This study shows, for the first time, that ADF is an effective strategy for moderate weight loss (6%) in normal weight and overweight subjects. This diet strategy may also have cardio-protective effects in non-obese subjects, by way of lowering triacylglycerols, CRP and leptin, while increasing LDL particle size and adiponectin concentrations.
The primary goal of this study was to determine if non-obese individuals could benefit from ADF in terms of weight loss. Previous ADF studies implementing non-obese subjects report inconsistent findings [5, 6]. While one study demonstrated decreases in body weight of 2% from baseline after 3 weeks of ADF , another study showed no effect after 2 weeks of diet . The limited amount of weight loss reported previously is undoubtedly a factor of the short trial durations implemented [5, 6]. Thus, we wanted to determine if the degree of weight loss could be amplified if the trial duration was extended to 12 weeks. We show here that normal weight and overweight subjects can indeed benefit from ADF, as body weight was reduced by 6% (5 kg) by the end of the trial. This degree of weight loss in non-obese participants is similar to what has been reported for obese individuals undergoing ADF [2–4]. For instance, Bhutani et al.  demonstrated 5% (5 kg) weight loss after 12 weeks of ADF in obese men and women. In line with these findings, Klempel et al.  and Varady et al.  report 5-6% (5–6 kg) weight loss after 8 weeks of treatment in obese subjects. Thus, ADF may produce a mean rate of weight loss of approximately 0.5 kg/week, independent of the starting weight or BMI class of the subject. Fat free mass was also retained after 12 weeks of ADF in non-obese individuals. This finding is similar to what has been reported in previous short-term studies of ADF [2–4]. As such, the beneficial preservation of fat free mass observed in obese individuals [2–4] may be replicated in non-obese subjects participating in ADF protocols.
Our findings also indicate that normal weight and overweight subjects have no problem adhering to the fast day protocol for 12 weeks. Dietary adherence was very high at baseline (98%), and did not wane over the course of the study. It should be noted, however, that one normal weight subject dropped out of the trial due to an inability to adhere to the diet. Notwithstanding, our dropout rate was still less than 10%, which is similar to the dropout rate of studies performed in obese individuals [2–4]. Complementary to previous reports [12, 13], there was very little or no hyperphagic response on the feed day in response to the lack of food on the fast day. This lack of hyperphagia allowed for overall energy restriction to remain high throughout the study, and undoubtedly contributed to the sizeable degree of weight loss observed here. As for eating behaviors, perceived hunger was moderate at baseline and did not change by week 12. This is contrary to findings in obese participants, which consistently show declines in hunger after 8–12 weeks of ADF [11, 12]. Dietary satisfaction and feelings of fullness, on the other hand, increased from baseline to post-treatment. These increases in satisfaction and fullness have also been noted in obese subjects [11, 12], and may play a role in long-term adherence to the diet.
The cardio-protective effects of ADF were also examined. Reductions in triacylglycerol concentrations (20%) were noted after 12 weeks of ADF. LDL particle size also increased post-treatment (4 Å from baseline). These changes in lipid risk factors are in line with what has been reported for obese ADF subjects [14, 15]. In two recent ADF studies, triacylglycerols decreased by 15% and LDL particle size increased by 2–3 Å after 8 weeks of treatment in obese men and women [14, 15]. Thus, ADF may improve plasma lipids to the same extent in non-obese subjects as it does in obese subjects. Additional vascular benefits, including decreases in circulating leptin and CRP concentrations, in conjunction with increases in adiponectin, were also noted in non-obese subjects undergoing ADF. As for HDL cholesterol, homocysteine, and resistin concentrations, no effect was observed. This lack of effect is not surprising as these CHD risk parameters are generally only improved with >10% weight loss [16–18].
It will be of interest in future studies to determine how alterations in macronutrient intake on the fast day may affect weight loss and cardiovascular outcomes. For instance, it has been well established that Mediterranean  and certain low-carbohydrate diets  help to maintain a healthy body weight and reduce CHD risk. Whether further reductions in body weight and CHD risk would occur if ADF were combined with Mediterranean or low-carbohydrate diets, undoubtedly warrants investigation.
A couple of adverse events were reported during the study. Two subjects experienced mild headaches during week 1 of the trial, which may or may not be related to dietary treatment. One other subject reported constipation during week 1 and 2 of the trial. The subject was advised to consume more fruits and vegetables on feed days, and the constipation subsided by week 3 of the dietary intervention period.
This study has several limitations. First and foremost, it must be acknowledged that this pilot study was originally designed to compare the effects of ADF in normal weight versus overweight individuals on body weight and CHD risk. Due to a low recruitment rate, we were only able to recruit n = 8 subjects into the normal weight group and n = 8 subjects into the overweight group. In view of this, we decided to combine the normal weight and overweight groups into one group to increase sample size. This post hoc change should be taken into consideration when interpreting the findings of this paper. Secondly, physical activity was not assessed throughout the trial, thus the degree of weight loss associated with increased energy expenditure from exercise is not known. Thirdly, the sample size of each group was small (n = 15). Thus, this study may not be adequately powered to detect changes in certain CHD risk parameters (e.g. resistin). Fourthly, this study employed food records to assess dietary intake/adherence. It is well known that overweight subject underreport food intake by ~30% [21, 22]. Thus, our findings for the hyperphagic response on the feed day may be inaccurate.
In summary, these preliminary findings suggest that ADF is a viable weight loss strategy for normal weight and overweight individuals wishing to lose a moderate amount of weight (5–6 kg) within a relatively short period of time (12 weeks). This diet may also help lower CHD risk in non-obese individuals, though further investigation is warranted to confirm these effects. It should also be noted that the purpose of this paper is to report pilot feasibility findings. It is our hope that this preliminary data will be utilized to design larger-scale longer-term trials with similar objectives, in normal weight and overweight participants undergoing ADF.