Plant sterol and probiotic supplement significantly lowers cholesterol, says study
Cardiovascular diseases (CVDs) are the number one cause of death globally, representing 31% of all global deaths. The retention of low-density lipoprotein cholesterol (LDL-C) and similar cholesterol-rich lipoproteins is a key initiating event in atherogenesis.
Statins are the main drug used to control LDL-C levels but these come with many potential side effects, making dietary supplements of increasing interest.
The most studied nutraceuticals in this field include monacolin K (a structural analogue of lovastatin) found in red yeast rice (RYR) which is chemically identical to the active ingredient in the cholesterol-lowering drug lovastatin. This ingredient can lower blood cholesterol levels but can cause the same types of side effects and drug interactions as lovastatin.
The gut microbiota has also been implicated in the regulation of host cholesterol homeostasis and a meta-analysis showed some probiotics may have a significant effect on blood cholesterol, mostly pertaining to species Lactoplantibacillus plantarum and Limosilactobacillus reuteri (formerly known as Lactobacillus plantarum and Lactobacillus reuteri).
The current study sought to evaluate the effect of a novel nutraceutical combining 109 colony-forming units (CFUs) of three L. plantarum strains (CECT7527, CECT7528, and CECT7529) and RYR extract (containing 10 mg of monacolin K) compared to placebo on LDL-C and other blood lipid parameters of hypercholesterolemic subjects.
A total of 39 patients with raised total cholesterol (TC) levels were included in the study which was scheduled across 4 visits: Visit 0 (week −1, prescreening), visit 1 (week 0, baseline), visit 2 (week 6), and visit 3 (week 12). A fasting blood sample was taken at the pre-screening.
In the baseline visit, the team collected demographic data, clinical history, waist perimeter, body mass index (BMI), body weight, and percent body fat, and patients were randomised, stratified by age, sex, and BMI, to receive either active capsules (21 participants) or placebo (18 participants).
All patients were given the same dietary recommendations from the Spanish Endocrinology and Nutrition Society. In visits 2 and 3, data was collected on blood lipids from a fasting blood sample, and safety and treatment compliance were checked. Body mass index (BMI), body weight, percent body, and patient satisfaction were also recorded at the end of the intervention.
Unadjusted analysis of LDL-C and TC levels across the study did not reveal significant differences between groups. However, upon accounting for the strong imbalance in history of recent hypercholesterolemia treatment, a statistically significant improvement was observed both for LDL-C and TC in the active group compared to placebo. What's more, no adverse effects were noted.
Conversely, no significant effect was observed on HDL-C, triglycerides (TG), BMI, or percent of body fat.
Various mechanisms have been proposed for bacteria with high bile salt hydrolase (BSH) activity (such as L. plantarum strains CECT7527, CECT7528, and CECT7529) in lowering blood cholesterol. These include: reducing apical sodium-dependent bile acid transporter (ASBT) transporter-mediated intestinal reabsorption of bile salts due to its lower affinity for deconjugated bile salts; increased expression of host genes involved in the cholesterol efflux system (Abcg5/8), lipid metabolism (Pparγ, Angptl4), circadian rhythm (Dbp and Per1/2), or intestinal homeostasis (RegIIIγ); and changes in bile-dependent signalling on farnesoid X receptor (FXR), Takeda G-protein receptor 5 (TGR5), or vitamin D receptor.
Research background
The clinical effect of the specific combination of L. plantarum strains used in this study was previously assessed in a 12-week intervention study involving 60 patients. It found a similar reduction in LDL-C and TC compared to baseline (14% and 13%, respectively), which were slightly reduced when accounting for the placebo effect (to 8% and 9%, respectively).
LDL-C and TC reductions from baseline averaged 13% and 11% in the present study, which are increased to 15% and 13% when accounting for placebo. Conversely, the former study observed a significant reduction in TG (16% vs. baseline and 14% vs. placebo), as opposed to the present study. However, baseline TG levels averaged 180 mg/dL in the former study, compared to 143 mg/dL in the present one.
More recently, an observational study was conducted involving more than 340 patients taking the same L. plantarum strains, alone or in combination to pre-existing statins at a stable dose of moderate or high intensity. In those subjects taking probiotic alone, a large reduction from baseline was observed in LDL-C (23%). However, the lack of randomisation and treatment concealment makes comparisons to the current study difficult. A significant reduction in TG was also observed (22% vs. baseline), but baseline TG levels were much higher in said study (averaging 340 mg/dL), compared to the present study.
Of note, subjects who added the probiotic treatment to already ongoing statin therapy obtained even larger reductions in LDL-C, averaging 29%, and no side effects were noted.
The current report concludes that the present study, taken together with previous studies, suggest "these probiotic strains may have a beneficial effect on TG in subjects with raised levels at baseline (the higher the baseline, the larger the effect) but not in subjects with normal (i.e., <150 mg/dL) or borderline TG levels. This observation should be verified in future clinical studies."Additionally, since monacolin K is known to be structurally equivalent to lovastatin, the former observational study and the present randomized study support the safety of combining this particular probiotic formula to statin-type therapy."
Source: Nutrients
Espadaler-Mazo. J., et al
"A Combination of Lactoplantibacillus plantarum Strains CECT7527, CECT7528, and CECT7529 Plus Monacolin K Reduces Blood Cholesterol: Results from a Randomized, Double-Blind, Placebo-Controlled Study"
https://doi.org/10.3390/nu13041206
