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Scientific evidence of interventions using the Mediterranean diet: A systematic review

Serra-Majem, L., B. Roman, R. Estruch, 2006. Scientific evidence of interventions using the Mediterranean diet: A systematic review. Nutrition Reviews. 64(2):S27-S47.

The Mediterranean Diet has been associated with greater longevity and quality of life in epidemiological studies, the majority being observational. The application of evidence-based medicine to the area of public health nutrition involves the necessity of developing clinical trials and systematic reviews to develop sound recommendations. The purpose of this study was to analyze and review the experimental studies on Mediterranean diet and disease prevention. A systematic review was made and a total of 43 articles corresponding to 35 different experimental studies were selected. Results were analyzed for the effects of the Mediterranean diet on lipoproteins, endothelial resistance, diabetes and antioxidative capacity, cardiovascular diseases, arthritis, cancer, body composition, and psychological function. The Mediterranean diet showed favorable effects on lipoprotein levels, endothelium vasodilatation, insulin resistance, metabolic syndrome, antioxidant capacity, myocardial and cardiovascular mortality, and cancer incidence in obese patients and in those with previous myocardial infarction. Results disclose the mechanisms of the Mediterranean diet in disease prevention, particularly in cardiovascular disease secondary prevention, but also emphasize the need to undertake experimental research and systematic reviews in the areas of primary prevention of cardiovascular disease, hypertension, diabetes, obesity, infectious diseases, age-related cognitive impairment, and cancer, among others. Interventions should use food scores or patterns to ascertain adherence to the Mediterranean diet. Further experimental research is needed to corroborate the benefits of the Mediterranean diet and the underlying mechanisms, and in this sense the methodology of the ongoing PREDIMED study is explained.

Dietary fiber, nuts and cardiovascular diseases

Salas-Salvado’, J., M. Bullo’, A. Pe’rez-Heras, E. Ros, 2006. Dietary fiber, nuts and cardiovascular diseases. British Journal of Nutrition. 96, Suppl. 2, S45-S51.

Dietary fiber has a range of metabolic health benefits. Through a variety of mechanisms, dietary fiber, and the viscous variety in particular, slows down gastric emptying and intestinal transit, decreases the rate of intestinal carbohydrate absorption, and increases fecal bile acid excretion. Therefore, consumption of some types of soluble fiber can enhance satiety, which is associated with a lower BMI, and reduce blood cholesterol and the postprandial glucose response. Surprisingly, the consumption of insoluble fiber from whole grains, though metabolically inert, has been associated with a reduction in the risk of developing coronary heart disease and diabetes in epidemiological studies. The likely reason is that whole grains, like nuts, legumes and other edible seeds, contain many bioactive phytochemicals and various antioxidants. After cereals, nuts are the vegetable foods that are richest in fiber, which may partly explain their benefit on the lipid profile and cardiovascular health.

Nuts: source of energy and macronutrients

Brufau, G., J. Boatella, M. Rafecas, 2006. Nuts: source of energy and macronutrients. British Journal of Nutrition. 96, Suppl. 2, S24-S28.

On the basis of the high fat content of nuts, they are traditionally considered as foods that provide a high amount of energy. However, epidemiologic and clinical observations do not indicate an association between nut intake and increased BMI. There is a notorious variability in macronutrient composition among nuts, although they have some consistent patterns. Nuts contain all major macronutrients: protein, carbohydrate, and fat. The total protein content is relatively high, which makes them a good source of plant protein (especially for vegetarians). Although nuts contain low amounts of some essential amino acids, this is not a nutritional concern due to the complement of protein. In addition, nuts have a low lysine:arginine ratio, which is inversely associated with the risk of developing hypercholesterolemia and atherosclerosis. Carbohydrates are the second highest macronutrient in nuts in terms of total calories provided. The fat fraction is characterized by a high amount of unsaturated fatty acids and a low content of saturated fatty acids. In conclusion, the high content in unsaturated fatty acids, the low lysine:arginine ratio, and the presence of other bioactive molecules (such as fiber, phytosterols, vitamin and other antioxidants, and minerals) make the addition of nuts to healthy diets a useful tool for the prevention of cardiovascular heart diseases.

Fatty acid composition of nuts – implications for cardiovascular health

Ros, E., J. Mataix, 2006. Fatty acid composition of nuts – implications for cardiovascular health. British Journal of Nutrition. 96, Suppl. 2, S29-S35.

It is well established that, due to their high content of saturated fatty acids (SFA), the intake of meat and meat products is strongly associated with elevated blood cholesterol concentrations and an increased risk of hypertension, diabetes and cardiovascular diseases. Conversely, the intake of foods rich in unsaturated fatty acids, such as those contained in most vegetable fats and oils and oily fish, is associated with improved lipid profiles, a lower potency of intermediate biomarkers of atherosclerosis and lesser incidence of cardiovascular diseases. There are persuasive evidences that dietary substitution of monounsaturated fatty acids (MUFA) or n-6 polyunsaturated fatty acids (PUFA) for SFA lowers blood cholesterol and may have beneficial effects on inflammation, thrombosis, and vascular reactivity. MUFA may have an advantage over PUFA because enrichment of lipoprotein lipids with MUFA increases their resistance to oxidation. Marine n-3 PUFA have a number of anti-atherosclerotic effects, including anti-arrhythmic properties and, at relatively high doses, reduce serum triglycerides. These effects appear to be shared in part by vegetable n-3 PUFA. Nuts are natural foods rich in unsaturated fatty acids; most nuts contain substantial amounts of MUFA, while walnuts are especially rich in both n-6 and n-3 PUFA. Healthy fats in nuts contribute to the beneficial effects of frequent nut intake observed in epidemiological studies (prevention of coronary heart disease, diabetes, and sudden death) and in short-term feeding trials (cholesterol lowering, LDL resistance to oxidation, and improved endothelial function).

Nuts and coronary heart disease: an epidemiological perspective

Kelly Jr., J.H., J. Sabaté’, 2006. Nuts and coronary heart disease: an epidemiological perspective. British Journal of Nutrition. 96, Suppl. 2, S61-S67

The epidemiological evidence for the cardio-protective effect of nut consumption is presented and reviewed. Four large prospective epidemiological studies of primary prevention of coronary heart disease are reviewed and discussed (Adventist Health Study, Iowa Women’s Health Study, Nurses’ Health Study and the Physicians’ Health Study). Other studies of nuts and coronary heart disease risk are addressed. The combined evidence for a cardio-protective effect from nut consumption is summarized and presented graphically. The risk of coronary heart disease is 37% lower for those consuming nuts more than four times per week compared to those who never or seldom consume nuts, with an average reduction of 8·3% for each weekly serving of nuts. The evidence for a causal relationship between nut consumption and reduced risk of coronary heart disease is outlined using Hill’s criteria for causality and is found to support a causal cardio-protective relationship.

Nut and seed consumption and inflammatory markers in the multi-ethnic study of atherosclerosis

Jiang, R., D.R. Jacobs, Jr., E. Mayer-Davis, M. Szkio, D. Herrington, N.S. Jenny, R. Kronmal, R. G. Barr, 2006.  Nut and seed consumption and inflammatory markers in the multi-ethnic study of atherosclerosis. Am J Epidemiol. 163:222-231.

Nuts and seeds are rich in unsaturated fat and other nutrients that may reduce inflammation. Frequent nut consumption is associated with lower risk of cardiovascular disease and type 2 diabetes. The authors examined associations between nut and seed consumption and C-reactive protein, interleukin-6 and fibrinogen in the Multi-Ethnic Study of Atherosclerosis. This 2000 cross-sectional analysis included 6,080 US participants aged 45-84 years with adequate information on diet and biomarkers. Nut and seed consumption was categorized as never/rare, less than once/week, 1-4 times/week and five or more times/week. After adjustments for age, gender, race/ethnicity, site, education, income, smoking, physical activity, use of fish oil supplements, and other dietary factors, mean biomarker levels in categories of increasing consumption were as follows: C-reactive protein-1.98, 1.97, 1.80, and 1.72 mg/liter, interleukin-6 – 1.25, 1.24, 1.21 and 1.15 pg/ml; and fibrinogen-343, 338, 338, and 331 mg/dl (all p’s for trend < 0.01). Further adjustment for hypertension, diabetes, medication use, and lipid levels yielded similar results. Additional adjustment for body mass index moderately attenuated the magnitude of the associations, yielding borderline statistical significance. Associations of nut and seed consumption with these biomarkers were not modified by body mass index, waist:hip ratio, or race/ethnicity. Frequent nut and see consumption was associated with lower levels of inflammatory markers, which may partially explain the inverse association of nut consumption with cardiovascular disease and diabetes risk.

Tree nuts and the lipid profile: a review of clinical studies

Griel, A.E., P.M. Kris-Etherton, 2006. Tree nuts and the lipid profile: a review of clinical studies. British Journal of Nutrition. 96, Suppl. 2, S68-S78

Tree nuts have a fatty acid profile that favorably affects blood lipids and lipoproteins. They are low in saturated fat and high in unsaturated fatty acids and are rich sources of other nutrients. An extensive database consistently shows total and LDL cholesterol-lowering effects of diets low in saturated fat and cholesterol and high in unsaturated fat provided by a variety of tree nuts. Collectively, a summary of studies conducted to date shows that tree nuts reduce LDL cholesterol by 3-19% compared with Western and lower-fat diets. Nuts also contain many nutrients and bioactive compounds that appear to contribute to the favorable effects on lipids and lipoproteins – these include plant sterols, dietary fiber and antioxidants. Because of their unique nutrient profile, nuts can be part of a diet that features multiple heart-healthy foods resulting in a cholesterol lowering response that surpasses that of cholesterol-lowering diets typically used to reduce CVD risk.

Effects of a Mediterranean-style diet in cardiovascular risk factors: A randomized trial

Estruch, R., M.A. Martínez-González, D. Corella, J. Salas-Salvadó, V. Ruiz-Gutiérrez, M.I. Covas, M. Fiol, E. Gómez-Gracia, M.C. López-Sabater, E. Vinyoles, F. Arós, M. Conde, C. Lahoz, J. Lapetra. G. Sáez, E. Ros for the PREDIMED Study, 2006. Effects of a Mediterranean-style diet in cardiovascular risk factors: A randomized trial. Annals of Inter Med. 145:1-11.

Background: The Mediterranean diet has been shown to have beneficial effects on cardiovascular risk factors. Objective: To compare the short-term effects of 2 Mediterranean diets versus those of a low-fat diet on intermediate markers of cardiovascular risk. Design: Substudy of a multicenter, randomized, primary prevention trial of cardiovascular disease (Prevencio’ n con Dieta Mediterra’nea [PREDIMED] Study). Setting: Primary care centers affiliated with 10 teaching hospitals. Participants: 772 asymptomatic persons 55 to 80 years of age at high cardiovascular risk who were recruited from October 2003 to March 2004. Interventions: Participants were assigned to a low-fat diet (n=257) or to 1 of 2 Mediterranean diets. Those allocated to Mediterranean diets received nutritional education and either free virgin olive oil, 1 liter per week (n = 257), or free nuts, 30 g/d (n= 258). The authors evaluated outcome changes at 3 months. Measurements: Body weight, blood pressure, lipid profile, glucose levels, and inflammatory molecules. Results: The completion rate was 99.6%. Compared with the low-fat diet, the 2 Mediterranean diets produced beneficial changes in most outcomes. Compared with the low-fat diet, the mean changes in the Mediterranean diet with olive oil group and the Mediterranean diet with nuts group were -0.39 mmol/L (95% CI, -0.70 to -0.07 mmol/L) and -0.30 mmol/L (CI, -0.58 to -0.01 mmol/L), respectively, for plasma glucose levels; -5.9 mm Hg (CI, -8.7 to -3.1 mm Hg) and -7.1 mm Hg (CI, -10.0 to -4.1 mm Hg), respectively, for systolic blood pressure; and -0.38 (CI, -0.55 to -0.22) and -0.26 (CI, -0.42 to -0.10), respectively, for the cholesterol-high-density lipoprotein cholesterol ratio. The Mediterranean diet with olive oil reduced C-reactive protein levels by 0.54 mg/L (CI, 1.04 to 0.03 mg/L) compared with the low-fat diet. Limitations: This short-term study did not focus on clinical outcomes. Nutritional education about low-fat diet was less intense than education about Mediterranean diets. Conclusion: Compared with a low-fat diet, Mediterranean diets supplemented with olive oil or nuts have beneficial effects on cardiovascular risk factors.

The potential of nuts in the prevention of cancer

Gonzalez, C.A., J. Salas-Salvado’, 2006. The potential of nuts in the prevention of cancer. British Journal of Nutrition. 96, Suppl. 2, S87-S94.

Cancer is a disease that is characterized by the loss of genetic control over cell growth and proliferation, mainly as a result of the exposure to environmental factors. Cessation of smoking and a high consumption of fruits and vegetables are the most important means of reducing the risk of cancer in our society. Like fruits and vegetables, nuts are a source of vegetable protein, monounsaturated fatty acids, vitamin E, phenolic compounds, selenium, vegetable fiber, folic acid and phytoestrogens. There are numerous mechanisms of action by which these components can intervene in the prevention of cancer, although they have not been fully elucidated. There are very few epidemiological studies analyzing the relationship between nuts consumption and risk of cancer. One of the greatest difficulties in interpreting the results is that the consumption of nuts, seeds and legumes are often presented together. The most commonly studied location is the colon/rectum, an organ in which the effect of nuts is biologically plausible. Although the results are not conclusive, a protective effect on colon and rectum cancer is possible. Likewise, some studies show a possible protective effect on prostate cancer, but there is insufficient data on other tumor locations. New epidemiological studies are required to clarify the possible effects of nuts on cancer, particularly prospective studies that make reliable and complete estimations of their consumption and which make it possible to analyze their effects independently of the consumption of legumes and seeds.

Health benefits of nuts: Potential role of antioxidants.

Blomhoff, R., M.H. Carlsen, L.F. Andersen, D.R. Jacobs Jr, 2006. Health benefits of nuts: potential role of antioxidants. British Journal of Nutrition. 96, Suppl. 2, S52-S60.

A diet rich in fruits, vegetables and minimally refined cereals is associated with lower risk for chronic degenerative diseases. Since oxidative stress is common in chronic degenerative disease, it has been assumed that dietary antioxidants may explain this protective effect. Every dietary plant contains numerous types of antioxidants with different properties. Many of these antioxidants cooperate in oxidative stress reduction in plants, and we hypothesize that many different antioxidants may also be needed for the proper protection of animal cells. To test this hypothesis, it is useful to identify dietary plants with high total antioxidant content. Several nuts are among the dietary plants with the highest content of total antioxidants. Of the tree nuts, walnuts, pecans and chestnuts have the highest contents of antioxidants. Walnuts contain more than 20 mmol antioxidants per 100 g, mostly in the walnut pellicles. Peanuts (a legume) also contribute significantly to dietary intake of antioxidants. These data are in accordance with our present extended analysis of an earlier report on nut intake and death attributed to various diseases in the Iowa Women’s Health Study. We observed that the hazard ratio for total death rates showed a U-shaped association with nut/peanut butter consumption. Hazard ratio was 0.89 (CI= 0.81-0.97) and 0.81 (CI= 0.75-0.88) for nut/peanut butter intake once per week and 1-4 times per week, respectively. Death attributed to cardiovascular and coronary heart diseases showed strong and consistent reductions with increasing nut/peanut butter consumption. Further studies are needed to clarify whether antioxidants contribute to this apparent beneficial health effect of nut