Beta-glucan- or rice bran-enriched foods: a comparative crossover clinical trial on lipidic pattern in mildly hypercholesterolemic men.

BACKGROUND/OBJECTIVES: There has been growing interest in using dietary intervention to improve the lipid profile. This work aims at analyzing the effects and the comparison of the enrichment of a diet with beta-glucans or rice bran in mildly hypercholesterolemic men. SUBJECTS/METHODS: The subjects initially consumed a 3-week Step 1 American Heart Association diet with rice bran-enriched foods. After this adaptation period, volunteers were randomly assigned to follow a crossover, controlled trial that consisted of two treatment with beta-glucan- or rice bran-enriched foods, each of 4 weeks, with a 3-week wash-out, like the adaptation period, between periods. Fasted blood samples were collected on days 0, 21, 49, 70 and 98 in both study arms for measuring low-density lipoprotein (LDL)-cholesterol (primary outcome), total cholesterol, high-density lipoprotein (HDL)-cholesterol, triglycerides, apolipoprotein (apo) A-I, apo B and glucose levels. RESULTS: Twenty-four men (mean age: 50.3±5.3, mean body mass index: 24.9±1.9) completed the 14-week trial. Subjects in the 3-week adaptation period experienced significant reductions in the mean level of LDL cholesterol, total cholesterol, total cholesterol/HDL cholesterol, LDL cholesterol/HDL cholesterol, apo A-I, apo A-I/apo B and glucose. During the intervention diet periods, a difference was found between treatment groups for the mean change in LDL (0.21 (95% confidence interval (CI): 0.02-0.40), P=0.033) and total cholesterol (0.34 (95% CI: 0.20-0.47), P<0.001). Other parameters evaluated were not significantly affected by the diet consumed. CONCLUSIONS: The results of the present crossover clinical trial showed that beta-glucan-enriched foods are more effective in lowering serum LDL levels, compared with rice bran-enriched foods.

Increased lipid peroxidation in adult GH-deficient patients: effects of short-term GH administration.

OBJECTIVE: Adult GH deficiency (GHD) syndrome is characterized by increased risk of atherosclerosis and hence of cardio- and cerebrovascular mortality. Oxidative stress appears to play an important role in early atherogenesis. Oxidized LDL represents an important predictor of cardiovascular risk and is mainly responsible for oxidative damage of the endothelium. Its concentrations are increased in GHD, but the association between this abnormality and oxidative stress is still unclear, due to the discordant results yielded by the few available studies. DESIGN AND METHODS: In 13 GHD patients, plasma lipid peroxide concentrations were measured before and after a 4-month treatment with recombinant human GH (rhGH) and compared with those of 13 age- and sex-matched controls. In the same subjects, the so-called "lag-time", an index of anti-oxidant activity and thus of plasma oxidative balance, was also measured using a fluorescence kinetics method. RESULTS: Before treatment, peroxide levels were significantly higher in patients than in controls (374.0+/-31.52 vs 268.0+/-8.51 U.C., p<0.01), whereas the lag-time was significantly lower (113.0+/-10.70 vs 168.0+/-7.80 min, p<0.01). RhGH administration to patients resulted both in a significant decrease in lipid peroxide levels (from 374.0+/-31.52 to 336.0+/-33.17 U.C., p<0.01) and a significant prolongation of lag-time (from 113.0+/-10.70 to 144.0+/-15.00 min, p<0.01). After treatment, both parameters were no longer significantly different in patients and controls. Lag-time and peroxide levels at baseline did not show any correlation with IGF-I concentrations in GHD patients. After replacement therapy, however, lag-time was positively (r2= 0.62, p<0.01), and peroxide levels negatively (r2=0.41, p<0.05), correlated with IGF-I levels. CONCLUSIONS: These data support the view that adult GHD syndrome is characterized by an unbalance between pro- and anti-oxidant factors with marked preponderance of the former. This abnormality, likely contributing to the increased atherogenic risk of GHD patients, is corrected by short-term GH administration at a dose able to increase, although not to fully normalize, IGF-I levels.

Hydrolyzed milk-serum peptides reduce body weight and fat content of dietary obese rats ameliorating their antioxidant status and liver functions.

AIM: Recent studies suggested that weight reduction under energy restriction required protein supplementation. Moreover, a significant decrease in serum cholesterol and triglycerides was observed when milk-serum proteins and, in particular, their hydrolyzed peptides were compared to milk casein. METHODS: Six Sprague-Dawley rats were fed with the standard diet for 8 weeks. Eighteen rats were fed with the obesity- producing diet for 4 weeks. After this period and for the remaining 4 weeks, these rats were divided into 3 groups, the 1st was fed with the obesity-diet, the 2nd and the 3rd were fed with the casein--and with the hydrolyzed milk-serum peptides--restricted diet, respectively. RESULTS: Treatment with the obesity-diet, compared to standard-diet, induced an increase in the body weight and fat content, with a decrease in protein mass and dehydration state. There was also an increase in blood levels of cholesterol, triglycerides and glucose. The lipoperoxides content in the plasma, heart, brain and liver had also increased, while the content of glutathione and ATP and the membrane fluidity in the liver had significantly decreased. The administration of the restricted caloric diet, in particular the one containing the hydrolyzed peptides were capable of an improvement of all these parameters. CONCLUSIONS: The metabolic modifications induced by the hydrolyzed peptides-restricted diet contribute to control better the over-weight thus reducing the risk of the onset of the dismetabolic pathologies correlated to it.

Erythrocyte membrane alterations during ageing affect beta-D-glucuronidase and neutral sialidase in elderly healthy subjects.

In this study, a comparison between elderly (>70 years) and young subjects reveals that elder people are subject to a higher oxidative stress, which causes an increase in plasma hydroperoxide levels (18%) and a decrease in antioxidant defenses (25%). Moreover, the marked decrease of the erythrocyte membrane fluidity observed in elderly subjects was likely to affect the behavior of some membrane glycohydrolases. In fact, a significant decrease of beta-d-glucuronidase and neutral sialidase (30 and 50%, respectively) was detected. Activity differences were also observed when erythrocytes were further distinguished according to their biological age. Striking differences between young and elderly subjects were observed for beta-d-glucuronidase and neutral sialidase in young and senescent erythrocytes, respectively. Overall beta-d-glucuronidase decreases with the subjects' age, while neutral sialidase levels are higher in the elderly. This is presumably due to the localization of these enzymes in distinct plasma membrane micro-domains, which are differently peroxidized. A possible role of these enzymes in signaling praecox membrane alterations has also been evidenced.

Biochemical assessments of oxidative stress, erythrocyte membrane fluidity and antioxidant status in professional soccer players and sedentary controls.

BACKGROUND: Physical exercise is characterized by an increase in oxygen consumption by the whole body. This leads to a decrease in antioxidant levels that could promote both an increase in the markers of lipoprotein peroxidation and damage to the erythrocyte membrane with consequent modification of membrane fluidity. MATERIALS AND METHODS: Different markers of oxidative stress, erythrocyte membrane fluidity and antioxidant status were determined in 20 professional soccer players and 20 sedentary controls. Plasma lipoperoxides and kinetics of Cu-stimulated plasma peroxidation were measured together with hydrosoluble (albumin, uric acid and vitamin C), liposoluble (vitamin E and bilirubin) and enzymatic (superoxide dismutase and glutathione peroxidase) serum antioxidants. Erythrocyte membrane rigidity was determined by measuring fluorescence anisotropy (rs) of the fluorescent probe 1, 3, 5 diphenylexatriene. RESULTS: The sportsmen showed higher levels of the following plasmatic antioxidants: ascorbic acid (P<0.0001), uric acid (P<0.0001), alpha-tocopherol (P=0.03) and superoxide dismutase activity (P=0.0001). According to this evidence, the lipoperoxide levels (P=0.0158), the duration of the latency phase of plasma peroxidation (P=0.0123) and erythrocytes membrane fluidity (P=0.0152) were found to be significantly higher in the soccer players. DISCUSSION: Athletes undergoing regular and adequate training show improved antioxidant status together with a more fluid membrane status, which could contribute to improving both peripheral resistance to insulin and all the functional metabolic interchanges in the cellular membrane.

Oxidative stress, vitamin A and vitamin E behaviour in patients submitted to conservative surgery for complicated Crohn's disease.

AIMS: To assess whether plasma peroxidation and plasma levels of antioxidant compounds are correlated with clinical and biochemical activity in complicated Crohn's disease patients, and to evaluate whether the relief of obstructive complication by conservative surgery has any effect on the oxidative stress. PATIENTS AND METHODS: From May 1998 to May 2000, 20 Crohn's disease patients were studied. Basal peroxidative state (basal thiobarbituric acid reactive substances), peroxidative state after stimulation with copper sulfate (stimulated thiobarbituric acid reactive substances], lag time of plasma peroxidation susceptibility, plasma levels of vitamin E and A, C reactive protein, erythrocyte sedimentation rate and Crohn's disease activity index, were determined, before surgery, then 2 months and 1 year after surgery. A group of 134 healthy volunteers were used as controls. All patients were treated by conservative surgical procedures (i.e., strictureplasty and/or minimal resections). Student t test for paired and unpaired data and Spearman R correlation coefficient were calculated. RESULTS: Peroxidative plasma levels, as well as inflammatory indices, are significantly reduced 2 months and 1 year after surgery (p < 0.005), but basal levels of peroxidation and antioxidant scavengers seem to be disregulated in Crohn's disease patients compared to those in controls (p < 0.005). A correlation was found between basal thiobarbituric acid reactive substances, lag-time and erythrocyte sedimentation rate (R:0.51; p < 0.05. R:0.56; p < 0.05) and C reactive protein (R:0. 6; p < 0.005. R:0. 65; p < 0.005). CONCLUSIONS: An imbalance between pro- and antioxidant mechanisms, due to chronic gut inflammation, is present in complicated Crohn's disease, and an excess of lipid peroxidation is probably an important pathogenetic factor Conservative surgery can reduce the oxidative stress avoiding repeated or extended resections that could lead to intestinal malabsorption and short bowel syndrome.

[Membrane fluidity and obesity: the correct food approach]. / Fluidità di membrana e obesità (il corretto approccio alimentare).

Modifications in dietary fat profile have shown to affect body weight gain and adiposity. This may occur through the changes of cell membrane fluidity, in particular of the peripheral muscle tissue. The decreased availability of diet polyunsaturated fatty acids (in particular of the to-3 series), that are able to induce membrane fluidification, together with an excessive intake of both saturated fatty acids and cholesterol, that on the contrary are able to rigidify the same membranes, promoter both a progressive immobilization of membrane proteins and a consequent decrease in their functional rate of liver lipoproteins VLDL, enriched in saturated fats and cholesterol. This lipoprotein increase promotes both the fat deposition in the adipose tissues and a further increase in the muscle membrane rigidity that is followed by a further enhancement in the peripheral resistance to insulin. A diert rich both in polyunsaturated fatty acids and antioxidants (vitamin and oligoelements), and in essential amino acids together with a preferential choice of complex carbohydrates (amylose, amylopectine, etc) in comparison to simple sugars (glucose, fructose, saccharose, lactose, etc) may significantly contribute to the maintenance of the correct degree of membrane fluidity and, as a consequence, to the physiologically correct body weight.

[Dietary restriction and oral administration of antioxidant and omega-3: what are the effects on the clinical variables in a group of obese women?]. / La dietoterapia ipocalorica bilanciata personalizzata ed il trattamento con integratori a base di antiossidanti e omega-3 (quali gli effetti sulle variabili cliniche di outcome in un gruppo di donne in sovrappeso?)

BACKGROUND: Obesity is now recognized as a major risk factor for many pathologies. The state of obesity is associated with an increase in reactive oxygen species; persistent overconsumption of calories in the obese may be exposing them to excessive damage besides maintaining the state of obesity. It is possible that dietary modification and association with assumption of antioxidant and omega-3 oral integration contributes to a reduction in reactive oxygen species generation and a corresponding reduction in indexes of oxidative damage, including lipid peroxidation. METHODS: Given this back-ground, the pro/anti-oxidant balance, biochemical parameters and the body composition were studied in two groups of obese women: a first group of 10 obese women were studied before and after eight weeks of dietary restriction and a second group of 12 obese women were studied before and after eight weeks of dietary restriction and oral administration of antioxidant and omega-3. RESULTS: In summary, as regards the preliminary results of clinical outcome parameters, interestingly enough the glycemic levels fall markedly in association with both dietary restriction and oral integration with antioxidant and omega-3. Another important finding of this study is that of calcium levels and phase angle (measured by impedenzometry) increase in the group treated with dietary restriction and oral administration of antioxidant and omega-3. CONCLUSIONS: Studies that aimed to explore whether oxidative status predicts clinical outcome would provide important details on the putative link between oxidative status and state of obesity.

[The hypocaloric balanced diet therapy and the supplementation with antioxidant and omega-3: what are the effects on the oxidative balance and erythrocytes membrane fluidity status?]. / La dietoterapia ipocalorica bilanciata personalizzata ed il trattamento con integratori a base di antiossidanti e omega-3: quali gli effetti sullo stato della bilancia ossidativa e della fluidità delle membrane eritrocitarie in un gruppo di donne in sovrappeso?

BACKGROUND: To investigate the effects of a hypocaloric balanced diet therapy and a supplementation with antioxidant and omega-3 polyunsaturated fatty acids on the oxidative balance and erythrocytes membrane fluidity status. METHODS: A randomised, double-blind, placebo-controlled study of the association between a hypocaloric balanced diet therapy and a supplementation with antioxidant and omega-3 was done on 40 women with 25 < BMI < 33. The inclusion criteria were the following: absence of dismetabolic pathologies, of previous hypocaloric diet therapy and/or supplementation and of hormonal treatments. Each subjects consumed a balanced diet with a daily caloric intake equal to: Kcal of basal metabolism (determined by indirect calorimetry) x LAF (1.64) 800 Kcal. At the start and after two months of treatment, the blood chemistry and anthropometrics parameters, the plasmatic reactive oxygen species (ROS) and antioxidant defence levels and erythrocyte membrane fluidity status were measured. RESULTS: The preliminary results of this study show that the weight loss, found in both groups investigated, determines a significant decrease of ROS. Furthermore, the association of the hypocaloric diet with antioxidant and omega-3 polyunsaturated fatty acids caused a significant increase of both plasmatic antioxidant defences and erythrocytes membrane fluidity status. CONCLUSIONS: The correlations found between the above parameters and the blood chemistry and anthropometrics variables suggest that the supplementation with antioxidant and omega-3 polyunsaturated fatty acids could ameliorate the effects of hypocaloric diet on the obesity treatment and may give some clinical benefit through the decrease of the values of atherosclerosis risk factors.

Adipose tissue and cytokines.

Adipose tissue is not simply a storage depot for excess energy intake, it is also able to produce and release several substances with local (autocrine) and systemic (endocrine) actions. An up-to-date review of our knowledge in this area is given here. Several of the compounds deriving from adipose tissue have been shown to play a role in obesity-related health complications. The production of cytokines, such as Tumor Necrosis Factor-alpha (TNF-alpha), IL-6, and leptin, is implicated in the development of several disorders. Insulin resistance is one of the most clinically significant.

[Osteoporosis and phytoestrogens: an assessment of bone mineral density via quantitative peripheral computed tomography in milk-egg-vegetarian women in the premenopause]. / Osteoporosi e fitoestrogeni: valutazione della densità minerale ossea mediante Tomografia Computerizzata quantitativa periferica nelle donne lattoovovegetariane nella premenopausa.

PURPOSE: Noninvasive assessment of bone mineral density, geometrical and biomechanical properties in premenopausal women with dietary intake of phytoestrogens and comparison of these parameters with those of age-matched female subjects with "Mediterranean" dietary intake lacking in these substances. MATERIAL AND METHODS: Volumetric cortical, trabecular and total mineral density and bone geometrical properties were evaluated in 15 female subjects with phytoestrogens dietary intake. Peripheral quantitative Computed Tomography (pQCT) was used to make measurements at the distal radius of the nondominant forearm. Fifteen age-matched subjects with "Mediterranean" dietary intake were chosen as a control group. Cross-sectional area (Total A), trabecular area (TA), cortical area (CA), cortical thickness (CThk) and strength strain index (SSI) were assessed as biomechanical parameters. RESULTS: Daily consumption of phytoestrogens was significatively different in the two groups (phy: 17.45 mg/die vs ctr: 0.35; p < 0.0005), while calcium intake was similar (phy: 652 mg/die vs ctr: 650). Total (0.460 g/cm3 vs ctr: 0.433) and trabecular (phy: 0.209 g/cm3 vs ctr: 0.189) bone mineral densities, such as SSI (phy: 925 mm3 vs ctr: 894) values, were higher in women with dietary intake of phytoestrogens, in comparison with the relative controls, but not significantly (p = ns). Among geometrical parameters, total area and cortical area were tendential in women with a vegetarian diet while cortical thickness was the same in both groups. CONCLUSIONS: pQCT showed higher bone mineral density (total and trabecular) and SSI values in premenopausal women with dietary intake of phytoestrogens. Despite the lack of statistical significance, these preliminary results, should further support the few literature findings about the potential role of phytoestrogens consumption in preventing trabecular bone loss. However, further studies are warranted to evaluate definitively the efficacy of phytoestrogens in preventing postmenopausal osteoporosis.

Study of the effect of lactobacillus GG supplementation in combination with and without arginine aspartate on lipoproteins and liver peroxidation in cholesterol-fed rats.

The effect of diet integration with lactobacillus GG and arginine aspartate administered singly or together to rats submitted to a cholesterol-enriched diet have been evaluated by measuring both the changes in the levels of cholesterol and triglycerides and the variations of the most indicative parameters of peroxidation in plasma lipoproteins and livers. The administration of lactobacillus GG alone is able to induce a significant hypocholesterolaemic effect while the arginine aspartate singly or together with the lactobacillus does not seem to promote any significant hypocholesterolaemic effect. The cholesterol levels (expressed as mg x dL-1) are in fact: 45.5 for the control diet; 185.4 for the cholesterol-enriched diet; 131.1 for the cholesterol-enriched diet + lactobacillus; 178.2 for the cholesterol enriched diet + arginine aspartate and 122.4 for the cholesterol-enriched diet + lactobacillus + arginine aspartate. On the contrary, the co-administration of lactobacillus and arginine aspartate gives rise to a very high preventive activity against the cholesterol-induced peroxidation damages both in the plasma lipoproteins and in the liver. Such preventive activity is higher by far than that obtainable when lactobacillus or arginine aspartate are administered singly to the rats.

A fluorescence method for the determination of plasma susceptibility to lipid peroxidation.

OBJECTIVE: We propose a fluorescence kinetics method for monitoring plasma susceptibility to peroxidation. DESIGN AND METHOD: Plasmatic peroxidation was induced by CuSO4 (500 microM), and fluorescence was measured every 30 min. Kinetics were represented by a sigmoidal curve from which it was possible to calculate the latency time (lag-time) and the propagation velocity (slope) of plasma peroxidation. RESULTS: The lag-time monitored by the fluorescence kinetics method corresponded to the formation of thiobarbituric acid reactive substances, and to progressive depletion of polyunsaturated fatty acids and alpha-tocopherol. The mechanism of reaction appeared to be dependent upon plasmatic hydroperoxides, and independent of oxygen radicals. Plasma storage is possible for at least two months at -80 degrees C, and reproducibility of the method is very good. CONCLUSIONS: Fluorescence kinetics provide a highly comprehensive picture of plasma susceptibility to peroxidation in comparison with the conventional measurements of anti- and pro-oxidant ratios.

Variability in alpha-tocopherol antioxidant activity in the core and surface layers of low- and high-density lipoproteins.

The effect of alpha-tocopherol enrichment of low- and high-density lipoproteins on Cu(2+)-catalyzed lipid peroxidation in the hydrophobic core and in the hydrophilic envelope of lipoproteins was investigated by using two pyrene derivatives, namely, cholesteryl pyrenyl hexanoate (P6Chol) and pyrene dodecanoyl sulfatide (P12CS). The progressive decrease in fluorescence of P6Chol was used to monitor lipid peroxidation in the core of LDL and HDL, whereas that of P12CS was used to follow lipid peroxidation in the envelope of both lipoproteins. alpha-Tocopherol enrichment of LDL and HDL was obtained by incubating blood plasma at 37 degrees C with different concentrations of the vitamin (25-500 microM) before lipoprotein separation. The incorporation of alpha-tocopherol in LDL and HDL presents a progressive, time-dependent increase up to 200 microM alpha-tocopherol, then a plateau up to 500 microM. In the envelopes, the added tocopherol causes a great decrease in the rate of peroxidation and a dramatic increase in the latency phase in both lipoproteins. In the cores the lengthening of latency phase resulting from alpha-tocopherol enrichment was by far greater in LDL than in HDL, and the decrease in the rate of peroxidation in both lipoproteins was less than in the envelopes.

Studies on the antioxidant activity of milk caseins.

The antioxidant properties of milk casein subunits (alpha-casein, beta-casein and kappa-casein) were evaluated in liposomal models. All the subunits of casein are able to inhibit Fe-induced peroxidation of arachidonic acid inserted into multilamellar liposomes of dipalmitoylphosphatidylcholine (0.2 mM and 0.8 mM, respectively). The peroxidation was monitored as thiobarbituric acid reactive substances, and the strongest inhibitory effect occurred when 500 micrograms of alpha-casein were added to 0.5 ml of liposomal suspension. At this concentration, peroxidation was completely inhibited in our experimental conditions (incubation for 2 h at room temperature, with a mixture of ferrous sulfate and ascorbate, 50 and 500 microM final concentration, respectively). The mechanisms of antioxidant action are complex, but the strongest effect is achieved by modifying the Fe2+/Fe3+ equilibrium; in fact, caseins seem to favour the autoxidation of iron, and thus inhibit lipid peroxidation.

pH sensitivity and plasma stability of liposomes containing N-stearoylcysteamine.

In this study, we investigated the pH sensitivity of different liposomal formulations containing 10 mol% N-stearoylcysteamine, as pH sensitive molecule. Liposome stability was monitored by determining the release of different entrapped water soluble molecules, 5,6-carboxyfluorescein (CF) being the marker of leakage mainly used. Small unilamellar vesicles composed of egg phosphatidylcholine (EPC) and N-stearoylcysteamine (9:1 molar ratio) incubated at 20 degrees C in citrate phosphate buffer released, at pH 6.8, 2.5 fold the amount of CF released at pH 7.4. The addition of plasma to the incubation medium and an increase of temperature to 37 degrees C led to significantly increased the CF release from EPC/N-stearoylcysteamine SUV, both at pH 7.4 and 6.8. The addition of cholesterol had a stabilizing effect on liposomal vesicles with respect to both temperature and plasma, without affecting pH sensitivity. In fact, at 37 degrees C and in 25% plasma the ternary mixture showed the highest CF release, as a consequence of the moderate acidification of the medium from 7.4 to 6.8. Thus, these liposome formulations are potentially a useful tool for specific drug delivery to pathological tissues such as tumours, inflammation sites and ischemic areas where it is known that a lowering of the pH can occur.

Free radicals, atherosclerosis, ageing and related dysmetabolic pathologies: biochemical and molecular aspects.

In human ageing and with many pathologies correlated to the senile functional decay of cells, membrane damage often occurs in some organ or tissue, which provokes lipid peroxidation in the membrane and accelerates the disorder in structure and function of the membrane. When lipid peroxides accumulate sufficiently, they leak from the organ or tissue into the bloodstream and increase the lipid peroxide level in blood lipoproteins. The increased lipid peroxides in the blood attack the blood vessel and promote atherogenesis. This paper describes the possible involvement of free radicals in this damage, both to tissues and to blood vessels, which contributes to the senile functional decay of the tissues.

Free radicals, atherosclerosis, ageing, and related dysmetabolic pathologies: pathological and clinical aspects.

An excess of free-radical production has been linked to many diseases and to the ageing process. Oxidant by-products of normal metabolism can cause extensive damage to DNA, protein and lipid. Exposure to ultraviolet light, cigarette smoke and other environmental pollutants may also increase the free radical burden. The accumulation of unrepaired oxidative damage products is likely to be a major factor in cellular ageing. Many repair processes are available to the cell, including enzyme and structural defences. The large group of natural antioxidants is also part of a protective mechanism. High consumption of fruit and vegetables in the diet is associated with a lowered risk of degenerative diseases. At present, however, there are few data to support the routine use of exogenous antioxidants to prevent and treat these diseases.

Exercise, free radical generation and vitamins.

Physical activity raises oxygen demand by many fold, causing a parallel increase in the formation of oxygen radical species. Vitamins are concerned with either energy metabolism or free radical scavenging. This review outlines the possible damage to cell structures following strenuous exercise and the role of vitamins as part of natural anti-oxidant defence systems. A brief discussion is included on the relationship between physical activity, the immune system and cancer.

Vitamin requirements: present recommendations and future prospects.

Dietary recommendations evolved from instructions directed at prevention of starvation diseases to the level of intake of essential nutrients that are adequate to meet the known nutrient needs of practically all healthy persons. Vitamin requirements have been modified various times over the years and there are still differences in recommended intakes in different countries. A debate on optimal vitamin intake is ongoing, based on the concepts of deficiency, sufficiency and hypothetical identification of a range within which a further biological advantage can be expected. In establishing appropriate criteria for food and nutrient intakes, additional studies are warranted on the physiological interactions between nutrients and non-nutrients and on many other factors such as genetic determinants and lifestyle which could interfere with disease prevention.