Biomarkers of fruit and vegetable intake in Human intervention studies a systematic review

Observational evidence consistently shows that consumption of a diet rich in fruit and vegetables may offer protection against diseases such as cardiovascular disease and cancer. Assessment of dietary intake is complex and prone to many sources of error. More objective biomarkers of fruit and vegetable intake are therefore of interest. The aim of this review is to examine the usefulness of the main biomarkers of fruit and vegetable intake to act as objective indicators of compliance in dietary intervention studies. A comprehensive search of the literature was conducted using six databases. Suitable papers were selected and relevant data extracted. The papers were categorized into 3 sub-groups: whole diet interventions; mixed fruit and vegetable interventions; and studies involving individual varieties of fruits or vegetables. Ninety-six studies were included in the review. Overall, the most commonly measured, and most consistently responsive, biomarkers were the carotenoids and vitamin C. Based on the results of this systematic review, it remains prudent to measure a panel of biomarkers in fruit and vegetable intervention studies. The only possible exception to this is “fruit only” intervention studies where assessment of vitamin C alone may suffice.

Effect of fruit and vegetable intake on oxidative stress and inflammation in COPD: a randomised controlled trial

Epidemiological evidence supports a positive relationship between fruit and vegetable (FV) intake, lung function and chronic obstructive pulmonary disease (COPD). Increasing FV intake may attenuate the oxidative stress and inflammation associated with COPD.

An exploratory randomised controlled trial to examine the effect of increased consumption of FV on oxidative stress and inflammation in moderate-to-severe COPD was conducted. 81 symptomatically stable patients with a habitually low FV intake (two or fewer portions of FV per day) were randomised to the intervention group (five or more portions of FV per day) or the control group (two or fewer portions of FV per day). Each participant received self-selected weekly home deliveries of FV for 12 weeks.

75 participants completed the intervention. There was a significant between-group change in self-reported FV intake and biomarkers of FV intake (zeaxanthin (p=0.034) and ß-cryptoxanthin (p=0.015)), indicating good compliance; post-intervention intakes in intervention and control groups were 6.1 and 1.9 portions of FV per day, respectively. There were no significant changes in biomarkers of airway inflammation (interleukin-8 and myeloperoxidase) and systemic inflammation (C-reactive protein) or airway and systemic oxidative stress (8-isoprostane).

This exploratory study demonstrated that patients with moderate-to-severe COPD were able to comply with an intervention to increase FV intake; however, this had no significant effect on airway or systemic oxidative stress and inflammation.

Serum amyloid A-related inflammation is lowered by increased fruit and vegetable intake, while high-sensitive C-reactive protein, IL-6 and E-selectin remain unresponsive

The present study assessed whether increased fruit and vegetable (F&V) intake reduced the concentrations of the inflammatory marker serum amyloid A (SAA) in serum, HDL2 and HDL3 and whether the latter reduction influenced any of the functional properties of these HDL subfractions. The present study utilised samples from two previous studies: (1) the FAVRIT (Fruit and Vegetable Randomised Intervention Trial) study - hypertensive subjects (systolic blood pressure (BP) range 140-190 mmHg; diastolic BP range 90-110 mmHg) were randomised to receive a 1-, 3- or 6-portion F&V/d intervention for 8 weeks, and (2) the ADIT (Ageing and Dietary Intervention Trial) study - older subjects (65-85 years) were randomised to receive a 2- or 5-portion F&V/d intervention for 16 weeks. HDL2 and HDL3 were isolated by rapid ultracentrifugation. Measurements included the following: serum high-sensitive C-reactive protein (hsCRP) by an immunoturbidimetric assay; serum IL-6 and E-selectin and serum-, HDL2- and HDL3-SAA by ELISA procedures; serum-, HDL2- and HDL3-cholesterol ester transfer protein (CETP) activity by a fluorometric assay. Although the concentrations of hsCRP, IL-6 and E-selectin were unaffected by increasing F&V intake in both studies (P>0·05 for all comparisons), those of SAA in HDL3 decreased in the FAVRIT cohort (P= 0·049) and those in HDL2 and HDL3 decreased in the ADIT cohort (P= 0·035 and 0·032), which was accompanied by a decrease in the activity of CETP in HDL3 in the FAVRIT cohort (P= 0·010) and in HDL2 in the ADIT cohort (P= 0·030). These results indicate that SAA responds to increased F&V intake, while other inflammatory markers remain unresponsive, and this leads to changes in HDL2 and HDL3, which may influence their antiatherogenic potential. Overall, the present study provides tangible evidence of the effectiveness of increased F&V intake, which may be of use to health policy makers and the general public.

A randomised controlled trial of increasing fruit and vegetable intake and how this influences the carotenoid concentration and activities of PON-1 and LCAT in HDL from subjects with type 2 diabetes

Background

High density lipoproteins (HDL) have many cardioprotective roles; however, in subjects with type 2 diabetes (T2D) these cardioprotective properties are diminished. Conversely, increased fruit and vegetable (F&V) intake may reduce cardiovascular disease risk, although direct trial evidence of a mechanism by which this occurs in subjects with T2D is lacking. Therefore, the aim of this study was to examine if increased F&V consumption influenced the carotenoid content and enzymes associated with the antioxidant properties of HDL in subjects with T2D.

Eighty obese subjects with T2D were randomised to a 1- or ≥6-portion/day F&V diet for 8-weeks. Fasting serum was collected pre- and post-intervention. HDL was subfractionated into HDL₂ and HDL₃ by rapid ultracentrifugation. Carotenoids were measured in serum, HDL₂ and HDL₃ by high performance liquid chromatography. The activity of paraoxonase-1 (PON-1) was measured in serum, HDL₂ and HDL₃ by a spectrophotometric assay, while the activity of lecithin cholesterol acyltransferase (LCAT) was measured in serum, HDL₂ and HDL₃ by a fluorometric assay.

In the ≥6- vs. 1-portion post-intervention comparisons, carotenoids increased in serum, HDL₂ and particularly HDL₃, (α-carotene, p = 0.008; β-cryptoxanthin, p = 0.042; lutein, p = 0.012; lycopene, p = 0.016), as did the activities of PON-1 and LCAT in HDL₃ (p = 0.006 and 0.044, respectively).

To our knowledge, this is the first study in subjects with T2D to demonstrate that increased F&V intake augmented the carotenoid content and influenced enzymes associated with the antioxidant properties of HDL. We suggest that these changes would enhance the cardioprotective properties of this lipoprotein.

Fruit and vegetable intake and risk of cardiovascular disease

A high intake of fruit and vegetables (FV) has been shown to be associated with reduced risk of a number of chronic diseases, including CVD. This review aims to provide an overview of the evidence that increased FV intake reduces risk of CVD, focusing on studies examining total FV intake. This evidence so far available is largely based on prospective cohort studies, with meta-analyses demonstrating an association between increased FV intake and reduced risk of both CHD and stroke. Controlled intervention trials examining either clinical or cardiovascular risk factor endpoints are scarce. However, such trials have shown that an increase in FV consumption can lower blood pressure and also improve microvascular function, both of which are commensurate with a reduced risk of CVD. The effects of increased FV consumption on plasma lipid levels, risk of diabetes and body weight have yet to be firmly established. In conclusion, evidence that FV consumption reduces the risk of CVD is so far largely confined to observational epidemiology, with further intervention studies required.

Increasing Fruit and Vegetable Intake Has No Dose-Response Effect on Conventional Cardiovascular Risk Factors in Overweight Adults at High Risk of Developing Cardiovascular Disease

BACKGROUND: Improving diet and lifestyle is important for prevention of cardiovascular disease (CVD). Observational evidence suggests that increasing fruit and vegetable (FV) consumption may lower CVD risk, largely through modulation of established risk factors, but intervention data are required to fully elucidate the mechanisms by which FVs exert benefits on vascular health.

OBJECTIVE: The aim of this study was to examine the dose-response effect of FV intake on cardiovascular risk factors in adults at high CVD risk.

METHODS: This was a randomized controlled parallel group study involving overweight adults (BMI: >27 and ≤35 kg/m(2)) with a habitually low FV intake (≤160 g/d) and a high total risk of developing CVD (estimated ≥20% over 10 y). After a 4-wk run-in period where FV intake was limited to <2 portions/d (<160 g/d), 92 eligible participants were randomly assigned to 1 of 3 groups: to consume either 2, 4, or 7 portions (equivalent to 160 g, 320 g, or 560 g, respectively) of FVs daily for 12 consecutive weeks. Fasting venous blood samples were collected at baseline (week 4) and post-intervention (week 16) for analysis of lipid fractions and high-sensitivity C-reactive protein (hsCRP) concentrations. Compliance with the FV intervention was determined with use of self-reported FV intake and biomarkers of micronutrient status. Ambulatory blood pressure and body composition were also measured pre- and post-intervention.

RESULTS: A total of 89 participants completed the study and body composition remained stable throughout the intervention period. Despite good compliance with the intervention, no significant difference was found between the FV groups for change in measures of ambulatory blood pressure, plasma lipids, or hsCRP concentrations.

CONCLUSIONS: There was no evidence of a dose-response effect of FV intake on conventional CVD risk factors measured in overweight adults at high CVD risk. This trial was registered at clinicaltrials.gov as NCT00874341.

Combining vitamin C and carotenoid biomarkers better predicts fruit and vegetable intake than individual biomarkers in dietary intervention studies

PURPOSE: The aim of this study was to determine whether combining potential biomarkers of fruit and vegetables is better at predicting FV intake within FV intervention studies than single biomarkers.

DESIGN: Data from a tightly controlled randomised FV intervention study (BIOFAV; all food provided and two meals/day on weekdays consumed under supervision) were used. A total of 30 participants were randomised to either 2, 5 or 8 portions FV/day for 4 weeks, and blood samples were collected at baseline and 4 weeks for plasma vitamin C and serum carotenoid analysis. The combined biomarker approach was also tested in three further FV intervention studies conducted by the same research team, with less strict dietary control (FV provided and no supervised meals).

RESULTS: The combined model containing all carotenoids and vitamin C was a better fit than either the vitamin C only (P < 0.001) model or the lutein only (P = 0.006) model in the BIOFAV study. The C-statistic was slightly lower in the lutein only model (0.85) and in the model based upon factor analysis (0.88), and much lower in the vitamin C model (0.68) compared with the full model (0.95). Results for the other studies were similar, although the differences between the models were less marked.

CONCLUSIONS: Although there was some variation between studies, which may relate to the level of dietary control or participant characteristics, a combined biomarker approach to assess overall FV consumption may more accurately predict FV intake within intervention studies than the use of a single biomarker. The generalisability of these findings to other populations and study designs remains to be tested. 

Increasing fruit and vegetable intake has no effect on retinal vessel caliber in adults at high risk of developing cardiovascular disease

BACKGROUND AND AIM: Retinal vessel abnormalities are associated with cardiovascular disease (CVD) risk. To date, there are no trials investigating the effect of dietary factors on the retinal microvasculature. This study examined the dose response effect of fruit and vegetable (FV) intake on retinal vessel caliber in overweight adults at high CVD risk.

METHODS AND RESULTS: Following a 4 week washout period, participants were randomized to consume either 2 or 4 or 7 portions of FV daily for 12 weeks. Retinal vessel caliber was measured at baseline and post-intervention. A total of 62 participants completed the study. Self-reported FV intake indicated good compliance with the intervention, with serum concentrations of zeaxanthin and lutein increasing significantly across the groups in a dose-dependent manner (P for trend < 0.05). There were no significant changes in body composition, 24-h ambulatory blood pressure or fasting blood lipid profiles in response to the FV intervention. Increasing age was a significant determinant of wider retinal venules (P = 0.004) whereas baseline systolic blood pressure was a significant determinant of narrower retinal arterioles (P = 0.03). Overall, there was no evidence of any short-term dose-response effect of FV intake on retinal vessel caliber (CRAE (P = 0.92) or CRVE (P = 0.42)).

CONCLUSIONS: This study demonstrated no effect of increasing FV intake on retinal vessel caliber in overweight adults at high risk of developing primary CVD.

How much is '5-a-day'? A qualitative investigation into consumer understanding of fruit and vegetable intake guidelines

BACKGROUND: Despite the known health benefits of fruit and vegetables (FV), population intakes remain low. One potential contributing factor may be a lack of understanding surrounding recommended intakes. The present study aimed to explore the understanding of FV intake guidelines among a sample of low FV consumers.

METHODS: Six semi-structured focus groups were held with low FV consumers (n = 28, age range 19-55 years). Focus groups were recorded digitally, transcribed verbatim and analysed thematically using nvivo (QSR International, Melbourne, Australia) to manage the coded data. Participants also completed a short questionnaire assessing knowledge on FV intake guidelines. Descriptive statistics were used to analyse responses.

RESULTS: The discussions highlighted that, although participants were aware of FV intake guidelines, they lacked clarity with regard to the meaning of the '5-a-day' message, including what foods are included in the guideline, as well as what constitutes a portion of FV. There was also a sense of confusion surrounding the concept of achieving variety with regard to FV intake. The sample highlighted a lack of previous education on FV portion sizes and put forward suggestions for improving knowledge, including increased information on food packaging and through health campaigns. Questionnaire findings were generally congruent with the qualitative findings, showing high awareness of the '5-a-day' message but a lack of knowledge surrounding FV portion sizes.

CONCLUSIONS: Future public health campaigns should consider how best to address the gaps in knowledge identified in the present study, and incorporate evaluations that will allow the impact of future initiatives on knowledge, and ultimately behaviour, to be investigated.

Fruit and vegetable intake and risk of incident of type 2 diabetes: results from the consortium on health and ageing network of cohorts in Europe and the United States (CHANCES)

BACKGROUND/OBJECTIVES: There is limited information to support definitive recommendations concerning the role of diet in the development of type 2 Diabetes mellitus (T2DM). The results of the latest meta-analyses suggest that an increased consumption of green leafy vegetables may reduce the incidence of diabetes, with either no association or weak associations demonstrated for total fruit and vegetable intake. Few studies have, however, focused on older subjects.

SUBJECTS/METHODS: The relationship between T2DM and fruit and vegetable intake was investigated using data from the NIH-AARP study and the EPIC Elderly study. All participants below the age of 50 and/or with a history of cancer, diabetes or coronary heart disease were excluded from the analysis. Multivariate logistic regression analysis was used to calculate the odds ratio of T2DM comparing the highest with the lowest estimated portions of fruit, vegetable, green leafy vegetables and cabbage intake.

RESULTS: Comparing people with the highest and lowest estimated portions of fruit, vegetable or green leafy vegetable intake indicated no association with the risk of T2DM. However, although the pooled OR across all studies showed no effect overall, there was significant heterogeneity across cohorts and independent results from the NIH-AARP study showed that fruit and green leafy vegetable intake was associated with a reduced risk of T2DM OR 0.95 (95% CI 0.91,0.99) and OR 0.87 (95% CI 0.87,0.90) respectively.

CONCLUSIONS: Fruit and vegetable intake was not shown to be related to incident T2DM in older subjects. Summary analysis also found no associations between green leafy vegetable and cabbage intake and the onset of T2DM. Future dietary pattern studies may shed light on the origin of the heterogeneity across populations.European Journal of Clinical Nutrition advance online publication, 17 August 2016;