Vayarol® is a prescription medical food used under
Mechanism Of Action
The exact mechanism by which Vayarol® exerts its effects
is not fully understood. Potential mechanisms of action include inhibition of
triglyceride (TG) synthesis and very-low density lipoprotein (VLDL) secretion
(by inhibition of diacyl-glycerol acyltransferase and phosphatidic acid
phosphohydrolase), stimulation of fatty acid-oxidation (by activation of
peroxisomal proliferator-activated receptors (PPARs)), and increase of TG
clearance rates (by increasing plasma lipolytic activity)1.
Furthermore, inflammation and vasodilation might be influenced through
modification of eicosanoid profiles2, 3. In addition, Vayarol® may
reduce the absorption of both dietary and biliary cholesterol from the intestinal
tract, by displacing cholesterol from micelles 4, 5.
Metabolism And Absorption
Phytosterol esters are usually hydrolyzed in the
gastrointestinal tract into their phytosterol and fatty acid components6.
Phytosterols have been reported to be poorly absorbed from the gastrointestinal
tract, and as a result, low levels of phytosterols are present in the blood7.
Of the phytosterols that are absorbed, the majority are quickly secreted back
into the bile, where they are re-circulated back to the gastrointestinal tract8.
Sanders9 reported that the predominant route of excretion is via the
feces, in which 75% to 96% of the administered amount is recovered within 24
hours of dosing. In contrast to phytosterols, DHA and EPA are absorbed from the
gastrointestinal tract efficiently. Sixty to ninety percent of an administered
dose of EPA or DHA is absorbed and incorporated into plasma phospholipids
primarily in the liver, and then circulate in the blood stream10.
From plasma phospholipids, DHA and EPA can be distributed to cellular membranes
in a variety of tissues including the brain, eye, liver, kidney, red blood
cells and adipose tissue11-14. Further metabolism of DHA and EPA
results from their removal from the membrane phospholipids, for use as fatty
acid precursors in the synthesis of eicosanoids, which are endogenous compounds
involved in blood clotting and immune responses.
Cholestyramine administration should be separated from phytosterol
use by two to four hours to avoid binding of the latter in the gut. There are
no formal studies with Vayarol® and concomitant anticoagulants. Several
clinical trials have examined the effect of DHA and EPA consumption on bleeding
time and other parameters related to blood clotting and fibrinolysis. Out of these
studies, some studies reported decrease in platelet aggregation and clotting
factor levels, while others reported that these parameters did not change
significantly15-23. Patients receiving treatment with Vayarol® and
an anticoagulant or other drug affecting coagulation (e.g., aspirin, NSAIDS,
warfarin, coumarin) should be monitored periodically. No significant pharmacokinetic
interactions have been noted between statins and phytosterols to date.
In vitro and in vivo studies have indicated that
phytosterols are not mutagenic or genotoxic24. In an acute toxicity
study (in which a single dose of 3.2 g sitosterol/kg body weight was
administered to mice25) and in a 13-week subchronic toxicity studies
(in which rats were administered phytosterol ester doses of 0, 1,000, 3,000, or
9,000 mg/kg body weight/day26), no toxicological effects were
observed following the administration of these doses. Neither developmental nor
reproductive performance toxicity following DHA supplementation was observed in
either rats or rabbits27, 28. In general, the scientific literature
indicates that doses of up to 1.3 g/kg body weight/day of EPA or DHA are well tolerated
and produce no serious adverse effects in laboratory animals29, 30.
Vayarol® was evaluated in a randomized, double blind, placebo-controlled
study of 12 weeks31.
Ninety one men and women (aged 18–65 years) with mixed hyperlipidemia
were randomly assigned to receive Vayarol® or placebo. Fasting blood samples
were obtained at baseline and endpoint for assessing lipids and lipoprotein
profiles, as well as other cardiovascular disease (CVD) risk factors. Of the 91
randomized subjects, 84 subjects completed the study, of them, 67 subjects were
included in the per-protocol (PP) analysis (17 subjects were excluded from the
PP analysis since they failed to maintain their lifestyle habits, or failed to
meet the compliance criteria). The two study groups were comparable with regard
to age, gender, weight, Body Mass Index (BMI), and lipid profile.
Triglyceride Levels Following Vayarol® Administration
The values are presented as mean ± standard error (SE). *
p = 0.025 based on two-tailed student's t-test comparison of the mean
difference from baseline for independent samples.
Low Density Lipoprotein - Cholesterol (LDL-C) Levels Following
The values are presented as mean ± SE.
The typical increase-in LDL-C levels, frequently seen
with omega-3 fatty acids, was not observed.
Diastolic Blood Pressure and CRP Levels Following
|Diastolic BP (mmHg)
||82.03 ± 1.6
||83.15 ± 2.65
||83.00 ± 1.68
||2.46 ± 0.42
The values are presented as mean ± SE. *p value based on comparison
of the mean difference from baseline for independent samples (student's t-test
and Mann Whitey test for BP and CRP, respectively). BP-blood pressure; CRP-C
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