Changes In Caloric Intake Research Articles

Impact of food craving and calorie intake on body mass index (BMI) changes during an 18-month behavioral weight loss trial.

The purpose of this study was to explore relations between food craving, caloric intake, and body mass index (BMI) changes over the course of an 18-month weight loss trial. Two-hundred two obese adults (mean BMI=34.9kg/m2; mean age=51.30years, 92.2% White; 57.8% female) who participated in a behavioral weight loss trial completed measures of food craving, caloric intake, and BMI at baseline, 6 and 18months. From baseline to 6months, higher initial food cravings were associated with more gradual and less steep reductions in BMI. Additionally, the relation between changes in food craving and BMI changes varied by levels of change in caloric intake, such that BMI change and change in food cravings were positively associated at low levels of change in caloric intake, but were unrelated at average and high levels of change in caloric intake. Similarly, from baseline to 6months and from 6 to 18months, the relation between changes in food craving and BMI changes also varied by initial levels of caloric intake. Explicit clinical targeting of food craving management may be beneficial for individuals beginning weight loss programs, especially for those who report higher levels of food craving at baseline. Baseline caloric intake and change in calorie intake over time may serve as moderators of the relation between food cravings and BMI.

Physiological Effort in Submaximal Fitness Tests Predicts Weight Loss in Overweight and Obese Men with Prostate Cancer in a Weight Loss Trial.

BackgroundObesity and weight gain after the diagnosis of prostate cancer are associated with an increased risk of prostate cancer recurrence and mortality; individualized plans to help prostate cancer survivors maintain or lose weight may be beneficial for recurrence risk reduction. Herein, we explore whether gains in cardiovascular fitness predict successful weight loss in men participating in a weight loss trial (NCT01886677).MethodsForty men were randomized to receive twice-weekly in-person and telephone-based guidance on calorie-restricted diets and aerobic exercise to promote ~0.91 kg/week weight loss, or wait-list control. Thirty-two men completed submaximal VO2 Treadmill Tests (TT), anthropometric measures and two 24-hour dietary recalls at baseline and follow-up. For this secondary analysis, study arms were combined and associations between baseline and longitudinal changes in physiological effort (PE, measured by heart rate during TT), predicted VO2max, caloric intake and weight loss were analyzed.ResultsMen lost 3.4 kg in 50 ± 23 days on the study. Multivariate linear regression indicated weight change was associated with change in PE at stage 2TT (Partial R = 0.635, p < 0.001), days on study (Partial R = −0.589, p = 0.002) and change in caloric intake (Partial R = 0.457, p = 0.019).ConclusionsUntrained men experiencing elevated heart rates during stage 2TT at baseline were able to achieve greater weight loss over the study period; this association was strengthened by a decrease in PE at the same level from baseline to follow-up concomitant with reduced caloric intake. Therefore, for these middle-aged and older men with lower aerobic fitness, exercise appears to be a key factor in achieving higher degrees of weight loss.

Marrow Adipose Tissue Expansion Coincides with Insulin Resistance in MAGP1-Deficient Mice.

Marrow adipose tissue (MAT) is an endocrine organ with the potential to influence skeletal remodeling and hematopoiesis. Pathologic MAT expansion has been studied in the context of severe metabolic challenge, including caloric restriction, high fat diet feeding, and leptin deficiency. However, the rapid change in peripheral fat and glucose metabolism associated with these models impedes our ability to examine which metabolic parameters precede or coincide with MAT expansion. Microfibril-associated glycoprotein-1 (MAGP1) is a matricellular protein that influences cellular processes by tethering signaling molecules to extracellular matrix structures. MAGP1-deficient (Mfap2−/−) mice display a progressive excess adiposity phenotype, which precedes insulin resistance and occurs without changes in caloric intake or ambulation. Mfap2−/− mice were, therefore, used as a model to associate parameters of metabolic disease, bone remodeling, and hematopoiesis with MAT expansion. Marrow adiposity was normal in Mfap2−/− mice until 6 months of age; however, by 10 months, marrow fat volume had increased fivefold relative to wild-type control at the same age. Increased gonadal fat pad mass and hyperglycemia were detectable in Mfap2−/− mice by 2 months, but peaked by 6 months. The development of insulin resistance coincided with MAT expansion. Longitudinal characterization of bone mass demonstrated a disconnection in MAT volume and bone volume. Specifically, Mfap2−/− mice had reduced trabecular bone volume by 2 months, but this phenotype did not progress with age or MAT expansion. Interestingly, MAT expansion in the 10-month-old Mfap2−/− mice was associated with modest alterations in basal hematopoiesis, including a shift from granulopoiesis to B lymphopoiesis. Together, these findings indicate MAT expansion is coincident with insulin resistance, but not excess peripheral adiposity or hyperglycemia in Mfap2−/− mice; and substantial MAT accumulation does not necessitate a proportional decrease in either bone mass or bone marrow cellularity.

Safety of minimizing preoperative starvation in critically ill and intubated trauma patients.

Cessation of enteral nutrition prior to an operation/procedure is the most common reason for feeding interruption in critically ill trauma patients and contributes to substantial calorie deficits. This study reports on a strategy to increase calorie intake by continuing feeds until transfer for operations/procedures. Nutrition guidelines were modified in 2006 to allow continuation of feeding in intubated patients up until transfer to the operating room. Prior to 2006, enteral feeding was stopped at least 6 hours prior to surgery. A retrospective cohort design from 2003 to 2010 compared clinical outcomes in groups of adult trauma subjects before and after guideline changes and in subjects at other centers without guideline changes. During the first week, subjects in the preimplementation cohort (n = 245) received a median of 3,787 kcal per person per week, while subjects in the postimplementation cohort (n = 368) received a median of 6,662 kcal per person per week (p < 0.001). There was no change in calorie intake for subjects at other centers (n = 1,002). The risks of acute respiratory distress syndrome, pneumonia, and mortality were decreased after implementation relative to the preimplementation cohort (acute respiratory distress syndrome: relative risk ratio [RR], 0.69; 95% confidence interval [CI], 0.59-0.81; pneumonia: RR, 0.82; 95% CI, 0.65-1.00; mortality: RR, 0.67; 95% CI, 0.46-0.99). Ventilator-free days increased by 1.4 days (95% CI, 0.1-2.7), while intensive care unit stay and hospital length of stay were unchanged. These outcomes showed similar trends over time at other participating centers. Allowing intubated trauma patients to continue enteral nutrition until transfer for operations or procedures was associated with increased caloric intake without evidence of increased pulmonary complications. This represents an important strategy to reduce calorie deficits in the trauma intensive care unit. Therapeutic study/care management, level III.

Roux-en-Y gastric bypass in rats progressively decreases the proportion of fat calories selected from a palatable cafeteria diet.

Roux-en-Y gastric bypass surgery (RYGB) decreases caloric intake in both human patients and rodent models. In long-term intake tests, rats decrease their preference for fat and/or sugar after RYGB, and patients may have similar changes in food selection. Here we evaluated the impact of RYGB on intake during a "cafeteria"-style presentation of foods to assess if rats would lower the percentage of calories taken from fat and/or sugar after RYGB in a more complex dietary context. Male Sprague-Dawley rats that underwent either RYGB or sham surgery (Sham) were presurgically and postsurgically given 8-days free access to four semisolid foods representative of different fat and sugar levels along with standard chow and water. Compared with Sham rats, RYGB rats took proportionally fewer calories from fat and more calories from carbohydrates; the latter was not attributable to an increase in sugar intake. The proportion of calories taken from protein after RYGB also increased slightly. Importantly, these postsurgical macronutrient caloric intake changes in the RYGB rats were progressive, making it unlikely that the surgery had an immediate impact on the hedonic evaluation of the foods and strongly suggesting that learning is influencing the food choices. Indeed, despite these dietary shifts, RYGB, as well as Sham, rats continued to select the majority of their calories from the high-fat/high-sugar option. Apparently after RYGB, rats can progressively regulate their intake and selection of complex foods to achieve a seemingly healthier macronutrient dietary composition.

Variations of body composition, physical activity and caloric intake in schoolchildren during national holidays.

Scientific literature has described that a significant body weight increase in schoolchildren occurs during some holiday periods (summer, winter, and thanksgiving holidays), harming their health. In this regard, it is thought that this phenomenon is mainly due to changes in eating habits and the variation in levels of physical activity; however, this approach has not yet been explored during national holidays (NAH) in Chile. To determine any changes in body composition, physical activity and caloric intake during NAH. A total of 46 schoolchildren (24 boys, age 10.5±0.5; BMI 21.7±4.7) participated. Measurements were performed 2days before and after the NAH (9days). Weight was measured and fat percentage was established using the Slaughter formula. Levels of physical activity were measured with accelerometers, validating 3weekdays and 1weekend; caloric intake was established through a 24-h recall. Weight, percentage of fat and caloric intake increased significantly (250g, 2.2% and 733.3kcal, respectively; p<0.05); however, none of the variables of physical activity showed significant changes. The change in caloric intake seems to be the main cause of weight and fat gain during the NAH.

Hypothyroidism Exacerbates Thrombophilia in Female Rats Fed with a High Fat Diet.

Clotting abnormalities are discussed both in the context with thyroid dysfunctions and obesity caused by a high fat diet. This study aimed to investigate the impact of hypo-, or hyperthyroidism on the endogenous thrombin potential (ETP), a master indicator of clotting activation, on Sprague Dawley rats fed a normal or high fat diet. Female Sprague Dawley rats (n = 66) were grouped into normal diet (ND; n = 30) and high-fat diet (HFD; n = 36) groups and subdivided into controls, hypothyroid and hyperthyroid groups, induced through propylthiouracil or triiodothyronine (T3) treatment, respectively. After 12 weeks of treatment ETP, body weight and food intake were analyzed. Successfully induced thyroid dysfunction was shown by T3 levels, both under normal and high fat diet. Thyroid dysfunction was accompanied by changes in calorie intake and body weight. In detail, compared to euthyroid controls, hypothyroid rats showed significantly increased—and hyperthyroid animals significantly decreased—ETP levels. High fat diet potentiated these effects in both directions. In summary, we are the first to show that hypothyroidism and high fat diet potentiate the thrombotic capacity of the clotting system in Sprague Dawley rats. This effect may be relevant for cardiovascular disease where thyroid function is poorly understood as a pathological contributor in the context of clotting activity and obesogenic nutrition.

Oxidized LDL Is Strictly Limited to Hyperthyroidism Irrespective of Fat Feeding in Female Sprague Dawley Rats.

Metabolic dysfunctions might play a crucial role in the pathophysiology of thyroid dysfunctions. This study aimed to investigate the impact of a controlled diet (normal versus high fat feeding) on hypothyroid and hyperthyroid Sprague Dawley rats. Female Sprague Dawley rats (n = 66) were grouped into normal diet (n = 30) and high-fat diet (n = 36) groups and subdivided into controls, hypothyroid and hyperthyroid groups, induced through propylthiouracil or triiodothyronine (T3) treatment, respectively. After 12 weeks of treatment metabolic parameters, such as oxidized LDL (oxLDL), malondialdehyde (MDA), 4-hydroxynonenal (HNE), the lipid profile, body weight and food intake parameters were analyzed. Successfully induced thyroid dysfunctions were shown by T3 levels, both under normal and high fat diet. Thyroid dysfunctions were accompanied by changes in calorie intake and body weight as well as in the lipid profile. In detail, hypothyroid rats showed significantly decreased oxLDL levels, whereas hyperthyroid rats showed significantly increased oxLDL levels. These effects were seen under high fat diet and were less pronounced with normal feeding. Taken together, we showed for the first time in female SD rats that only hyper-, but not hypothyroidism, is associated with high atherogenic oxidized LDL irrespective of normal or high-fat diet in Sprague Dawley rats.

Role of VMH ketone bodies in adjusting caloric intake to increased dietary fat content in DIO and DR rats.

The objective of this study was to determine the potential role of astrocyte-derived ketone bodies in regulating the early changes in caloric intake of diet induced-obese (DIO) versus diet-resistant (DR) rats fed a 31.5% fat high-energy (HE) diet. After 3 days on chow or HE diet, DR and DIO rats were assessed for their ventromedial hypothalamic (VMH) ketone bodies levels and neuronal ventromedial hypothalamic nucleus (VMN) sensing using microdialysis coupled to continuous food intake monitoring and calcium imaging in dissociated neurons, respectively. DIO rats ate more than DR rats over 3 days of HE diet intake. On day 3 of HE diet intake, DR rats reduced their caloric intake while DIO rats remained hyperphagic. Local VMH astrocyte ketone bodies production was similar between DR and DIO rats during the first 6 h after dark onset feeding but inhibiting VMH ketone body production in DR rats on day 3 transiently returned their intake of HE diet to the level of DIO rats consuming HE diet. In addition, dissociated VMN neurons from DIO and DR rats were equally sensitive to the largely excitatory effects of β-hydroxybutyrate. Thus while DR rats respond to increased VMH ketone levels by decreasing their intake after 3 days of HE diet, this is not the case of DIO rats. These data suggest that DIO inherent leptin resistance prevents ketone bodies inhibitory action on food intake.

Aerobic Training Increases Expression Levels of SIRT3 and PGC-1α in Skeletal Muscle of Overweight Adolescents Without Change in Caloric Intake.

Sirtuin 3 enzyme (SIRT3) is involved in the regulation of mitochondrial energy homeostasis by activating Peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α). Murine models have shown that the protein SIRT3 was modified by exercise and diet, however, the effect of exercise without diet in humans has not been examined. Propose of this paper was to analyze the effect of aerobic training on SIRT3 and PGC-1α in skeletal muscle of overweight adolescents without change in caloric intake. Fourteen overweight or obese male adolescents (15.5 ± 0.8 years) trained 3 days-week/50 min × session, at 70-80% of maximal heart rate for 12 weeks. Anthropometrics and skeletal muscle biopsies from the vastus lateralis were taken before and after the exercise program to measure adiposity, SIRT3, and PGC-1α proteins. Peak aerobic capacity (VO2peak) was estimated before and after training. The participants did not change their eating habits during the intervention. SIRT3 (1.05 ± 0.11 vs. 1.25 ± 0.14 AU, p = .014) and PGC-1a (1.06 ± 0.15 Vs 1.39 ± 0.20 AU, p = .009) increased. Fat percentage and waist circumference decreased (p < .05). VO2peak increased after training (p < .001). There was a significant association between SIRT3 and PGC-1α after training program. These data suggest that aerobic training increased SIRT3 and PGC-1a expression levels in sedentary, overweight, or obese adolescents.

Modeling body mass variation: incorporating social influence into calculations of caloric intake and energy expenditure.

Variations in individual body mass and composition have long been a key focus in the health sciences, particularly now that overweight and obesity are considered as public health problems. We study a mathematical model that describes body mass variations which are determined by the energy balance between caloric intake and total energy expenditure. To calculate the change in caloric intake and energy expenditure over time, we proposed a relationship for each of these quantities, and we used measured values that are reported in the literature for the initial conditions. To account for small variations in the daily energy balance of an individual, we include social interactions as the multiplication of two terms: social proximity and social influence. We observe that social interactions have a considerable effect when the body mass of an individual is quite constant and social interactions take random values. However, when an individual's mass value changes (either increases or decreases), social interactions do not have a notable effect. In our simulation, we tested two different models that describe the body mass composition, and it resulted that one fits better the data.

PC-FACS

PC-FACS

A metabolic-epidemiological microsimulation model to estimate the changes in energy intake and physical activity necessary to meet the Healthy People 2020 obesity objective.

We combined a metabolic and an epidemiological model of obesity to estimate changes in calorie intake and physical activity necessary to achieve the Healthy People 2020 objective of reducing adult obesity prevalence from 33.9% to 30.5%. We used the National Health and Nutrition Examination Survey (1999-2010) to construct and validate a microsimulation model of the US population aged 10 years and older, for 2010 to 2020. Obesity prevalence is expected to shift toward older adults, and disparities are expected to widen between White, higher-income groups and minority, lower-income groups if recent calorie consumption and expenditure trends continue into the future. Although a less than 10% reduction in daily calorie intake or increase in physical activity would in theory achieve the Healthy People 2020 objective, no single population-level intervention is likely to achieve the target alone, and individual weight-loss attempts are even more unlikely to achieve the target. Changes in calorie intake and physical activity portend rising inequalities in obesity prevalence. These changes require multiple simultaneous population interventions.

Alpha-Lipoic Acid Reduces LDL-Particle Number and PCSK9 Concentrations in High-Fat Fed Obese Zucker Rats

We characterized the hypolipidemic effects of alpha-lipoic acid (LA, R-form) and examined the associated molecular mechanisms in a high fat fed Zucker rat model. Rats (n = 8) were assigned to a high fat (HF) diet or the HF diet with 0.25% LA (HF-LA) for 30 days and pair fed to remove confounding effects associated with the anorectic properties of LA. Compared with the HF controls, the HF-LA group was protected against diet-induced obesity (102.5±3.1 vs. 121.5±3.6,% change BW) and hypercholesterolemia with a reduction in total-C (−21%), non-HDL-C (−25%), LDL-C (−16%), and total LDL particle number (−46%) and an increase in total HDL particles (∼22%). This cholesterol-lowering response was associated with a reduction in plasma PCSK9 concentration (−70%) and an increase in hepatic LDLr receptor protein abundance (2 fold of HF). Compared with the HF-fed animals, livers of LA-supplemented animals were protected against TG accumulation (−46%), likely through multiple mechanisms including: a suppressed lipogenic response (down-regulation of hepatic acetyl-CoA carboxylase and fatty acid synthase expression); enhanced hepatic fat oxidation (increased carnitine palmitoyltransferase Iα expression); and enhanced VLDL export (increased hepatic diacylglycerol acyltransferase and microsomal triglyceride transfer protein expression and elevated plasma VLDL particle number). Study results also support an enhanced fatty acid uptake (2.8 fold increase in total lipase activity) and oxidation (increased CPT1β protein abundance) in muscle tissue in LA-supplemented animals compared with the HF group. In summary, in the absence of a change in caloric intake, LA was effective in protecting against hypercholesterolemia and hepatic fat accumulation under conditions of strong genetic and dietary predisposition toward obesity and dyslipidemia.

The Many Faces of Sirtuins: Sirtuins and the Warburg effect

Metabolic regulators that permit adaptation to changes in caloric intake have been shown to be needed to protect from age-related disorders. Sirtuins play a crucial part in this program, impinging on not only aging but also other diseases. New findings are uncovering the multifaceted activity of sirtuins in living organisms and their effects on healthspan. In 'Bedside to Bench', Leonard Guarente discusses how different sirtuins are hindering cancer metabolism through suppression of the Warburg effect. The apparent antitumor effects of several sirtuins through their regulation of different metabolic pathways suggest therapeutic approaches to induce sirtuin function or that of downstream targets may block cancer growth. In 'Bench to Bedside', Eric Verdin peruses a few studies in different animal models showing that increased amounts of nicotinamide adenine dinucleotide (NAD), a cofactor of sirtuins, may have a positive effect in longevity and span of healthy life, or healthspan, by increasing sirtuin enzymatic activity. Whether harnessing NAD therapeutically is a potential way to extend lifespan and ameliorate diseases is still open to debate.

Confronting fear using exposure and response prevention for anorexia nervosa: A randomized controlled pilot study

Anorexia nervosa (AN) is a severe illness with high rates of relapse. Exposure and Response Prevention for AN (AN-EXRP) is a new approach that specifically addresses maladaptive eating behavior by targeting eating-related fear and anxiety. The aim of this study was to evaluate AN-EXRP as an adjunctive strategy to improve eating behavior during weight restoration, at a pivotal moment when treatment goals shift toward relapse prevention. A randomized controlled trial was conducted to compare AN-EXRP with a comparison condition, Cognitive Remediation Therapy (CRT). Hospitalized patients with AN (n = 32) who had achieved weight restoration to a BMI > 18.5 kg/m(2) received 12 sessions of either AN-EXRP or CRT. Outcome was assessed by change in caloric intake in an objective assessment of eating behavior. The average test meal caloric intake of participants who received AN-EXRP increased from 352 ± 263 kcal at baseline to 401 ± 215 kcal post-treatment, while that of participants who received CRT decreased from 501 ± 232 kcal at baseline to 424 ± 221 kcal post-treatment [t(28) = 2.5, p = .02]. Improvement in intake was significantly associated with improvement in eating-related anxiety (Spearman's ρ = 0.40, p = .03). These data demonstrate that AN-EXRP, compared to a credible comparison intervention, is associated with better caloric intake in a laboratory meal over time in AN. Additional studies are required to determine whether incorporation of these techniques into a longer treatment program leads to enduring and clinically significant change.

Treatment with the Nitric Oxide Donor SNP Increases Triiodothyronine Levels in Hyper- and Hypothyroid Sprague-Dawley Rats

Nitric oxide pathway might play a crucial role in the pathophysiology of thyroid dysfunctions. This study aimed to investigate the impact of nitric oxide (NO) on hypothyroid and hyperthyroid Sprague-Dawley rats under controlled diet. Furthermore, the effects of the nitric oxide donor sodium nitroprusside (SNP) on thyroid dysfunctions were also assessed. Sprague-Dawley rats (n=107) were subdivided into normal diet and high-fat diet (HFD) groups and grouped into controls, hypothyroid, hyperthyroid, and SNP treated groups. Hypothyroidism was induced through propylthiouracil, whereas hyperthyroidism by triiodothyronine (T3). After 12 weeks of T3 treatment, serum nitric oxides (NOX), endogenous asymmetric dimethylarginine (ADMA), body weight and food intake were analyzed. Hypothyroid rats showed decreased serum T3 levels, hyperthyroid rats increased T3 compared to controls. Diet had no impact on T3. Thyroid dysfunctions were accompanied by changes in calorie intake and body weight. Serum NOX was significantly reduced in normal diet hypothyroid rats. SNP administration compensated the decrease and markedly increased T3. NO synthase inhibitor ADMA levels were significantly higher in the HFD control group than in the normal diet controls. ADMA was declined in both hypothyroid groups and increased in normal diet hyperthyroid rats. An association of thyroid dysfunctions with reduced bioavailability of NO and alterations of ADMA levels could be established. Treatment with the NO donor SNP resulted in an increase of serum T3 levels. These results demonstrate that the NO pathway is implicated in thyroid dysfunctions, which may be of clinical relevance.

Gut microbiota after gastric bypass in human obesity: increased richness and associations of bacterial genera with adipose tissue genes

Roux-en-Y gastric bypass (RYGB) surgery is one of the most efficient procedures for treating morbid obesity and results in weight-loss and improvements in metabolism and inflammation. We examined the impact of RYGB on modifications of gut microbiota and its potential associations with changes in gene expression in white adipose tissue (WAT). Gut microbiota were profiled from fecal samples by using pyrosequencing in morbidly obese individuals, explored before (0 mo), 3 mo after, and 6 mo after RYGB. WAT gene expression was studied at 0 and 3 mo. We explored associations between microbial genera and differentially expressed genes in WAT and clinical markers. The richness of gut microbiota increased after RYGB; 37% of increased bacteria belonged to Proteobacteria. The associations between gut microbiota composition and WAT gene expression increased after RYGB. Fourteen discriminant bacterial genera (7 were dominant and 7 were subdominant) and 202 WAT genes changed after RYGB. Variations in bacterial genera correlated with changes in both clinical phenotype and adipose tissue gene expression. Some genes encode metabolic and inflammatory genes. Almost half of the correlations were independent of the change in calorie intake. These results show an increase in gut microbiota richness and in the number of associations between gut microbiota and WAT genes after RYGB in obesity. Variations of gut microbiota were associated with changes in WAT gene expression. These findings stimulate deeper explorations of the mechanisms linking gut microbiome and WAT pathological alterations in human obesity and its changes after weight loss.

Effects of chronic mild stress on rats selectively bred for behavior related to bipolar disorder and depression

To test the possibility that chronic mild stress (CMS) might be unreliable in producing its often-intended outcome (i.e., decreased preference for sucrose, hypothesized to represent depression-relevant anhedonia) because it is typically applied to “normal” rats, a CMS procedure was applied to rats that may possess genetic susceptibility to affective disorders, having had been selectively-bred to show behavior indicative of such disorders. These rat lines were: Hyperactive (HYPER) rats, which show characteristics of bipolar disorder, Swim-test Susceptible (SUS) and Swim-test Resistant (RES) rats, being susceptible or resistant to effects of stress in the swim test, Swim High-active (SwHi) and Swim Low-active (SwLo) rats, which innately show high or low activity in the swim test. These selectively-bred lines were compared to normal, non-selectively bred (NS) rats. During CMS, HYPER rats, both females and males, as well as RES and SwHi rats, showed reduced consumption of a palatable 2% sucrose solution, and reduced preference for sucrose (vs. water) in comparison to non-stressed rats (no CMS) of the same lines. In contrast, CMS produced no decrease in sucrose consumption or in preference for sucrose in normal NS rats, and actually a caused a slight increase in sucrose consumption and preference in male NS rats. Other measures that indicate depression – food intake and motor activity in the home cage – were also assessed. SwLo and SwHi showed greater sensitivity to having their home-cage ambulatory activity reduced by CMS than did NS rats, but no other such differences relative to NS rats were seen for these other measures; thus, changes in sucrose intake or preference could not be explained by a change in caloric intake. These results suggest that the genetic attributes of animals can influence the outcome of CMS, and that the application of CMS to normal, non-selected rats may account, at least in part, for the unreliability of CMS in decreasing consumption of palatable substances and decreasing preference for such substances.

The medical use of cannabis for reducing morbidity and mortality in patients with HIV/AIDS

The use of cannabis (marijuana) or of its psychoactive ingredient delta-9-tetrahydrocannabinol (THC) as a medicine has been highly contested in many settings.There have been claims that smoked or ingested cannabis, either in its natural form or artificial form (pharmaceutically manufactured drug such as dronabinol), improves the appetites of people with AIDS, results in weight gain and lifts mood, thus improving the quality of life. The objectives of this review were to assess whether cannabis (in its natural or artificially produced form), either smoked or ingested, decreases the morbidity or mortality of patients infected with HIV. The search strategy was conducted to July 2012 and was based on that of the Cochrane HIV/AIDS Review Group. We searched the following databases: CENTRAL/CCTR, MEDLINE and EMBASE. In addition, searching was performed where necessary of journals, reference lists of articles, and conference proceedings. The review included randomised controlled trials (RCTs) of any cannabis intervention, in any form, and administered by any route, in adults with HIV or AIDS, compared with placebo or with a known effective treatment, and conducted in a hospital, outpatient clinic, or home care setting. Quasi-randomised studies using any form of cannabis as an intervention in patients with HIV or AIDS were also included. Data from the eligible studies were extracted and coded independently by two researchers, using a standardised data extraction form. Data were then analysed using RevMan 5.0. No meta-analyses were performed. A total of seven relevant studies were included in the review, reported in eight publications. All were randomised controlled studies, with four utilising a parallel group design, two a within-subject randomisation and two a cross-over design. All of the studies were of a fairly short duration, ranging from 21 days to 84 days. In only four papers (in effect, three studies) were sequence generation and allocation concealment judged to be adequate. The use of cannabis and rapidly acting cannabinoids posed considerable challenges for blinding, as the psychoactive effects are expected to be quickly discernible to study participants, particularly those who have been previous users of such products. Dronabinol was expected to be more easily blinded. The outcomes measured were variable, including change in weight, change in body fat (measured as a percentage of total body weight), change in appetite (measured on a visual analogue scale), change in caloric intake (measured in kcals/kg/24hr), change in nausea and vomiting (measured on a visual analogue scale), change in performance (measured by Karnofsky performance score or specific tests for memory and dexterity) and change in mood (measured on a visual analogue scale).The evidence for substantial effects on morbidity and mortality is currently limited. Data from only one relatively small study (n=139, of which only 88 were evaluable), conducted in the period before access to highly-active antiretroviral therapy (HAART), showed that patients administered dronabinol were twice as likely to gain 2kg or more in body weight (RR 2.09), but the confidence interval for this measure (95% CI 0.72 - 6.06) included unity. The mean weight gain in the dronabinol group was only 0.1kg, compared with a loss of 0.4kg in the placebo group. However, the quality of sequence generation and allocation concealment in this study, in which participants were randomised by centre, could not be assessed. Despite dronabinol being registered by at least some medicines regulatory authorities for the treatment of AIDS-associated anorexia, and some jurisdictions making allowances for the "medical" use of marijuana by patients with HIV/AIDS, evidence for the efficacy and safety of cannabis and cannabinoids in this setting is lacking. Such studies as have been performed have been of short duration, in small numbers of patients, and have focused on short-term measures of efficacy. Long-term data, showing a sustained effect on AIDS-related morbidity and mortality and safety in patients on effective antiretroviral therapy, has yet to be presented. Whether the available evidence is sufficient to justify a wide-ranging revisiting of medicines regulatory practice remains unclear.