy. In this context, the review systematizes the mechanistic and clinical signals, formulating a cautious but practical vector: a diet that reduces inflammation and supports microbiota metabolites (SCFAs) can theoretically improve cancer outcomes - while sun protection and standard therapy remain a priority.

Why is this important?

Melanoma is one of the most aggressive skin cancers, and patients often ask, “What lifestyle changes can I make other than sun protection?” The review neatly ties together disparate evidence: plant-based, “anti-inflammatory” diets rich in omega-3s and antioxidants are associated with a more favorable inflammation and immune response profile, while excess processed foods and saturated/omega-6 fats are associated with increased pro-inflammatory signaling. There is also growing interest in how fiber and microbiota support the response to checkpoint inhibitors, key drugs in the treatment of melanoma.

What the data says - by section

Oxidative stress and antioxidants. Melanocytes are vulnerable to ROS (reactive oxygen species), both from UV radiation and from the melanin biosynthesis “kitchen” itself. A diet rich in antioxidants and plant polyphenols theoretically reduces this background, which may inhibit tumor initiation and progression - but clinical evidence is scattered.

Inflammation and fats. The key is not “how much fat,” but what kind of fat. Omega-6 (vegetable oils, processed foods) fuel the arachidonic acid/PGE₂ pathway, which is associated with immune suppression and tumor growth; omega-3 (EPA/DHA), on the other hand, reduces PGE₂, supports T-cell responses, and in preclinical studies inhibits proliferation and metastasis. The omega-6/omega-3 balance is more important than the percentage of fat itself.

Plant bioactive compounds. Polyphenols, flavonoids, carotenoids from vegetables, fruits, nuts and olive oil inhibit NF-κB, reducing the production of proinflammatory cytokines, and enhance endogenous antioxidant defense - this is one of the mechanisms why the Mediterranean diet is associated with more favorable cancer outcomes in observational studies.

Gut microbiota and immunotherapy. High-fiber diets support bacteria producing short-chain fatty acids (SCFA), primarily butyrate; SCFA modulate T-cell immunity and have been associated with better response to PD-1/PD-L1 inhibitors in melanoma patients in clinical series and small cohorts. This is not a guide to self-treatment, but a direction for clinical trials.

How does this fit into the “picture of the day”

In summary, a clear “axis” emerges from the review: diet → microbiota/metabolites → inflammation/immunity → tumor behavior and response to therapy. The protective vector in most studies is shown by plant-oriented patterns (vegetables, fruits, whole grains, nuts/seeds, fish) with a moderate content of animal fats and processed meat. In contrast, the Western diet with an excess of omega-6, sugars and processed foods is associated with pro-inflammatory shifts that are unfavorable for immune surveillance. At the same time, the authors emphasize: causality has not been proven, large prospective studies and RCTs are needed.

Shortlists - What looks promising and what is risky

Promising nutritional highlights (not medical advice):

• 2-3 times a week fatty fish (source of EPA/DHA);
• vegetables/fruits, whole grains, nuts/seeds daily (polyphenols + fiber → SCFA);
• olive oil as a base fat;
• "stretching" fiber to 25-35 g/day (as tolerated).

What to limit:

• excess processed meats and refined sugars;
• omega-6-overloaded oils/processed foods (shift the balance of eicosanoids);
• ultra-processed foods with "long" compositions.

Where “diet + therapy” is especially interesting

• Immunotherapy period: Data on the role of fiber/SCFA and microbiota diversity in response to checkpoint inhibitors encourage careful dietary interventions in research settings (not a substitute for treatment!).
• Prevention in risk groups: People with multiple nevi, family history or high UV exposure may want to consider the Mediterranean pattern as a “base setting” against inflammation and oxidative stress.

Limitations and what's next

The authors write directly: there is a lack of data, the results are multidirectional, and the clinical trials are small and heterogeneous, so it is not yet possible to write out “dietary instructions for all patients with melanoma.” Large prospective projects and interventional studies with biomarkers (inflammation, SCFA, microbiota) and “hard” endpoints (risk, survival, response to ICT) are needed. Nevertheless, a conservative but practical recommendation is already emerging: nutrition that “quenches” inflammation and feeds the microbiota is logically combined with oncological goals.

Source: Abigail E. Watson, Nabiha Yusuf. The Influence of Dietary Factors on Melanoma Development and Progression: A Comprehensive Review. Nutrients 17(11):1891. https://doi.org/10.3390/nu17111891