**5.1. Dietary fiber**

Dietary fiber can be classified in different ways: soluble versus insoluble based on water solubility; fermentable versus non-fermentable based on whether or not it can be fermented by the microbiota in the large intestine; and viscous versus non-viscous related to its viscosity [90]. Fruit, vegetables, and cereals are the major sources of dietary fiber. The analysis of 67 clinical trials on diets high in soluble fibers suggested that these fibers lower total cholesterol and LDL-C [91]. Water insoluble fibers remain unchanged during digestion and have no effect unless they displace foods supplying saturated fats and cholesterol [92]. Most of the available epidemiologic studies suggest that dietary fiber is inversely related to coronary artery disease [93]. Diet rich in dietary fiber is beneficial for the treatment of T2DM [94], as dietary fiber ameliorates postprandial hyperglycemia by delaying digestion and absorption of carbohydrates [95]. A recent systematic review of the literature reported that moderate amounts of fiber supplements (4–19 g/day) achieved little improvement in glycemic control or CVD risk factors [96]. It has been reported that increased intake of dietary fiber and low GI diet with legumes reduced blood pressure compared with wheat fiber diet in T2DM patients [95]. A cross-sectional study in adults men and women indicated that the highest total dietary fiber and insoluble dietary fiber intakes were associated with a significantly lower risk of overweight, high blood pressure, plasma apolipoprotein (apo) B, apo B, apo A–I, cholesterol, triacylglycerols, and homocysteine [97]. The fiber intake should, ideally, be 40 g/day (or 20 g/1000 kcal/day) or more and about half should be of the water-soluble type. People with T2DM are encouraged to choose ≥5 servings of fiber-rich vegetables or fruit and ≥4 servings of legumes per week to achieve the fiber intake goals set for the general population [98].

myocardial infarction, and breast cancer (EURAMIC) study found that the risk of MI was 60% lower for the highest quintile of adipose lycopene concentration compared to the lowest quintile, after adjustment for age, family history of CVD and cigarette smoking [109]. In a crosssectional study comparing Lithuanian and Swedish populations showing diverging mortality rates from CVD, lower blood lycopene levels were found to be associated with increased risk and mortality from CVD [110]. Many studies show that high consumption of tomato products can improve resistance to oxidation in people with T2DM [111]. Eating a lycopene-rich Mediterranean diet increases lycopene levels and can reduce the levels of hemoglobin A1c from 7.1 to 6.8% [112]. In a case-control study on serum β-carotene and the risk of T2DM, participants in the highest tertile of serum β-carotene levels had a 55% lower risk of developing T2DM [113]. In a quasi-experimental study, 32 T2DM patients received 200 g raw tomato daily for 8 weeks. There were significant decreases in systolic and diastolic blood pressure and also a significant increase in apoA-I compared with initial values, which suggests the beneficial role of tomato consumption in reducing cardiovascular risk associated with T2DM [114, 115].

Dietary Recommendations for Patients with Cardiovascular Disease and Diabetes

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N−3 fatty acids including α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) have a significant role in the prevention of CVD [116]. The evidence supports a dietary recommendation of ≈500 mg/day of eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) for CVD risk reduction [117]. A meta-analysis suggests that ALA consumption may also confer cardiovascular benefits, and each 1 g/d increment in ALA intake was associated with a 10% lower risk of CVD death [118]. Dietary sources of ALA include flaxseeds and flaxseed oil, walnuts and walnut oil, soybeans and soybean oil, pumpkin seeds, rapeseed oil, and olive oil [119]. In the GISSI Prevention Study, treatment with n-3 PUFA significantly lowered the risk of the primary endpoint (death, non-fatal MI, and stroke) [120]. Several mechanisms explaining the cardioprotective effect of the n-3 PUFA have been

Several groups are now beginning to use animal models of myocardial ischemia and reperfusion to explore whether certain nutrients, including ethanol and non-ethanolic components of wine, may have a specific protective effect on the myocardium, independently from the classical risk factors for coronary disease involved in vascular atherosclerosis and thrombosis [121]. Most epidemiological studies have suggested an inverse association between regular light to moderate drinking and the risks of CVD [122]. Researchers have wondered whether moderate alcohol consumption mediates some of its cardioprotective effects by stimulating NO, and conversely, whether binge drinking diminishes NO availability [123]. In a swine model of chronic ischemia, alcohol administration promoted angiogenesis, increased capillary and arteriolar density in non-ischemic myocardium [122]. Numerous studies indicate that moderate red wine consumption is associated with a protective effect on the cardiovascular system, which has largely been attributed to the rich content of phenolic compounds [124, 125]. Polyphenolic antioxidants scavenge the free radicals, inhibit lipid peroxidation (lipoproteins,

suggested including antiarrhythmic and antithrombotic roles [119].

**5.5. Ethanol and non-ethanolic components of wine**

**5.4. Fatty acids**

## **5.2. Polyphenols**

A number of antioxidants showed beneficial effect in experimental models of atherosclerosis and CVD [99, 100]. The main polyphenol dietary sources are fruit and beverages (fruit juice, wine, tea, coffee, chocolate, and beer), dry legumes, and cereals [101]. Dietary polyphenols have been shown to possess cardioprotective effects. Oleuropein inhibits the oxidation of LDL-C in vitro [102]. Dietary quercetin decreases lipid peroxidation and upregulates the expression of serum HDL-associated paraoxonase-1 (PON-1) in the liver [101]. PON-1 may mediate anti-atherogenic properties by protecting LDL-C from oxidation. Several studies have indicated that red wine polyphenolic compounds (RWPCs) were able to inhibit proliferation and migration of vascular cells. RWPCs induced NO-mediated endothelium-dependent relaxations in isolated arteries. The activation of eNOS led to an increase in [Ca2+]i and phosphorylation of eNOS by the PI3-kinase/Akt pathway [103]. RWPCs also increased endothelial prostacyclin release and inhibited the synthesis and the effects of endothelin-1 in endothelial cells [101].

#### **5.3. Lycopene**

Lycopene is a natural carotenoid found in tomatoes, which has biochemical functions as an antioxidant scavenger, hypolipidemic agent, and inhibitor of pro-inflammatory and prothrombotic factors [104]. Red fruits and vegetables, including tomatoes, watermelons, pink grapefruits, apricots, and pink guavas, contain lycopene. Processed tomato products are good dietary sources of lycopene [105]. Two major hypotheses have been proposed to explain the anti-atherogenic activities of lycopene. The non-oxidative action of lycopene results in an increase of gap-junction communication between cells and modulation of immune function [106] .The oxidative hypothesis supports the prevention of the oxidization of LDL-C as the initial step leading to its uptake by the macrophages inside the arterial wall and the formation of foam cells and atherosclerotic plaque [105]. A possible mechanism for the protective role of lycopene in CVD is via the inhibition of cellular 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, the rate-limiting enzyme in cholesterol synthesis [107]. Results from the Harvard Medical School's Women's Health Study showed that women with the highest intake of tomato-based foods rich in lycopene had a reduced risk for CVD compared to women with a low intake of these foods [108]. The European multicenter case-control study on antioxidants, myocardial infarction, and breast cancer (EURAMIC) study found that the risk of MI was 60% lower for the highest quintile of adipose lycopene concentration compared to the lowest quintile, after adjustment for age, family history of CVD and cigarette smoking [109]. In a crosssectional study comparing Lithuanian and Swedish populations showing diverging mortality rates from CVD, lower blood lycopene levels were found to be associated with increased risk and mortality from CVD [110]. Many studies show that high consumption of tomato products can improve resistance to oxidation in people with T2DM [111]. Eating a lycopene-rich Mediterranean diet increases lycopene levels and can reduce the levels of hemoglobin A1c from 7.1 to 6.8% [112]. In a case-control study on serum β-carotene and the risk of T2DM, participants in the highest tertile of serum β-carotene levels had a 55% lower risk of developing T2DM [113]. In a quasi-experimental study, 32 T2DM patients received 200 g raw tomato daily for 8 weeks. There were significant decreases in systolic and diastolic blood pressure and also a significant increase in apoA-I compared with initial values, which suggests the beneficial role of tomato consumption in reducing cardiovascular risk associated with T2DM [114, 115].
