An extra virgin olive oil-enriched chocolate spread positively modulates insulin-resistance markers compared with a palm oil-enriched one in healthy young adults: A double-blind, cross-over, randomised controlled trial.

AIMS: To investigate if extra virgin olive oil (EVOO) or palm oil enriched chocolate spreads consumption leads to different results in terms of plasma ceramides concentration, glucose and lipid metabolism, inflammatory markers and appetite regulation in young healthy subjects. METHODS: In a 2-week, double-blind, cross-over, randomised controlled trial, 20 healthy, normal-weight subjects with a mean age of 24.2 years (SD: 1.2), consumed chocolate spread snacks (73% of energy [%E] from fat, 20% from carbohydrates and 7% from proteins), providing 570 Kcal/day added to an isocaloric diet. The chocolate spreads were identical, except for the type of fat: EVOO oil, rich in monounsaturated fatty acids (MUFAs), or palm oil, rich in Saturated Fatty Acids (SFAs). RESULTS: EVOO-enriched chocolate spread consumption led to better circulating sphingolipids and glucose profile, with reduced plasma ceramide C16:0, ceramide C16:0/ceramide C22:0-ceramide C24:0 ratio and sphingomyelin C18:0 (P = 0.030, P= 0.032 and P = 0.042, respectively) compared to the palm oil-enriched chocolate spread diet. HOMA-IR and plasma insulin were lower, while the Quicki and the McAuley Index were higher after the EVOO diet compared to the palm oil diet (P = 0.046, P = 0.045, P = 0.018 and P = 0.039 respectively). Subjects maintained a stable weight throughout the study. No major significant changes in total cholesterol, triglycerides, HDL, inflammatory markers, and appetite-regulating hormones/visual analogue scale were observed between the groups. CONCLUSIONS: Partially replacing SFAs with MUFAs in a chocolate-based snack as part of a short-term isocaloric diet in healthy individuals may limit SFAs detrimental effects on insulin sensitivity and decrease circulating harmful sphingolipids in young adults.

The Mediterranean diet increases glucagon-like peptide 1 and oxyntomodulin compared with a vegetarian diet in patients with type 2 diabetes: A randomized controlled cross-over trial.

AIM: To compare a Mediterranean diet (MED) with a high-fibre vegetarian diet (HFV) in terms of hunger-satiety perception through post-prandial assessment of appetite-related hormones glucagon-like peptide 1 (GLP-1) and oxyntomodulin, as well as self-rated visual analogue scale (VAS) quantification, in overweight/obese subjects with type 2 diabetes (T2D). MATERIALS AND METHODS: Twelve T2D subjects (Male to female ratio = 7:5), mean age 63 ± 8.5 years, were enrolled in a randomized, controlled, crossover study. Participants consumed an MED meal as well as an isocaloric meal rich in complex carbohydrate as well as an isocaloric MED meal in two different visits with a 1-week washout period between the two visits. Appetite ratings, glucose/insulin, and gastrointestinal hormone concentrations were measured at fasting and every 30' until 210' following meal consumption. RESULTS: GLP-1 and oxyntomodulin levels were significantly higher following MED meal compared with HFV meals (210' area under the curve, p < 0.022 and p < 0.023, respectively). Both MED and HFV meal resulted in a biphasic pattern of GLP-1 and oxyntomodulin, although MED meal was related to a delayed, significantly higher second GLP-1 peak at 150' compared with that of HFV meal (p < 0.05). MED meal was related to lower glucose profile compared with HFV meal (p < 0.039), whereas we did not observe significant changes in terms of self-reported VAS scores and insulin trend. CONCLUSIONS: In T2D overweight/obese subjects, an MED meal is more effective than a HFV meal in terms of post-prandial plasma glucose homoeostasis and GLP-1 and oxyntomodulin release. These changes were not confirmed by VAS appetite self-assessment over a 210' period.

Benefits of caloric restriction for cardiometabolic health, including type 2 diabetes mellitus risk.

In the United States, life expectancy has markedly increased during the past century, and population ageing is expected to double within the next 25 years. The process of ageing in a population is associated with the development of chronic diseases, such as type 2 diabetes mellitus, that can be prevented, and even reversed, with the implementation of healthy lifestyle interventions. The evidence to date, consolidated by the numerous epidemiological studies and clinical trials conducted, suggests that caloric restriction is an effective nutritional intervention for preventing most of these age-related conditions. At a metabolic level, caloric restriction with adequate nutrition has been shown to improve insulin sensitivity, reduce fasting glucose and insulin concentration and prevent obesity, type 2 diabetes, hypertension and chronic inflammation. The purpose of this article is to review current knowledge of the metabolic and clinical implications of caloric restriction with adequate nutrition for the prevention of type 2 diabetes and cardiovascular disease.

Increased sclerostin and bone turnover after diet-induced weight loss in type 2 diabetes: a post hoc analysis of the MADIAB trial.

BACKGROUND: Sclerostin has been directly related to bone turnover increase in dietary-induced weight loss in non-diabetics. This has not been studied in type 2 diabetes, a condition characterized by increased circulating sclerostin and impaired bone turnover. PURPOSE: To study the effect of dietary weight loss and quality of the dietary intervention on changes of sclerostin and bone turnover markers in type 2 diabetes. METHODS: This was a post-hoc analysis of the MADIAB trial, a 21-day randomized controlled trial on overweight/obese type 2 diabetes patients. Patients were randomly assigned 1:1 to the Ma-Pi2 macrobiotic diet or a control diet based on dietary guidelines for type 2 diabetes. Serum sclerostin and circulating markers of bone resorption and formation (P1NP) were measured by enzyme linked immunosorbent assay in 40 subjects (1:1) at baseline and after 21 days treatment. RESULTS: Both Ma-Pi2 and the control diet groups had significant decreases in body weight (6.0 ± 0.2 vs. 3.2 ± 0.1 %, p < 0.001). Sclerostin increased significantly in the two groups (all p < 0.001) but Ma-Pi2 diet group experienced a greater increase in sclerostin (34.5 vs. 15 %; p = 0.024). Serum circulating markers of bone resorption increased in the two groups (all p < 0.001); circulating markers of bone resorption at the end of the treatment tended to be higher in Ma-Pi2 diet than the control diet group (p = 0.06). P1NP did not change significantly in the two group compared to baseline. Sclerostin changes were related to body mass index reduction (r = -0.37; p = 0.02). CONCLUSIONS: Diet-induced weight loss may induce significant and rapid changes in bone turnover and sclerostin levels. These changes may further impair bone health in subjects with type 2 diabetes.

Treatment of reactive hypoglycemia with the macrobiotic Ma-pi 2 diet as assessed by continuous glucose monitoring: The MAHYP randomized crossover trial.

BACKGROUND AND AIMS: Nutritional therapy is recommended for management of reactive hypoglycemia (RH), a condition characterized by hypoglycemia that occurs within four hours after a meal. The macrobiotic Ma-Pi 2 diet improves glycemic control in subjects with type 2 diabetes. We explored the effect of this diet on outcomes in non-diabetic individuals with RH. MATERIALS AND METHODS: Twelve subjects with RH were randomized to the Ma-Pi 2 diet for three days and a control diet for three days in a randomized crossover design. Subjects received snacks on two days out of each three-day period only, and were monitored using continuous glucose monitoring. The 24-h period was divided into daytime (08:00-22:30h [subdivided into 'daytime without snacks' and 'daytime with snacks']) and night-time (22:31-07:59h). The effects of the two diets on the number of RH events (blood glucose <70mg/dL [3.9mmol/L]) and the percentage distribution of glucose readings within each of 16 glycemic intervals from <40mg/dL (2.2mmol/L) to >180mg/dL (4.4mmol/L) were determined. RESULTS: There were significantly fewer RH events on the Ma-Pi 2 diet than the control diet during daytime without snacks (-2.5 events; 95% CI: -7.5, 0.0; P=0.022) and daytime with snacks (-4.25 events; 95% CI: -7.5; -2.0; P=0.013) but no difference at night. The percentage of glucose readings in the interval 71-80mg/dL (3.9-4.4mmol/L) was significantly higher on the control diet during daytime with and without snacks (P=0.03 for both), while the percentage of glucose readings in the interval 91-100mg/dL (5.1-5.6mmol/L) was significantly higher on the Ma-Pi 2 diet during daytime without snacks (P=0.02). CONCLUSIONS: The macrobiotic Ma-Pi 2 diet reduced blood glucose excursions during the day, thereby facilitating glycemic control in subjects with RH. The Ma-Pi 2 diet represents an effective nutritional tool for management of RH.

The effect of macrobiotic Ma-Pi 2 diet on systemic inflammation in patients with type 2 diabetes: a post hoc analysis of the MADIAB trial.

INTRODUCTION: Current guidelines for the management of type 2 diabetes (T2D) emphasize diet as essential therapy. However, the effect of diet on systemic inflammation remains unclear. We investigated the effects of consuming a macrobiotic Ma-Pi 2 diet versus a standard recommended diet (control diet) on markers of inflammation in patients with T2D. METHODS: This was a post hoc analysis of the MADIAB trial, a 21-day randomized controlled trial conducted in 51 patients (25 males and 26 females) with T2D. Patients were randomized 1:1 to the Ma-Pi 2 macrobiotic diet or a control diet based on dietary guidelines for T2D. Biological antioxidant potential of plasma and circulating levels of high-sensitivity C reactive protein, interleukin-6, tumor necrosis factor-α, and insulin-like growth factor-1 were assessed. RESULTS: After 21 days on the Ma-Pi 2 or control diet, markers of inflammation were reduced in both groups. The antioxidant potential of plasma improved significantly in the Ma-Pi group. A significant reduction in insulin growth factor-1 was observed in the Ma-Pi group versus control group (p<0.001). CONCLUSIONS: Findings of this post hoc analysis demonstrated that the Ma-Pi 2 diet is a safe dietary strategy to reduce levels of the markers of insulin resistance and inflammation, compared with baseline values, in the short term. Furthermore, the Ma-Pi 2 diet was superior to the control diet in reducing insulin growth factor-1 and may be beneficial for patients with T2D. TRIAL REGISTRATION NUMBER: Current Controlled Trials ISRCTN10467793.

Multiple dietary supplements do not affect metabolic and cardio-vascular health.

Dietary supplements are widely used for health purposes. However, little is known about the metabolic and cardiovascular effects of combinations of popular over-the-counter supplements, each of which has been shown to have anti-oxidant, anti-inflammatory and pro-longevity properties in cell culture or animal studies. This study was a 6-month randomized, single-blind controlled trial, in which 56 non-obese (BMI 21.0-29.9 kg/m(2)) men and women, aged 38 to 55 yr, were assigned to a dietary supplement (SUP) group or control (CON) group, with a 6-month follow-up. The SUP group took 10 dietary supplements each day (100 mg of resveratrol, a complex of 800 mg each of green, black, and white tea extract, 250 mg of pomegranate extract, 650 mg of quercetin, 500 mg of acetyl-l-carnitine, 600 mg of lipoic acid, 900 mg of curcumin, 1 g of sesamin, 1.7 g of cinnamon bark extract, and 1.0 g fish oil). Both the SUP and CON groups took a daily multivitamin/mineral supplement. The main outcome measures were arterial stiffness, endothelial function, biomarkers of inflammation and oxidative stress, and cardiometabolic risk factors. Twenty-four weeks of daily supplementation with 10 dietary supplements did not affect arterial stiffness or endothelial function in nonobese individuals. These compounds also did not alter body fat measured by DEXA, blood pressure, plasma lipids, glucose, insulin, IGF-1, and markers of inflammation and oxidative stress. In summary, supplementation with a combination of popular dietary supplements has no cardiovascular or metabolic effects in non-obese relatively healthy individuals.

The effect of the macrobiotic Ma-Pi 2 diet vs. the recommended diet in the management of type 2 diabetes: the randomized controlled MADIAB trial.

BACKGROUND: Diet is an important component of type 2 diabetes therapy. Low adherence to current therapeutic diets points out to the need for alternative dietary approaches. This study evaluated the effect of a different dietary approach, the macrobiotic Ma-Pi 2 diet, and compared it with standard diets recommended for patients with type 2 diabetes. METHODS: A randomized, controlled, open-label, 21-day trial was undertaken in patients with type 2 diabetes comparing the Ma-Pi 2 diet with standard (control) diet recommended by professional societies for treatment of type 2 diabetes. Changes in fasting blood glucose (FBG) and post-prandial blood glucose (PPBG) were primary outcomes. HbA1c, insulin resistance (IR), lipid panel and anthropometrics were secondary outcomes. RESULTS: After correcting for age, gender, BMI at baseline, and physical activity, there was a significantly greater reduction in the primary outcomes FBG (95% CI: 1.79; 13.46) and PPBG (95% CI: 5.39; 31.44) in those patients receiving the Ma-Pi 2 diet compared with those receiving the control diet. Statistically significantly greater reductions in the secondary outcomes, HbA1c (95% CI: 1.28; 5.46), insulin resistance, total cholesterol, LDL cholesterol and LDL/HDL ratio, BMI, body weight, waist and hip circumference were also found in the Ma-Pi 2 diet group compared with the control diet group. The latter group had a significantly greater reduction of triglycerides compared with the Ma-Pi 2 diet group. CONCLUSIONS: Intervention with a short-term Ma-Pi 2 diet resulted in significantly greater improvements in metabolic control in patients with type 2 diabetes compared with intervention with standard diets recommended for these patients. TRIAL REGISTRATION: Current Controlled Trials ISRCTN10467793.

Caloric restriction may reverse age-related autonomic decline in humans.

Caloric restriction (CR) retards aging in laboratory rodents. No information is available on the effects of long-term CR on physiologic markers of aging and longevity in humans. Heart rate variability (HRV) is a marker for cardiac autonomic functioning. The progressive decline in HRV with aging and the association of higher HRV with better health outcomes are well established. Heart rate variability assessment is a reliable tool by which the effects of CR on autonomic function can be assessed. Time- and frequency-domain analyses compared 24-h HRV in 22 CR individuals aged 35-82 years and 20 age-matched controls eating Western diets (WD). The CR group was significantly leaner than the WD group. Heart rate was significantly lower, and virtually, all HRV values were significantly higher in the CR group than in the WD group (P < 0.002). Heart rate variability in the CR individuals was comparable with published norms for healthy individuals 20 years younger. In addition, when differences in heart rate (HR) and HRV between CR and WD were compared with previously published changes in HRV induced in healthy adults given atenolol, percent differences in each measure were generally similar in direction and magnitude and suggested declines in sympathetic and increases in parasympathetic modulation of HR and increased circadian variability associated with CR. These findings provide evidence that CR has direct systemic effects that counter the expected age-associated changes in autonomic function so that HRV indexes in CR individuals are similar to those of individuals 20 years younger eating WDs.

Long-term calorie restriction, but not endurance exercise, lowers core body temperature in humans.

Reduction of body temperature has been proposed to contribute to the increased lifespan in calorie restricted animals and mice overexpressing the uncoupling protein-2 in hypocretin neurons. However, nothing is known regarding the long-term effects of calorie restriction (CR) with adequate nutrition on body temperature in humans. In this study, 24-hour core body temperature was measured every minute by using ingested telemetric capsules in 24 men and women (mean age 53.7 ± 9.4 yrs) consuming a CR diet for an average of 6 years, 24 age- and sex-matched sedentary (WD) and 24 body fat-matched exercise-trained (EX) volunteers, who were eating Western diets. The CR and EX groups were significantly leaner than the WD group. Energy intake was lower in the CR group (1769 ± 348 kcal/d) than in the WD (2302 ± 668 kcal/d) and EX (2798 ± 760 kcal/d) groups (P < 0.0001). Mean 24-hour, day-time and night-time core body temperatures were all significantly lower in the CR group than in the WD and EX groups (P ≤ 0.01). Long-term CR with adequate nutrition in lean and weight-stable healthy humans is associated with a sustained reduction in core body temperature, similar to that found in CR rodents and monkeys. This adaptation is likely due to CR itself, rather than to leanness, and may be involved in slowing the rate of aging.