Characteristics of the groups at baseline are reported in . The groups were of comparable age, weight and demographics and were mainly Caucasian. A small number had co-morbidities, which were equally frequent in the two groups. Six IER (11%) and 10 CER (18%) met the Diabetes Federation Criteria for the metabolic syndrome (41
). The majority of subjects reported previous attempts to diet (IER 92%, CER 78%), with comparable previous attempts between the groups; IER 2.8 (2.1) and CER 2.4 (1.9) (P=0.29).
Baseline Characteristics of Subjects
Eighteen women withdrew from the study before 6 months (IER=11, CER=7) representing 21% IER and 13% CER subjects (χ2 =1.16, P=0.28). The main reasons for drop out were comparable between the groups: stress (IER=3, CER=2), pregnancy (IER=2, CER=1), change in employment (IER=2, CER=1), problems adhering to the diet (IER=3, CER=3) and personal illness (infected pacemaker, IER=1).
Changes in weight, body composition and circumferences
Weight loss was comparable between the groups. LOCF analysis at 6 months showed weight reduced from mean (95% CI) 81.5 (77.5 to 85.4) kg to 75 (71.2 to 78.8) kg in the IER group compared to a reduction from 84.4 (79.7 to 89.1) kg to 78.7 (74.2 to 83.2) kg in the CER group. The percentage of women in the IER and CER groups losing 5–10% body weight were 30 and 33% respectively, and losing 10% or more body weight were 34 and 22% respectively (χ2=1.89, P=0.39). Both groups experienced comparable reductions in body fat, FFM, hip, bust and thigh circumference and composition of weight loss. Percentage of weight lost which was fat in the IER and CER groups was 79 (±24) and 79 (±26) % respectively (P=0.99) (). GEE modelling over 6 months showed no group or group by month interactions for weight (P=0.41) () or body fat () (P=0.36) but a non-significant greater decline in waist measurement with IER at three months (mean difference between groups [95% CI] −1.1 [−2.3 to 0.1] cm, group by month 3 interaction P=0.07) ().
Change in weight and circumferences over 6 months
Weekly dietary records were available for 82 (76%) subjects at baseline, 72 (67%) at 1 month, 65 (60%) at 3 months and 58 (54%) at 6 months. There were no significant differences in energy or macronutrient intakes between the groups at baseline. Changes in dietary intake during the study are reported in . Both groups reported reductions in average weekly energy and macronutrient intakes, however the IER group reported greater reductions for average daily intake of energy (mean difference between groups [95% CI] −716 [−1240 to −192] kJ, −9 [−14 to −2] %, P<0.01), protein (−5.5 [−10.0 to −0.8] g, −6 [−13.0 to 0.0] %, P=0.02) and carbohydrate (−24 [−41 to −8] g, −11 [−18 to −3] %, P=0.004).
Changes in dietary intake and physical activity over 6 months
Intention to treat analysis assuming women who left the study or who did not complete food diaries did not adhere to the diets shows reported adherence to 2 days VLCD amongst the IER group to be 63% at 1 month, 43% at 3 months and 44% at 6 months. A further 7, 24, and 13% of IER subjects completed one day of VLCD at 1, 3 and 6 months respectively. The proportion of CER subjects reporting adhering to the 25% CER was 46% at 1 month, 37% at 3 months and 32% at 6 months. Completers only analysis showed adherence to 2 days or 1 day VLCD in the IER group to be respectively 70 and 8% at 1 month, 56 and 32% at 3 months and 64% and 19% at 6 months, whilst the 25% CER was achieved by 71% at 1 month, 61% at 3 months and 55% at 6 months. At the end of the trial 31 of IER (58%) and 46 (85%) of CER subjects planned to continue the diet allocated at randomisation. Neither group received counselling on exercise, there was no overall change in physical activity in either group.
Changes in insulin sensitivity and associated markers
Both groups experienced modest declines in fasting serum insulin and improvements in insulin sensitivity which were greater amongst the IER group (). Mean difference between groups [95% CI] for fasting insulin was −1.2 [−1.4 to −1.0] μU/ml, −16 [−19 to −13] %, P=0.04; and for insulin resistance was −1.2 [−1.5 to −1.0] μU/mmol/L, −45 [−86 to −3] %, P=0.04) (). GEE modelling showed that the IER group had greater reductions in insulin resistance than the CER group at 3 months (mean difference [95% CI] between groups −17 [−33.2 to −0.2] %, group by month 3 interaction, P=0.046) and 6 months (−23 [−38.1 to −8.6] %, group by month 6 interaction, P=0.001) (). Correspondingly there was a modest increase in adiponectin in the IER group but not the CER group, (mean difference [95% CI] +9 [−2 to 21] %, P=0.08). Changes in the IGF-axis were comparable between the groups with increased IGFBP-1 and IGFBP-2 but negligible changes in total and free IGF-1.
Changes in insulin and related parameters over 6 months
Both groups experienced modest decreases in the inflammatory marker hsCRP, but no change in sialic acid levels. The groups had comparable reductions in the oxidative stress marker, fast acting AOPP by 6 months, which appeared to occur earlier in IER compared to CER. Slow acting AOPP appeared to decrease in the IER group and have a slight increase in the CER group (mean difference between groups at 6 month [95% CI] −10 [−19 to 2] %, P=0.12). Women in the IER group had a non-significant greater increase in serum total ketone bodies at 6 months compared to the CER group suggesting higher rates of fat oxidation (mean difference between groups [95% CI] 33 [−8 to 93] %, P=0.12). There were no significant changes in either group for ghrelin, the growth factor BDNF or for fasting glucose.
Breast cancer risk markers
Both groups experienced large reductions in serum leptin, decreases in the ratio of leptin: adiponectin, no changes in serum levels of testosterone, androstenedione and prolactin. The CER group had a greater reduction in DHEAS compared to IER (mean difference [95% CI] CER vs. IER −6 [−14 to 1] %, P=0.08) however both groups experienced comparable increases in SHBG and a decrease in FAI (). Menstrual cycle data was available for 44 IER (83%) and 47 CER (87%). During the 6 month study period the mean (±SD) length of menstrual cycle was significantly longer in the IER group compared to the CER group (29.7 [±3.8] vs. 27.4 [±2.7] days, P=0.002).
Changes in risk markers for breast cancer and cardiovascular disease
Cardiovascular risk markers
Both diets led to comparable reductions in total and LDL cholesterol, triglycerides, systolic and diastolic BP. Neither group experienced changes in HDL levels ()
Effects of IER and CER on serum markers over one week
A sub-set of women (15 IER and 9 CER) provided fasting serum samples over 1 week during the study period. The IER group demonstrated acute reductions in fasting insulin (−23%), HOMA (−29%) and triglycerides (−18%), in the morning after the 2 day VLCD which normalised within 2 days of resuming normal diet. There were no significant changes in the CER group ().
Quality of life
There were no major adverse effects of the diets. A small number of the IER group (4, 8%), but none of the CER group experienced minor adverse physical symptoms including lack of energy, headaches, feeling cold and constipation. Eight (15%) of the IER and none of the CER complained of hunger, whilst a further 3 (6%) of the IER and 7 (13%) of the CER group reported increased energy and improved health. Eight (15%) of the IER and 4 (7%) of the CER group reported minor adverse psychological effects including lack of concentration, bad temper and preoccupation with food, whilst 17 (32%) of the IER and 25 (46%) of the CER group reported increased self confidence and positive mood. Predictably both groups acknowledged the limited food choice of the diets; 55% IER and 53% CER. More of the IER group reported problems fitting the diet into daily routine; 51% IER vs. 30% CER. RAND SF-36 quality of life scores were available for 96 patients at baseline (88%), 91 at 1 and 3 months (84%) and 75 at 6 months (69%). There was a modest increase in the physical component summary score in the IER but not the CER group (mean difference [95% CI] 2.1 [−0.1 to 4.3] units, 4 [0.0 to 8.0] %, P=0.06). In comparison there was a slightly greater increase in the mental component summary score in the CER compared to the IER group (2.8 [0.1 to 5.6] units, 5 [0.0 to 12.0] %, P=0.04).