In this study, the energy deficit meal plan including meal replacements resulted in significant weight loss typical of meal replacement plans in both groups [15
]. Since there was no run-in period, early dropouts were significant but 70 out of 85 subjects were retained after that point of the study. Because both diets were isocaloric the amounts of weight loss were the same enabling a meaningful comparison of the effects of the dietary intervention on liver function, renal function, and bone density in an outpatient setting. No special efforts were made to assess compliance which could be considered a limitation of the study. Compliance with diets is known to decrease on an outpatient basis and is an unmeasured effect that may account for the lack of findings of adverse events in our study. Nonetheless, this was a practical applied test of the issue as it would be encountered in people undertaking a weight management regimen.
Concerns that diets high in protein may have deleterious effects on renal function were not supported by the results of this study. There was no difference in creatinine clearance with either dietary pattern during weight reduction over one year. A previous study also reported that creatinine clearance was not altered by dietary protein in the context of weight loss while nitrogen balance was more positive in subjects who consumed a high protein diet than in those who consumed a high carbohydrate diet [16
]. Skov et al [8
] assessed changes in renal function by measuring the glomerular filtration rate (GFR) during high-protein and high-carbohydrate diets over a 6-month period and found that the high protein diet had no adverse effects on kidney function. More recently, Knight et al. determined whether protein intake influences the rate of renal function change in women prospectively studied over an 11-year period [7
]. The Nurses' Health Study evaluated 1624 enrolled women between the ages of 42 to 68 years in 1989 who provided blood samples in 1989 and 2000. Ninety-eight percent of women were white, while 1% were African American. In multivariate linear regression analyses, high protein intake was not significantly associated with change in estimated GFR in women with normal renal function (defined as an estimated GFR ≥ 80 mL/min per 1.73 m2
It has been suggested that a high protein diet may generate acidosis because of the presence of ketone bodies in the blood promoting calcium mobilization from bone to buffer the blood and maintain pH. This could promote urinary calcium loss [17
]. There were no deleterious effects of increased protein intake at 2.2 g/kg LBM on markers of bone turnover in our study. In a 12- week study [19
], a high protein diet increased the bone turnover markers while calcium excretion was decreased by 0.8 mmol/d. Evidence also indicates that high protein intake particularly higher animal protein intake is associated with decreased bone loss in older persons [20
The trend of reduction in urinary calcium in this study was also unusual because dietary protein metabolism is associated with increased urinary calcium [21
]. The high vegetable consumption with both dietary patterns may prevent this because high vegetable intakes have been shown to decrease urinary calcium [22
]. An increase in calcium excretion was observed with the consumption of a high protein diet in the study by Johnston et al [16
] which stated that this was due to the high calcium content of the high protein diet in their study. However, we did not observe this high protein pattern in which dietary calcium was very high.
Non-alcoholic fatty liver disease (NAFLD) is now the most common liver disease and is strongly linked to obesity and metabolic syndrome [23
]. In middle aged women in the UK, Liu and colleagues [24
] found that the relative risk of liver cirrhosis increased by 28% for every 5 unit increase in BMI above 22.5 in each stratum of alcohol consumption and estimated 17% of incident or fatal liver cirrhosis is attributable to excess body weight. Hart and colleagues [25
] also show that being overweight or obese and drinking alcohol has a synergistic effect, which amplifies the insult to the liver and greatly increases the risk of liver related morbidity and mortality. Therefore, it is important to demonstrate that an effective weight management program does not elevate liver function tests and add insult to the liver. In this study, there were no adverse effects on liver function tests at either level of protein intake.
The one-year duration of the study may have led to reduced compliance to the meal plans. The study subjects met for a total of 8 sessions with our dietitian. These sessions were designed to support and encourage participants to follow the meal plan including the MR. At each visit, qualitative food logs for macronutrients and meal replacement were collected and reviewed. While we did not measure biochemical compliance, the overall weight loss we observed suggest relatively good compliance to our meal plans.
Noakes et al [19
] reported that subjects with high serum triacylglycerol (>1.5 mmol/L) lost more fat mass with the high protein diet than with the high carbohydrate diet and suggesting a variation in responsiveness to diet based on other metabolic factors such as the presence of insulin resistance which was not measured in the current study.
As in many outpatient diet interventions long-term compliance is undercut by some unmeasured factors likely unrelated to the demonstrated satiety effects of added protein. Therefore, the expected effects on increased weight loss resulting from a high protein diet were not seen in this study. In our previous study, protein-enriched meal led to increased fat mass loss based on bioelectrical impedance analysis in spite of similar overall weight loss as the standard protein meal plan over 12 weeks [26
]. The use of MR may have been the major influence on the weight loss by simplifying their weight loss efforts so that the power of the MR intervention may have obscured the difference between the weight losses of subjects using protein-enriched meal plans by comparison to standard meal plans [5
The Institute of Medicine (IOM) of the National Academy of Sciences [27
] has set acceptable macronutrient distribution ranges for carbohydrate (45%-65% of energy), protein (10%-35% of energy), and fat (20%-35% of energy; limit saturated and trans fats). These proportions provide a range broad enough to cover the macronutrient needs of most active individuals, but specific carbohydrate and protein recommendations are also typically made based on a g/kg body weight formula. These ranges are 5 to 12 g of carbohydrate/kg body weight and 1.2 to 1.8 g/kg body weight for protein depending on the level of physical activity. Clearly, for both the HP and SP group dietary protein intakes were within this recommended range for protein intake. Therefore, our research can only be applied to structured meal plans using protein-enriched shakes for their ability to increase satiety and should not be interpreted as a blanket endorsement of very high protein diets popular with some athletes exceeding the IOM recommendations by including pure protein supplements, high fat animal meats or other sources of organic acids and hidden fat which could adversely affect liver function, renal function, or bone density.