A Review of Three Recently Published Papers on Dietary Approaches to Weight Loss and Fat Mobilization

A Review of Three Recently Published Papers on Dietary Approaches to Weight Loss and Fat Mobilization

By Kristen N Smith, PhD, RD; Mary R Dicklin, PhD; Kevin C Maki, PhD, CLS



There have been multiple papers published this year focusing on various dietary approaches for producing weight loss and their effects on weight-related outcomes, including changes in body composition and cardiovascular disease risk factors. This post will summarize three recently published original research articles.


  1. Low-Fat vs. Low-Carbohydrate and Weight-Loss Diets (DIETFITS)1:

It is well-established that obesity is a major public health challenge and that dietary modifications are essential for successful weight loss. Commonly investigated approaches include diets that restrict intake of fat or carbohydrate2-4. No matter what macronutrient is emphasized or restricted, most trials have reported modest (~ 5% or less) mean weight loss after 12 months, with negligible differences between the different diet groups.5 However, when assessing weight-loss outcomes of individual subjects, these have varied widely within diet groups and ranged from weight loss of ~25 kg (~55 lbs) to weight gain of ~5 kg (11 lbs).2-4 There appears to be no one specific dietary strategy that is consistently superior for weight management within the general population. Additionally, results from some prior studies have suggested that an individual’s genotype or insulin-glucose dynamics may have an impact on the outcomes associated with certain diets. For example, it has been hypothesized that individuals with higher insulin resistance or insulin secretion may respond more favorably to a low-carbohydrate dietary regimen.6


The objective of the Diet Intervention Examining the Factors Interacting with Treatment Success (DIETFITS) trial was to assess the effect of a healthy low-fat (HLF) diet vs. a healthy low-carbohydrate (HLC) diet on weight change and to examine whether genotype pattern or insulin secretion are related to dietary effects on weight loss. This study was a single-site, parallel-group, weight-loss trial that randomized individuals to either a HLF diet or a HLC diet for 12 months. Subjects (N = 609) were men and premenopausal women aged 18 to 50 y with body mass index (BMI) 28 to 40 kg/m2. The study began with a 1-month run-in during which subjects were instructed to maintain their habitual diet, physical activity and body weight. Throughout the study period, registered dietitian health educators led 22 diet-specific instructional sessions guiding the participants to follow their assigned plan. The researchers also investigated whether three single-nucleotide polymorphism multi-locus genotype patterns or insulin secretion (blood concentration of insulin 30 min after a glucose challenge) were associated with weight loss.


Primary Outcome

Secondary Outcomes

§  12-month weight change

§  Other anthropometric measures (BMI, % body fat, waist circumference)

§  Plasma lipids

§  Plasma insulin and glucose (fasting and after a glucose challenge)

§  Blood pressure


Subject characteristics:

  • Mean (standard deviation) age: 40 (7) y,
  • 57% women,
  • Mean (standard deviation) BMI: 33 (3) kg/m2,
  • Mean baseline blood concentration of insulin 30 min after glucose challenge 93 µU/mL,
  • 481 (79%) completed the trial.


Weight change at 12 months did not vary between the two diet groups (-5.3 kg for HLF vs -6.0 kg for HLC; mean between-group difference, 0.7 kg 95% confidence interval, -0.2 to 1.6 kg). There were no significant diet x genotype (p = 0.20) or diet x insulin secretion interactions (p = 0.47). Overall, both diets produced a mean weight loss of ~6 kg over 12 months, but no new knowledge was gained regarding how to identify which diet would be better suited for whom.


  1. Vegetarian vs. Mediterranean Diet and Cardiovascular Disease Risk (CARDIVEG)7:

A lacto-ovo vegetarian diet (VD) is the most common type of vegetarian diet. It excludes meat, fish and poultry in all forms, but allows intake of eggs and dairy products.8 A 2017 meta-analysis of >130,000 vegetarians found that adherence to a VD was associated with many favorable health characteristics, including lower levels of cardiovascular disease risk factors and reduced risk for ischemic heart disease.9 The potential health benefits associated with a VD may require additional investigation for several reasons: most of the studies on VD were 1) observational, 2) conducted in countries at high risk for cardiovascular disease (like the United States), 3) conducted in people who were already vegetarians. These are possible sources of bias because populations already following vegetarian patterns may be more health conscious and not fully representative of the overall population.10 Consequently, additional investigation of healthy VD and omnivorous patterns is warranted.


The aim of the Cardiovascular Prevention with Vegetarian Diet (CARDIVEG) study was to compare, in an omnivorous, low-cardiovascular-risk European population, the effects of a 3-month period on a VD versus a low-calorie Mediterranean diet (MedD) on markers of cardiovascular disease risk.11 It is important to note that the MedD is often reported as one of the healthiest models for preventing cardiovascular disease.12  The study was a randomized, open, crossover trial with 2 intervention periods of VD or MedD, each lasting 3 months, after an initial 2-week run-in period to assess participants’ motivation, commitment and availability.11 Participants underwent face-to-face, individual counseling sessions where they also received 1-week menu plans. Both interventions were low-calorie in nature and aimed at reducing body weight and risk factors for cardiovascular disease.


Both diet plans consisted of ~50-55% energy from carbohydrate, ~25-30% energy from total fat (≤7% energy from saturated fat, <200 mg cholesterol), and ~15-20% energy from protein. The VD was characterized by abstinence from consumption of meat and meat products, poultry, fish and seafood, and the flesh of any other animal, but it included eggs and dairy products and all other food groups. The MedD was characterized by consumption of all food groups, including meat and meat products, poultry and fish.


Primary Outcomes

Secondary Outcomes

Changes from baseline in:

§  Total body weight

§  BMI

§  Fat mass

Changes from baseline in:

§  Circulating cardiovascular risk parameters

o   Lipid profile

o   Glycemic profile

o   Oxidative stress profile

o   Inflammatory profile


Of the 118 subjects randomized, 104 completed the VD period and 103 completed the MedD period. No differences were observed between the two diets in body weight. Similar outcomes were also reported for BMI and fat mass. However, responses in laboratory outcomes including low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), vitamin B12 and uric acid levels varied. The VD significantly produced significantly larger reductions in LDL-C, vitamin B12 and uric acid levels, whereas the MedD led to a significantly greater reduction in TG levels.


The authors concluded that both low-calorie diets contributed to weight loss to a similar degree and cardiovascular risk factor levels at the end of the two diet periods were similar, although LDL-C was slightly lower during the VD period and TG was slightly lower during the MedD period. These results provide further evidence that both the VD and MedD are useful options for weight loss and managing the cardiovascular risk factor profile.


  1. Lifestyle and Diet Strategies and Fat Mobilization (CENTRAL)13

Visceral adipose tissue (VAT) is the most strongly implicated fat storage pool connecting obesity to cardiometabolic disease risk. This may be attributed to the propensity of abdominal fat to activate obesity-related stress-sensing pathways14 and release secretory products and free fatty acids into the portal vein.15


Results from prior studies have been controversial regarding whether specific interventions can preferentially reduce VAT.16-20 Some studies have shown that dietary interventions did not preferentially impact abdominal fat depots,18,19 whereas others in both humans and in animal models suggest dietary changes might impact VAT, with higher intakes of simple sugars and trans fatty acids being associated with increased VAT, and higher intakes of unsaturated fatty acids associated with reductions in VAT. It is unclear whether lifestyle patterns and interventions can impact losses in specific fat depots (e.g., abdominal, pericardial, and renal sinus) and deposits (e.g., hepatic, intermuscular, and pancreatic), thus producing differential effects on the cardiometabolic risk factor profile.21 The objective of the CENTRAL trial was to test the hypothesis that, beyond long-term moderate weight loss, it is possible to induce differential mobilization of VAT and other specific fat depots by lifestyle interventions, and to link the changes to specific clinical biomarkers.


This was an 18-month randomized controlled trial of 278 sedentary men and women with abdominal obesity or dyslipidemia. Subjects were randomly assigned to either a low-fat (LF) diet or a Mediterranean/low-carbohydrate (MED/LC) diet. Both diets were designed for moderate, long-term weight loss and restricted intakes of refined carbohydrates and trans fats, and to have increased vegetable intakes. The LF diet had <30% of calories from total fat, ≤10% of calories from saturated fat and ≤200 mg/d cholesterol. The MED/LC diet had <40 g/d carbohydrate intake in the first 2 months, gradually increased to ≤70 g/d, and increased protein and fat intakes (rich in vegetables and legumes and low in red meat). Lunch was provided daily in a workplace cafeteria, and subjects received nutritional counseling periodically throughout the study. After 6 months of dietary intervention, each group was further randomized into added moderate physical activity (PA; 80% aerobic; supervised/free gym membership) or no added PA groups.


Primary Outcomes

Secondary Outcomes and Biomarker Measurements

§  Body fat redistribution (VAT)

§  Dynamics of different fat depots:

o   Deep and superficial subcutaneous

o   Liver

o   Pericardial

o   Muscle

o   Pancreas

o   Renal sinus

§  Lipid profile

§  Glycemic profile

§  Leptin

§  C-reactive protein


Although final weight loss was not different between dietary interventions, exercise reduced waist circumference with the greatest impact in the MED/LC/PA+ group (p<0.05). VAT (-22%), intrahepatic (-29%), and intrapericardial (-11%) fat reductions from baseline were greater than pancreatic and intramuscular fat declines. PA with either dietary intervention contributed to a significantly greater loss in VAT (mean of difference, -6.67 cm2; 95% CI, -14.8 to -0.45) compared with no PA. The MED/LC diet yielded greater reductions in intrahepatic, intrapericardial, and pancreatic fats (p<0.05 for all) compared with the LF diet. Renal sinus and femoral intramuscular fats were not preferentially impacted by one diet vs. the other.


The study outcomes described support dietary and PA interventions for weight loss as the goal.  It also appears that the MED/LC diet pattern was more effective than a LF diet for reducing storage of intrahepatic, intrapericardial and pancreatic fat, which may have long-term implications for effects on the cardiometabolic risk factor profile, although this needs to be verified. PA, regardless of diet, independently contributed to VAT loss.


Although both diets produced similar moderate weight loss, the MED/LC diet resulted in greater improvements in certain cardiometabolic risk factors, including greater reductions in waist circumference, TG and TG/high-density lipoprotein cholesterol ratio and increased high-density lipoprotein cholesterol. These changes remained significant after adjusting for weight loss.



No significant differences were noted in weight loss between the dietary interventions in the three studies reviewed, although some differences were noted in the effects of the different types of diets on cardiometabolic risk factors. It is no surprise that incorporating PA into the weight loss regimen enhanced reductions in VAT and intrahepatic fat. The take-away message seems to be that energy restricted low-fat, low-carbohydrate, or Mediterranean-style diet patterns can all be effective for promoting weight/fat loss and improving the cardiometabolic risk factor profile. Individual responses and personal preferences vary widely, and those attempting to lose weight and body fat can be reassured that it is acceptable to employ any of the energy restricted dietary patterns studied in these trials, particularly when combined with sufficient PA.



  1. 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.
  2. Gardner CD, Kiazand A, Alhassan S, et al. Comparison of the Atkins, Zone, Ornish, and LEARN diets for change in weight and related risk factors among overweight premenopausal women: the A TO Z Weight Loss Study: a randomized trial. JAMA. 2007;297(9):969-977.
  3. Sacks FM, Bray GA, Carey VJ, et al. Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates. N Engl J Med. 2009;360(9):859-873.
  4. Shai I, Schwarzfuchs D, Henkin Y, et al. Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. N Engl J Med. 2008;359(3):229-241.
  5. Johnston BC, Kanters S, Bandayrel K, et al. Comparison of weight loss among named diet programs in overweight and obese adults: a meta-analysis. JAMA. 2014;312(9):923-933.
  6. Fleming JA, Kris-Etherton PM. Macronutrient content of the diet: What do we know about energy balanace and weight maintenance. Curr Obes Rep. 2015;5(2):208-213.
  7. Sofi F, Dinu M, Pagliai G, et al. Low-calorie vegetarian versus mediterranean diets for reducing body weight and improving cardiovascular risk profile: CARDIVEG Study (Cardiovascular Prevention With Vegetarian Diet). Circulation. 2018;137(11):1103-1113.
  8. Leitzmann C. Vegetarian nutrition: past, present, future. Am J Clin Nutr. 2014;100 Suppl 1:496S-502S.
  9. Dinu M, Abbate R, Gensini GF, Casini A, Sofi F. Vegetarian, vegan diets and multiple health outcomes: A systematic review with meta-analysis of observational studies. Crit Rev Food Sci Nutr. 2017;57(17):3640-3649.
  10. Kwok CS, Umar S, Myint PK, Mamas MA, Loke YK. Vegetarian diet, Seventh Day Adventists and risk of cardiovascular mortality: a systematic review and meta-analysis. Int J Cardiol. 2014;176(3):680-686.
  11. Dinu M, Pagliai G, Casini A, Sofi F. Mediterranean diet and multiple health outcomes: an umbrella review of meta-analyses of observational studies and randomised trials. Eur J Clin Nutr. 2018;72(1):30-43.
  12. Sofi F, Dinu M, Pagliai G, Cesari F, Marcucci R, Casini A. Mediterranean versus vegetarian diet for cardiovascular disease prevention (the CARDIVEG study): study protocol for a randomized controlled trial. Trials. 2016;17(1):233.
  13. Gepner Y, Shelef I, Schwarzfuchs D, et al. Effect of distinct lifestyle interventions on mobilization of fat storage pools: CENTRAL Magnetic Resonance Imaging Randomized Controlled Trial. Circulation. 2018;137(11):1143-1157.
  14. Rudich A, Kanety H, Bashan N. Adipose stress-sensing kinases: linking obesity to malfunction. Trends Endocrinol Metab. 2007;18(8):291-299.
  15. Item F, Konrad D. Visceral fat and metabolic inflammation: the portal theory revisited. Obes Rev. 2012;13 Suppl 2:30-39.
  16. Rosqvist F, Iggman D, Kullberg J, et al. Overfeeding polyunsaturated and saturated fat causes distinct effects on liver and visceral fat accumulation in humans. Diabetes. 2014;63(7):2356-2368.
  17. Maersk M, Belza A, Stodkilde-Jorgensen H, et al. Sucrose-sweetened beverages increase fat storage in the liver, muscle, and visceral fat depot: a 6-mo randomized intervention study. Am J Clin Nutr. 2012;95(2):283-289.
  18. Bray GA, Smith SR, de Jonge L, et al. Effect of dietary protein content on weight gain, energy expenditure, and body composition during overeating: a randomized controlled trial. JAMA. 2012;307(1):47-55.
  19. Haufe S, Engeli S, Kast P, et al. Randomized comparison of reduced fat and reduced carbohydrate hypocaloric diets on intrahepatic fat in overweight and obese human subjects. Hepatology. 2011;53(5):1504-1514.
  20. Rokling-Andersen MH, Rustan AC, Wensaas AJ, et al. Marine n-3 fatty acids promote size reduction of visceral adipose depots, without altering body weight and composition, in male Wistar rats fed a high-fat diet. Br J Nutr. 2009;102(7):995-1006.
  21. Tchernof A, Despres JP. Pathophysiology of human visceral obesity: an update. Physiol Rev. 2013;93(1):359-404.


Photo by Joel Filipe

Changes in Diet Quality and Mortality

Changes in Diet Quality and Mortality

Changes in Diet Quality and Mortality

By Kevin C Maki, PhD

Sotos-Prieto and colleagues from the Departments of Nutrition and Epidemiology at Harvard University published an analysis of the relationships between changes in diet quality scores and mortality [all-cause, cardiovascular (CV), and cancer] in a recent issue of the New England Journal of Medicine.1  These relationships were examined in two large cohorts of health professionals, the US Nurses’ Health Study (women) and the US Health Professionals Follow-up Study (men).

Previous studies have shown that higher diet quality scores are associated with lower mortality.  Of course, the potential problem with observational evidence is that it is difficult to know whether it is higher diet quality per se that is responsible for the relationship to lower mortality, or other differences between those with lower and higher diet quality scores.  People who consume diets that conform to recommendations from health authorities often have other characteristics that might contribute to better outcomes.  They tend to be more health conscious, have higher educational attainment, exercise more regularly, have lower body mass index, and be less likely to smoke, use illicit substances and consume alcohol to excess, just to name a few of the differences.

Epidemiologists attempt to adjust for these differences using statistical techniques to reduce the potential for bias and confounding by differences other than the exposure of interest; in this case diet quality score.  It is often impossible to identify and adjust for all of the variables that may be relevant.  The ultimate goal is to identify exposures that are causally related to disease status and modifiable, which can serve as the basis for public health actions, including recommendations for the characteristics of a healthy diet.

While far from perfect, it is useful to investigate the relationships between changes in exposure variables over time and disease risk.  For example, it bolstered the case for a causal relationship between cigarette smoking and risks for lung cancer and heart disease when it was shown that risks declined over time in those who quit smoking, but did not in those who continued to smoke.  Similarly, the Harvard group sought to assess whether changes in diet quality scores over time predicted risks for all-cause and cause-specific mortality.

In order to address this question, the researchers calculated changes over time in three scores:  the Alternative Healthy Eating Index (aHEI), the Alternative Mediterranean Diet (aMED) score, and the Dietary Approaches to Stop Hypertension (DASH) score.  Scores were calculated based on responses to the Willett Food Frequency Questionnaire that was administered every 4 years over long periods in both cohorts.  For the main analysis, changes in diet quality were calculated from 1986 to 1998 and follow-up was through 2010 (12 years).  The analysis included data from 73,739 participants (65% women).

The aHEI used scores from 0-10 for 11 food components selected on the basis of their relationships with chronic diseases.  Thus, the score could be from 0 to 110.  The aMED score included 9 components and were scored as 0 or 1 according to whether intake was above or below the cohort-specific median, allowing a score from 0 to 9.  The DASH score included 8 components, each scored 1-5, thus producing scores ranging from 8 to 40.  For all, a higher score indicated higher diet quality.

Participants who increased their diet quality scores reported increased intakes of whole grains, vegetables and omega-3 fatty acids, as well as reduced intakes of sodium.  Compared to participants with relatively stable scores (middle quintile for change), those in the top 20% for increases (roughly 15-16 points for aHEI, 2-3 points for aMED, and 5-6 points for DASH), had 9-14% lower mortality risk, all p < 0.05 for the fifth vs. the third quintile in multivariable-adjusted models.  Similar results were obtained when a 20-percentile increase in score was modeled (8-17% lower risk for mortality).

Results were somewhat less consistent for deaths from CV causes and cancer.  A 20-percentile increase in aHEI was associated with 15% lower CV mortality (p < 0.05), while the same increase in aMED was associated with a 7% lower CV mortality (p < 0.05), and a 20-percentile increase in DASH score was associated with a non-significant 4% reduction in mortality.  For cancer mortality, a 20-percentile increase was associated with 6-9% lower mortality, which was only statistically significant (p < 0.05) for the DASH score (9%).

Having constant high diet quality score was associated with reductions of 9-14% in all-cause mortality over 12 years compared to those with constant low scores.  The investigators also looked at 8-year and 16-year changes.  In general, the effect became more pronounced with longer periods.  This was particularly evident for the aHEI, although that may be due to the greater range of values possible, which increases the variation in the populations studied.

This study adds support for the healthy eating patterns recommended in the Dietary Guidelines for Americans (2015-2020).2  Although confounding by unmeasured, or crudely measured, factors cannot be ruled out, the available data are consistent with a causal association between a healthy diet pattern and reduced risks for all-cause and CV mortality.  The evidence for a reduction in cancer mortality with a healthy dietary pattern is less convincing.  These results particularly support the recommendations for increased consumption of whole grains, fruits, vegetables, and fish/omega-3 fatty acids, compared with the average American diet, since these were the foods that were primarily responsible for changes in diet quality scores over time.

As I have stated repeatedly, public policy recommendations regarding diet often have to be based on evidence from observational studies assessing disease risk and intervention studies of biomarkers for disease risk, because few randomized, controlled dietary intervention studies have been completed to assess effects on disease incidence.  The strongest recommendations should be reserved for those areas where we have alignment between results from all three types of studies.

The results from the Prevención con Dieta Mediterránea (PREDIMED) study support health benefits, including reduced incidence of CV events (particularly stroke) and diabetes associated with advice to consume a Mediterranean diet pattern supplemented with nuts or olive oil, compared to low-fat diet advice.3 PREDIMED was not a perfect trial.  More randomized, controlled dietary intervention trials with outcomes of disease incidence are badly needed to answer questions about risks and benefits of various types of dietary advice.  PREDIMED demonstrates the feasibility of completing such studies.

For now, despite a number of caveats and uncertainties, the best available evidence suggests that the dietary patterns recommended in the Dietary Guidelines for Americans (healthy US diet, Mediterranean diet, DASH diet) are associated with a variety of favorable outcomes, including reduced total and CV mortality.


  1. Sotos-Prieto M, Bhupathiraju SN, Mattei J, et al. Association of changes in diet quality with total and cause-specific mortality. N Engl J Med. 2017;377:143-153.
  2. US Department of Health and Human Services and US Department of Agriculture. Dietary Guidelines for Americans 2015-2020. 8th December 2016. Available at https://health.gov/dietaryguidelines/2015/resources/2015-2020_Dietary_Guidelines.pdf.
  3. Estruch R, Martínez-González MA, Corella D, et al.; PREDIMED Study Investigators. Effects of a Mediterranean-style diet on cardiovascular risk factors: a randomized trial. Ann Intern Med. 2006;145:1-11.



Changes in Diet Quality and Mortality

MB Clinical Academy Releases its First Two Educational Programs

MB Clinical Academy

MB Clinical Academy Releases its First Two Educational Programs

MB Clinical Academy produces educational materials to help clinicians, clinical research professionals and students more effectively manage the cardiometabolic health of their patients/clients, and to understand the strengths and limitations of the available evidence, including gaps that can be filled with future studies.

We have just completed two new programs, which will be available for purchase and download during the week of July 10, 2017.

Short Course

Diet and Prevention of Type 2 Diabetes Mellitus:  Beyond Weight Loss and Exercise

This short course will review the evidence for dietary factors in the prevention of type 2 diabetes mellitus (T2D).  It contains three modules that will cover:

  • Module 1: Epidemiology and pathophysiology of T2D
  • Module 2: Predictors of T2D risk and effects of interventions on incidence
  • Module 3: Summary of the associations and mechanisms through which diet may affect T2D risk, with an emphasis on insulin sensitivity and glycemic load

Short Course

Interpreting Efficacy Results from Cardiovascular Outcomes Trials

Cardiovascular outcomes trials are integral to evidence-based medicine, and they are the most effective means for demonstrating that an intervention reduces major adverse cardiovascular events.  A sound understanding of the fundamentals of clinical study design and statistical methodology is essential for the interpretation of efficacy results from cardiovascular outcomes trials.  However, most clinicians have not had extensive training on how to interpret measures of association and statistical procedures used to assess the efficacy of interventions intended to reduce cardiovascular event risk.  This course will review of the following concepts and their use in cardiovascular outcomes studies:

  • Measures of cardiovascular event incidence
    1. Relative risk
    2. Hazard ratio
    3. Odds ratio
  • Comparing event rates and treatment effects
    1. Relative risk reduction
    2. Absolute risk reduction
    3. Number needed to treat (or harm)
  • Pitfalls when making comparisons between cardiovascular outcomes trials, including the three most important questions
    1. Who was studied (risk profile)?
    2. What outcomes were assessed?
    3. Over what time period?
  • Additional factors to consider in the interpretation of findings from cardiovascular outcomes trials
    1. Evaluating the roles of chance, bias and confounding
    2. Factors affecting validity and generalizability
    3. Assessing the potential for type I and type II statistical errors

We expect that those who purchase these programs will find them informative and practical.  If you have suggestions for future programs, don’t hesitate to send us an email:  info@mbclinicalresearch.com.


MB Clinical Academy