One‐Year Effects of Increasingly Fat‐Restricted, Carbohydrate‐Enriched Diets on Lipoprotein Levels in Free‐Living Subjects

Abstract

Abstract. Restriction of all dietary fat is a popular strategy for restricting saturated fat intake to lower LDL cholesterol. Some authorities advise the restriction of fat intake to the extreme of less than 10% of daily energy on the assumption that more fat restriction is better. The two studies described herein address questions relating to whether increasing fat restriction produces proportionally increasing benefit on cardiovascular risk factors in hyperlipidemic subjects.The first study is the Dietary Alternatives Study (DAS). The DAS was conducted in 531 male Boeing employees over a 2‐year period. Subjects were defined as hypercholesterolemic (HC) or combined hyperlipidemic (CHL) based on age‐specific 75th percentiles for plasma LDL‐C and triglyceride levels. Hypothesis test analyses were performed at 1 year. HC subjects were randomized to diets taught to attain fat intakes of 30, 26, 22, and 18% (Diets levels 1–4, respectively). CHL subjects (slightly fewer in number) were randomized to Diets 1–3. After 1 year, subjects' total fat intakes were 27, 26, 25, and 22% of energy (en%), resulting in saturated fat intakes of 8, 7, 7, and 6%, respectively. In HC subjects the greatest LDL‐C decrease was with Diet 2 (mean of 13.4%) and in CHL subjects with Diet 1 (7.0%). Surprisingly, plasma triglyceride concentrations rose in HC subjects 20% and 40% above baseline on Diets 3 and 4, respectively, with reciprocal reductions in HDL cholesterol of 2.5% and 3%, respectively. Furthermore, apo B reductions were attenuated below Diet 2 in HC subjects and Diet 1 in CHL subjects, and no further reductions were seen in plasma glucose and insulin concentrations, blood pressure, or body weight. Measurements of plasma total fatty acid composition showed a slight increase in plasma palmitate, whereas stearate decreased slightly, supporting the idea that de novo synthesis of palmitic acid was increased in the chronic high‐carbohydrate feeding condition. The second study asked if the most effective diet in HC subjects, Diet 2, has an equivalent effect in women and men. To answer this question, men and women Boeing employees were taught the closely similar National Cholesterol Education Program (NCEP) Step II diet. After 6 and 12 months, equivalent reductions in LDL cholesterol were observed in women compared with men. HDL cholesterol levels in men were unchanged from baseline at 6 and 12 months, but were reduced 8% in HC women, with accompanying decreases of 18% in HDL2‐cholesterol and 5% in apoprotein A‐I (all P < 0.01). These data indicate that intakes of fat below about 25 en% and carbohydrate intake above ≈ 60 en% yield no further LDL‐C lowering in HC and CHL male subjects and can be counterproductive to triglyceride, HDL‐C, and apo B levels. This lack of benefit appears to be explained by an enhanced endogenous synthesis of palmitic acid, which negates the benefit of further saturated fat restriction. The HDL‐C decrease in HC women may have a similar cause and points to an underlying male‐female difference. Alternative dietary...

Activation of NF-κB by Palmitate in Endothelial Cells

“…Palmitic, oleic, and linoleic acids constitute up to 70% of circulating FFA in humans, with each typically being present in concentrations between 10–50 μM 21, 22. Although the current cell culture studies relied upon concentrations of palmitic acid (100 μM) higher than those usually found in humans, lower concentrations of palmitic/BSA (50 μM) also increase endothelial levels of IL-6.…”

Endogenous red blood cell membrane fatty acids and sudden cardiac arrest

“…21 Interestingly, membrane levels of 16:1n-7 in the present study was also related to body weight, possibly reflecting the effects of low-fat high-carbohydrate diets on de novo synthesis and hypertriglyceridemia. 10, 11 The fatty acid 16:1n-7 was highly correlated with its precursor 16:0 and the association of 16:0 with SCA risk appeared more robust than that of 16:1n-7. However, this difference in level of association cannot be concluded from the study data.…”

“…29 The occurrence of fatty acid synthesis from dietary carbohydrates in the absence of excess caloric intake is supported by dietary trials. 8, 9 10-12 Further studies are needed to investigate dietary and genetic factors that promote fatty acid synthesis. The associations of end products of fatty acid synthesis with SCA risk raise the possibility that dietary carbohydrates in the setting of low fat intake might also be associated with SCA risk.…”

Plasma Phospholipid Saturated Fatty Acids and Incident Atrial Fibrillation: The Cardiovascular Health Study

“…This suggests that metabolic pathways are the primary determinant of circulating levels. One key driver of higher circulating 16:0 appears to be de novo lipogenesis, an endogenous enzymatic pathway by which dietary carbohydrates are converted into circulating fatty acids in the presence of low‐fat and high‐carbohydrate diets . Alcohol intake may also drive the endogenous synthesis of 16:0 …”

“…The SFAs palmitic acid (16:0) and stearic acid (18:0) are found in animal products, such as meat and hard cheeses, and in tropical oils, whereas arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0) are found in peanuts and canola oil. SFA 16:0 is also the primary end product of fatty acid synthesis, and circulating levels of 16:0 are influenced by carbohydrate and alcohol intake …”