Strawberries Are a Great-Tasting, Effective Component of the “Portfolio” Diet: University of Toronto Study

University of Toronto researchers presented findings at the Experimental Biology 2007 meeting that showed strawberries can be an important part of the “Portfolio” diet designed to lower cholesterol.

The study aimed to test the palatability and cholesterol-lowering ability of the traditional portfolio diet and one modified to contain strawberries. Twenty- eight subjects who had been following the traditional portfolio diet for an average of 18 months were instructed to eat either three, one-cup servings of strawberries or their typical 2 ounces of oat bran bread daily for one month with a washout period between each trial.

The subjects rated the palatability of strawberries as an 8.8 out of a maximum of 10 compared to oat bran at 6.2 out of 10. On both the strawberry and oat bran interventions, LDL-cholesterol levels were about 13% reduced from baseline, but were not significantly different from each other.

In 2003, the University of Toronto researchers first reported on the cholesterol-lowering effects of a combination of plant-based cholesterol-lowering foods (soy, nuts, soluble fiber and sterols) eaten together for maximum benefit. The scientists have reported that up to a third of individuals following the portfolio approach experienced more than a 20% reduction in LDL-cholesterol levels and another one- third experienced a 15% reduction. The only downside to the approach is that the portfolio plan is hard to follow due to the strict combination of foods that many individuals do not find appealing.

Nguyen TH, Kendall WC, Faulkner DA et al. (2007) Strawberries to improve the palatability of a cholesterol lowering diet. 2007 Experimental Biology meeting, Abstract # 847.27,; accessed April 20, 2007.

Strawberries and Esophageal Cancer: Are They Protective?

The first patients are being recruited for a human clinical trial to investigate if strawberries may help prevent esophageal squamous cell carcinoma (SCC). The research is a collaborative effort between scientists at The Ohio State University Comprehensive Cancer Center and the Peking Union Medical College Hospital in Beijing, China.

Esophageal cancer is one of the most common cancers worldwide, and is one of the most deadly. The Chinese have one of the highest incidence rates of esophageal cancer in the world, accounting for 50% of all cases worldwide. Esophageal cancer is a cancer known to be influenced by diet and lifestyle, including nutrient-poor diets, excess alcohol and nitrosamine carcinogens from tobacco smoke or certain processed or cured foods.

Strawberries are rich in many bioactive phytonutrients that are thought to help down-regulate cancer-related molecular events including inflammation, cell proliferation and genetic damage. Results from preliminary animal model research conducted by researchers at The Ohio State University revealed that freeze-dried strawberries inhibited tumor development in the rat esophagus by inhibiting the metabolism of nitrosamines to DNA-damaging species and by reducing the growth rate of premalignant cells.3

Cancer ranks second behind heart disease as a leading cause of death. According to the American Cancer Society, nearly 560,000 deaths are expected in 2007 from cancer. Esophageal cancer will claim the lives of nearly 14,000 this year. Approximately 30% of all cancers are related to lifestyle factors such as poor nutrition, physical inactivity and obesity.4

Chen Tong et al. The Ohio State University Comprehensive Cancer Center, Columbus, OH and Peking Union Medical College Hospital, Beijing, China

3 Carlton, P.S., Kresty, L.A., Siglin, J.C., Morse, M.A., Lu, J., Morgan, C., and Stoner, G.D. Inhibition of N-nitrosomethylbenzylamine-induced tumorigenesis in the rat esophagus by dietary freeze-dried strawberries. Carcinogenesis 2001;22: 441 – 446.

4 American Cancer Society. Cancer Facts & Figures 2007. Atlanta: American Cancer Society; 2007.

Can Strawberries Help Slow Neurological Declines That Occur With Aging? If So, How?

At the USDA Human Nutrition Research Center on Aging, the neuroscience laboratory is trying to answer those questions.

Several studies have suggested that oxidative stress or the production of excess reactive oxygen species (ROS) is associated with a loss of neuronal functioning, and may, in part, be associated with declines in memory and cognitive function that occur with aging. Diets rich in antioxidants and anti- inflammatory compounds are thought to be a promising approach to help reduce the deleterious effects of brain aging from ROS.

Tufts neuroscientists reported their preliminary findings when they supplemented aged rodents diets with 1-2% strawberry extract, then evaluated them on several memory and behavioral tests to compare before and after results to a control group of animals of the same age that consumed a normal chow diet. With 1-2% strawberry supplementation in the diet, the aged rodents performed better on all tests to measure memory and cognitive function compared to the control rodents. The studies found that strawberry supplementation was equally beneficial as the same percentage of blueberry extract added to the diet.

Currently in the second year of a three-year project, the researchers are further studying the mechanisms by which strawberry anthocyanins, the flavonoid pigments, are neuro-protective. Anthocyanins may help protect the neuronal cells from reactive oxygen species (ROS), inhibiting inflammation and impacting neuronal cell signaling that are linked to declines in cognitive function. Through additional studies that are able to evaluate the regional localization of the strawberry compounds on the animals’ brain, the researchers are assessing the mechanisms involved in the motor and cognitive benefits found with strawberries to gain more insight into exactly how strawberry bioactives influence the brain.

Joseph JA. The USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA.

Mild to Moderate Hypertensives Recruited to Study Association between Strawberries and Blood Pressure Control

High blood pressure is a cardiovascular disease that afflicts nearly one in three US adults. Over 1/3 of adults are also thought to have “pre-hypertension” which is borderline high blood pressure that should be managed through diet and exercise. 2 Hypertension is called the “silent killer” because millions of Americans are unaware that they have it, yet it decreases life expectancy and increases the risk of heart attack, stroke, heart failure, and renal disease.

The California Strawberry Commission is funding a multi-year randomized, controlled trial involving 80 men and women, ages 30 to 50 years old, who have prehypertension (defined as systolic pressures between 120 and 139 mm Hg or diastolic pressures between 80 and 89 mm Hg).

There is substantial evidence to suggest that strawberries will help reduce blood pressure, but the UC Davis clinical trial will be the first study designed to meet the highest level of scientific scrutiny, and is able to draw cause and effect answers. In previous studies, the UC Davis researchers previously found in laboratory studies that strawberries had potent vasodilator properties, through, at least in part, endothelial nitric oxide synthase activation. In addition, the CSC has previously analyzed NHANES and CSFII data and has found a positive correlation between strawberry consumption and lower blood pressure.

Burton-Freeman et al. University of California at Davis, Department of Nutrition, Davis, CA

2 American Heart Association and American Stroke Association. Heart Disease and Stroke Statistics—2007 Update At–a-Glance.

Study Investigates Strawberries Role in Cardiovascular Disease Prevention

Researchers at UCLA are set to enroll subjects with high blood cholesterol levels into a clinical feeding study where they will be given either 500g strawberries daily or an isocaloric snack supplement to determine if strawberries positively impact biomarkers for cardiovascular disease.

The biomarkers to be evaluated at baseline and throughout the study will include oxidized phospholipids (ApoB), oxidized LDL, total cholesterol, triglycerides and HDL-cholesterol and C-reactive protein. There is sufficient basic science and animal data that suggests the high antioxidant activity of strawberries may help reduce levels of oxidized LDL cholesterol, the most atherogenic cholesterol particle. Flavonoids in strawberries may also provide cardio protection by inhibiting platelet aggregation and thromboxane synthesis.

Nearly 2,400 people die each day of cardiovascular disease, an average of one death every 36 seconds. 1 One of the major modifiable risk factors for development of coronary heart disease is hypercholesterolemia. According to the American Heart Association, one in three Americans has blood cholesterol levels at or above the desirable limit of 200 mg/dL and a 10% reduction in total cholesterol nationwide could result in a 30% reduction in the incidence rates of cardiovascular disease. Diets rich in plant-based foods and, specifically fruits and vegetables are thought to provide protective vitamins, minerals and phytonutrients while helping to keep the diet low in nutrients known to increase risk for heart disease, such as saturated fat, trans fats, cholesterol and sodium.

Seeram et al. UCLA Center for Human Nutrition, University of California, Los Angeles

1 American Heart Association and American Stroke Association. Heart Disease and Stroke Statistics— 2007 Update At–a-Glance.

Research Round-Up

New insights on the relationship between diet, body weight, inflammation and chronic disease will be presented by nutritional experts in the field at a symposium, “Taming the Fires of Inflammation Through Diet,” sponsored by the California Strawberry Commission at the American Dietetic Association Food and Nutrition Conference and Expo in Honolulu, Hawaii on September 16, 2006. Zhaoping Li, MD, PhD, Associate Professor of Medicine, Center for Human Nutrition, David Geffen School of Medicine at University of California, Los Angeles will share a detailed look at the process of inflammation, discuss the effects of inflammation in normal weight adults, and emerging research from clinical trials looking at strawberry consumption’s impact on inflammation in normal weight adults. Britt Burton- Freeman, PhD, Assistant Research Nutritionist, Department of Nutrition, University of California, Davis will discuss the effects of inflammation in overweight and obese adults and emerging research from clinical trials looking at strawberry consumption’s impact on inflammation in overweight and obese adults. Below is a summary of their presentation.

Zhaoping Li, MD, PhD – “The Secret Killer,” a Time magazine cover story in February 2004 brought inflammation center stage, discussing the role of inflammation in cancer, diabetes, and cardiovascular, pulmonary, neurological, and autoimmune diseases. Inflammation is the first response of the immune system to infection or irritation, causing the production of cytokines. A cascade occurs as various leukocytes cause the initiation and maintenance of inflammation, further stimulated by lymphocytes such as T cells, B cells and antibodies. C-reactive protein (CRP) is produced by the liver in response to cytokine production. High-sensitivity CRP (hs-CRP) has been suggested to predict future cardiovascular events in healthy men and women. In fact, a meta-analysis published in the New England Journal of Medicine indicated that hs-CRP is a stronger predictor of future cardiovascular events than the total cholesterol/HDL cholesterol ratio, LDL cholesterol, total cholesterol, and homocysteine.

A correlation has been established between inflammation and diet. There is an inverse relationship between phytonutrients, non-nutritive compounds found in fruits and vegetables, and CRP. In a study published in the American Journal of Clinical Nutrition, participants who consumed eight servings of fruits and vegetables per day had significantly lower CRP levels than those who consumed two and five per day. Researchers at UCLA are identifying phytonutrients in strawberries, developing methods to detect strawberry phytonutrients and their biological activities in human blood and urine. They have found that strawberry phytonutrients include flavanoids such as anthocyanins and flavonols, hydrolyzable tannins such as ellagic acid and glycosides, and phenolic acids such as hydroxycinnamic acids and esters. Their research has suggested that bioactives of compounds in human plasma and urine have desirable effects on hs-CRP and inflammation.

Britt Burton-Freeman, PhD – Obesity is a major risk factor for many chronic diseases and increasing adiposity is associated with increased CRP. In fact, multiple studies showed that CRP was significantly higher in overweight and obese individuals than normal weight individuals. Adipose tissue is actually a dynamic tissue with endocrine function. Obesity represents a pro-inflammatory state and weight loss decreases the inflammatory state. Obesity can be a model for studying inflammatory response and researchers are asking the following questions: Can changing the dietary pattern, independent of weight loss, decrease the pro/anti-inflammatory response profile, and reduce disease risk? Can changing the dietary pattern in addition to weight loss augment/enhance the anti- inflammatory benefits of weight loss? Dietary intervention that increases phytonutrient intake does make a difference according to research published in the American Journal of Clinical Nutrition. These bioactive compounds quiet the endothelium, increase anti-oxidant activity, and decrease cytokine synthesis.

Research at UC Davis is focusing on human studies in overweight and obese subjects. Individuals are being fed a Strawberry Intervention diet (4 servings per day) or a Standard Diet. Endpoints being investigated include changes in lipid profile, the inflammatory profile, endothelial function, and oxidative stress.

View from the Lab

Navindra Seeram PhD, assistant director of the UCLA Center for Human Nutrition and adjunct assistant professor at the David Geffen School of Medicine at UCLA, and a member of the Commission’s Scientific Advisory Committee, discusses the potential chemopreventative benefits of berries in a chapter of the recently-published Nutritional Oncology. In the chapter, Seeram discusses the research supporting the role of berry consumption on cancer prevention and the disparate nutrients that may be responsible for berries’ positive benefits. A wide number of laboratory and animal studies have shown that berries may have anticancer properties which can be attributed to bioactive phytochemicals including flavanoids (anthocyanins, flavonols, and flavanols); tannins, such as proanthocyanidins (PAs), ellagitannins (ETs), and gallotannins (GTs); stilbenoids, such as resveratrol; phenolic acid (hydroxybenzoic and hydroxycinnamic acids); and lignans. Below is a summary of the research in the chapter relating to strawberries.

While flavonols are typically present in the leaves of plants and skins of fruits, they are found in the flesh of strawberries. Two of the most common flavonols, quercetin and kaempferol are present in substantial quantities in strawberries. Lignans, which are commonly found in flaxseed and linseed, have also been found in strawberries. The main phenolics in strawberries after anthocyanins are ellagitannins (ETs). Studies have suggested that berries high in ETs, including ellagic acid, show greater effects against oral cavity and esophageal cancers than berries abundant in tannins.

In a study investigating effects of purified berry bioactives as well as whole strawberry fruit extract on the viability and apoptosis of human hepatoma HepG2 cells, only quercetin and whole strawberry fruit extract inhibited viability and induced apoptosis. Another study demonstrated the inhibitory effects of strawberries on well-known tumor promoters, tetradecanoylphorbol-13-acetate (TPA) and ultraviolet B (UVB), which may be due to the antioxidant properties of strawberries.

Seeram, NP; Berries. Nutritional Oncology, second edition. Eds. Heber, D, Blackburn, G, Go, VLW, Milner, J; Academic Press, London, UK.

Increased Fruit Consumption Associated with Lower HbA1C

NHANES III data on more than 14,000 adults were analyzed for HbA1C (glycosylated hemoglobin) levels by tertiles of fruit and vegetable intake. Fruit and vegetable intake was measured by food frequency questionnaire. Data was examined within groups stratified by BMI (normal, overweight, obese) and sex/age (males aged 19 to 65 and pre- and post- menopausal females). Individuals with diabetes were excluded, as were subjects with extreme weight or height, and women who were pregnant, lactating, or missing menopausal status. Results indicated that increased frequency of fruit consumption was associated with lower HbA1C among overweight premenopausal and normal and overweight men . Increased frequency of vegetable intake was associated with lower HbA1C levels among normal premenopausal women. There appears to be a relationship between increased frequency of fruit or vegetable consumption and this long term marker of glycemic regulation.

Kimmons, J.E., et. al. HbA1C levels by frequency of fruit and vegetable consumption and BMI from NHANES III. Center for Disease Control and Prevention.

Anthocyanin-rich Diet and Type 2 Diabetes Risk

Noting that low intake of fruits is a risk factor for the development of diseases such as Type 2 diabetes, researchers from The University of Maine suggest that this may due to the ability of flavonoid pigments in red and blue fruits rich in anthocyanins to modulate alpha-glucosidase and aldose reductase activity and insulin production in vitro. When fruits are lacking from the diet, anthocyanins would also be absent. The researchers investigated the potential benefits of anthocyanin consumption in individuals at risk for developing diabetes. Subjects were paired by gender, age, and fasting blood glucose levels, and then each member of the pair were randomly assigned to the control or treatment group. The control group was instructed to make no changes in their diet or exercise habits and to limit consumption of anthocyanin-containing foods to no more than 3 servings per week. The treatment group was provided with a list of serving sizes for common fruits that provided 150 mg anthocyanins and instructed to consume at least two servings daily for three months. Fasting blood glucose, insulin, glycosylated hemoglobin, cholesterol, triglycerides, antioxidant capacity and urinary microalbumin were measured at baseline and at 6 and 12 weeks of the study. Results from the study are anticipated this spring.

Henderson, A., et. al. Can an anthocyanin-rich diet reduce risks for developing Type 2 diabetes? The University of Maine.

Metabolites of Strawberry Anthocyanins

Among berry bioactives, the metabolism and bioavailability of anthocyanins in both human and animal models have been well studied. Researchers from the United States Department of Agriculture (USDA) are currently working to identify four urinary metabolites of strawberry anthocyanins. Results on the identity of these metabolites are expected in the spring. What they have determined thus far in their investigation is the stability of the metabolites. The results suggest that three metabolites degrade over time while one peak area increased over time, indicating it may be a degradation product of the other metabolites.

Carkeet, C., et. al. Stability of Urinary Metabolites of Strawberry Anthocyanins. Beltsville Human Nutrition Research Center, USDA.

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