Potential Micronutrients and Phytochemicals against the Pathogenesis of Chronic Obstructive Pulmonary Disease and Lung Cancer

Abstract

Lung cancer and chronic obstructive pulmonary disease have shared etiology, including key etiological changes (e.g., DNA damage and epigenetics change) and lung function impairment. Focusing on those shared targets may help in the prevention of both. Certain micronutrients (vitamins and minerals) and phytochemicals (carotenoids and phenols) have potent antioxidant or methyl-donating properties and thus have received considerable interest. We reviewed recent papers probing into the potential of nutrients with respect to lung function preservation and prevention of lung cancer risk, and suggest several hypothetical intervention patterns. Intakes of vitamins (i.e., A, C, D, E, B₁₂), carotenoids, flavonoids, curcumins, resveratrol, magnesium, and omega-3 fatty acids all show protective effects against lung function loss, some mainly by improving average lung function and others through reducing decline rate. Dietary interventions early in life may help lung function reserve over the lifespan. Protective nutrient interventions among smokers are likely to mitigate the effects of cigarettes on lung health. We also discuss their underlying mechanisms and some possible causes for the inconsistent results in observational studies and supplementation trials. The role of the lung microbiome on lung health and its potential utility in identifying protective nutrients are discussed as well. More prospective cohorts and well-designed clinical trials are needed to promote the transition of individualized nutrient interventions into health policy.

Keywords: COPD; antioxidants; epigenetics; lung cancer; lung function; phytochemicals; precision medicine; primary prevention; respiratory disease; vitamins.

Figure 1

Hypothetic model for the effect of dietary interventions on lung function over the lifespan. (a) Symptom-improving intervention and decline rate-reducing intervention patterns by dietary nutrients or phytochemicals in the older life stage; (b) A conceptual model about nutrient intervention by life stage before lung function peak for lung function preservation over the lifespan. Life stage A: the maternal and prenatal period; B: childhood; C: young adulthood; D: older life.

Figure 2

Summary of potential protective micronutrients and phytochemicals in the pathogenesis of chronic obstructive pulmonary disease (COPD) and lung cancer (LC). External and internal factors lead to oxidative stress and inflammation and thus initiate COPD and LC pathogenesis. Interventions against external exposure are not satisfying, while targeting the lung microbiome is promising. Recent studies have revealed strong evidence on protective nutrients in DNA methylation and damage but studies on histone modulation are limited to animal or cell experiments. Epidemiological studies about micronutrients and phytochemicals in later key event lung function impairment are abundant, and have identified different intervention patterns, including symptom improvement and a decline rate-reducing pattern. PUFA: polyunsaturated fatty acid; EPA: eicosapentaenoic acid; DHA: docosahexaenoic acid; SCFA: short-chain fatty acid; RCT: randomized controlled trials.