Effects of C16:0 versus C18:0 on HDL metabolism and other cardiometabolic risk markers:
A dietary intervention study in healthy normal-weight and overweight subjects

Dietary recommendations to prevent coronary heart disease (CHD) are focused on
lowering cholesterol concentrations in the atherogenic low-density lipoproteins
(LDL-C) by decreasing the intake of saturated fatty acids (SAFAs). However,
SAFAs refer to a mixture of different fatty acids, predominantly palmitic acid
(C16:0) and stearic acid (C18:0). Stearic acid lowers LDL-C as compared with
palmitic acid. However, whether palmitic and stearic acids truly have different
cardiometabolic effects is unknown, as LDL-C is not the only determinant of
cardiovascular health. For example, stearic acid lowers cholesterol
concentrations in the *anti-atherogenic* high-density lipoprotein particles
(HDL-C) compared with palmitic acid. Simply increasing HDL-C levels, however,
does not necessarily lower CHD-risk. In this respect, targeting
HDL-functionality is more important. Effects of palmitic acid and stearic acid
on HDL-functionality have never been compared.

The primary objective of the present study is to investigate the effect of
palmitic acid versus stearic acid on HDL metabolism during the fasted state.
Secondary objectives are to investigate the effects of palmitic acid versus
stearic acid on the fasting serum lipoprotein profile, and on fasted and
postprandial triacylglycerol concentrations. Exploratory objectives are to
investigate the effect of palmitic acid versus stearic acid on other markers of
fasting lipid metabolism, glucose metabolism, inflammation, endothelial
function and blood pressure.

This is a double-blind, randomized, cross-over study with two different diets:
one diet will be high in palmitic acid and the other diet will be high in
stearic acid.

Subjects will receive both diets for 4 weeks with a wash-out period of 4 weeks
in between. Contrast in the intakes of palmitic acid and stearic acid is 6% of
energy. A postprandial test will be carried out at the end of each dietary
period.

Before the start of the study subjects will be screened to determine
eligibility during one 20 min visit. During this visit, body weight, and height
will be measured and a blood sample (4 mL) will be drawn by means of
venapunction. Thereafter, subjects will be asked to fill in a medical and
general questionnaire, including information on physical activity. During the
study, subjects will receive products based on the experimental fats. In
addition, dietary guidelines will be provided to standardize total fat and
fatty acid intake between subjects and periods. On 8 occasions a fasting blood
sample will be drawn (with a total of 188 mL spread over the eight visits),
body weight and blood pressure will be measured. At the last visit of each
period, subjects will participate in a postprandial test. An intravenous
cannula will be inserted in an antecubital vein. Before and after meal
consumption, 13 blood samples (120 mL) will be drawn during an 8 hour period.
During the test, subjects are allowed to drink water and to walk freely around.
Subjects may visit the research facilities in between to pick up the
experimental products. All subjects will be asked to complete a food frequency
questionnaire two times. Subjects will register daily the intake of the
experimental foods, and the remaining products in a diary, as well as any signs
of illness, medication used, and any deviations from the protocol. On rare
occasions, blood sampling might cause bruises or hematoma. Total time
investment for the subjects will be approximately 29 hours.