INTRODUCTION: In a recent article, I established that low carbohydrate diets are not new and that recently published six-month results of a non-randomized, parallel arm, outpatient intervention demonstrated it was so effective at improving blood sugar control in Type 2 Diabetes, that at the end of six months >75% of people had HbA1c that was no longer in the Diabetic range (6.5%).
But what about the long term safety and effectiveness of low carb diets?
To date, there have been 3 long-term clinical trials (2 years) published over the past 10 years, demonstrating that low-carbohydrate diets are both safe and effective. Not only do they support weight loss, they result in significant beneficial metabolic effects.
In this article I present the methodology and findings of the first study from 2008 and have strived to write it to be understandable by health professionals and lay-people, alike.
Note: In Part II and III of this series, I will present each of the other two studies.
Weight Loss with a Low-Carbohydrate, Mediterranean, or Low-Fat Diet
The first study published in 2008, with research conducted between July 2005 and June 2007 was a 2-year Dietary Intervention Randomized Controlled Trial (DIRECT) to compare the effectiveness and safety of (1) a low-fat calorie-restricted diet, (2) a Mediterranean calorie-restricted diet and (3) a low-carbohydrate non–calorie-restricted diet.
The criteria for recruitment to the study was age between 40 and 65 years and a body-mass index (BMI) – which is the weight in kilograms divided by the square of the height in meters of at least 27, or the presence of Type 2 Diabetes (according to the American Diabetes Association criteria) or coronary heart disease regardless of age and BMI.
Subjects were randomly assigned within strata i.e. gender, age (below or above the median), BMI (below or above the median), history of coronary heart disease (yes or no), history of Type 2 Diabetes (yes or no), and current use of statins (none, <1 year, or ≥1 year).
Subjects in each of the 3 diet groups were assigned to subgroups of ~18 participants (total of 6 subgroups in each group) and each diet group was assigned a Registered Dietitian that met with their groups in weeks 1, 3, 5, and 7 and after that at 6-week intervals, for a total of 18 sessions of 90 minutes each.
Low Fat Diet– Participants were counseled to consume low-fat grains, vegetables, fruits, and legumes and to limit added fats, sweets, and high-fat snacks. For the low-fat, restricted-calorie diet they were instructed to consume up to 30% of calories from fat, 10% from saturated fat and up to 300 mg cholesterol/day, with 1500 kcal for women and 1800 kcal/day for men.
Mediterranean Diet– The moderate-fat, calorie-restricted diet is rich in vegetables and low in meat, with poultry and fish replacing beef and lamb. Subjects were instructed to consume 35% of calories from fat; the main sources of added fat were from 30-45 grams of olive oil and a handful of nuts (5-7, less than 20 grams) per day. Subjects were instructed to restrict energy to 1500 kcal for women and 1800 kcal/day for men.
Low Carbohydrate Diet– This low-carb, non-calorie restricted diet was modeled after the Dr. Atkins Diet and aimed to provide 20 g/day of carbohydrates during the induction phase (first 2 months), and returned to this level of carb restriction after each religious holiday. At other times participants were instructed to increase carbs gradually up to maximum of 120 g/day to maintain the weight loss. Total calories, protein and fat intake from any source (except trans fats) were not limited.
Adherence to the diets was evaluated by a validated food-frequency questionnaire (127 food items with portion-size pictures) at baseline and at 6, 12, and 24 months of follow-up, and the questionnaires were self-administered electronically. A validated questionnaire was also used to assess physical activity.
Weight – The participants were weighed without shoes to the nearest 0.1 kg every month.
Blood Samples – Blood samples were obtained by at 8 a.m. after a 12-hour fast at baseline and at 6, 12, and 24 months.
Results – Dietary Intake, Energy Expenditure, and Urinary Ketones
At baseline, there were no significant differences in the composition of the diets consumed by participants assigned to the low-fat, Mediterranean, and low-carbohydrate diets.
Daily energy intake as assessed by the food-frequency questionnaire, decreased significantly at 6, 12, and 24 months in all diet groups as compared with baseline and there were no significant differences among the groups in the amount of decrease.
The low-carbohydrate group had a lower intake of carbohydrates and higher intakes of protein, total fat, saturated fat, and total cholesterol than the other groups.
The Mediterranean-diet group had a higher ratio of monounsaturated to saturated fat than the other groups, and a higher intake of dietary fiber than the low-carbohydrate group.
The low-fat group had a lower intake of saturated fat than the low-carbohydrate group.
Physical Activity – The amount of physical activity increased significantly from baseline in all groups, with no significant difference among groups in the amount of increase.
Urinary Ketone Production – The proportion of participants with detectable urinary ketones at 24 months was higher in the low-carbohydrate group (8.3%) than in the low-fat group (4.8%) or the Mediterranean-diet group (2.8%).
Note: of interest, participants in all groups produce urinary ketones.
A phase of maximum weight loss occurred from 1 to 6 months and a maintenance phase from 7 to 24 months.
All groups lost weight, but the reductions were greater in the low-carbohydrate and the Mediterranean-diet groups than in the low-fat group.
The overall weight changes among the 322 participants at 24 months were −4.7 (10.3 lbs) ±6.5 kg (± 14.3 lbs) for the low-carbohydrate group, −4.4 (9.68 lbs) ±6.0 kg (± 13.2 lbs) for the Mediterranean-diet group and
−2.9 (6.38 lbs) ±4.2 kg (± 9.24 lbs) for the low-fat group.
Changes in lipid profiles during the weight-loss and maintenance phases are as followed;
HDL cholesterol increased during the weight-loss and maintenance phases in all groups, with the greatest increase in the low-carbohydrate group (0.22 mmol per liter (8.4 mg per deciliter) compared to the low-fat group which increased by 0.16 mmol per liter (6.3 mg per deciliter).
Triglyceride levels decreased significantly in the low-carbohydrate group 0.27 mmol per liter (23.7 mg per deciliter) as compared with the low-fat group 0.03 mmol per liter (2.7 mg per deciliter).
Of significance, LDL cholesterol levels did not change significantly within any of the groups, and there were no significant differences between the groups in the amount of change.
Overall, the ratio of total cholesterol to HDL cholesterol decreased during both the weight-loss and the maintenance phases. The low-carbohydrate group had the greatest improvement, with a relative decrease of 20% as compared with a decrease of 12% in the low-fat group.
High-Sensitivity C-Reactive Protein, High-Molecular-Weight Adiponectin, and Leptin
The level of high-sensitivity C-reactive protein (an assessor of inflammation often used to may be used to evaluate risk of cardiovascular disease.) decreased significantly in the low-carbohydrate group (29%), and also in the Mediterranean-diet group (21%) during both the weight-loss and the maintenance phases, with no significant differences among the groups in the amount of decrease.
The level of high-molecular-weight adiponectin (which regulates glucose levels, as well as fatty acid breakdown) increased significantly in all diet groups, with no significant differences among the groups in the amount of increase.
Circulating leptin, which reflects body-fat mass, decreased significantly in all diet groups, with no significant differences among the groups in the amount of decrease.
Fasting Plasma Glucose, HOMA-IR, and Glycated Hemoglobin
Fasting Blood Glucose
Among the 36 participants with Type 2 Diabetes, those in the Mediterranean diet group and low carb diet group had a decrease in fasting plasma glucose levels of 2.1 mmol/L (32.8 mg per deciliter) and 0.1 mmol/L (1.2 mg/dl) respectively, whereas those in the low-fat group had an increase 0.7 mmol/L (12.1 mg/dl).
There was no significant change in fasting plasma glucose level among the participants without Type 2 Diabetes.
Insulin levels decreased significantly in participants with Type 2 Diabetes and without Type 2 Diabetes in all diet groups, with no significant differences among groups in the amount of decrease.
Not surprisingly, since HOMA-IR is determined from fasting blood glucose and fasting insulin, among subjects with Type 2 Diabetes the decrease in HOMA-IR at 24 months was significantly greater in those assigned to the Mediterranean diet (-2.3) and low carbohydrate diet (-1.0) than in those assigned to the low-fat diet (-0.3).
Glycated Hemoglobin (HbA1C)
Among the participants with with Type 2 Diabetes HbA1C at 24 months decreased most noticeably in the low-carbohydrate group (0.9 ±0.8%), and moderately in the Mediterranean-diet group (0.5 ±1.1%) and low-fat group (0.4 ±1.3%). The changes were significant only in the low-carbohydrate group.
In this 2-year dietary-intervention study, the low-carbohydrate diets was found to be both an effective and safe alternative to the low-fat diet for weight loss.
In addition to producing weight loss in moderately obese subjects, the low-carbohydrate demonstrated some marked beneficial metabolic effects including;
- lower fasting plasma glucose: 0.1 mmol/L (1.2 mg/dl)
- lower HbA1C: -0.9 ±0.8%
- significantly lower triglycerides: -0.27 mmol per liter (23.7 mg per deciliter)
- significantly higher HDL: +0.22 mmol per liter (8.4 mg per deciliter)
- lower C-reactive protein: -29%
These results suggest that a low carbohydrate, non-calorie restricted diet that provides 20 g of carbs per day during the induction phase of 2 months, with slightly higher amounts of carbohydrates with the addition of nuts, low-carb vegetables and small amounts of fruit until goal weight is achieved (~30-50 g carbs) is both safe and effective over a two-year period.
Astrup A et al, Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. N Engl J Med. 2008 Nov 13;359(20):2169-70.
free pdf available here: www.nejm.org/doi/full/10.1056/nejmoa0708681
Note: Everyone's results following a LCHF lifestyle will differ as there is no one-size-fits-all approach and everybody's nutritional needs and health status is different. If you want to adopt this kind of lifestyle, please discuss it with your doctor, first. If you are taking medication to lower blood sugar or blood pressure, you should be monitored by your physician while following a low carb diet, as medication dosages will need to be adjusted - often soon after beginning.
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