Dietary isoflavone intake is associated with evoked responses to inflammatory cardiometabolic stimuli and improved glucose homeostasis in healthy volunteers

Abstract

Background and Aims Consumption of foods that modulate inflammatory stress in genetically-prone individuals may influence development of cardiometabolic diseases. Isoflavones in soy-derived foods function as phytoestrogens, have antioxidant and anti-inflammatory activity, inhibit protein-tyrosine kinase activity, and may be atheroprotective. We examined the relationship between soy food consumption and inflammatory responses to endotoxemia, postprandial responses to oral lipid tolerance test (OLTT), and insulin sensitivity from frequently sampled intravenous tolerance tests (FSIGTT). Methods and Results We administered low-dose endotoxin (LPS 1 ng/kg) to induce transient endotoxemia in young, healthy volunteers (N=215) of African (AA), and European (EA) ancestry as part of the GENE Study. We further supported these findings in two independent samples: the MECHE Study and NHANES. Soy food consumption was a significant predictor of peak cytokine response following LPS. Individuals with moderate-high (>1.48mg/day, N=65) vs. low-no (<1.48mg/day, N=150) isoflavone consumption had significantly higher tumor necrosis factor alpha (TNFα) post-LPS (AUC, P=0.009). Further, high-isoflavone consumers were protected against inflammation-induced decline in insulin sensitivity (SI) in GENE. We observed significant differences by soy consumption in the interferon gamma (IFNγ) response to OLTT, and the insulin response to OGTT in MECHE, as well as significantly lower fasting insulin, and 2-hour glucose post-OGTT in EA NHANES subjects. Conclusion We demonstrate that soy consumption may influence inflammatory and metabolic responses. In research of nutritional exposures, measuring evoked phenotypes may be more informative than describing resting characteristics. Clinical Trial Registry The GENE Study was registered under NCT00953667 and the MECHE Study under NCT01172951, both at clinicaltrials.gov.

Nutrigenomics, the Microbiome, and Gene-Environment Interactions: New Directions in Cardiovascular Disease Research, Prevention, and Treatment

“…The use of evoked endotoxemia (low-dose lipopolysaccharide) as a model of cardiometabolic disease is well documented [279][280][281][282] and has shown great utility as a discovery tool both in omic 283,284 and nutritional contexts. 88,285,286 The combination of nutritional and omic profiling in the context of evoked endotoxemia has great promise for understanding nutritional effects on inflammatory responses. Other challenges have also been successfully used in an integrative omic context, for example, the use of vaccination as a model for activation of immune response by Franco et al, 287 which revealed novel genes acting in response to immune activation.…”

Human Experimental Endotoxemia in Modeling the Pathophysiology, Genomics, and Therapeutics of Innate Immunity in Complex Cardiometabolic Diseases

“…Notably, the anti-inflammatory properties of omega-3 polyunsaturated fatty acids have been assessed by administering fish oil either parenterally 126 or through dietary supplementation 125, 127 prior to the endotoxin challenge, while habitual dietary intake of soy-derived foods may also modify the response to endotoxemia. 128 …”

Relationship Between the Consumption of Soy and Its Derivatives During Critical Periods of Development and in Adulthood and Endocrine-Metabolic Disorders

“…Furthermore, there was protection on induced inflammation by decline of insulin resistance, and better response to oral glucose tolerance test [31].…”

“…Ferguson et al [31] evaluated the relationship between consumption of foods containing isoflavones on the inflammatory response caused by the transient endotoxemia, noticing an increase of the immune response related to the consumption of isoflavones. Furthermore, there was protection on induced inflammation by decline of insulin resistance, and better response to oral glucose tolerance test [31].…”

“…In spite of existing controversy in the literature on the effect of soy in some metabolic endocrine parameters, there is strong evidence of the benefits of soy in morbidities control [2,6,28,31]. However, some studies have questioned the safety of early introduction of foods that contain phytoestrogens in its composition, which can cause long-term hormonal changes, leading to the development of pathologies in adulthood [10,14,15,45].…”