Effect of Black Raspberry Phytochemicals on Oral Microbiome in Current Smokers and Non-smokers

PRIMARY OBJECTIVES:

I. Determine the effect of black raspberry phytochemicals on community dynamics within oral
biofilms.

II. Examine the effect of oral bacterial communities on metabolism of black raspberry
phytochemicals in current and never smokers.

III. Evaluate the efficacy of black raspberry phytochemicals and their metabolites in
reversing the effect of smoking on oral host-microbial interactions.

OUTLINE: Participants are randomized to 1 of 2 arms.

ARM I: Participants receive bioactivity of black raspberry phytochemical-rich delivery
vehicle (BRB nectar) orally (PO) once daily (QD) for 12 weeks.

ARM II: Participants receive placebo nectar PO QD for 12 weeks.

Inclusion Criteria:

- Subjects must be periodontally healthy; this is defined as all sites with attachment
levels =< 2 mm and probing depths =< 3 mm) and caries-free, as evidenced by a DMF
(decayed, missing, filled teeth) Index of less than 5

- Subject must be either a current smoker or a never smoker; to define a smoker, we will
utilize the Centers for Disease Control definitions; any individual who is currently
smoking and has smoked more than 100 cigarettes in their lifetime will be identified
as a current smoker; smoking status will be assessed by a questionnaire; since only
current and never smokers are included, it is not necessary to measure cotinine
levels; the number of cigarettes smoked per day and years of smoking will be used to
calculate pack-years, which will be used as a measure of tobacco exposure; a never
smoker is defined as a person who never smoked, or smoked less than 100 cigarettes in
their lifetime, and who has not had a cigarette in over ten years

- Agree to consume a standardized vitamin/mineral supplement and avoid other nutrition,
dietary or alternative medications/supplements for the duration of the study

- Agree to follow a controlled ellagitannin/low polyphenolic diet and to document
consumption of polyphenolic foods each day of the study using our easy to document
daily form

Exclusion Criteria:

- Have history of oral cancer or carcinoma in-situ

- Have had antibiotic therapy or professional cleaning within the previous 3 months

- Require antibiotic therapy prior to oral cleaning

- Have an active metabolic or digestive illness that impact phytochemical absorption and
metabolism, including: diabetes, malabsorptive disorders (Crohn's disease, documented
celiac disease, etc.), renal insufficiency (creatinine [Cr] > 1.4), hepatic
insufficiency (nonalcoholic steatohepatitis [NASH], cirrhosis, active viral
hepatitis), hyper- or hypothyroidism, or short bowel syndrome

- Are alcohol consumers (defined as an average consumption of greater than 1 drink/day
over one week [wk] [one drink = 1 oz. liquor, 12 oz. beer])

- Are taking immunosuppressant medications, bisphosphonates or steroid medications

- Currently undergoing treatment for cancer with chemotherapy, hormone therapy,
radiation, or biological therapy

- Have a known allergy or food intolerance to ingredients in study products (black
raspberries or other berries)

- Are planning to conceive, or are currently pregnant or lactating

- Have had any active oral lesions in the past month or currently have any oral disease
or obvious open sores in the oral cavity or surrounding the oral opening

- Are taking any medications that have known impact on immune responses (e.g.
nonsteroidal anti-inflammatory drugs [NSAIDs] for chronic pain) or are actively being
investigated for the prevention of tobacco related cancers will not be acceptable; a
single 81 mg aspirin per day will be acceptable