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Acute responses of hepatic fat content to consuming fat, glucose and fructose alone and in combination in non-obese non-diabetic individuals with non-alcoholic fatty liver disease.
Kovar, J, Dusilova, T, Sedivy, P, Bruha, R, Gottfriedova, H, Pavlikova, P, Pitha, J, Smid, V, Drobny, M, Dezortova, M, et al
Journal of physiology and pharmacology : an official journal of the Polish Physiological Society. 2021;72(1)
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Non-alcoholic fatty liver disease (NAFLD) is often associated with obesity or conditions related to obesity, such as type 2 diabetes. Steatosis is one of the four stages of NAFLD, where there is a small layer of fat build-up on the liver. Currently, one in three people in the UK has simple fatty liver or steatosis. A fascinating aspect of this study is exploring the long-term cumulative effects of daily fat intake when consumed with glucose or fructose and in the pathogenesis of steatosis. In this randomised controlled study, the researchers examined the immediate impact of high-fat loads on hepatic fat content (HFC) when administered with glucose or fructose in eight healthy overweight males with NFALD. The experiments lasted only eight hours. HFC was only transiently elevated by co-administration of glucose and high-fat loading. However, fructose co-administration with multiple high-fat loads promoted HFC. Small sample size and short duration are the limitations of this study. Long-term robust studies are needed to confirm the findings. Yet, healthcare professionals can use this study to distinguish between the immediate effects of fructose or glucose when combined with multiple doses of high fat on HFC in healthy and NAFLD subjects.
Abstract
We have recently demonstrated that a high-fat load can induce immediate increase in hepatic fat content (HFC) and that such an effect can be modified differently by co-administration of fructose or glucose in healthy subjects. Therefore, we addressed the question how consumption of these nutrients affects changes in HFC in subjects with non-alcoholic fatty liver disease (NAFLD). Eight male non-obese non-diabetic patients with NAFLD underwent 6 experiments each lasting 8 hours: 1. fasting, 2. high-fat load (150 g of fat (dairy cream) at time 0), 3. glucose (three doses of 50 g at 0, 2, and 4 hours), 4. high-fat load with three doses of 50 g of glucose, 5. fructose (three doses of 50 g at 0, 2, and 4 hours), 6. high-fat load with three doses of 50 g of fructose. HFC was measured using magnetic resonance spectroscopy prior to meal administration and 3 and 6 hours later. Plasma triglycerides, non-esterified fatty acids, glucose and insulin were monitored throughout each experiment. HFC increased by 10.4 ± 6.9% six hours after a high-fat load and by 15.2 ± 12.5% after high-fat load with fructose. When co-administering glucose with fat, HFC rose only transiently to return to baseline at 6 hours. Importantly, NAFLD subjects accumulated almost five times more fat in their livers than healthy subjects with normal HFC. Consumption of a high-fat load results in fat accumulation in the liver of NAFLD patients. Fat accumulation after a fat load is diminished by glucose but not fructose co-administration.
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Effect of intermittent vs. daily calorie restriction on changes in weight and patient-reported outcomes in people with multiple sclerosis.
Fitzgerald, KC, Vizthum, D, Henry-Barron, B, Schweitzer, A, Cassard, SD, Kossoff, E, Hartman, AL, Kapogiannis, D, Sullivan, P, Baer, DJ, et al
Multiple sclerosis and related disorders. 2018;23:33-39
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Multiple sclerosis (MS) is a disease of the central nervous system. Dietary modification is emerging as a safe intervention to potentially modify disease course. The main aim of this study was to assess the safety and feasibility of an intermittent fasting diet in people with MS. Secondary outcomes explored the effects of calorie restriction (CR) diets on body weight and anthropometric characteristics as well as on patient-reported outcomes including fatigue, sleep and mood. The study is a pilot randomised controlled feeding study of three different types of diets. Each participant (n=36) was randomized to 1 of 3 diets: a control diet (placebo), a daily CR diet and intermittent CR diet. Results indicate that daily CR diet was associated with marginally greater weight loss than the intermittent CR diet. Both CR diets were associated with trends toward improvements in cardiometabolic outcomes. Furthermore, CR diets were associated with in improvements in emotional well-being. Authors conclude that CR and weight loss represent interventions for clinically relevant symptoms due to MS, such as emotional well-being, without adding meaningful risks or adverse outcomes.
Abstract
An intermittent fasting or calorie restriction diet has favorable effects in the mouse forms of multiple sclerosis (MS) and may provide additional anti-inflammatory and neuroprotective advantages beyond benefits obtained from weight loss alone. We conducted a pilot randomized controlled feeding study in 36 people with MS to assess safety and feasibility of different types of calorie restriction (CR) diets and assess their effects on weight and patient reported outcomes in people with MS. Patients were randomized to receive 1 of 3 diets for 8 weeks: daily CR diet (22% daily reduction in energy needs), intermittent CR diet (75% reduction in energy needs, 2 days/week; 0% reduction, 5 days/week), or a weight-stable diet (0% reduction in energy needs, 7 days/week). Of the 36 patients enrolled, 31 (86%) completed the trial; no significant adverse events occurred. Participants randomized to CR diets lost a median 3.4 kg (interquartile range [IQR]: -2.4, -4.0). Changes in weight did not differ significantly by type of CR diet, although participants randomized to daily CR tended to have greater weight loss (daily CR: -3.6 kg [IQR: -3.0, -4.1] vs. intermittent CR: -3.0 kg [IQR: -1.95, -4.1]; P = 0.15). Adherence to study diets differed significantly between intermittent CR vs. daily CR, with lesser adherence observed for intermittent CR (P = 0.002). Randomization to either CR diet was associated with significant improvements in emotional well-being/depression scores relative to control, with an average 8-week increase of 1.69 points (95% CI: 0.72, 2.66). CR diets are a safe/feasible way to achieve weight loss in people with MS and may be associated with improved emotional health.
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Effect of Low-Fat vs Low-Carbohydrate Diet on 12-Month Weight Loss in Overweight Adults and the Association With Genotype Pattern or Insulin Secretion: The DIETFITS Randomized Clinical Trial.
Gardner, CD, Trepanowski, JF, Del Gobbo, LC, Hauser, ME, Rigdon, J, Ioannidis, JPA, Desai, M, King, AC
JAMA. 2018;319(7):667-679
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Obesity is a major public health challenge and different dietary strategies are employed to lose weight. This randomised clinical trial of 609 obese adults between the age of 18 and 50 aimed to determine the effects of a healthy low-fat diet in comparison to a healthy low-carbohydrate diet on weight change over a 12 month period. The study also assessed whether 3 genetic markers and blood sugar management affected weight loss in the 2 groups. Participants in the study were offered 22 group sessions of health coaching to support adherence to the programme. 481 participants completed the study. The low-carbohydrate group lost on average 6kg and the low-fat group lost on average 5.4kg. The difference between the 2 groups did not achieve significance for weight loss. There was also no significant genetic or blood sugar management effect in relation to dietary pattern and weight loss. The authors of this study conclude that the results of this study do not help in identifying which dietary type is better for whom in relation to 3 genetic markers and blood sugar management.
Abstract
Importance: Dietary modification remains key to successful weight loss. Yet, no one dietary strategy is consistently superior to others for the general population. Previous research suggests genotype or insulin-glucose dynamics may modify the effects of diets. Objective: To determine the effect of a healthy low-fat (HLF) diet vs a healthy low-carbohydrate (HLC) diet on weight change and if genotype pattern or insulin secretion are related to the dietary effects on weight loss. Design, Setting, and Participants: The Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) randomized clinical trial included 609 adults aged 18 to 50 years without diabetes with a body mass index between 28 and 40. The trial enrollment was from January 29, 2013, through April 14, 2015; the date of final follow-up was May 16, 2016. Participants were randomized to the 12-month HLF or HLC diet. The study also tested whether 3 single-nucleotide polymorphism multilocus genotype responsiveness patterns or insulin secretion (INS-30; blood concentration of insulin 30 minutes after a glucose challenge) were associated with weight loss. Interventions: Health educators delivered the behavior modification intervention to HLF (n = 305) and HLC (n = 304) participants via 22 diet-specific small group sessions administered over 12 months. The sessions focused on ways to achieve the lowest fat or carbohydrate intake that could be maintained long-term and emphasized diet quality. Main Outcomes and Measures: Primary outcome was 12-month weight change and determination of whether there were significant interactions among diet type and genotype pattern, diet and insulin secretion, and diet and weight loss. Results: Among 609 participants randomized (mean age, 40 [SD, 7] years; 57% women; mean body mass index, 33 [SD, 3]; 244 [40%] had a low-fat genotype; 180 [30%] had a low-carbohydrate genotype; mean baseline INS-30, 93 μIU/mL), 481 (79%) completed the trial. In the HLF vs HLC diets, respectively, the mean 12-month macronutrient distributions were 48% vs 30% for carbohydrates, 29% vs 45% for fat, and 21% vs 23% for protein. Weight change at 12 months was -5.3 kg for the HLF diet vs -6.0 kg for the HLC diet (mean between-group difference, 0.7 kg [95% CI, -0.2 to 1.6 kg]). There was no significant diet-genotype pattern interaction (P = .20) or diet-insulin secretion (INS-30) interaction (P = .47) with 12-month weight loss. There were 18 adverse events or serious adverse events that were evenly distributed across the 2 diet groups. Conclusions and Relevance: In this 12-month weight loss diet study, there was no significant difference in weight change between a healthy low-fat diet vs a healthy low-carbohydrate diet, and neither genotype pattern nor baseline insulin secretion was associated with the dietary effects on weight loss. In the context of these 2 common weight loss diet approaches, neither of the 2 hypothesized predisposing factors was helpful in identifying which diet was better for whom. Trial Registration: clinicaltrials.gov Identifier: NCT01826591.
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Micronutrient Gaps in Three Commercial Weight-Loss Diet Plans.
G Engel, M, J Kern, H, Brenna, JT, H Mitmesser, S
Nutrients. 2018;10(1)
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Globally, around 39% of adults are overweight and 13% obese, and more than one third of American adults are obese. Being overweight or obese is associated with many chronic conditions, such as heart disease, high blood pressure and type 2 diabetes. Weight loss, even at moderate level, can reduce the risk of these obesity-related chronic conditions. Commercial weight-loss diet plans can vary greatly, not only in energy content but also in macronutrient and micronutrient composition. Most plans restrict calories or certain macronutrients, particularly carbohydrate or fat, and in doing so, often overlook micronutrient, i.e. vitamin and mineral, content. Previous studies have shown that many weight-loss plans do not provide adequate amounts of all micronutrients, and in order to reach the reference daily intakes for various vitamins and minerals, dieters would need to increase their calorie intake significantly and often unrealistically. The authors of this paper analysed seven single-day menus of three select commercial diet plans to determine their micronutrient sufficiency. The diet plans included were Eat to Live-Vegan, Aggressive Weight Loss (ETL-VAWL), Fast Metabolism Diet (FMD), and Eat, Drink and Be Healthy (EDH). ETL-VAWL diet provided less than 90% of recommended amounts for B12, B3, D, E, calcium, selenium and zinc. The FMD diet was low in B1, D, E, calcium, magnesium and potassium, while EDH diet didn’t meet the recommended amounts for vitamin D, calcium and potassium. Even after adjusting all the plans to an intake of 2000 kcal/day, several micronutrients were found to remain inadequate (vitamin B12 in ETL-VAWL, calcium in FMD and EDH and vitamin D in all diets). The authors conclude that, in order to reduce the risk of micronutrient deficiencies, more attention needs to be paid to micronutrient rich foods when designing commercial diet plans. Alternatively, these nutrient gaps should be filled in other ways, e.g. using appropriate dietary supplements.
Abstract
Weight-loss diets restrict intakes of energy and macronutrients but overlook micronutrient profiles. Commercial diet plans may provide insufficient micronutrients. We analyzed nutrient profiles of three plans and compared their micronutrient sufficiency to Dietary Reference Intakes (DRIs) for male U.S. adults. Hypocaloric vegan (Eat to Live-Vegan, Aggressive Weight Loss; ETL-VAWL), high-animal-protein low-carbohydrate (Fast Metabolism Diet; FMD) and weight maintenance (Eat, Drink and Be Healthy; EDH) diets were evaluated. Seven single-day menus were sampled per diet (n = 21 menus, 7 menus/diet) and analyzed for 20 micronutrients with the online nutrient tracker CRON-O-Meter. Without adjustment for energy intake, the ETL-VAWL diet failed to provide 90% of recommended amounts for B12, B₃, D, E, calcium, selenium and zinc. The FMD diet was low (<90% DRI) in B₁, D, E, calcium, magnesium and potassium. The EDH diet met >90% DRIs for all but vitamin D, calcium and potassium. Several micronutrients remained inadequate after adjustment to 2000 kcal/day: vitamin B12 in ETL-VAWL, calcium in FMD and EDH and vitamin D in all diets. Consistent with previous work, micronutrient deficits are prevalent in weight-loss diet plans. Special attention to micronutrient rich foods is required to reduce risk of micronutrient deficiency in design of commercial diets.
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Acute Endothelial Benefits of Fat Restriction over Carbohydrate Restriction in Type 2 Diabetes Mellitus: Beyond Carbs and Fats.
Barbosa-Yañez, RL, Dambeck, U, Li, L, Machann, J, Kabisch, S, Pfeiffer, AFH
Nutrients. 2018;10(12)
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The control of type 2 diabetes mellitus has become a global challenge. Cardiovascular disease is a major cause of mortality in type 2 diabetes. The aim of the study is to examine and compare the effect of a hypocaloric very low carbohydrate diet versus hypocaloric low-fat diet on vascular function and visceral adipose tissue in type 2 diabetic patients. The study is a randomised parallel group intervention study with adult type 2 diabetes patients with an age range between 42 and 76 years. Results show that both dietary strategies effectively reduced body weight, total adipose tissue, visceral adipose tissue and lipid accumulation in the liver. However, participants following the low-fat diet experienced greater vascular function enhancements. Authors conclude that low-fat diet elicited advantageous effects on vascular function in patients with type 2 diabetes.
Abstract
BACKGROUND Cardiovascular diseases (CVD) are the major cause of mortality in type 2 diabetes patients (T2DM). The causes are embedded in a complex interplay between excess body fat, insulin resistance and serum lipid anomalies. Endothelial homeostasis is strongly affected by this pathogenic network. Even though metabolic changes and weight loss improve vascular endothelial function, the effect of different dietary approaches is still uncertain for type 2 diabetes patients. OBJECTIVE We aimed to compare the acute effects of a hypocaloric very low carbohydrate (VLC) diet versus a hypocaloric low fat (LF) diet on flow mediated dilation (FMD), intrahepatic lipid (IHL) accumulation and visceral adipose tissue as independent risk factors of CVD in T2DM patients. DESIGN 36 T2DM patients (age 63 ± 8 years, 60% females) were randomly assigned to the VLC diet (4⁻10% of total energy intake (E)) or to the LF diet (<30% E) for 3 weeks. Endothelial function was assessed by the flow mediated dilation (FMD) method. Adipose tissue depots and IHL were determined by magnetic resonance. RESULTS Both dietary strategies reduced body weight, body fat content and IHL. Unexpectedly, the LF group experienced significantly greater enhancement of FMD, compared to the VLC group. The FMD showed a positive correlation with protein intake and fat intake in the LF group, while it revealed a negative correlation with protein intake in the VLC diet group. CONCLUSIONS Reduction of total and hepatic adiposity was shown to be successful using either the VLC or LF hypocaloric diets, however, improvements in FMD may be related to the interplay of fat and protein intake.
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Changes in Visceral Adiposity, Subcutaneous Adiposity, and Sex Hormones in the Diabetes Prevention Program.
Kim, C, Dabelea, D, Kalyani, RR, Christophi, CA, Bray, GA, Pi-Sunyer, X, Darwin, CH, Yalamanchi, S, Barrett-Connor, E, Golden, SH, et al
The Journal of clinical endocrinology and metabolism. 2017;102(9):3381-3389
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It is not currently known to what extent changes in different types of fat stores (visceral fat that surrounds organs and subcutaneous fat that sits under the surface of the skin) relate to changes in sex hormones. This study was a secondary analysis of a randomised controlled trial including 555 individuals. It examined whether changes to visceral and subcutaneous fat were associated with changes in sex hormones (DHEA, testosterone, oestrogen and sex hormone binding globulin - SHBG) among overweight individuals with glucose intolerance under the care of a diabetes program. Participants were randomly assigned to an intensive lifestyle modification programme (goals for weight reduction and 150 mins exercise weekly), medication (metformin) or placebo for 12 months. The authors found that among men, reductions in both types of fat were associated with significant increases in total testosterone and SHBG. Among women, reductions in both types of fat were associated with increases in SHBG and associations with estrone differed by menopausal status. No associations were found between changes in fat stores and estradiol or DHEA. The authors conclude that weight loss may affect sex hormone profiles via reductions in visceral and subcutaneous fat. -
Abstract
Context: The degree to which changes in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) relate to corresponding changes in plasma sex steroids is not known. Objective: We examined whether changes in VAT and SAT areas assessed by computed tomography were associated with changes in sex hormones [dehydroepiandrosterone sulfate (DHEAS), testosterone, estradiol, estrone, and sex hormone binding globulin (SHBG)] among Diabetes Prevention Program participants. Design: Secondary analysis of a randomized trial. Participants: Overweight and glucose-intolerant men (n = 246) and women (n = 309). Interventions: Intensive lifestyle change with goals of weight reduction and 150 min/wk of moderate intensity exercise or metformin administered 850 mg twice a day or placebo. Main Outcome Measures: Associations between changes in VAT, SAT, and sex hormone changes over 1 year. Results: Among men, reductions in VAT and SAT were both independently associated with significant increases in total testosterone and SHBG in fully adjusted models. Among women, reductions in VAT and SAT were both independently associated with increases in SHBG and associations with estrone differed by menopausal status. Associations were similar by race/ethnicity and by randomization arm. No significant associations were observed between change in fat depot with change in estradiol or DHEAS. Conclusions: Among overweight adults with impaired glucose intolerance, reductions in either VAT and SAT were associated with increased total testosterone in men and higher SHBG in men and women. Weight loss may affect sex hormone profiles via reductions in visceral and subcutaneous fat.
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Reduction of dietary fat absorption by the novel gastrointestinal lipase inhibitor cetilistat in healthy volunteers.
Bryson, A, de la Motte, S, Dunk, C
British journal of clinical pharmacology. 2009;67(3):309-15
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Obesity is epidemic and many obese patients seek drug treatment. Orlistat (a lipase inhibitor) is effective, but associated with gastrointestinal side effects. This study aimed to demonstrate that Cetilistat inhibits gastrointestinal lipase and is well tolerated in comparison to Orlistat. Results from three Phase I clinical studies (all double-blind, randomized, placebo-controlled, parallel-group studies in healthy male volunteers (age 18-45y, BMI ≤30 kg m−2, minimum weight of 60 kg) (total n=99) resident in a clinical unit) are reported. Subjects receives placebo (n=24), one of a range of Cetilistat doses (n=66) or 120mg Orlistat x3/daily (n=9) for 5 days, whilst maintained on a strict diet. 30% of calories were derived from fat. Each dose of Cetilistat in the 3 studies increased mean faecal fat excretion relative to both baseline and placebo. Increased faecal fat excretion was significant compared with placebo at 150 mg t.i.d. (study 1). Faecal fat excretion was significantly higher in both the Cetilistat 120 and 240 mg t.i.d. groups (study 3). Overall, fecal fat excretion for Orlistat 120 mg t.i.d. was similar to Cetilistat. Gastroinetstinal side effects were most common (51%) for Cetilistat. Steatorrhoea (oily stool) was more frequent in the Orlistat group (4.11 events per subject) than in any Cetilistat dose group. Most side-effects (98%) were mild or moderate. 3 subjects taking Cetilistat were withdrawn from the study after developing maculopapular rash, but no reaction was observed (pin-prick). The chemical structure of Orlistat and Cetistat are different which may affect how they interact with fat micelles in the intestines. The author speculates that Cetilistat may act more like a detergent, whereas Orlistat may promote the coalescence of micelles, leading to oils and increased gastrointestinal adverse events. Cetilistat is an effective inhibitor of gastrointestinal lipases, increasing faecal fat excretion in at all doses studied. Cetilistat is well tolerated across a range of doses, and comparison with Orlistat suggests improved tolerability.
Abstract
AIMS: To assess the efficacy, pharmacodynamics, safety and tolerability of a range of doses of cetilistat, a novel inhibitor of gastrointestinal lipases, in healthy volunteers. METHODS Three Phase I, randomized, placebo-controlled, parallel-group studies were conducted. Enrolled subjects in the three studies (n = 99) received a controlled calorie diet (total intake 2160 calories daily, 30% from fat). Twenty-four subjects were randomized to placebo and 66 were randomized to the following cetilistat doses: 50 mg three times daily [t.i.d. (n = 7)], 60 mg t.i.d. (n = 9), 100 mg t.i.d. (n = 7), 120 mg t.i.d. (n = 9), 150 mg t.i.d. (n = 16), 240 mg t.i.d. (n = 9) and 300 mg t.i.d. (n = 9). Nine subjects received the approved orlistat dose (120 mg t.i.d.). Treatment was for 5 days, with a 2-day run-in period and 1-day post-treatment follow-up. The primary outcome measure was daily faecal fat excretion. Secondary outcomes included plasma lipid levels, tolerability [gastrointestinal adverse events (AEs)] and safety. RESULTS Cetilistat increased faecal fat excretion relative to baseline at all doses. Cetilistat was well tolerated, with gastrointestinal AEs the most common (51%). Steatorrhoea (oily stool) was more frequent in the orlistat group (4.11 events per subject) than in any cetilistat dose group (0.14-1.81 events per subject). Most AEs (98%) were mild or moderate in intensity. CONCLUSIONS Cetilistat increased dietary fat excretion in healthy volunteers receiving a controlled calorie diet. Cetilistat was well tolerated at all doses examined and tolerability appeared to be improved relative to orlistat. Faecal fat excretion in the cetilistat groups was at least comparable to the orlistat 120 mg t.i.d. group.