There was no significant difference in weight change between a healthy low-fat diet vs a healthy low-carbohydrate diet, found a year-long Stanford University randomised clinical trial. Also, neither genotype pattern nor baseline insulin secretion was associated with the dietary effects on weight loss.
A major new randomised clinical trial (RCT) on low-fat vs low-carb diet has cleared three of the biggest hurdles seen in weight loss studies: recruiting a large number of participants; retaining and tracking them over a long period of time; and carefully monitoring compliance with the assigned diet. This year-long study involved 600+ participants. It was conducted by Dr Christopher Gardner of Stanford University in conjunction with the US National Institutes of Health (NIH), the Nutrition Science Initiative (NuSI), and a team of nutrition experts.
This says an Exam.com report, is notable, since NuSI was co-founded by Gary Taubes, a prominent low-carb advocate and champion of the carbohydrate-insulin hypothesis of obesity.
Previous studies comparing low-fat to low-carb diets have shown that individual weight loss can vary greatly within assigned diet groups. The reasons for these individual responses are not well understood, leading scientists to hypothesise that perhaps insulin sensitivity or certain genetic components might explain the success or failure of different diets. The present study tested whether differences in genetics or insulin production could help predict weight-loss success in participants undertaking either a low-fat or a low-carb diet for one year.
This RCT assigned 609 participants to either a low-fat diet or a low-carb diet for 12 months. In total, 263 males and 346 premenopausal females free of major health conditions (no diabetes, cancer, heart disease, high cholesterol, etc) were included in the study. Average BMI was 33 (class I obesity), and average age was 40±7 years.
Over the course of the study, each subject was instructed to attend 22 dietary counselling sessions with a registered dietitian; average attendance was 66% for both groups. During the first two months of the study, the low-fat group was instructed to consume only 20 g of fat per day and the low-carb group only 20 g of carbs per day. However, they were not expected to stay at these levels indefinitely: at the end of this 2-month period, they started adding fats or carbs back to their diet until they felt they’d reached the lowest intake level they could sustainably maintain. Neither group was able to stick to the very low starting intakes: by month 3, the low-fat group was already consuming an average of 42 g of fat per day, whereas the low-carb group was consuming an average of 96.6 g of carbs per day.
It’s possible some in the low-carb group may have been in ketosis during these first two months due to the very low carb intake prescribed. While the low-carb group was able to achieve reduced carb intake throughout the trial (≈115 g/day), only a very small minority reported consuming ≤50 g/day – the intake threshold typically required to stay in ketosis.
While no caloric intake targets were given, both groups were instructed to consume high-quality whole foods and drinks. Specifically, they were instructed to “maximise vegetable intake … minimise intake of added sugars, refined flours, and trans fats; and … focus on whole foods that were minimally processed, nutrient dense, and prepared at home whenever possible.”
A total of 12 random and unannounced multi-pass 24-hour dietary recalls were taken over the course of the study to assess food intake. With this method, an interviewer asks individuals to recall all the foods and drinks they have consumed in the previous 24-hours. Dietary compliance was also corroborated by changes in blood lipids and in respiratory exchange ratio (RER – this can indicate whether you are primarily “burning” fat or carbs).
The first primary hypothesis being tested was a potential link between genotype pattern and diet type for weight-loss success.
All participants were screened for 15 genotypes, including 5 “low-fat” genotypes (hypothesised to do better on a low-fat diet), 9 “low-carb” genotypes (hypothesized to do better on a low-carb diet), and 1 “neutral” genotype.
The second primary hypothesis being tested was a potential link between insulin secretion and diet type for weight-loss success. At the start of the trial and at months 3, 6, and 12, all participants completed an oral glucose tolerance test (OGTT) to measure insulin production. An OGTT is a test that can measure your blood glucose and/or insulin levels after you’ve consumed a fixed amount of carbohydrate (normally 75 g of glucose).
Other outcomes measured included changes in body composition (assessed by DXA scan), cholesterol levels, blood pressure, fasting glucose and insulin levels, resting energy expenditure, and total energy expenditure.
In total, 481 participants completed the entire trial, which translates to a 21% dropout rate – not unexpected for a diet study of this duration. While there were no significant dietary differences between groups at baseline (before the dietary interventions started), there were significant differences at months 3, 6, and 12 with regard to the percent intake of carbohydrate, fat, protein, fibre, and added sugars (as seen in Figure 1).
Additionally, saturated fat intake was significantly reduced in the low-fat group, whereas the overall glycaemic index was lower in the low-carb group. While both groups saw reductions in glycaemic load, the decline was much larger in the low-carb group.
At 12 months, the low-fat group had lost 11.7 lbs (5.3 kg) and the low-carb group 13.2 lbs (6.0 kg); this difference of 1.5 lbs over 12 months (0.125 lbs/month) is neither statistically significant nor clinically relevant.
Additionally, within each group, differences in genotypes or insulin secretion made no significant difference in weight change. This suggests that neither the genotype tested for in this study nor the amount of insulin produced during the OGTT can predict weight-loss success on either a low-fat or a low-carb diet. Ironically, a potential confounding factor masking an interaction could have been that both diets were based on whole foods. If, say, the low-fat diet had consisted mostly of sodas and refined grains, the resulting insulin resistance might have had an effect on weight change.
Both groups were able to improve certain health markers (BMI, body fat percentage, waist circumference, blood pressure, and fasting insulin and glucose levels), although no significant differences were seen between groups. At the 12-month mark, low-density lipoprotein cholesterol (LDL-C) had significantly decreased in the low-fat group (-2.12 mg/dL), while it had increased in the low-carb group (+3.62 mg/dL). However, the low-carb group also saw a significant increase in high-density lipoprotein cholesterol (HDL-C) (+2.64, vs +0.40 mg/dL in the low-fat group) and greater reductions in triglycerides (-28.20, vs -9.95 mg/dL in the low-fat group).
Resting energy expenditure (REE) was not significantly different between groups at any point. By month 12, REE had decreased significantly from baseline for both groups (-66.45 kcals for low-fat, -76.93 kcals for low-carb). Total energy expenditure (TEE) was not significantly different between groups or compared to baseline. Lastly, although a little over 10% of each group improved their metabolic syndrome during the trial, there was no significant difference between diets.
The results of this study contribute to a large body of evidence indicating that, for weight loss, neither low-fat nor low-carb is superior (as long as there’s no difference in caloric intake or protein intake).
In this trial, overall caloric intake was nearly identical between groups throughout the intervention period, and the low-carb group consumed just a little more protein (an additional 12.5 g/day on average).
The weight loss results in this study are echoed both by short-term, tightly controlled clinical trials and by long-term, less controlled free-living clinical trials. While the present study is a free-living trial, it offers some advantages not seen in most others: the programme offered intensive dietary counselling and guidance for the entire length of the study. Many free-living trials provide instruction and/or support up front, after which the participants are left to their own devices; it confirmed the participants’ dietary intakes through random multi-pass 24-hour dietary recalls, bolstered by lipid panels and RER tests. Most long-term diet trials simply use 24-hour recalls or food-frequency questionnaires; the study strongly encouraged its participants to consume healthy diets rich in whole foods and not to fill their pantries with low-fat or low-carb junk food; and it is one of the larger studies of its kind, which reduces the odds of a result being due to random error (aka “noise”).
While our understanding of the interactions between genetics and diet are still growing, this trial has tested 15 genotype patterns suspected of being able to influence weight-loss success or failure on low-fat or low-carb diets. Even though no effect was seen, the authors have stated that they will analyse “all the genomic data obtained … to evaluate whether other genetic signatures” could be studied in the future.
While the measure of insulin production used in this trial failed to predict weight changes, the authors note that, based on other studies, fasting insulin measures may be worth investigating further as weight-loss predictors.
Lastly, not every participant adhered perfectly to the assigned diet, which reduces our ability to draw a direct relationship between genotype, insulin production, and diet intervention. However, the study results are still very suggestive of a relationship, and the authors plan to make further analyses that will take dietary adherence into account.
One important aspect of this trial we need to consider, and one that is often overlooked, is interindividual variability. A second important aspect to consider is adherence. In the beginning of the study, all participants were instructed to consume either ≤20 g of fat (if in the low-fat group) or ≤20 g of carbs (if in the low-carb group) for the first two months, after which they could increase either their fat or carb intake to levels they felt they could sustain indefinitely. By the end of the trial, the vast majority had not been able to maintain such low levels. The final dietary recalls reported an average daily fat intake of ≈57 g (low-fat group) and an average daily carb intake of ≈132 g (low-carb group).
Real-life applicability matters greatly when extrapolating from a study’s results. The results from this study send a clear message that, when choosing an eating style, sustainability is a component whose importance cannot be understated.
Importance: Dietary modification remains key to successful weight loss. Yet, no one dietary strategy is consistently superior to others for the general population. Previous research suggests genotype or insulin-glucose dynamics may modify the effects of diets.
Objective: To determine the effect of a healthy low-fat (HLF) diet vs a healthy low-carbohydrate (HLC) diet on weight change and if genotype pattern or insulin secretion are related to the dietary effects on weight loss.
Design, Setting, and Participants: The Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) randomized clinical trial included 609 adults aged 18 to 50 years without diabetes with a body mass index between 28 and 40. The trial enrollment was from January 29, 2013, through April 14, 2015; the date of final follow-up was May 16, 2016. Participants were randomized to the 12-month HLF or HLC diet. The study also tested whether 3 single-nucleotide polymorphism multilocus genotype responsiveness patterns or insulin secretion (INS-30; blood concentration of insulin 30 minutes after a glucose challenge) were associated with weight loss.
Interventions: Health educators delivered the behavior modification intervention to HLF (n = 305) and HLC (n = 304) participants via 22 diet-specific small group sessions administered over 12 months. The sessions focused on ways to achieve the lowest fat or carbohydrate intake that could be maintained long-term and emphasized diet quality.
Main Outcomes and Measures: Primary outcome was 12-month weight change and determination of whether there were significant interactions among diet type and genotype pattern, diet and insulin secretion, and diet and weight loss.
Results: Among 609 participants randomized (mean age, 40 [SD, 7] years; 57% women; mean body mass index, 33 [SD, 3]; 244 [40%] had a low-fat genotype; 180 [30%] had a low-carbohydrate genotype; mean baseline INS-30, 93 μIU/mL), 481 (79%) completed the trial. In the HLF vs HLC diets, respectively, the mean 12-month macronutrient distributions were 48% vs 30% for carbohydrates, 29% vs 45% for fat, and 21% vs 23% for protein. Weight change at 12 months was −5.3 kg for the HLF diet vs −6.0 kg for the HLC diet (mean between-group difference, 0.7 kg [95% CI, −0.2 to 1.6 kg]). There was no significant diet-genotype pattern interaction (P = .20) or diet-insulin secretion (INS-30) interaction (P = .47) with 12-month weight loss. There were 18 adverse events or serious adverse events that were evenly distributed across the 2 diet groups.
Conclusions and Relevance: In this 12-month weight loss diet study, there was no significant difference in weight change between a healthy low-fat diet vs a healthy low-carbohydrate diet, and neither genotype pattern nor baseline insulin secretion was associated with the dietary effects on weight loss. In the context of these 2 common weight loss diet approaches, neither of the 2 hypothesized predisposing factors was helpful in identifying which diet was better for whom.
Christopher D Gardner; John F Trepanowski ; Liana C Del Gobbo; Michelle E Hauser; Joseph Rigdon; John PA Ioannidis; Manisha Desai; Abby C King