INTRODUCTION: To date, there have been 3 long-term clinical trials (2 years) published over the past 10 years involving “low carb diets”. In this post I review the third study which compares the effects of a low fat calorie restricted diet compared with a low carbohydrate diet and finding significantly better lipids at 1 year, before carbs were liberalized.
Purpose and Overview of the Study
The purpose of this randomized, controlled trial was to evaluate the long-term (2-year) effects of treatment with either a low-carbohydrate or low-fat, calorie-restricted diet on weight, cardiovascular risk factors, and bone mineral density — with the primary outcome being weight loss at 2 years.
All participants received comprehensive behavioral treatment to enhance weight loss associated with both diets and assessments were conducted at baseline, 3 months, 6 months, 12 and 24 months.
Primary inclusion criteria were age of 18 to 65 years, Body Mass Index (BMI) of 30 to 40 kg/ (m) x (m) and body weight less than 136 kg (300 pounds).
Exclusion criteria were participants with serious medical illnesses such as Type 2 Diabetes, lipid-lowering medications for dyspidemia, medications that affect body weight (including anti-obesity agents), blood pressures of 140/90 mm Hg or more (regardless of whether it was treated), and pregnancy or lactation.
A total of 307 adults (208 women and 99 men) with a mean age of 45.5 years and a mean Body Mass Index of 36.1 kg /(m) x (m) participated in this study.
Most (74.9%) participants were white; 22.1% were African American and 3% were of other race or ethnicity.
After a scripted phone screening, eligible participants attended an in-person screening during which the study’s purpose and requirements were discussed, eligibility confirmed and written informed consent was obtained.
Using a random-number generator, researchers randomly assigned participants (within each of 3 sites) to either a low carbohydrate treatment for 2 years, or a low fat calorie restricted diet for 2 years.
All participants completed a comprehensive medical examination and routine blood tests. There were no statistically significant differences between the two diet groups in any baseline variables.
The study, including recruitment and enrollment took place from March 2003 to June 2007.
Low Carbohydrate Diet
Approximately half of the participants (n = 153) were assigned to a low carbohydrate diet, which limited carbohydrate intake but allowed unrestricted consumption of fat and protein.
First 12 weeks of treatment
During the first 12 weeks of treatment, participants were instructed to limit carbohydrate intake to 20 g / day in the form of low–glycemic index vegetables.
After 12 weeks on very low carbohydrates
After the first 12 weeks, participants gradually increased carbohydrate intake each week by 5 g / day per week by consuming more vegetables, a limited amount of fruits, small quantities of whole grains and dairy products, until a stable and desired weight was achieved.
Subjects followed the guidelines outlined in Dr. Atkins’ New Diet Revolution, but were not provided with a copy of the book.
Participants were instructed to focus on limiting carbohydrate intake and to eat foods rich in fat and protein until they were satisfied.
The primary behavioral target was to limit carbohydrate intake.
Low-Fat Calorie Restricted Diet
Approximately half of the participants (n= 154) were assigned to eat a low fat diet which limited energy to 1200 to 1500 kcal / day for women and 1500 to 1800 kcal / day for men.
Approximately 55% of calories came from carbohydrate, 30% from fat and 15% from protein (comparable to the recommendations of Canada’s Food Guide for Healthy Living).
Participants were instructed to limit calorie intake, with a focus on decreasing fat intake, however limiting overall energy intake (kcal / day) was the primary behavioral target.
Group Behaviour Treatment
All participants received comprehensive, in-person group behavioral treatment weekly for 20 weeks, every other week for 20 weeks and then every other month for the remainder of the 2-year study period.
Each treatment session lasted 75 to 90 minutes.
Topics included self-monitoring, stimulus control and relapse management.
Group sessions reviewed participants’ completion of their eating and activity records, as well as other skill builders.
Participants in both groups were instructed to take a daily multivitamin supplement (provided by the study).
All participants were prescribed the same level of physical activity (mainly walking), beginning at week 4, with four sessions of 20 minutes each and progressing by week 19 to four sessions of 50 minutes each.
Outcomes and Measurements
Body Weight— measured at each treatment visit on calibrated scales while participants wore light clothing and no shoes. The primary outcome was weight at 2 years.
Height — measured by a stadiometer at baseline.
The following measurements were collected at baseline and at 3, 6, 12 and 24 months:
Serum Lipoproteins — measured plasma high-density lipoprotein (HDL) cholesterol and triglyceride levels. Very-low-density lipoprotein (VLDL) cholesterol and low-density
lipoprotein (LDL) cholesterol concentrations were directly measured by β-quantification. Blood samples were obtained after participants fasted overnight (12 hours).
Blood Pressure— assessed after participants were sitting quietly for 5 minutes and using automated instruments with cuff sizes based on measured arm circumference. Two readings of blood
pressure were obtained, separated by a 1-minute rest period with the average of the two readings used.
Urine Ketones— Bayer Ketostix were used to measure fasting urinary ketones and were characterized as negative (0 mg/dL) or positive (trace, 5 mg/dL; small, 15 mg/dL; moderate, 40 mg/dL; or large, 80 to 160 mg/dL).
Bone Mineral Density and Body Composition (percentage of body fat)—assessed using dual-energy x-ray absorptiometry at baseline and at 6, 12 and 24 months.
Attrition—There were no statistically significant differences between the two groups in terms of attrition; defined as not undergoing an assessment at a specific time point, independent of the reason.
Body Weight— participants in both groups lost approximately 11% of initial weight at 6 and 12 months, with subsequent weight regain to a 7% weight loss at 2 years . There was no statistically significant differences in weight loss at any time point between the low carbohydrate and low-fat calorie restricted groups, although there was a strong trend for greater weight loss in the low-carbohydrate group at 3 months.
Urinary Ketones—percentage of participants who had positive test results for urinary ketones was greater in the low carbohydrate than in the low fat calorie restricted group at 3 months (63% vs. 20%) and at 6 months (28% vs. 9%). Researchers found no statistically significant differences between groups after 6 months and they noted that the decrease from 3 to 24 months is consistent with liberalization of carbohydrate intake over time, as part of the study protocol.
Blood Pressure—Systolic blood pressure decreased with weight loss in both diet groups relative to baseline and did not significantly differ between groups at any time. Reductions in diastolic pressure were significantly greater (2 to 3 mm Hg) in the low carbohydrate than in the low-fat group at 3 and 6 months with a strong trend at 24 months.
Plasma Lipid Concentrations—Most of the differences in plasma lipid concentrations between the two groups were observed during the first 6 months of the diets.
LDL cholesterol: Researchers found a significantly greater decrease in LDL cholesterol levels at 3 and 6 months in the low-fat calorie restricted group than in the low carbohydrate group, but this difference did not persist at 12 or 24 months. There may be reasons for this, discussed below.
Triglyceride levels: Decreases in triglyceride levels were greater in the low-carbohydrate group than in the low-fat calorie restricted group at 3 and 6 months, but not at 12 or 24 months.
VLDL cholesterol: Decreases in VLDL cholesterol levels were significantly greater in the low-carbohydrate group than in the low-fat calorie restricted group at 3, 6, and 12 months but not at 24 months.
HDL cholesterol: Increases in HDL cholesterol levels were significantly greater in the low-carbohydrate group than in the low-fat calorie restricted group at 3, 6, 12 and 24 months.
Total-cholesterol : HDL cholesterol: The ratio of total-cholesterol to HDL cholesterol levels decreased significantly in both groups through 24 months but did not significantly differ between groups at any time. There was a trend for greater reductions in the low-carbohydrate group at 6 months and 12 months.
Summary: The only effect on plasma lipid concentrations that persisted at 2 years was the significantly greater increases in HDL cholesterol levels among low-carbohydrate participants.
Bone Mineral Density and Body Composition— researchers found no differences between the two groups in changes in bone mineral density or body composition over 2 years.
- Neither dietary fat nor carbohydrate intake influenced
weight loss when combined with a comprehensive lifestyle intervention. That is, participants had similar and clinically significant weight losses with either a low carbohydrate or low-fat calorie restricted diet at 1 year (11%) and 2 years (7%). Researchers concluded that this demonstrates that either diet
can be used to achieve successful long-term weight loss. if coupled with behavioral treatment.
- Researchers concluded that because both diet groups achieved nearly identical weight loss, a low-carbohydrate diet has greater beneficial long-term effects on HDL cholesterol concentrations
than a low-fat calorie restricted diet.
- While researchers found a significantly greater decrease in LDL cholesterol levels at 3 and 6 months in the low-fat calorie restricted group than in the low-carbohydrate group, this difference did not persist at 12 or 24 months. Researchers concluded that since assessment of LDL cholesterol concentration was without information on LDL particle size, no information was obtained in terms of coronary heart disease risk (small, dense LDL particles are more atherogenic than large LDL particles).
- The low-carbohydrate diet caused a decrease in plasma triglyceride concentration that was more than double the reduction observed with a low-fat calorie restricted diet at 3, 6, and 12 months however plasma triglyceride concentration returned toward baseline in the low-carbohydrate
group, such that the two groups did not differ significantly at 2 years.
[Note: The rise in triglycerides after desired weight was achieved may have been the result of the liberalization of the low carbohydrate diet by the inclusion of fruit, dairy and small amounts of whole grains which may have been responsible for driving triglyceride levels up.]
- The greater decline in directly measured VLDL cholesterol concentration in the low-carbohydrate at 3, 6, and 12 months was not sustained at 2 years. Researchers found no significant differences between the two groups in VLDL cholesterol. Researchers concluded that the close relationship and tracking between fasting plasma triglyceride concentrations (which are primarily contained within VLDL) and VLDL cholesterol concentrations supports a model in which during the first year of the study the low-carbohydrate diet (a) decreased hepatic VLDL secretion, (b) enhanced VLDL clearance, or both when compared with the low-fat calorie restricted diet.
[Note: Again, the liberalization of the low carbohydrate diet after desired weight was reached and the inclusion of fruit, dairy and small amounts of whole grains into the diet may have been responsible.]
- Plasma HDL cholesterol concentration increased by approximately 20% at 6 months in the low-carbohydrate diet group, which persisted throughout the study and was more than twice the increase observed in the low-fat calorie restricted diet group. Researchers concluded that the magnitude of the change observed in the low-carbohydrate diet group approximates that obtained with the maximal doses of nicotinic acid (niacin), the most
effective HDL-raising pharmacologic intervention that was available at the time of the study (2010).
This 2-year, randomized control study of more than 300 participants found that both diet groups achieved clinically significant and nearly identical weight loss (11% at 6 months and 7% at 24 months) and that people who ate the low-carbohydrate diet had greater 24-month increases in HDL-cholesterol concentrations than those who ate a low-fat calorie restricted diet.
As well, an significant finding of this study was a very favourable lowering of LDL for the first 6 months and lowering of both TG and VLDL for the first year. It is unknown whether these results would have persisted and been sustained had the low carb group not been permitted to liberalize their diet by the inclusion of fruit, dairy and small amounts of grain products, once they achieved their desired weight loss.
These long-term data certainly provide evidence that a low-carbohydrate diet is both a safe and effective option for weight loss and that this style of eating has a prolonged, positive effect on lipid profiles – certainly while intake of carb-containing foods are restricted.
Foster GD, Wyatt HR, Hill JO et al, Weight and metabolic outcomes after 2 years on a low-carbohydrate versus low-fat diet: a randomized trial, Ann Intern Med. 2010 Aug 3;153(3):147-57