This systematic review focuses on randomized controlled trials (RCTs) of LC/HP diets compared with LF/high‐carbohydrate (HC) conventional diets. The systematic review also examines the outcomes of such trials in relation to effects on cardiovascular disease risk. This systematic review focuses on updating the literary evidence from RCTs of LC/HP diets compared with LF/HC diets to assess their impact on weight loss and cardiovascular risk. In addition, it demonstrates lower attrition rates in the LC/HP groups compared with the LF/HC groups suggesting patient preference for the former approach.

Recently, low‐carbohydrate/high‐protein (LC/HP) diets have become popular as an aid to weight loss. Significant weight loss on a LC/HP diet without significant elevations of serum cholesterol has been reported. Studies comparing the ‘Atkins’ diet with the classical low‐fat (LF) diet have appeared in the literature recently and are the subject of increasing public interest 5 due to the beneficial improvements in cardiovascular risk and weight loss achieved with this type of dietary approach 6 , 7 .

The prevalence of overweight and obesity is already high and continues to increase in both the developed and developing world 1 . Obesity has been implicated as the second most preventable cause of death in the United States. After remaining reasonably constant in the 1960s and 1970s, the prevalence of obesity among adults in the United States increased by around 50% per decade throughout the 1980s and 1990s. Two‐thirds of adults in the United States today are obese or overweight. In the United States, 28% of men, 34% of women and nearly 50% of non‐Hispanic black women are at present obese 2 . At any time, approximately 45% of women and 30% of men in the UK are trying to lose weight 3 . Most adults in England are now overweight, and nearly one‐quarter are obese ( http://www.foresight.gov.uk/obesity/17.pdf ). Obesity has been shown to be associated with increased risk of type 2 diabetes mellitus, hypertension, dyslipidemia and consequent cardiovascular disease. Obesity ranks second only to smoking in the aetiology of cancer and is an important factor in osteoarthritis and obstructive sleep apnoea 4 .

Data processing for this review in Review Manager required the input of the mean and the standard deviation (SD) of the change between two time points. Where weight or risk factors were reported as actual values instead of changes, the differences were calculated by subtracting the end point value from the baseline value. If SD for changes in weight and risk factors were missing, the following assumption was made – a previously published linear regression of the SD of the mean change in weight on the absolute mean change for weight 8 , derived from weight‐loss RCTs, was used to supply missing SD. Similar data were used to infer missing SD for the other variables analysed in this review.

The computer program Review Manager 4.2.2 was used for the analysis of the data from the reviews. If results from studies could be quantitatively combined, a statistical meta‐analysis of the data was undertaken to determine the typical effect size of the intervention. For continuous data, a weighted mean difference (WMD) was calculated. The chi‐square test was used to test for heterogeneity across the studies. The significance value was set at 0.05.

Full copies of studies were assessed by two researchers for methodological quality using a standard form. The researchers were not blinded to author, journal or institution. Differences of opinion were resolved by discussion. Trial quality was assessed, including whether or not the analysis was undertaken on an intention to treat basis.

This systematic review was restricted to RCTs where the full study report was available. A wide search strategy was applied to identify as many RCTs evaluating dietary interventions as possible and which were relevant to the management of obesity and cardiovascular disease risk factors. Thirteen electronic databases were searched including MEDLINE, Commonwealth Agricultural Bureau (CAB) abstracts and the Cochrane Central Register of Controlled Trials. The search strategy incorporated weight loss, cardiovascular disease and obesity‐related terms and text terms, specific to each database. Seven obesity and nutrition journals were hand‐searched including the International Journal of Obesity and Obesity Research . Reference lists of included studies were searched and authors contacted for further details of their trials.

Weight loss or prevention of weight gain was the main outcomes assessed from the RCTs included in the review. With regard to cardiovascular disease risk factors, the following outcomes were also included:

The focus of this review was to examine LC/HP diets against other types of diets designed to induce weight loss and/or prevent weight gain, and induce changes in cardiovascular risk factors. The types of dietary intervention evaluated were:

The protocol used for this systematic review follows the methods recommended by the Cochrane Collaboration 8 . RCTs were included if they assessed the weight‐loss effects of LC/HP diets against LF/HC diets. Only RCTs from January 2000 to March 2007 were evaluated, as this review is intended to assess the current literature in this field and update the National Health Service R&D Health Technology Assessment systematic review of diet and lifestyle on weight loss and cardiovascular risk published by Avenell et al. 8 . Only studies conducted in an adult population were included, as defined by minimum age greater than 18 years. RCTs where the participants had a mean or median body mass index (BMI) of ≥28 kg m −2 were included. A BMI cut‐off of ≥28 kg m −2 was used to allow the inclusion of studies of ethnic groups where the classification of obesity is at a lower BMI cut‐off 9 . RCTs evaluated in this review had to be of at least 6‐month duration, including the period of active intervention and follow‐up.

The WMD between the groups in fasting plasma glucose was not significant and there was no evidence of statistical heterogeneity at either time ( Fig. 9 ).

The WMD decrease in diastolic blood pressure of 0.49 mmHg at 6 months favouring the LC/HP group was not significant ( Fig. 8a ). At 12 months, the WMD between the two groups of 0.81 mmHg lowering favouring the LC/HP group was greater, but was also not significant ( Fig. 8b ). There was no evidence of statistical heterogeneity across the studies at either time.

The WMD drop in systolic blood pressure of −1.35 mmHg at 6 months favouring the LC/HP group was not significant ( Fig. 7a ). At 12 months the WMD between the groups was a decrease of 2.19 mmHg favouring the LC/HP group ( P = 0.05) ( Fig. 7b ). There was no difference between the studies at either time.

The WMD in triacylglycerol was −0.17 mmol L −1 at 6 months ( P = 0.0001) favouring the LC/HP group ( Fig. 6a ). At 12 months the WMD between the groups was −0.19 mmol L −1 favouring the LC/HP group ( P = 0.04). Again, there was evidence of heterogeneity across the groups ( P = 0.01).

The WMD in HDL cholesterol change was 0.04 mmol L −1 at 6 months ( P = 0.03) favouring the LC/HP group ( Fig. 5a ). There was a slightly greater increase in the WMD in HDL cholesterol at 12 months (0.06 mmol L −1 ) favouring the LC/HP group ( P < 0.05). There were no differences found between the studies at 6 months ( P = 0.46) or 12 months ( P = 0.49).

The WMD in LDL cholesterol change was 0.14 mmol L −1 at 6 months ( P < 0.00001) with the LC/HP group demonstrating the increased LDL cholesterol ( Fig. 4a ). The difference between the groups was greater at 12 months (0.37 mmol L −1 ) ( P < 0.00001) with the LC/HP group again demonstrating the increased LDL cholesterol ( Fig. 4b ). There were no differences among the studies at 6 months ( P = 0.65), but there were differences found between the studies at 12 months ( P < 0.00001).

The WMD in total cholesterol change was 0.19 mmol L −1 at 6 months ( P < 0.0001) with the LC/HP group demonstrating the increased cholesterol ( Fig. 3a ). This was also the case at 12 months, although the difference between the groups was smaller and not significant (0.10 mmol L −1 , P = 0.31) ( Fig. 3b ). There were no differences among the studies at 6 ( P = 0.84) and 12 ( P = 0.14) months.

The WMD in weight change was −4.02 kg in favour of the LC/HP group at 6 months ( Fig. 2a ) (P < 0.00001). At 12 months this difference had fallen to only −1.05 kg ( P < 0.05) ( Fig. 2b ). There were differences ( P < 0.0001) among the studies at 6 months, but agreement shown by lack of heterogeneity at 12 months.

A total of 1222 volunteers were recruited between the 13 studies. Fig. 1 shows the percentage attrition rates. Out of the 1222 participants assigned to the diets, there were 441 (36%) attritions during the interventions. There was a higher attrition rate in the conventional/LF/medium‐protein groups compared with the LC/HP intervention groups. The difference in attrition rates between the two groups was significant ( P = 0.001) after performing a chi‐squared test.

Ten of the studies compared LC/HP diets with LF/HC diets and two studies compared medium‐protein diets with HP diets. Table 2 gives a summary of the diets and carbohydrate content for each of the studies.

All the included studies were RCTs ranging from 6‐ to 36‐month duration. Five of the trials were of 6‐month duration and six of 12‐month. One trial lasted 17 months and another lasted 36 months. As there was only one study lasting 17 months 11 and one lasting 36 months 12 data reported at that time point in that study were not included in the analysis. All of the studies were designed to reduce or prevent weight gain and also examined cardiovascular disease risk factors.

A total of 13 10 - 22 out of 123 1 articles met the inclusion criteria and were included in the systematic review. Reasons for which they were not included are summarized in Table 1 .

Discussion

The results of the present review show that weight loss was significantly greater in the LC/HP (treatment) group after 6 and 12 months compared with the LF/HC group. The difference was greater at 6 months and at that time there was significant heterogeneity among the studies, probably due to the different study designs, but at 12 months the heterogeneity was no longer significant. The 36‐month follow‐up by Cardillo et al.12 reported that mean weight change between baseline and 36 months was not different between the LC/HP and the LF/HC group. However, they do report that between 6 and 36 months weight was unchanged for the LF/HC group but that subjects on the LC/HP approach regained weight, but this change was not significant.

Avenell et al.23 examined the effects of a protein sparing modified fast (PSMF) compared with a low‐calorie diet and a very low‐calorie diet. A PSMF is a LC diet, which allows a maximum of 40 g of carbohydrate per day. The review examined weight loss comparing the PSMF with low‐calorie diets after 12, 18, 24, 36 and 60 months. There was a greater weight loss favouring the PSMF group compared with the control after 12, 24 and 36 months, but only seven RCTs were included in this analysis, which included a total of 480 participants 23. These results are consistent with the results of the present systematic review.

A review by Nordmann et al.24 comparing LC diets with LF diets showed significant weight loss with the LC group at 6 months, but not at 12 months. The meta‐regression by Krieger et al.25 also reports a greater weight loss in addition to a greater body fat and percentage body fat loss in studies lasting more than 3 months. Bravata et al.26, however, showed no significant differences in weight loss for both groups at either 6 or 12 months, but this review included studies with dietary approaches that are not considered LC, which may have affected their outcomes.

The present review showed that there was a significant improvement in HDL cholesterol and triacylglycerols at 6 and 12 months favouring the LC/HP group, but this was not significant at 17 months. The lack of significance at 17 months may be caused by the reintroduction of carbohydrates in the LC/HP group. There was heterogeneity between the studies for triacylglycerols, but this may have been due to differences in study design.

Low HDL cholesterol and raised triacylglycerol levels are risk factors for cardiovascular disease and impact on the atherogenicity of the LDL particle and these results indicate that a LC/HP diet may be a better approach to weight loss and lowering the risk of cardiovascular disease. These results are consistent with the review carried out by Nordmann et al.24. However, Bravata et al.26 did not show any significant improvement in these parameters, which again may have been affected by their choice of studies.

The present review showed a significant improvement in total cholesterol and LDL cholesterol favouring the LF/HC group at 6 months, at which point total cholesterol and LDL cholesterol increased more in the LC/HP group but not at 12 months or 17 months. Nordmann et al.24 in a meta‐analysis of LC vs. LF diets found reports on four groups of patients demonstrating an improvement in total and LDL cholesterol favouring LF diets rather than LC diets. This finding is consistent with the studies included in the present review. An elevated total cholesterol could in part be explained by an increase in HDL cholesterol observed in the LC/HP group. Also, although an elevated LDL cholesterol increases the risk of acute cardiovascular events, we have just shown evidence that LC/HP diets increase HDL and decrease triacylglycerol which impacts on the atherogenicity of the LDL particle. These studies failed to investigate changes in LDL particle size. Furthermore, evidence from Sharman et al. 27 suggests that on a LC/HP LDL particle sizes change from small to large and therefore resulting in a less atherogenic profile.

There was a trend towards improvement in diastolic and systolic blood pressure at 6, 12 and 17 months favouring the LC/HP group. The difference was significant at 12 months favouring the LC/HP group for systolic blood pressure. Bravata et al.26 reported no change in systolic blood pressure after the low‐ and very‐low‐carbohydrate diets 26. Nordmann et al.24 showed no significant difference in blood pressure at any time point.

At 6 months there was a trend towards improvement in fasting plasma glucose only slightly favouring the LF/HC group in which there was a greater decrease in fasting plasma glucose in the LF/HC group. This was surprising when compared with the review by Layman et al. where there is clear evidence of improvements in fasting glucose, postprandial glucose and insulin responses and glycosylated haemoglobin (HbA 1c ) for individuals on an LC/HP diet 6. At 12 months, the opposite occurred in which there was a greater decrease in fasting plasma glucose, favouring the LC/HP group. The difference was not significant at 6, 12 and 17 months. Bravata et al.26 reported no change in fasting serum glucose among recipients of the low‐ and very‐low‐carbohydrate diets. Nordmann et al.24 showed a greater improvement in fasting plasma glucose favouring the LC group at 6 months, but this was no longer significant at 12 months.

Furthermore, fasting glucose provides a limited assessment of overall glycaemic status; therefore, future studies should use HbA1c values or more direct measurements of insulin sensitivity.

There was a higher attrition rate in the LF/HC compared with the LC/HP groups (Fig. 1). Reasons for attrition included difficulty in complying with the diet or disliking the diet, difficulty in maintaining the scheduled visits and significant events such as pregnancy and surgery.