Nutrient reference value: non-communicable disease endpoints--a conference report.

Nutrition is complex-and seemingly getting more complicated. Most consumers are familiar with "essential nutrients," e.g., vitamins and minerals, and more recently protein and important amino acids. These essential nutrients have nutrient reference values, referred to as dietary reference intakes (DRIs) developed by consensus committees of scientific experts convened by the Institute of Medicine of the National Academy of Sciences, Engineering, and Medicine and carried out by the Food and Nutrition Board. The DRIs comprise a set of four nutrient-based reverence values, the estimated average requirements, the recommended dietary allowances (RDAs), the adequate intakes and the tolerable upper intake levels for micronutrient intakes and an acceptable macronutrient distribution range for macronutrient intakes. From the RDA, the US Food and Drug Administration (FDA) derives a labeling value called the daily value (DV), which appears on the nutrition label of all foods for sale in the US. The DRI reports do not make recommendations about whether the DV labeling values can be set only for what have been defined to date as "essential nutrients." For example, the FDA set a labeling value for "dietary fiber" without having the DV. Nutrient reference values-requirements are set by Codex Alimentarius for essential nutrients, and regulatory bodies in many countries use these Codex values in setting national policy for recommended dietary intakes. However, the focus of this conference is not on essential nutrients, but on the "nonessential nutrients," also termed dietary bioactive components. They can be defined as "Constituents in foods or dietary supplements, other than those needed to meet basic human nutritional needs, which are responsible for changes in health status (Office of Disease Prevention and Health Promotion, Office of Public Health and Science, Department of Health and Human Services in Fed Regist 69:55821-55822, 2004)." Substantial and often persuasive scientific evidence does exist to confirm a relationship between the intake of a specific bioactive constituent and enhanced health conditions or reduced risk of a chronic disease. Further, research on the putative mechanisms of action of various classes of bioactives is supported by national and pan-national government agencies, and academic institutions, as well as functional food and dietary supplement manufacturers. Consumers are becoming educated and are seeking to purchase products containing bioactives, yet there is no evaluative process in place to let the public know how strong the science is behind the benefits or the quantitative amounts needed to achieve these beneficial health effects or to avoid exceeding the upper level (UL). When one lacks an essential nutrient, overt deficiency with concomitant physiological determents and eventually death are expected. The absence of bioactive substances from the diet results in suboptimal health, e.g., poor cellular and/or physiological function, which is relative and not absolute. Regrettably at this time, there is no DRI process to evaluate bioactives, although a recent workshop convened by the National Institutes of Health (Options for Consideration of Chronic Disease Endpoints for Dietary Reference Intakes (DRIs); March 10-11, 2015; http://health.gov/dietaryguidelines/dri/ ) did explore the process to develop DVs for nutrients, the lack of which result in increased risk of chronic disease (non-communicable disease) endpoints. A final report is expected soon. This conference (CRN-International Scientific Symposium; "Nutrient Reference Value-Non-Communicable Disease (NRV-NCD) Endpoints," 20 November in Kronberg, Germany; http://www.crn-i.ch/2015symposium/ ) explores concepts related to the Codex NRV process, the public health opportunities in setting NRVs for bioactive constituents, and further research and details on the specific class of bioactives, n-3 long-chain polyunsaturated fatty acids (also termed omega-3 fatty acids) and their constituents, specifically docosahexaenoic acid and eicosapentaenoic acid.

mCPP-induced hypophagia in rats is unaffected by the profile of dietary unsaturated fatty acids.

The n-3 and n-6 polyunsaturated fatty acids (PUFAs) have been shown to modify central serotonergic parameters relevant to ingestive behavior. Evidence suggests an association between the 5-HT(2C) receptor and fat intake. The present research sought to examine the role of the 5-HT(2C) receptor subtype on food intake when diets with different fatty acid compositions are consumed. The effects of 1-(3-chlorophenyl)piperazine (mCPP) on consumption of both low-fat (Experiment 1) and high-fat diets (Experiment 2) differing in their predominant PUFA profiles were compared in rats. Regardless of the PUFA profile, mCPP induced hypophagia within each experiment. Although the present results lend further support to a large body of evidence demonstrating the ability of mCPP to reduce food intake, they do not support the idea that the essential fatty acid composition of the diet can differentially modulate mCPP-induced hypophagia.

Food intake in rats is unaffected by the profile of dietary essential fatty acids.

Food intake may be differentially responsive to the type of fat in the diet. The present investigation sought to evaluate the energy intake of rats maintained on either a low-fat or a high-fat diet mixed with an oil rich in either linoleic (18:2; n-6; safflower oil) or linolenic (18:3; n-3; flaxseed oil) acid. In Experiment 1, rats (n=28) consumed low-fat versions of either the safflower oil diet or the flaxseed oil diet, each at 9.28% fat (wt/wt). In Experiment 2, different rats (n=28) consumed high-fat versions of these diets, each at 23.6% fat (wt/wt). Within each experiment, the energy intake of rats receiving the safflower oil diet was compared to the energy intake of rats receiving the flaxseed oil diet. Food intake was measured under short-term, long-term and food-deprived conditions. In Experiment 1, short-term energy intakes were not different between the groups, thus demonstrating equal acceptance of the test diets. There were no consistent differences in long-term energy intakes between the safflower group and the flaxseed group. In addition, there were no differences in energy intake under the food-deprivation condition. Results from Experiment 2 paralleled those of Experiment 1. Taken together, the present results suggest that the essential fatty acid profile of the maintenance diet does not influence food intake when nutritive oils are the predominant fatty acid source.

Effects of limited access to a fat option on food intake and body composition in female rats.

OBJECTIVE: The present investigation sought to determine if limiting access to an optional fatty food would induce binge-type behavior patterns in non-energy-deprived female rats. METHOD: Four groups of rats had continuous access to a commercial rodent diet throughout the 8-week study. In addition: (1) the control group had no access to vegetable shortening; (2) the high limitation group had access to shortening for 2 hr for 3 days each week; (3) the low limitation group had access to shortening for 2 hr every day; and (4) the no limitation group had continuous access to shortening. RESULTS: As access to the shortening decreased, intake during the 2-hr access period increased. Total energy intake and body weight did not differ among groups. Body fat was greatest in the rats that ate the most cumulative shortening. DISCUSSION: These results indicate that, even under non-energy-deprived conditions, limiting access to a preferred fatty food can induce binge-type behavior in female rats.

Different preferences for oils with similar fatty acid profiles.

While preference for fat can be influenced by concentration and physical form, the influence of fatty acid composition on relative preference for oils has not been systematically investigated. Therefore, the purpose of the present investigation was to assess the relative preference for oils rich in oleic (Extra Light Olive Oil and Extra Virgin Olive Oil) and linoleic (Safflower Oil) acid. Male Fischer rats (n = 10) were used to determine preference in a two-choice testing procedure in which three pairs of oils were each tested twice. Preference testing occurred at dark onset at which time the rodent diet and water were removed and each rat was allowed 2-h access to his assigned pair of oils. There was a main effect of oil type (p<0.01), but no significant effect of oil pairing and no interaction between oil pairing and oil type. Rats preferred the Extra Light Olive Oil to the Extra Virgin Olive Oil (p<0.05). This is the first report of preference testing in which two oils with similar fatty acid profiles were included. The present data indicate that the fats with similar fatty acid profiles were not equally preferred, suggesting that a property other than the fatty acid composition of the oils accounts for the demonstrated preference.

Effects of enterostatin in non-food-deprived rats with limited or continuous access to oil or sucrose.

The peptide enterostatin has been proposed to function as a selective signal for fat-induced satiety. In the majority of enterostatin studies, however, rats were food-deprived, and the test food was also the maintenance diet. The present study sought to determine if enterostatin would selectively reduce consumption of oil that was provided in addition to a standard diet in non-food-deprived rats. Rats had either continuous (24-h/day) or limited access (120-min/day) to either a 32% sucrose solution or 100% corn oil. In addition to the sucrose and the oil, rats also had 22-h access to a standard pelleted rodent diet. Control rats had unlimited access to the standard diet but no access to oil or sucrose. Rats were maintained on their respective diets for 3 weeks before enterostatin testing. Food intake and body weight were monitored. Rats with continuous access to oil or sucrose consumed more calories and gained more weight than control rats. Caloric intake and body weight of the rats with limited access to oil or sucrose did not differ significantly from controls. Enterostatin, administered intraperitoneally (i.p.) at doses of 0 (vehicle), 89, 178, and 356 microg/kg, had no effect on consumption of oil, sucrose, or standard diet in these non-food-deprivation paradigms; however, 356 microg/kg reduced standard-diet intake when rats were overnight food-deprived, thus verifying peptide activity. These results do not support a role for enterostatin in the regulation of fat intake when optional high-fat foods are provided in addition to a readily available standard diet.

Effects of enterostatin on consumption of optional foods in non-food-deprived rats.

Enterostatin, the activation peptide of procolipase, has been reported to reduce high-fat food consumption in rats. This reduction has been reliably demonstrated using procedures in which the test diet was also the maintenance diet of the animals. Other reports, though, have shown that peripherally administered enterostatin had no effect on the consumption of oil provided as an option to the diet, and that centrally administered enterostatin had no effect on the consumption of an optional high-fat mixed food. However, the effects of peripherally administered enterostatin on the consumption of an optional high-fat mixed food have not been examined. This experiment, then, examined the effects of peripherally administered enterostatin on the consumption of optional, mixed foods (no-fat and high-fat cookies) provided in addition to a standard diet under choice and nonchoice conditions. Four experiments were conducted. In experiment I, the effect of enterostatin in a two-choice feeding paradigm was assessed. In experiment II, the effect of enterostatin in a nonchoice feeding paradigm was assessed. In experiment III, the effect of enterostatin administered at five different pretreatment times in a non-choice feeding paradigm was assessed. Enterostatin had no effect on cookie intake in any of these experiments. Finally, experiment IV was undertaken to verify the activity of the peptide. Enterostatin significantly reduced the consumption of a standard diet in overnight food-deprived rats, thus confirming the activity of the peptide used in experiments I to III. Enterostatin may not play a major role in the regulation of food intake that is stimulated by optional foods that are periodically provided in addition to a standard well-balanced diet.

Limited access to a dietary fat option affects ingestive behavior but not body composition in male rats.

Restricting access to high-fat foods is a common strategy utilized to promote health. This strategy may contribute to episodes of overconsumption, however, when the restricted foods subsequently become available. The present study utilized a rat feeding procedure to determine if restricting access to an optional source of dietary fat would increase later consumption of that food under nonenergy-deprived conditions. Five groups of male Sprague-Dawley rats were used, all of which had continuous access to a standard rodent diet and water. The control group had no access to shortening. The low-restriction group had 2-h access to shortening every day. The high-restriction group had 2-h access to shortening on Monday, Wednesday, and Friday. Two additional groups were switched between the high and low conditions. Two-hour and 24-h food intakes were measured every day for 6 weeks. At the end of the study rats were sacrificed and carcass composition determined. As access to the shortening decreased, consumption during the 2-h access period increased. Rats compensated for the increased shortening consumption by decreasing intake of the standard diet. Thus, cumulative energy consumption did not differ among the groups. When switched between the high and low conditions, rats rapidly adjusted to the change in shortening availability. There were no effects of access schedule on carcass composition. These results indicate that restricting access to an optional high-fat food, even under nonenergy-deprived conditions, can promote significant increases in the consumption of that food when it subsequently becomes available.

Intracerebroventricular enterostatin stimulates food intake in non-food-deprived rats.

Previous studies reported that ICV enterostatin reduced high-fat food intake in food-deprived rats. The present study sought to determine if ICV enterostatin would decrease intake of a high-fat food in non-food-deprived rats. Eight doses (0-32 micrograms) were tested. Enterostatin (32 micrograms) significantly stimulated cookie intake at 30 min. Enterostatin did not reduce food intake at any dose. These results conflict with previous reports and suggest that central enterostatin does not play a role in suppressing, but may play a role in stimulating, high-fat food consumption in non-food-deprived rats.