Intermittent fasting 5:2 diet: What is the macronutrient and micronutrient intake and composition?

BACKGROUND & AIM: Intermittent fasting (IF) is a dietary intervention that has been investigated as an alternative weight-loss diet due to conventional approaches having poor long-term adherence. However, the macronutrient and micronutrient intake and composition of IF diets have been overlooked. The primary aim of this study was to describe the macronutrient and micronutrient intake of individuals following the 5:2 intermittent fasting diet (IF 5:2). METHODS: Thirty eight overweight and obese participants were included from two previous studies of IF 5:2. The participants selected included 27 males and 11 females, with and without Type 2 Diabetes. The dietary intervention, IF 5:2, consisted of two days per week fasting, either consecutive or non-consecutive, and five days per week of habitual intake. Prospectively completed 4-day estimated food records were used to assess macronutrient and micronutrient intake at baseline and week six. The 4-day records were weighted to give a mean daily intake during IF 5:2. RESULTS: During IF 5:2 the median (25th, 75th quartile) daily macronutrient composition was 22 (19, 24)% from protein, 33 (29, 37)% from fat and 39 (36, 43)% from carbohydrates. The intake (g/d) of carbohydrates and fibre decreased significantly from baseline to week six (p < 0.001) as well as on fasting days compared to non-fasting days (p < 0.001). The intake of calcium, zinc, magnesium and potassium were lower than recommended guidelines. Sodium intake exceeded the suggested daily target. On fasting days, the percent of total energy from protein significantly increased from 21% to 25% (p = 0.02). Despite intake being unrestricted on non-fasting days the energy intake decreased by week six when compared with baseline. CONCLUSION: The composition of IF 5:2 was a high protein, moderate fat, low carbohydrate diet with a low fibre intake. Some micronutrients have lower than recommended intake. However, overall IF 5:2 is a safe acceptable weight-loss diet strategy.

Intermittent fasting in Type 2 diabetes mellitus and the risk of hypoglycaemia: a randomized controlled trial.

AIMS: To establish whether the risk of hypoglycaemia is greater with 2 consecutive days of very-low-calorie diet compared with 2 non-consecutive days of very-low-calorie diet in people with Type 2 diabetes. METHODS: This was a non-blinded randomized parallel group interventional trial of intermittent fasting in adults. The participants had a BMI of 30-45 kg/m2 , Type 2 diabetes treated with metformin and/or hypoglycaemic medications and an HbA1c concentration of 50-86 mmol/mol (6.7-10%). The participants followed a 2092-2510-kJ diet on 2 days per week for 12 weeks. A total of 41 participants were randomized 1:1 to consecutive (n=19) or non-consecutive (n=22) day fasts, of whom 37 (n=18 and n=19, respectively) were included in the final analysis. The primary outcome was difference in the rate of hypoglycaemia between the two study arms. Secondary outcomes included change in diet, quality of life, weight, lipid, glucose and HbA1c levels, and liver function. RESULTS: The mean hypoglycaemia rate was 1.4 events over 12 weeks. Fasting increased the rate of hypoglycaemia despite medication reduction (RR 2.05, 95% CI 1.17 to 3.52). There was no difference between fasting on consecutive days and fasting on non-consecutive days (RR 1.54, 95% CI 0.35 to 6.11). Improvements in weight, HbA1c , fasting glucose and quality of life were experienced by participants in both arms. CONCLUSIONS: In individuals with Type 2 diabetes on hypoglycaemic medications, fasting of any type increased the rate of hypoglycaemia. With education and medication reduction, fewer than expected hypoglycaemic events occurred. Although it was not possible to determine whether fasting on consecutive days increased the risk of hypoglycaemia, an acceptable rate was observed in both arms.

Weight-based carbohydrate treatment of hypoglycaemia in people with Type 1 diabetes using insulin pump therapy: a randomized crossover clinical trial.

AIM: To test whether weight-based treatment is more effective than usual care in people with Type 1 diabetes receiving continuous subcutaneous insulin infusion therapy with regard to both hypoglycaemia and avoiding excessive rebound hyperglycaemia. METHODS: Children and adults on continuous subcutaneous insulin infusion were enrolled into a study with a crossover design. Each episode of hypoglycaemia (defined as capillary glucose <4.0 mmol/l) was randomly assigned one of two treatment protocols using glucose tablets: either 0.3 g/kg body weight or usual treatment with 15 g (adults) or 10 g (children) for capillary glucose levels 3-3.9 mmol/l or twice these doses for capillary glucose levels <3 mmol/l. All participants received each treatment in random order for up to 10 hypoglycaemic episodes. Glucose levels were re-tested 10 min after treatment, with a repeat dose if still <4 mmol/l. RESULTS: Of the 37 participants enrolled, 35 (aged 6-68 years) completed the study. Twenty-four participants completed all treatment episodes, while 10 participants had <10 hypoglycaemic episodes and two withdrew without data. The mean glucose difference between weight-based and usual treatment after 10 min was 0.33 mmol/l (95% CI 0.005 to 0.66; P=0.047) in adults and 0.45 (95% CI 0.18 to 0.72; P=0.001) in children. The odds ratios for resolution of hypoglycaemia at 10 min with a single treatment using weight-based compared with usual treatment were 3.12 (95% CI 1.38 to 7.02; P=0.0070) in adults and 2.61 (95% CI 1.19 to 5.74; P=0.017) in children. CONCLUSIONS: Weight-based treatment using 0.3 g/kg glucose was more effective for symptomatic hypoglycaemia in children and adults with Type 1 diabetes who were using continuous subcutaneous insulin infusion than treatment based on current international recommendations.

Weight-based hypoglycaemia treatment protocol for adults with Type 1 diabetes: a randomized crossover clinical trial.

AIM: To determine whether a weight-based hypoglycaemia treatment using 0.3 g/kg (or 0.2 g/kg) glucose effectively treats adults with Type 1 diabetes mellitus compared with an internationally recommended 15-g treatment. METHODS: Patients with frequent hypoglycaemia were recruited from hospital-based diabetes clinics. The treatment for each hypoglycaemic episode, defined as capillary glucose <4.0 mmol/l, was randomly assigned to one of three protocols: 0.2 g/kg, 0.3 g/kg, or 15 g, using Dextro(TM) glucose tablets (Dextro Energy, Krefeld, Germany). Each participant received each treatment in random order for up to 15 hypoglycaemic episodes. Capillary glucose was re-tested 10 min after treatment, with a repeat dose if still < 4 mmol/l. RESULTS: The study recruited 34 participants aged 22-71 years, whose mean (sd) BMI was 25.2 (3.1) kg/m(2) and HbA1c 63 (10.4) mmol/mol [7.9 (0.9)%]. Two people withdrew because they did not like the taste of the Dextro tablets and one was excluded because they used their own glucose preparation. Unadjusted for clustering within participants, the mean (sd) capillary glucose after 10 min was 4.67 (1.25) mmol/l for 0.3 g/kg (141 episodes), 4.29 (0.94) mmol/l for 0.2 g/kg (132 episodes), and 4.37(0.99) mmol/l for 15 g (136 episodes). Capillary glucose, adjusted for clusters and baseline, was higher after 10 min for 0.3 g/kg glucose compared with 15 g glucose; a difference of 0.26 (95% CI 0.04-0.48) mmol/l (P = 0.02), but not for 0.2 g/kg; -0.07 (95% CI -0.29-0.16) mmol/l (P = 0.56). Capillary glucose for only three hypoglycaemic episodes rose above 8 mmol/l. CONCLUSIONS: A weight-based protocol of 0.3 g/kg glucose appears more effective for treating symptomatic hypoglycaemia in adults with Type 1 diabetes than either the most common current recommendation of 15 g glucose or a 0.2 g/kg glucose dose.

A structured, group-based diabetes self-management education (DSME) programme for people, families and whanau with type 2 diabetes (T2DM) in New Zealand: an observational study.

BACKGROUND: Group-based diabetes self-management education (DSME) programmes have been shown to be effective. A programme tailored for the unique social and ethnic environment of New Zealand (NZ) was developed using concepts from internationally developed programmes. AIM: To assess the effectiveness of a 6 week New Zealand specific DSME programme. METHODS: In this observational study people with type 2 diabetes (aged 18-80 years) from diverse cultural backgrounds were recruited from primary care. Seventeen groups of six education sessions were run. Clinical data were collected from primary care at baseline, 3, 6 and 9 months. Participants also completed a self-administered questionnaire on diabetes knowledge, and self-management behaviours. RESULTS: 107 participants, mean age 56.7±11.3 years and mean duration of diabetes 7.5±7 years (NZ European (44%), Maori (24%), Pacific (16%) and Indian (16%)), were enrolled. Confidence in self-managing diabetes, regular examination of feet, physical activity levels and smoking rates all improved. Glycaemic control improved between baseline and 6 months (HbA1C 64.9±20.0 mmol/mol to 59.9±13.9 mmol/mol (p<0.05) (baseline 8.07%±1.80, 6 months 7.62%±1.25)), but was no different to baseline at 9 months. Systolic BP reduced from 131.9±16.4 to 127.4±18.2 mmHg (p<0.05) at 6 months, but increased to baseline levels by 9 months. Diastolic BP, triglycerides and urine microalbumin:creatinine ratio were significantly reduced at 3, 6 and 9 months. CONCLUSION: A group-based DSME programme designed specifically for the NZ population was effective at improving aspects of diabetes care at 6 months. The attenuation of these improvements after 6 months suggests a refresher course at that time may be beneficial.

The Diabetes Excess Weight Loss (DEWL) Trial: a randomised controlled trial of high-protein versus high-carbohydrate diets over 2 years in type 2 diabetes.

AIMS/HYPOTHESIS: To compare the effectiveness of low-fat high-protein and low-fat high-carbohydrate dietary advice on weight loss, using group-based interventions, among overweight people with type 2 diabetes. Study design Multicentre parallel (1:1) design, blinded randomised controlled trial. METHODS: Individuals with type 2 diabetes aged 30­75 years and a BMI >27 kg/m2 were randomised, by an independent statistician using sequentially numbered sealed envelopes, to be prescribed either a low-fat high-protein (30% of energy as protein, 40% as carbohydrate, 30% as fat) or a low-fat high carbohydrate(15% of energy as protein, 55%as carbohydrate,30% as fat) diet. Participants attended 18 group sessions over 12 months. Primary outcomes were change in weight and waist circumference assessed at baseline, 6 and 12 months.Secondary outcomes were body fatness, glycaemic control,lipid profile, blood pressure and renal function. A further assessment was undertaken 12 months after the intervention.Research assessors remained blinded to group allocation throughout. Intention-to-treat analysis was performed. RESULTS: A total of 419 participants were enrolled (mean±SDage 58±9.5 years,BMI 36.6±6.5 kg/m2 and HbA1c 8.1±1.2%(65 mmol/mol)). The study was completed by 70%(294/419).No differences between groups were found in change in weight or waist circumference during the intervention phase or the 12-month follow-up. Both groups had lost weight (2­3 kg, p<0.001) and reduced their waist circumference (2­3 cm, p<0.001) by 12 months and largely maintained this weight loss for the following 12 months. By 6 months, the difference in self-reported dietary protein between groups was small (1.1%total energy; p<0.001). No significant differences between groups were found in secondary outcomes: body fatness, HbA1c, lipids, blood pressure and renal function.There were no important adverse effects. CONCLUSIONS/INTERPRETATION: In a 'real-world' setting, prescription of an energy-reduced low-fat diet, with either increased protein or carbohydrate, results in similar modest losses in weight and waist circumference over 2 years

The impact of long chain n-3 polyunsaturated fatty acid supplementation on inflammation, insulin sensitivity and CVD risk in a group of overweight women with an inflammatory phenotype.

BACKGROUND: Inflammation is strongly related to obesity and the risk of cardiovascular disease (CVD). The metabolic benefits of long chain (LC) n-3 polyunsaturated fatty acid (PUFA) may be attributable to its anti-inflammatory properties. OBJECTIVE: To investigate whether an individual's habitual inflammatory status influences the impact of a LC n-3 PUFA intervention on CVD risk. DESIGN: The study was a randomized crossover design. Subjects received LC n-3 PUFA capsules or a placebo for 12 weeks, with 4-week washout between phases. Thirty women, in the top and bottom tertiles of baseline sialic acid concentration, formed raised inflammatory status (top, n = 12) and reference (bottom, n = 18) groups. Baseline data were analysed using one-way anova, differences between treatment phases were calculated at each timepoint and analysed using a random effects model. RESULTS: At baseline, the raised inflammatory status group had significantly higher body mass index and area under the curve (AUC) insulin than the reference group. With LC n-3 PUFA supplementation, both groups showed significantly higher plasma eicosapentaenoic acid and docosahexaenoic acid at 4 and 12 weeks (p < 0.001), and lower triacylglycerols (4 weeks p < 0.01 and 12 weeks p < 0.05). The difference in AUC insulin between the two treatment phases at 12 weeks was significantly greater in the raised inflammatory status group compared to the reference group (p < 0.05). Inflammatory markers were significantly lower after 12 weeks LC n-3 PUFA supplementation compared to baseline (C-reactive protein p < 0.05 and interleukin-6 p < 0.01), but there was no significant group effect. CONCLUSIONS: Habitual inflammatory status influences the impact of LC n-3 PUFA supplementation, but it is not clear whether the effect of LC n-3 PUFA on AUC insulin is mediated through inflammatory mechanisms.

Additive benefits of long-chain n-3 polyunsaturated fatty acids and weight-loss in the management of cardiovascular disease risk in overweight hyperinsulinaemic women.

BACKGROUND: Obesity, inflammation, insulin resistance and cardiovascular disease (CVD) risk are inter-related. Both weight-loss and long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) are independently known to reduce metabolic risk, but the combined effects are unclear. OBJECTIVE: This study examines whether addition of LC n-3 PUFA to a low fat/high carbohydrate weight-loss programme results in greater improvements in inflammation, insulin sensitivity and CVD risk, than weight-loss alone. DESIGN: One hundred and sixteen overweight insulin-resistant women entered a 24-week randomised intervention study. Thirty-nine women were randomised to a weight-loss programme, with LC n-3 PUFA (WLFO), 38 to a weight-loss programme with placebo oil (WLPO), and 39 to receive placebo oil, with no weight-loss programme (control). RESULTS: Ninety-three women completed the study (35 WLFO, 32 WLPO and 26 control), with significant weight-loss in WLFO (10.8+/-1.0%) and WLPO (12.4+/-1.0%) compared to the control group (P<0.0001). The WLFO, but not WLPO or control group, showed significant increases in adipose tissue LC n-3 PUFA (0.34+/-0.20 vs 0.17+/-0.10 and 0.16+/-0.10 %DHA, P<0.0001). Weight-loss showed significant improvements in insulin sensitivity (P<0.001), lipid profile (triglycerides P<0.05) and inflammation (sialic acid P<0.05). Time*group effects showed significant decreases in triglycerides (P<0.05) and increases in adiponectin (P<0.01) with LC n-3 PUFA, in the WLFO vs WLPO groups. CONCLUSIONS: Weight-loss improved risk factors associated with CVD, with some additional benefits of LC n-3 PUFA on triglycerides and adiponectin. Given the current low dietary intake of LC n-3 PUFA, greater attention should be given to increase these fatty acids in the treatment of obesity.

Discrimination ratio analysis of inflammatory markers: implications for the study of inflammation in chronic disease.

To understand the role of inflammation in chronic disease it is important to have a reliable measure of habitual inflammatory status. A number of acute-phase response markers have been used as measures of inflammatory status, but the ability of a single measure to appropriately reflect habitual inflammatory status has not been assessed. This study compares the ability of different inflammatory markers to characterize habitual inflammatory status in overweight women. A single fasting blood sample was taken from 86 overweight women (mean body mass index [BMI], 35.2 kg/m2; range, 26.2 to 47.6 kg/m2) and a number of inflammatory markers (both acute-phase response markers and cytokines) were measured. A randomly selected subpopulation of 15 women attended on 2 further occasions for further blood samples. Using the subpopulation, discrimination ratios (DRs) were calculated for each inflammatory marker to assess the within-subject variability. The DRs were then used to determine the relationship between these markers, adjusted for within-subject variability, in the whole population. In this highly controlled experimental environment, interleukin-6 (IL-6), with a DR of 3.71, was the cytokine with the greatest ability to discriminate between subjects, suggesting that it is best able to characterize habitual inflammatory status. Sialic acid was the acute-phase response marker with the highest DR (3.16), and showed stronger correlations with other inflammatory markers, including C-reactive protein (CRP), than IL-6. This study suggests that use of some inflammatory markers, such as CRP, with large within-individual variability, will underestimate the relationship between inflammation and disease, and thus relationships between inflammation and chronic disease may be stronger than previously appreciated. Future studies should consider IL-6 or sialic acid to provide a more robust measure of inflammatory status.

Elevated sialic acid, but not CRP, predicts features of the metabolic syndrome independently of BMI in women.

AIMS: C-reactive protein (CRP) is a predictor of many diseases including type II diabetes and cardiovascular disease. Fewer studies have similarly shown sialic acid (SA) to be a predictor of obesity-related diseases, but importantly SA shows less intra-individual variability than CRP and acts as an integrated marker of the activity of a number of acute-phase proteins. This study examines the association between both CRP and SA with individual and combined features of the metabolic syndrome. SUBJECTS: In all, 257 women with a body mass index (BMI) ranging from 25.1 to 54.5 kg/m2 (geometric mean 33.1+/-5.8 kg/m2) and aged 19-71 y (mean 45.6+/-12.1 y) were studied. Subjects had no symptoms of intercurrent infection, known diabetes, treated dyslipidaemia, a chronic inflammatory condition, liver disease or malignancy. RESULTS: Linear regression demonstrates that both CRP and SA were positively associated with weight, BMI, insulin resistance, dyslipidaemia and hypertension. There was a highly significant (P<0.0001) positive association of both SA and CRP with none, one, two, three or four features of the metabolic syndrome. For a 1 s.d. (4.0 mg/l) increase in CRP, there was a significant increased risk when comparing the odds of having metabolic syndrome (defined as three or more individual features) compared with the remainder of the population (odds ratio=1.7, P<0.0001), but this was not significant after adjustment for BMI. However, for a 1 s.d. (0.34 mmol/l) increase in SA, the odds of having metabolic syndrome compared with those without metabolic syndrome was 2.5 (P<0.0001), and persisted after additional adjustment for BMI (adjusted odds ratio=1.9, P<0.0001). CONCLUSIONS: While SA and CRP are both univariately associated with individual features of the metabolic syndrome, SA, but not CRP, is significantly associated with the metabolic syndrome, independent of BMI. We conclude that SA identifies a subgroup of overweight individuals with an inflammatory phenotype, who are at the greatest risk of metabolic syndrome.

Changes in risk factors for cardiovascular disease with body fat loss in obese women.

BACKGROUND: Current guidelines for obesity management emphasize the improvements in health risks associated with weight losses of 5-10% initial weight. However, most of the data is derived from periods of acute weight loss and may not represent the true effect in the longer term or in obese but otherwise healthy individuals. This study examines the temporal changes in risk factors for cardiovascular disease with weight change over 52 weeks. METHODS: In total, 57 overweight women (age 43.7 +/- 9.1 years, mean BMI of 31.7 kg/m2, range 27.2-38.5 kg/m2) with no other significant medical history, entered a milk-based, low-energy weight loss programme for 12 weeks and were then monitored without further intervention until 52 weeks. Weight, fat mass, fasting plasma insulin, lipids and blood pressure were measured at 0, 12, 24 and 52 weeks. RESULTS: The mean weight change in sequential periods was -11.6% (p < 0.0001), +1.1% (p = 0.02) and +5.2% (p < 0.0001). The change from baseline to 1 year being -6.0% (p < 0.0001) an 11% (p < 0.0001) reduction in initial body fat mass. Initial weight loss (0-12 weeks) was positively correlated with greater longer term weight loss (0-52 weeks, r = 0.75, p < 0.0001) and not with weight regain (12-52 weeks, r = 0.14, p = 0.28). Despite significant improvements in insulin sensitivity, lipid profile and blood pressure (BP) with acute weight loss, in the group overall, only benefits in BP were maintained after 52 weeks. However, improvements in insulin sensitivity were sustained in those who maintained more than 5% weight loss, and those with higher baseline metabolic risk had greater benefits with weight loss. Change in waist circumference was better than BMI or fat mass in predicting improvements in metabolic risk in these obese women. CONCLUSIONS: This study suggests, in otherwise apparently healthy obese women, the rationale of targeting individuals most likely to benefit from weight management. Most importantly it highlights the need to focus on achieving initial weight losses of greater than 10% to maintain longer term losses of at least 5% and the associated health benefits.

Follow up testing of hyperglycaemia during hospital admission: combined use of fasting plasma glucose and HbA1c.

AIM: To follow up patients without known diabetes, but with hyperglycaemia in hospital for diabetes at one year. METHODS: 159 patients with a random plasma glucose > or = 7.8 mmol/L recorded during hospital admission were sent a questionnaire and invited to have the following test one year following discharge: fasting plasma glucose, HbA1c and fasting lipid profile. Those with a fasting plasma glucose > or = 5.5 and < 7.0 mmol/L, and/or those with a HbA1c > or = 6.0%, were asked to have an oral glucose tolerance test. Those with a fasting plasma glucose > or = 7.0 mmol/L were defined as having diabetes. RESULTS: There were 88 full responses. Nineteen (21.6%) had diabetes and nine impaired glucose tolerance. Hb1Ac was > or = 6% in five subjects with a fasting plasma glucose < 5.5 mmol/L. Two had impaired glucose tolerance and one diabetes. If a random plasma glucose in-hospital of 10 mmol/L is used as a threshold for later testing, as suggested by previous studies, then 25% of those with an abnormal result would have been missed. CONCLUSIONS: A high proportion of those with hyperglycaemia in hospital have diabetes or impaired glucose tolerance at one year. Initial testing with fasting plasma glucose and HbA1c avoided oral glucose tolerance test in 76% of cases. Use of HbA1c detected otherwise missed diabetes and impaired glucose tolerance. A random plasma glucose of > or = 7.8 mmol/L in hospital targets patients who should be tested for impaired glucose tolerance or diabetes following discharge.