Monday, April 21, 2014

High This, Low That

“The beginning of wisdom is the definition of terms”
- Socrates
High carb, low fat, moderate protein.  These are words to describe diets, but what do they mean?  The problem is that it really depends on how ‘high’, ‘low’ and ‘moderate’ are defined*.  For example: the Zone (30P:30F:40C) has been called a low carb diet, but is 40% carbohydrate really low?  Or is it simply ‘lower’ than the conventional guidelines and so should be described as a 'lower carb' diet. 

I’m going to propose some definitions for ‘high’, ‘moderate’ and ‘low’ to clear this up and base it on simplicity and some observations 

  • ~10% protein is essentially the RDI for the average person, which is the sufficient intake to meet nutrient requirements of 97-98% of the population [1]
  • Modeling has suggested that at least 15% protein is required to obtain sufficient micronutrients [2]
  • The recommended protein intake for chronic disease is 15-25% [1]
  • Protein intakes of 30-40% (depending who you speak to) and greater are thought to exceed the body’s ability to metabolise protein and/or get rid of urea
  • The average protein intake in Australia in about 16.5% [3].  You could argue that protein intake would be slightly higher if 35% [4] of calories didn’t come from junk food (high in refined grains (~10%), added fats and added sugar) 

Very Low
Very High

  • If moderate protein is 20% then it would be nice if moderate carbs + fat = 80%
  • There is an ongoing debate as to whether fat or carbohydrate is generally healthier.  At this point I don’t know, and probably no one does
  • Eating ~0% fat or carbs is doable (no need for dietary carbs, PUFA requirement is extremely low), although very restrictive and probably not too healthy.  Anyway, it would be more accurate to refer to such a diet as zero fat/carb
  • In PHD, the Jaminets calculated carbohydrate requirements (dietary or not, in the absence of ketosis) to be approximately 30% [5] 

Very Low
Very High

There are two main issues with this kind of classification: 

1.     A 1% increase in carbs from 47% to 48% magically results in the diet changing from a moderate carb diet to a high carb diet.  This is silly.  Think of the cut-off points not as thresholds, but as gradients
2.     These numbers are proportions, not absolute amounts.  The absolute amounts are more important to determine whether you’re getting enough of something.  In some circumstances the % can be misleading.  For example: an athlete on a low carb diet may eat more carbs than an inactive elderly person on a high carb diet like the dietary guidelines (45-65%) 

Finally ‘high’, ‘low’ and ‘moderate’ aren’t some judgment of whether a diet is ‘good’ or ‘bad’ 

* The field of diet is full of people using ambiguous labels to promote an agenda, for example: veg*ns say the SAD is high in animal protein and fat; mainstream dieticians say the SAD is high in red meat, SFA and salt; low carbers say the SAD is low fat and high carb; and everyone says the cliché of the SAD being high in sugar, fat and salt (if they choose their words poorly they might imply salt contains calories).  I heard a dietician say Australians eat a high meat diet and handed out some information suggesting we should eat 1 serve of meat per day.  You shouldn’t be surprised when you conclude that Australians eat a ‘high meat diet’ if you define ‘high meat’ as > 1 serve/day

Wednesday, April 16, 2014

The Women's Health Initiative

Studies Associated with the Trial 

The evolution of the Women's Health Initiative: perspectives from the NIH (1995) [1] (no access)
Design of the Women's Health Initiative clinical trial and observational study (1998) [2]
Low-fat dietary pattern and risk of cardiovascular disease: the Women's Health Initiative Randomized Controlled Dietary Modification Trial (2006) [3] (this post only used this study) 

Participants and Diets 

48835 post-menopausal women, between 50-79, of diverse backgrounds and ethnicities were randomised to either a low fat diet or a control group. 

The low fat diet was intended to reduce total fat intake to 20% of calories and increase intakes of vegetables/fruits to 5 servings/d and grains to at least 6 servings/d”.  The comparison group received diet-related education materials”.  The low fat diet wasn’t calorie restricted, didn’t set weight loss goals, and didn’t try to alter fat composition. 

The groups were very similar at baseline, which is what you would expect with that many participants.  There was a significant difference in aspirin use, but I don’t think 17.4 vs. 18.1 is very noteworthy, which goes to show how much easier it is to attain statistical significance with a larger sample.  This leads me to the next point 


There were a few statistically significant differences between the groups in how the CVD risk factors changed over the 3 years, all in favour of the low fat group.  Once again, most of them aren’t that noteworthy as you can see below.  There was no difference in SBP, trigs, markers of IR and fibrinogen* 

3 Years
Low Fat
Low Fat
Physical Activity (METs/week)
Diastolic Blood Pressure
Total Cholesterol (mg/dl)#
LDL-C (mg/dl)#
Total Carotenoids (µg/mL)
Factor VIII* (%)
* Increases blood coagulation in response to injury
# P < 0.001 

Nutrient intake changed the way you would expect.  The low fat group increased protein, carbs, fibre, folate and servings of fruits and vegetables and grains; while decreasing total fat (and all types roughly in proportion), dietary cholesterol and nuts.  They achieved the target for fruit and vegetables and were close to the fat target after 1 year, but compliance got worse as the study went on and they actually consumed fewer grains at 6 years than at baseline.  The control group also made similar changes in the diet but to a much lesser extent** 

1 Year
6 Years
Total Fat (%)
(Expected: 7.0)
Serves of Fruit & Vegetables
Serves of Grains
(No Target)

The low fat group tended to have fewer CVD endpoints, but none of the differences were significant
After doing a subgroup analysis the researchers found that those with hypertension were more likely to benefit from the LF diet and those with a history of CVD (3.4% of the women) were more likely to have an CVD endpoint on the LF diet (HR=1.26, CI=1.03-1.54, P<0.006) (I’ve got no idea why that’s the case) 

In summary, a low fat diet with more fruits and vegetables had a minimal effect on CVD risk factors and didn’t significantly reduce CVD in post-menopausal women 

* The low fat group had a modest weight loss and improvement in blood lipids which is contrary to ideas that low fat is responsible for the obesity epidemic and ruins blood lipids (mainly triglycerides).  It depends on what the fat in replaced with, and in this case the fat seems to be replaced by fruits and vegetables at least to some extent 

** Since refined grains are nutrient poor and most of the grains eaten by these women were refined, it’s surprising that there was no specification for whole grains 

*** In the subgroup analysis they also found that those who consumed less SFA and TFA and/or more fruits and vegetables had lower LDL-C levels and rates of CHD.  As I usually say, associations of this kind are probably just markers of compliance

Sunday, April 6, 2014

Low-Fat Diet in Myocardial Infarction (Ball, et al)

Low-fat diet in myocardial infarction (1965) 

Participants and Diets 

264 men, under 65, who had recently had their first heart attack, were randomised to one of two diet groups: a low fat diet or the control diet.  The low fat diet group were advised to eat only 40g of fat per day.  “The daily allowance included 14 g. (1/2 oz.) butter, 84 g. (3 oz.) of meat, 1 egg, 56 g. (2 oz.) cottage cheese, and skimmed milk. The nature of the fat consumed was not altered, nor were any additional unsaturated fats given”
We have a limited amount of data on what they actually ate, but we’re told the low fat group had a large reduction in fat (~ 45g vs. 110-130g*) and ate fewer calories (~ 1900-2000 vs. 2300-2600) compared to the control group

Those who were overweight (21% of controls and 15% of LF group) were put on calorie restricted diets.  In the control group the calories that were restricted mostly came from carbohydrate instead
* Even though they didn’t meet the target of 40g, it’s a good effort considering “the diet was often unpleasant” and there was a large difference between the groups
Both groups, particularly the low fat group, lost weight and lowered their cholesterol.  (The reduction of cholesterol in the control group may have been due to weight loss) 

Low Fat Diet
Control Diet
Total Cholesterol
6 Months
4 years
6 Months
4 years
* This difference was almost significant (01 > p > 005)
** Unfortunately we aren’t told whether the differences were significant, but they probably were
Ultimately though, despite the large difference in fat consumption and the reduction in cholesterol levels, there was no difference in either relapses or death, both in the general study population (table VII), and among those with severe CHD (table VIII).  (Fortunately the people who assessed the CHD events in this trial were blinded)

Also, “the mean follow-up time to first relapse or end of trial was 3-04 years for the low-fat group, and 3-05 years for the control group”.

One might argue that the lack of difference was because the low fat group almost doubled their intake of added sugar, but the researchers found that carbohydrate and added sugar consumption wasn’t associated with relapses.  Although if you ignore the 0-5 g/day group in table VI (which I find difficult to believe) there’s a trend, but it’s not that exciting

Sunday, March 30, 2014

Low Fat and CHD

I originally didn’t think about writing on low fat and CHD because I didn’t see the point.  After all, throughout the literature and the dietary guidelines there was no suggestion that low fat diets would reduce the risk of CHD.  But then I don’t subscribe to pop science, where calories make you fat, protein damages your kidneys, fat clogs your arteries, carbs give you diabetes and everything causes cancer.  For most people fat (of any kind) still remains the villain in CHD. 

Remember that the three main lines of evidence against saturated fat were: 

1.      Observational studies
2.      Clinical trials measuring blood lipids
3.      Clinical trials measuring end-points (events and mortality) 

I’m going to briefly go through each of these as they relate to low fat and CHD 

Observational Studies 

The Australian National Heart Foundation’s ‘Summary of evidence. Dietary fats and dietary cholesterol for cardiovascular health’ (2009) cites a review by Mozaffarian as evidence for “there is no direct relationship between total fat intake and the incidence of CHD”. 

The Australian Heart Foundation later use a meta-analysis of cohort studies by Jakobson, et al as evidence against saturated fat.  The Jakobson, et al meta-analysis found that replacing SFA with PUFA was associated with less CHD events and death, but replacing SFA with MUFA or carbohydrate had no effect* [1]. 

Another meta-analysis of cohort studies by Skeaff & Miller found that intake of total fat wasn’t significantly associated with CHD events or CHD mortality [2]. 

And finally, there’s also the well-known meta-analysis of cohort studies by Siri-Tarino, et al, which found “no significant evidence for concluding that dietary saturated fat is associated with an increased risk of CHD or CVD” [3] 

* So if you’re going to debate the National Heart Foundation I don’t think you should spend much time arguing against low fat diets, because they will simply say that they don’t recommend a low fat diet, which is exactly what they did on Catalyst.  I would rather argue that (1) it’s unwise to make recommendations from observational studies and clinical trials measuring blood lipids; and (2) the better controlled fat modification trials don’t support the DHH and suggest some harm.  If you want to argue that they are recommending a low fat diet (because it seems most people challenging mainstream advice are pro-low carb), please define what ‘low fat’ means (I’ll be providing my take in a future post), otherwise it’s going to be one of those pointless ‘yes you are, no I’m not’ type of debate 

Clinical Trials Measuring Blood Lipids 

Two meta-analyses of clinical trials found that replacing fat with carbohydrate increases the total cholesterol to HDL-C ratio* [4] [5], which is perhaps the best CHD risk factor based on blood lipids [6]
* Only palmitic acid and artificial TFA increased the ratio, but the fats in food are comprised of many different fatty acids so even fat sources high in palmitic acid and/or artificial TFA like butter, shortening and palm oil reduce the total cholesterol to HDL-C ratio relative to carbohydrate 

** They also found replacing fat with carbohydrate increased triglycerides [4] [5] 

Clinical Trials Measuring End-Points (Events and Mortality) 

But we shouldn’t dismiss low fat diets based on findings of observational studies and their effect on blood lipids.  Just as it’s wrong to use observational studies to ‘prove’ there is an effect, it’s also wrong to use them to ‘prove’ there isn’t one either 

To my knowledge, there are two main meta-analyses looking at low fat (fat reduction) and CHD: the same Hooper, et al meta-analysis and the meta-analysis by Skeaff & Miller (who also did one for the fat modification trials*).  The results of the meta-analyses are in the table below: 

CHD Events
CHD Mortality
Total Mortality
Hooper, et al
0.97 (0.87, 1.08)
0.96 (0.82, 1.13)
0.97 (0.90, 1.04)
Skeaff & Miller
0.93 (0.84, 1.04)
1.00 (0.80, 1.24)
0.98 (0.90, 1.06)

Skeaff & Miller only included a trial by Ball, et al and the Women’s Health Initiative (WHI), while Hooper, et al included several others that were either very small (only a few events or deaths in each group), for cancer (mostly breast cancer and one bowel cancer) and one (the DO IT trial) that looks more like a fish oil trial.  So I’m only going to do Ball, et al and the WHI. 

This won’t limit me (or Skeaff & Miller) that much.  The WHI was a huge trial, lasting 8.1 years with 46,558 participants.  Consequently the WHI has well over 50% of the weighting in statistical analyses, which is probably a main reason why the results of the two meta-analyses are so similar, even though Hooper, et al included several other trials 

* They included Rose (but only compared olive oil to corn oil), LA Vets, MRC, Oslo, Finnish, DART and STARS and found for: CHD events RR = 0.83 (0.69, 1.00), p = 0.073; CHD mortality RR = 0.84 (0.62, 1.12), p = 0.335; and total mortality RR = 0.88 (0.76, 1.02), p = 0.005.  The somewhat positive result isn’t surprising considering their poor trial selection (pretty much as bad as Mozaffarian, et al) 

** My main objection to the fat modification trials was that the trials changed a lot more than SFA and PUFA intakes.  Some accidental changes would be expected when you make a dietary change.  For example: you would expect the control group (higher SFA) to have a higher vitamin A and cholesterol intake and the experimental group (higher PUFA) to have a higher vitamin E intake.  Other changes, like the amount of hydrogenated oil and junk food, is not expected and makes for a poorly controlled trial.  In the fat reduction trials you would expect the low fat diet would have more accidental changes, like increasing intake of vegetables, fruit and grains, as a function of increasing carbohydrate intake 


Despite the dogma that ‘fat will clog your arteries’, low fat diets wouldn’t be expected to reduce CHD based on both observational studies and their effect on blood lipids.  Also, low fat diets haven’t been found to reduce CHD events, CHD mortality or total mortality in clinical trials.