Clinical trial NCT01173380: Soy Nut Study on Markers of Health
Official title: Effects of Soy on Metabolite Markers of Health
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Metabolic Syndrome X
Keywords: Soy
Equol
Metabolic syndrome
Endothelial function
Lead sponsor: University of California, Davis
Sponsor class: OTHER
First posted: 2010-08-02
Enrollment: 18
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The investigators hope to learn about the effects of soy nuts on markers of health. When some people eat soy foods, their gut bacteria make equol. Equol is a soy metabolite (small molecule made during metabolism). The investigators will be testing blood samples to determine if markers of health are different for people who make equol versus people who do not make equol.

Detailed description: The objective of the study is to investigate the metabolomic response to consumption of soy protein containing polyphenolic phytochemicals (isoflavones). The aim of this pilot study is to demonstrate proof of concept and ability to detect metabolomic changes that are responsive to soy. This preliminary data will then be used to design future research projects.

Food phytochemicals such as the polyphenolic flavonoids from a wide variety of foods and beverages have been associated with cardiovascular protective effects in epidemiologic studies. Significant controversy exists in the literature regarding the efficacy and mechanisms for the cardiovascular protection of soy foods. The soy hypothesis for cardiovascular risk reduction has been focused mainly on the isoflavone content of soy, but uncertainty still exists regarding the bioactive component(s). In particular, consumption of soy protein foods has been associated with favorable cardiovascular disease (CVD) risk profiles in population based studies. Controlled clinical trials and meta-analyses however, have resulted in the conclusions that soy protein with associated isoflavones has only modest hypocholesterolemic effects in the range of 3-5% reduction in LDL-cholesterol. Additional cardioprotective effects have been demonstrated in clinical trials, promoting small but significant changes in vascular endothelial function and antioxidant protection. An important observation is that animal studies have shown reduction in atherosclerotic lesion size both with and without decreased blood lipid levels. These results taken together suggest that soy and soy phytochemicals can promote positive risk factors and outcomes by mechanisms in addition to, and other than lowering serum cholesterol levels. There is a need for greater understanding of the cellular and molecular mechanisms underlying the physiologic responses to isoflavones in the vascular compartment. Increasing evidence is emerging that biologically relevant concentrations of isoflavones may impact cell signaling processes in vascular and other tissues.

The large body of literature on human clinical trials of soy proteins and isoflavones has focused primarily on traditional lipid and lipoprotein parameters, biomarkers of CVD risk, and functional changes in endothelial function, platelet activation and total blood antioxidant capacity as described above. It is possible and likely that the effect of soy consumption on CVD risk is a net result of multiple subtle changes in metabolic pathways, vascular inflammatory responses and cell-signaling pathways which are not readily detected in healthy individuals. Since individuals with metabolic syndrome (MetS) present with many of the metabolic aberrations purported to be improved through soy food ingestion, these individuals may be an excellent study population in order to investigate the effects of a soy food intervention on metabolic markers of health. Equol is the end-product of daidzein biotransformation, and is produced only by some humans, resulting in a phenotypic characteristic in response to dietary soy. It is hypothesized by some researchers that the "equol producers" may have additional metabolic and phenotypic responses to soy which may help to explain some of the variances in the literature. Few investigators have examined this question in existing studies, with two reporting an association with outcomes and one no association. A recent study using microarray analysis of lymphocytes from postmenopausal women demonstrated differential gene expression in women who form equol compared to those who do not, suggesting that equol status may be an important modulator of responses to soy isoflavones. No studies have examined this question in a metabolomic investigation. This demonstrates a gap in the literature and provides an opportunity to contribute significant novel data using cutting-edge approaches.

Eligibility criteria: Inclusion Criteria:

* Postmenopausal women
* Men ages 45 or above
* Blood pressure greater than or equal to 130/85 mmHg but not greater than 160/100 and meeting an additional 2 of the remaining 4 Metabolic syndrome diagnostic criteria as defined by NCEP ATP III:

  1. Elevated waist circumference: men equal to or greater than 40 inches, women equal to or greater than 35 inches
  2. Reduced HDL cholesterol: men less than 40 mg/dL, women less than 50 mg/dL
  3. Fasting glucose greater than or equal to 100 mg/dL
  4. Fasting blood triglycerides greater than or equal to 150 mg/dL but less than 400 mg/dL
* Weight of at least 110 pounds

Exclusion Criteria:

* Smokers
* Chronic disease, such as diabetes, cancer, renal disease, and blood disorders
* History of intestinal disorders, which affect absorption or transit, such as ulcerative colitis or crohns disease
* Allergy to soy
* Antioxidant supplement usage

Primary outcomes:
measure: Improve lipid profile
timeFrame: After 4 week intervention
measure: Increase endothelial function
timeFrame: After 4 week intervention
measure: Attenuate glycemic responses
timeFrame: After 4 week intervention
Secondary outcomes:
measure: Decrease inflammatory markers
timeFrame: After 4 week intervention
measure: Follow anthropometrics for stable weight
timeFrame: After 4 week intervention
Other outcomes:
Locations:
city: Davis
country: United States
facility: Ragle Human Nutrition Center
state: California
Study officials:
affiliation: UC Davis
name: Francene M Steinberg, PhD, RD
role: PRINCIPAL_INVESTIGATOR
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