Effects of Low-Carbohydrate and Low-Fat Diets: A Randomized Trial

Overall the study has several strengths and many similarities when compared to other Low-Fat vs. Low-Carb diet studies. Retention of 80% is good. Duration of 1-year is better than 3m or 6m but not as long as 2 years. NDS-R diet assessment repeatedly throughout the study is stronger than many studies, some of which did little to assess adherence. Diet adherence data suggest the two diets were clearly differentiated early in the study, and still clearly differentiated at 12 months - better than several studies where recidivism left little difference between diet groups by the end of the protocol. Sample size is reasonable - bigger than some, smaller than other studies.

Primary concern is with the goals of Low-Fat vs. Low-Carb. Authors state that, with no calorie restriction, main objective for Low-Fat was to achieve <30% energy from fat, and for Low-Carb <40 g carbohyrdates. With a baseline intake of ~35% fat, this means the Low-Fat group had the objective of reducing their fat % intake by 1/7th, a very modest change. In contrast, with a baseline mean intake of 242 grams of carbohydrate, the Low-Carb group objective was to cut this by 5/6ths, a hugely ambitious goal. Despite clearly differentiating the diets the two groups were on, this researcher considers it problematic that one group had a modest goal, leading to a modest weight change, while the other group had a wildly ambitious goal, and eventually achieved a larger weight loss.

Also of concern is that even with all the counseling described, and the provision of meal replacements once/day, the magnitude of weight loss among adults (mostly women) with a BMI of 30-45 kg/m^2 and baseline average weight just shy of 100 kg lost <2% vs. ~5% after a year of working at it.

Yes a 5% reduction in weight can lead to clinically meaningful improvements in risk factors, as was reported. But did we really need yet another study to point out that comparing a wildly ambitious diet with "usual care" (30% fat) could yield generally disappointing weight loss in both groups with a slight (and temporary?) reduction in risk factors?

What if the Low-Carb objective had been to drop from the baseline average (of both diets) of ~47% energy to <42% energy (modest goal), and the Low-Fat objective had been to drop from the baseline average (of both diets) of ~78 grams of fat/day to 1/6th of that, which would have been 13 grams of fat/day (ambitious goal).

Unequal effort demanded of participants on Low-Fat vs. Low-Carb brings comparison of these loosely defined terms into question, and with it the main conclusion of the paper.

Bazanno et al. hypothesised that participants following a diet low in carbohydrate would have lower body weight compared to those adhering to a diet low in fat; the results of their trial, they conclude, confirm this hypothesis (1). Neither diet included a specific calorie or energy intake goal, however, it appears that the behavioural curriculum followed by participants targeted weight loss because reported energy intakes declined from baseline during the intervention in both the low carbohydrate and low fat diet groups. Mean weight loss was greater amongst participants assigned to follow a diet low in carbohydrate. However, we estimate that underreporting of dietary energy intake was close to 50% in both groups during the intervention. Mean daily energy intakes at 3, 6, and 12 mo of the intervention were reported to be between 1258 and 1527 kcal. Energy intakes this low for a full year should have led to weight loss in excess of 30 kg rather than the 2 to 5 kg that occurred. The degree of under-reporting evident from these results makes it very difficult to know what participants actually ate and more importantly creates considerable uncertainty about the extent to which the greater weight loss in one diet group can be attributed to the macronutrient composition of the diet. This severe disconnection between reported and actual energy intake begs the question about the composition of the unreported and under-reported foods and suggests that forces other than the macronutrient composition of the diet may explain the weight differences. In this regard, the lack of blinding in weight loss trials makes it particularly difficult to disentangle the effect of macronutrients from the behaviours the diets may invoke. Katan remarked in an editorial several years ago (2) that participants in weight loss trials “may eat less not because of the protein or carbohydrate content of a diet but because of the diet’s reputation or novelty or because of the taste of particular foods in the diet.”. The widespread promotion of low carbohydrate diets may well explain these findings. A series of meta-analyses including one published recently (3) demonstrate little to differentiate long-term effects on body weight of various dietary patterns intended to achieve weight loss. The present study certainly does not refute this conclusion.

Murray Skeaff, Jim Mann, Lisa Te Morenga, and Rachael McLean

Department of Human Nutrition, University of Otago, New Zealand, no conflict of interest to declare.

1. Bazzano LA, Hu T, Reynolds K, Yao L, Bunol C, Liu Y, et al. Effects of Low-Carbohydrate and Low-Fat Diets. Ann Intern Med. 2014;161:309–18.
2. Katan MB. Weight-loss diets for the prevention and treatment of obesity. N Engl J Med. 2009;360:923–5.
3. Naude CE, Schoonees A, Senekal M, Young T, Garner P, Volmink J. Low Carbohydrate versus Isoenergetic Balanced Diets for Reducing Weight and Cardiovascular Risk: A Systematic Review and Meta-Analysis. PLoS ONE. 2014;9:e100652.

To the Editor
In their randomized trial Bazzano, Hu and colleagues report that a low-carbohydrate diet is more effective for weight loss than a low-fat diet (1). Notably, such a difference was significant at 3- and 6-month follow up, but no longer obvious after 1 year (1). A similar pattern has been also evidenced in a recent meta-analysis (2). Of interest, the only parameters significantly different between the two diets at 12-month follow up were high-density lipoprotein (HDL) cholesterol level and 10-year Framingham risk score, which were remarkably not different at 3-month evaluation (1). Supporting this finding, the original Framingham Study unveiled that the risk for coronary artery disease increases sharply as HDL levels fall progressively below 40 mg/dL (3).
Equally important, approximately one third of the population enrolled in the trial was under a not better specified antihypertensive treatment (1). Given the complex relationship between endothelial dysfunction and HDL (4, 5), it would be noteworthy to know the results of the analysis distinguishing between hypertensive and non-hypertensive subjects, in order to explore new pathophysiological insights in the association linking hypertension and obesity.

References
1. Bazzano LA, Hu T, Reynolds K, Yao L, Bunol C, Liu Y, et al. Effects of low-carbohydrate and low-fat diets: a randomized trial. Ann Intern Med. 2014;161(5):309-18.
2. Nordmann AJ, Nordmann A, Briel M, Keller U, Yancy WS, Jr., Brehm BJ, et al. Effects of low-carbohydrate vs low-fat diets on weight loss and cardiovascular risk factors: a meta-analysis of randomized controlled trials. Arch Intern Med. 2006;166(3):285-93.
3. Castelli WP, Garrison RJ, Wilson PW, Abbott RD, Kalousdian S, Kannel WB. Incidence of coronary heart disease and lipoprotein cholesterol levels. The Framingham Study. JAMA. 1986;256(20):2835-8.
4. Bonaa KH, Thelle DS. Association between blood pressure and serum lipids in a population. The Tromso Study. Circulation. 1991;83(4):1305-14.
5. Yuhanna IS, Zhu Y, Cox BE, Hahner LD, Osborne-Lawrence S, Lu P, et al. High-density lipoprotein binding to scavenger receptor-BI activates endothelial nitric oxide synthase. Nat Med. 2001;7(7):853-7.

Bazzano and colleagues provide confirmation of many recent studies that low-carbohydrate diets are at least as effective as low-fat diets for weight loss and can reduce some cardiovascular risk factors to a greater extent (1). However, an integral, early statement in the American Heart Association (AHA) dietary recommendations pertaining to weight loss is to incorporate a regular pattern of physical activity (2). It is well recognized that despite consuming high-carbohydrate diets endurance athletes have low concentrations of fasting and postprandial triglycerides (TG), high HDL-cholesterol levels and a lean body mass; factors which show little or no improvement with low-fat diets (1). From a public health standpoint, more compelling is an early randomized controlled trial in moderately overweight and obese males and females who followed a hypocaloric National Cholesterol Education Program (NCEP) Step I diet of 55% carbohydrate and 30% fat over 1 year (3). Males who walked or jogged an average of 2.1 km/day significantly lowered their TG by a further 0.36 mmol/L and increased their HDL-cholesterol by a further 0.12 mmol/L compared with those randomized to diet only. Moreover, they lost 3.5 kg more in fat mass and had a larger reduction in systolic blood pressure. The extent of these differences was not as great in women who walked or jogged an average of 1.8 km/day, but they were able to maintain their HDL-cholesterol levels over the year compared with a 0.15 mmol/L decrease in women who followed the diet only. Subsequent work from the same group in middle-aged individuals with high cholesterol showed that only a NCEP Step II diet in combination with walking or jogging ~16 km/wk over 1 year significantly reduced total and LDL-cholesterol and not the same diet or exercise alone (4). These interventions are supported by experimental data showing that when 60 minutes of daily brisk walking was added to a short-term, low-fat diet all increases in fasting and postprandial TG and TG-rich lipoproteins over a low-carbohydrate diet were obviated in postmenopausal women (5). Collectively, such evidence demonstrates the importance of physical activity in the AHA recommendations.

Bazzano and colleagues correctly suggest that restricting carbohydrate as an option for weight loss which helps reduce cardiovascular risk factors. We propose that if current AHA recommendations of reducing energy and fat intake and increasing physical activity are followed then the choice for individuals who wish to lose weight is widened but equally effective.

References
1. Bazzano LA, Hu T, Reynolds K, Yao L, Bunol C, Liu Y, et al. Effects of low-carbohydrate and low-fat diets: a randomized trial. Ann Intern Med. 2014; 161:309-18.
2. Krauss RM, Eckel RH, Howard B, Appel LJ, Daniels SR, Deckelbaum RJ, et al. AHA Dietary Guidelines: revision 2000: A statement for healthcare professionals from the Nutrition Committee of the American Heart Association. Circulation. 2000; 102:2284-99.
3. Wood PD, Stefanick ML, Williams PT, Haskell WL. The effects on plasma lipoproteins of a prudent weight-reducing diet, with or without exercise, in overweight men and women. N Engl J Med. 1991; 325:461-6.
4. Stefanick ML, Mackey S, Sheehan M, Ellsworth N, Haskell WL, Wood PD. Effects of diet and exercise in men and postmenopausal women with low levels of HDL cholesterol and high levels of LDL cholesterol. N Engl J Med. 1998; 339:12-20.
5. Koutsari C, Karpe F, Humphreys SM, Frayn KN, Hardman AE. Exercise prevents the accumulation of triglyceride-rich lipoproteins and their remnants seen when changing to a high-carbohydrate diet. Arterioscler Thromb Vasc Biol.

In a trial with 148 obese patients, carried out in a single medical center(1), a low-carbohydrate diet (<40 g/day) had greater reductions in weight, fat mass, ratio of total-HDL cholesterol and triglyceride level than a low-fat diet (<30% of daily energy intake from fat), at 12 months of follow-up. The authors’ conclusion was: “The low-carbohydrate diet was more effective for weight loss and cardiovascular risk factors reduction. Restricting carbohydrate may be an option for persons seeking to lose weight and reduce cardiovascular risk factors”.
The conclusion is in line with the results of this single trial, but the media echo (“low-carb is better than low-fat for losing weight”) is not.
The attention should be brought to the whole scientific evidence, and into ethical perspective, as well.
A meta-analysis(2) of 48 trials and 7286 individuals (fifty times more than the participants in this trial(1)) concluded that significant weight loss was observed with any low-carb or low-fat diet (-7.25 kg versus -7.27 kg at 12 months of follow-up, respectively), with an ephemeral advantage of 7.4 hg for low-carb diets in the first six months.
The extension of DIRECT trial(3) showed that, at six years, the advantage of a Mediterranean diet over a low-carb diet is becoming evident.
Moreover, in the middle-to-long time the high-protein diets are associated with an increase in BMI during the adult life(4), possibly with a higher all-cause mortality(5).
Last but not least, regardless of any other consideration, the low-carb/high-protein diets are environmentally unsustainable. This reason is enough to avoid promoting low-carb/high-protein diets at population level.

References
1. Bazzano LA, Hu T, Reynolds K, Yao L, Bunol C, Liu Y, et al. Effects of Low-Carbohydrate and Low-Fat Diets. Ann Intern Med. 2014;161:309-18.
2. Johnston BC, Kanters S, Bandayrel K, Wu P, Naji F, Siemieniuk SA, et al. Comparison of Weight Loss Among Named Diet Programs in Overweight and Obese Adults. JAMA. 2014;312:923-33.
3. Schwarzfuchs D, Golan R, Shai I. Four-Year Follow-up after Two-Year Dietary Interventions. N Engl J Med 2012; 367:1373-4.
4. Fung T, van Dam RM, Hankinson SE, Stampfer M, Willett WC, Hu FB. Low Carbohydrate Diets and All-Cause and Cause-Specific Mortality. Two Cohort Studies. Ann Intern Med. 2010;153:289-98.
5. Vergnaud AC, Norat T, Mouw T, Romaguera D, Anne M. May AM, Buenode-Mesquita HB, et al. Macronutrient Composition of the Diet and Prospective Weight Change in Participants of the EPIC-PANACEA Study. PLOS ONE 2013;8: e57300.

We agree wholeheartedly with Dr. Burns that physical activity is a vital component of weight management and cardiovascular health. In our clinical trial, levels of physical activity were not significantly different between the groups at baseline or during the intervention. While it was not the aim of our study, future studies should examine whether the differences in efficacy of low-fat and low-carbohydrate diets are modified by levels of physical activity.
Drs. Donzelli and Lafranconi raise several concerns regarding low carbohydrate diets. They note that in meta-analysis, similar effectiveness is observed for low carbohydrate and low fat diets for weight loss at 12 months of follow-up (1). However, cardiovascular disease risk factors were not examined in the latter study, which focused on named low-carbohydrate diets such as Atkins and Zone, unlike our study. They also point out that a Mediterranean diet may have advantages over a low-carbohydrate diet (2). Although our study was not designed to examine this question, in the DIRECT trial, both Mediterranean and low-carbohydrate diet groups experienced more favorable post-intervention effects than the low-fat diet group. They note that low-carbohydrate diets may be associated with higher adult body mass index and/or all-cause mortality in observational studies. However, evidence from clinical trials does not support an increased body mass index (1-3), and many observational cohort studies have identified no association between low-carbohydrate diets and mortality (4,5). Finally, Both state that low-carbohydrate/high-protein diets are environmentally unsustainable at a population level. We disagree. Legume proteins and those from nuts and seeds, provide a potentially sustainable pathway to diets higher in both protein and healthy fats.
Dr. Santulli stated that the difference in weight loss was significant only at 3- and 6-month follow up but not at 12 months, and the only parameters significantly different between the two diets at 12-month follow up were high-density lipoprotein (HDL) cholesterol level and 10-year Framingham risk score; we disagree. In fact, changes in body weight, lean mass, fat mass, total/HDL ratio and C-reactive protein were also significantly different between the groups at 12 months (Table 3 in our manuscript). Framingham risk score was significantly different at each of 3, 6 and 12 months. Among our participant, 60 were hypertensive. There were no significant differences between hypertensive and normotensive participants by diet group.
Dr. Skeaff's concern about under-reporting in our trial was based mean daily energy intakes reported at 3, 6 and 12 months. These quantities are in line with the caloric intakes and weight loss results reported by 23 studies of low-fat and low-carbohydrate diets in a meta-analysis of randomized controlled trials (3). Participants in behavioral dietary trials are free-living volunteers from the community and their exact caloric intake and output cannot be measured in the idealized manner of physiologic studies conducted on metabolic wards. In terms of the speculation that the widespread promotion of low-carbohydrate diets for weight loss may have influenced weight loss difference between the diets, we would submit that low-fat diets have been far more heavily promoted over the course of many decades than low-carbohydrate diets.

1. Johnston BC, Kanters S, Bandayrel K, Wu P, Naji F, Siemieniuk SA, et al. Comparison of Weight Loss Among Named Diet Programs in Overweight and Obese Adults. JAMA. 2014;312:923-33.
2. Schwarzfuchs D, Golan R, Shai I. Four-Year Follow-up after Two-Year Dietary Interventions. N Engl J Med 2012; 367:1373-4.
3. Hu T, Mills KT, Yao L, Demanelis K, Eloustaz M, Yancy WS Jr, Kelly TN, He J, Bazzano LA. Effects of low-carbohydrate diets versus low-fat diets on metabolic risk factors: a meta-analysis of randomized controlled clinical trials. Am J Epidemiol. 2012 Oct 1;176 Suppl 7:S44-54.
4. Fung T, van Dam RM, Hankinson SE, Stampfer M, Willett WC, Hu FB. Low Carbohydrate Diets and All-Cause and Cause-Specific Mortality. Two Cohort Studies. Ann Intern Med. 2010;153:289-98.
5. Nilsson LM, Winkvist A, Eliasson M, Jansson JH, Hallmans G, et al. (2012) Low-carbohydrate, high-protein score and mortality in a northern Swedish population-based cohort. Eur J Clin Nutr 66: 694–700

I did a 2mos long religiously strict trial of low carb high fat no exercise diet 7yrs ago (<50 net carbs per day) and dropped triglycerides from 170 to 82, total cholesterol 221 to 158, HDL down, A1C down-only neg was a decrease in LDL. My main source of carbs was a small bowl of oatmeal 5 mornings a week. Flax seeds ground into flour were an important additive. I continue (with less fervor) 7yrs later, unmedicated.