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Title: The effects of fruit and vegetable-derived bioactive compounds on bone
Author: Macdonald-Clarke, Claire Joanne
ISNI:       0000 0004 2737 5662
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2012
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A diet rich in fruit and vegetables is associated with better bone health although the reason behind this remains unclear. Mounting evidence suggests that it may be particular fruit and vegetables or a variety of fruit and vegetables that are important and it has been suggested that bioactive compounds, considered to be non-essential nutrients, may play a role. The aims of this project were to study the roles of three classes of dietary compounds on bone health: flavonoids (represented by hesperetin), anthocyanidins and carotenoids. Methods The influence of six major anthocyanidins, six major carotenoids and the citrus flavanone hesperetin were examined by three methodological approaches: (i) a cross-sectional study using outcomes of bone mineral density (BMD) and markers of bone turnover, (ii) a randomised controlled trial with bone turnover markers as the outcome measures and (iii) in vitro examinations in osteoblasts and osteoclasts. The epidemiological part of this thesis was carried out in the Aberdeen Prospective Osteoporosis Screening Study (APOSS) cohort. Women were recuited to the study between 1990 and 1994 and returned for a follow-up visit between 1997 and 1999 (n=3214, mean age 54.8 y at follow-up). Measurements of BMD at the spine and hip were taken at both visits; and urinary markers of bone resorption total deoxypyridinolines (DPD) and total pyridinolines (PYD), and a serum bone formation marker N-terminal propeptides of type 1 procollagen (P1NP), were analysed at the follow-up visit. Diet was recorded by food frequency questionnaire and dietary anthocyanidins and carotenoids were estimated using a database of food compositions developed for this purpose. Analysis was carried out to determine if anthocyanidin or carotenoid intakes were associated with BMD, change in BMD (between the 2 visits), or markers of bone resorption or formation, within the APOSS population. The effect of the carotenoid lycopene on bone turnover was assessed in a 3-month randomised controlled trial in 214 apparently healthy men and women. Participants were randomised into 3 groups: high dietary lycopene (minimum 10 mg/d); low tomato diet with lycopene capsule vi (10 mg/d) or a low tomato diet as the control. Marker of bone resorption plasma carboxyterminal collagen crosslinks (CTX) and marker of bone formation serum P1NP were analysed at baseline (after washout) and after 12 weeks of intervention. In order to study if the aglycone or glycoside compounds directly affect bone metabolism, the effects of a series of anthocyanidins on osteoblast differentiation were analysed in vitro. The effects of hesperetin on osteoblast differentiation and mineralisation and on osteoclast formation and function in vitro were also assessed. Results Regarding the epidemiological part of the project, associations between both dietary anthocyanidins and carotenoids and markers of bone health were observed in the APOSS population. Higher total dietary anthocyanidin intake was found to be associated with higher spine BMD and lower concentrations of bone resorption markers. In addition higher total dietary anthocyanidin intake was associated with less BMD loss at the spine in the period between baseline and follow-up, which was illustrated by a 13.2% difference in annual percent bone loss between the highest and lowest quartiles of anthocyanidin consumption. Individual anthocyanidins were also found to be associated with different markers of bone turnover. Total dietary carotenoid intake was found to be associated with BMD at the spine and lower concentrations of bone resorption markers. Analysis of the individual carotenoids showed that lycopene was associated with higher BMD at the hip; β-carotene was associated with less BMD loss at the spine; and β-carotene, lycopene, β-cryptoxanthin and lutein/zeaxanthin were found to be associated with lower concentrations of bone resorption markers. Each of these findings remained significant after adjusting for confounding factors. In the 3-month randomised controlled trial, lycopene supplementation did not alter bone turnover markers CTX or P1NP. These results are in contrast to those of a previous, smaller randomised controlled trial in postmenopausal women where a decrease in a marker of bone resorption (N-telopeptide of collagen cross-links (NTX)) was observed. Therefore these results suggest that the potential beneficial effect of lycopene may be specific to a population at risk of bone loss. Alternatively, lycopene may have a cumulative protective effect over the lifetime but short-term effects may only be observed in groups with high bone turnover, where there is greater potential to see measureable effects. The results of the in vitro investigations of this project showed that neither anthocyanidins nor hesperetin had an affect on osteoblasts or osteoclasts at physiologically relevant concentrations. Almost all of the anthocyanidin compounds tested had no effect on osteoblast differentiation, and none at physiological concentrations. Similarly, hesperetin had no effect on osteoblast differentiation or mineralisation although it did have an effect on both osteoclast formation and function, but only at concentrations which were not considered to be physiologically relevant. These results add weight to the suggestion that the metabolites of dietary compounds may be responsible for the action on bone metabolism rather than the dietary compounds directly or that a combination of compounds, as found in foods, may be required. Conclusions Taken together, these results support the evidence that a diet rich in fruit and vegetablederived bioactive compounds is beneficial to bone health. Future work could include: observational studies to examine the association of lifetime consumption and long-term risk of fracture; larger dietary intervention trials; and in vitro studies to examine the effects of the compound metabolites and elucidate their mechanism of action.
Supervisor: Not available Sponsor: Nuffield Foundation's Oliver Bird Rheumatism Programme
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Bioactive compounds ; Bone ; Flavonoids ; Carotenoids ; Fruit ; Vegetables