The generation of reactive oxygen species (free radicals) is an important factor in the development and maintenance of rheumatoid arthritis in humans and animal models. One source of free radicals is nitric oxide produced within the synoviocytes and chondrocytes and giving rise to the highly toxic radical peroxynitrite. Several cytokines, including tumour necrosis factor-α (TNFα) are involved in the formation of free radicals, partly by increasing the activity of nitric oxide synthase. Indeed, nitric oxide may mediate some of the deleterious effects of cytokines on bone resorption. Aspirin, tetracyclines, steroids and methotrexate can suppress nitric oxide synthase. Dietary antioxidants include ascorbate and the tocopherols and beneficial effects of high doses have been reported especially in osteoarthritis. There is also evidence for beneficial effects of β-carotene and selenium, the latter being a component of the antioxidant enzyme glutathione peroxidase. The polyunsaturated fatty acids (PUFA) include the n-3 compounds, some of which are precursors of eicosanoid synthesis, and the n-6 group which can increase formation of the pro-inflammatory cytokines TNFα and interleukin-6, and of reactive oxygen species. Some prostaglandins, however, suppress cytokine formation, so that n-3 PUFA often oppose the inflammatory effects of some n-6-PUFA. γ-linolenic acid (GLA) is a precursor of prostaglandin E1, a fact which may account for its reported ability to ameliorate arthritic symptoms. Fish oil supplements, rich in n-3 PUFA such as eicosapentaenoic acid have been claimed as beneficial in rheumatoid arthritis, possibly by suppression of the immune system and its cytokine repertoire. Some other oils of marine origin (e.g. from the green-lipped mussel) and a range of vegetable oils (e.g. olive oil and evening primrose oil) have indirect anti-inflammatory actions, probably mediated via prostaglandin E1. Overall, there is a growing scientific rationale for the use of dietary supplements as adjuncts in the treatment of inflammatory disorders such as rheumatoid arthritis and osteoarthritis.

Food energy values used for nutrition labelling and other purposes are traditionally based on the metabolisable energy (ME) standard, which has recent support from Warwick & Baines (2000). By reference to current practices and published data, the present review critically examines the ME standard and support for it. Theoretical and experimental evidence on the validity of ME and alternatives are considered. ME and alternatives are applied to 1189 foods to assess outcomes. The potential impact of implementing a better standard in food labelling, documentation of energy requirements and food tables, and its impact on users including consumers, trade and professionals, are also examined. Since 1987 twenty-two expert reviews, reports and regulatory documents have fully or partly dropped the ME standard. The principal reason given is that ME only approximates energy supply by nutrients, particularly fermentable carbohydrates. ME has been replaced by net metabolisable energy (NME), which accounts for the efficiency of fuel utilisation in metabolism. Data collated from modern indirect calorimetry studies in human subjects show NME to be valid and applicable to each source of food energy, not just carbohydrates. NME is robust; two independent approaches give almost identical results (human calorimetry and calculation of free energy or net ATP yield) and these approaches are well supported by studies in animals. By contrast, the theoretical basis of ME is totally flawed. ME incompletely represents the energy balance equation, with substantial energy losses in a missing term. In using NME factors an account is made of frequent over-approximations by the ME system, up to 25 % of the NME for individual foods among 1189 foods in British tables, particularly low-energy-density traditional foods. A new simple general factor system is possible based on NME, yet the minimal experimental methodology is no more than that required for ME. By accounting for unavailable carbohydrate the new factor system appears as specific to foods as the USA's food-specific Atwater system, while it is more representative of energy supply from food components. The NME content of foods is readily calculable as the sum from fat (37 kJ/g), protein (13 kJ/g), available carbohydrate (16 kJ/g), fully-fermentable carbohydrate (8 kJ/g), alcohol (26 kJ/g) and other components. Obstacles to the implementation of NME appear to be subjective and minor. In conclusion, the ME standard is at best an approximate surrogate for NME, and inadequately approximates food energy values for the purpose of informing the consumer about the impact on energy balance of the energy supply for equal intake of individual foods. NME is superior to ME for nutrition labelling and other purposes.

The uridine (5′-)diphosphate-glucuronosyltransferases (UGT) are involved in the phase II of various xenobiotics and endogenous compounds. They are responsible for glucuronidation of many substrates, especially including bilirubin (UGT1A1) and phenolic compounds (UGT1A6). We previously showed that the expression of both isoforms is regulated at the transcriptional level by thyroid hormone in rat liver. In this present study, effects of vitamin A dietary intake (0, 1.72, 69 ug retinol acetate/g food) on the regulation of UGT1A1 and UGT1A6 activity and expression by 3,5,3′ triiodo-L-THYRONINE (l-T3) were examined in the same organ. Activities were determined toward bilirubin and 4-nitrophenol. UGT mRNA were analysed by reverse transcription and amplification methods (reverse transcription–polymerase chain reaction) and quantified by capillary electrophoresis. In rats fed a vitamin A-balanced diet, a single injection of l-T3 (500 μg/kg body weight) increased UGT1A6 mRNA expression whereas this hormone decreased UGT1A1 mRNA expression. In addition we observed that the specific effect of l-T3 on UGT1A1 and UGT1A6 was reduced in animals receiving a vitamin A-enriched diet and disappeared in those fed a vitamin A-free diet. The modulations observed in mRNA expression are concomitant with those found for UGT activities. Our results demonstrate for the first time the existence of a strong interaction between vitamin A and thyroid hormone on the regulation of genes encoding cellular detoxification enzymes, in this case the UGT.

The aim of the present study was to investigate the effects of photoperiod and feeding level on lipid metabolism in ovine perirenal and subcutaneous adipose tissues (AT) and in skeletal and cardiac muscles. Twenty dry non-pregnant ovariectomised ewes were divided into two groups and subjected to either 8 h or 16 h light/d, and underfed at 22 % energy requirements for 7 d. Half of the ewes in each group were slaughtered and the remaining ewes were refed at 190 % energy requirements for 14 d, until slaughtering. Refeeding increased (2.6–4.3-fold) malic enzyme (ME), fatty acid synthase (FAS), glucose-6-phosphate dehydrogenase (G6PDH) and glycerol-3-phosphate dehydrogenase (G3PDH) activities in subcutaneous AT as well as lipoprotein lipase (LPL) activity in perirenal (3.5-fold) and subcutaneous (10-fold) AT and to a lesser extent (1.4-fold) in the skeletal longissimus thoracis and cardiac muscles. Moreover, variations of LPL mRNA level followed variations of LPL activity: refeeding increased perirenal AT- and cardiac muscle-mRNA levels (7.4- and 2-fold respectively). The main finding of this study is that, for a given level of food intake, long days (compared with short days) increased the LPL activity in the longissimus thoracis muscle and, in refed ewes, the activities of LPL and ME in subcutaneous AT. Furthermore, long days increased LPL mRNA level in cardiac muscle and perirenal AT. Thus, our results show that there are direct effects of photoperiod on sheep AT lipogenic potential, as well as on muscle LPL activity, which are not caused by changes in nutrient availability.

The dose-dependent bone-sparing effects of dietary isoflavones (IF) were investigated in adult (7-month-old) Wistar rats. Forty animals were ovariectomised, allocated into four groups of ten rats each, and immediately treated orally with IF at 0 (OVX), 20 (IF20), 40 (IF40) or 80 (IF80) μg/g body weight per d for 91 d; ten sham-operated (SH) controls received the same diet without added IF. Animals were killed on day 91. Both femoral failure load and total femoral, diaphyseal or metaphyseal bone mineral densities (BMD) were lower in OVX animals than in SH animals. Urinary deoxypyridinoline (DPD) excretion, a marker of bone resorption, and plasma osteocalcin (OC) levels, a marker of osteoblast activity, were higher in OVX animals than in SH animals. Total femoral and diaphyseal BMD and femoral failure load were similar in IF-treated rats and SH rats. Although metaphyseal BMD in IF40 or IF80 rats was similar to that in SH rats, its value was lower in IF20 rats than in controls. The day 91 urinary DPD excretion in IF40 and IF80 rats, but not in IF20 rats, was similar to that in SH rats. Day 91 plasma OC concentrations in IF-treated rats were similar to day 45 values, but were decreased in OVX and SH rats. Thus, daily IF consumption prevented ovariectomy-induced bone loss, both by depressing bone resorption and stimulating osteoblast activity. Moreover, as only the highest IF level induced a weak uterotrophic activity, the optimal IF dose which preserves both cancellous and cortical bone, but exhibits no oestrogen-like effects on the uterus, was 40 μg/g body weight per d.

The present study investigated the digestion and cholesterol-lowering effects of the water-soluble NSP guar gum (GG) and sodium alginate (SA) in laboratory animals. Groups of five male Wistar strain rats were fed semi-purified cholesterol-free diets containing 0, 50 or 100 g NSP source/kg for 21 d which comprised a 14-d adaptation period followed by a 7-d balance period. Weight gain over the balance period and food conversion ratio decreased linearly with increasing NSP intake (P=0.006 and P=0.07 respectively). DM digestibility decreased with increasing NSP intake (P=0.001) and this effect was greater for SA-containing diets compared with GG-containing diets (P=0.001). At the lower inclusion rate, 0.9–1.0 of the additional NSP was digested, but this value fell to 0.8 for both NSP sources at the 100 g/kg inclusion rate, implying that the capacity for near complete digestion of the test NSP had been exceeded. Intestinal tissue mass was increased in response to inclusion of both NSP sources. Caecal digesta pH decreased linearly with additional GG, but increased slightly with consumption of SA. Total caecal short-chain fatty acid concentrations (μmol/g caecal contents) increased markedly with 50 g GG/kg but did not increase further with 100 g GG/kg, and were slightly lower than control values in rats consuming SA. Plasma cholesterol concentration fell linearly (P=0.03) with increasing NSP in the diet and the effect was similar for both GG and SA. Total output of faecal bile acids rose in rats fed 50 g GG/kg and 50 g SA/kg (59 μmol/7 d v. 24 μmol/7 d for control rats) with no further increase at the higher inclusion rate. These results show that SA has a strong hypocholesterolaemic effect in rats which is similar to that of GG, and that this effect is most likely to be mediated through an interruption in the entero-hepatic circulation of bile acids and not through increased hepatic supply of propionate from fermentation of the NSP in the large bowel.

The effects of an exogenous enzyme preparation, the application method and feed type on ruminal fermentation and microbial protein synthesis were investigated using the rumen simulation technique (Rusitec). Steam-rolled barley grain and chopped alfalfa hay were sprayed with water (control, C), an enzyme preparation with a predominant xylanase activity (EF), or autoclaved enzyme (AEF) 24 h prior to feeding, or the enzyme was supplied in the buffer infused into the Rusitec (EI). Microbial N incorporation was measured using (15NH4)2SO4 in the buffer. Spent feed bags were pummelled mechanically in buffer to segregate the feed particle-associated (FPA) and feed particle-bound (FPB) bacterial fractions. Enzymes applied to feed reduced neutral-detergent fibre content, and increased the concentration of reducing sugars in barley grain, but not alfalfa hay. Ruminal cellulolytic bacteria were more numerous with EF than with C. Disappearance of DM from barley grain was higher with EF than with C, but alfalfa was unaffected by EF. Treatment EF increased incorporation of 15N into FPA and FPB fractions at 24 and 48 h. In contrast, AEF reduced the 24 h values, relative to C; AEF and C were similar at 48 h. Infused enzyme (EI) did not affect 15N incorporation. Xylanase activity in effluent was increased by EF and EI, compared to C, but not by AEF. Xylanase activity in FPA was higher at 48 h than at 24 h with all treatments; it was higher with EF than C at 24 and 48 h, but was not altered by AEF or EI. Applying enzymes onto feeds before feeding was more effective than dosing directly into the artificial rumen for increasing ruminal fibrolytic activity.

The objective of the present study was to describe the intake of dietary fatty acids among healthy 15-year-old boys and girls and to relate the intake of specific fatty acids and the fatty acid composition of the serum cholesterol esters to serum lipid, apolipoprotein (Apo) and insulin concentrations respectively. Fifty-two girls and forty-two boys were randomly selected from the official population register. Unexpectedly, significant inverse associations were found between the dietary content of saturated fatty acids with a chain length of four to fifteen C atoms, mainly derived from milk fat, as well as the corresponding fatty acids in the serum cholesterol esters, on the one hand and the serum concentrations of cholesterol and ApoB on the other. The estimated dietary intake of 4:0–10:0, 12:0 and 14:0 respectively, were all significantly inversely related to the serum cholesterol (r -0.32, r -0.31, r -0.30, all P<0.05) and ApoB (r -0.42, r -0.42, and r -0.40, all P<0.05) concentrations in girls and 12:0 to the ApoB concentration (r -0.55, P<0.01) in boys. The proportions of 12:0 and 15:0 in the serum cholesterol esters were negatively correlated with the serum cholesterol concentrations in both girls (r -0.34, r -0.32, P<0.05) and boys (r -0.53, P<0.01; r -0.32, P<0.05) and with the ApoB concentrations among boys (r -0.61, P<0.01; r -0.43, P<0.05). It is conceivable that milk fat contains or is associated with some component in the diet, or some other characteristics of the food intake, which counterbalances the expected positive relationships between saturated fat intake and lipid levels.

The effect of dietary fibre on the gastric emptying rate of solids is controversial. Similarly, the mechanisms by which it modulates food intake are partially unknown. Gastric emptying and proximal v. distal stomach filling were evaluated in triplicate on four conscious pigs using scintigraphic imaging. Each animal received in an isoenergetic manner a concentrate low-fibre diet enriched in starch (S) and two high-fibre diets based on sugar beet pulp (BP) or wheat bran (WB). All meals had the same viscosity before ingestion (100.0–100.5 Pa.s). Viscosity of the gastric contents was measured in four additional animals fitted with a gastric cannula. The gastric emptying rate of BP diet was significantly slower than S and WB diets (t1/2 78.4 (SEM 5.68), 62.8 (sem 10.01) and 111.6 (sem 10.82) min for S, WB and BP diets respectively, P<0.05). For BP diet only, rate of distal stomach filling was steady during the first 120 min after the meal whereas that of S and WB diets decreased in an exponential manner. Numerous backflow episodes from the distal into the proximal stomach were observed for BP diet that generated the larger intragastric viscosity (0.26 (sem 0.03), 0.3 (sem 0.02) and 0.52 (sem 0.002) Pa.s for S, WB and BP respectively). In conclusion, viscosity of the meal or the percentage total fibre, unlike viscosity of the gastric contents, are poor predictors for emptying. The reduced emptying rate observed with BP is associated with major changes in intragastric distribution of the meal absent with WB and S diets.

The relationship between energy density (ED) of food and drink consumption ad libitum and energy intake (EI) was analysed. EI was taken as average daily EI over the long term, and as EI during a single meal. Moreover, the distribution of EI over three ED categories was analysed. Average daily EI was related to ED of the food and drinks when ED was strongly influenced by specific macronutrients. When ED was strongly influenced by the weight of water, it was not related to EI. During a meal subjects monitored mainly weight, and to a lesser extent, the energy content of the food ingested. Therefore, covertly manipulated ED of a meal affected EI directly. The impact of ED on EI was modulated by dietary behaviours such as restraint. Overt manipulation of ED for 6 months showed that EI was adjusted to a decreased but not to an increased ED in dietary-unrestrained subjects, and that EI was adjusted to an increased but not to a decreased ED in dietary-restrained subjects. Knowledge of ED was shown to lead to an inverse relationship between portion sizes and ED during a meal. Average daily EI consisted of a distribution of EI over the three different categories of ED, so that obese women ate more of foods with a high ED and less of foods with a low ED compared with normal weight women (and nutritional guidelines). In conclusion, ED affected daily EI by means of macronutrient specific effects. EI from a meal with an unknown ED can become inversely related to EI through learning or conditioning. Therefore, the effect of ED on EI during a single meal observation cannot be extrapolated directly to the 24 h effect on EI. With regard to the treatment of obesity, a conscious decreased consumption of foods high in ED and an increase in consumption of low-ED food is necessary to decrease and subsequently maintain body weight, particularly in subjects with a sedentary lifestyle.

Dietary pattern analysis has recently received growing attention, as it might be more appropriate in studies of diet–disease associations than the single food or nutrient approach that has dominated past epidemiological research. Factor analysis is a technique which is commonly used to identify dietary patterns within study populations. However, the ability of factor solutions to account for variance of food and nutrient intake has so far remained unclear. The present study therefore explored the statistical properties of dietary patterns with regard to the explained variance. Food intake of 8975 men and 13 379 women, assessed by a food-frequency questionnaire, was aggregated into forty-seven separate food groups. Dietary patterns were identified by principal component analysis and subsequent varimax rotation. Seven factors were retained for both men and women, which accounted for about 31 % of the total variance. The explained variance was relatively high (>40 %) for cooked vegetables, sauce, meat, dessert, cake, bread other than wholemeal, raw vegetables, processed meat, high-fat cheese, butter and margarine. Factor scores were used to investigate associations between the factors and nutrient intake. The patterns accounted for relatively large proportions of variance of energy and macronutrient intake, but for less variance of alcohol and micronutrient intake, especially of retinol, β-carotene, vitamin E, Ca and ascorbic acid. In addition, factors were related to age, BMI, physical activity, education, smoking and vitamin and mineral supplement use.

The purpose of the present study was to describe the longitudinal development of nutrient intake and to determine the stability of this intake from adolescence into adulthood. Longitudinal data of the Amsterdam Growth and Health Longitudinal Study were analysed; the dietary intake of 200 subjects (males and females) was repeatedly measured (eight times) over a period of 20 years, covering the age period of 13–33 years. Dietary intake was determined with the detailed crosscheck dietary history interview. With use of multivariate ANOVA for repeated measurements, trends in macro- and micronutrients over time and differences between genders were analysed. Furthermore, stability coefficients, corrected for time-dependent (biological age) and time-independent covariates (gender) were calculated, taking into account all the measurements. The results showed significant (P<0.001) time and gender effects for energy intake (kJ) and the following macronutrients: protein (g and % total energy supply), fat (g) and carbohydrate (g). Interaction effects between time and gender diminished when the macronutrients were calculated as a percentage of total energy intake. The micronutrients Ca, Fe and vitamins changed significantly (P<0.001) over time and showed an interaction effect with gender, with the exception of cholesterol intake (mg/MJ), which did not show an interaction effect of time and gender. The tracking of the nutrient intake showed relatively low but significant (P<0.05) stability coefficients for all macro- and micronutrients (0.28–0.52). In conclusion, dietary intake does change considerably over time, with the exception of polyunsaturated fat intake (% total energy supply) for both males and females and fat intake in females. Furthermore, stability coefficients for nutrients appeared to be low to moderate. Although these coefficients may be somewhat attenuated as a result of the relatively large measurement error of the dietary intake measurement, they suggest moderate stability of diet over time. These findings may imply that dietary intake is changeable and suggest that disease prevention measures can be implemented in adulthood.

Trans isomers of α-linolenic acid, which are formed by deodorization of refined vegetable oils, can be found in significant amounts in edible oils. Effects of trans α-linolenic acid on plasma lipoproteins are unknown. We therefore investigated the effects of trans α-linolenic acid on plasma lipids and lipoproteins in healthy European men. Eighty-eight healthy men from three European countries (France, Scotland, UK and the Netherlands) first consumed for 6 weeks a diet with experimental oils ‘free’ of trans fatty acids (run-in period). For the next 6 weeks, they were randomly allocated to a diet with experimental oils ‘high’ or ‘low’ in trans α-linolenic acid. Daily total trans α-linolenic acid intake in the high trans group was 1410 (range 583–2642) mg. Experimental oils were provided as such, or incorporated into margarines, cheeses, muffins and biscuits. The high trans α-linolenic acid diet significantly increased the plasma LDL-:HDL-cholesterol ratio by 8.1 % (95 % CI 1.4, 15.3; P=0.02), and the total cholesterol:HDL-cholesterol ratio by 5.1 % (95 % CI 0.4, 9.9; P=0.03) compared with the low-trans diet. This was largely explained by an increase in LDL-cholesterol on the high-trans diet, while no change was observed in the low-trans group (mean treatment effect of 4.7 % (95 % CI -0.8, 10.5; P=0.10). No effects were found on total cholesterol and HDL-cholesterol, triacylglycerols, apolipoprotein B and A-1, and lipoprotein(a) concentrations. In conclusion, trans α-linolenic acid may increase plasma LDL-:HDL-cholesterol and total cholesterol:HDL-cholesterol ratios. Whether diet-induced changes in these ratios truly affects the risk for CHD remains to be established.

The effect of carbohydrate, protein and fat ingestion on simple as well as complex cognitive functions and the relationship between the respective postprandial metabolic changes and changes in cognitive performance were studied in fifteen healthy male students. Subjects were tested in three sessions, separated by 1 week, for short-term changes in blood variables, indirect calorimetry, subjective performance and different objective performance tasks using a repeated-measures counterbalanced cross-over design. Measurements were made after an overnight fast before and hourly during 3 h after test meal ingestion. Test meals consisted of either pure carbohydrates, protein or fat and were served as isoenergetic (1670 kJ) spoonable creams with similar sensory properties. Most aspects of subjective performance did not differ between test meals. For all objective tasks, however, postprandial cognitive performance was best after fat ingestion concomitant with an almost constant glucose metabolism and constant metabolic activation state measured by glucagon:insulin (G:I). In contrast, carbohydrate as well as protein ingestion resulted in lower overall cognitive performance, both together with partly marked changes (P<0.001) in glucose metabolism and metabolic activation. They also differently affected specific cognitive functions (P<0.05) in relation to their specific effect on metabolism. Carbohydrate ingestion resulted in relatively better short-term memory and accuracy of tasks concomitant with low metabolic activation, whereas protein ingestion resulted in better attention and efficiency of tasks concomitant with higher metabolic activation. Our findings support the concept that good and stable cognitive performance is related to a balanced glucose metabolism and metabolic activation state.