Published Science

OBJECTIVE: The ketogenic diet is a high-fat, low-protein, low-carbohydrate diet developed in the 1920s for the treatment of children with difficult to control seizures. Despite advances in both the pharmacotherapy and the surgery of epilepsy, many children continue to have difficult-to-control seizures. This prospective study sought to determine the ketogenic diet's effectiveness and tolerability in children refractory to today's medications. METHODS: One hundred fifty consecutive children, ages 1 to 16 years, virtually all of whom continued to have more than two seizures per week despite adequate therapy with at least two anticonvulsant medications, were prospectively enrolled in this study, treated with the ketogenic diet, and followed for a minimum of 1 year. Seizure frequency was tabulated from patients' daily seizure calendars and seizure reduction calculated as percentage of baseline frequency. Adverse events and reasons for diet discontinuation were recorded. RESULTS: The children (mean age, 5.3 years), averaged 410 seizures per month before the diet, despite an exposure to a mean of 6.2 antiepileptic medications. Three months after diet initiation, 83% of those starting remained on the diet and 34% had >90% decrease in seizures. At 6 months, 71% still remained on the diet and 32% had a >90% decrease in seizures. At 1 year, 55% remained on the diet and 27% had a >90% decrease in seizure frequency. Most of those discontinuing the diet did so because it was either insufficiently effective or too restrictive. Seven percent stopped because of intercurrent illness. CONCLUSIONS: The ketogenic diet should be considered as alternative therapy for children with difficult-to-control seizures. It is more effective than many of the new anticonvulsant medications and is well tolerated by children and families when it is effective.

OBJECTIVE: To determine if introduction of a low carbohydrate diet might be a useful option for type 2 diabetic patients who do not achieve glucose target levels despite conventional treatment. METHODS: Subjects with type 2 diabetes, either treated with diet alone (n=9) or second generation sulfonylurea agents (n= 19), which were discontinued, were placed on a diet based on ideal body weight and comprised of 25% carbohydrate. After a mean of 8 weeks, they were then switched to a caloricly equivalent diet, but composed of 55% carbohydrate. RESULTS: Compared to baseline diet, after 8 weeks of a 25% diet, subjects showed significantly improved glycemia as evidenced by fasting blood glucose values (p<0.005) and hemoglobin A1c levels (p<0.05). Those previously treated with oral hypoglycemic agents showed, in addition, a significant decrease in weight and diastolic blood pressure despite the discontinuation of the oral agent. When then placed on a 55% carbohydrate diet, the hemoglobin A1c rose significantly over the ensuing next 12 weeks (p

OBJECTIVE: To determine the efficacy of the ketogenic diet in multiple centers. DESIGN: A prospective study of the change in frequency of seizures in 51 children with intractable seizures who were treated with the ketogenic diet. SETTING: Patients were enrolled from the clinical practices of 7 sites. The diet was initiated in-hospital and the patients were followed up for at least 6 months. PATIENTS: Fifty-one children, aged 1 to 8 years, with more than 10 seizures per week, whose electroencephalogram showed generalized epileptiform abnormalities or multifocal spikes, and who had failed results when taking at least 2 appropriate anti-epileptic drugs. INTERVENTION: The children were hospitalized, fasted, and a 4:1 ketogenic diet was initiated and maintained. MAIN OUTCOME MEASURES: Frequency of seizures was documented from parental calendars and efficacy was compared with prediet baseline after 3, 6, and 12 months. The children were categorized as free of seizures, greater than 90% reduction, 50% to 90% reduction, or lower than 50% reduction in frequency of seizures. RESULTS: Eighty-eight percent of all children initiating the diet remained on it at 3 months, 69% remained on it at 6 months, and 47% remained on it at 1 year. Three months after initiating the diet, frequency of seizures was decreased to greater than 50% in 54%. At 6 months, 28 (55%) of the 51 initiating the diet had at least a 50% decrease from baseline, and at 1 year, 40% of those starting the diet had a greater than 50% decrease in seizures. Five patients (10%) were free of seizures at 1 year. Age, sex, principal seizure type, and electroencephalogram were not statistically related to outcome. CONCLUSION: The ketogenic diet is effective in substantially decreasing difficult-to-control seizures and can successfully be administered in a wide variety of settings.

The incidence of certain ageing sequelae such as lung and cardiovascular disease and cataract are higher in smokers than in non-smokers. We recently proposed that certain components of mainstream cigarette smoke can react with plasma and extracellular matrix proteins to form covalent adducts with many of the properties of advanced glycation endproducts (AGE). AGEs have been implicated previously in the pathogenesis of the end-organ complications of diabetes and ageing, including cataract, atherosclerosis and renal insufficiency. In these circumstances, AGEs arise in vivo from the non-enzymatic reaction of reducing sugars with amino groups. Over time the initial Schiff base and Amadori products that form gradually undergo dehydration and rearrangement to produce reactive, carbonyl containing compounds with characteristic fluorescence and covalent crosslinking properties. Recent studies indicate that in smokers, tobacco-derived AGEs accumulate on plasma low density lipoprotein (LDL), structural proteins present within the vascular wall, and the lens proteins of the eye. These data point to a new and significant source of Maillard products in the human environment, significantly broaden the role of Maillard chemistry in pathological processes, and provide new insight into the pathogenesis of atherosclerosis and other diseases associated with tobacco usage.

A male-specific bacteriophage plaque assay was evaluated as a faecal contamination or process integrity indicator for aspects of the pork slaughter process. Over 400 samples were tested including: sponge swabs from animal hauling trailer floors and dressed carcass surfaces; faecal material; water from slaughter sites; and water from each stage of wastewater treatment. Bacteriophage were observed in wastewater, trailers, slaughter process water and swine faeces. No bacteriophage were observed on dressed carcasses. Numbers of phage plaque-forming units per gram or millilitre showed greater variation and were usually lower than standard indicators, including total coliform or Escherichia coli counts. Among the applications studied, male-specific bacteriophage appear to be best suited for process control verification for wastewater treatment.

Obesity, strongly associated with the risk for coronary heart disease (CHD), is becoming increasingly prevalent. This study was designed to establish first whether systemic arterial compliance (SAC), an index of arterial function, is improved with weight loss and second, whether cardiovascular risk factors that improve with weight loss are reduced equally with lean meat or with an equivalent amount of plant protein in the diet. Thirty-six women, mostly overweight or obese, aged 40+/-9 years, were allocated nonrandomly to a 16-week parallel-design trial of two equienergetic diets designed to lead to weight loss, with one arm of the study emphasizing red meat and the other soybeans as the major protein source. Body weight, waist and hip circumference, and plasma lipids, glucose, insulin, and leptin levels were measured, and SAC was calculated from ultrasound measurement of aortic flow velocity and aortic root driving pressure. Subjects lost weight (9% of body weight in 16 weeks) and showed decreased plasma total and low-density lipoprotein (LDL) cholesterol (12% and 14%, P < .0001, respectively), triacylglycerol (17%, P < .05), and leptin (24%, P < .01) concentrations. However, lipoprotein(a) [Lp(a)] levels did not change significantly. Mean arterial pressure (MAP) decreased 7% and SAC increased 28% (P < .001 for both). However, only the decrease in arterial pressure correlated significantly with the reduction in the waist to hip ratio (WHR), and the improvement in SAC correlated inversely with the blood pressure reduction (P

Urines from 25 normal subjects living in Rome and 25 normal subjects living in Ny-Alesund (Svaldbard) were analysed by 1HNMR spectroscopy. The observed differences in the concentration of the major metabolites were correlated to the composition of the diet. It was found that a diet rich of carbohydrates, such as the Italian diet, is responsible for an increased excretion of citrate, lactate, alanine, and glycine. Thus, a correct diagnostical interpretation of urinary metabolites needs to consider feeding habits.

Lipoproteins are able to bind to lipopolysaccharide (LPS) and neutralize its deleterious effects. However, it is not clear why the LPS-binding capacity of circulating lipoproteins, which is 10- to 10 000-fold above the maximal LPS concentrations found in septic patients, is not sufficient to inhibit the effects of LPS during an infection, whereas infusion of exogenous lipoproteins has a potent inhibitory action. In this study, the kinetics of LPS-neutralization by VLDL, LDL, and HDL were investigated, at lipoprotein-to-LPS ratios found in severe Gram-negative sepsis. At least 4-8-h preincubation of LPS with either LDL or HDL were necessary to inhibit 50% of the LPS-induced TNF-alpha production by human peripheral blood mononuclear cells (PBMC), whereas after 24 h of preincubation LDL or HDL strongly inhibited the TNF-alpha synthesis (70-90%, P

BACKGROUND: Several epidemiological studies have implicated hypercholesterolemia and hypertriglyceridaemia as a dietary risk factor in the etiology of vascular disease. To date, there are virtually no blood lipid data available for Negroid Black African Seventh-Day Adventist vegetarians. This study was undertaken to gain a preliminary and better understanding of the relationships between BP, blood lipids, and diets in adults at the Seventh-Day Adventist Seminary of West Africa, Ilisan-Remo, Nigeria. METHODS: Three randomly selected groups of the Nigerian populace with different dietary habits were investigated. The Seventh-Day Adventist Seminary of West Africa was the study area. Anthropometric measurements, blood pressure, serum cholesterol, triglycerides, and serum glucose were estimated using standard methods. FINDINGS: The vegetarians (VEGs) had significantly lower body weight 75.0 +/- 1.9 kg than the semi-vegetarians (SEMI-VEGs) 77.3 +/- 1.8 kg (p < 0.05). There was no significant difference between the blood pressure (BP) of the three groups studied, although the VEGs exhibited lower systolic BP. The VEGs had significantly lower serum total cholesterol and triglycerides (p

Background The congenital long-QT syndrome, caused by mutations in cardiac potassium-channel genes (KVLQT1 at the LQT1 locus and HERG at the LQT2 locus) and the sodium-channel gene (SCN5A at the LQT3 locus), has distinct repolarization patterns on electrocardiography, but it is not known whether the genotype influences the clinical course of the disease. Methods We determined the genotypes of 541 of 1378 members of 38 families enrolled in the International Long-QT Syndrome Registry: 112 had mutations at the LQT1 locus, 72 had mutations at the LQT2 locus, and 62 had mutations at the LQT3 locus. We determined the cumulative probability and lethality of cardiac events (syncope, aborted cardiac arrest, or sudden death) occurring from birth through the age of 40 years according to genotype in the 246 gene carriers and in all 1378 members of the families studied. Results The frequency of cardiac events was higher among subjects with mutations at the LQT1 locus (63 percent) or the LQT2 locus (46 percent) than among subjects with mutations at the LQT3 locus (18 percent) (P<0.001 for the comparison of all three groups). In a multivariate Cox analysis, the genotype and the QT interval corrected for heart rate were significant independent predictors of a first cardiac event. The cumulative mortality through the age of 40 among members of the three groups of families studied was similar; however, the likelihood of dying during a cardiac event was significantly higher (P

OBJECTIVE: The accuracy of the multiple-pass 24-hour recall method for estimating energy intake in low-income women in the United States was ascertained by comparing the method with measurements of total energy expenditure. The multiple-pass 24-hour recall is designed to provide respondents with multiple cues and opportunities to report their food intake. It consists of 3 distinct passes: the quick list, detailed description, and review. Predictors of energy intake misreporting (energy intake--total energy expenditure) in the sample were determined. DESIGN: Four multiple-pass 24-hour recalls (2 in person, 2 by telephone) were obtained over a 14-day period to estimate energy intake. Total energy expenditure was measured over the same 14-day period using the doubly labeled water method. Body composition was measured using dual energy x-ray absorptiometry, and literacy was measured by the Wide Range Achievement Test (WRAT) for reading and spelling. SUBJECTS/SETTINGS: Thirty-five low-income women between the ages of 19 and 46 years were tested at the General Clinical Research Center at the University of Vermont, Burlington. Low income was defined as a household income at or below 130% of the federal poverty level. STATISTICAL ANALYSIS: Pearson product moment correlation coefficients, t tests, paired t tests, and stepwise multiple regression analysis were used to test the relationships among study variables. RESULTS: Mean energy intake was significantly lower than mean total energy expenditure (2,197 +/- 607 vs 2,644 +/- 503 kcal, P = .001) and the correlation between the 2 measures was poor (r = .22, P = .20). Percentage body fat and the combined age-adjusted reading and spelling WRAT scores were the best predictors of misreporting of energy intake (R = .52, P = .006). CONCLUSIONS: The multiple-pass 24-hour recall did not generate a group measure of energy intake that was accurate or unbiased in this sample. Underreporting was strongly associated with increased body fatness. The ability to read and spell as measured by the WRAT improved the accuracy of the women's recall of their food intake. APPLICATIONS: Dietetics professionals should take into consideration the problem of underreporting whenever conclusions are made about associations between diet and health and/or when evaluating the impact of food assistance programs on dietary intake.

The aim of this study was to determine the effect of fatty acid intake and insulin dependent diabetes on the fatty acid composition of maternal erythrocytes, the placenta and cord. Fatty acid intake (from food frequency questionnaire) and the fatty acid composition of maternal erythrocytes, the placenta and cord from pregnant vegetarians (n = 4) and insulin dependent diabetics (n = 5) was compared with pregnant omnivores (n = 10). There was a significantly lower intake of n-6 long chain polyunsaturated fatty acid (LCPUFA) (-75% P < 0.01) and n-3 LCPUFA (-92% P < 0.01) and increased ratio of n-6/n-3 LCPUFA in the vegetarians (103%; P < 0.001). The concentrations of 22:4 n-6 (+28%; P < 0.05) and 22:5 n-3 (+40%; P < 0.05) were higher in vegetarian erythrocytes. Placental 18:2 n-6 (+26.9%; P < 0.05) 18:3 n-3 (+139%; P < 0.05) and 22:5 n-3 (+24%; P < 0.05) were increased while 20:5 n-3 (-36%; P < 0.05), 22:6 n-3 (-16%; P = 0.059), and the ratios of 20:4 n-6/18:2 n-6 (P < 0.01) and 22:6 n-3/18:3 n-3 were reduced. 22:6 n-6 (-49%; P < 0.05) and total n-3 LCPUFA (-11%; P < 0.01) were reduced in vegetarian cord. For the diabetic mothers, all of the n-6 LCPUFA and n-3 LCPUFA were reduced in the maternal erythrocytes; 22:4 n-6 (-42%; P < 0.05), 22:5 n-6 (-46%; P < 0.05) and 22:6 n-3 (-41%; P

By changes in nutrition it is possible to manipulate fat oxidation. It is often theorized that increasing fat oxidation may reduce glycogen breakdown and thus enhance performance. Therefore, the effects of acute, short-term and long-term fat feeding have been subjects of investigation for many years. Ingestion of long-chain triacylglycerols (LCT) during exercise may reduce the gastric emptying rate and LCT will appear in the plasma only slowly. Medium-chain triacylglycerols (MCT) do not have these disadvantages and they are rapidly oxidized. However, the contribution of MCT to energy expenditure is only small because they can only be ingested in small amounts without causing gastrointestinal distress. So at present, fat supplementation in the hours preceding to or during exercise (either long chain or medium chain triacylglycerols) cannot be recommended. High-fat diets and fasting have been suggested to increase fatty acid availability and spare muscle glycogen resulting in improved performance. Both fasting and short term high-fat diets will decrease muscle glycogen content and reduce fatigue resistance. Chronic high-fat diets may provoke adaptive responses preventing the decremental effects on exercise performance. However, at present, there is little evidence to support this hypothesis. Also from a health perspective, caution should be exercised when recommending high-fat diets to athletes.

Hunger may be delayed and food intake reduced under metabolic conditions that spare carbohydrate oxidation, especially during oxidation of medium-chain triacylglycerols (MCTs) or monounsaturated triacylglycerols. In 12 healthy, adult, male volunteers isolated and deprived of any time cues, we compared the effects of 4 high-carbohydrate breakfasts (1670 kJ) supplemented either with a fat substitute (Sub; 70 kJ) or with 1460 kJ fat as monounsaturated long-chain triacylglycerols (LCT-U), saturated long-chain triacylglycerols (LCT-S), or MCTs. In the first session we investigated the effects of these breakfasts on the following food intake variables: hunger ratings at repeated intervals, the time until the spontaneous request for the next 2 free-choice meals, and the amount of food consumed. In a second session with fixed lunches, we studied the effects of the same breakfasts on plasma glucose, insulin, triacylglycerol, fatty acid, and beta-hydroxybutyrate concentrations. The addition of any of the fats to the high-carbohydrate breakfasts did not alter hunger ratings, but significantly delayed the request for lunch compared with the low-fat breakfast. The free-choice lunch eaten after the MCT breakfast was also significantly smaller. Blood glucose and insulin concentrations were lower after the 3 fat breakfasts, followed by larger increases in glucose and enhanced insulin responses 30 min after the lunch. No differences were observed between the LCT-U and LCT-S conditions. We conclude that MCTs decreased food intake by a postabsorptive mechanism, although the exact effect of these lipids on carbohydrate oxidation will require further studies involving nutrient balance measurements.

This article deals with the question whether metabolic activity of neurons interferes with their survival during brain aging and Alzheimer's disease (AD). This 'use it or lose it' concept assumes that active neurons have a better chance to survive these conditions. We have monitored activity changes in human hypothalamic nuclei, that show differential survival patterns in aging and AD. The size of the Golgi apparatus (GA) was measured in e.g. the nucleus basalis of Meynert (NBM), that is severely affected in AD, and in the vasopressin (AVP) containing neurons of the supraoptic nucleus (SON) that remain very stable and show no cell loss. In the affected NBM, a strong reduction in activity was found in AD, whereas in the stable SON, an increased activity was present in both conditions. These findings agree with the concept that activation is associated with pronounced stability in aging and AD. Another hypothalamic nucleus is the biological clock (SCN), which is very sensitive to light input. It loses about 35% of its AVP cells in old rats. In order to test the hypothesis that extra stimulation prevents degeneration, the SCN in old rats was activated by means of an increased light input. This could indeed prevent the age-related loss of AVP-neurons in the SCN in low light conditions. Increased light also restored the age-related decreased amplitude in the sleep-wake rhythm. Furthermore, in AD patients, increased amounts of environmental light improved day-night rhythms and reduced behavioural disturbances. These observations are in line with the 'use it or lose it' concept. Furthermore, oxidative damage to the DNA was studied as a) it may accumulate during neuronal aging, and b) activated cells repair their DNA more efficiently. Whereas biochemical measurements of 8OHDG levels were not different in aging or AD, in situ end labeling, that detects fragmented DNA histologically, showed many positive neurons and glial cells in the AD, but not control, hippocampus, whereas in SON and PVN, hardly any damage was detected, which agrees with the 'use it or lose it' concept. Supported by related literature, we conclude that activation may be effective for neuronal maintenance during aging and in AD, and may provide a fruitful basis in the search for future treatment strategies in AD.

This part discusses the complex regulation of fat metabolism. Catecholamines as a stimulator of lipolysis and insulin as a suppressor play very important roles in the regulation of fat oxidation. The interaction of carbohydrate and fat metabolism has been extensively studied in the past decennia but the understanding of this multifactorial regulation is complex and still incompletely understood. In 1963, Randle et al. proposed the glucose-fatty acid cycle as a possible mechanism, and more recently, regulation through malonyl-CoA has been put forward as a possible way to explain shifts in carbohydrate and fat metabolism at rest and during exercise. The exercise intensity affects fat oxidation mainly by increasing lipolysis and fatty acid availability during exercise of low to moderate intensity. At high exercise intensities, both a reduction in fatty acid availability (decreased RaFa) and intramuscular factors reduce fat oxidation. These intramuscular factors are largely unknown. The increased mitochondrial density after training and increased oxidative enzymes may partly explain the increased fatty acid oxidation during exercise as observed after training. However, also supply of fatty acids to the mitochondria may be important. The available evidence suggests that the additional fatty acids oxidized after training are primarily derived from intramuscular triacylglycerols and not from adipose tissue derived fatty acids or circulating triacylglycerols.

BACKGROUND/AIMS: While the social significance of flatus derives mainly from its odour, previous studies have focused on the non-odoriferous components of rectal gas. The aims of the present study were to determine the role of sulphur-containing gases in flatus odour and test the efficacy of a device purported to reduce this odour. METHODS: Flatus was quantitatively collected via rectal tube from 16 healthy subjects who ingested pinto beans and lactulose to enhance flatus output. The concentrations of sulphur-containing gases in each passage were correlated with odour intensity assessed by two judges. Odour intensity was also determined after treatment of flatus samples with zinc acetate, which binds sulphydryl compounds (hydrogen sulphide and methanethiol), or activated charcoal. Utilising gastight Mylar pantaloons, the ability of a charcoal lined cushion to adsorb sulphur-containing gases instilled at the anus of eight subjects was assessed. RESULTS: The main sulphur-containing flatus component was hydrogen sulphide (1.06 (0.2) mumol/l), followed by methanethiol (0.21 (0.04) mumol/l) and dimethyl sulphide (0.08 (0.01) mumol/l) (means (SEM)). Malodour significantly correlated with hydrogen sulphide concentration (p

OBJECTIVE: To compare spinal bone mineral density (BMD) and 1-year BMD change between premenopausal vegetarian and nonvegetarian women. DESIGN: Cross-sectional comparison of spinal BMD at baseline and prospective comparison of a subsample. SETTING: A western Canadian metropolitan area. SUBJECTS/SAMPLES: Healthy vegetarian (n = 15 lacto-ovo-vegetarian, n = 8 vegan) and nonvegetarian (n = 22) women aged 20 to 40 years, with regular menstrual cycles and stable body weight completed baseline measurements. Twenty of these women (6 lacto-ovo-vegetarian, 5 vegan, 9 nonvegetarian) participated in repeat measurements at approximately 13 months. STATISTICAL ANALYSES PERFORMED: Descriptive statistics, independent sample and paired t tests, 1-way analysis of variance, correlation analysis, and stepwise multiple regression were used to compare groups and to assess associations with BMD. RESULTS: At baseline, subjects were 27.2 +/- 5.1 years old. Vegetarians had lower body mass index (21.1 +/- 2.3 vs 22.7 +/- 1.9, P < .05) and percent body fat (24.0 +/- 5.5% vs 27.4 +/- 5.1%, P

Malabsorption-maldigestion syndromes are commonly found in several gastrointestinal diseases. Quantitative measures of fecal nutrients are important tools for the detection and diagnosis of these syndromes. Adequate food intake is important in the nutrition of children, especially during the first year of life. We have analyzed 180 stools of healthy children, divided into four age groups, to obtain the reference intervals of the major nutrients such as water, fat, nitrogen, sugar, and starch. Quantification of the nutrients was done by means of a near-infrared analyzer (Fenir 8820). Results show that this instrument exhibits a low coefficient of variation for all the nutrients except for starch. Fecal water, fat, nitrogen, and sugar concentrations ranged from 68.7 to 96.1 g/100 g, 0 to 14.5 g/100 g, 1.3 to 2.3 g/100 g, and 0.7 to 3.8 g/100 g, respectively. The results for the starch analyses were not acceptable because of instrument limitations. Near-infrared reflectance spectroscopy appears to be an alternative to standard chemical methods.

OBJECTIVE: Dieting obese subjects are at risk of developing gallstones. A gallbladder motor dysfunction could have a pathogenetic role. The principal aim of this study was to evaluate the long term effects of two very low calorie diets differing in fat content on gallbladder emptying and gallstone formation in obese subjects. DESIGN AND SUBJECTS: Gallbladder emptying in response to meals (breakfast, lunch and dinner) in two different diet regimens (3.0 vs 12.2 g of fat/d) was evaluated by ultrasonography in 32 gallstone-free obese patients on different days, before and during (at 45 d intervals) one or two 6-month weight reduction diets (for the first three months: 2.24 MJ (535.2 kcal), 3.0 g fat/d vs 2.415 MJ (577.0 kcal), 12.2 g fat/d; for the second three months, the same low calorie diet of 4.194 MJ (1002 kcal)/d for both groups). In 10 subjects, bile analysis was also performed. RESULTS: Twenty-two (69%) subjects concluded the study, eleven in each group, and a significant weight loss was achieved by all subjects. Gallstones (asymptomatic) developed in 6/11 (54.5%) (P

OBJECTIVE: Dieting obese subjects are at risk of developing gallstones. A gallbladder motor dysfunction could have a pathogenetic role. The principal aim of this study was to evaluate the long term effects of two very low calorie diets differing in fat content on gallbladder emptying and gallstone formation in obese subjects. DESIGN AND SUBJECTS: Gallbladder emptying in response to meals (breakfast, lunch and dinner) in two different diet regimens (3.0 vs 12.2 g of fat/d) was evaluated by ultrasonography in 32 gallstone-free obese patients on different days, before and during (at 45 d intervals) one or two 6-month weight reduction diets (for the first three months: 2.24 MJ (535.2 kcal), 3.0 g fat/d vs 2.415 MJ (577.0 kcal), 12.2 g fat/d; for the second three months, the same low calorie diet of 4.194 MJ (1002 kcal)/d for both groups). In 10 subjects, bile analysis was also performed. RESULTS: Twenty-two (69%) subjects concluded the study, eleven in each group, and a significant weight loss was achieved by all subjects. Gallstones (asymptomatic) developed in 6/11 (54.5%) (P

A fat diet, rich in saturated fatty acids (SFA) and low in polyunsaturated fatty acids (PUFA), is said to be an important cause of atherosclerosis and cardiovascular diseases (CVD). The evidence for this hypothesis was sought by reviewing studies of the direct link between dietary fats and atherosclerotic vascular disease in human beings. The review included ecological, dynamic population, cross-sectional, cohort, and case-control studies, as well as controlled, randomized trials of the effect of fat reduction alone. The positive ecological correlations between national intakes of total fat (TF) and SFA and cardiovascular mortality found in earlier studies were absent or negative in the larger, more recent studies. Secular trends of national fat consumption and mortality from coronary heart disease (CHD) in 18-35 countries (four studies) during different time periods diverged from each other as often as they coincided. In cross-sectional studies of CHD and atherosclerosis, one group of studies (Bantu people vs. Caucasians) were supportive; six groups of studies (West Indians vs. Americans, Japanese, and Japanese migrants vs. Americans, Yemenite Jews vs. Yemenite migrants; Seminole and Pima Indians vs. Americans, Seven Countries) gave partly supportive, partly contradictive results; in seven groups of studies (Navajo Indians vs. Americans; pure vegetarians vs. lacto-ovo-vegetarians and non-vegetarians, Masai people vs. Americans, Asiatic Indians vs. non-Indians, north vs. south Indians, Indian migrants vs. British residents, Geographic Study of Atherosclerosis) the findings were contradictory. Among 21 cohort studies of CHD including 28 cohorts, CHD patients had eaten significantly more SFA in three cohorts and significantly less in one cohort than had CHD-free individuals; in 22 cohorts no significant difference was noted. In three cohorts, CHD patients had eaten significantly more PUFA, in 24 cohorts no significant difference was noted. In three of four cohort studies of atherosclerosis, the vascular changes were unassociated with SFA or PUFA; in one study they were inversely related to TF. No significant differences in fat intake were noted in six case-control studies of CVD patients and CVD-free controls; and neither total or CHD mortality were lowered in a meta-analysis of nine controlled, randomized dietary trials with substantial reductions of dietary fats, in six trials combined with addition of PUFA. The harmful effect of dietary SFA and the protective effect of dietary PUFA on atherosclerosis and CVD are questioned.

This is the first part in a series of three articles about fat metabolism during exercise. In this part the mobilization of fatty acids and their metabolism will be discussed as well as the possible limiting steps of fat oxidation. It is known for a long time that fatty acids are an important fuel for contracting muscle. After lipolysis, fatty acids from adipose tissue have to be transported through the blood to the muscle. Fatty acids derived from circulating TG may also be used as a fuel but are believed to be less important during exercise. In the muscle the IMTG stores may also provide fatty acids for oxidation after stimulation of hormone sensitive lipase. In the muscle cell, fatty acids will be transported by carrier proteins (FABP), and after activation, fatty acyl CoA have to cross the mitochondrial membrane through the carnitine palmytoyl transferase system, after which the acyl CoA will be degraded to acetyl CoA for oxidation. The two steps that are most likely to limit fat oxidation are fatty acid mobilization from adipose tissue and transport of fatty acids into the mitochondria along with mitochondrial density and the muscles capacity to oxidize fatty acids.

Previous studies in humans and animals have shown that the presence of lipid in the small intestine can reduce food intake. Studies that have combined intraduodenal lipid infusions with gastric distension produced a greater reduction in food intake than when these two stimuli were separated. In this study, subjects received duodenal lipid (Intralipid 20%) infusions for varying periods before and during the consumption of a liquid test meal. The aim of this procedure was to maximise the interaction between intestinal nutrient stimulation and gastric distension. A dose-dependent decrease in food intake was observed that corresponded to the duration of infusion; 90- (180 kcal) and 45-min (90 kcal) infusions but not 15-min (30 kcal) infusions significantly reduced intake compared to saline. These results show that concomitant intestinal nutrient stimulation and gastric distension is an effective test for the measurement of suppression of food intake by intestinal nutrients.

Lipoprotein lipase (LPL) is an adipocyte enzyme that cleaves fatty acids from circulating lipoproteins. Fatty acids enter the cell to be oxidized or esterified. Hormone-sensitive lipase (HSL) is an adipocyte enzyme that cleaves fatty acids from intracellular triacylglycerol. The HSL is activated by phosphorylation. Assays for the two lipases are complex because the hydrophobic substrate, triacylglycerol, must be presented as a gum-based suspension or as a detergent-based emulsion to a relatively hydrophilic enzyme. A convenient, stable glycerol/phospholipid suspension of the substrate was used for measurement of porcine adipose tissue LPL and HSL in vitro. This substrate was excellent for LPL. It produced rates five times those using a more complex and less convenient gum-based substrate suspension. The LPL activity was released by heparin, had a pH optimum of approximately 8.5, was activated by serum, and was inhibited by NaCl and protamine. This LPL assay measures enzyme capacity. The same substrate was used to measure an adipose tissue lipase activity that had a pH optimum below 7, was not activated by serum, and was not inhibited by NaCl or protamine. These are all characteristics of HSL. Despite the convenience, this substrate was not appropriate for porcine adipose tissue HSL because the rates were only 30 to 50% of those produced with a more complex, less convenient gum-based substrate suspension. Furthermore, incubation of enzyme or tissue slices with insulin, or agents that elevate cAMP concentration, did not modulate this lipase activity, as expected. These incubations poorly modulated LPL activity.

Lipoproteins can bind lipopolysaccharide (LPS) and decrease LPS-stimulated cytokine production. Lipoprotein(a) [Lp(a)] was as potent as low-density lipoproteins (LDL) in inhibiting LPS-stimulated tumor necrosis factor synthesis by human mononuclear cells. The kinetics of LPS inhibition by Lp(a) was similar to that of LDL. This suggests that circulating Lp(a) may be an important factor determining the amplitude of the response to LPS in humans.

This study compared vegetarian and non-vegetarian teenage English girls' attitudes towards meat. A convenience sample of 15 vegetarian (mean age 17.2 years) and 15 non-vegetarian (mean age 17.3 years) girls was recruited from a teenage health clinic. Attitudes towards meat were assessed in a single, tape-recorded, semi-structured interview. Eight themes of the cultural meaning of meat were identified; five were common to both groups: Animal (66% of vegetarians, 33% of non-vegetarians); Taste/Texture/Smell (66%, 60%); Flesh and Blood (86%, 26%); Colour (33%, 20%); Miscellaneous (60%, 46%). The theme Eating Well was unique to the non-vegetarian group (40%). The themes Life/Death and Health-related were unique to the vegetarian group (66 and 20%, respectively). The vegetarians generally abhorred killing animals for food, meat's sensory characteristics and ingesting blood. A meat-free diet was not particularly associated with health in either group. The non-vegetarians tended to characterize meat positively, both liking meat's sensory characteristics and associating meat with luxury and special occasions. We speculate on possible reasons for the current popularity of vegetarianism in teenage girls.

Compared with the limited capacity of the human body to store carbohydrate (CHO), endogenous fat depots are large and represent a vast source of fuel for exercise. However, fatty acid (FA) oxidation is limited, especially during intense exercise, and CHO remains the major fuel for oxidative metabolism. In the search for strategies to improve athletic performance, recent interest has focused on several nutritional procedures which may theoretically promote FA oxidation, attenuate the rate of muscle glycogen depletion and improve exercise capacity. In some individuals the ingestion of caffeine improves endurance capacity, but L-carnitine supplementation has no effect on either rates of FA oxidation, muscle glycogen utilisation or performance. Likewise, the ingestion of small amounts of medium-chain triglyceride (MCT) has no major effect on either fat metabolism or exercise performance. On the other hand, in endurance-trained individuals, substrate utilisation during submaximal [60% of peak oxygen uptake (VO2peak)] exercise can be altered substantially by the ingestion of a high fat (60 to 70% of energy intake), low CHO (15 to 20% of energy intake) diet for 7 to 10 days. Adaptation to such a diet, however, does not appear to alter the rate of working muscle glycogen utilisation during prolonged, moderate intensity exercise, nor consistently improve performance. At present, there is insufficient scientific evidence to recommend that athletes either ingest fat, in the form of MCTs, during exercise, or "fat-adapt" in the weeks prior to a major endurance event to improve athletic performance.

OBJECTIVE: To determine the effect of carbohydrate restriction on perinatal outcome in patients with diet-controlled gestational diabetes mellitus (GDM). METHODS: Women with diet-controlled GDM were divided non-randomly into two groups based on their dietary carbohydrate content: those with low dietary carbohydrate content (below 42%) and those with high dietary carbohydrate content (exceeding 45%). Subjects kept dietary accounts and were followed with daily fasting and postprandial glucose assessments. Subjects also were tested daily for urinary ketones. Glycosylated hemoglobin, mean fasting and postprandial glucose values, incidence of macrosomia and large for gestational age (LGA) infants, cesarean deliveries for cephalopelvic disproportion and macrosomia, and need for insulin therapy were compared between the groups. RESULTS: The two groups were identical in terms of demographic characteristics. Significant reductions in the postprandial glucose values were seen among subjects in the low-carbohydrate group (P < .04). Fewer subjects in the low-carbohydrate group required the addition of insulin for glucose control (P < .047; relative risk [RR] 0.14; 95% confidence interval [CI] 0.02, 1.00). The incidence of LGA infants was significantly lower in the low-carbohydrate group (P < .035; RR 0.22; 95% CI 0.05, 0.91). Subjects in the low carbohydrate group also had a lower rate of cesarean deliveries for cephalopelvic disproportion and macrosomia (P

We estimated phylogenetic relationships among 12 species or variants of the cestode genus Taenia, including all 3 species that typically use humans as the definitive host, using published sequences of cytochrome c oxidase subunit I (COI) and 28s rDNA. Analyses of all the data combined using maximum parsimony, neighbor-joining, and maximum likelihood methods give well resolved trees. The trees are similar regardless of the analytical method used. Most of the phylogenetically informative characters are contained in the COI sequence, and trees obtained from analyses of COI alone are similar to the combined data trees. All of the phylogeny estimates suggest that Taenia tapeworms have switched from carnivore definitive hosts to human definitive hosts twice in their history. This result is also supported by bootstrap analyses using all 3 of the above methods of phylogeny estimation.

CONCLUSIONS: Twenty-four-hour urinary 3-MH excretion can be applied for estimating SM in healthy adult men on a meat-free diet.

The percentage of energy from dietary fat is widely believed to be an important determinant of body fat, and several mechanisms have been proposed to account for such a relation. Comparisons of both diets and the prevalence of obesity between affluent and poor countries have been used to support a causal association, but these contrasts are seriously confounded by differences in physical activity and food availability. Within areas of similar economic development, regional intake of fat and prevalence of obesity have not been positively correlated. Randomized trials are the preferable method to evaluate the effect of dietary fat on adiposity, and are feasible because the number of subjects needed is not large. In short-term trials, a modest reduction in body weight is typically seen in individuals randomly assigned to diets with a lower percentage of energy from fat. However, compensatory mechanisms appear to operate because in trials lasting > or = 1 y, fat consumption within the range of 18-40% of energy appears to have little if any effect on body fatness. Moreover, within the United States, a substantial decline in the percentage of energy from fat consumed during the past two decades has corresponded with a massive increase in obesity. Diets high in fat do not appear to be the primary cause of the high prevalence of excess body fat in our society, and reductions in fat will not be a solution.;

We tested the effects of an uncooked vegan diet, rich in lactobacilli, in rheumatoid patients randomized into diet and control groups. The intervention group experienced subjective relief of rheumatic symptoms during intervention. A return to an omnivorous diet aggravated symptoms. Half of the patients experienced adverse effects (nausea, diarrhoea) during the diet and stopped the experiment prematurely. Indicators of rheumatic disease activity did not differ statistically between groups. The positive subjective effect experienced by the patients was not discernible in the more objective measures of disease activity (Health Assessment Questionnaire, duration of morning stiffness, pain at rest and pain on movement). However, a composite index showed a higher number of patients with 3-5 improved disease activity measures in the intervention group. Stepwise regression analysis associated a decrease in the disease activity (measured as change in the Disease Activity Score, DAS) with lactobacilli-rich and chlorophyll-rich drinks, increase in fibre intake, and no need for gold, methotrexate or steroid medication (R2=0.48, P=0.02). The results showed that an uncooked vegan diet, rich in lactobacilli, decreased subjective symptoms of rheumatoid arthritis. Large amounts of living lactobacilli consumed daily may also have positive effects on objective measures of rheumatoid arthritis.

During endurance exercise, skeletal muscle relies mainly on both carbohydrate (CHO) and fat oxidation to cover energy needs. Numerous scientific studies have shown that increasing the exercise intensity leads to a progressive utilization of CHO. The latter will induce a state of glycogen depletion which is generally recognized as being a limiting factor for the continuation of strenuous exercise. Different dietary interventions have been proposed to overcome this limitation. A high-CHO diet during periods of intense training and competition, as well as CHO intake during exercise, are known to maintain a high rate of CHO oxidation and to delay fatigue. However, it has been recognized also that enhancing fatty acid (FA) oxidation during exercise induces a reduced rate of glycogen degradation, resulting in an improved endurance capacity. This is most strikingly observed as a result of frequent endurance exercise which improves a number of factors known to govern the FA flux and the oxidative capacity of skeletal muscle. Such factors are: (1) blood flow and capillarization; (2) lipolysis of triacylglycerol (TAG) in adipose tissue and circulating TAG and transport of FA from blood plasma to the sarcoplasm; (3) availability and rate of hydrolysis of intramuscular TAG; (4) activation of the FA and transport across the mitochondrial membrane; (5) the activity of enzymes in the oxidative pathway; (6) hormonal adaptations, i.e. sensitivity to catecholamines and insulin. The observation that the plasma FA concentration is an important factor in determining the rate of FA oxidation, and that some dietary factors may influence the rate of FA supply to muscle as well as to the mitochondria, has led to a number of dietary interventions with the ultimate goal to enhance FA oxidation and endurance performance. It appears that experimental data are not equivocal that dietary interventions, such as a high-fat diet, medium-chain TAG-fat emulsions and caffeine intake during exercise, as well as L-carnitine supplementation, do significantly enhance FA oxidation during exercise. So far, only regular endurance exercise can be classified as successful in achieving adaptations which enhance FA mobilization and oxidation.

Fasting samples of 1329 apparently healthy vegetarian Gujarati population were tested for total cholesterol, triglycerides and three major fractions of lipoproteins, i.e. high density lipoproteins, low density lipoproteins and very low density lipoproteins. All the values showed marked increase with the age. Except for serum triglycerides, values differ in males and females in the age group of above 45 years. Compared to Northern Indian population low density lipoprotein and high density lipoprotein values were higher, but values of triglycerides and very low density lipoproteins were lower. There is no significant difference in total cholesterol values. Compared to Southern Indian population low density lipoprotein and very low density lipoprotein values were higher but values of triglycerides, total cholesterol and high density lipoprotein were lower. All serum lipid values were significantly lower than the Westem population. The range of values for both the sexes is presented for different age groups.

The effects on mood of reducing dietary fat while keeping the energy constant were examined in ten male and ten female healthy volunteers aged between 20 and 37 years. Each volunteer consumed a diet containing 41% energy as fat for 1 month. For the second month half of the subjects changed to a low-fat diet (25% energy from fat) and the remainder continued to eat the diet containing 41% energy from fat. Changes in mood and blood lipid concentrations were assessed before, during and at the end of the study. Profile of mood states (POMS) ratings of anger-hostility significantly increased in the intervention group after 1 month on the low-fat diet, while during the same period there was a slight decline in anger-hostility in the control subjects (group F 6.72; df 1.14; P = 0.021). Tension-anxiety ratings declined in the control group consuming the higher fat diet but did not change in the group consuming the low-fat diet (group F 6.34; df 1.14; P = 0.025). There was a decline in fasting concentrations of HDL-cholesterol after the low-fat diet and a small increase in subjects consuming the medium-fat diet (group F 4.96; df 1.12; P = 0.046), but no significant changes in concentrations of total serum cholesterol, LDL-cholesterol or triacylglycerol were observed. The results suggest that a change in dietary fat content from 41 to 25% energy may have adverse effects on mood. The alterations in mood appear to be unrelated to changes in fasting plasma cholesterol concentrations.

OBJECTIVE: Sulfide, a product of sulfate-reducing bacteria, has been proposed to play an etiologic role in ulcerative colitis. Ulcerative colitis feces have increased numbers and activity of sulfate-reducing bacteria, but only modestly increased sulfide. However, fecal sulfide exists largely in the volatile, highly toxic H2S form that moves rapidly from feces to surrounding gas. Our aim was to quantify the fecal release of H2S and other volatiles (CO2, H2, CH4, methanethiol, and dimethylsulfide). METHODS: Fecal samples from 25 subjects with ulcerative colitis and 17 controls were incubated in 4-L containers, and gas release was assessed at intervals over 24 h. RESULTS: H2S release by ulcerative colitis feces was elevated 3-4-fold at every measurement point compared with normal feces (p

Carbohydrate (CHO) ingestion during exercise, in the form of CHO-electrolyte beverages, leads to performance benefits during prolonged submaximal and variable intensity exercise. However, the mechanism underlying this ergogenic effect is less clear. Euglycaemia and oxidation of blood glucose at high rates late in exercise and a decreased rate of muscle glycogen utilisation (i.e. glycogen 'sparing') have been proposed as possible mechanisms underlying the ergogenic effect of CHO ingestion. The prevalence of one or the other mechanism depends on factors such as the type and intensity of exercise, amount, type and timing of CHO ingestion, and pre-exercise nutritional and training status of study participants. The type and intensity of exercise and the effect of these on blood glucose, plasma insulin and catecholamine levels, may play a major role in determining the rate of muscle glycogen utilisation when CHO is ingested during exercise. The ingestion of CHO (except fructose) at a rate of > 45 g/h, accompanied by a significant increase in plasma insulin levels, could lead to decreased muscle glycogen utilisation (particularly in type I fibres) during exercise. Endurance training and alterations in pre-exercise muscle glycogen levels do not seem to affect exogenous glucose oxidation during submaximal exercise. Thus, at least during low intensity or intermittent exercise, CHO ingestion could result in reduced muscle glycogen utilisation in well trained individuals with high resting muscle glycogen levels. Further research needs to concentrate on factors that regulate glucose uptake and energy metabolism in different types of muscle fibres during exercise with and without CHO ingestion.

OBJECTIVE: To evaluate the efficacy and metabolic impact of a high-protein, low-carbohydrate, low-fat ketogenic diet (K diet) in the treatment of morbidly obese adolescents with initial weights of >200% of ideal body weight. METHODS: Six adolescents, aged 12 to 15 years, weighing an average of 147.8 kg (range, 120.6-198.6 kg) and having an average body mass index of 50.9 kg/m (39.8-63.0 kg/m), consumed the K diet for 8 weeks. Daily intake consisted of 650 to 725 calories, which was substantively in the form of protein (80-100 g). The diet was very low in carbohydrates (25 g) and fat (25 g). This was followed by 12 weeks of the K diet plus two carbohydrates (30 g) per meal (K+2 diet). MAIN OUTCOME MEASURES: Anthropometric data and blood and urine were collected at enrollment, during week 1, and at 4-week intervals throughout the course of the study. Resting energy expenditure was measured by indirect calorimetry. Body composition was estimated using dual-energy x-ray absorptiometry, bioelectrical impedance analysis, and urinary creatinine excretion at enrollment and on completion of each phase of the diet. Nocturnal polysomnography and multiple sleep latency testing were conducted at baseline and repeated after an average weight loss of 18.7 kg to determine sleep architecture, frequency and duration of apneas, and daytime sleepiness. RESULTS: Subjects lost 15.4 +/- 1.4 kg (mean +/- SEM) during the K diet and an additional 2.3 +/- 2.9 kg during the K+2 diet. Body mass index decreased 5.6 +/- 0.6 kg/m(2) during the K diet and an additional 1.1 +/- 1.1 kg/m(2) during the K+2 diet. Body composition studies indicated that weight was lost equally from all areas of the body and was predominantly fat. Dual-energy x-ray absorptiometry showed a decrease from 51.1% +/- 2.1% body fat to 44.2% +/- 2.9% during the K diet and then to 41.6% +/- 4.5% during the K+2 diet. Lean body mass was not significantly affected. Weight loss was accompanied by a reduction in resting energy expenditure of 5.2 +/- 1.8 kcal/kg of fat-free mass per day. Blood chemistries remained normal throughout the study and included a decrease in serum cholesterol from 162 +/- 12 to 121 +/- 8 mg/dL in the initial 4 weeks of the K diet. An increase in calcium excretion was accompanied by a decrease in total-body bone mineral content. A paucity of rapid eye movement sleep and excessive slow-wave sleep were seen in all subjects at enrollment. Weight loss led to an increase in rapid eye movement sleep (P < .02) and a decrease in slow-wave sleep (P

ANIMAL FAT AND CHOLESTEROL MAY HAVE HELPED PRIMITIVE MAN EVOLVE A LARGE BRAIN FRANK D. MANN* In 1962, James V. Neel published a paper entitled "Diabetes Mellitus: A 'Thrifty' Genotype Rendered Detrimental by 'Progress'?" [I]; 20 years later, Neel revisited his theory, suggesting appropriate revisions because of significant additions to our knowledge of diabetes. During the intervening period, just as predicted by Neel's theory, a high frequency of diabetes was observed in populations emerging from the sparse diet of a primitive economy into the "progress" of a developed economy [2]. A prominent example of such a population, the Pima Indian tribe, has been and continues to be thoroughly studied [3]. Neel himself carried out a difficult field investigation of two South American tribes, showing that, in accordance with his theory, they were not diabetic while remaining in a primitive state [2]. An interest of many years' duration in Neel's original concept of a "thrifty" genotype led me to consider the possibility of an analogous case of a heritage now detrimental but originally advantageous. Overproduction of cholesterol, associated with consumption of animal fat but probably also with evolutionary changes in hepatic physiology, may have been helpful in meeting increased need for cholesterol in the evolution of the large brain of modern humans. I shall present an analysis of evidence for this hypothLeakey 's Reasoning: A Rich Meat Diet was Required for the Large Human Brain Leakey has been led by his reading of the anthropological language of fossil teeth and skulls to an unequivocal judgment of the importance of a meat diet [4]. Leakey does not attempt to evaluate the individual nutritional components of the meat diet, but considers a nutritionally richer diet to *5316 E. Roadrunner Road, Scottsdale, AZ 83253.© 1998 by The University of Chicago. All rights reserved. 0031-5982/98/4103-1060$01.00 Perspectives in Biology and Medicine, 41, 3 ¦ Spring 1998 | 417 be necessary for the maintenance of the metabolically expensive large brain. The modern human brain surely is metabolically expensive, requiring 20 percent of the total resting oxygen consumption of the body, although it is only 2 percent of the body weight [5]. Chamberlain also considers the meat diet to be important and focuses on the essential fatty acids. While noting that these substances are present in vegetable sources, he suggests that the ample supply of the essential as well as other unsaturated fatty acids in meat could have conferred a survival advantage, a three-fold increase in the size of the human brain within 3 million years of evolution [6]. To obtain meat as the principal constituent of diet, primitive man would have had to compete with animals such as cats, which had already evolved formidable built-in equipment for killing: fangs and claws. Rapid evolution of a large brain was needed in this deadly competition. A diet rich in animal fat would have markedly increased the intake and hepatic synthesis of cholesterol. Would this have helped the development of the large brain? Evidence regarding the functions of cholesterol and the mechanisms of the supply and distribution is pertinent to this hypothesis. Cholesterol and Membranes Cholesterol has long been known to be an essential constituent of cell membranes and has been reported to comprise, on a molecular basis, half of the lipid content of the external cell membrane [7]. Myelinated nerve fibers make up a large part of the total mass of the brain. Their highly specialized covering membranes contain a large quantity of various lipids. Thus, early biochemists found brain to be a convenient source material from which to prepare cholesterol. Fielding has described the complex mechanism of transporters and receptors which have evolved to assure that all membranes have the appropriate individual content of free cholesterol [8]. Tight regulation of the very different amounts of free cholesterol in different membranes is necessary for various vital functions performed by structures located in the membranes . These include the ion pumps necessary for the life ofevery cell, and adenylate cyclase, which is required for the cell to respond to transmitter substances such as norepinephrine. Schroeder and colleagues have recently reviewed the evidence that highly asymmetric distributions of free cholesterol, within the membranes themselves...

A diet including 2-3 portions of fatty fish per week, which corresponds to the intake of 1.25 g EPA (20:5n-3) + DHA (22:6n-3) per day, has been officially recommended on the basis of epidemiological findings showing a beneficial role of these n-3 long-chain PUFA in the prevention of cardiovascular and inflammatory diseases. The parent fatty acid ALA (18:3n-3), found in vegetable oils such as flaxseed or rapeseed oil, is used by the human organism partly as a source of energy, partly as a precursor of the metabolites, but the degree of conversion appears to be unreliable and restricted. More specifically, most studies in humans have shown that whereas a certain, though restricted, conversion of high doses of ALA to EPA occurs, conversion to DHA is severely restricted. The use of ALA labelled with radioisotopes suggested that with a background diet high in saturated fat conversion to long-chain metabolites is approximately 6% for EPA and 3.8% for DHA. With a diet rich in n-6 PUFA, conversion is reduced by 40 to 50%. It is thus reasonable to observe an n-6/n-3 PUFA ratio not exceeding 4-6. Restricted conversion to DHA may be critical since evidence has been increasing that this long-chain metabolite has an autonomous function, e.g. in the brain, retina and spermatozoa where it is the most prominent fatty acid. In neonates deficiency is associated with visual impairment, abnormalities in the electroretinogram and delayed cognitive development. In adults the potential role of DHA in neurological function still needs to be investigated in depth. Regarding cardiovascular risk factors DHA has been shown to reduce triglyceride concentrations. These findings indicate that future attention will have to focus on the adequate provision of DHA which can reliably be achieved only with the supply of the preformed long-chain metabolite.