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Effect of green-Mediterranean diet on intrahepatic fat: the DIRECT PLUS randomised controlled trial.Gut Nov 2021To examine the effectiveness of green-Mediterranean (MED) diet, further restricted in red/processed meat, and enriched with green plants and polyphenols on non-alcoholic... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To examine the effectiveness of green-Mediterranean (MED) diet, further restricted in red/processed meat, and enriched with green plants and polyphenols on non-alcoholic fatty liver disease (NAFLD), reflected by intrahepatic fat (IHF) loss.
DESIGN
For the DIRECT-PLUS 18-month randomized clinical trial, we assigned 294 participants with abdominal obesity/dyslipidaemia into healthy dietary guidelines (HDG), MED and green-MED weight-loss diet groups, all accompanied by physical activity. Both isocaloric MED groups consumed 28 g/day walnuts (+440 mg/day polyphenols provided). The green-MED group further consumed green tea (3-4 cups/day) and Mankai (a aquatic plant strain; 100 g/day frozen cubes) green shake (+1240 mg/day total polyphenols provided). IHF% 18-month changes were quantified continuously by proton magnetic resonance spectroscopy (MRS).
RESULTS
Participants (age=51 years; 88% men; body mass index=31.3 kg/m; median IHF%=6.6%; mean=10.2%; 62% with NAFLD) had 89.8% 18-month retention-rate, and 78% had eligible follow-up MRS. Overall, NAFLD prevalence declined to: 54.8% (HDG), 47.9% (MED) and 31.5% (green-MED), p=0.012 between groups. Despite similar moderate weight-loss in both MED groups, green-MED group achieved almost double IHF% loss (-38.9% proportionally), as compared with MED (-19.6% proportionally; p=0.035 weight loss adjusted) and HDG (-12.2% proportionally; p<0.001). After 18 months, both MED groups had significantly higher total plasma polyphenol levels versus HDG, with higher detection of and 2-5-dihydroxybenzoic-acid in green-MED. Greater IHF% loss was independently associated with increased Mankai and walnuts intake, decreased red/processed meat consumption, improved serum folate and adipokines/lipids biomarkers, changes in microbiome composition (beta-diversity) and specific bacteria (p<0.05 for all).
CONCLUSION
The new suggested strategy of green-Mediterranean diet, amplified with green plant-based proteins/polyphenols as Mankai, green tea, and walnuts, and restricted in red/processed meat can double IHF loss than other healthy nutritional strategies and reduce NAFLD in half.
TRIAL REGISTRATION NUMBER
NCT03020186.
Topics: Araceae; Diet, Mediterranean; Diet, Reducing; Female; Humans; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Polyphenols; Tea
PubMed: 33461965
DOI: 10.1136/gutjnl-2020-323106 -
Nutrients Aug 2020Ketogenic diet (KD) has been used to treat epilepsy for 100 years. It is a high-fat, low-carbohydrate, and sufficient-protein-for-growth diet that mimics the metabolic... (Review)
Review
Ketogenic diet (KD) has been used to treat epilepsy for 100 years. It is a high-fat, low-carbohydrate, and sufficient-protein-for-growth diet that mimics the metabolic changes occurring during starvation. Except for classic KD, its modified counterparts, including modified Atkins diet and low-glycemic-index treatment, have gained grounds to increase palatability and adherence. Strong evidence exists that the KD offers protection against seizures in difficult-to-treat epilepsy and possesses long-lasting anti-epileptic activity, improving long-term disease outcome. The KD can also provide symptomatic and disease-modifying activity in a wide range of neurodegenerative diseases. In an era of highly available new anti-seizure medications (ASMs), the challenge of refractory epilepsy has still not been solved. This metabolic therapy is increasingly considered due to unique mechanisms and turns out to be a powerful tool in the hands of a skillful team. Despite decades of extensive research to explain the mechanism of its efficacy, the precise mechanism of action is to date still largely unknown. The key feature of this successful diet is the fact that energy is derived largely from fat but not from carbohydrates. Consequently, fundamental change occurs regarding the method of energy production that causes alterations in numerous biochemical pathways, thus restoring energetic and metabolic homeostasis of the brain. There are barriers during the use of this special and individualized therapy in many clinical settings worldwide. The aim of this review is to revisit the current state of the art of therapeutic application of KD in refractory epilepsy.
Topics: Diet, Ketogenic; Drug Resistant Epilepsy; Humans; Treatment Outcome
PubMed: 32867258
DOI: 10.3390/nu12092616 -
Nutrients Dec 2021The optimal dietary pattern to improve metabolic function remains elusive. In a 21-day randomized controlled inpatient crossover feeding trial of 20 insulin-resistant... (Comparative Study)
Comparative Study Randomized Controlled Trial
A High Protein Diet Is More Effective in Improving Insulin Resistance and Glycemic Variability Compared to a Mediterranean Diet-A Cross-Over Controlled Inpatient Dietary Study.
The optimal dietary pattern to improve metabolic function remains elusive. In a 21-day randomized controlled inpatient crossover feeding trial of 20 insulin-resistant obese women, we assessed the extent to which two isocaloric dietary interventions-Mediterranean (M) and high protein (HP)-improved metabolic parameters. Obese women were assigned to one of the following dietary sequences: M-HP or HP-M. Cardiometabolic parameters, body weight, glucose monitoring and gut microbiome composition were assessed. Sixteen women completed the study. Compared to the M diet, the HP diet was more effective in (i) reducing insulin resistance (insulin: Beta (95% CI) = -6.98 (-12.30, -1.65) µIU/mL, = 0.01; HOMA-IR: -1.78 (95% CI: -3.03, -0.52), = 9 × 10); and (ii) improving glycemic variability (-3.13 (-4.60, -1.67) mg/dL, = 4 × 10), a risk factor for T2D development. We then identified a panel of 10 microbial genera predictive of the difference in glycemic variability between the two diets. These include the genera and , previously associated with glucose homeostasis and insulin resistance. Our results suggest that morbidly obese women with insulin resistance can achieve better control of insulin resistance and glycemic variability on a high HP diet compared to an M diet.
Topics: Adult; Cross-Over Studies; Diet, High-Protein; Diet, Mediterranean; Female; Gastrointestinal Microbiome; Glycemic Index; Homeostasis; Humans; Insulin Resistance; Middle Aged; Obesity; Treatment Outcome; Young Adult
PubMed: 34959931
DOI: 10.3390/nu13124380 -
Nutrients Jan 2020Very low-calorie ketogenic diets (VLCKD) are an effective and increasingly used tool for weight loss. Traditionally considered high protein, ketogenic diets are often... (Clinical Trial)
Clinical Trial
Very low-calorie ketogenic diets (VLCKD) are an effective and increasingly used tool for weight loss. Traditionally considered high protein, ketogenic diets are often looked at with concern by clinicians due to the potential harm they pose to kidney function. We herein evaluated the efficacy and safety of a VLCKD in patients with obesity and mild kidney failure. A prospective observational real-life study was conducted on ninety-two patients following a VLCKD for approximately 3 months. Thirty-eight had mild kidney failure and fifty-four had no renal condition and were therefore designated as control. Anthropometric parameters, bioelectrical impedance and biochemistry data were collected before and at the end of the dietary intervention. The average weight loss was nearly 20% of initial weight, with a significant reduction in fat mass. We report an improvement of metabolic parameters and no clinically relevant variation regarding liver and kidney function. Upon stratification based on kidney function, no differences in the efficacy and safety outcomes were found. Interestingly, 27.7% of patients with mild renal failure reported normalization of glomerular filtrate after dietary intervention. We conclude that, when conducted under the supervision of healthcare professionals, a VLCKD is an effective and safe treatment for weight loss in patients with obesity, including those affected by mild kidney failure.
Topics: Adult; Caloric Restriction; Diet, Ketogenic; Female; Humans; Male; Middle Aged; Obesity; Renal Insufficiency; Weight Loss
PubMed: 32012661
DOI: 10.3390/nu12020333 -
Nutrients Aug 2023In recent years, the use of the ketogenic diet as a proper nutritional treatment for lipedema has been hypothesized in the literature. This is the first clinical study...
In recent years, the use of the ketogenic diet as a proper nutritional treatment for lipedema has been hypothesized in the literature. This is the first clinical study evaluating the ketogenic diet and carboxytherapy in lipedema patients. In the present study, it was decided to use a modified Mediterranean ketogenic diet (MMKD) in combination with carboxytherapy. Since lipedema is characterized by microangiopathy, local hypoxia, and increased subcutaneous adipose tissue (SAT) deposition, carboxytherapy could improve painful symptoms and skin tone. A total of 22 subjects were included in the data analysis, divided into three groups; 8 patients underwent MMKD combined with carboxytherapy sessions (KDCB group), 8 underwent MMKD nutritional treatment alone (KD group), and 6 patients underwent only carboxytherapy sessions (CB group), for a total of 10 weeks of treatment for all three groups. It was observed that the ketogenic diet effectively induced weight and fat mass loss, including in the limbs, areas considered unresponsive to diet therapy in lipedema patients. However, the best results were obtained from the combination of the ketogenic diet and carboxytherapy, which showed improvements in both body composition and skin texture and a reduction in pain, along with an improvement in sleep quality. It would be helpful to conduct a clinical trial on a larger scale and over a more extended period to observe the results in the long term as well.
Topics: Humans; Lipedema; Pilot Projects; Diet, Ketogenic; Diet, Mediterranean; Subcutaneous Fat; Pain
PubMed: 37630844
DOI: 10.3390/nu15163654 -
Journal of Translational Medicine Oct 2019The epidemic of obesity is growing steadily across the whole world. Obesity is not only a merely aesthetic disease but is the "mother" of most chronic diseases such as... (Review)
Review
The epidemic of obesity is growing steadily across the whole world. Obesity is not only a merely aesthetic disease but is the "mother" of most chronic diseases such as associated with a range of type 2 diabetes, cardiovascular disease, obstructive sleep apnea, and cancer. However, although there is a need to find a strategy to stop this epidemic disease, most of the times the current nutritional strategies are not effective in weight loss and in long term weight maintenance. Very low-calorie ketogenic diets (VLCKD) is increasingly establishing as a successful nutritional pattern to manage obesity; this is due to rapid weight loss that gives rise to a positive psychological cycle which in turn increases the compliance to diet. Another important key point of VLCKD is the ability to preserve fatty free mass which is known to play a role of paramount importance in glucose metabolism. Despite the clinical evidence of VLCKD there are paucity of data regarding to its management. Therefore, we will provide a useful guide to be used by nutrition experts taking care of subjects with obesity. In particular, we will report recommendations on the correct use of this therapeutic approach for weight loss and management of side effects.
Topics: Ambulatory Care Facilities; Caloric Restriction; Clinical Protocols; Contraindications; Diabetes Mellitus, Type 2; Diet, Ketogenic; Diet, Reducing; Female; Humans; Male; Nutritional Physiological Phenomena; Obesity; Practice Guidelines as Topic; Translational Research, Biomedical; Treatment Outcome
PubMed: 31665015
DOI: 10.1186/s12967-019-2104-z -
The Cochrane Database of Systematic... Jun 2020Ketogenic diets (KDs) are high in fat and low in carbohydrates and have been suggested to reduce seizure frequency in people with epilepsy. Such diets may be beneficial... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ketogenic diets (KDs) are high in fat and low in carbohydrates and have been suggested to reduce seizure frequency in people with epilepsy. Such diets may be beneficial for children with drug-resistant epilepsy. This is an update of a review first published in 2003, and last updated in 2018.
OBJECTIVES
To assess the effects of ketogenic diets for people with drug-resistant epilepsy.
SEARCH METHODS
For this update, we searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid, 1946 to 26 April 2019) on 29 April 2019. The Cochrane Register of Studies includes the Cochrane Epilepsy Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), and randomised controlled trials (RCTs) from Embase, ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We imposed no language restrictions. We checked the reference lists of retrieved studies for additional relevant studies.
SELECTION CRITERIA
RCTs or quasi-RCTs of KDs for people of any age with drug-resistant epilepsy.
DATA COLLECTION AND ANALYSIS
Two review authors independently applied predefined criteria to extract data and evaluated study quality. We assessed the outcomes: seizure freedom, seizure reduction (50% or greater reduction in seizure frequency), adverse effects, cognition and behaviour, quality of life, and attrition rate. We incorporated a meta-analysis. We utilised an intention-to-treat (ITT) population for all primary analyses. We presented the results as risk ratios (RRs) with 95% confidence intervals (CIs).
MAIN RESULTS
We identified 13 studies with 932 participants; 711 children (4 months to 18 years) and 221 adults (16 years and over). We assessed all 13 studies to be at high risk of performance and detection bias, due to lack of blinding. Assessments varied from low to high risk of bias for all other domains. We rated the evidence for all outcomes as low to very low certainty. Ketogenic diets versus usual care for children Seizure freedom (RR 3.16, 95% CI 1.20 to 8.35; P = 0.02; 4 studies, 385 participants; very low-certainty evidence) and seizure reduction (RR 5.80, 95% CI 3.48 to 9.65; P < 0.001; 4 studies, 385 participants; low-certainty evidence) favoured KDs (including: classic KD, medium-chain triglyceride (MCT) KD combined, MCT KD only, simplified modified Atkins diet (MAD) compared to usual care for children. We are not confident that these estimated effects are accurate. The most commonly reported adverse effects were vomiting, constipation and diarrhoea for both the intervention and usual care group, but the true effect could be substantially different (low-certainty evidence). Ketogenic diet versus usual care for adults In adults, no participants experienced seizure freedom. Seizure reduction favoured KDs (MAD only) over usual care but, again, we are not confident that the effect estimated is accurate (RR 5.03, 95% CI 0.26 to 97.68; P = 0.29; 2 studies, 141 participants; very low-certainty evidence). Adults receiving MAD most commonly reported vomiting, constipation and diarrhoea (very low-certainty evidence). One study reported a reduction in body mass index (BMI) plus increased cholesterol in the MAD group. The other reported weight loss. The true effect could be substantially different to that reported. Ketogenic diet versus ketogenic diet for children Up to 55% of children achieved seizure freedom with a classical 4:1 KD after three months whilst up to 85% of children achieved seizure reduction (very low-certainty evidence). One trial reported a greater incidence of seizure reduction with gradual-onset KD, as opposed to fasting-onset KD. Up to 25% of children were seizure free with MAD and up to 60% achieved seizure reduction. Up to 25% of children became seizure free with MAD and up to 60% experienced seizure reduction. One study used a simplified MAD (sMAD) and reported that 15% of children gained seizure freedom rates and 56% achieved seizure reduction. We judged all the evidence described as very low certainty, thus we are very unsure whether the results are accurate. The most commonly reported adverse effects were vomiting, constipation and diarrhoea (5 studies, very low-certainty evidence). Two studies reported weight loss. One stated that weight loss and gastrointestinal disturbances were more frequent, with 4:1 versus 3:1 KD, whilst one reported no difference in weight loss with 20 mg/d versus 10 mg/d carbohydrates. In one study, there was a higher incidence of hypercalcuria amongst children receiving classic KD compared to MAD. All effects described are unlikely to be accurate. Ketogenic diet versus ketogenic diet for adults One study randomised 80 adults (aged 18 years and over) to either MAD plus KetoCal during the first month with MAD alone for the second month, or MAD alone for the first month followed by MAD plus KetoCal for the second month. No adults achieved seizure freedom. More adults achieved seizure reduction at one month with MAD alone (42.5%) compared to MAD plus KetoCal (32.5%), however, by three months only 10% of adults in both groups maintained seizure reduction. The evidence for both outcomes was of very low certainty; we are very uncertain whether the effects are accurate. Constipation was more frequently reported in the MAD plus KetoCal group (17.5%) compared to the MAD only group (5%) (1 study, very low-certainty evidence). Diarrhoea and increase/change in seizure pattern/semiology were also commonly reported (17.5% to 20% of participants). The true effects of the diets could be substantially different to that reported.
AUTHORS' CONCLUSIONS
The evidence suggests that KDs could demonstrate effectiveness in children with drug-resistant epilepsy, however, the evidence for the use of KDs in adults remains uncertain. We identified a limited number of studies which all had small sample sizes. Due to the associated risk of bias and imprecision caused by small study populations, the evidence for the use of KDs was of low to very low certainty. More palatable but related diets, such as the MAD, may have a similar effect on seizure control as the classical KD, but could be associated with fewer adverse effects. This assumption requires more investigation. For people who have drug-resistant epilepsy or who are unsuitable for surgical intervention, KDs remain a valid option. Further research is required, particularly for adults with drug-resistant epilepsy.
Topics: Adolescent; Adult; Age Factors; Aged; Child; Child, Preschool; Diet, Carbohydrate-Restricted; Diet, High-Protein Low-Carbohydrate; Diet, Ketogenic; Dietary Carbohydrates; Dietary Fats; Drug Resistant Epilepsy; Humans; Infant; Intention to Treat Analysis; Middle Aged; Prospective Studies; Quality of Life; Randomized Controlled Trials as Topic; Retrospective Studies; Sample Size; Young Adult
PubMed: 32588435
DOI: 10.1002/14651858.CD001903.pub5 -
Nutrients Mar 2021Despite being a focal issue to patients, the effect of diet on adult inflammatory bowel disease (IBD) remains underexplored with limited guidance. While promising... (Review)
Review
Despite being a focal issue to patients, the effect of diet on adult inflammatory bowel disease (IBD) remains underexplored with limited guidance. While promising clinical trials are currently underway, there is a need for further evidence-based recommendations. As such, we summarize the current evidence on various diets used in the treatment of IBD and also explore the potential applications of dietary data from related immune-mediated inflammatory diseases (IMIDs), such as rheumatoid arthritis and psoriasis, to provide additional information to inform IBD providers. To date, there have been multiple diets investigated as adjunctive therapy in IBD, but many associated studies are small, non-randomized, and not controlled. Mediterranean, vegetarian/vegan, and reduced-calorie/fasting diets have been studied and have shown some positive results in other IMIDs, which may suggest potential applicability to those with IBD, but larger, well-designed clinical trials are needed for further guidance. Gluten-free and low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP)diets do not appear to have an impact on IBD disease activity, but low FODMAP may potentially be helpful for those with concurrent functional gastrointestinal symptoms. Specific carbohydrate diets have been mainly assessed in children but show some potential in small adult studies.
Topics: Arthritis, Rheumatoid; Caloric Restriction; Diet; Diet, Carbohydrate-Restricted; Diet, Gluten-Free; Diet, High-Protein Low-Carbohydrate; Diet, Mediterranean; Diet, Paleolithic; Diet, Vegan; Diet, Vegetarian; Fasting; Humans; Inflammatory Bowel Diseases; Psoriasis
PubMed: 33801883
DOI: 10.3390/nu13030890 -
Nutrients Oct 2020High protein calorie restriction diets have shown clinical efficacy for obesity, but the mechanisms are not fully known. The intestinal microbiome is a mediator of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
High protein calorie restriction diets have shown clinical efficacy for obesity, but the mechanisms are not fully known. The intestinal microbiome is a mediator of obesity and preclinical data support an effect of high protein diet (HPD) on the gut microbiome of obesity, but there are few studies in humans.
METHODS
To address this, we conducted a dietary intervention trial of 80 overweight and obese subjects who were randomized to a calorie-restricted high protein diet (HPD) (30% calorie intake) or calorie-restricted normal protein diet (NPD) (15%) for 8 weeks. Baseline dietary intake patterns were assessed by the Diet History Questionnaire III. Longitudinal fecal sampling was performed at baseline, week 1, week 2, week 4, week 6, and week 8, for a total of 365 samples. Intestinal microbiome composition was assessed by 16S rRNA gene sequencing.
RESULTS
At baseline, microbial composition was associated with fiber and protein intake. Subjects on the HPD showed a significant increase in microbial diversity as measured by the Shannon index compared to those on the NPD. The HPD was also associated with significant differences in microbial composition after treatment compared to the NPD. Both diets induced taxonomic shifts compared to baseline, including enrichment of and and depletion of Conclusion: These findings provide evidence that weight loss diets alter the gut microbiome in obesity and suggest differential effects of HPDs compared to NPDs which may influence the clinical response to HPD.
Topics: Adult; Aged; Caloric Restriction; Diet, High-Protein; Diet, Reducing; Dietary Carbohydrates; Dietary Fiber; Energy Intake; Feces; Female; Gastrointestinal Microbiome; Humans; Male; Middle Aged; Obesity
PubMed: 33096810
DOI: 10.3390/nu12103221 -
Aging Cell Oct 2021Several biomarkers of healthy aging have been proposed in recent years, including the epigenetic clocks, based on DNA methylation (DNAm) measures, which are getting... (Randomized Controlled Trial)
Randomized Controlled Trial
Several biomarkers of healthy aging have been proposed in recent years, including the epigenetic clocks, based on DNA methylation (DNAm) measures, which are getting increasingly accurate in predicting the individual biological age. The recently developed "next-generation clock" DNAmGrimAge outperforms "first-generation clocks" in predicting longevity and the onset of many age-related pathological conditions and diseases. Additionally, the total number of stochastic epigenetic mutations (SEMs), also known as the epigenetic mutation load (EML), has been proposed as a complementary DNAm-based biomarker of healthy aging. A fundamental biological property of epigenetic, and in particular DNAm modifications, is the potential reversibility of the effect, raising questions about the possible slowdown of epigenetic aging by modifying one's lifestyle. Here, we investigated whether improved dietary habits and increased physical activity have favorable effects on aging biomarkers in healthy postmenopausal women. The study sample consists of 219 women from the "Diet, Physical Activity, and Mammography" (DAMA) study: a 24-month randomized factorial intervention trial with DNAm measured twice, at baseline and the end of the trial. Women who participated in the dietary intervention had a significant slowing of the DNAmGrimAge clock, whereas increasing physical activity led to a significant reduction of SEMs in crucial cancer-related pathways. Our study provides strong evidence of a causal association between lifestyle modification and slowing down of DNAm aging biomarkers. This randomized trial elucidates the causal relationship between lifestyle and healthy aging-related epigenetic mechanisms.
Topics: Aging; DNA Methylation; Diet Therapy; Exercise; Female; Humans; Male; Time Factors
PubMed: 34535961
DOI: 10.1111/acel.13439