Dietary Seaweed and Early Breast Cancer: A Randomized Trial

This study has been completed.
Sponsor:
Collaborator:
U.S. Army Medical Research and Materiel Command
Information provided by (Responsible Party):
University of South Carolina
ClinicalTrials.gov Identifier:
NCT01663792
First received: August 9, 2012
Last updated: NA
Last verified: August 2012
History: No changes posted
  Purpose

Could daily consumption of seaweed help explain lower postmenopausal breast cancer (BC) incidence and mortality rates in Japan? This small proof of principle clinical trial was designed to test the idea that the same amount of seaweed normally eaten in Japan would induce metabolic changes when given to non-seaweed consuming healthy postmenopausal American women. The participants were given 10 capsules a day (about 1 tablespoon) for 3 months. During the first month the capsules contained placebo, the second month seaweed, and the third month placebo. We collected blood and urine samples after each treatment period and tested for changes in protein expression that might be related to consuming seaweed.


Condition Intervention
Seaweed Associated Changes in Healthy Subjects
Other: Seaweed

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Bio-availability Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
Primary Purpose: Basic Science
Official Title: Dietary Seaweed and Early Breast Cancer: A Randomized Trial

Resource links provided by NLM:


Further study details as provided by University of South Carolina:

Primary Outcome Measures:
  • Urinary urokinase receptor concentration [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    ELISA test for uPAR concentration

  • Surface Enhanced Laser Desorption/Ionization-Time Of Flight-Mass Spectrometry (SELDI-TOF-MS)identification of urinary and serum protein changes [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    SELDI-TOF-MS was used to measure urinary and serum protein changes


Secondary Outcome Measures:
  • Urinary iodine concentrations [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Urinary iodine concentration changes were used to indicate adherence to taking the seaweed supplement.


Enrollment: 15
Study Start Date: October 2006
Study Completion Date: December 2007
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
5 g/d placebo (maltodextrin)in 10 500-mg capsules for 1 month
Experimental: Seaweed
Seaweed (Undaria pinnatifida) given orally in ten 500-mg capsules for 1 month
Other: Seaweed
Ten 500-mg capsules to be taken orally each day for 1 month
Other Name: Undaria pinnatifida
Placebo Comparator: Placebo2
5 g/d placebo in 10 500-mg capsules for one month

  Hide Detailed Description

Detailed Description:

The relationship between the relative breast cancer (BC) risk and seaweed intake among humans is only now unfolding. A small body of research, both in vivo and in vitro, suggests seaweed may be useful in BC prevention (Funahashi et al. 1999; Teas et al. 1984; Yamamoto et al. 1987) . Seaweeds are specifically used to treat tumors in Traditional Chinese Medicine and Japanese folk medicine. On a population level, those people for whom seaweed is a regular part of their diet, most notably in Japan, have dramatically lower rates of BC (Hebert et al. 1998; Hebert and Rosen 1996; Kodama et al. 1991).

Epidemiologic studies done in Japan in the 1980s, before Westernized diets were common, reported that Japanese women had 1/3 the rate of premenopausal BC and 1/9 the rate of postmenopausal BC (Ferlay et al. 2001; Reddy et al. 1980). Even today, BC incidence rates for women in Japan are 20/100,000 compared to the U.S. average of 118/100,000 (Statistics 2007) . Although genetic predisposition has been proposed, when rates among migrants from Japan to the US are compared, BC incidence almost doubles after 10 years of residence in the US (20/100,000 to 35/100,000) (Shimizu et al. 1991), increase with each successive generation (LeMarchand et al. 1985). Japanese-American women who develop BC have significantly better survival rates than other American ethnic groups (Kanemori and Prygrocki 2005; Pineda et al. 2001). On the other hand, Asian-American women over 50 years of age living in Los Angeles, especially Japanese-American women, have one of the most rapidly increasing BC incidence rates (Deapen et al. 2002). These data support the hypothesis that lifestyle changes and possibly gene-nutrient interactions are important in BC susceptibility.

Seaweed is a typical part of East-Asian diets, although consumption varies widely among individuals (Fukuda et al. 2007). Seaweeds have no land equivalents in terms of their specific components of fiber (alginate), primary carotenoid (fucoxanthin), sulfated polysaccharide (fucoidan and laminarin), and polyphenol defense compounds, each of which has been reported to have strong anti-cancer activity (Kotake-Nara et al. 2005; Koyanagi et al. 2003; Miao et al. 1999; Son et al. 2003).

Many in vivo and in vitro studies of dietary seaweed report decreased angiogenesis and increased apoptosis of tumor cells (Konishi et al. 2006; Koyanagi et al. 2003; Sekiya et al. 2005), inhibition of tumor cell adhesion and metastasis (Liu et al. 2005) and enhanced immune responses (Maruyama et al. 2003; Maruyama et al. 2006). Nishino and colleagues have investigated seaweed modulation of the urokinase plasminogen system (Nishino et al. 1999; Nishino et al. 2000). Based on the wide range of antitumor effects, we investigated the possibility that seaweed could affect uPAR concentrations in women who consume seaweed. The urokinase-type plasminogen activator (uPA), urokinase-type plasminogen activator receptor (uPAR, CD87), and its plasminogen inhibitors 1 and 2 are central to the maintenance of homeostasis, directly affecting the extracellular matrix (ECM), inflammation, tissue repair. Increased concentrations have been shown to be associated with more rapid cancer progression (Foekens et al. 2000). Urinary concentration of uPAR is highly correlated with urinary uPA concentrations, and both are correlated with tissue concentration (Foekens et al. 2000; Sier et al. 2004).When uPA/uPAR concentrations are increased, there is increased ECM degradation that allows cancer cells to migrate, leading to metastases. Urokinase is also used therapeutically to treat serious conditions involving blood clots. In clinical studies, tissue concentration of uPA is an independent prognostic predictor of BC progression (Ceccarelli et al. 2010; Look et al. 2002).

We therefore included evaluation of one part of the urokinase system, uPAR, in this study as a possible biomarker for seaweed activity that might be related to BC prevention.

To further assess whether a dietary seaweed intervention could alter protein expression in urine and serum in a non-seaweed consuming population of healthy postmenopausal women, we used surface enhanced laser desorption/ionization time of flight coupled with mass spectrometer (SELDI-TOF-MS). Proteomic analyses have been used to identify cancer biomarkers with high sensitivity and specificity, including those related to BC (Gast et al. 2008; Shimizu et al. 1991; van Winden et al. 2009). SELDI has also been shown to be sensitive enough to be used to identify changes in serum associated with the addition of a novel food (green tea) (Tsuneki et al. 2004).

  Eligibility

Ages Eligible for Study:   45 Years to 68 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy
  • Postmenopausal (verified by follicle stimulating hormone (FSH) [23.0-116 mIU/ml]
  • Omnivorous eating habits (including meat and dairy products more than twice per week)
  • Limit alcoholic intake to ≤ 1 drink (12 g alcohol)/week

Exclusion Criteria:

  • No allergies to seaweed, soy, shellfish or iodine
  • No current use of tobacco
  • No hormone replacement therapy
  • For BC survivors, no chemotherapy or radiation treatments within the preceding 6 months
  • No history of cancer (other than BC or squamous cell skin cancer) within the previous 20 years
  • No current gastrointestinal disorders or diabetes
  • No oral antibiotics taken in the previous 3 months
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01663792

Locations
United States, South Carolina
University of South Carolina Cancer Research Center
Columbia, South Carolina, United States, 29208
Sponsors and Collaborators
University of South Carolina
U.S. Army Medical Research and Materiel Command
Investigators
Principal Investigator: Jane Teas, Ph.D. University of South Carolina
  More Information

Publications:

Responsible Party: University of South Carolina
ClinicalTrials.gov Identifier: NCT01663792     History of Changes
Other Study ID Numbers: DAMD-17-98-1-8207
Study First Received: August 9, 2012
Last Updated: August 9, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by University of South Carolina:
urokinase receptor
protein expression
seaweed (Undaria pinnatifida)

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases

ClinicalTrials.gov processed this record on April 17, 2014