How can I increase Natural Killer (NK) cells?

How to Increase Natural Killer (NK) Cells

Regular moderate-intensity exercise training is the most evidence-based intervention to increase NK cell activity and function, with both moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) demonstrating approximately 10-fold increases in NK cell cytotoxicity compared to untrained states. 1

Exercise-Based Interventions

Structured Exercise Programs

Progressive exercise training combining MICT followed by HIIT produces the most robust improvements in NK cell function:

• Moderate-intensity continuous training (MICT) at 60% maximal oxygen consumption for 30 minutes daily, 5 days per week significantly increases NK cell cytotoxicity, mitochondrial membrane potential, and cellular perforin and granzyme B levels 2

• High-intensity interval training (HIIT) using 3-minute intervals alternating between 80% and 40% maximal oxygen consumption produces similar NK cell improvements while also enhancing maximal work rate superior to MICT 2

• A 4-week MICT program followed by 4-week HIIT intervention increased NK cell cytotoxicity approximately 10-fold compared to baseline in previously untrained adults 1

Exercise During Cancer Treatment

• Moderate-high intensity resistance and aerobic exercise during the first 9-12 weeks of (neo)adjuvant chemotherapy preserves NK cell degranulation (11.4% higher CD107a+ degranulated NK cells compared to controls) and may maintain tumor cell lysis capacity 3

• Exercise intervention during chemotherapy prevents the decline in NK cell activity typically observed in non-exercising patients undergoing treatment 3

Mechanisms of Exercise-Induced NK Cell Enhancement

Exercise improves NK cell function through multiple cellular pathways:

• Increases mitochondrial bioenergetic functionality, including maximal and reserve oxygen consumption rates and bioenergetic health index in NK cells 2

• Reduces mitochondrial matrix oxidant burden (MOB) in NK cells that is typically elevated by acute exercise stress 2

• Upregulates key proteins involved in NK cell function, including COP9 signalosome subunit 3 (COPS3), PIK3R1, and multiple heat shock proteins 1

• Diminishes mobilization of senescent CD57+ NK cells into circulation following acute exercise bouts 2

Dietary Interventions

Fat Reduction

Lowering dietary fat intake to less than 30% of total calories significantly increases NK cell activity:

• Each 1% absolute reduction in calories from fat produces approximately 0.53% increase in NK cell activity across all individuals 4

• Men consuming greater than 25% of calories as fat at baseline show highly significant improvements (approximately 1.22% increase per percent reduction in dietary fat, p=0.009) 4

• The effect persists after accounting for changes in total caloric intake, weight, exercise, and other confounding variables 4

Specific Dietary Components

Multiple dietary constituents modulate NK cell function and should be incorporated:

• Vitamins A, D, and E can enhance NK cell activities through various immunomodulatory mechanisms 5

• Water-soluble mushroom constituents demonstrate capacity to modulate NK cell function 5

• Polyphenolic compounds found in fruits and vegetables support NK cell activities 5

• Omega-3 fatty acids from fish oil can enhance NK cell function while potentially reducing regulatory T cell (Treg) accumulation that suppresses NK activity 5

Clinical Context and Mechanistic Considerations

Balance with Regulatory T Cells

• Tumor cells can block NK cell tumoricidal activity by inducing localized accumulation of regulatory T (Treg) cells 5

• Dietary interventions that simultaneously enhance NK cell function while modulating Treg cell properties may provide optimal cancer prevention benefits 5

• The balance between NK cells and Treg cells is critical for maintaining effective immune surveillance against malignant transformation 5

Protein Expression Changes

Exercise training induces specific proteomic alterations in NK cells:

• Upregulation of proteins involved in cellular signaling (PIK3R1, TAOK3), chromosome regulation (RCC2, RNF40), and cellular transport (NUP88) 1

• Modulation of pathways related to transmembrane transport, cellular composition, and oxidation-reduction reactions 1

• These molecular changes correlate with functional improvements in cytotoxicity and tumor surveillance capacity 1

Common Pitfalls to Avoid

• Excessive high-intensity exercise without proper progression can temporarily suppress immune function rather than enhance it; gradual progression from moderate to high intensity is preferable 1, 2

• Focusing solely on acute exercise bouts rather than sustained training programs will not produce the durable improvements in NK cell function seen with regular training 1

• Ignoring dietary fat intake while attempting other interventions may limit potential NK cell improvements, particularly in individuals with high baseline fat consumption 4

• Overlooking the importance of mitochondrial health in NK cells; interventions should support mitochondrial bioenergetics rather than increase oxidative stress 2