The influence of low-carbohydrate diets on the metabolic response to androgen-deprivation therapy in prostate cancer.

BACKGROUND: Prostate cancer (PC) is the second most lethal cancer for men. For metastatic PC, standard first-line treatment is androgen deprivation therapy (ADT). While effective, ADT has many metabolic side effects. Previously, we found in serum metabolome analysis that ADT reduced androsterone sulfate, 3-hydroxybutyric acid, acyl-carnitines but increased serum glucose. Since ADT reduced ketogenesis, we speculate that low-carbohydrate diets (LCD) may reverse many ADT-induced metabolic abnormalities in animals and humans. METHODS: In a multicenter trial of patients with PC initiating ADT randomized to no diet change (control) or LCD, we previously showed that LCD intervention led to significant weight loss, reduced fat mass, improved insulin resistance, and lipid profiles. To determine whether and how LCD affects ADT-induced metabolic changes, we analyzed serum metabolites after 3-, and 6-months of ADT on LCD versus control. RESULTS: We found androsterone sulfate was most consistently reduced by ADT and was slightly further reduced in the LCD arm. Contrastingly, LCD intervention increased 3-hydroxybutyric acid and various acyl-carnitines, counteracting their reduction during ADT. LCD also reversed the ADT-reduced lactic acid, alanine, and S-adenosyl methionine (SAM), elevating glycolysis metabolites and alanine. While the degree of androsterone reduction by ADT was strongly correlated with glucose and indole-3-carboxaldehyde, LCD disrupted such correlations. CONCLUSIONS: Together, LCD intervention significantly reversed many ADT-induced metabolic changes while slightly enhancing androgen reduction. Future research is needed to confirm these findings and determine whether LCD can mitigate ADT-linked comorbidities and possibly delaying disease progression by further lowering androgens.

Randomised clinical trial: reducing the intake of dietary FODMAPs of breastfeeding mothers is associated with a greater improvement of the symptoms of infantile colic than for a typical diet.

BACKGROUND: Therapeutic diets for infantile colic lack evidence. In breastfed infants, avoiding "windy" foods by the breastfeeding mother is common. AIM: To examine the effects of a maternal low-FODMAP (Fermentable, Oligosaccharides, Disaccharides, Monosaccharides, And Polyols) diet compared to a typical-Australian diet on infant crying-fussing durations of infants with colic in a randomised, double-blind, crossover feeding study. METHODS: Between 2014 and 2016 exclusively breastfed infants aged ≤9 weeks meeting Wessel criteria for colic were recruited. Mothers were provided a 10-day low-FODMAP or typical-Australian diet, then alternated without washout. Infants without colic (controls) were observed prospectively and mothers remained on habitual diet. Infant crying-fussing durations were captured using a Barr Diary. Measures of maternal psychological status and samples of breast milk and infant faeces were collected. RESULTS: Mean crying-fussing durations were 91 min/d in seven controls compared with 269 min/d in 13 colicky infants (P < 0.0001), which fell by median 32% during the low-FODMAP diet compared with 20% during the typical-Australian diet (P = 0.03), confirmed by a two-way mixed-model analyses-of-variance (ƞp 2  = 0.719; P = 0.049) with no order effect. In breast milk, lactose concentrations remained stable and other known dietary FODMAPs were not detected. Changes in infant faecal calprotectin were similar between diets and groups, and faecal pH did not change. Median maternal anxiety and stress fell with the typical-Australian diet (P < 0.01), but remained stable on the low-FODMAP diet. CONCLUSIONS: Maternal low-FODMAP diet was associated with enhanced reduction in crying-fussing durations of infants with colic. This was not related to changes in maternal psychological status, gross changes in breast milk or infant faeces. Mechanisms require elucidation. Trial Registration Australian New Zealand Clinical Trials Registry (ANZCTR): 12616000512426 - anzctr.org.au.

Ketogenic diet therapies in France: State of the use in 2018.

Ketogenic diets (KDs) are well-established treatments for pharmacoresistant epilepsies and some metabolic disorders. The amount of publications including evidence-based trials has continuously increased in the last 10 years. We evaluated the use of KDs in France using 2 surveys from more than ten years ago (2005 and 2008). METHODS: We conducted a new survey based on 10 questions to evaluate the evolution of the practice since 2008 and the thoughts of French pediatric neurologists on the barriers as well as possible ways to support the use of KDs. RESULTS: All centers increased their use of KDs over time. There are now 5 out of 25 centers that are prescribing the modified Atkins diet. French pediatric neurologists reported the acceptability and the everyday life burden due to KDs as the most important barriers. CONCLUSION: The use of the diet in France seems to follow the increase of knowledge in this field.

Dietary Patterns in Secondary Prevention of Heart Failure: A Systematic Review.

BACKGROUND: Diet is an important factor in secondary prevention of heart failure (HF) but there is still no consensus as to which dietary model should be adopted by this population. This systematic review aims to clarify the relationship between dietary patterns and secondary prevention in HF. METHODS: We searched the Medline, Embase and Cochrane databases for studies with different dietary patterns and outcomes of secondary prevention in HF. No limitation was used in the search. RESULTS: 1119 articles were identified, 12 met the inclusion criteria. Studies with Dietary Approaches to Stop Hypertension (DASH), Mediterranean, Hyperproteic and Low-carb diets were found. The DASH pattern showed improvement in cardiac function, functional capacity, blood pressure, oxidative stress and mortality. The Mediterranean diet had a correlation with inflammation, quality of life and cardiac function but just on cross-sectional studies. Regarding the Hyperproteic and Low-carb diets only one study was found with each pattern and both were able to improve functional capacity in patients with HF. CONCLUSIONS: DASH pattern may have benefits in the secondary prevention of HF. The Mediterranean diet demonstrated positive correlation with factors of secondary prevention of HF but need more RCTs and cohort studies to confirm these effects. In addition, the Hyperproteic and Low-carb diets, despite the lack of studies, also demonstrated positive effects on the functional capacity in patients with HF.

Headache in mitochondrial disorders.

Headache is a prominent feature in mitochondrial disorders (MIDs) but no comprehensive overview is currently available. This review aims at summarising and discussing findings concerning type, frequency, pathogenesis, and treatment of headache in MIDs. The most frequent headache types in MIDs are migraine and migraine-like headache (MLH). MLH is classified as secondary headache. More rarely, tension-type headache, trigemino-autonomic headache, or different secondary headaches can be found. Migraine or MLH may manifest with or without aura. MLH is frequently associated with an ongoing or previous stroke-like episode (SLE) or a seizure but may also occur independently of other neurological features. MLH may be associated with prolonged aura or visual phenomena after headache. Except for MLH, treatment of headache in MIDs is not at variance from other causes of headache. Beyond the broadly accepted subtype-related headache treatment, diet, cofactors, vitamins, and antioxidants may provide a supplementary benefit. Midazolam, l-arginine, or l-citrulline may be beneficial for MLH. The pathogenesis of headache in MIDs largely remains unsolved. However, since migraine and MLH respond both to triptanes, a shared pathomechanism is likely. In conclusion, migraine and MLH are the prominent headache types in MIDs. MLH may or may not be associated with current or previous SLEs. MLH is pathophysiologically different from migraine and requires treatment at variance from that of migraine with aura.

Maintenance diets following rapid weight loss in obstructive sleep apnea: a pilot 1-year clinical trial.

Very low energy diets (VLED) appear to be the most efficacious dietary-based obesity reduction treatments in obstructive sleep apnea (OSA); however, effective weight loss maintenance strategies remain untested in this condition. Our study aimed to assess the feasibility, tolerability and efficacy of two common maintenance diets during a 10-month follow-up period after rapid weight loss using a 2-month VLED. In this two-arm, single-centre, open-label pilot trial, obese adult OSA patients received a 2-month VLED before being allocated to either the Australian Guide to Healthy Eating diet (AGHE) or a low glycaemic index high-protein diet (LGHP). Outcomes were measured at 0, 2 and 12 months. We recruited 44 patients [113.1 ± 19.5 kg, body mass index (BMI): 37.2 ± 5.6 kg m-2 , 49.3 ± 9.2 years, 12 females]. Twenty-four patients were on continuous positive airway pressure (CPAP) or mandibular advancement splint (MAS) therapy for OSA. Forty-two patients completed the VLED. The primary outcome of waist circumference was reduced by 10.6 cm at 2 months [95% confidence interval (CI): 9.2-12.1], and patients lost 12.9 kg in total weight (95% CI: 11.2-14.6). There were small but statistically significant regains in waist circumference between 2 and 12 months [AGHE = 3.5 cm (1.3-5.6) and LGHP = 2.8 cm (0.6-5.0]. Other outcomes followed a similar pattern of change. After weight loss with a 2-month VLED in obese patients with OSA, a structured weight loss maintenance programme incorporating commonly used diets was feasible, tolerable and efficacious for 10 months. This programme may be deployed easily within sleep clinics; however, future research should first test its translation within general clinical practice.

Approaches to obesity management.

This review will provide an overview of the currently available approaches to obesity management available in Australia, including the various approaches to lifestyle intervention, in addition to evaluating the safety and efficacy of adjuvant therapies, including pharmacotherapy and bariatric surgery.

Sugars and health: a review of current evidence and future policy.

The automation of the process of extracting sugars in the 1900s reduced cost and increased availability of sugars leading to a dramatic rise in consumption, which reached a peak in the 1970s. There are different definitions for sugars not naturally available in foods, and free sugars is the term used by WHO. The epidemiological evidence of the associations between sugars and obesity and type 2 diabetes mellitus is fairly strong and consistent, particularly for sugar sweetened drinks in adults. The Department of Health in the UK and many other countries have recently updated their recommendations for free sugars as a result of this scientific evidence. In the UK the recommended amount of free sugars is currently 5 % of energy (reduced from 10 %), which is difficult to meet and very different from current British dietary patterns. Reducing intakes of free sugars is a challenge and will necessitate a range of different actions and policies. Public Health England has put forward eight suggestions but the four most likely to improve dietary behaviour based on available evidence are social marketing, reduction of marketing of high sugar foods and drinks to children, reformulation and reductions in portion size and a sugar excise tax. Any action taken needs to be evaluated to check inequalities are not widened. The new childhood obesity strategy has incorporated some but not all of these strategies and may not go far enough. It is likely that government policies alone will not be sufficient and a change in the food culture is necessary to see real progress.

Establishing an Adult Epilepsy Diet Center: Experience, efficacy and challenges.

OBJECTIVES: Over 250 medical centers worldwide offer ketogenic diets to children with epilepsy; however, access to these therapies has been extremely limited for adults until recent years. We examine our 5-year experience creating and implementing a dedicated Adult Epilepsy Diet Center designed to provide adults with epilepsy access to ketogenic diets. MATERIAL AND METHODS: Outpatients seen at the Johns Hopkins Adult Epilepsy Diet Center from August 2010 thru September 2015 age 18years and older were enrolled in a prospective open-label observational study. Patients that also enrolled in ongoing clinical diet trials were excluded from this study. Participant demographics, diet type, urine and/or serum ketones, laboratory studies, seizure frequency, diet duration, reason for discontinuing diet therapy, and side effects were recorded. A subgroup analysis of participants that met International League Against Epilepsy (ILAE) criteria for drug-resistant epilepsy (DRE) and were treated de novo with a Modified Atkins Diet (MAD) was performed to compare outcomes with the current literature regarding efficacy of other antiseizure treatments for DRE. RESULTS: Two hundred and twenty-nine adults attended the Adult Epilepsy Diet Center, and 168 met inclusion criteria. Two-thirds (n=113, 67%) were women with an age range of 18-86years at the initial visit. Thirty-five participants (21%, n=133) were already on a therapeutic diet while 79% (n=133) were naïve to diet therapy at the time of the initial visit. Diet-naïve participants were typically prescribed MAD (n=130, 98%), unless unable to intake adequate oral nutrition, in which case they were prescribed KD (n=1) or a combination of oral MAD and ketogenic formula (n=2). Twenty-nine of 130 (22%) participants prescribed MAD elected not to start or were lost to follow-up, and 101 (78%) began MAD. A subgroup analysis was performed on one hundred and six participants naïve to diet therapy that met International League Against Epilepsy criteria for DRE, were able to tolerate oral nutrition, and were prescribed a MAD. Relative to the number of enrolled participants who had reliable follow-up results for a given duration (including those that ultimately elected not to start or were later lost to follow-up), at 3months, 36% of these participants responded (≥50% seizure reduction) to diet therapy, and 16% were seizure-free. At 1year, 30% responded, and 13% were seizure-free. At 4years, 21% responded, and 7% were seizure-free. Hyperlipidemia was the most common side effect (occurring in 39% of screened participants, including those on a therapeutic diet prior to the initial visit). Weight loss was also common (occurring in 19% of all participants treated with a ketogenic diet therapy) yet was often an intended effect. SIGNIFICANCE: This study, the largest series of adults with epilepsy treated with ketogenic diet therapies to date, provides evidence that ketogenic diets may be feasible, effective, and safe long-term in adults, although long-term adherence was limited and further adequately controlled studies are necessary to determine the efficacy of ketogenic diets in the treatment of adults with epilepsy.

Moderate dietary weight loss reduces myocardial steatosis in obese and overweight women.

BACKGROUND: Excessive myocardial triglyceride (MTG) content in obesity and type 2 diabetes is associated with impaired cardiac function. Previous studies suggest that MTG could be mobilized through lifestyle interventions. We assessed influences of moderate dietary weight loss in non diabetic obese and overweight women on MTG content and cardiac function. METHODS: We selected a subgroup of 38 women from the B-SMART study population. The B-SMART study compared weight loss and associated metabolic and cardiovascular markers with reduced-carbohydrate and reduced-fat hypocaloric diets. Selected subjects had completed a cardiac magnetic resonance (MR) scan including imaging and proton spectroscopy to assess cardiac structure and function as well as MTG content. RESULTS: An average weight reduction of 5.4 ± 4.3 kg at six months was associated with a relative decrease of MTG of 25% (from 0.72 ± 0.29% at baseline to 0.54 ± 0.23% at follow-up, p<0.001). The response was similar with carbohydrate and fat restriction. Diastolic function expressed as ratio of peak filling rate in E- and A-Phase (PFRE/PFRA) was unchanged. Reductions of left atrial size (from 21.9 ± 4.0 cm(2) to 20.0 ± 3.7 cm(2), p=0.002), the normalized ratio of PFRE and early diastolic lengthening velocity PLV (from 8.2 ± 2.6 to 7.5 ± 2.5, p<0.001) and fat free mass (from 55.1 ± 6.9 kg to 52.7 ± 6.5 kg, p=0.007) reflected altered cardiac volume loading after diet, but did not correlate to MTG content. CONCLUSIONS: Moderate dietary weight loss significantly reduced MTG content in women with uncomplicated overweight or obesity. Macronutrient composition of the diet did not significantly affect the extent of MTG reduction.

A decade of the modified Atkins diet (2003­2013): Results, insights, and future directions.

The modified Atkins diet has been used since 2003 for the treatment of children and adults with refractory epilepsy.This "alternative" ketogenic diet is started in clinic, without fasting, hospitalization, and restriction of protein,calories, or fluid intake. Now after 10 years of continued use, approximately 400 patients have been reported in over 30 studies of the modified Atkins diet as treatment for intractable seizures, with results demonstrating similar efficacy to the ketogenic diet and improved tolerability. The modified Atkins diet is being increasingly used in the adult population. Clinical trials have provided insight into the mechanisms of action of dietary therapies overall. This review will discuss the past decade of experience with the modified Atkins diet as well as predictions for its role in the treatment of epilepsy a decade from now.

Sex differences in dieting trends, eating habits, and nutrition beliefs of a group of midwestern college students.

The influence of sex on dietary trends, eating habits, and nutrition self-assessment and beliefs of a group of college students at a large Midwestern university was investigated. A questionnaire was completed by 105 male and 181 female undergraduate students. Men had significantly higher (P<0.0001) height, weight, and body mass index values. Significantly higher percentages of women than men had tried a low-fat diet (P=0.0075) and a low-carbohydrate diet (P=0.0285). Significantly lower percentages of women than men had never tried a diet (P=0.0173). Significantly higher percentages of women than men reported gaining nutrition knowledge from family (P=0.0033) and magazines/newspapers (P=0.0345). Significantly higher percentages of women than men agreed that they had too much sugar in their diets (P=0.0157), that it is important to limit carbohydrate consumption (P=0.0077), that it is important to limit the amount of fat consumed to lose weight (P=0.0194), and that they needed to lose weight (P<0.0001). It is important to eat a variety of foods for good health according to 94.4% of subjects. Sex differences existed in these college students with regard to anthropometric measurements, certain choices of diets, some sources of nutrition knowledge, and some nutrition beliefs.

An update on low-carbohydrate, high-protein diets.

PURPOSE OF REVIEW: The use of low-carbohydrate diets in weight loss is an area of great controversy. In recent years, a significant amount of research has been conducted to evaluate the efficacy of these diets. This review aims to discuss mechanisms of action for weight loss; to assess impact on metabolic parameters including insulin sensitivity and cardiovascular risk parameters and to evaluate the data regarding safety and effectiveness for weight loss. RECENT FINDINGS: Most studies demonstrate that subjects following low carbohydrate diets lose more weight over the first 3-6 months than subjects consuming control diets. This weight loss is not sustained, however, at 1 year. Carbohydrate controlled diets may be associated with increased insulin sensitivity and improved glycemic control. High carbohydrate, low fat diets appear to have a more favorable impact on total and LDL cholesterol, whereas low carbohydrate diets have been shown to significantly decrease triglyceride and increase HDL cholesterol levels in short-term studies. SUMMARY: Low carbohydrate diets may be effective in helping people to lose weight. More long-term studies need to be performed, however, to better evaluate efficacy, safety, and impact on metabolic profile.