The identification of nutrients and the study of their bioactivity were significant developments in the evolution of contemporary nutrition science. This review argues for shifting the focus towards food in order to better understand the nutrition-health interface. It begins by introducing the concept of food synergy (a perspective that more information can be obtained by looking at foods than at single food components) to denote the action of the food matrix (the composite of naturally occurring food components) on human biological systems. A proposal is then made for the means by which food-focused research might build the knowledge base for etiologic discovery and appropriate dietary advice. The diet-heart disease dilemma is put forward as an example of where a nutrient-based approach has limitations, and a summary of studies targeting food composition strengthens the case for a food-based approach. Finally, the argument is made that evidence from interventions points back to the central position of food in the relationship between nutrition and health, a position that begs for more whole food-based research.

The relationship between frequency of consumption of whole grain food and risk of selected neoplasms has been analysed using data from an integrated series of case-control studies conducted in northern Italy between 1983 and 1996. The overall dataset included the following incident, Odds ratios (OR) for subsequent scores (never/occasional/ frequent) of whole grain food consumption were derived after allowance for age, sex, education, smoking, alcohol intake and body mass index. High intake of whole grain foods consistently reduced risk of neoplasm at all sites, except thyroid. The ORs for the highest category of consumption were 0.2-0.3 for upper digestive and respiratory tract neoplasms, 0.5 for stomach, colon and gallbladder, 0.7 for rectum, 0.6 for liver, 0.8 for pancreas and prostate, 0.9 for breast and endometrium, 0.6 for ovary, 0.4 for bladder and kidney, 1.3 for thyroid and around 0.5 for lymphomas and myeloma. The tests for trend in risks were significant for all neoplasms, except pancreas, endometrium, Hodgkin's disease and multiple myeloma. No significant heterogeneity was found across strata of age at diagnosis, sex, education, smoking habit, alcohol intake and body mass index. Thus, even in the absence of a univocal and satisfactory biological interpretation, the consistency of the patterns observed indicate that, in this population, higher frequency of whole grain food intake is an indicator of reduced risk of several neoplasms. Int.

OBJECTIVE -Recently, we reported increased cardiovascular disease mortality among supplemental vitamin C users with type 2 diabetes in a prospective cohort study. Because vitamin C may cause oxidative stress in the presence of redox active iron, we hypothesized that nontransferrin-bound iron (NTBI), a form of iron susceptible to redox activity, may be present in patients with type 2 diabetes.RESEARCH DESIGN AND METHODS -We measured serum NTBI levels using highperformance liquid chromatography in 48 patients with known diabetes (at least 5 years duration since diagnosis), 49 patients with newly diagnosed diabetes, and 47 healthy control subjects (frequency matched on age and sex).RESULTS -NTBI was commonly present in diabetes: 59% in newly diagnosed diabetes and 92% in advanced diabetes. Mean NTBI values varied significantly between the three groups, with the highest values being observed in patients with known diabetes and the lowest in the control subjects (0.62 Ϯ 0.43 vs. 0.24 Ϯ 0.29 vs. 0.04 Ϯ 0.13 mol/l Fe). Serum total iron or percent transferrin saturation were very similar among the three groups, yet NTBI was strongly associated with serum total iron (r ϭ 0.74, P Ͻ 0.01) and percent transferrin saturation (r ϭ 0.70, P Ͻ 0.01) among the patients with known diabetes.CONCLUSIONS -Consistent with our hypothesis, these data demonstrate the common existence of NTBI in type 2 diabetic patients with a strong gradient with severity. Prospective cohort studies are required to clarify the clinical relevance of increased NTBI levels. Diabetes Care 29:1090 -1095, 2006R ecently, we reported that supplemental vitamin C intake in excess of 300 mg/day increased cardiovascular disease (CVD) mortality among postmenopausal women with type 2 diabetes in a prospective cohort study (1). This finding was unexpected in that it is contrary to the general belief that supplemental vitamin C intake is beneficial for patients with type 2 diabetes because they tend to have lower serum vitamin C levels (2,3). One explanation for this finding is that vitamin C may interact with redox active iron in patients with type 2 diabetes (4,5).Although the prooxidant reaction of vitamin C occurs readily in vitro, its relevance in vivo has been a matter of some controversy, the main point of contention being the availability of redox active iron in vivo (6). Levels of redox active iron are thought to be low due to their sequestration by various metal-binding proteins such as transferrin (7). It is generally believed that non-transferrin-bound iron (NTBI) possesses redox activity but only appears in serum when transferrin is fully iron saturated (8). However, recent studies have demonstrated that NTBI can be detected when transferrin is not fully saturated, leading to a revision of the original understanding that NTBI results from a simple spillover phenomenon (9 -11). Interestingly, a disturbance of iron metabolism and/or iron overload has recently been suggested as a mechanism of the pathogenesis of both diabetes and CVD complications (12,13).The ...

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