van Rooijen Merel Anne

Estetrol (E4) represents a novel estrogen of interest to relieve vasomotor symptoms. E4 activates the nuclear estrogen receptor α (ERα) but antagonizes the estradiol ERα-dependent membrane-initiated steroid signaling pathway. The distinct pharmacological properties of E4 could explain its low impact on hemostasis. This study aimed to assess the effect of E4 on coagulation in postmenopausal women, using the thrombin generation assay (TGA). Data were collected from a multicenter, randomized, placebo-controlled, dose-finding study in postmenopausal women (NCT02834312). Oral E4 (2.5 mg, n = 42; 5 mg, n = 29; 10 mg, n = 34; or 15 mg, n = 32) or placebo (n = 31) was administered daily for 12 weeks. Thrombograms and TGA parameters were extracted for each subject at baseline and after 12 weeks of treatment. After 12 weeks of treatment, all treatment groups showed a mean thrombogram (±95% confidence interval [CI] of the mean) within the reference ranges, that is, the 2.5th-97.5th percentile of all baseline thrombograms (n = 168), as well as for TGA parameters. The intake of E4 15 mg for 12 weeks led to significant but not clinically relevant changes compared to baseline as the mean values (±95% CI of the mean) remained within reference ranges, demonstrating a neutral profile of this estrogen on hemostasis.

Purpose: Palmitic and stearic acids have different effects on fasting serum lipoproteins. However, the effects on postprandial lipemia and glycemia are less clear. Also, the effects of a second meal may differ from those of the first meal. Therefore, we studied the effects of two consecutive mixed meals high in palmitic acid- or stearic acid-rich fat blends on postprandial lipemia and glycemia. Methods: In a randomized, crossover study, 32 participants followed 4-week diets rich in palmitic or stearic acids, At the end of each dietary period, participants consumed two consecutive meals each containing ± 50 g of the corresponding fat blend. Results: Postprandial concentrations of triacylglycerol (diet-effect: − 0.18 mmol/L; p = 0.001) and apolipoprotein B48 (diet-effect: − 0.68 mg/L; p = 0.002) were lower after stearic-acid than after palmitic-acid intake. Consequently, total (iAUC_0–8 h) and first meal (iAUC_0–4 h) responses were lower after stearic-acid intake (p ≤ 0.01). Second meal responses (iAUC_4–8 h) were not different. Postprandial changes between the diets in non-esterified fatty acids (NEFA) and C-peptide differed significantly over time (p < 0.001 and p = 0.020 for diet*time effects, respectively), while those for glucose and insulin did not. The dAUC_0–8 h, dAUC_0–4 h, and dAUC_4–8 h for NEFA were larger after stearic-acid intake (p ≤ 0.05). No differences were observed in the iAUCs of C-peptide, glucose, and insulin. However, second meal responses for glucose and insulin (iAUC_4–8 h) tended to be lower after stearic-acid intake (p < 0.10). Conclusion: Consumption of the stearic acid-rich meals lowered postprandial lipemia as compared with palmitic acid. After the second stearic acid-rich meal, concentrations of C-peptide peaked earlier and those of NEFA decreased more. Clinical trial registry This trial was registered at clinicaltrials.gov as NCT02835651 on July 18, 2016.

Fats that are rich in palmitic or stearic acids can be interesterified to increase their applicability for the production of certain foods. When compared with palmitic acid, stearic acid lowers low-density lipoprotein (LDL)-cholesterol, which is a well-known risk factor for coronary heart disease (CHD), but its effects on other cardiometabolic risk markers have been studied less extensively. In addition, the positional distribution of these two fatty acids within the triacylglycerol molecule may affect their metabolic effects. The objective was to compare the longer-term and postprandial effects of (interesterified) fats that are rich in either palmitic or stearic acids on cardiometabolic risk markers in humans. Two searches in PubMed/Medline, Embase (OVID) and Cochrane Library were performed; one to identify articles that studied effects of the position of palmitic or stearic acids within the triacylglycerol molecule and one to identify articles that compared side-by-side effects of palmitic acid with those of stearic acid. The interesterification of palmitic or stearic acid-rich fats does not seem to affect fasting serum lipids and (apo) lipoproteins. However, substituting palmitic acid with stearic acid lowers LDL-cholesterol concentrations. Postprandial lipemia is attenuated if the solid fat content of a fat blend at body temperature is increased. How (the interesterification of) palmitic or stearic acid-rich fats affects other cardiometabolic risk markers needs further investigation.