Am J Clin Nutr. 2003 Aug;78(2):201-8.
The age of molecular biology began in 1953 with the discovery of the structure of DNA. By 1961 the genetic code for the translation of the sequence of bases in DNA to amino acids in proteins was underway, and a model for the genetic regulation of protein synthesis was proposed. My interest in the genetic regulation of nutrient metabolism began in that year during my sabbatical leave in the laboratory of Sir Hans Krebs at Oxford University. In the present article, I describe 2 episodes in my career during which I used genetic concepts to explain a nutritional phenomenon; the first episode occurred before doing the experimental work, and the second occurred after the experimental work was completed. My first brainstorm, which occurred in 1961, was to investigate the hypothesis that all of the fat-soluble vitamins act by the regulation of a cluster of genes. Unfortunately, I selected vitamin K as my model and discovered that it is the only fat-soluble vitamin that does not work in full or in part by the regulation of a set of genes. In 1967 I undertook a second problem, which was to determine the mode of action of polyunsaturated fatty acids in lowering plasma lipid concentrations in humans. We discovered that linoleic acid reduced the storage and enhanced the oxidation of fatty acids. The genetic interpretation of this study has come only recently: polyunsaturated fats have been shown to down-regulate enzymes that accomplish storage of fatty acids and to up-regulate genes that enhance fatty acid oxidation.
Am J Clin Nutr 2003 Jul;78(1):47-56
Effects of dietary monounsaturated fatty acids on lipoprotein concentrations, compositions, and subfraction distributions and on VLDL apolipoprotein B kinetics: dose-dependent effects on LDL.
Gill JM, Brown JC, Caslake MJ, Wright DM, Cooney J, Bedford D, Hughes DA, Stanley JC, Packard CJ Department of Pathological Biochemistry, University of Glasgow, Glasgow, United Kingdom . firstname.lastname@example.org
BACKGROUND: Replacing dietary
saturated fatty acids (SFAs) with monounsaturated fatty acids (MUFAs)
lowers LDL cholesterol, but the underlying mechanisms remain unclear.
J Nutr 2003 May;133(5):1409-14
Dietary (n-3)/(n-6) Fatty Acid Ratio: Possible Relationship to Premenopausal but Not Postmenopausal Breast Cancer Risk in U.S. Women.
Goodstine SL, Zheng T, Holford TR, Ward BA, Carter D, Owens PH, Mayne ST Yale University School of Medicine and Yale Cancer Center, New Haven, CT.
Recent research has suggested that an increased (n-3) fatty acid intake and/or increased (n-3)/(n-6) polyunsaturated fatty acid (PUFA) ratio in the diet is associated with a lower breast cancer risk. This case-control study investigated the association between intake of (n-3) and other fatty acids and the (n-3)/(n-6) PUFA ratio and breast cancer risk. After combining data from two related case-control studies in Connecticut, we had information available on a total of 1119 women (565 cases and 554 controls). Cases were all histologically confirmed, incident breast carcinoma patients. Controls were hospital-based (Yale-New Haven Hospital study site) and population-based (Tolland County study site). Information on dietary intake was obtained through a validated food-frequency questionnaire. Standard multivariate methods were used to address the independent effects of specific fatty acids, fat classes and macronutrients on breast cancer risk. In the full study population, there were no significant trends for any macronutrient/fatty acid when comparing the highest to the lowest quartile of intake. When the analysis was restricted to premenopausal women, consumption of the highest compared with the lowest quartile of the (n-3)/(n-6) PUFA ratio was associated with a nonsignificant 41% lower risk of breast cancer [odds ratio (OR) = 0.59, 95% confidence interval (CI) 0.29, 1.19, P for trend = 0.09]. A higher (n-3)/(n-6) PUFA ratio was significantly associated with a lower risk of breast cancer when the data were restricted to the Tolland County (population-based) study site; OR = 0.50, 95% CI 0.27, 0.95, P for trend = 0.02. These results are consistent with the hypothesis that a higher (n-3)/(n-6) PUFA ratio may reduce the risk of breast cancer, especially in premenopausal women.
Br J Nutr 2003 Mar;89(3):341-50
Dietary cholesterol reduces lipoprotein lipase activity in the atherosclerosis-susceptible Bio F1B hamster.
Salter AM, McAteer MA, Grimsditch DC, Vidgeon-Hart M, Martin Benson G Division of Nutritional Biochemistry, School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, Leicestershire LE12 5RD.
We have compared lipoprotein metabolism in, and susceptibility to atherosclerosis of, two strains of male Golden Syrian hamster, the Bio F1B hybrid and the dominant spot normal inbred (DSNI) strain. When fed a normal low-fat diet containing approximately 40 g fat and 0.3 g cholesterol/kg, triacylglycerol-rich lipoprotein (chylomicron+VLDL) and HDL-cholesterol were significantly higher (P<0.001) in Bio F1B hamsters than DSNI hamsters. When this diet was supplemented with 150 g coconut oil and either 0.5 or 5.0 g cholesterol/kg, significant differences were seen in response. In particular, the high-cholesterol diet produced significantly greater increases in plasma cholesterol and triacylglycerol in the Bio F1B compared with the DSNI animals (P=0.002 and P<0.001 for cholesterol and triacylglycerol, respectively). This was particularly dramatic in non-fasting animals, suggesting an accumulation of chylomicrons. In a second experiment, animals were fed 150 g coconut oil/kg and 5.0 g cholesterol/kg for 6 and 12 months. Again, the Bio F1B animals showed dramatic increases in plasma cholesterol and triacylglycerol, and this was confirmed as primarily due to a rise in chylomicron concentration. Post-heparin lipoprotein lipase activity was significantly reduced (P<0.001) in the Bio F1B compared with the DSNI animals at 6 months, and virtually absent at 12 months. Bio F1B animals were also shown to develop significantly more (P<0.001) atherosclerosis. These results indicate that, in the Bio F1B hybrid hamster, cholesterol feeding reduces lipoprotein lipase activity, thereby causing the accumulation of chylomicrons that may be associated with their increased susceptibility to atherosclerosis.
Lipids 2002 Sep;37(9):901-6
Relationship between platelet phospholipid FA and mean platelet volume in healthy men.
Li D, Turner A, Sinclair AJ. Department of Food Science, RMIT University, Melbourne 3001, Australia. email@example.com
Increased mean platelet volume (MPV) has been suggested as an independent risk factor for acute myocardial infarction and the increased reactivity of large platelets. The aim of this study was to investigate the correlation between platelet phospholipid (PL) PUFA composition and MPV in 139 free-living healthy men ages 20-55 yr (vegans, n = 18; ovolacto vegetarians, n = 43; moderate meat-eaters, n = 60; and high meateaters, n = 18). Each subject completed a semiquantitative Food Frequency Questionnaire and gave a blood sample. Platelet PL FA composition and MPV were determined by standard methods. MPV was significantly greater in the vegans than in the ovolacto vegetarian, moderate, or high meat-eater groups (P < 0.01). Both vegan and ovolacto vegetarian groups had significantly higher platelet PL 18:2n-6 and 22:4n-6, and lower 20:5n-3 and 22:6n-3 compared with the moderate and high meat-eater groups. The vegans demonstrated a significant reduction in 20:4n-6 and 22:5n-3 compared with the ovolacto vegetarian, high meat-eater, and moderate meat-eater groups. Bivariate analysis results showed that MPV was significantly positively correlated with platelet PL 18:2n-6 (P = 0.048) and negatively correlated with 20:3n-6 (P = 0.02), 20:5n-3 (P = 0.005), and 22:5n-3 (P< 0.0001), respectively. In a multiple linear regression analysis, after controlling for potential confounding factors such as dietary group, age, exercise, body mass index, and dietary polyunsaturated and saturated fat, cholesterol, carbohydrate, and fiber intake, the MPV was still strongly negatively correlated with platelet PL 20:3n-6 (P = 0.003) and 22:5n-3 (P = 0.001). The present data suggest that 22:5n-3 and 20:3n-6 may play a role in the structural function of the platelet membrane.
Int J Vitam Nutr Res 2001 Jul;71(4):223-8
The alpha-linolenic acid content of green vegetables commonly available in Australia.
Pereira C, Li D, Sinclair AJ. Department of Food Science, RMIT University, Melbourne 3001, Australia.
Green vegetable consumption has long been considered to have health benefits mainly due to the vitamins, minerals and phytonutrients (such as vitamin C, folate, antioxidants etc) contained in a vegetable-rich diet. Additionally, green vegetables are known to contain a relatively high proportion of omega-3 polyunsaturated fatty acids (PUFAs), primarily in the form of alpha-linolenic acid (18:3n-3). However, there are no data available on the fatty acid composition and concentration of green vegetables commonly consumed in Australia. The present study determined the fatty acid content of 11 green vegetables that are commonly available in Australia. The total fatty acid concentrations of the vegetables under study ranged from 44 mg/100 g wet weight in Chinese cabbage to 372 mg/100 g in watercress. There were three PUFAs in all vegetables analyzed; these were 16:3n-3, 18:2n-6, and 18:3n-3 fatty acids. Sample vegetables contained significant quantities of 16:3n-3 and 18:3n-3, ranging from 23 to 225 mg/100 g. Watercress and mint contained the highest amounts of 16:3n-3 and 18:3n-3, and parsley had the highest amount of 18:2n-6 in both percentage composition and concentration. Mint had the highest concentration of 18:3n-3 with a value of 195 mg/100 g, while watercress contained the highest concentration of 16:3n-3 at 45 mg/100 g. All 11 green vegetables contained a high proportion of PUFAs, ranging from 59 to 72% of total fatty acids. The omega-3 PUFA composition ranged from 40 to 62% of total fatty acids. Monounsaturated fatty acid composition was less than 6% of total fatty acids. The proportion of saturated fatty acids ranged from 21% in watercress and mint to 32% of total fatty acids in Brussels sprouts. No eicosapentaenoic and docosahexaenoic acids were detected in any of the samples. Consumption of green vegetables could contribute to 18:3n-3 PUFA intake, especially for vegetarian populations.
J Am Coll Cardiol 2001 Jun 1;37(7):1929-35
Post-prandial remnant lipids impair arterial compliance.
Nestel PJ, Shige H, Pomeroy S, Cehun M, Chin-Dusting J. Baker Medical Research Institute, Melbourne, Australia. firstname.lastname@example.org OBJECTIVES:
We sought to examine the effects
of plasma lipids, especially in remnants after a fat meal, on systemic
arterial compliance (SAC), a newly recognized cardiovascular risk factor.
Atherosclerosis 2000 Dec;153(2):397-402
Impaired flow-mediated vasoactivity during post-prandial phase in young healthy men.
Marchesi S, Lupattelli G, Schillaci G, Pirro M, Siepi D, Roscini AR, Pasqualini L, Mannarino E. Sezione di Medicina Interna, Angiologia e Malattie da Arteriosclerosi, University of Perugia, Policlinico Monteluce, Italy. email@example.com
Impaired flow-mediated vasodilation in large arteries is an expression of endothelial dysfunction and an established marker of early atherosclerosis. Post-prandial lipemia can induce an impairment of the endothelial function. The aim of our study was to evaluate the effects of post-prandial phase on flow-mediated vasodilation in a group of ten young (23 +/- 2 years) healthy men without cardiovascular risk factors, who underwent an oral fat-loading test. Flow-mediated vasodilation of the brachial artery and serum lipid profile were assessed under fasting conditions and 2, 4, 6 and 8 h after a high-fat meal. Triglycerides increased from 0.6 +/- 0.2 fasting to 1.1 +/- 0.5 and 1.3 +/-0.6 mmol/l at the 2nd and 4th hour (both P < 0.01), and decreased thereafter. Flow-mediated vasodilation fell significantly from 14.5 +/- 6.6% fasting to 3.5 +/- 1.5% and 4.0 +/- 2.2% at the 2nd and 4th hour (both P < 0.01), and returned to the basal values at the 6th and 8th hour. A strong inverse correlation was observed between the area under the incremental curve of post-prandial triglycerides (i.e. after subtraction of baseline triglycerides) and the area under the decremental curve of post-prandial flow-mediated vasodilation (r = -0.70, P = 0.025). No association was found between post-prandial vasodilation changes and fasting triglycerides, other lipid parameters or insulin. We conclude that a transient post-prandial impairment in brachial artery flow-mediated vasodilation is evident in young healthy men after a high-fat meal, and is closely associated with triglyceride levels. These data provide support for a role of post-prandial phase in vascular regulation in young healthy subjects.
Am J Cardiol 2000 Apr 15;85(8):969-72
Effectiveness of a low-fat vegetarian diet in altering serum lipids in healthy premenopausal women.
Barnard ND, Scialli AR, Bertron P, Hurlock D, Edmonds K, Talev L. Physicians Committee for Responsible Medicine, Washington DC, USA. firstname.lastname@example.org
Few controlled trials have studied cholesterol-lowering diets in premenopausal women. None has examined the cholesterol-lowering effect of a low-fat vegetarian diet, which, in other population groups, leads to marked reductions in serum cholesterol concentrations and, in combination with other life-style changes, a regression of atherosclerosis. We tested the hypothesis that a low-fat, vegetarian diet significantly reduces serum total and low-density lipoprotein (LDL) cholesterol concentrations in premenopausal women. In a crossover design, 35 women, aged 22 to 48, followed a low-fat vegetarian diet deriving approximately 10% of energy from fat for 2 menstrual cycles. For 2 additional cycles, they followed their customary diet while also taking a "supplement" (placebo) pill. Serum lipid concentrations were assessed at baseline and during each intervention phase. Mean serum LDL, high-density lipoprotein (HDL), and total cholesterol concentrations decreased 16. 9%, 16.5%, and 13.2%, respectively, from baseline to the intervention diet phase (p<0.001), whereas mean serum triacylglycerol concentration increased 18.7% (p<0.01). LDL/HDL ratio remained unchanged. Thus, in healthy premenopausal women, a low-fat vegetarian diet led to rapid and sizable reductions in serum total, LDL, and HDL cholesterol concentrations.
Trial PMID: 10760336
Eur J Clin Nutr 1999 Oct;53(10):802-7
Dietary habits affect the susceptibility of low-density lipoprotein to oxidation.
Korpela R, Seppo L, Laakso J, Lilja J, Karjala K, Lahteenmaki T, Solatunturi E, Vapaatalo H, Tikkanen MJ. Institute of Biomedicine, Department of Pharmacology and Toxicology, PO Box 8, FIN-00014 University of Helsinki. riitta.korpela.valio.fi
OBJECTIVE: To study, if there
are differences in the fatty acid composition of low-density lipoprotein
(LDL) in people eating three different long-standing habitual diets: vegetarian,
high fish intake, or high saturated fat (milk fat) diet as a control group,
and to study if these differences influence the oxidation susceptibility
Cancer Epidemiol Biomarkers Prev. 1999 Jun;8(6):519-24.
A case-control study of colorectal adenomatous polyps and consumption of foods containing partially hydrogenated oils.
McKelvey W, Greenland S, Chen MJ, Longnecker MP, Frankl HD, Lee ER, Haile RW. Department of Environmental Sciences and Engineering, School of Public Health, University of North Carolina at Chapel Hill, 27599-7400, USA. email@example.com
The trans fatty acids produced by partially hydrogenating vegetable oils may cause colorectal neoplasia by interfering with cell membrane function or eicosanoid synthesis. This possibility provides a rationale for looking at the relation between colorectal adenomatous polyps and consumption of foods containing partially hydrogenated vegetable oils (PHVOs). A total of 516 cases and 551 controls who underwent screening sigmoidoscopy from 1991-1993 were recruited from a prepaid Los Angeles health plan. Subjects were interviewed and given a self-administered food frequency questionnaire. Food items containing PHVOs were divided into four groups characterized by principal ingredients and preparation methods: sweetened baked goods, candy bars, oils and condiments, and french fries and chips. After adjusting for age, sex, physical activity, body mass index, smoking, total energy, and red meat and vegetable intake, there was a positive association between polyps and sweetened baked goods [350+ versus <50 kcal/day (odds ratio, 2.1; 95% confidence interval, 1.3-3.5)]. No association was found with the other food groups after adjustment for dietary and nondietary covariates. Neither was total dietary trans fatty acid associated with adenomas after adjustment for sweetened baked goods and other covariates. These results do not support the hypothesis that eating foods containing PHVOs increases the risk of colorectal adenomas, but they are consistent with the hypothesis that foods high in fat and sugar and low in fiber and correlated micronutrients increase the risk of adenomas.
Eur J Clin Invest 1999 Apr;29(4):301-8
Comment in: Eur J Clin Invest. 1999 Apr;29(4):271-3.
Delayed post-prandial lipid metabolism in subjects with intra-abdominal visceral fat accumulation.
Taira K, Hikita M, Kobayashi J, Bujo H, Takahashi K, Murano S, Morisaki N, Saito Y. Chiba University, Chiba 260-8670, Japan.
BACKGROUND: Individuals with obesity,
in particular those with intra-abdominal visceral fat accumulation, are
known to have various complications, such as hyperlipidaemia, impaired
glucose tolerance, hyperinsulinaemia and hypertension, leading to the
development of coronary heart disease. Post-prandial hyperlipidaemia has
repeatedly been shown to be an independent risk factor for coronary heart
disease. The aim of the present study was to investigate post-prandial
lipoprotein metabolism in subjects with excessive visceral fat accumulation.
Am J Clin Nutr 1994 Apr;59(4):853-60
Sucrose in a lipid-rich meal amplifies the postprandial excursion of serum and lipoprotein triglyceride and cholesterol concentrations by decreasing triglyceride clearance.
Grant KI, Marais MP, Dhansay MA. National Research Programme for Nutritional Intervention, South African Medical Research Council, Tygerberg.
Nineteen young male normolipidemic volunteers sequentially consumed three test meals consisting of cream only, sucrose only, or cream with sucrose. These oral fat-tolerance tests showed an amplification of the postprandial excursion of serum triglyceride and cholesterol concentrations when sucrose was included in a lipid-rich meal compared with both the cream-only meal and the sucrose-only meal. The triglyceride concentration increase occurred only in the late postprandial phase whereas the cholesterol concentration was increased for the entire 8 h studied. The increased triglyceride and cholesterol concentrations in the triglyceride-rich lipoprotein (TRL) fraction accounted for most of the increase. The clearance of an intravenous lipid emulsion was measured before and 2 and 4 h after a sucrose meal. The two postprandial clearance rates were 34% slower than the fasting value. These data indicate that sucrose-induced postprandial hypertriglyceridemia may be induced by an inhibition of the clearance of triglyceride. The slower rate of lipolysis may cause the accumulation of cholesterol in TRL.
Am J Clin Nutr 1996 Sep;64(3):361-7
Effect of dietary cholesterol on postprandial lipoproteins in three phenotypic groups.
Clifton PM, Nestel PJ. CSIRO, Division of Human Nutrition, Adelaide, South Australia.
Dietary cholesterol appears to be associated with long-term cardiovascular risk even after its potential for cholesterol elevation has been accounted for, but the mechanism is unknown. Our aim in this study was to determine the postprandial lipoprotein changes after a high-cholesterol load (equal to about three eggs) eaten with a low-fat meal by three phenotypic groups [normal, high low-density-lipoprotein (LDL)-cholesterol concentration, and high plasma triacylglycerol concentration] and compare them with the changes seen after a low-fat meal without cholesterol. Twenty-one normolipidemic and hyperlipidemic men and women were studied on two occasions after a single meal, one containing 19 g fat and 700 mg cholesterol, the other containing a similar amount of fat but no cholesterol. Their plasma intermediate-density lipoproteins (IDLs), LDLs, and high-density lipoproteins (HDLs) were separated by isopycnic ultracentrifugation. The addition of 700 mg cholesterol to the meal increased the amount of cholesterol and triacylglycerol in the large triacylglycerol-rich lipoproteins (Sf > 1000), particularly in the hypertriacylglycerolemic group (P = 0.02, fat meal compared with fat and cholesterol meal). In the hypertriacylglycerolemic group the normal fall in HDL cholesterol after a fat meal was reduced by 87% (P = 0.02, fat meal compared with fat and cholesterol meal). Both of these changes may be atherogenic. There was no increase in any candidate atherogenic particle (e.g., small very-low-density lipoprotein, IDL, or LDL) with the acute dietary cholesterol load. Thus, dietary cholesterol does not acutely alter postprandial lipoproteins to produce a more atherogenic profile except possibly in hypertriacylglycerolemic subjects.
J Appl Physiol 1998 Oct;85(4):1516-22
Effect of exercise timing on postprandial lipemia and HDL cholesterol subfractions.
Zhang JQ, Thomas TR, Ball SD. Exercise Physiology Laboratory, Department of Food Science and Human Nutrition, University of Missouri-Columbia, Columbia, Missouri 65212, USA.
The purpose of the study was to examine the effect of exercise timing on postprandial lipemia responses. Subjects were 21 recreationally trained men (ages 27 +/- 1.7 yr). Each subject performed four trials: 1) Control (fat meal only), 2) Post (exercise 1 h after a fat meal), 3) 1 h-Pre (exercise 1 h before a fat meal), and 4) 12 h-Pre (exercise 12 h before a fat meal). In each trial, subjects had a standard fat meal to induce postprandial hypertriglyceridemia. Blood samples were taken at 0 h (immediately before the fat meal) and at 2, 4, 6, 8, and 24 h after the meal. In the exercise trials, each subject exercised at 60% of maximal O2 consumption for 1 h. The results indicated that triglyceride area under the curve scores in premeal-exercise trials were lower (P < 0. 05) than those in Post and Control. At 24 h, total high-density lipoprotein (HDL)-cholesterol in the premeal-exercise trials was higher (P < 0.05) than that at 0 h, whereas total HDL-cholesterol was not changed in Control and Post. At 24 h, HDL subtype 2-cholesterol was higher (P < 0.05) in the premeal-exercise trials than in Control, which did not differ from Post. These results suggest that exercising before a fat meal may have a beneficial effect on the triglyceride response and HDL metabolism, which may blunt atherosclerotic process induced by the fat meal.
J Am Coll Cardiol 1999 Mar 15;33(4):1050-5
Impaired endothelial function following a meal rich in used cooking fat.
Williams MJ, Sutherland WH, McCormick MP, de Jong SA, Walker RJ, Wilkins GT. Department of Medicine, University of Otago, Dunedin, New Zealand. firstname.lastname@example.org
OBJECTIVES: The purpose of this
study was to test the hypothesis that intake of used cooking fat is associated
with impaired endothelial function.