OST DIETARY MANIPULAtions result in modest cholesterol reductions of 4% to 13%, 1-10 and diet has been considered by some as a relatively ineffective therapy. 11 In contrast, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) repeatedly have been shown to reduce mean serum low-density lipoprotein cholesterol (LDL-C) concentrations by 28% to 35% in long-term trials, [12][13][14] with corresponding reductions in cardiovascular death of 23% to 32% in both primary and secondary prevention trials. 13,14 Recently, to boost effectiveness of diet for primary prevention of cardiovascular disease, the Adult Treatment Panel (ATP III) of the National Cholesterol Education Program has recommended addition of plant sterols (2 g/d) and viscous fibers (10-25 g/d) to the diet. 15 The American Heart Association has also drawn atten-Author Affiliations and Financial Disclosures are listed at the end of this article.

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Consumption of tree nuts such as almonds has been associated with a reduced risk of coronary heart disease. Flavonoids, found predominantly in the skin of almonds, may contribute to their putative health benefit, but their bioactivity and bioavailability have not previously been studied. Almond skin flavonoids (ASF) were extracted with HCl:H2O:methanol (1:19:80) and their content of catechins and flavonols identified by HPLC with electrochemical detection. ASF bioactivity was assessed in vitro by their capacity to increase the resistance of human LDL to oxidation induced by 10 micromol/L Cu2+. ASF from 0.18 to 1.44 mumol gallic acid equivalent (GAE)/L increased the lag time to LDL oxidation in a dose-dependent manner (P < or = 0.0001). Combining ASF with vitamin E or ascorbic acid extended the lag time >200% of the expected additive value (P < or = 0.05). The bioavailability and in vivo antioxidant activity of 40 micromol ASF were examined in BioF1B hamsters. Peak plasma concentrations of catechin, epicatechin, and flavonols (quercetin, kaempferol, and isorhamnetin) occurred at 60, 120, and 180 min, respectively. The concentration of isorhamnetin was significantly elevated in liver at 180 min. Absorbed ASF enhanced the ex vivo resistance of hamster LDL collected at 60 min to oxidation by 18.0% (P = 0.028), and the in vitro addition of 5.5 micromol/L vitamin E synergistically extended the lag time of the 60-min sample by 52.5% (P < or = 0.05). Thus, ASF possess antioxidant capacity in vitro; they are bioavailable and act in synergy with vitamins C and E to protect LDL against oxidation in hamsters.

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Dietary combinations may not differ in potency from first-generation statins in achieving current lipid goals for primary prevention. They may, therefore, bridge the treatment gap between current therapeutic diets and newer statins.

Background-Although recent studies have indicated that nut consumption may improve levels of blood lipids, nuts are not generally recommended as snacks for hyperlipidemic subjects because of their high fat content. Furthermore, the effective dose is still unknown. Methods and Results-The dose-response effects of whole almonds, taken as snacks, were compared with low-saturated fat (Ͻ5% energy) whole-wheat muffins (control) in the therapeutic diets of hyperlipidemic subjects. In a randomized crossover study, 27 hyperlipidemic men and women consumed 3 isoenergetic (mean 423 kcal/d) supplements each for 1 month. Supplements provided 22.2% of energy and consisted of full-dose almonds (73Ϯ3 g/d), half-dose almonds plus half-dose muffins, and full-dose muffins. Fasting blood, expired air, blood pressure, and body weight measurements were obtained at weeks 0, 2, and 4. Mean body weights differed Ͻ300 g between treatments. The full-dose almonds produced the greatest reduction in levels of blood lipids. Significant reductions from baseline were seen on both halfand full-dose almonds for LDL cholesterol (4.4Ϯ1.7%, Pϭ0.018, and 9.4Ϯ1.9%, PϽ0.001, respectively) and LDL:HDL cholesterol (7.8Ϯ2.2%, Pϭ0.001, and 12.0Ϯ2.1%, PϽ0.001, respectively) and on full-dose almonds alone for lipoprotein(a) (7.8Ϯ3.5%, Pϭ0.034) and oxidized LDL concentrations (14.0Ϯ3.8%, PϽ0.001), with no significant reductions on the control diet. No difference was seen in pulmonary nitric oxide between treatments. Conclusions-Almonds used as snacks in the diets of hyperlipidemic subjects significantly reduce coronary heart disease risk factors, probably in part because of the nonfat (protein and fiber) and monounsaturated fatty acid components of the nut.

Almonds provide a nutrient-dense source of vitamin E, manganese, magnesium, copper, phosphorus, fibre, riboflavin, monounsaturated fatty acids and protein. Although almost 50% of almond weight is fat, incremental intakes of 7 g day −1 of this tree nut reduce low-density lipoprotein (LDL) cholesterol concentration by 1%, especially within the context of diets recommended by the National Cholesterol Education Program. Habitual almond consumption does not lead to weight gain, and their inclusion in low-calorie diets appears to promote more weight loss than a comparable carbohydrate-based low-calorie diet. Also, almonds have a low glycemic index and do not adversely impact insulin sensitivity. Almonds are an excellent source of bioavailable α-tocopherol, and increasing their intake enhances the resistance of LDL against oxidation. In addition, the polyphenolic constituents of almonds have been characterised recently and found to possess antioxidant actions. While benefits of almonds for cardiovascular health and obesity-related diseases appear promising, the potential allergenic reaction among susceptible individuals can present a risk. Further research is required to achieve a better understanding of the role that the bioavailability and bioaccessibility of almond constituents and the synergy between them play in their associated health outcomes.

More than 30% of motivated participants who ate the dietary portfolio of cholesterol-lowering foods under real-world conditions were able to lower LDL-cholesterol concentrations >20%, which was not significantly different from their response to a first-generation statin taken under metabolically controlled conditions.