Pharmacokinetics of Anthocyanins and Ellagic Acid in Healthy Volunteers Fed Freeze‐Dried Black Raspberries Daily for 7 Days

Stoner, Gary D.; Sardo, Christine; Apseloff, Glen; Mullet, D.; Wargo, Wayne F; Pound, Vickie; Singh, Alpana; Sanders, James E.; Aziz, Robeena; Casto, Bruce C.; Sun, Xiaoli

doi:10.1177/0091270005279636

Cited by 140 publications

(112 citation statements)

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“…On the basis of their chemical composition as well as strongly supportive preclinical in-vitro and in-vivo data generated by our laboratories, FBR was selected as the bioactive constituents to incorporate into these gels (9-13). Essential for human applications, our Phase I clinical trial demonstrated that consumption of large quantities of FBR are well tolerated in humans (14). A final consideration is the pharmacologic benefit derived from local delivery formulations; specifically the ability to obtain therapeutically relevant local levels without development of systemic complications.…”

Section: Discussionmentioning

confidence: 99%

“…The berries were harvested mechanically (with a picker) in a total period of 4 hr, washed, and frozen at −20°C within an hour of the time of harvest. The berries remain frozen until they are transported frozen to Van Drunen Farms in Momence, IL, where they are then freeze-dried and ground into a powder as described previously (9)(10)(11)(12)(13)(14).…”

Section: Methodsmentioning

confidence: 99%

“…Further, treatment of oral SCC cell lines with an ethanol/water extract of FBR (RO-ET) elicited a wide array of chemopreventive effects that included reduction in pro-angiogenic cytokine release, inhibition of proliferation, induction of differentiation, and suppression of the "high output" nitric oxide synthase isoform (NOS-2) (13). Phase I human clinical trials conducted by our laboratories have confirmed that dietary administration of high dosages of freeze-dried black raspberries for periods up to 7 days is well tolerated (14). Finally, when contemplating development of a natural product based treatment, it is beneficial to first identify its bioactive constituents because preservation of these agents indicates compound stability in the final formulation.…”

Section: Introductionmentioning

confidence: 90%

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Formulation and In-Vitro and In-Vivo Evaluation of a Mucoadhesive Gel Containing Freeze Dried Black Raspberries: Implications for Oral Cancer Chemoprevention

et al. 2007

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Purpose-The purpose of these studies was to formulate mucoadhesive gels containing freeze dried black raspberries (FBR) and to determine optimum parameters for a subset of FBR bioactive compounds including anthocyanin stability, absorption and penetration in-vitro and in-vivo.Materials and Methods-Berry gels were prepared having FBR at 5% and 10% w/w and final pHs ranging from 3.5 to 7.5. A HPLC assay was developed to quantify and determine the stability of the anthocyanins in the gels. A single time-point study was performed to determine anthocyanin uptake when the gels were applied to oral mucosa. Penetration of anthocyanins into human oral tissue explants was determined as a function of gel pH and FBR content. A HPLC-mass spectroscopy assay was utilized to quantify the anthocyanin levels in human oral tissue explants, saliva, and blood.Results-The stability of anthocyanins in the gel was directly related to gel pH and storage temperature. Maximum stability of anthocyanins was found at lower pH (pH 3.5) and storage temperature (4°C). Anthocyanins contained in mucoadhesive berry gel formulations were readily absorbed into human oral mucosa tissue as evidenced by detectable blood levels within 5 min after gel application. There was a trend for greater penetration of anthocyanins into tissue explants for berry gels with a final pH of 6.5 versus pH 3.5.Conclusions-Formulation and characterization of a novel gel formulation for local delivery of chemopreventive compounds to human oral mucosal tissues has been described. The results show anthocyanin stability was dependent upon gel pH and storage temperature and also demonstrate that the gel composition is well-suited for absorption and penetration into the target oral mucosal tissue site.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 90%

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Formulation and In-Vitro and In-Vivo Evaluation of a Mucoadhesive Gel Containing Freeze Dried Black Raspberries: Implications for Oral Cancer Chemoprevention

et al. 2007

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“…A trial with eleven subjects was undertaken to determine the safety/tolerability of freeze-dried BRBs and to measure anthocyanins and ellagic acid in the plasma and urine [49] in subjects fed 45 grams (equivalent to a 5% BRB diet in animals) of freeze-dried BRB powder as a slurry in water daily for 7 days. Blood samples were collected predose on days 1 and 7 and at 10 time points over a period of 12 hours postdose.…”

Section: Toxicitymentioning

confidence: 99%

Cancer prevention with freeze-dried berries and berry components

Stoner

Wang

Zikri

et al. 2007

Seminars in Cancer Biology

151

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Our laboratory is developing a food-based approach to the prevention of esophageal and colon cancer utilizing freeze-dried berries and berry extracts. Dietary freeze-dried berries were shown to inhibit chemically-induced cancer of the rodent esophagus by 30-60% and of the colon by up-to 80%. The berries are effective at both the initiation and promotion/progression stages of tumor development. Berries inhibit tumor initiation events by influencing carcinogen metabolism, resulting in reduced levels of carcinogen-induced DNA damage. They inhibit promotion/progression events by reducing the growth rate of premalignant cells, promoting apoptosis, reducing parameters of tissue inflammation and inhibiting angiogenesis. On a molecular level, berries modulate the expression of genes involved with proliferation, apoptosis, inflammation and angiogenesis. We have recently initiated clinical trials; results from a toxicity study indicated that freeze-dried black raspberries are well tolerated in humans when administered orally for 7 days at a dose of 45 grams per day. Several Phase IIa clinical trials are underway in patients at high risk for esophagus and colon cancer; i.e., Barrett's esophagus, esophageal dysplasia and colonic polyps, to determine if berries will modulate various histological and molecular biomarkers of development of these diseases.

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“…6 The research has shown that acylated ACNs may behave quite differently from their nonacylated counterparts, in terms of their stability and bioavailability; (Stoner et al, 2005), hence it is not reasonable to consider all ACNs equally. Therefore, knowledge regarding the concentrations and daily intake of specific ACNs is essential.…”

Section: Introductionmentioning

confidence: 99%