Our findings show, for the first time, that the combination of IF plus CR is an effective means of reducing body weight, fat mass, and visceral fat mass in obese women. This novel regimen also decreased key indicators of CHD risk, such as LDL cholesterol, triglycerides, and the proportion of small LDL particles. When liquid meal replacements were incorporated into the IFCR regimen, greater reductions in body weight and indicators of heart disease risk were noted.
Studies of IF in human populations are very limited. To our knowledge, only two studies have examined the effect of IF on body weight
[4, 13]. In a trial conducted by Williams et al.
, obese subjects consumed a very-low calorie diet (VLCD; <500 kcal/d) 1 day per week, and ate ad libitum every other day of the week. After 20 weeks of treatment, body weight decreased by 9% (9 kg) from baseline
. Similar decreases in body weight were also observed in a recent trial by Harvie et al.
. In this study, obese women underwent 2 days of VLCD (600 kcal/d) and ate ad libitum on every other day of the week, for 24 weeks
. Body weight was reduced by 7% (6 kg), fat mass decreased by 13% (4 kg), and waist circumference (an indirect indicator of visceral fat) decreased by 6% (6 cm)
. In the present study, we observed modest weight loss in both the IFCR-L and IFCR-F groups after 8 weeks of treatment. We also observed that the addition of liquid meals to the protocol resulted in greater weight loss (IFCR-L group: 4.1% weight loss versus IFCR-F group: 2.6% weight loss). Reductions in fat mass and visceral fat mass were also demonstrated at the end of the trial, but did not differ between groups. As for fat free mass, no significant changes were noted in either intervention group. This is surprising as a previous study that implemented energy restricted liquid meals observed small but significant decreases in fat free mass (i.e. 3% reductions from baseline) after 8 weeks of treatment
. The greater weight loss by the IFCR-L intervention is most likely due to better dietary adherence. Analysis of food intake revealed a greater degree of energy restriction in the IFCR-L group (29%) compared to the IFCR-F group (22%) over the course of the trial. This greater overall restriction in the IFCR-L group, and hence better adherence, is not surprising as these subjects were given portion-controlled liquid meals for breakfast and lunch everyday. Providing such meals has been shown to boost initial weight loss during dietary restriction protocols as it takes the guesswork out of having to estimate calories from varying foods
. Although these liquid meals are effective for helping with initial weight loss, lasting weight loss and weight maintenance requires extensive dietary counseling to instill healthy behaviors that can be employed long-term
[8, 15]. In view of this, both groups met with a Registered Dietician weekly to incorporate TLC dietary guidelines into their daily lives and to help make the leap from the liquid diet to a wholesome food-based regimen after the study was over.
Beneficial modulations in key lipid risk factors were also observed by both diets. For instance, total and LDL cholesterol decreased in the IFCR-L group (19% and 20%, respectively) and IFCR-F group (8% and 7%, respectively), with greater changes noted for IFCR-L. In contrast, only the IFCR-L group experienced reductions in triglycerides (17% from baseline). The proportion of small LDL particles was also decreased by both the IFCR-L group (week 3: 37 ± 1%, week 10: 28 ± 2%) and IFCR-F group (week 3: 39 ± 1%, week 10: 36 ± 1%). However, increases in LDL peak particle size and the proportion of large LDL particles, were only noted in the IFCR-L group. Taken together, these results suggest that IF combined with CR is an effective means of improving lipid profile in a short-term (8 week) intervention. We also show that adding a liquid diet component may enhance this lipid-lowering effect. The greater decreases in plasma lipids by the IFCR-L diet is most likely due to the greater weight loss noted in this group. For every kg of body weight loss, LDL cholesterol is estimated to decrease by 2 mg/dl
. Since the IFCR-L group lost 1.4 kg more body weight than the IFCR-F group, this may explain why the reductions in LDL cholesterol by the liquid diet intervention were more pronounced. The decreases in lipids demonstrated in the present study are similar to what has been reported in previous trials of IF
[4, 13]. Williams et al.
 noted a 10% and 52% lowering of LDL cholesterol and triglycerides, respectively, after 20 weeks of treatment. In accordance with these findings, Harvie et al.
 observed a 10% decrease in LDL cholesterol and a 17% reduction in triglycerides. No trial to date has examined the effect of IF on LDL particle size, thus there is no data for which to compare our findings.
Modulations in other CHD risk parameters were also more pronounced in the IFCR-L group compared to the IFCR-F group. For instance, fasting plasma glucose and insulin were only decreased by the liquid intervention, suggesting that this diet therapy may benefit glycemic control. Heart rate and homocysteine concentrations were reduced solely in the IFCR-L group. Leptin concentrations, on the other hand, were lowered by both diets. The decreases in leptin are most likely mediated by the reductions in fat mass and visceral fat mass observed in both groups
. Leptin may be involved in atherosclerotic plaque formation through its effect on cholesterol biosynthesis in monocytes
. Thus, these reductions in leptin by IFCR may play a systemic anti-atherogenic role
. Adiponectin levels were also decreased by both diet interventions. This finding is not surprising, as adiponectin levels have been shown to decrease during the first 8–12 weeks of CR, and then increase only once a 10% weight loss has been achieved
. Since the present trial only ran for 8 weeks, and since weight loss was <5%, this may explain why adiponectin concentrations were lowered from baseline. Blood pressure and CRP also remained unchanged throughout the course of the trial in both groups. Accumulating evidence suggest that a 5 and 10% reduction in body weight is required to decrease blood pressure and CRP, respectively
[21, 22]. This degree of weight loss was not attained, which may explain why these two variables were unaffected by either treatment.
This study is limited in that it did not tease apart the effect of IF and CR on body weight and CHD risk. Thus, the independent contributions of the IF diet versus the CR diet on these various parameters, are not known. In order to answer these key questions, a future study should be performed that compares the effect of IF combined with CR, to that of IF alone, and CR alone. An additional limitation of the study was that it did not carefully control for food intake by providing food-based meals to the intervention groups (i.e. dinner meal for the IFCR-L subjects, and 3 meals/d for the IFCR-F subjects). If meals were provided, a more precise measurement of energy restriction and dietary adherence could have been obtained. The study is also limited in that it employed HippoFat software to quantify visceral fat mass from MRI images. This software is limited in that it underestimates visceral fat and overestimates subcutaneous fat, particularly in larger individuals
. Another limitation of the study is that we employed food records to estimate overall calorie restriction in each group. It is well known that obese individuals underreport food intake by 20-40% when completing food records
. Future studies in this field should therefore implement more robust measures of energy assessment such as the doubly-labeled water technique
. The last disadvantage of the study is that only female subjects were employed, and as such, the applicability of these findings to males remains uncertain.
In summary, these findings suggest that IFCR may be effective for reducing body weight, visceral fat mass, and CHD risk in obese women. We also report that incorporating liquid meal replacements into an IFCR regimen may facilitate greater weight loss and lipid-lowering. From a clinical standpoint, we would recommend this diet to individuals who wish to boost the weight loss they see with IF, by adding a daily CR regimen. This combination may also help reduce the boredom typically associated with attempting only one dietary plan. Although these short-term findings are promising, the long-term effects of this novel diet strategy still require confirmation in a large-scale human trial.