Ditte A. Hobbs

Blood pressure-lowering effects of beetroot juice and novel beetroot- enriched bread products in normotensive male subjects

A number of vegetables have a high nitrate content which after ingestion can be reduced to nitrite by oral bacteria, and further to vasoprotective NO endogenously. In the present study, two separate randomly controlled, single-blind, cross-over, postprandial studies were performed in normotensive volunteers. Ambulatory blood pressure (BP) was measured over a 24 h period following consumption of either four doses of beetroot juice (BJ), 0, 100, 250 and 500 g (n 18), or three bread products, control bread (0 g beetroot), red beetroot- and white beetroot-enriched breads (n 14). Total urinary nitrate/nitrite (NO(x)) was measured at baseline, and at 2, 4 and 24 h post-ingestion. BJ consumption significantly, and in a near dose-dependent manner, lowered systolic BP (SBP, P < 0·01) and diastolic BP (DBP, P < 0·001) over a period of 24 h, compared with water control. Furthermore, bread products enriched with 100 g red or white beetroot lowered SBP and DBP over a period of 24 h (red beetroot-enriched bread, P <0·05), with no statistical differences between the varieties. Total urinary NO(x) significantly increased following the consumption of 100 g (P < 0·01), 250 g (P <0·001) and 500 g BJ (P <0·001) and after red beetroot-enriched bread ingestion (P <0·05), but did not reach significance for white beetroot-enriched bread compared with the no-beetroot condition. These studies demonstrated significant hypotensive effects of a low dose (100 g) of beetroot which was unaffected by processing or the presence of betacyanins. These data strengthen the evidence for cardioprotective BP-lowering effects of dietary nitrate-rich vegetables.

A central role for heme iron in colon carcinogenesis associated with red meat intake

Epidemiology shows that red and processed meat intake is associated with an increased risk of colorectal cancer. Heme iron, heterocyclic amines, and endogenous N-nitroso compounds (NOC) are proposed to explain this effect, but their relative contribution is unknown. Our study aimed at determining, at nutritional doses, which is the main factor involved and proposing a mechanism of cancer promotion by red meat. The relative part of heme iron (1% in diet), heterocyclic amines (PhIP + MeIQx, 50 + 25 μg/kg in diet), and NOC (induced by NaNO₂+ NaNO₂; 0.17 + 0.23 g/L of drinking water) was determined by a factorial design and preneoplastic endpoints in chemically induced rats and validated on tumors in Min mice. The molecular mechanisms (genotoxicity, cytotoxicity) were analyzed in vitro in normal and Apc-deficient cell lines and confirmed on colon mucosa. Heme iron increased the number of preneoplastic lesions, but dietary heterocyclic amines and NOC had no effect on carcinogenesis in rats. Dietary hemoglobin increased tumor load in Min mice (control diet: 67 ± 39 mm²; 2.5% hemoglobin diet: 114 ± 47 mm², P = 0.004). In vitro, fecal water from rats given hemoglobin was rich in aldehydes and was cytotoxic to normal cells, but not to premalignant cells. The aldehydes 4-hydroxynonenal and 4-hydroxyhexenal were more toxic to normal versus mutated cells and were only genotoxic to normal cells. Genotoxicity was also observed in colon mucosa of mice given hemoglobin. These results highlight the role of heme iron in the promotion of colon cancer by red meat and suggest that heme iron could initiate carcinogenesis through lipid peroxidation. .

Acute Ingestion of Beetroot Bread Increases Endothelium-Independent Vasodilation and Lowers Diastolic Blood Pressure in Healthy Men: A Randomized Controlled Trial

Dietary nitrate, from beetroot, has been reported to lower blood pressure (BP) by the sequential reduction of nitrate to nitrite and further to NO in the circulation. However, the impact of beetroot on microvascular vasodilation and arterial stiffness is unknown. In addition, beetroot is consumed by only 4.5% of the UK population, whereas bread is a staple component of the diet. Thus, we investigated the acute effects of beetroot bread (BB) on microvascular vasodilation, arterial stiffness, and BP in healthy participants. Twenty-three healthy men received 200 g bread containing 100 g beetroot (1.1 mmol nitrate) or 200 g control white bread (CB; 0 g beetroot, 0.01 mmol nitrate) in an acute, randomized, open-label, controlled crossover trial. The primary outcome was postprandial microvascular vasodilation measured by laser Doppler iontophoresis and the secondary outcomes were arterial stiffness measured by Pulse Wave Analysis and Velocity and ambulatory BP measured at regular intervals for a total period of 6 h. Plasma nitrate and nitrite were measured at regular intervals for a total period of 7 h. The incremental area under the curve (0-6 h after ingestion of bread) for endothelium-independent vasodilation was greater (P = 0.017) and lower for diastolic BP (DBP; P = 0.032) but not systolic (P = 0.99) BP after BB compared with CB. These effects occurred in conjunction with increases in plasma and urinary nitrate (P < 0.0001) and nitrite (P < 0.001). BB acutely increased endothelium-independent vasodilation and decreased DBP. Therefore, enriching bread with beetroot may be a suitable vehicle to increase intakes of cardioprotective beetroot in the diet and may provide new therapeutic perspectives in the management of hypertension.

Heme-Induced Biomarkers Associated with Red Meat Promotion of colon Cancer Are Not Modulated by the Intake of Nitrite

Red and processed meat consumption is associated with the risk of colorectal cancer. Three hypotheses are proposed to explain this association, via heme-induced oxidation of fat, heterocyclic amines, or N-nitroso compounds. Rats have often been used to study these hypotheses, but the lack of enterosalivary cycle of nitrate in rats casts doubt on the relevance of this animal model to predict nitroso- and heme-associated human colon carcinogenesis. The present study was thus designed to clarify whether a nitrite intake that mimics the enterosalivary cycle can modulate heme-induced nitrosation and fat peroxidation. This study shows that, in contrast with the starting hypothesis, drinking water added with nitrite to mimic the salivary nitrite content did not change the effect of hemoglobin on biochemical markers linked to colon carcinogenesis, notably lipid peroxidation and cytotoxic activity in the colon of rat. However, ingested sodium nitrite increased fecal nitroso-compounds level, but their fecal concentration and their nature (iron-nitrosyl) would probably not be associated with an increased risk of cancer. We thus suggest that the rat model could be relevant for study the effect of red meat on colon carcinogenesis, in spite of the lack of nitrite in the saliva of rats.

New perspectives on dairy and cardiovascular health.

CVD are the leading cause of mortality and morbidity worldwide. One of the key dietary recommendations for CVD prevention is reduction of saturated fat intake. Yet, despite milk and dairy foods contributing on average 27 % of saturated fat intake in the UK diet, evidence from prospective cohort studies does not support a detrimental effect of milk and dairy foods on risk of CVD. The present paper provides a brief overview of the role of milk and dairy products in the diets of UK adults, and will summarise the evidence in relation to the effects of milk and dairy consumption on CVD risk factors and mortality. The majority of prospective studies and meta-analyses examining the relationship between milk and dairy product consumption and risk of CVD show that milk and dairy products, excluding butter, are not associated with detrimental effects on CVD mortality or risk biomarkers that include serum LDL-cholesterol. In addition, there is increasing evidence that milk and dairy products are associated with lower blood pressure and arterial stiffness. These apparent benefits of milk and dairy foods have been attributed to their unique nutritional composition, and suggest that the elimination of milk and dairy may not be the optimum strategy for CVD risk reduction.

Differential effect of beetroot bread on postprandial DBP according to Glu298Asp polymorphism in the eNOS gene: a pilot study

Our objective was to investigate whether the presence of Glu298Asp polymorphism in the endothelial NO synthase (eNOS) gene differentially affects the postprandial blood pressure response to dietary nitrate-rich beetroot bread. A randomised, single-blind, controlled, crossover acute pilot study was performed in 14 healthy men (mean age: 34±9 years) who were retrospectively genotyped for Glu298Asp polymorphism (7GG; T carriers 7). Volunteers were randomised to receive 200 g beetroot-enriched bread (1.1 mmol nitrate) or control bread (no beetroot; 0.01 mmol nitrate) on two separate occasions 10 days apart. Baseline and incremental area under the curve of blood pressure and NOx (nitrate/nitrite) were measured for a 6-h postprandial period. A treatment × genotype interaction was observed for diastolic blood pressure (P<0.02), which was significantly lower in T carriers (P<0.01) after consumption of beetroot bread compared with control bread. No significant differences were observed in the GG group. The beneficial diastolic blood pressure reduction was observed only in the T carriers of the Glu298Asp polymorphism in the eNOS gene after consumption of nitrate-rich beetroot bread. These data require confirmation in a larger population group.

Dairy Products: Their Role in the Diet and Effects on Cardiovascular Disease

The majority of the population are aware that milk and dairy products are important sources of calcium and iodine, but there is concern that these foods contribute to increased risk of cardiovascular and other chronic diseases. This is due to the fact that dairy foods are often the largest single source of dietary saturated fatty acids. However, the evidence from long-term cohort studies shows that high milk consumption does not increase cardiovascular disease risk and indeed may provide benefit, although the effects of butter, cheese, total fat, and saturated fat reduced milk are less certain and require further evaluation in suitably powered dietary intervention studies.

Role of flavonoids and nitrates in cardiovascular health

CVD remain the leading cause of death globally. Effective dietary strategies for their reduction are of high priority. Increasing evidence suggests that phytochemicals, particularly dietary flavonoids and nitrates, are key modulators of CVD risk reduction through impact on multiple risk factors. The aim of this review is to explore the evidence for the impact of flavonoid- and nitrate-rich foods and supplements on CVD risk, with specific reference to their importance as mediators of vascular health and platelet function. There is accumulating evidence to support benefits of dietary flavonoids on cardiovascular health. Dose-dependent recovery of endothelial function and lowering of blood pressure have been reported for the flavanol (-)-epicatechin, found in cocoa, apples and tea, through production and availability of endothelial nitric oxide (NO). Furthermore, flavonoids, including quercetin and its metabolites, reduce in vitro and ex vivo platelet function via inhibition of phosphorylation-dependent cellular signalling pathways, although further in vivo studies are required to substantiate these mechanistic effects. Hypotensive effects of dietary nitrates have been consistently reported in healthy subjects in acute and chronic settings, although there is less evidence for these effects in patient groups. Proposed mechanisms of actions include endothelial-independent NO availability, which is dependent on the entro-salivary circulation and microbial conversion of dietary nitrate to nitrite in the mouth. In conclusion, flavonoid- and nitrate-rich foods show promising effects on vascular function, yet further randomly controlled studies are required to confirm these findings and to determine effective doses.

Red Wine and Pomegranate Extracts Suppress Cured Meat Promotion of Colonic Mucin-Depleted Foci in Carcinogen-Induced Rats

ABSTRACT Processed meat intake is carcinogenic to humans. We have shown that intake of a workshop-made cured meat with erythorbate promotes colon carcinogenesis in rats. We speculated that polyphenols could inhibit this effect by limitation of endogenous lipid peroxidation and nitrosation. Polyphenol-rich plant extracts were added to the workshop-made cured meat and given for 14 days to rats and 100 days to azoxymethane-induced rats to evaluate the inhibition of preneoplastic lesions. Colons of 100-d study were scored for precancerous lesions (mucin-depleted foci, MDF), and biochemical end points of peroxidation and nitrosation were measured in urinary and fecal samples. In comparison with cured meat-fed rats, dried red wine, pomegranate extract, α-tocopherol added at one dose to cured meat and withdrawal of erythorbate significantly decreased the number of MDF per colon (but white grape and rosemary extracts did not). This protection was associated with the full suppression of fecal excretion of nitrosyl iron, suggesting that this nitroso compound might be a promoter of carcinogenesis. At optimized concentrations, the incorporation of these plant extracts in cured meat might reduce the risk of colorectal cancer associated with processed meat consumption.

Milk and Dairy Products: Dietary Partners for Life?

The importance of milk in the human diet as a supplier of energy, high quality protein and other key nutrients, including calcium, is broadly accepted yet in the mind of many there remains uncertainty about whether or not these foods contribute to increased risk of cardiovascular and other chronic diseases. The evidence from long term prospective cohort studies that high milk consumption does not increase cardiovascular disease risk and indeed may provide benefit is now pretty unequivocal, although the effects of butter and cheese and benefits of fat reduced milk and saturated fat reduced milk are less certain. Milk is a crucial supplier of calcium, phosphorus and magnesium for bone growth and development in children and it is concerning that due to reduced milk consumption intake of these nutrients is often sub-optimal, particularly for female children. In addition, specific health issues in pregnant women and the elderly can be alleviated by milk or components of milk and these effects are not all explained by traditional nutrition.