Dietary fat induces changes in factor VII coagulant activity through effects on plasma free stearic acid concentration.

Abstract

Previous studies have demonstrated activation of the contact system of coagulation and an increase in factor VII coagulant activity (VIIc) when citrated plasma is incubated in the presence of micellar stearate. The products of contact activation, factors Xlla and IXa, were responsible in this system for the activation of factor VII, thereby increasing factor VIIc. To obtain evidence that these in vitro interactions also operate in vivo, factor VIIc was examined in relation to plasma free fatty acid concentrations in five healthy individuals during the consumption of isocaloric high-saturated fat, high-unsaturated fat, and low-fat diets, each taken for 4 weeks in random order and separated by intervals of 12 weeks. For all but the final 3 days of each phase, subjects selected appropriate foods from prepared lists to meet the dietary requirements. Experimental diets of predetermined fat content and composition were fed on days 26 through 28 in each phase. Fat supplied on average 62% of energy in two of the experimental diets and less than 20% of energy in the third. On the final day of each dietary phase, the concentrations of the various free fatty acids and factor VIIc were measured before breakfast and at three 150-minute intervals thereafter. Plasma factor VIIc was, respectively, 6.5% and 13.1% of standard higher on the unsaturated and saturated fat diets than on the low-fat diet. Furthermore, the plasma concentration of stearic acid was strongly associated with factor VIIc (r=.58, /><.0001), and this relation remained significant (P=.OO3) after allowance for the plasma concentrations of palmitic, oleic, and linoleic acids. Plasma factor VII antigen levels were increased on the saturated fat diet but were very similar on the other two diets. These results suggest that the effects of saturated fatty acids observed in vitro on factor VIIc also operate in vivo. (Arterioscler Thromb. 1994;14:214-222

High Levels of Nonesterified Fatty Acids Are Associated With Increased Familial Risk of Cardiovascular Disease

“…40 In addition, fat intake influences NEFA concentrations and factor VII activity. 41 Although NEFAs represent the main energy source for the resting heart, high NEFA concentrations also predispose to arrhythmia. 42,43 Paolisso et al 44 recently showed in patients with type 2 diabetes that a high basal plasma NEFA concentration was associated with a high frequency of ventricular premature complexes and that increased NEFA concentration (by intralipid infusion) increases ventricular premature complexes whereas decreased NEFA concentration (by acipimox administration) decreases them.…”

Influences of lipid and non‐lipid nutritional parameters on factor VII coagulant activity in normal subjects: the Nove Study

“…Tholstrup et al [8] reported a favourable effect of a diet high in stearic acid vs. diets rich in other short-chain SFAs (lauric, myristic and palmitic); however, in this study there was a pronounced reduction of plasma cholesterol after a stearic-rich diet and the effect on FVII c of the change of this interrelated variable, as well as the plasma concentration of FAs, were not evaluated. On the other hand, Mitropoulos et al [7] reported a substantial increase of FVII c after a highsaturated fat diet. Moreover, in this study the plasma concentration of stearic acid, which increased significantly after the high-saturated fat diet, was strongly associated with FVII c .…”

“…A methodological aspect should be taken into account when a comparison between our study and that of Mitropoulos et al [7] presence of tissue thromboplastin and calcium ions [26]. Very recently (after the beginning of our study) a sensitive method for measuring directly the two-chain activated form of FVII (FVII a ) has become available [27].…”

“…More recently, two interventional studies with experimental diets in small samples of healthy subjects have given opposite results. In one study [7], FVII c increased after a highsaturated fat diet and the plasma concentration of stearic acid was strongly associated with FVII c . In the other study [8], the intake of fat high in stearic acid decreased FVII c .…”

Diet and blood coagulation factor VII—a key protein in arterial thrombosis

“…In another study, small FVIIc differences (2%) between fats rich in either palmitic (palm oil) or myristic acid (synthetic fat) were found (Tholstrup et al, 1994b). Finally, one study reported that a SFA-rich high-fat diet is associated with higher FVIIc, FVIIag, and FVIIa levels than a n-6 PUFA-rich high-fat diet (Mitropoulos et al, 1994). We would suggest that the low number of participants (®ve) and limited dietary control of this study might have led to the con¯icting ®nding by chance.…”