Dietary enrichment with almond (Prunus amygdalis) supplementation: effects on CVD risk biomarkers

Epidemiological evidence suggests that diets rich in fruits, vegetables and pulses reduce the risk of CVD. The Physicians Health Study has demonstrated reduction of CHD death with regular nut consumption1. One major modifiable risk factor for CHD is an unhealthy diet. Thus, an almondenrichment study has been undertaken to examine the benefit of almonds (Prunus amygdalis) in healthy individuals either with or without significant risk of vascular disease. Almonds contain various macronutrients (low SFA content, absence of cholesterol and high MUFA content) and micronutrients, including vitamin E, polyphenols and arginine, which afford vascular benefit. The effects of almond consumption (25 g/d for 4 weeks followed by 50 g/d for 4 weeks) were evaluated in three non-smoking subject groups: healthy male volunteers between the ages of 18 and 35 years (n 15); men at risk of heart disease between the ages of 18 and 35 years (n 12); mature men and women >50 years of age (n 18). A fourth control group (n 14) were followed over 8 weeks without dietary almond enrichment as a treatment control. None of the subjects withdrew from the study and 90% completed the study. The interim results of the study showed that in the three active groups there was little evidence for a change in total cholesterol, LDL-cholesterol or HDL-cholesterol. In the mature group there was a trend towards increasing HDL-cholesterol. The mature and ‘at-risk’ groups also showed a significant changes in systolic blood pressure (P<0.05) during almond consumption. The healthy group showed a decrease in diastolic blood pressure (P<0.05). The ‘at-risk’ group showed a significant increase (P<0.05) in flowmediated dilation after 8 weeks of almond consumption. Data analysis is ongoing, with completion of the study in November 2007. The beneficial effects of almond consumption on flow-mediated dilation and blood pressure may be attributed to the high content in almonds of arginine, which serves as a precursor to the vasodilatory molecule, NO.

Fatty acids, monocytes and ageing

Elevated free fatty acids (FFA) are a feature of ageing and a risk factor for metabolic disorders such as cardiovascular disease (CVD) and type-2 diabetes (T2D). Elevated FFA contribute to insulin resistance, production of inflammatory cytokines and expression of adhesion molecules on immune cells and endothelial cells, risk factors for CVD and T2D. Molecular mechanisms of FFA effects on monocyte function and how FFA phenotype is affected by healthy ageing remain poorly understood. This thesis evaluated the effects of the two major FFA in plasma, oleate and palmitate on monocyte viability, cell surface antigen expression, and inflammatory activation in THP-1 monocytes. Palmitate but not oleate increased cell surface expression of CD11b and CD36 after 24h, independent of mitochondrial superoxide, but dependent on de novo synthesis of ceramides. LPS-mediated cytokine production in THP-1 monocytes was enhanced and decreased following incubation with palmitate and oleate respectively. In a model of monocyte-macrophage differentiation, palmitate induced a pro-inflammatory macrophage phenotype which required de novo ceramide synthesis, whilst oleate reduced cytokine secretion, producing a macrophage with enhanced clearance apoptotic cells. Plasma fatty acid analysis in young and mid-life populations revealed age-related increases in both the SFA and MUFA classes, especially the medium and very long chain C14 and C24 fatty acids, which were accompanied by increases in the estimated activities of desaturase enzymes. Changes were independently correlated with increased PBMC CD11b, plasma TNF-a and insulin resistance. In conclusion, the pro-atherogenic phenotype, enhanced LPS responses in monocytes, and pro-inflammatory macrophage in the presence of palmitate but not oleate is reliant upon de novo ceramide synthesis. Age-related increases in inflammation, cell surface integrin expression are related to increases in both the MUFA and SFA fatty acids, which in part may be explained by altered de novo fatty acid synthesis.