Three-month Diet Research Articles

Moderate Weight Loss is associated with Reductions in LH Pulse Frequency and Increases in 24-hour Cortisol with no change in Perceived Stress in Young Ovulatory Women

ObjectiveDetermine the potential role of cortisol as an indicator of both metabolic and psychosocial stress and its relation to LH pulse dynamics during a three-month diet and exercise intervention causing moderate weight loss. MethodsSecondary analysis of a randomized controlled trial that demonstrated the causal role of low energy availability in the disruption of the menstrual cycle. Twenty-one women aged 18-24 yrs (BMI 21.7± 1.9 kg·m−2), completed a baseline menstrual cycle and three intervention menstrual cycles of a controlled diet and supervised exercise program. Twenty-four-hour LH pulse dynamics (q10 min) and diurnal patterns of cortisol (q60 min) as well as Perceived Stress Scale scores were determined in the early follicular phase prior to the intervention and in the post intervention cycle. Pre to post comparisons were determined with paired t-tests, and Pearson bivariate correlations assessed associations. ResultsSubjects lost weight (-2.8±1.97 kg) and LH pulse frequency declined pre=0.79±0.23 pulses·hr−1 to post=0.60±0.29 pulses·hr−1 (p=0.014). Weight loss was associated with an increase in cortisol AUC R= -0.473, (p=0.03) and the decline in LH pulse frequency R= 0.523; (p=0.026). Increases in cortisol AUC were associated with declines in LH pulse frequency R= -0.472; (p=0.048). The morning cortisol rise AUC increased from pre=2140±878 µg·dL−1 · day to post=2556±1067 µg·dL−1 · day (p=0.034). Changes in PSS were not associated with changes in LH or cortisol. ConclusionThe initial perturbation of LH pulsatility with moderate diet and exercise is associated with metabolically driven increases in cortisol AUC with no influence of psychological stress.

Ketogenic diets as an adjuvant therapy for glioblastoma (KEATING): a randomized, mixed methods, feasibility study

PurposeWe conducted a feasibility study to investigate the use of ketogenic diets (KDs) as an adjuvant therapy for patients with glioblastoma (GBM), investigating (i) trial feasibility; (ii) potential impacts of the trial on patients’ quality of life and health; (iii) patients’ perspectives of their decision-making when invited to participate in the trial and (iv) recommending improvements to optimize future phase III trials.MethodsA single-center, prospective, randomized, pilot study (KEATING), with an embedded qualitative design. Twelve newly diagnosed patients with GBM were randomized 1:1 to modified ketogenic diet (MKD) or medium chain triglyceride ketogenic diet (MCTKD). Primary outcome was retention at three months. Semi-structured interviews were conducted with a purposive sample of patients and caregivers (n = 15). Descriptive statistics were used for quantitative outcomes and qualitative data were analyzed thematically aided by NVivo.ResultsKEATING achieved recruitment targets, but the recruitment rate was low (28.6%). Retention was poor; only four of 12 patients completed the three-month diet (MCTKD n = 3; MKD n = 1). Participants’ decisions were intuitive and emotional; caregivers supported diet implementation and influenced the patients’ decision to participate. Those who declined made a deliberative and considered decision factoring diet burden and quality of life. A three-month diet was undesirable to patients who declined and withdrew.ConclusionRecruitment to a KD trial for patients with GBM is possible. A six-week intervention period is proposed for a phase III trial. The role of caregivers should not be underestimated. Future trials should optimize and adequately support the decision-making of patients.

Ketogenic diets as an adjuvant therapy in glioblastoma (KEATING): A mixed methods randomised feasibility study

Abstract Background There is increasing interest in the use of ketogenic diets (KD) as adjuvant therapy for glioblastoma (GBM). Trial aims: i) investigate protocol feasibility; ii) assess patient/carer acceptability; iii) explore the decision-making of patients’ invited to participate in KEATING; and iv) inform phase III trial design. Methods Prospective, feasibility study, with embedded qualitative design randomised 12 newly-diagnosed GBM patients to three months of medium chain triglyceride ketogenic diet (MCTKD) or the modified ketogenic diet (MKD) during chemoradiotherapy. Primary outcome was retention; secondary outcomes included recruitment rate, dietary acceptability, progression free survival (PFS) and overall survival (OS). Semi-structured interviews were conducted with a representative sample of patients and relatives (n=15). Results Recruitment targets were achieved, but recruitment rate was low (28.6%). Retention was poor; only 4 of 12 completed the three-month diet (MCTKD n=3; MKD n=1). Median duration until discontinuing was 5.2 weeks (0–7 weeks; n=8). Participants made instantaneous decisions without deliberation: relatives supported diet implementation. Decliners made considered decisions factoring diet burden and quality of life. A three-month diet was undesirable to these patients. Median PFS was 11.4 weeks and OS was 67.3 weeks. Conclusion Recruitment to a ketogenic-glioblastoma trial is possible. To assess effectiveness in a phase III clinical trial, a six week intervention period is proposed. Future trials should optimise and adequately support the decision-making of patients. The role of relatives should not be underestimated.

SAT-208 Effects of Metabolic and Psychological Stressors on Serum 24-Hour Cortisol and Luteinizing Hormone

Exercising women with functional hypothalamic amenorrhea (FHA) experience disrupted luteinizing hormone pulsatility which has been linked to low energy availability. While the susceptibility to life stressors in also linked to reproductive axis suppression, the contribution of psychosocial stress to FHA in exercising women is unclear. Our aim was to prospectively determine the relations between indicators of psychosocial and metabolic stressors on the change in LH pulse dynamics during a three-month diet and exercise intervention causing moderate weight loss in previously untrained, ovulatory, collage age women studied across an academic year. We also explored the potential role of cortisol as an indicator of both metabolic and psychosocial stress in the change in LH. This is a secondary analysis from a previously published randomized, controlled trial demonstrating the causal role of low energy availability in the disruption of the menstrual cycle. Here, we report on 21 women aged (18 to 24 yrs), BMI (21.7± 1.9 kg/m2), aerobic capacity (37.5 ± 5.3 ml/kg/min) who completed a baseline menstrual cycle and three intervention menstrual cycles of a controlled diet (55% carbohydrates, 30% protein, 15% fat) and supervised aerobic exercise (5 days/wk, 30-90 min/day, 60-80% maximum heart rate). We assessed anthropometrics, aerobic capacity, psychosocial stress (Perceived Stress Scale), and metabolic hormones throughout the intervention. 24 hour LH pulse dynamics (q10 min) and diurnal patterns of cortisol (q60 min) were determined in the early follicular phase prior to the intervention and in the follicular phase of the 3rd intervention cycle or in the post intervention cycle. Pre to post comparisons were determined with paired t-tests, and Pearson bivariate correlations assessed associations. Subjects lost weight pre=57.8±4.9 kg to post=55.0±4.6 kg (p<0.001) and gained aerobic capacity pre=37.5 ± 5.3 ml/kg/min to post= 42.3 ± 5.9 ml/kg/min (p=.003). LH pulse frequency declined pre=0.79±0.23 pulses/hr to post=0.60±.29 pulses/hr (p=0.014), but mean LH and pulse amplitude were unchanged. 24 hour cortisol area under the curve increased significantly from pre=6716 ±3839 µg*day/dL to post=8515 ±2259 µg*day/dL (p=0.003). Increases in cortisol AUC were associated with a decline in LH pulse frequency R=-0.472; (p=0.048). The change in PSS was not associated with the change in LH or the change in cortisol. Body weight declines were associated with increases in cortisol AUC R= -0.473, (p=0.03) and the decline in LH pulse frequency R= 0.523; (p=0.026). These results suggest that the initial perturbation of LH pulsatility with moderate diet and exercise is largely metabolically driven and not influenced by individual responses to life stressors experienced across the academic year.

Effect of a Three-month Period of Diet and pPhysical Activity on Adipokines and Inflammatory Status in Children with Metabolic Syndrome

The prevalence of metabolic syndrome (MetS) in the young population continues to rise. This study aimed to determine whether adipokines are significant markers in defining MetS in a pediatric population and to assess the effect of a hypocaloric diet and physical activity on serum concentrations of adiponectin, leptin, and high-sensitivity C-reactive protein (hs-CRP). A prospective study was conducted over a period of 1 year, between January and December 2015, on 66 cases of obesity in children diagnosed at the Louis Turcanu Emergency Hospital for Children in Timisoara, Romania. The patients diagnosed with MetS were put on diet and physical exercise for 3 months. MetS was present in 63.6 % of obese children. There was a significant and positive correlation between MetS and both leptin and hs-CRP and a significant, negative correlation between MetS and adiponectin. After diet and physical activity, 3 patients no longer met the criteria for MetS. Leptin, adiponectin and hs-CRP concentrations statistically improved after a three-month diet and physical activity program. In conclusion, hs-CRP, leptin and adiponectin can be used as predictors of cardiovascular risk in the pediatric population. Diet and physical activity have an impact on metabolic status.

APOB-516 T allele homozygous subjects are unresponsive to dietary changes in a three-month primary intervention study targeted to reduce fat intake

Dietary guidelines aim to control fat intake and reduce cardiovascular risk but an important interindividual variability occurs among subjects. The objective was to investigate whether the response of lipid and glucose homeostasis parameters after a three-month diet aimed at reducing cardiovascular risk could be modulated by the -516C/T polymorphism in the apolipoprotein B gene (APOB). Middle-aged men (n = 69) and women (n = 100) with moderate cardiovascular disease risk were advised to reduce total energy and fat intakes and replace saturated dietary fat by monounsaturated and polyunsaturated fat. Subjects were genotyped for APOB-516C/T polymorphism. At the entry and at the end of the three-month period, fasting and postprandial plasma lipid analyses were performed. At entry, subjects homozygous for the APOB-516 T allele exhibited significantly lower fasting plasma concentrations of apolipoprotein B 48, triglycerides and triglyceride-rich lipoproteins-triglycerides compared to C carrier subjects. After the diet period, while C carrier subjects presented a clear improvement of most biological parameters, paradoxically T/T subjects did not modify them. In addition, the apoB 48 postprandial response after a standardized mixed test meal was not improved in T/T subjects after the three-month diet, contrary to C allele carriers. Even though their phenotype at entry does not show any significant increase of risk factors when compared to other groups, subjects homozygous for the APOB-516 T allele are unresponsive to a healthy diet that improves cardiovascular risk status in the whole population.

Does Relief of Critical Arterial Stenosis Accelerate Distal Atherosclerosis?

Progression of atherosclerosis following balloon angioplasty, arterial bypass, or endarterectomy often limits long-term success of revascularization procedures. Therefore, the authors studied the effect of stenosis and relief of stenosis on the development of distal atherosclerosis in a primate model of diet-induced atherosclerosis. Severe stenosis (78 ± 2% diameter reduction) was produced in the midthoracic aorta in 14 cynomolgus monkeys by a constricting band. In 8 monkeys, the stenosis was left in place for three months, after which the distal aorta was revascularized by removal of the constricting band and by balloon angioplasty of the residual stenosis. The results in this group were compared with those in 6 animals whose stenoses were not reversed and with those in 10 animals with no preexisting stenosis. All three groups received an atherogenic diet for three months with no difference in serum cholesterol (836 to 1059 mg/o) during the three-month diet period. Animals with a stenosis had a significant decrease in surface atherosclerosis in the distal aorta (7 ± 6%) compared with control animals (51 + 8%, P &lt; 0.05). This was accompanied by marked reduction in mural cholesterol content (1.5 ± 0.4 mcg/mm2 vs 6.3 ± 1.8 mcg/mm2 in controls, P &lt; 0.05) and a decrease in intimal thickness (0.04 ± 0.02 mm vs 0.07 ± 0.01 mm in controls, P &lt; 0.05). After relief of the stenosis, the percent surface atherosclerosis (58 ± 8%), mural cholesterol (5.4 ± 1.0 mcg/mm2), and intimal thickness (0.09 ± 0.01 mm) were no different from controls. Thus, severe stenosis protects the distal vascular tree from intimal plaque formation, despite marked hypercholesterolemia. Following reversal of a stenosis, distal plaque progression does not occur at an accelerated rate but instead occurs at the same rate as without a preexisting stenosis.