Saturday, October 31, 2015

Addressing Some Questions from my Presentation: Part 2

The Importance of Total Mortality

To save time I only presented results for major coronary events, but not coronary mortality and total mortality.  But both coronary mortality and total mortality are both important to determine whether an intervention is effective.  Consider the following scenarios


RR for
CHD Events
RR for
CHD Mortality
RR for
Total Mortality
Scenario 1
0.90
0.90
1.00
Scenario 2
0.90
1.00
1.00

Which treatment would you prefer?  I would prefer scenario 2

In scenario 1 there are less CHD events and mortality in experimental group.  But because total mortality is the same, there is more non-CHD mortality in the experimental group, and therefore non-CHD events is also likely to be higher

In scenario 2 there are less non-fatal CHD events in experimental group, but no difference in CHD mortality, non-CHD mortality and total mortality.  Therefore it’s unlikely for there to be a difference in non-fatal non-CHD events

To summarise:


CHD
Events
CHD
Mortality
Non-CHD
Events
Non-CHD
Mortality
Total
Mortality
Scenario 1
Down
Down
Up???
Up
Equal
Scenario 2
Down
Equal
Equal???
Equal
Equal

Therefore:


Morbidity
Mortality
Scenario 1
Likely Equal
Equal
Scenario 2
Likely Down
Equal

When pooling the results from all the saturated fat vs. polyunsaturated fat trials together the results are like scenario 1.  People who promote the replacement of SFA with PUFA like to cite the Mozaffarian meta-analysis.  This is probably because of its large and significant risk reductions for coronary events and coronary mortality.  However, that meta-analysis found no benefit for total mortality.  And so with this information such an intervention wouldn’t be worth our time because total mortality is the same and the benefit of quality of life from reduction of CHD events is likely to be offset by the loss of quality of life from the increase in non-CHD events

Saturated Fat and Inflammation

I was asked about whether saturated fat increases inflammation.  This is certainly an interesting and relevant question.  My understanding is that most of evidence here comes from: (1) cell culture studies where very high levels of saturated free fatty acids are added to induce inflammation; (2) and animal studies (see below); and (3) studies measuring postprandial inflammation, which probably has more to do with the presence or absence of beneficial substances (blog)

The animal studies used as evidence that saturated fat is inflammation usually involves putting mice who are genetically susceptible to obesity from a high fat diet (C57BL/6 mice) on a high fat diet.  It doesn’t seem to matter whether the fat comes from SFA, MUFA or n-6 PUFA, all are inflammatory for these mice (MCTs and n-3 PUFA tend not to be).  On such high fat diets these mice dramatically overeat and develop impaired glucose tolerance, insulin resistance and hypothalamic inflammation in a few days to a week, before obesity has time to develop.  Chronic systemic inflammation usually develops later

Despite these high fat rodent diets being high in SFA and MUFA, due to the regular use of lard, it’s often SFA that get the blame.  However, these animals likely become inflamed and develop those health problems simply because a fat intake of at least 40% of total calories is inappropriate for their physiology.  The proportion of energy from fat in rodent high fat diets is often 40% and sometimes 60%.  Notably 40% fat is about the proportion of energy from fat in the Mediterranean diet.  Clearly the Mediterranean diet does not have these effects 

The purpose of animal studies is not to provide specific dietary advice for humans, but rather to test mechanisms in a controlled way

5 comments:

  1. Interesting that you mention the saturated fat: inflammation interplay. My own research group did a study (not published yet) in which a diet shift from 30%E fat to 45%E fat was evaluated. The additional 15 %E of fat were mainly derived from saturated fats which finally contributed 15-20% of total energy. What we can see is that plasma CRP rises, together with inflammatory markers in adipose tissue, including evidence of macrophage infiltration. However, the intervention study only lasted for 6 weeks. So, I am not sure whether this is just an acute response (or who knows a hormetic response even..)

    Cheers
    Thomas

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    Replies
    1. Hi Thomas, that's interesting. I'm wondering whether calorie intake and food quality were roughly the same in each group

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    2. Thomas, your results are unique, because all the chronic dietary studies I've seen that measured CRP (a dozen or so) have not found increases in CRP due to increased SAFA intake. Therefore, it would be interesting to know the details and circumstances of the experiment.

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  2. I wouldn't be too much concerned about the CRP data, now that I che3cked it a second time. Actually, it just rises from <1mg/L to roughly 1.6 mg/L which is not a dramatic increase, albeit statistically significant. The study involved about 80 participants (monozygous and dizygous twin pairs - study interest was heritability of the metabolic response). Metabolic characterization took place after 6 wks of carb-rich diet, after 1 wk of HFD and after 6 wks of HFD. The carb-rich diet followed the advice for a healthy diet (German Nutrition Society). Nutritional counselling also was provided for the weeks under HFD. During the week before each clinical investigation day, foods were provided to the participants that ensured some extra adherence to the diets (standardization). I am sorry that I am not able to give more information as I was not involved in the study. Dietary records exist, but I doubt that food quality was assessed in a quantitative and objective manner.

    Cheers

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    Replies
    1. Thanks Thomas, you're probably right, CRP statistically significant but perhaps not clinically significant. I'll check the paper out when it gets published.

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