Dietary Strategies to Increase Endogenous IL-15
There is no established dietary intervention proven to directly increase endogenous IL-15 levels in humans. The most reliable method to elevate IL-15 is through exercise, particularly resistance training, which stimulates skeletal muscle to secrete IL-15 as a myokine 1.
Why Diet Cannot Directly Increase IL-15
IL-15 is not obtained from food sources—it is a cytokine produced endogenously by various tissues, particularly skeletal muscle, monocytes, and dendritic cells 2, 3. Unlike nutrients that can be consumed and absorbed, IL-15 must be synthesized by your own cells in response to specific physiological stimuli 4.
The primary physiological trigger for IL-15 production is muscle contraction during exercise, not dietary intake 1. Research examining IL-15 responses to exercise shows inconsistent results regarding acute increases, but the mechanism is clear: skeletal muscle tissue releases IL-15 during physical activity, not in response to food consumption 1.
The Exercise-IL-15 Connection
Resistance and endurance exercise of varying intensities represent the only evidence-based approach to stimulate endogenous IL-15 production 5. When skeletal muscle contracts during exercise, it functions as an endocrine organ secreting myokines including IL-15, which then:
- Supports proliferation and maturation of Natural Killer (NK) cells and CD8+ T cells 1
- Provides immunomodulatory effects that may improve outcomes in cancer and cardiovascular disease 6, 1
- Maintains homeostasis of NK cells and memory CD8 T cells 3
The ESPEN guidelines specifically emphasize that physical activities, including both aerobic exercise and resistance training, are essential anabolic stimuli for maintaining body resources 5.
Indirect Dietary Support for IL-15 Function
While diet cannot directly increase IL-15, optimal nutrition supports the muscle tissue that produces IL-15 and the immune cells that respond to it:
Protein and Amino Acids for Muscle Maintenance
- Consume adequate protein with essential amino acids (EAA) or high-dose leucine to support muscle protein synthesis, which maintains the tissue responsible for IL-15 secretion 5
- This is particularly important in inflammatory states where muscle breakdown is accelerated 5
Anti-Inflammatory Dietary Pattern
Follow a whole-food, plant-based dietary framework that reduces systemic inflammation, allowing IL-15 to function optimally 7, 8:
- Vegetables and fruits: 5-7 servings daily with variety in colors, emphasizing dark green, red, and orange varieties 5, 9
- Whole grains: Choose minimally processed options with carbohydrate-to-fiber ratio <10:1 7, 9
- Legumes: At least twice weekly as a primary protein source 5, 9
- Nuts and seeds: 2 tablespoons daily or 4 meals per week 5, 9
- Fish: Prioritize oily fish rich in omega-3 fatty acids (salmon, mackerel, sardines) 8-9 meals monthly 5, 9
- Lean poultry and limited red meat: Unprocessed red meat limited to 4-6 meals monthly 5, 9
Foods to Minimize
Eliminate or severely restrict processed foods that promote inflammation and may impair immune function 7, 9:
- Processed and cured meats: limit to maximum 1 meal weekly 5, 9
- Sugar-sweetened beverages: eliminate completely 7, 9
- Industrial trans fats and partially hydrogenated oils: avoid entirely 9
- Ultra-processed foods high in refined grains, saturated fat, salt, and sugar 5, 7
Critical Clinical Caveat
Do not pursue IL-15 elevation indiscriminately. While IL-15 has protective effects in myocardial infarction and supports anti-tumor immunity 6, 1, dysregulated IL-15 expression participates in autoimmune inflammatory diseases and hematological malignancies 3. IL-15 also promotes atherogenesis in cardiovascular disease 6.
The goal should be physiologic IL-15 production through exercise and a healthy dietary pattern that supports muscle mass and reduces systemic inflammation—not pharmacologic elevation through supplementation or other artificial means.