Sunday, November 22, 2015

Is Saturated Fat Associated with Cholesterol Levels in Cohort Studies? Part 2

In part 1 I mentioned that people have argued that in ‘observational studies performing a multivariate analysis that includes cholesterol levels is over-adjustment for the relationship between saturated fat and coronary heart disease and then listed many that cohort studies haven’t actually reported the baseline relationship between saturated fat and cholesterol levels.  The saturated fat intake and cholesterol levels in the studies that reported them are presented in the table below

Quintile/Quartile
1
2
3
4
5
P Value
HPFS [5] Table 1
(g/day & mmol/l)
15.9
21.5
24.8
27.7
32.4

5.2
5.3
5.3
5.3
5.3
???
(g/day & mmol/l)
5.0
8.5
11.9
18.3


4.81
4.82
4.95
5.07

< 0.001
JPHC [27] Table 1
(g/day & mg/dl)
9.6
13.4
16.3
19.4
24.9

203±36
206±36
207±35
208±35
209±34
< 0.001
Kuopio [29] Suppl 2
(g/day & mmol/l*)
32.3
42.4
53.0
66.8


6.06
6.11
6.24
6.38


* Calculated from average HDL-C and total-C:HDL-C values.  Association between saturated fat with both LDL-C and HDL-C in Kuopio was significant

HPFS found no association between saturated fat and cholesterol levels, whereas the other three cohorts did.  Yet even when saturated fat intake is associated with cholesterol levels, the difference between the top and bottom quartile/quintiles is a lot smaller than expected considering the large difference in saturated fat (even considering the higher intake of PUFA).  The only other study that reported a relationship between saturated fat intake and cholesterol levels just correlated the two variables instead of reporting the data in quintiles/etc as is typically done in more modern observational studies.  This paper (published in 1981) also discusses that associations between saturated fat and cholesterol in cross-sectional studies are inconsistent.  So clearly there have been more studies that looked at this if you’re interested and that the evidence seems to be inconsistent and seems to have been for some time

There are some explanations for this:

1) Some people have commented that a reason saturated fat may not be associated with cholesterol levels in observational studies is because of the large inter-individual variation in cholesterol levels that makes statistical significance so difficult.  I don’t think this is a good explanation because having a very large sample size, which is necessary for this kind of observational study, means that even a small difference despite large inter-individual variation would still highly significant.  An example of this is the JPHC study in the table above with a weak, yet still significant relationship between saturated fat intake and cholesterol levels because those cholesterol measurements came from 8765 men and 16047 women

2) The feeding studies are confounded by trans fats, dietary cholesterol, phytosterols and other phytochemicals, fibre, etc.  Or perhaps that the effects seen in short term feeding studies aren’t really long term and are compensated for quite slowly by feedback mechanisms

3) It’s interesting that in the NHS and HPFS that saturated fat intake is associated with a lower incidence of ‘hypercholesterolemia’.  Perhaps there is some reverse causality going on whereby people with genetically high cholesterol are informed of this and change their diet accordingly, but still have somewhat cholesterol levels despite a low intake of saturated fat.  This would explain how the relationship between saturated fat and cholesterol levels was absent in the HPFS and less than expected in the other three cohorts.  The NHS and HPFS are nurses and ‘health professionals’ and so presumably quite health conscious, which may explain how there was no relationship between saturated fat and cholesterol levels in the HPFS (more health consciousness >> more reverse causality) whereas the other three cohorts had a weak relationship (less health consciousness >> less reverse causality)

Anyway, the argument that ‘a multivariate analysis that adjusts for cholesterol levels is an over-adjustment’ should be taken with a grain of salt until relevant figures are provided

Finally, whether or not saturated fat intake is associated with higher cholesterol levels in the long term doesn’t necessarily invalidate your response.  A lot of science (clinical trials, observational studies, etc) is based on averages and your response could be quite different to the average

No comments:

Post a Comment