Feasibility and preliminary efficacy of the LEAD trial: a cluster randomized controlled lifestyle intervention to improve hippocampal volume in older adults at-risk for dementia.

BACKGROUND: Healthy diet and exercise are associated with reduced risk of dementia in older adults. The impact of diet and exercise interventions on brain health is less consistent, especially with dietary interventions which rely on varying approaches. Our objective was to evaluate the feasibility and preliminary efficacy of a 6-month intervention combining exercise with a novel dietary counseling approach to improve hippocampal volume among older adults at-risk for dementia. METHODS: Participants with vascular risk factors and subjective cognitive decline or early mild cognitive impairment were cluster randomized in groups of 3-4 to the diet intervention (DIET) or control education (ED) group. All participants engaged in 1 h of supervised exercise per week and additional exercise at home. DIET involved 1 h per week of group-based dietary counseling comprising education, goal setting, and strategy training. ED involved 1 h per week of group-based brain health education classes. Our primary outcome was change in hippocampal volume from baseline to 6 months. Secondary outcomes included changes in cognitive function, blood biomarkers, diet, and fitness. Recruitment challenges and early discontinuation of the trial due to COVID-19 necessitated a revised focus on feasibility and preliminary efficacy. RESULTS: Of 190 older adults contacted, 14 (7%) were eligible and enrolled, constituting 21% of our recruitment target. All participants completed the intervention and attended 90% of exercise and DIET/ED sessions on average. All 6-month assessments prior to COVID-19 were completed but disruptions to in-person testing resulted in incomplete data collection. No serious adverse events occurred and all participants expressed positive feedback about the study. Preliminary findings did not identify any significant changes in hippocampal volume; however, substantial improvements in diet and HbA1c were observed with DIET compared to ED (d = 1.75 and 1.07, respectively). CONCLUSIONS: High adherence and retention rates were observed among participants and preliminary findings illustrate improvements in diet quality and HbA1c. These results indicate that a larger trial is feasible if difficulties surrounding recruitment can be mitigated. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03056508 .

Increased dopamine synthesis in aging substantia nigra neurons.

Striatal dopamine (DA) and metabolite (DOPAC) levels in 8-, 21-, 52- and 104-week-old C57BL mice were compared with those in 11-week-old mice, 20 days after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. DA and DOPAC concentrations expressed relative to striatal wet weight did not change with age. In contrast, DA and DOPAC levels increased almost linearly when values were expressed relative to the proportion of remaining tyrosine hydroxylase-positive (TH+) SNc neurons, reaching a 5-7-fold increase per average remaining TH+ neuron by 104 weeks of age (corresponding to neuronal loss of 70%) relative to that found per average neuron in 8-week-old mice. DA and DOPAC levels per average remaining TH+ SNc neuron following MPTP increased for low doses (neuronal losses less than 42%) but decreased for higher doses (55 and 70% losses) but the DOPAC/DA ratio per SNc neuron increased and was 9-fold higher in the 300 mg/kg MPTP-treated animals in comparison to saline controls. Cytoplasmic TH protein (estimated by somal TH immunodensity) was increased by 45% in SNc somata from mice treated with 150 mg/kg MPTP in comparison to saline controls, and by 63% in 104-week-old mice in comparison to 8-week-old animals. This study provides evidence that an average surviving TH+ SNc neuron compensates for the age-related loss of other SNc neurons by increasing dopamine synthesis similar to younger SNc neurons surviving low levels of toxically induced damage and that the compensation may be in part mediated by increased synthesis of TH.

Different rates of age-related loss for four murine monoaminergic neuronal populations.

The age-related loss of locus coeruleus (LC) noradrenergic neurons, substantia nigra compacta (SNc) dopaminergic neurons, dopaminergic retinal amacrine (rAm) neurons and raphe serotonergic neurons, identified using antibodies against tyrosine hydroxylase (TH) and serotonin (5HT) was investigated in C57B1 mice aged 8 to 104 weeks. The neuronal somata were counted and their locations three-dimensionally reconstructed from serial sections alternately immunoreacted or Nissl stained. Nonlinear estimation analysis showed that decaying exponential equations best fitted the plots of neuronal numbers versus age and each subtype was lost according to different exponential constants of -0.015, -0.013, -0.004 and -0.001 for LC TH+, SNc TH+, rAm TH+ and raphe 5HT+ neurons, respectively. Neurons were lost from all different subregions within the nuclei or the retinae. Counts of immediately adjacent TH-immunoreacted and Nissl-stained sections through the LC at different ages indicate that the neuronal loss was due to neuronal death rather than loss of TH immunoreactivity. The markedly different rates of age-related neuronal loss for the four monoaminergic subtypes offer a model to study the underlying molecular and cellular mechanisms.

Cognitive performance is associated with glucose regulation in healthy elderly persons and can be enhanced with glucose and dietary carbohydrates.

BACKGROUND: A glucose drink has been shown to improve memory in persons with poor glucose regulation and poor cognition. OBJECTIVE: The objective of this study was to determine 1) whether an association between cognition and glucose regulation is apparent in healthy seniors and 2) the effects of dietary carbohydrates on cognition. DESIGN: After an overnight fast, 10 men and 10 women (aged 60-82 y) consumed 50 g carbohydrate as glucose, potatoes, or barley or a placebo on 4 separate mornings. Cognitive tests were administered 15, 60, and 105 min after ingestion of the carbohydrate. Plasma glucose and serum insulin were measured. RESULTS: In a multiple regression analysis, poor baseline (placebo) verbal declarative memory (immediate and 20-min delayed paragraph recall and word list recall) and visuomotor task performance were predicted by poor beta cell function, high incremental area under the glucose curve, low insulin resistance, and low body mass index. The difference in plasma glucose after food consumption [glucose > potatoes > barley > placebo (P: < 0.03)] did not predict performance. Although overall performance did not differ with consumption of the different test foods, baseline score and beta cell function correlated with improvements in immediate and delayed paragraph recall for all 3 carbohydrates (compared with placebo); the poorer the baseline memory or beta cell function, the greater the improvement (correlation between beta cell function and improvement in delayed paragraph recall: r > -0.50, P: < 0.03). Poor beta cell function correlated with improvement for all carbohydrates in visuomotor task performance but not on an attention task. CONCLUSIONS: Glucose regulation was associated with cognitive performance in elderly subjects with normal glucose tolerance. Dietary carbohydrates (potatoes and barley) enhanced cognition in subjects with poor memories or beta cell function independently of plasma glucose.

Dietary protein, carbohydrate, and fat enhance memory performance in the healthy elderly.

BACKGROUND: Dietary carbohydrates can improve memory. Whether these effects are related to elevations in blood glucose or to energy ingestion is unknown. OBJECTIVES: Our objectives were to determine 1) the influence of isoenergetic protein-, carbohydrate-, and fat-containing drinks on cognitive performance and 2) whether the time period after ingestion affects cognition. DESIGN: After fasting overnight, 11 men and 11 women aged 61-79 y consumed either a 300-mL drink containing 774 kJ as pure protein (whey), carbohydrate (glucose), or fat (safflower oil) or a nonenergy placebo on 4 separate mornings. Cognitive tests were administered 15 and 60 min after ingestion of the drinks. Plasma glucose and serum insulin concentrations were measured. RESULTS: Only the carbohydrate drink increased blood glucose (P < 0.0001). Compared with the placebo, all 3 macronutrients improved delayed paragraph recall (PR) (P < 0.001) and improved or tended to improve immediate PR (P < 0.04) 15 min after ingestion. Beneficial effects on other cognitive tests were confined to one or more of the macronutrients: carbohydrate improved Trail Making Test (Trails) performance at 60 min (P = 0.02) and tended to improve Trails at 15 min (P = 0.04) and PR at 60 min in men, carbohydrate and fat improved or tended to improve performance on Trails at 15 and 60 min in subjects with poor baseline scores (r > -0.41, P < 0.03), fat tended to improve attention at 60 min (P < 0.05), and protein reduced the rate of forgetting on the PR at 15 min (P = 0.002). CONCLUSIONS: Energy intake from protein, carbohydrate, or fat can enhance memory independently of elevations in blood glucose. Each macronutrient may also exert unique effects on cognition.

Variations in age-related decline in striatal D2-dopamine receptors in a variety of mouse strains.

To determine the importance of inheritance on the age-associated decline in D2-dopamine receptor number, the binding of [3H]spiperone to mouse striatal membranes was measured in animals ranging from 7 to 104 weeks of age from 5 murine strains (C57BL/6J, C3/HeJ, A/J, SJL/J and DBA/1J). In young mice, receptor number (Bmax) was influenced by genetic background such that C57BL/6J less than SJL/J less than A/J = DBA/1J = C3H/HeJ. A 50-60% decline in Bmax with age was found in all strains except for C57BL/6J. Bmax in the C57BL/6J mice were lower than in the other strains of young animals (7-15 weeks) but remained relatively constant throughout life (measured up to 104 weeks of age). Furthermore, the maximal decline in receptor number was observed relatively early in life (16-30 weeks) and remained constant thereafter. Neither age nor genetic background influenced ligand affinity (Kd). Thus the results of this study suggest that the maximal decline in Bmax for the dopamine receptor occurs before the second half of life and that the magnitude of this decline is polymorphic.

Cognitive impairment in rats fed high-fat diets: a specific effect of saturated fatty-acid intake.

One-month-old rats were fed 1 of 4 high-fat diets (20% fat) or chow (4.5% fat) for 3 months. Dietary saturated (SFA), monounsaturated (MUFA), or polyunsaturated (PUFA) fatty acids varied such that their independent effects on cognitive performance could be tested. Rats were tested on a variable-interval delayed-alternation task. Impairment in both the ability to learn the basic alternation rule and remembering trial-specific information over time was observed in rats fed the experimental diets relative to those fed chow. The degree of impairment was highly associated with the level of SFAs fed and independent of the MUFAs or PUFAs. Dietary fat altered brain phosphatidylcholine fatty-acid profile, but the membrane changes did not correlate with cognitive impairment. The results demonstrate that cognitive impairment is directly associated with SFA intake but suggest that the mechanism is independent of bulk brain membrane compositional changes.

Shift in diurnal feeding patterns in nursing home residents with Alzheimer's disease.

BACKGROUND: Individuals with Alzheimer's disease (AD) are highly susceptible to weight loss and malnutrition, which, to date, have not been associated with decreased food consumption. The current study examined food intake patterns and how they change in relation to body mass index (BMI), behavioral function, and cognitive status in institutionalized seniors with AD. METHODS: Twenty-one consecutive days of investigator-weighed food intake collections were conducted on 25 subjects with likely AD residing at a home for the aged. All subjects maintained the ability to self-feed. RESULTS: Eighty-eight percent of participants did not meet targeted energy needs, including an estimated 37% prevalence of protein inadequacy. Subjects with increased behavioral difficulties, based on the London Psychogeriatric Rating Scale, had reduced meal-related intakes that were highly associated with decreased energy consumption at dinner. With behavioral changes, particularly increased mental disorganization and confusion, there was a shift in circadian eating patterns such that the greatest proportion of daily energy was consumed at breakfast. Individuals with low BMIs tended to be those with more behavioral difficulties, such that BMI was also associated with the shift in overall eating patterns. CONCLUSIONS: Changes in behavioral function in seniors with AD result in a circadian shift in intake patterns with the preponderance of calories consumed at breakfast in those with increased behavioral difficulties. This shift in eating patterns associates both with poor overall intake and poor BMI.

Meal delivery practices do not meet needs of Alzheimer patients with increased cognitive and behavioral difficulties in a long-term care facility.

BACKGROUND: Alterations in circadian rhythms and behavioral difficulties likely impact meal consumption patterns in elderly individuals with probable Alzheimer's disease (AD). Despite these known changes, the profile of meals provided in the institution parallels the needs of younger, free-living, healthy populations. This investigation examined the impact of food delivery patterns on achieved intakes in elderly individuals with probable AD in a long-term care facility and how this relationship changes depending on time of day, body weight status, behavioral function, and cognitive ability. METHODS: Twenty-one consecutive days of investigator-weighed food intake and delivery collections were conducted on 25 elderly individuals with probable AD who maintained the ability to self-feed. RESULTS: Energy consumed was positively associated with energy delivered for the majority of subjects, although the strength of this relationship varied across subjects and throughout the day. Energy delivered had the greatest impact on energy consumed at breakfast and the least impact at dinner in those with the greatest behavioral difficulties and cognitive impairment. Although those with low body mass indexes (BMIs) were likely to be delivered more energy, the impact of delivery on intakes decreased as energy delivered increased. CONCLUSIONS: Delivering excess energy to patients with poor BMIs likely does not result in increased energy consumption. Behavioral and cognitive deterioration leads to a shift in the time of day that energy delivered has an impact on energy consumption, with the most progressed individuals being most impacted by foods delivered in the morning, suggesting that traditional meal practices are inappropriate for elderly individuals with AD.

The effects of high fat diets and environmental influences on cognitive performance in rats.

As part of a continuing investigation of the relationship between dietary factors and cognitive function, the present study examined the combined effects of environmental influences and high-fat diets on learning and memory. Following 3 months of dietary (20% by weight fat diets, composed primarily of either beef tallow or soybean oil versus standard laboratory chow) and environmental treatments (standard, enriched or impoverished), subjects were tested on a variable interval delayed alternation (VIDA) task which measures learning and memory functions that differentially involve specific brain regions. The results confirmed the negative effects of high fat diets, relative to chow, on all aspects of VIDA performance and showed that environmental enrichment overcame deficits associated with dietary fat. Housing rats fed high-fat diets in an impoverished environment did not further exacerbate cognitive deficits observed in such rats living under standard conditions. By comparison, chow-fed rats exhibited no benefit associated with the enriched environment on any aspect of task performance, and only a transitory learning impairment when housed in an impoverished environment. The results show that high fat diets and environmental conditions influence cognitive function and that these two factors interact with one another to produce different profiles of benefits and impairments.

Cholinergic differentiation triggered by blocking cell proliferation and treatment with all-trans-retinoic acid.

This study determined whether the effect of all-trans-retinoic acid (t-RA) on markers of cholinergic differentiation in a murine septal cell line, SN56.B5.G4, differed depending upon the cell's proliferative status. To develop a model of non-proliferating cells, aphidicolin, a DNA alpha-polymerase inhibitor, was used. Cessation of proliferation by aphidicolin increased intracellular choline and acetylcholine (ACh) levels in the absence of change to choline acetyltransferase (ChAT) activity and mRNA and vesicular ACh transporter (VAChT) mRNA. Importantly, the response to t-RA differed depending upon proliferative status. Consistent with previous reports, t-RA increased ChAT and VAChT mRNA, ChAT activity and intracellular ACh levels in proliferating SN56 cells with no effect on intracellular choline levels. When cells were treated with t-RA while undergoing proliferative arrest, an additive effect of combined treatment was observed on ACh levels; nevertheless, this was only accompanied by an increase in choline levels, VAChT and ChAT mRNAs, but not ChAT activity. Indeed, aphidicolin treatment completely suppressed the t-RA-induced increase in ChAT activity observed in proliferating cells. To explore the response to t-RA in post-mitotic cells, a sequential treatment of aphidicolin and t-RA was employed. t-RA treatment was ineffective in increasing ACh and choline levels, over and above that observed with the aphidicolin treatment alone. Comparable to the combined treatment, sequential treatment lead to an increase in ChAT mRNA without any increase in ChAT activity. In conclusion, both the magnitude and the mechanism(s) of action whereby t-RA enhances the cholinergic phenotype of SN56 cells is dependent upon the cell's proliferative status.

Dose-dependent destruction of the coeruleus-cortical and nigral-striatal projections by MPTP.

In order to determine whether 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces neuronal death or the loss of tyrosine hydroxylase (TH) immunoreactivity, 4 catecholaminergic nuclei in the mouse: substantia nigra compacta (SNc), locus coeruleus (LC), ventral tegmental area (VTA) and the A13 nucleus in the hypothalamus were quantitatively examined. Serial sections were taken through the rostrocaudal extent of each nucleus: alternate sections were incubated with TH antiserum and reacted with an immunoperoxidase technique while the alternate set was Nissl stained. Counts and 3 dimensional reconstructions of TH reactive somata were made for each nucleus for saline-treated controls and mice treated with different doses of MPTP (37.5, 75, 150 and 300 mg/kg). TH-positive neurons were counted along with their counterparts on the Nissl-stained alternative sections to both identify the catecholaminergic neurons and to measure their destruction. Concentrations of striatal dopamine and cortical norepinephrine were measured for all dosages of MPTP in order to determine the relationship between dosage, target tissue neurotransmitter concentration and neuronal destruction. By 20 days after MPTP injection there was a dose-dependent random loss of TH-immunoreactive neurons that was almost identical in all 4 nuclei examined. Analysis of the Nissl versus TH cell counts revealed that MPTP resulted in neuronal destruction in the SNc and the LC rather than just a loss of TH immunoreactivity. There was no difference in sensitivity to MPTP between the SNc and the LC. Decreases in cortical norepinephrine concentrations were about one third of the decreases of LC neuronal counts for all MPTP doses; while decreases in striatal dopamine and SNc cell loss was similar to the LC for the two lower doses of MPTP but for the higher doses, the relationship approached or exceeded a one to one ratio. Hence estimates of neuronal death based upon target tissue transmitter concentrations could not be made using the same relationship for SNc and the LC catecholaminergic neurons and use of the same relationship for higher MPTP dosages results in an underestimate of LC neuronal destruction relative to that in the SNc.

Transmitter synthesis increases in substantia nigra neurons of the aged mouse.

Striatal dopamine concentrations are relatively well maintained with age despite extensive death of the nigrostriatal neurons whose terminals contain the dopamine. Counts of nigrostriatal dopaminergic neurons in C57BL mice identified using immunocytochemistry, Fluoro-Gold retrograde axonal transport and Nissl staining were combined with measures of striatal dopamine and DOPA after saline, pargyline or NSD-1015 treatment. On average, 68% of the dopaminergic nigrostriatal neurons died between ages 8 and 104 weeks and there was a 3-fold increase in dopamine synthesis per average neuron in the aged mice. Increased transmitter synthesis by surviving neurons may serve to compensate brain function in old age.

Nutrients as trophic factors in neurons and the central nervous system: role of retinoic acid.

In multicellular organisms, death, survival, proliferation, and differentiation of a given cell depend on signals produced by neighboring and/or distant cells, resulting in the coordinated development and function of the various tissues. In the nervous system, control of cell survival and differentiation is achieved through the action of a distinct group of polypeptides collectively known as neurotrophic factors. Recent findings support the view that trophic factors also are involved in the response of the nervous system to acute injury. By contrast, nutrients are not traditionally viewed as potential trophic factors; however, there is increasing evidence that at least some influence neuronal differentiation. During development the brain is responsive to variations in nutrient supply, and this increased sensitivity or vulnerability of the brain to nutrient supply may reappear during neuronal repair, a period during which a rapid membrane resynthesis and reestablishment of synthetic pathways occur. To further evaluate the potential of specific nutrients to act as pharmacologic agents in the repair of injured neurons, the effects of retinoic acid, an active metabolite of vitamin A, and its role as a trophic factor are discussed. This literature review is intended to provide background information regarding the effect of retinoic acid on the cholinergic phenotype and the differentiation of these neurons and to explain how it may promote neuronal repair and survival following injury.

Dietary fat-induced changes in protein and carbohydrate selection are not explained by alterations in neuronal membrane fatty acid composition.

We previously showed changes in protein and carbohydrate selection in response to qualitative differences in dietary fat. Alterations in macronutrient selection were specifically related to changes in dietary saturated fat, but not to relative or absolute differences in dietary essential fatty acids. Three experiments were conducted to determine if changes in specific fatty acids in bulk phase neural membranes were associated with differences in macronutrient selection. For each experiment, specific fatty acid profiles were achieved by blending dietary fat sources. Rats consumed 20% (w/w) fat diets varying only in their fatty acid composition. After 2 weeks, rats were challenged with a selection paradigm. Each experiment showed a significant effect of dietary fat on neural membrane fatty acid composition (p less than 0.05) and alterations in individual fatty acids were correlated with changes in dietary fatty acids (p less than 0.05). However, dietary fat had no consistent effect with respect to which particular neural membrane fatty acids were modified, and there was no correlation between changes in specific membrane fatty acids and macronutrient selection. These findings suggest that alteration of specific fatty acids in bulk phase neural membranes do not mediate macronutrient selection behavior.

Protein and carbohydrate selection respond to changes in dietary saturated fatty acids but not to changes in essential fatty acids.

We previously reported differences in protein and carbohydrate selection patterns in post-weanling rats fed beef tallow or soybean oil-based diets. Two experiments were designed to determine the characteristic of the dietary fat which mediates the selection behavior. For each experiment, dietary fat was 20% (w/w) of diets and fatty acid profiles were obtained by blending fat sources. Rats were randomly assigned to diets (24% protein, 40% carbohydrate) which varied only in fatty acid composition. After 2 weeks, rats selected from 2 diets with the fat composition previously fed, but varying in their protein and carbohydrate composition (55% protein, 4% carbohydrate and 5% protein, 61% carbohydrate). Experiment 1 was designed to test the effect of relative (omega 6: omega 3 ratios of 1 and 20) and absolute (15% or 4% omega 6, 0.7% or 0.2% omega 3) differences in essential fatty acids on macronutrient selection patterns. Differences in dietary essential fatty acids had no effect on energy intake or the proportion of energy consumed as protein and carbohydrate. Experiment 2 examined the effect of differences in the level of saturated fat (3-10% diet (w/w] on protein and carbohydrate selection. Animals selecting from diets with higher levels of saturated fat consumed more energy as protein and less as carbohydrate than rats selecting from diets with lower levels of saturated fat (p less than 0.0001). Regression analysis was used to examine the relationship between percent protein or carbohydrate energy and classes of dietary fat. The strongest relationship existed between percent dietary saturated fat and percent protein or carbohydrate energy (p less than 0.0001). Polyunsaturated:saturated fat ratio was also weakly associated with percent protein and carbohydrate energy (p less than 0.05). Polyunsaturated, monounsaturated, omega 6 and omega 3 fatty acids were not significantly related to percent protein or carbohydrate energy. These results indicated that protein and carbohydrate selection patterns are altered in response to qualitatively different dietary fatty acids, and that the amount of saturated fat in the diet is the important characteristic of dietary fat mediating the behavioral alteration.

Learning is improved by a soybean oil diet in rats.

A semi-synthetic diet containing 20% polyunsaturated fat (soybean) oil was fed to young male hooded rats for 21 days. These animals exhibited improved performance on an environmentally-cued testing paradigm which is thought to reflect cognitive learning skills (i.e., Place Navigation Water Task). Other rats fed the same base diet but containing 20% saturated fat (lard) showed no such improvement compared to chow-fed (4.5% mixed fat) controls. The animals fed soybean oil also exhibited a transient resistance to extinguish this learning. This improved learning could not be explained by changes in general motor activity, basal body temperature, energy consumption, body weight, or in the brain activity of choline acetyltransferase, the marker enzyme for cholinergic neurons. These findings constitute the first evidence that short-term variations in the quality of dietary fat can enhance mammalian learning.

Nutrient contribution of infant cereals used as fluid thickening agents in diets fed to the elderly.

OBJECTIVE: To evaluate whether a nutrient-fortified fluid-thickening agent (Pablum, H. J. Heinz Co of Canada, North York, Ontario, Canada) replaces nutrients lost to food displacement associated with its use. DESIGN: Seven-day, investigator-weighted, food intake records were evaluated to determine the prevalence of nutrient inadequacy. Nutrient intakes, including and excluding those associated with Pablum, were assessed to determine the ability of Pablum to protect from nutrient inadequacy. SUBJECTS/SETTING SUBJECTS: (19 women and 2 men aged 69 to 109 years) were residents of a home for the aged or a chronic-care hospital who required pureed food and thickened fluids. STATISTICAL ANALYSES PERFORMED: Probability analysis was used to estimate the prevalence of nutrient inadequacy for micronutrients and protein. RESULTS: Approximately 15% of consumed energy (mean +/- standard deviation: 1.534 +/- 310 kcal/day; 1.38 +/- 0.37 and 1.46 +/- 0.26 multiplied by basal metabolic rate for men and women) came from the thickener. If a nonfortified thickener was used, risk of inadequacy (percentage of sample) would be apparent for protein (16%), calcium (95%), thiamin (57%), riboflavin (28%), niacin (55%), and folate (47% for women and 97% for men); no risk was estimated for iron and vitamins A and C. The nutrients contained in Pablum reduced or eliminated the risk of inadequacy for some nutrients, including protein (8%), calcium (9%), thiamin (0%), riboflavin (0%), and niacin (0%). In contrast, inadequate consumption of water and folate occurred even when the contribution of Pablum was considered. APPLICATIONS: The use of a nutrient-fortified thickening agent has merit; however, the current formulation of Pablum does not allow for complete protection against nutrient inadequacy.

Dietary fat source influences neuronal mitochondrial monoamine oxidase activity and macronutrient selection in rats.

We previously reported that qualitative changes in dietary fat influence certain monoaminergic mediated behaviours such as pain sensitivity and thermoregulation in a cold environment after an amphetamine challenge. The purpose of this study was to further explore the behavioural consequences of alterations in dietary fat intake by examining another behaviour known to be mediated by the monoamines--food intake regulation--and to begin investigating a biochemical link between dietary fat composition and behaviour. Rats were stabilized to 20% (w/w) soybean oil (SBO) or lard diets for 10 days and then allowed to select for protein (PRO) and carbohydrate (CHO) intake. While total food intake was unchanged, rats fed the SBO diet selected lower PRO (3.1 +/- 0.6 vs. 4.9 +/- 0.6 g/day, SBO vs. lard, respectively) and higher CHO (9.6 +/- 0.7 vs. 7.8 +/- 1.2) intakes than those consuming the lard based diet. Comparable differences were seen in a second trial. Current evidence suggests that the regulation of PRO and CHO intake is under serotonergic control. Therefore to determine whether dietary fat is mediating its effect on macronutrient selection via alterations in serotonin (5HT) metabolism, brain stem concentrations of 5HT and its metabolite 5-hydroxyindole acetic acid (5HIAA) and whole brain (minus brain stem) mitochondrial monoamine oxidase (MAO) activity were measured in a separate set of animals fed the SBO or lard diets for 28 days. Vmax of MAO was decreased in rats fed the SBO diets (20.2 +/- 7.4 vs. 27.9 +/- 8.9 nmol/mg prot/20') compared to those fed the lard diets. Km was unaltered by dietary fat fed. The change in activity of MAO was insufficient to alter steady-state levels of 5HT or 5HIAA. We propose that changes in neuronal functioning, induced by altered dietary fat, contributed to the differences seen in PRO and CHO selection.

Blood and tissue tocopherol levels in rats following intraperitoneally administered alpha-tocopheryl acetate.

The correction or maintenance of blood and tissue alpha-tocopherol (alpha-Toc) levels by intraperitoneally administered all-rac-alpha-tocopheryl acetate (alpha-Tac) was compared with RRR- alpha-tocopherol (alpha-Toc) in vitamin E-depleted and control rats. Rats received 1.3 TE vitamin E daily for 7 days. alpha-Tac was detected in plasma of one-third of alpha-Tac-treated rats 24 hr after the first treatment, although not in subsequent samplings. Both alpha-Tac and alpha-Toc increased tocopherol levels in plasma and liver of E-deprived rats, while little or no change was observed in adipose tissue and brain. Similarly, control rats treated with alpha-Tac or alpha-Toc had significantly greater (p less than 0.05) plasma and liver alpha-Toc levels at day 3 and day 7 than did saline-treated rats. There was no significant difference in adipose alpha-Toc levels among treatment groups of control rats. The results of this study suggest that alpha-Tac is rapidly hydrolyzed to its biologically active alcohol form and results in similar effects to that of intraperitoneally administered alpha-Toc.