Julia M. W. Wong

Colonic Health: Fermentation and Short Chain Fatty Acids

Interest has been recently rekindled in short chain fatty acids (SCFAs) with the emergence of prebiotics and probiotics aimed at improving colonic and systemic health. Dietary carbohydrates, specifically resistant starches and dietary fiber, are substrates for fermentation that produce SCFAs, primarily acetate, propionate, and butyrate, as end products. The rate and amount of SCFA production depends on the species and amounts of microflora present in the colon, the substrate source and gut transit time. SCFAs are readily absorbed. Butyrate is the major energy source for colonocytes. Propionate is largely taken up by the liver. Acetate enters the peripheral circulation to be metabolized by peripheral tissues. Specific SCFA may reduce the risk of developing gastrointestinal disorders, cancer, and cardiovascular disease. Acetate is the principal SCFA in the colon, and after absorption it has been shown to increase cholesterol synthesis. However, propionate, a gluconeogenerator, has been shown to inhibit cholesterol synthesis. Therefore, substrates that can decrease the acetate: propionate ratio may reduce serum lipids and possibly cardiovascular disease risk. Butyrate has been studied for its role in nourishing the colonic mucosa and in the prevention of cancer of the colon, by promoting cell differentiation, cell-cycle arrest and apoptosis of transformed colonocytes; inhibiting the enzyme histone deacetylase and decreasing the transformation of primary to secondary bile acids as a result of colonic acidification. Therefore, a greater increase in SCFA production and potentially a greater delivery of SCFA, specifically butyrate, to the distal colon may result in a protective effect. Butyrate irrigation (enema) has also been suggested in the treatment of colitis. More human studies are now needed, especially, given the diverse nature of carbohydrate substrates and the SCFA patterns resulting from their fermentation. Short-term and long-term human studies are particularly required on SCFAs in relation to markers of cancer risk. These studies will be key to the success of dietary recommendations to maximize colonic disease prevention.

The effect of a plant-based low-carbohydrate ("Eco-Atkins") diet on body weight and blood lipid concentrations in hyperlipidemic subjects.

BACKGROUND Low-carbohydrate, high-animal protein diets, which are advocated for weight loss, may not promote the desired reduction in low-density lipoprotein cholesterol (LDL-C) concentration. The effect of exchanging the animal proteins and fats for those of vegetable origin has not been tested. Our objective was to determine the effect on weight loss and LDL-C concentration of a low-carbohydrate diet high in vegetable proteins from gluten, soy, nuts, fruits, vegetables, cereals, and vegetable oils compared with a high-carbohydrate diet based on low-fat dairy and whole grain products. METHODS A total of 47 overweight hyperlipidemic men and women consumed either (1) a low-carbohydrate (26% of total calories), high-vegetable protein (31% from gluten, soy, nuts, fruit, vegetables, and cereals), and vegetable oil (43%) plant-based diet or (2) a high-carbohydrate lacto-ovo vegetarian diet (58% carbohydrate, 16% protein, and 25% fat) for 4 weeks each in a parallel study design. The study food was provided at 60% of calorie requirements. RESULTS Of the 47 subjects, 44 (94%) (test, n = 22 [92%]; control, n = 22 [96%]) completed the study. Weight loss was similar for both diets (approximately 4.0 kg). However, reductions in LDL-C concentration and total cholesterol-HDL-C and apolipoprotein B-apolipoprotein AI ratios were greater for the low-carbohydrate compared with the high-carbohydrate diet (-8.1% [P = .002], -8.7% [P = .004], and -9.6% [P = .001], respectively). Reductions in systolic and diastolic blood pressure were also seen (-1.9% [P = .052] and -2.4% [P = .02], respectively). CONCLUSION A low-carbohydrate plant-based diet has lipid-lowering advantages over a high-carbohydrate, low-fat weight-loss diet in improving heart disease risk factors not seen with conventional low-fat diets with animal products.

Direct comparison of dietary portfolio vs statin on C-reactive protein.

Background:3-Hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) markedly reduce serum cholesterol and have anti-inflammatory effects. The effect of cholesterol-lowering diets on inflammatory biomarkers is less well known.Objective:To compare the efficacy of a dietary combination (portfolio) of cholesterol-lowering foods vs a statin in reducing C-reactive protein (CRP) as a biomarker of inflammation linked to increased cardiovascular disease risk.Methods:In all, 34 hyperlipidemic subjects completed three 1-month treatments as outpatients in random order: a very low-saturated fat diet (control); the same diet with 20 mg lovastatin (statin); and a diet high in plant sterols (1.0 g/1000 kcal), soy protein (21.4 g/1000 kcal), viscous fibers (9.8 g/1000 kcal), and almonds (14 g/1000 kcal) (portfolio). Fasting blood samples were obtained at weeks 0, 2, and 4.Results:Using the complete data, no treatment reduced serum CRP. However, when subjects with CRP levels above the 75th percentile for previously reported studies (>3.5 mg/l) were excluded, CRP was reduced similarly on both statin, −16.3±6.7% (n=23, P=0.013) and dietary portfolio, −23.8±6.9% (n=25, P=0.001) but not the control, 15.3±13.6% (n=28, P=0.907). The percentage CRP change from baseline on the portfolio treatment (n=25) was greater than the control (n=28, P=0.004) but similar to statin treatment (n=23, P=0.349). Both statin and portfolio treatments were similar in reducing CRP and numerically more effective than control but only the change in portfolio was significant after the Bonferroni adjustment.Conclusions:A combination of cholesterol-lowering foods reduced C-reactive protein to a similar extent as the starting dose of a first-generation statin.

Health Effects of Mixed Fruit and Vegetable Concentrates: A Systematic Review of the Clinical Interventions

Diets rich in fruits and vegetables (FV) have been associated with a reduced risk of chronic disease, including cardiovascular disease. Unfortunately, public health campaigns to increase FV intake have had limited success. A number of mixed concentrated FV products have been studied, which may help certain individuals improve nutrient status. However, the possible health benefits of FV supplements have not been systematically reviewed. We, therefore, undertook a systematic search of MEDLINE and EMBASE to identify clinical interventions that examined the effect of commercially available concentrated mixed FV supplements on cardiovascular disease risk factors. Twenty-two reports, which used commercially available products, were identified. None of the studies reported any serious adverse effects. Overall, daily consumption of FV supplements significantly increased serum concentrations of the major antioxidant provitamins and vitamins found in plant foods (β-carotene, vitamins C and E) and folate. Functional changes, such as reduced serum homocysteine and markers of protein, lipid, and DNA oxidation, were also reported; in addition, the health advantages on markers of inflammation, immunity, and endothelial function are promising. Limitations of the available studies were related to the diversity of studies conducted with respect to design and study population and the variability in the measured outcomes and assays utilized. While mixed FV supplements may serve as an efficacious complement for individuals who have difficulty achieving their daily FV intake requirement, further research on additional retail preparations is warranted. Key teaching points: •  Mixed fruit and vegetable supplements produced from plant foods may serve as an efficacious complement to the habitual diet in individuals who have suboptimal intake or variety of nutrient-dense fruits and vegetables.•  Current research indicates that fruit and vegetable concentrates significantly increase serum levels of antioxidant provitamins and vitamins (β-carotene, vitamins C and E) and folate and reduce homocysteine and markers of oxidative stress.•  Mechanistic studies and larger, randomized, placebo-controlled double-blind trials in both healthy and high-risk populations are necessary to better understand the health effects of these supplements.

The Glycemic Index: Physiological Significance

The glycemic index (GI) is a physiological assessment of a foods carbohydrate content through its effect on postprandial blood glucose concentrations. Evidence from trials and observational studies suggests that this physiological classification may have relevance to those chronic Western diseases associated with overconsumption and inactivity leading to central obesity and insulin resistance. The glycemic index classification of foods has been used as a tool to assess potential prevention and treatment strategies for diseases where glycemic control is of importance, such as diabetes. Low GI diets have also been reported to improve the serum lipid profile, reduce C-reactive protein (CRP) concentrations, and aid in weight control. In cross-sectional studies, low GI or glycemic load diets (mean GI multiplied by total carbohydrate) have been associated with higher levels of high-density lipoprotein cholesterol (HDL-C), with reduced CRP concentrations, and, in cohort studies, with decreased risk of developing diabetes and cardiovascular disease. In addition, some case-control and cohort studies have found positive associations between dietary GI and risk of various cancers, including those of the colon, breast, and prostate. Although inconsistencies in the current findings still need to be resolved, sufficient positive evidence, especially with respect to renewed interest in postprandial events, suggests that the glycemic index may have a role to play in the treatment and prevention of chronic diseases.

Long-term effects of a plant-based dietary portfolio of cholesterol-lowering foods on blood pressure

Objective:To determine the effect on blood pressure of dietary advice to consume a combination of plant-based cholesterol-lowering foods (dietary portfolio).Methods:For 1 year, 66 hyperlipidemic subjects were prescribed diets high in plant sterols (1.0 g/1000 kcal), soy protein (22.5 g/1000 kcal), viscous fibers (10 g/1000 kcal) and almonds (22.5 g/1000 kcal). There was no control group. Seven-day diet record, blood pressure and body weight were monitored initially monthly and later at 2-monthly intervals throughout the study.Results:Fifty subjects completed the 1-year study. When the last observation was carried forward for non-completers (n=9) or those who changed their blood pressure medications (n=7), a small mean reduction was seen in body weight 0.7±0.3 kg (P=0.036). The corresponding reductions from baseline in systolic and diastolic blood pressure at 1 year (n=66 subjects) were −4.2±1.3 mm Hg (P=0.002) and −2.3±0.7 mm Hg (P=0.001), respectively. Blood pressure reductions occurred within the first 2 weeks, with stable blood pressures 6 weeks before and 4 weeks after starting the diet. Diastolic blood pressure reduction was significantly related to weight change (r=0.30, n=50, P=0.036). Only compliance with almond intake advice related to blood pressure reduction (systolic: r=−0.34, n=50, P=0.017; diastolic: r=−0.29, n=50, P=0.041).Conclusions:A dietary portfolio of plant-based cholesterol-lowering foods reduced blood pressure significantly, related to almond intake. The dietary portfolio approach of combining a range of cholesterol-lowering plant foods may benefit cardiovascular disease risk both by reducing serum lipids and also blood pressure.

The application of the glycemic index and glycemic load in weight loss: A review of the clinical evidence

Obesity is rapidly becoming a global epidemic. As it is a significant risk factor for several chronic diseases, including type 2 diabetes and cardiovascular disease, it is imperative to study dietary and lifestyle approaches that help reduce its prevalence. Recently, due to its possible link to appetite control and metabolism, several clinical studies have assessed the effect of low glycemic index (GI) and glycemic load (GL) diets on weight loss. To determine the application of GI/GL in the prevention and treatment of obesity, we searched several databases and identified 23 clinical trials that examined low GI/GL diets and weight loss as the primary outcome measure. In general, these studies showed much inconsistency in their findings. While a few studies found significantly greater weight loss on the low GI/GL diets, most of the other studies showed a non‐significant trend that favored low GI/GL diets; suggesting that factors other than GI/GL may play a role. It would be helpful if a pooled analysis were undertaken to clarify the current findings and outline the limitations of these studies. There is also a need for more long‐term randomized, controlled trials that not only focus on weight loss but also on weight maintenance and body composition.

Adding monounsaturated fatty acids to a dietary portfolio of cholesterol-lowering foods in hypercholesterolemia

Background Higher intake of monounsaturated fat may raise high-density lipoprotein (HDL) cholesterol without raising low-density lipoprotein (LDL) cholesterol. We tested whether increasing the monounsaturated fat content of a diet proven effective for lowering LDL cholesterol (dietary portfolio) also modified other risk factors for cardiovascular disease, specifically by increasing HDL cholesterol, lowering serum triglyceride and further reducing the ratio of total to HDL cholesterol. Methods Twenty-four patients with hyperlipidemia consumed a therapeutic diet very low in saturated fat for one month and were then randomly assigned to a dietary portfolio low or high in monounsaturated fatty acid for another month. We supplied participants’ food for the two-month period. Calorie intake was based on Harris–Benedict estimates for energy requirements. Results For patients who consumed the dietary portfolio high in monounsaturated fat, HDL cholesterol rose, whereas for those consuming the dietary portfolio low in monounsaturated fat, HDL cholesterol did not change. The 12.5% treatment difference was significant (0.12 mmol/L, 95% confidence interval [CI] 0.05 to 0.21, p = 0.003). The ratio of total to HDL cholesterol was reduced by 6.5% with the diet high in monounsaturated fat relative to the diet low in monounsaturated fat (−0.28, 95% CI −0.59 to −0.04, p = 0.025). Patients consuming the diet high in monounsaturated fat also had significantly higher concentrations of apolipoprotein AI, and their C-reactive protein was significantly lower. No treatment differences were seen for triglycerides, other lipids or body weight, and mean weight loss was similar for the diets high in monounsaturated fat (−0.8 kg) and low in monounsaturated fat (−1.2 kg). Interpretation Monounsaturated fat increased the effectiveness of a cholesterol-lowering dietary portfolio, despite statin-like reductions in LDL cholesterol. The potential benefits for cardiovascular risk were achieved through increases in HDL cholesterol, further reductions in the ratio of total to HDL cholesterol and reductions in C-reactive protein. (ClinicalTrials.gov trial register no. NCT00430430.)

The effect on the blood lipid profile of soy foods combined with a prebiotic: a randomized controlled trial

The value of soy protein as part of the cholesterol-lowering diet has been questioned by recent studies. The apparent lack of effect may relate to the absence of dietary factors that increase colonic fermentation and potentiate the cholesterol-lowering effect of soy. Therefore, unabsorbable carbohydrates (prebiotics) were added to the diet with the aim of increasing colonic fermentation and so potentially increasing the hypocholesterolemic effect of soy. Twenty-three hyperlipidemic adults (11 male, 12 female; 58 +/- 7 years old; low-density lipoprotein cholesterol [LDL-C], 4.18 +/- 0.58 mmol/L) completed three 4-week diet intervention phases-a low-fat dairy diet and 10 g/d prebiotic (oligofructose-enriched inulin, a fermentable carbohydrate), a soy food-containing diet (30 g/d soy protein, 61 mg/d isoflavones from soy foods) and 10 g/d placebo (maltodextrin), and a soy food-containing diet with 10 g/d prebiotic--in a randomized controlled crossover study. Intake of soy plus prebiotic resulted in greater reductions in LDL-C (-0.18 +/- 0.07 mmol/L, P = .042) and in ratio of LDL-C to high-density lipoprotein cholesterol (-0.28 +/- 0.11, P = .041) compared with prebiotic. In addition, high-density lipoprotein cholesterol was significantly increased on soy plus prebiotic compared with prebiotic (0.06 +/- 0.02 mmol/L, P = .029). Differences in bifidobacteria, total anaerobes, aerobes, and breath hydrogen did not reach significance. Soy foods in conjunction with a prebiotic resulted in significant improvements in the lipid profile, not seen when either prebiotic or soy alone was taken. Coingestion of a prebiotic may potentiate the effectiveness of soy foods as part of the dietary strategy to lower serum cholesterol.

Gut microbiota and cardiometabolic outcomes: influence of dietary patterns and their associated components

Many dietary patterns have been associated with cardiometabolic risk reduction. A commonality between these dietary patterns is the emphasis on plant-based foods. Studies in individuals who consume vegetarian and vegan diets have shown a reduced risk of cardiovascular events and incidence of diabetes. Plant-based dietary patterns may promote a more favorable gut microbial profile. Such diets are high in dietary fiber and fermentable substrate (ie, nondigestible or undigested carbohydrates), which are sources of metabolic fuel for gut microbial fermentation and, in turn, result in end products that may be used by the host (eg, short-chain fatty acids). These end products may have direct or indirect effects on modulating the health of their host. Modulation of the gut microbiota is an area of growing interest, and it has been suggested to have the potential to reduce risk factors associated with chronic diseases. Examples of dietary components that alter the gut microbial composition include prebiotics and resistant starches. Emerging evidence also suggests a potential link between interindividual differences in the gut microbiota and variations in physiology or predisposition to certain chronic disease risk factors. Alterations in the gut microbiota may also stimulate certain populations and may assist in biotransformation of bioactive components found in plant foods. Strategies to modify microbial communities may therefore provide a novel approach in the treatment and management of chronic diseases.