An Exploratory Critical Review on TNF as a Potential Inflammatory Biomarker Responsive to Dietary Intervention with Bioactive Foods and Derived Products

This review collects and critically examines data on the levels of tumour necrosis factor-alpha (TNF-alpha) in lean, overweight and obese subjects, and the effects of intervention with different foods and food products containing bioactive constituents in overweight/obese individuals. We additionally explore the influence of different single nucleotide polymorphisms (SNPs) on TNF-alpha levels and compare the response to food products with that to some anti-obesity drugs. Our aim was to provide an overview of the variability, consistency, and magnitude of the reported effects of dietary factors on TNF-alpha, and to envisage the reliability of measuring changes in the levels of this cytokine as a biomarker responsive to food intervention in association with the reduction in body weight. Regarding the circulating levels of TNF-alpha, we report: (i) a large intra-group variability, with most coefficients of variation (CV%) values being >=30% and, in many cases, >100%; (ii) a large between-studies variability, with baseline TNF-alpha values ranging from <1.0 up to several hundred pg/mL; (iii) highly variable effects of the different dietary approaches with both statistically significant and not significant decreases or increases of the protein, and the absolute effect size varying from <0.1 pg/mL up to ?50 pg/mL. Within this scenario of variability, it was not possible to discern clear differentiating limits in TNF-alpha between lean, overweight, and obese individuals or a distinct downregulatory effect on this cytokine by any of the different dietary approaches reviewed, i.e., polyunsaturated fatty acids (PUFAs), Vitamin-D (VitD), mixed (micro)nutrients, (poly)phenols or other phytochemicals. Further, there was not a clear relationship between the TNF-alpha responses and body weight changes. We found similarities between dietary and pharmacological treatments in terms of variability and limited evidence of the TNF-alpha response. Different factors that contribute to this variability are discussed and some specific recommendations are proposed to reinforce the need to improve future studies looking at this cytokine as a potential biomarker of response to dietary approaches.