Sunday, October 19, 2014

Summary of the Low Carb Diet Trials: Part 1

Over the past several weeks I looked at the low carb trials, specifically those with at least 100 participants and running for at least 12 months.  The links to those blog posts are below:
 
 
Overall, the trials had a good balance between men (796) and women (1064).  All of the studies set ambitious targets for the low carb group as a daily carbohydrate limit of 20-50g or even 100g is a major difference to what most people regularly eat.  In almost all the trials the low carb group returned to eating ~30-40% carbohydrate at the final time point (except in Stern and Brinkworth).  The targets for the low fat group were not too different from what people usually eat, but almost always featured deliberate calorie restriction (CR).
 
 
There wasn’t much difference between the low carb and low fat groups, although the low carb group far more often had better outcomes than the low fat group with one exception (more adverse symptoms during first 6 months in the Foster trial).
 
* In the Gardner trial the low carb group often had a trend for better results compared to the other groups but didn’t reach statistical significance.  This may have been at least partially due to there being 4 groups in the trial, which makes it more difficult for one group to reach statistical significance.


Y = Low carb had significantly better result than low fat
- = Not significantly different regarding low carb vs. low fat
N = Low carb had significantly worse result than low fat
 
Some trials (Stern, Shai, Foster, Bazzano) fairly consistently found a better outcome with the low carb diet while others (Dansinger, Brinkworth, Lim, Iqbal) fairly consistently found no difference.  This doesn’t seem to be related to gender or the intensity of the intervention.  I’ve speculated on the factors responsible below:
 
Low Carb > Low Fat Trials
Low Carb = Low Fat Trials
Trial
Possible Reasons Why
Trial
Possible Reasons Why
Stern
Fairly good adherence in LC group.  Very poor adherence in LF group
Protein intake higher in LC group
Dansinger
Self-selected adherence for last 10 months, therefore likely poor adherence
Shai
Protein intake higher in LC group
Brinkworth
Diets were isocaloric
Foster
?
Lim
?
Bazzano
Protein intake much higher in LC group
Iqbal
Very poor adherence to diets in both groups (no difference between groups regarding diet)
 
Protein intake may be a major factor in explaining this.  In 3/4 of the trials in the first column the low carb group had a higher protein intake (we aren’t given any dietary intake information in Foster).  Whereas only 1, maybe 2 (but not a big difference), of the trials in the second column had a higher protein intake in the low carb group and the diets in Brinkworth were isocaloric which explains the lack of difference between the groups anyway.
 
 
* When considering these results it’s important to remember that the carbohydrate intake in the low carb group was ~30-40% of total calories (rather than 20-50g) in all trials except Stern (251g to 120g carbs at 12 months) and Brinkworth (9% carbs at 12 months).  This means that generally these trials didn’t really test a true low carb diet (which I define as ~25% of total calories or ~100-150g) or a very low carb or ketogenic diet (where carbohydrate intake is ~10% of total calories/~50g or less).

Saturday, October 18, 2014

Low Carb Diet Trials: Bazzano, et al (2014)

 
Participants and Diets
 
148 people (mean age, 46.8 years; 88% female; 51% black) with a BMI of 30-45 and without CVD and T2D were randomised to a low carb diet or a low fat diet.  The groups were similar at baseline (Table 1)
 
Low Carb
Low Fat
<40g Carbs (excluding fibre)
Fibre 25g, prefer MUFA, limit/eliminate TFA
<30% Fat, <7% SFA, 55% carb
Fibre 25g, prefer MUFA, limit/eliminate TFA
 
“We also provided 1 low-carbohydrate or low-fat meal replacement (bar or shake) per day to participants in each group for the duration of the study”
 
“Participants met with a dietitian in weekly individual counseling sessions for the first 4 weeks, followed by small group counseling sessions every other week for the next 5 months (a total of 10 sessions) and monthly for the last 6 months of the intervention.”
 
 
Low Carb
Low Fat
Pro:Fat:Carb
Δ Calories
Pro:Fat:Carb
Δ Calories
Baseline
17:33:48
0
18:35:46
0
3 Months
26:43:29
-740
19:28:53
-616
6 Months
26:43:28
-674
18:28:52
-553
12 Months
24:41:34
-550
19:30:54
-507
 
Physical activity levels were similar throughout the study.  For more detailed info on nutrient intakes see table 2 below
 

Results
 
Both groups maintained significant weight loss at 12 months and the low carb group lost significantly more weight at all time points.  The weight loss in the low carb group came largely from fat loss as the % of lean body mass increased.  Whereas in the low fat group the % of lean and fat mass didn’t change.
 
 
 
At 12 months the low carb group had greater improvements in HDL-C, triglycerides, the TC:HDL-C ratio and the Framingham Risk Score.  In addition
 
  • There was no significant change in TC or LDL-C
  • Systolic blood pressure was significantly lower in both groups at 3 and 6 months, but was not maintained at 12 months
  • Diastolic blood pressure was significantly lower in the low carb group at 3 and 6 months
  • CRP slightly increased in the low fat group (NS) and slightly decreased in the low carb group (NS).  The difference between the groups was significant
  • Creatinine was significantly decreased in both groups at 12 months, perhaps indicating improved kidney function
 
 
75% completed the trial in the low carb group and 73% completed in the low fat group.  There were no differences between the groups regarding ‘symptoms’ except more participants in the low fat group reported headaches at 3 months

Wednesday, October 8, 2014

Low Carb Diet Trials: Iqbal, et al (2010)

 
Participants and Diets
 
144 people with obesity and T2D were randomly assigned to a low-carbohydrate or to a low fat diet.  The groups were similar at baseline except that the low carb group had more women and African Americans (who were well represented in this trial), whereas the low fat group had more people with high cholesterol.
 
Low Carb
Low Fat
30g of carbs.  Whole grains and high fibre carbs were encouraged
No restriction on fat and calories.  MUFA and PUFA were encouraged, SFA and TFA to be minimised
≤30% Total fat, <7% SFA
500 calorie deficit
Fruits and vegetables were encouraged
 
They described this trial as a low intensity intervention.  “Both diet groups were invited to attend separate weekly 2-h nutrition education classes for the first month. Thereafter, participants were provided sessions every 4 weeks for the duration of the study”
 
 
Low Carb
Low Fat
Pro:Fat:Carb
Δ Calories
Pro:Fat:Carb
Δ Calories
Baseline
19:40:40
0
18:39:43
0
6 Months
20:43:35
-201
21:37:42
-410
12 Months
20:36:40
-348
20:36:43
-516
24 Months
17:34:48
-397
18:34:47
-571
 
“There were no differences between groups in the amount of self-reported physical activity at any time point (P > 0.14).”
 
Results
 
Not unexpected from the poor adherence and lack of difference in dietary intake between the groups, both groups didn’t lose much weight and there were no significant differences between the groups.  Perhaps due to the poor weight loss overall, there was no correlation between number of sessions attended with weight loss.
 
 
 
There wasn’t much change in metabolic risk factors for CHD and no significant difference between groups or compared to baseline
 
  

“76 participants (52.8%) did not complete the 24-month study. A higher attrition rate was seen in the low-carbohydrate than in the low-fat condition (60.0% vs. 46.0%, respectively), but it was not statistically significant (P = 0.09).”

Sunday, September 28, 2014

Low Carb Diet Trials: Foster, et al (2010)

 
Participants and Diets
 
307 middle-aged (average age 45.5±9.7) people (99 men, 208 women) with obesity (average BMI 36.1±3.5) were randomised to follow either a low carb diet or a low fat diet.  “All participants received comprehensive behavioral treatment to enhance weight loss associated with both diets”.  The groups were similar at baseline (table 1)
 
Low Carb
Low Fat
Unrestricted fat and protein to eat until satisfied
Limit carbs to 20g/d for first 12 weeks (carbs from low GI vegetables).  Then increase 5g/d per week (more vegetables, small amount of fruit, whole grains and dairy)
Multivitamin
Calorie restriction (1200-1500 women, 1500-1800 men)
15P:30F:55C
Multivitamin
 
Unfortunately, we aren’t told what the groups actually ate, but we are told that the low carb group had more positive results for urinary ketones at 3 months (63% vs. 20%) and 6 months (28% vs. 9%) but not afterwards.  This isn’t surprising given the advice to increase carbs after 12 weeks but may also involve a decline in adherence over time
 
Results
 
Both groups lost ~11% of their initial weight at 6 and 12 months and then regained, achieving a weight loss of ~7% at 24 months.  There were no significant differences in weight loss between the groups at any time point except for greater weight loss in the low carb group at 3 months (table 2).
 
  
The changes in blood lipids were largely what you would expect: the low carb group had a greater increase in HDL-C at all time points and had had greater reductions in triglycerides at 3, 6 and 12 months.  LDL-C decreased in the low fat group whereas LDL-C increased in the low carb group at 3 months, was back to normal at 6 months and was lower at 12 and 24 months.  The lack of difference between the groups in LDL-C and triglycerides at 24 months is probably due to adherence (table 2).
 
Both groups had reductions in systolic and diastolic blood pressure and the low carb group and greater reductions in diastolic blood pressure at 3, 6 and 24 months.  There were no differences between the groups at any time point regarding bone mineral density in the spine and hip, lean mass lost and fat mass lost (table 2).
 
 
 
“A significantly greater percentage of participants who consumed the low-carbohydrate than the low-fat diet reported bad breath, hair loss, constipation, and dry mouth (Table 3). Except for constipation, all of these differences were limited to the first 6 months of treatment”
 
“Attrition included participants who withdrew and intermittent missingness at each time point. In the low-fat group, 6%, 12%, 25%, and 32% of participants did not participate in assessments at 3, 6, 12, and 24 months, respectively. Values for the low-carbohydrate participants were 9%, 16%, 26%, and 42%, respectively (Figure 1)”

Sunday, September 21, 2014

Low Carb Diet Trials: Lim, et al (2009)

 
Participants and Diets
 
113 people with a BMI 28-40 and aged 20-65 and with at least one CVD risk factor other than obesity were randomised to one of 4 diet groups:
 
1.      Very low carbohydrate diet (VLC)
2.      Very low fat diet (VLF)
3.      High unsaturated fat diet (HUF)
4.      Control
 
At baseline there were no differences between the three experimental groups (VLC, VLF, HUF), but the control group had lower total cholesterol, ApoB, SBP and DBP (Table 1).  The 3 diet groups received intensive support for the first 3 months then asked to maintain the diet for an additional 12 months
 
Pro:Fat:Carb (SFA)
VLC
VLF
HUF
3 Months
31:54:12 (17.7)
20:13:66 (5.1)
21:28:49 (6.0)
6 Months
24:39:33 (13.9)
21:26:51 (10.2)
21:28:48 (9.4)
9 Months
22:37:39 (14.0)
19:27:53 (11.1)
21:29:50 (10.1)
12 Months
21:39:38 (14.4)
22:27:51 (10.4)
20:29:48 (11.1)
15 Months
24:38:37 (13.2)
20:28:51 (10.7)
24:30:43 (9.9)
Target
35:60:4 (20.0)
20:10:70 (3.0)
20:30:50 (8.0)
 
Calorie Intake
VLC
VLF
HUF
3 Months
1848
1679
1837
6 Months
1767
1672
1547
9 Months
1628
1801
1688
12 Months
1853
1895
1708
15 Months
1641
1903
1581
Target
1560
1560
1560
 
Notably the groups had very good adherence to the diets at 3 months, which declined when the intensive support was gone
 
Results
 
The three diet groups had greater weight loss than the control group but there weren’t significant differences between groups (although at 15 months HUF was close with p = 0.065 vs. VLF)
 
Weight Loss (kg)
VLC
VLF
HUF
3 Months
−8.0 (2.8)
−6.7 (3.5)
−6.3 (2.9)
15 Months
−2.9 (4.9)
−2.1 (4.7)
−3.9 (6.3)
 
 
Below is table 3 (except weight loss).  ‘d’ refers to changes compared to baseline; ‘x’ and ‘y’ refer to significant differences between groups.  I’ve bolded cells containing those letters.  Overall there weren't much of difference between groups or compared to baseline, with most happening at 3 months, except blood pressure, which improved quite a bit at 15 months
 
 
VLC
VLF
HUF
Cholesterol, mmol/L
3 months
0.1 (1.1)
−0.5 (0.8)
−0.5 (0.6)
15 months
−0.4 (0.8)
−0.3 (0.8)
−0.3 (1.2)
HDL-C
mmol/L
3 months
0.1 (0.2)x
−0.1 (0.2)y
−0.1 (0.2)y
15 months
0.1 (0.3)
0.1 (0.3)
−0.1 (0.2)
LDL-C
(mmol/L)
3 months
0.3 (1.0)x
−0.4 (0.6)y
−0.6 (1.1)y
15 months
−0.3 (0.7)
−0.3 (0.7)
−0.1 (1.1)
Triglyceride
mmol/L
3 months
−0.7 (0.6)x
−0.1 (0.6)y
−0.2 (0.5)y
15 months
−0.2 (0.7)
0.1 (0.9)
−0.3 (0.8)
Chol:HDL
3 months
−0.2 (0.2)
−0.2 (0.1)
−0.2 (0.2)
15 months
−0.2 (0.2)
−0.3 (0.1)
−0.02 (0.4)
Trig:HDL
3 months
−0.6 (0.1)x
−0.03 (0.1)y
−0.04 (0.1)y
15 months
−0.09 (0.2)
0.05 (1.8)
−0.1 (0.2)
ApoB
g/L
3 months
−0.1 (0.3)
−0.1 (0.2)
−0.1 (0.1)
15 months
0.1 (0.3)
−0.1 (0.2)
−0.1 (0.3)
CRP
mg/L
3 months
1.2 (12.2)
0.3 (5.0)
−0.5 (3.2)
15 months
−1.7 (6.7)d
−2.1 (2.5)d
−1.8 (3.1)
Folate
nmol/L
3 months
−0.7 (4.2)
3.6 (6.2)
0.9 (8.4)
15 months
−1.3 (8.9)
0.1 (9.2)
−6.0 (8.7)d
Homocysteine
μmol/L
3 months
0.6 (1.4)x
−0.5 (1.5)y
0.1 (1.1)xy
15 months
0.4 (1.2)
−0.6 (1.1)d
0.1 (1.2)
Vitamin B12
pmol/L
3 months
6.8 (61.4)
−4.6 (49.1)
−4.1 (78.7)
15 months
33.5 (76.9)d
18.9 (66.9)
41.9 (73)d
Fasting insulin
mU/L
3 months
−3.9 (3.7)x
3.0 (13.8)y
−1.8 (2.7)x
15 months
−1.5 (4.4)
0.5 (5.5)
−1.7 (4)
Fasting glucose, mmol/L
3 months
−0.1 (0.3)
0.1 (0.6)
−0.2 (0.4)
15 months
0.1 (0.3)
0.3 (0.6)
−0.4 (1)
SBP
mmHg
3 months
−10.5 (12.7)
−7.1 (12.6)
−3.1 (14.5)
15 months
−10.6 (10.6)d
−6.0 (13.3)d
−5.4 (13.3)
DBP
mmHg
3 months
−3.8 (9.5)
−2.1 (11)
−2.0 (9.3)
15 months
−6.6 (12.1)d
−7.5 (8.7)d
−9.0 (9.3)d
 
“The attrition rate was 43%, 40%, 50% and 17% for VLC, VLF, HUF and the control group respectively (P = 0.098).”