Saturday, November 21, 2015

Is Saturated Fat Associated with Cholesterol Levels in Cohort Studies? Part 1

I previously discussed how in observational studies, when the participants are grouped by something like intake of saturated fat, the baseline characteristics of these groups of participants often differs in some respects.  In the case of saturated fat, those who ate more saturated fat tended to exercise less, smoke more, have lower diet quality (trans fats, whole grains), etc.  Observational studies now often adjust for these confounding variables in what’s called a multivariate analysis, which completely removed the previously highly significant association between saturated fat and coronary heart disease in the study (blog)

However, the reporting of multivariate adjusted risk ratios (RRs) has been criticised by a few people.  They argue that age-adjusted RRs show that saturated fat is associated with coronary heart disease, and that the multivariate adjustment is an over adjustment as it removes the relationship between saturated fat, total-C/LDL-C and coronary heart disease

I think this is a valid concern.  If I were only able to report one figure it would be multivariate without cholesterol levels, because total cholesterol is generally not that affected by other dietary/lifestyle factors or health status (whereas HDL-C and triglycerides tend to be very good markers of insulin resistance).  But why not report both: a multivariate adjustment with and without cholesterol levels?

But these people have made the assumption that saturated fat is associated with higher cholesterol levels, but from what I’ve seen so far there is a conspicuous lack of reporting of this in the observational studies.  This is quite suspicious as conventional nutrition/public health is completely obsessed with cholesterol levels and so if there was a relationship between saturated fat intake and cholesterol I’m sure this would be reported.  Interestingly in the two cohorts I mentioned previously (the Nurse’s Health Study and the Health Professionals Follow-up Study) saturated fat intake was associated with a lower incidence of ‘hypercholesterolemia’ (not sure how this is defined but may be > 240 mg/dl or > 6.3 mmol/l) although average or median cholesterol levels wasn’t reported (blog)

I’ve generally stayed out of the debate of whether saturated fat increases cholesterol.  Many studies suggest saturated fat increases both HDL-C and LDL-C, but doesn’t significantly alter the total-C:HDL-C ratio [1], although this has been debated [2].  But this got me curious: is saturated fat actually associated with higher cholesterol levels in observational studies?

I looked at the observational studies included by the Siri-Tarino (ST) [3] and de Souza (CHD events = DSE, CHD mortality = DSM) [4] meta-analyses.  The following table lists those studies and whether saturated fat intake was associated with cholesterol levels in each of these cohorts

Cohort
ST
DSE
DSM
Associated?
Health Professional’s Follow-up Study (HPFS) [5]
X
X
X
No
Health and Lifestyle Survey [6]
X

X
Not Reported*
Lipid research clinics prevalence follow-up study [7]
X

X
Not Reported
Multinational MONItoring of trends and determinants in CArdiovascular disease (MONICA) [8]
X
X

Not Reported
Honolulu Heart Program [9]
X
X

Not Reported
Strong Heart Study [10]
X
X
X
Not Reported
Framingham Study (1) [11]
X


Not Reported
Ireland–Boston Diet–Heart Study [12]
X

X
Not Reported
Malmö Diet and Cancer Study [13]
X
X

Not Reported
Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC) [14]
X
X
X
Not Reported
Framingham Study (2) [15]
X
X

Not Reported
Western Electric study [16]
X

X
Yes**
Baltimore Longitudinal Study of Aging [17]
X

X
Not Reported
Caerphilly Study [18]
X
X

Not Reported
Health professional follow up study (2) [19]
X


Not Reported
Fat and Protein Intakes and Risk of Intraparenchymal Hemorrhage among Middle-aged Japanese [20]
X


Yes
Nurses’ Health Study (1) (NHS) [21]
X


Not Reported*
Dietary determinants of ischaemic heart disease in health conscious individuals [22]
X

X
Not Reported
Nurse’s Health Study (2) (NHS) [23]
X
X

Not Reported*
Adult health study [24]
X


Not Reported
Israeli Ischemic Heart Disease Study [25]
X

X
No Access
Women’s Health Initiative (WHI) [26]

X

Inappropriate
Japan Public Health Center Study (JPHC) [27]

X

Yes
Zutphen Elderly Study [28]

X

Not Published
Kuopio Ischemic Heart Disease Risk Factor Study [29]


X
Yes
** Only reported a correlation and not by quartile/quintile

In summary most studies didn’t report whether people with a higher intake of saturated fat had level cholesterol levels.  Many of the studies were not specifically looking at saturated fat and coronary heart disease, so this is understandable.  Those marked with an asterisk (*) reported baseline characteristics for saturated fat intake but didn’t include cholesterol levels

I’ll discuss this in part 2

8 comments:

  1. I notice that the baseline characteristics in the Kuopio supplement show higher LDL and HDL for higher SAFA intake with no change in the TC/HDL ratio. Also, higher MUFA showed no association with LDL and the TC/HDL ratio, consistent with my claim that MUFA per se is not really a cholesterol lowering fat.

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    1. I started looking into this topic some time ago but eventually gave up, because as you noted, most studies did not report whether there was a relation or not. I thought that was strange also!

      I found another recent study showing a positive association between SAFA and cholesterol. It also found a positive relation between SAFA and ASVD mortality. However, it would be interesting to see the anti-SAFA folks citing this study, because neither total nor LDL cholesterol was associated with ASVD!







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    2. Forgot to link the study. See here - http://ajcn.nutrition.org/content/early/2015/05/06/ajcn.114.102392.short

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    3. Thanks, that's very interesting.
      Just a validated FFQ, and the cut-off for plausibility was 500 kcal/day. Surely anything under 1,400 or thereabouts should be implausible.
      No mention of food sources of SFA. No mention of trans fats or sugar.

      A likely explanation is that Perth women in this age group in high-SFA category consumed most SFA from commercial baked goods, such as sweet pastries and biscuits. They probably put a little skim milk in their tea while doing so. This placed them at different risk from say Nordic women eating lots of cream with their berries.

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    4. Geroge: "A likely explanation is that Perth women in this age group in high-SFA category consumed most SFA from commercial baked goods, such as sweet pastries and biscuits"

      Reminds me of the recent PREDIMED cohort. SAFA intake associated with CVD and total mortality, but when evaluated by food source SFAs from "pastries and other processed foods" were associated with harm whereas "No significant associations were found for SFAs from dairy products or from meat and processed meat and CVD and all-cause death" - http://www.ncbi.nlm.nih.gov/pubmed/26561617

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    5. I don't want to dismiss this study, because it gives an unexpected result, and I'd like to know why.
      But it is very poor at supplying data that might be used to make informed guesses about what was going on.
      Even compared to run-of-the-mill FFQ epidemiology from the past, this 2015 study seems to supply little information apart that needed to generate its conclusions.
      This is not good enough; are there better papers from this cohort?

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  2. Just book-marking a question this analysis reminded me of -
    There are low-carb studies where SFA is restricted and low-carb studies where SFA is not restricted.
    Some people believe dietary SFA affects insulin sensitivity, so is there any difference between glycemic control if low-carb studies that restrict SFA are compared with those that don't?
    Probably too much heterogeneity between studies for this at present. But a question that needs to be answered in some future trial.

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