Unraveling the Science Behind Personalized Diets and Low-Fat vs Low-Carb Genotypes

Doctor weighing patient.

By Lea Borgi, MD
May 1, 2018

The Centers for Disease Control reports that almost 71% of adults over the age of 20 are overweight or obese, making obesity one of the most pressing concerns in public health.1 While dietary guidelines set recommended intakes of the various food groups,2 some data suggests that patients may lose weight more effectively when recommendations are tailored to certain genetic traits.3,4 According to the Pew Research Center, 72% of Americans agree that healthy eating is an essential part of living a long and healthy life.5 However, only 37.9% of a nationally representative sample of adult Americans from the National Health and Nutrition Examination Survey (NHANES) were found to consume a healthy diet.6 Furthermore, within the field of nutrition, there are a range of opinions regarding whether low-fat or low-carbohydrate diets are more effective or more sustainable in achieving long-term weight loss.7,8

The Study

The Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) study aimed to address several of these issues. Patients were randomized to low-fat diet versus a low-carbohydrate diet. All enrolled patients were assessed for the presence of a set of 3 SNP genotype patterns (to identify those with low-fat versus low-carbohydrate genotype) or baseline differences in insulin secretion. The study aimed to answer two questions : 1) Would a low-fat versus low-carbohydrate diet lead to greater weight loss at 12 months? 2) Did the baseline genotype impact the efficacy of particular dietary changes in leading to weight loss.7

The study enrolled 609 adults between the ages of 18-50 with a body mass index (BMI) of 28-40. Patients with diabetes were excluded, as were those with uncontrolled hypertension, liver, or kidney disease. Patients were randomly assigned to diet groups and at baseline; around 40% of patients in each group had the low-fat genotype,  ~30% had the low-carbohydrate genotype, and the remainder showed neither. The intervention comprised 22 teaching sessions, given by trained dieticians over the 12 months, held at weekly, 2-weekly, and decreasing to monthly intervals as the study went on. The recommended diet had a macronutrient composition of 48% carbohydrate, 29% fat and 21% protein for the HLF group, whereas the HLC diet was comprised of 30% carbohydrate, 45% fat and 23% protein. Dietary compliance was assessed using several unannounced recall interviews and was judged to be good in both groups. Of note, despite being advised not to change overall calorie intake, participants had a decreased intake of approximately 500-600 calories/day in both groups.

The Results

Participants in both groups lost similar amounts of weight, varying from a 30kg loss to a 10kg gain.  However, there was no statistically significant difference in weight loss between the groups (5.3kg for HLF and 6kg for HLC). Furthermore, there was no significant effect of low-fat or low-carb genotype on weight loss, regardless of whether the diet matched their genotype pattern or not. Similar lack of effect was seen for baseline variations in insulin secretion, where low-carb or low-fat diet did not show any advantage. In terms of secondary outcomes, there were no differences in blood pressure, insulin, and glucose levels between the two groups. At 12 months, LDL levels were lower in the low-fat diet group, but HDL had increased and triglycerides markedly decreased in the low-carbohydrate group.


These findings are in contrast with several other smaller studies.8,9 The DIETFITS authors argue that previous studies were either secondary analyses of trials with a different primary outcome or were not powered to assess such interactions.7 They also contend that the overall quality of dietary advice was higher in this study, where both groups were advised to increase vegetable intake along with reducing intake of refined grains and added sugars as a standard intervention, than in several of the others . The authors suggest that when this basic approach is employed, there does not appear to be additional benefit of specific low-carbohydrate versus low-fat diet.

In conclusion, continued research in personalized nutrition may shed more light into how different diets might work in different people. In the meantime, most health care professionals agree: the best advice is to eat your vegetables and cut back on added sugar.

Prepare for the obesity board review online with Harvard Medical School:
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1. National Center for Health Statistics. Prevalence of Obesity and Overweight. Centers for Disease Control and Prevention. 2017. https://www.cdc.gov/nchs/fastats/obesity-overweight.htm

2. U.S. Department of Health and Human Services and U.S. Department of Agriculture. 2015 – 2020 Dietary Guidelines for Americans. 8th Edition. December 2015. Available at https://health.gov/dietaryguidelines/2015/guidelines/

3. Dopler Nelson  M, Prabakar  P, Kondragunta  V, Kornman  KS, Gardner  CD. Genetic phenotypes predict weight loss success: the right diet does matter. Paper presented at: joint conference of the 50th Cardiovascular Disease Epidemiology and Prevention and Nutrition, Physical Activity, and Metabolism; March 2-3, 2010; San Francisco, CA

4. Qi  Q, Bray  GA, Smith  SR, et al. Insulin receptor substrate 1 gene variation modifies insulin resistance response to weight-loss diets in a 2-year randomized trial: the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial Circulation. 2011;124(5):563-571.

5. Pew Research Center. The New Food Fights: U.S. Public Divides Over Food Science. 2016. http://www.pewinternet.org/2016/12/01/the-new-food-fights/ps_2016-12-01_food-science_1-03/

6. Loprinzi PD, Branscum A, Hanks J, et al. Healthy Lifestyle Characteristics and Their Joint Association With Cardiovascular Disease Biomarkers in US Adults. Mayo Clin Proc. 2016 Apr;91(4):432-42. doi: 10.1016/j.mayocp.2016.01.009

7. Ludwig, D.S. and M.I. Friedman, Increasing adiposity: consequence or cause of overeating? JAMA, 2014. 311(21): p. 2167-8.

8. Hall, K.D., A review of the carbohydrate-insulin model of obesity. Eur J Clin Nutr, 2017. 71(3): p. 323-326.

9. Gardner CD, Trepanowski JF, Del Gobbo LC, et al. Effect of Low-Fat vs Low-Carbohydrate Diet on 12-Month Weight Loss in Overweight Adults and the Association With Genotype Pattern or Insulin Secretion: The DIETFITS Randomized Clinical Trial. JAMA. 2018;319(7):667–679. doi:10.1001/jama.2018.0245

Lea Borgi_headshotDr. Borgi’s clinic research focuses on the link between nutrition and chronic diseases, such as hypertension and kidney disease. Dr. Borgi is also interested in food policy, and is completing a Master in Nutrition Sciences and Policy at the Friedman School of Nutrition Science and Policy at Tufts University. Dr. Borgi is currently interested in the recent changes made in food government programs regarding the inclusion of potatoes in food stamps.


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