N05044: Impact of fruit and vegetables on bone health - potential mechanisms at whole body and cellular level

Study Duration: January 2003 to December 2004

Contractor: Human Nutrition Research Centre (Medical Research Council, Cambridge)

Recent studies have shown that a higher intake of fruit and vegetables is positively associated with bone mineral density (BMD) in premenopausal women and the elderly. Since then, the researchers have, in collaboration with the Dietary Approaches to Stop Hypertension study investigators, found that subjects (23-75 years) consuming a diet high in fruit, vegetable and dairy products (DASH diet) for 3 months, had significantly reduced bone turnover. There was lower bone loss (measured by plasma C-terminal telopeptides of type I collagen (CTX) and bone formation (osteocalcin)) and lower urinary calcium excretion.

There are several potential mechanisms for this, including the lower potential renal acid load (PRAL) of the DASH diet - 12 mEq/d). A low PRAL is associated with higher dietary potassium, magnesium and calcium, and lower animal protein and cereal content, resulting in less generation of dietary acid in the intestine and liver, and as a result, lower urinary calcium losses and lower bone resorption. The DASH diet also provided higher levels of citrus fruit, tomatoes and tomato products, green leafy vegetables, allyl foods and cruciferous vegetables. Fruit and vegetables are rich sources of antioxidants, including vitamin C and carotenoids. Positive associations have been found between vitamin C intake, bone mineral status and reduced incidence of fracture. The carotenoids lycopene, canthaxanthin, alpha- and beta- carotene have been shown to directly stimulate mouse osteoblast activity in vitro. More recently lutein intake, as measured by food frequency questionnaire (FFQ), was found to be positively associated with BMD in older men.

This project will carry out an in-depth investigation of the effects of fruit and vegetable intake and associated dietary patterns on bone metabolism and bone mineral status (size-adjusted) in existing cohorts of older adolescent boys and girls (16-19 years), young women (23-36 years) and older men and women (60-83 years). The effects of antioxidant intake and status and dietary PRAL will also be explored. Using microarray technology, cellular mechanisms of action of specific antioxidants will be investigated in primary human osteoblasts, providing novel insight into their effects on bone cell activity. This work will result in a cost-effective, in-depth investigation into the effects of fruit and vegetable intake on bone health, generate new hypotheses and provide the basis for future studies and recommendations in relation to diet and bone health.

To build and advance on previous findings, the project will (1) Use an extended range of subjects to determine the effects of diet at key stages of the lifecycle; (2) Use more detailed dietary intake data, allowing more accurate profiling of fruit and vegetable intake, associated dietary patterns and PRAL; (3) Include antioxidant status, which will provide an accurate physiological index of fruit and vegetable intakes, and allow identification of specific antioxidant effects; (4) Use a novel range of bone markers to delineate mechanisms of action of diet on skeletal metabolism; (5) Examine the effect of seasonal dietary patterns and antioxidant status on bone metabolism; (6) Use powerful statistical methodology including factor and meta analysis to allow comparisons of effect across the life-stages and with previously published data; (7) Include confounders in the statistical analysis including body size, lean and fat mass, physical activity and lifestyle; (8) Extend the research into diet-gene interactions, using microarray technology.