This review, including 19 RCTs with 3209 participants showed there is probably little or no difference in changes in weight and cardiovascular and diabetes risk factors with low CHO weight loss diets compared to isoenergetic balanced weight loss diets. This was in both overweight and obese adults without diabetes and those with diabetes, with follow-up for up to two years. When reported, energy intake was similar in the diet groups being compared, but participants did not adhere fully to the prescribed macronutrient goals for both diets in most trials.

The primary reason for the moderate grade of evidence in most outcomes at 3–6 months and 1–2 years is the risk of selection, performance and attrition bias in most included trials. For serum triglycerides, inconsistency (as discussed above) in effects resulted in further downgrading to low quality indicative of less confidence in the findings. Similarly, for DBP at 3–6 months, inconsistency in the mean differences across the different trials resulted in further downgrading to low quality evidence. This inconsistency could not be explained by the different variants of the low CHO diet. Most of the inconsistency can be ascribed to two trials [32] , [41] with similar weights in the meta-analysis (19.5% and 15.5%, respectively) that produced significant opposite mean differences for DBP. Klemsdal and colleagues [32] found that the low CHO diet reduced DBP more than the balanced diet (−3.40 mmHg, 95%CI −6.02 to −0.78). They reported that this observation should be interpreted with some caution, since blood pressure was a secondary endpoint in the study and the effect on SBP did not differ between the two groups. This effect was no longer significant at one year. In contrast, Wycherley and colleagues [41] reported a greater reduction in DBP with the balanced diet compared to the low CHO diet (4.00 mmHg, 95%CI 0.58 to 7.42). Similarly, this difference in effect was not found for SBP and disappeared at one year. The heterogeneity may also be attributable to differences in dietary adherence, as well as mean baseline DBP in one trial [27] that could be judged as being imbalanced (85.8 and 80.7 mmHg in low CHO and balanced diet groups, respectively). Although not reported, it could be argued that differences in the sodium and potassium content of the intervention diets may explain some of the variable effects on DBP.

When considering blood lipid changes, a weight loss of 5 kg to 8 kg is reported to result in LDL cholesterol reduction of approximately 0.13 mmol/L and an increase in HDL cholesterol of between 0.05 to 0.08 mmol/L [44] . In overweight and obese adults with and without CVD risk who lose 3 kg on a lifestyle intervention, a weighted reduction in serum TG of approximately 0.17 mmol/L is observed [44] . In the trials in our review, effects on blood lipids and FBG with low CHO and balanced diets were variable, with greater and lesser average changes in LDL, HDL and TG than the observations described above. When comparing low CHO and isoenergetic balanced diets, the pooled mean differences across the trials and quality of evidence indicate that there is probably little or no difference in changes in LDL, HDL and total cholesterol and there may be little or no difference in TG change at 3–6 months. Similarly, after 1–2 years, there is probably little or no difference in serum LDL and total cholesterol and TG between the diet groups. Meta-analysis of HDL cholesterol difference was 0.04 mmol/L higher with low CHO diets compared to balanced diets after 1–2 years, but the difference was not clinically meaningful, and no difference was detected for LDL.

Weight loss improves markers of cardiovascular risk [45] – [47] . According to the 2013 AHA/ACC/TOS Guideline [44] , based largely on systematic reviews, clinically meaningful changes in CVD risk indicators are associated with a loss of at least 2.5 kg, or 2% of body weight, achieved with lifestyle interventions over one to four years. This document states that at a 5% weight loss, a weighted mean reduction in DBP of about 2 mmHg and in SBP of about 3 mmHg is observed [44] . Correspondingly, the weight loss in both diet groups in our review was accompanied by reductions in average DBP and SBP in all trials. In line with the weight loss findings, there is probably little or no difference in SBP changes after 3–6 months and there may be little or no difference in DBP changes between the low CHO and balanced diet groups. After 1–2 years, there is probably little or no difference in changes in DBP and SBP between the diet groups. These judgements are based on both the meta-analyses and the quality of the evidence for these outcomes per length of follow-up category.

Norms for defining “stable weight” are gaining less than or equal to 2 kg and losing less than 2 kg [44] indicating that both low CHO and balanced weight loss diets (or energy-restricted diets) result in meaningful weight loss. Clearly, the goal of any healthy weight loss strategy should be to achieve weight loss and to subsequently maintain this over the long-term. The 2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults state that strategies for weight maintenance after successful loss differ from the strategies for achieving weight loss and make recommendations in this regard [44] .

Participants lost weight in both groups, with similar before and after average loss after 3–6 months, and 1–2 years of follow-up. There was little or no difference in weight loss and change in BMI between the low CHO and balanced weight loss diets in the two follow-up periods. The similar reported mean energy intakes in the low CHO and balanced diet groups and the corresponding similar average weight loss in the diet groups supports the fundamental physiologic principle of energy balance, namely that a sustained energy deficit results in weight loss regardless of macronutrient composition of the diet [43] .

As in the non-diabetic overweight and obese population, the presence of risk of selection, performance and attrition bias in most included trials were the primary reasons for the moderate grade of evidence in most outcomes in the diabetic population. For weight loss at 3–6 months and 1–2 years follow-up, imprecision of the effect estimates resulted in further downgrading to low quality evidence. Similarly, the evidence for triglycerides for both follow-up categories and for SBP at 3–6 months was downgraded due to imprecision of the effect estimates. These imprecise estimates possibly relate to the smaller samples in the diabetes population.

Effects on blood lipids with low CHO and balanced diets were variable between included trials, as was seen in the non-diabetic population. Considering the meta-analyses and the quality of the evidence, there is probably little or no difference in changes in LDL, HDL and total cholesterol after 3–6 months and 1–2 years when comparing the two diets. There may be little or no difference in changes in TG concentrations after 3–6 months and 1–2 years.

Effects on DBP with low CHO and balanced diets were variable in most trials, showing both reductions and increases. Both the low CHO and balanced weight loss diets demonstrated reductions in average SBP in all trials after 3–6 months, but effects were variable with both diets after 1–2 years. Based on both the meta-analyses and the quality of the evidence, there is probably little or no difference in DBP change between the two diets and there may be little or no difference in SBP change after 3–6 months. After 1–2 years, there is probably little or no difference in changes in both DBP and SBP.

Weight loss is associated with improvements in glycaemia in overweight and obese adults with type 2 diabetes. According to the 2013 AHA/ACC/TOS Guideline, 2% to 5% weight loss achieved with one to four years of lifestyle intervention results in modest reductions in FBG and lowering of HbA1c by 0.2% to 0.3% [44] . Along with weight loss in both diet groups in our included trials, both low CHO and balanced diet groups showed similar reductions in average HbA1c in most trials after 3–6 months. At 1–2 years average HbA1c change was more variable. Comparing these changes by combining data across trials indicated that there is probably little or no difference in changes in HbA1c between the two diets at 3–6 months and 1–2 years. The meta-analysis at 3–6 months of two small trials [25] , [40] showed similar findings for FBG concentrations. Only one of these trials went on to report FBG at 15 months and had the same finding [25] .

Both low CHO diets and balanced weight loss diets showed similar weight loss on average after 3–6 months and after 1–2 years. Meta-analysis and quality of evidence indicate that in overweight and obese adults with type 2 diabetes there may be little or no difference in weight loss after 3–6 months and 1–2 years. The earlier discussion of the long-term effects of dieting on weight loss is also applicable in this population.

From the calculated adherence scores it was clear that strict adherence to prescribed macronutrient goals failed with both diets in most trials and generally declined with longer follow-up. This diminished adherence after the first few months has been well documented in weight loss trials [48] – [51] and is more likely in weight loss diets involving extreme dietary changes such as drastic restrictions of entire food groups. This is supported by the fact that trials of low CHO diets have reported a very low incidence of urinary ketosis after six months [49] – [51] , which suggests that most overweight participants in weight loss trials struggle to sustain a low intake of CHO. It could thus be argued that overweight participants following reduced energy weight loss diets in trials tend to revert to their usual macronutrient intakes over time, but may nonetheless, be able to lose weight if they are able to maintain the energy deficit. The novelty factor attached to a particular diet, media attention, and the opinion of the researchers involved could possibly affect the adherence of participants to any type of diet. It is clear from this and other research [52] that one of the pertinent issues in the treatment of overweight and obesity relates to the improvement of behavioural adherence to reduced dietary energy intake. It should be noted that the adherence score is based on calculations using mean reported intakes of macronutrients (% of total energy) and thus does not consider the variation around the mean.

Overall completeness and applicability of evidence

The findings of our review need to be interpreted in light of the presence of risk of bias or lack of power or both in many of the included trials, the possibility that adherence to dietary macronutrient goals were not optimal and that there was inter-trial variation in quantity (and type) of fat consumed. The interpretation of many weight loss trials is limited by a lack of blinded ascertainment of the outcome, small samples, large loss to follow-up, potentially limited generalisability and a lack of data on adherence to assigned diets [53]. These limitations all apply to the evidence assessed in our systematic review. Strengths of our review include the clear definitions used in relation to the energy content and macronutrient composition of treatment and control diets, as well as the restriction of included studies to those testing diets only thereby reducing the risk of confounding by co-interventions. By considering only isoenergetic comparisons we also avoided the problem of the effect of energy imbalance between the comparison groups being confounded with any potential effect of macronutrient manipulation on the outcomes being investigated. Furthermore, we only included studies with follow-up of 12 weeks or more to allow for sufficient time to detect weight and CVD risk factor changes and assessed outcomes at defined lengths of follow-up. These methods differentiate our systematic review from previous reviews on this topic.

Our results show that the weight loss in overweight and obese subjects with or without diabetes on isoenergetic low CHO or balanced weight loss diets was similar at 3–6 months and at 1–2 years. Thus, the weight loss is the result of a reduction in total dietary energy intake rather than manipulation of macronutrient contribution. It follows that when considering dietary strategies for weight loss, less emphasis should be placed on an ‘ideal’ macronutrient composition and more emphasis on reduction in total energy intake, as well as improvement of behavioural adherence to reduced energy intake. This will go a long way to ensure that weight loss is achieved and maintained to gain health benefits. Guidance on macronutrient composition to meet nutritional requirements and prevent disease [12]–[15] remains integral to healthy sustainable weight management.

The small size and short duration of weight loss trials often account for their lack of definitive evidence of the effectiveness of dietary interventions on CVD risk. By contrast sound observational data, population-level interventions and “natural experiments” in whole populations have demonstrated a reduction in population risk with adoption of recommended, balanced dietary strategies to lower cardiovascular risk. For example, over the past three decades, levels of population cardiovascular risk factors have declined in Finland, with the greatest change being dietary behaviour (reduction in total and saturated fat and increased vegetables and fruit intake). These declines explain most of the observed decline in CHD mortality in the Finnish middle-aged population over this period [54]. Mortality due to coronary heart disease was reduced in Poland over a ten year period by partly replacing dietary saturated fats with polyunsaturated fats while maintaining a low intake of trans fatty acids [55]. A large prospective cohort study in 30 to 49 year old Swedish women (n = 43396; average follow-up 15.7 years) reported significantly increased incidence of cardiovascular disease overall (n = 1270) with a one tenth decrease in carbohydrate intake or increase in protein intake, or a two unit increase in the low carbohydrate-high protein score [9].

Our systematic review did not address macronutrient quality of the diets, specifically the quality of CHO and fat, which along with total macronutrient quantities and proportions, explains the effects of diet on cardiovascular risk [56]. The replacement nutrient is central to these effects. When foods high in CHO are avoided and replaced with high protein foods, reliance on animal protein sources becomes necessary since most foods with significant amounts of plant protein are also high in CHO (e.g. legumes). This reliance on animal protein will result in a greater intake of both total and especially saturated fat leading to higher serum HDL and LDL cholesterol over time. Substitution of saturated fat with polyunsaturated fats reduces coronary heart disease risk [57], [58], while substitution with high glycaemic index CHO increases risk [59]. LDL-cholesterol is a causal risk factor for heart disease and reducing LDL cholesterol has been shown to be effective in reducing risk of heart disease irrespective of the presence of prior heart disease, age, sex, hypertension and diabetes [60]–[62]. Mendelian randomisation studies have demonstrated a 54% reduction in coronary heart disease risk per 1 mmol/l lower serum LDL cholesterol over a lifetime [62]. Treatment of elevated cholesterol levels reduces coronary heart disease risk, with clinical trials demonstrating a 24% reduction in risk per 1 mmol/l reduction in LDL over 5 years [60]. Furthermore, the role of ultra-processed products in the etiology and treatment of obesity and NCD is a pertinent consideration in this area [63], [64]. The inconsistent changes in blood lipids and markers of diabetes risk with both diets in the trials may be attributable to differences in the quality of macronutrients in the intervention diets, for example, different intakes of saturated fat and/or types of carbohydrates (low or high glycaemic), an issue which was beyond the scope of our review. These inconsistences may also be attributable to participants not fully adhering to the prescribed total macronutrient goals for each of the diets, as evident from the adherence data.

Any dietary guidelines for health should be sustainable in the long-term, specifically in terms of ease of adherence, availability and affordability of foods, as well as social and cultural acceptability. Bearing this in mind, the dietary approach for weight management should be one that is nutritionally sound, not harmful and feasible to maintain over time. Such diets can be tailored to the needs of individuals on the basis of each individual's complete health and risk profile, for example existing lipid abnormalities and comorbidities, as well as food preferences, socioeconomic circumstances and personal and cultural preferences, thereby improving the chances of longer term success. Suitably qualified healthcare professionals should guide the tailoring of dietary advice for individuals. Monitoring and follow-up by a healthcare professional during a dietary weight loss intervention is known to positively affect outcomes [16]. The demonstrated value of combining dietary and other positive lifestyle interventions such as increased physical activity for weight loss and reduction of cardiovascular risk, is also important to keep in mind [65], [66].