Monday, December 29, 2014

Does Saturated Fat Impair Endothelial Function?

Saturated fat (SFA) is thought to impair endothelial function.  As far as I can tell there are two clinical trials looking at how endothelial function is affected when SFA is replaced with other macronutrients:
Study 1:
This study used a crossover design, where 40 healthy people were randomly allocated to either a high SFA, MUFA, PUFA or a low fat, high glycemic load (GL) diet for 3 weeks each diet.  The participants were given ‘test’ foods to manipulate the macronutrient composition of the diet.  The macronutrient composition of these test foods can be seen in table 1.
“Subjects returned at the end of each intervention for a fasting venous blood sample and weight, FMD, and PWV measurements.”
Test Food
50g Butter
20g High MUFA Margarine
45g Almonds
20g High PUFA Margarine
35g Walnuts
70g Sultanas
50g Jam
The high SFA diet reduced flow mediated dilation (FMD) (measure of nitric oxide bioavailability/endothelial function) (figure 1), didn’t alter pulse wave velocity (measure of arterial stiffness) (table 4) and increased some markers of inflammation (table 4 and figure 3).
They also measured blood lipids and insulin (table 3).  The effects on blood lipids were predictable and there were no significant differences in fasting insulin.  They didn’t find an association between blood lipids and FMD
Study 2:
This study put 121 people with mild insulin resistance on a high SFA diet (>15%) for 1 month, then randomised them to a high SFA, MUFA or carbohydrate diet for 24 weeks.  The difference between the diets is described in the methods section, which I’ve summarised below.  The macronutrient composition of the diet can be seen in table 2
“Participants were advised before each visit for the measurement of vascular function to avoid strenuous physical activity, foods high in fat, caffeine, or alcohol on the previous day; subjects were provided with a list of foods to avoid and a low-fat evening meal (<10 g fat; 2–3 MJ) before fasting overnight from 2200.”
“After the completion of an intravenous glucose tolerance test, as reported elsewhere (17), participants were provided with a low-fat meal (2 MJ; <5 g fat) and a drink of water, and measures of vascular function a ≥2 h later were made at St Thomas’ Hospital between 1400 and 1700; both baseline and follow-up measures were made at the same time of day to minimize diurnal variations.”
Test Food
Full fat milk and cheese
High SFA spread
Standard salad dressing
Skim milk and half fat cheese
High MUFA spread
High MUFA salad dressing
Nuts and potato crisps
Skim milk and half fat cheese
Reduced fat spread
Reduced fat salad dressing
Bread, potatoes and rice
There were no significant differences between the groups in all the measurements taken, which related to blood pressure, FMD, arterial stiffness and lipid peroxidation (table 3 and table 4).
* This trial also measured glucose tolerance and insulin resistance (by an intravenous glucose tolerance test rather than an oral glucose tolerance test), blood lipids and inflammatory markers, which was reported in another paper.  Once again, the effects on blood lipids were predictable and there were no differences on the other measures except that the low fat group lost weight and the change in weight was significantly different to the high SFA group, and the high SFA group significantly lowered their microalbumin:creatinine ratio (suggests improved kidney function) and the change was significantly different to the low fat group (table 2 and table 5)
The first study says SFA impairs endothelial function and second one says it doesn’t.  So what to do make of this?
In favour of the first study:
The first study’s methodology was more what I was expecting.  Whereas in the second study all the participants reduced their fat intake the day before and they did an intravenous glucose tolerance test and a low fat meal prior to the measurements of vascular function.  Both of these may have affected the outcome, particularly by reducing the differences between the groups.  It’s certainly odd that there were so few differences between the groups.
In favour of the second study:
Trying to isolate the effects of one nutrient in diet studies is very difficult.  The second study did this much better than the first study, which I thought did this quite poorly.  The first study can be viewed not as a comparison of macronutrients, but rather as a trial comparing butter to nuts and processed fruit.  This gives the MUFA, PUFA and GL groups in this study an unfair advantage as nuts and sultanas are whole foods and contain more micronutrients and other beneficial compounds than butter.  Even though the second study “…set out to test the hypothesis that decreasing SFA intake would improve vascular function. Our hypothesis was based on the belief that decreasing SFA intake would improve insulin sensitivity, which the main report showed not to be the case.”  They were critical of the first study saying that: “However, the interpretation of the results of that study were confounded by the use of high intakes of walnuts, almonds, and sultanas, which contain polyphenolic compounds that have antioxidant and other pharmacologic properties and can influence endothelial function (23).”  In support of this, adding walnuts to the diet improves endothelial function [2].
Does SFA impair endothelial function?  I don’t know, it’s hard to say from only two studies, particularly when each has problems.  I would guess probably not based on these studies and that there’s no good evidence that replacing SFA with MUFA, carbohydrate [3] [4] or PUFA [5] reduces cardiovascular disease.


  1. There was also that study Dr. Masterjohn analyzed -

    These are also interesting:

    "In the current study, whether the meal was rich in MUFA or SFA had no differential effect on either brachial or aortic systolic blood pressure. There was no evidence that replacement of some of the SFA with MUFA had a differential effect on arterial stiffness"

    "NEFA elevation during consumption of the SFA-rich drinks was associated with a marked impairment of FMD, whereas consumption of SFAs + LC n-3 PUFAs improved FMD response"

    "whipping cream alone or whipping cream together with either caseinate or soy protein...Summarizing, the impairment of endothelial function following a fat-rich meal can be cancelled out when protein is added to the meal"

    Other researchers would also agree that the evidence is insufficient:

    "In summary, consideration of the epidemiological evidence suggests an adverse effect of SFA and a beneficial effect of LA and ALA on vascular function, but the quantity and quality of the experimental evidence is not sufficient to support this convincingly"

    "The 12-week CRESSIDA study, which compared current UK dietary guidelines with a traditional UK diet also found no effect of SFA reduction on FMD (Sanders TAB, Reidlinger D, Darzi J, Hall WL, Chowienczyk PJ, unpublished results). Meals high in fat cause acute impairment of endothelial function compared with low fat, high carbohydrate meals (39,40) that appears to be related to the extent to which plasma TAG is elevated in the postprandial period which appears greater following MUFA than after SFA. Therefore, the current evidence indicates that SFA do not have specific adverse effects on FMD"

    Nevertheless, I'm not sure that acute effects on vascular function are harmful. By reducing fat intake the day before, it appears that the second study was measuring chronic effects.

    1. Thanks for those links Zahc. I should have emphasised more that this post was about long term trials (to look at chronic effects) rather than postprandial studies (of which there are many).

      I agree with the links you shared. It seems as though fat (by itself) impairs endothelial function postprandially, but there are so many nutrients and other beneficial compounds that can negate that effect. So having fat in junk food would make the junk food less healthy, but having fat in a whole food diet almost certainly won't have those negative effects

      With the first study, I agree that reducing fat the day before likely had little impact. My main concern was the IVGTT and the low fat meal prior to the measurements of endothelial function