Representing 31 percent of all deaths, cardiovascular disease (CVD) is the No. 1 cause of death globally.1 Arterial wall retention of low-density lipoprotein cholesterol (LDL-C) and similar cholesterol-rich lipoproteins containing apolipoprotein B (ApoB) is a key initiating event in the development of CVD.2 Furthermore, a plethora of evidence shows that elevated low-density lipoprotein cholesterol (LDL-C) level is a major modifiable risk factor for CVD.3 This certainly makes LDL-C a major target for CVD risk reduction.4,5
Probiotics for Cholesterol Reduction
There has been significant interest in the use of dietary supplements to help lower LDL-C levels. This interest is likely due to the fact that some patients have milder forms of hypercholesterolemia or as an alternative to statins in patients who may have experienced or are worried about side effects.6 Heretofore, the most studied nutraceuticals include monacolin K (a structural analogue of lovastatin) found in red yeast rice, plant sterols and stanols, and beta-glucans.7,8 Additionally, the gut microbiota has also been implicated in the regulation of cholesterol homeostasis,9,10 which led to the study of probiotics for their effect on lipid metabolism and cholesterol-lowering effects. Among these, a combination of three Lactobacillus plantarum strains, collectively called Floradapt Cardio, has shown particular promise.
Mechanism of Action
So, what is the mechanism by which these three probiotic strains help reduce cholesterol? Consider that bile salts (a primary component of bile needed by our bodies to help break down fats, aid digestion, absorb important vitamins, and eliminate toxins) are synthesized in the liver from cholesterol. Bile salt hydrolase breaks down or deconjugates bile salts, which makes them (and the cholesterol they contain) less reabsorbed through the intestines resulting in higher excretion into the feces. Replacement of new bile salts from cholesterol as a precursor subsequently leads to decreased serum cholesterol levels.11
The three Lactobacillus plantarum strains (CECT 7527, 7528 and 7529) not only showed a high ability to survive under gastrointestinal tract conditions and to adhere to intestinal cells, but there they were also shown to stimulate the production of bile salt hydrolase. Researchers concluded that “these combined characteristics suggest that these strains could be excellent candidates for reducing high blood cholesterol levels.”12 Indeed, this was shown to be the case in human clinical research.
2013 Human Clinical Study
In 2013, the first 12-week, double-blind, placebo-controlled, randomized study was published in the British Journal of Nutrition,13 investigating the effects of the three Lactobacillus plantarum (CECT 7527, CECT 7528 and CECT 7529, aka Floradapt Cardio by Kaneka) strains of on cholesterol-lowering efficacy in hypercholesterolemic patients (i.e., patients with high cholesterol levels). This included a total of 60 volunteers (30 participants in the placebo group and 30 in the probiotic group), aged 18–65 years old. The study group received one capsule daily containing 1.2 billion CFU of Lactobacillus plantarum strains, while the placebo group consumed the same product without bacteria. Results showed a significant reduction of 13.6 percent in plasma total cholesterol (TC) in the L. plantarum group compared with the placebo group. The outcomes were also analyzed based on TC values at baseline: low initial levels v. high initial levels. In the group with high initial TC levels, the L. plantarum treatment showed reductions in a 17.4 percent reduction in TC, a 17.6 percent reduction in LDL-cholesterol (LDL-C), and a 15.6 percent reduction in oxidized LDL-C compared with the placebo group. By contrast, in the group with low initial TC levels, the L. plantarum treatment showed a reduction of 9.4 percent TC compared with the placebo. This difference demonstrates that the effects of the L. plantarum blend is proportional to the cardiovascular risk of the patient, having a better effect in patients with higher levels of cholesterol.
2016 Human Clinical Study
In 2016, another 12-week, double-blind, placebo-controlled, randomized study was published in Mediterranean Journal of Nutrition and Metabolism14 assessing the effect of the same three Lactobacillus plantarum strains (Floradapt Cardio) on LDL-C and other lipid parameters in 60 hypercholesterolemic patients (mean age 51.8 years) not receiving lipid-altering treatment. Patients were treated either with a capsule containing 10 billion CFU of the L. plantarum blend or placebo. Results were that, compared to placebo, the L. plantarum group had significantly (p < 0.001) larger reductions in LDL-C (24.4 vs. 9.8 mg/dL), total-C (33.7 vs. 10.6 mg/dL), LDL-C/high-density lipoprotein cholesterol (HDL-C) ratio (0.8 vs. 0.3), oxidized LDL (7.5 vs. 1.0 U/L) and triglycerides (29.1 vs. 4.1 mg/dL). Additionally, HDL-C was also significantly (p < 0.001) increased in the L. plantarum group compared to placebo. In conclusion, this study showed that the L. plantarum blend reduced LDL-C and improved other lipid parameters, demonstrating its potential for hypercholesterolemia treatment.
2019 Human Clinical Study: Alone or Adjunct With Statins
Thus far, the studies cited have demonstrated that the L. plantarum blend alone is effective at lowering cholesterol and improving lipid parameters. But what happens when it is combined with statin drugs? This was investigated in a 12-week observational, prospective, multicenter and open label study15 in which 381 men and women (18-75 years old, LDL cholesterol levels > 115 mg/dL or total cholesterol > 200 mg/dL) received one capsule with 1.2 billion CFU/day of the same three Lactobacillus plantarum strains (Floradapt Cardio) with or without additional statin treatment. Results showed a statistically significant and robust decrease in LDL-C, TC and TG values after probiotic supplementation when compared to baseline in the whole population. Furthermore, analysis of probiotic-only treated subpopulations also presented a significant LDL, TC and TG reduction. HDL concentration was significantly enhanced in the whole cohort, while there was a trend toward improved HDL values in probiotic-only treated subpopulations. Interestingly, LDL levels at baseline and statin potency did have an impact on LDL decrease. In addition, the incidence of adverse events was low, and neither the drop-out range nor the concomitant medication had an impact on adverse events. Such outcomes provide evidence of the safe and well tolerated profile of the L. plantarum blend as well as the fact that it can be safely used in combination with additional treatments.
2021 Human Clinical Study: In Combination With Red Yeast Rice
The last study examined the use of the L. plantarum blend with or without statin drugs. This 12-week randomized, double-blind, placebo-controlled clinical study16 examined the effects of 1 billion CFU/day of the L. plantarum blend in combination with red yeast rice (containing 10 mg/day of monacolin K) or placebo in 39 adult patients with total cholesterol (TC) ≥200 mg/dL and being statin-naïve or having recently stopped statin treatment because of intolerance. Results were that study groups were comparable at baseline, except for history of recent hypercholesterolemia treatment (81 percent in active vs. 22 percent in placebo). Changes in LDL cholesterol and TC became significant compared to placebo (mean difference between groups = 23.6 ± 1.5 mg/dL, p = 0.023 and 31.4 ± 1.9 mg/dL, p = 0.011, respectively). No adverse effects were noted during the study. In conclusion, this combination of 10 mg of monacolin K and L. plantarum strains was well tolerated and achieved a statistically significant greater reduction in LDL-C and TC in the intervention group compared to the placebo.
Conclusion
CVD is the No. 1 cause of death globally, and LDL-C a major target for CVD risk reduction. As a result, there has been significant interest in the use of dietary supplements to help lower LDL-C levels, and a combination of three Lactobacillus plantarum strains, collectively called Floradapt Cardio, has shown particular promise in multiple human clinical studies. These studies include the use of the L. plantarum blend alone or in combination with statins or red yeast rice. In all of these scenarios, the L. plantarum blend demonstrated efficacy and safety in significantly lowering LDL-C levels and improving other lipid parameters. VR
References:
1 World-Health-Organization. WHO Media Centre: Cardiovascular Diseases. Availabe online: www.who.int/nmh/publications/fact_sheet_cardiovascular_en.pdf (accessed on 6 March 2021).
2 Ference BA, Ginsberg HN, Graham I, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur. Heart J. 2017; 38, 2459–2472.
3 Silverman MG, Ference BA, Im K, et al. Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions: A Systematic Review and Meta-analysis. JAMA. 2016; 316: 1289–1297.
4 Grundy, S.M.; Stone, N.J.; Bailey, A.L.; Beam, C.; Birtcher, K.K.; Blumenthal, R.S.; Braun, L.T.; de Ferranti, S.; Faiella-Tommasino J, Forman DE, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019; 73: e285–e350.
5 Mach F, Baigent C, Catapano A, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS). Eur Heart J. 2019: 41: 111–188.
6 Ward NC, Pang J, Ryan JDM, Watts GF. Nutraceuticals in the management of patients with statin-associated muscle symptoms, with a note on real-world experience. Clin Cardiol. 2018; 41: 159–165.
7 Ward NC, Pang J, Ryan JDM, Watts GF. Nutraceuticals in the management of patients with statin-associated muscle symptoms, with a note on real-world experience. Clin Cardiol. 2018; 41: 159–165.
8 Bianconi V, Mannarino MR, Sahebkar A, et al. Cholesterol-Lowering Nutraceuticals Affecting Vascular Function and Cardiovascular Disease Risk. Curr Cardiol Rep. 2018; 20: 53.
9 Le Roy T, Lecuyer E, Chassaing B, et al. The intestinal microbiota regulates host cholesterol homeostasis. BMC Biol. 2019; 17: 94.
10 Molinero N, Ruiz L, Sanchez B, et al. Intestinal Bacteria Interplay With Bile and Cholesterol Metabolism: Implications on Host Physiology. Front Physiol. 2019; 10: 185.
11 Choi S-B, Lew L-C, Yeo S-K, et al. Probiotics and the BSH-related cholesterol lowering mechanism: a Jekyll and Hyde scenario. Crit Rev Biotechnol. 2015;35(3):392-401.
12 Bosch M, Fuentes MC, Audivert S, et al. Lactobacillus plantarum CECT 7527, 7528 and 7529: Probiotic candidates to reduce cholesterol levels. J Sci Food Agric. 2014; 94: 803–809.
13 Fuentes MC, Lajo TL, Carrión JM, Cuñé J. Cholesterol-lowering efficacy of Lactobacillus plantarum CECT 7527, 7528 and 7529 in hypercholesterolaemic adults. Br J Nutr. 2013 May 28;109(10):1866-72.
14 Fuentes MC, Lajo T, Carrión JM, Cuñé J. A randomized clinical trial evaluating a proprietary mixture of Lactobacillus plantarum strains for lowering cholesterol. Med J Nutrition Metab. 2016; 9:125–135.
15 Jumangit J, Paz J. An observational, multicenter and open-label study to determinate the efficacy and safety of AB-LIFE® alone or adjunct with statins to lower cholesterol level. AB-Biotics Internal Clinical Study Report. December 2019; 50 pgs.
16 Guerrero-Bonmatty R, Gil-Fernández G, Rodríguez-Velasco FJ, Espadaler-Mazo J. 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. Nutrients. 2021 Apr 6;13(4):1206.
Gene Bruno, MS, MHS, the dean of academics for Huntington University of Health Sciences, is a nutritionist, herbalist, writer and educator. For more than 30 years he has educated and trained natural product retailers and health care professionals, has researched and formulated natural products for dozens of dietary supplement companies, and has written articles on nutrition, herbal medicine, nutraceuticals and integrative health issues for trade, consumer magazines and peer-reviewed publications. He can be reached at gbruno@hchs.edu.
Representing 31 percent of all deaths, cardiovascular disease (CVD) is the No. 1 cause of death globally.1 Arterial wall retention of low-density lipoprotein cholesterol (LDL-C) and similar cholesterol-rich lipoproteins containing apolipoprotein B (ApoB) is a key initiating event in the development of CVD.2 Furthermore, a plethora of evidence shows that elevated low-density lipoprotein cholesterol (LDL-C) level is a major modifiable risk factor for CVD.3 This certainly makes LDL-C a major target for CVD risk reduction.4,5
Probiotics for Cholesterol Reduction
There has been significant interest in the use of dietary supplements to help lower LDL-C levels. This interest is likely due to the fact that some patients have milder forms of hypercholesterolemia or as an alternative to statins in patients who may have experienced or are worried about side effects.6 Heretofore, the most studied nutraceuticals include monacolin K (a structural analogue of lovastatin) found in red yeast rice, plant sterols and stanols, and beta-glucans.7,8 Additionally, the gut microbiota has also been implicated in the regulation of cholesterol homeostasis,9,10 which led to the study of probiotics for their effect on lipid metabolism and cholesterol-lowering effects. Among these, a combination of three Lactobacillus plantarum strains, collectively called Floradapt Cardio, has shown particular promise.
Mechanism of Action
So, what is the mechanism by which these three probiotic strains help reduce cholesterol? Consider that bile salts (a primary component of bile needed by our bodies to help break down fats, aid digestion, absorb important vitamins, and eliminate toxins) are synthesized in the liver from cholesterol. Bile salt hydrolase breaks down or deconjugates bile salts, which makes them (and the cholesterol they contain) less reabsorbed through the intestines resulting in higher excretion into the feces. Replacement of new bile salts from cholesterol as a precursor subsequently leads to decreased serum cholesterol levels.11
The three Lactobacillus plantarum strains (CECT 7527, 7528 and 7529) not only showed a high ability to survive under gastrointestinal tract conditions and to adhere to intestinal cells, but there they were also shown to stimulate the production of bile salt hydrolase. Researchers concluded that “these combined characteristics suggest that these strains could be excellent candidates for reducing high blood cholesterol levels.”12 Indeed, this was shown to be the case in human clinical research.
2013 Human Clinical Study
In 2013, the first 12-week, double-blind, placebo-controlled, randomized study was published in the British Journal of Nutrition,13 investigating the effects of the three Lactobacillus plantarum (CECT 7527, CECT 7528 and CECT 7529, aka Floradapt Cardio by Kaneka) strains of on cholesterol-lowering efficacy in hypercholesterolemic patients (i.e., patients with high cholesterol levels). This included a total of 60 volunteers (30 participants in the placebo group and 30 in the probiotic group), aged 18–65 years old. The study group received one capsule daily containing 1.2 billion CFU of Lactobacillus plantarum strains, while the placebo group consumed the same product without bacteria. Results showed a significant reduction of 13.6 percent in plasma total cholesterol (TC) in the L. plantarum group compared with the placebo group. The outcomes were also analyzed based on TC values at baseline: low initial levels v. high initial levels. In the group with high initial TC levels, the L. plantarum treatment showed reductions in a 17.4 percent reduction in TC, a 17.6 percent reduction in LDL-cholesterol (LDL-C), and a 15.6 percent reduction in oxidized LDL-C compared with the placebo group. By contrast, in the group with low initial TC levels, the L. plantarum treatment showed a reduction of 9.4 percent TC compared with the placebo. This difference demonstrates that the effects of the L. plantarum blend is proportional to the cardiovascular risk of the patient, having a better effect in patients with higher levels of cholesterol.
2016 Human Clinical Study
In 2016, another 12-week, double-blind, placebo-controlled, randomized study was published in Mediterranean Journal of Nutrition and Metabolism14 assessing the effect of the same three Lactobacillus plantarum strains (Floradapt Cardio) on LDL-C and other lipid parameters in 60 hypercholesterolemic patients (mean age 51.8 years) not receiving lipid-altering treatment. Patients were treated either with a capsule containing 10 billion CFU of the L. plantarum blend or placebo. Results were that, compared to placebo, the L. plantarum group had significantly (p < 0.001) larger reductions in LDL-C (24.4 vs. 9.8 mg/dL), total-C (33.7 vs. 10.6 mg/dL), LDL-C/high-density lipoprotein cholesterol (HDL-C) ratio (0.8 vs. 0.3), oxidized LDL (7.5 vs. 1.0 U/L) and triglycerides (29.1 vs. 4.1 mg/dL). Additionally, HDL-C was also significantly (p < 0.001) increased in the L. plantarum group compared to placebo. In conclusion, this study showed that the L. plantarum blend reduced LDL-C and improved other lipid parameters, demonstrating its potential for hypercholesterolemia treatment.
2019 Human Clinical Study: Alone or Adjunct With Statins
Thus far, the studies cited have demonstrated that the L. plantarum blend alone is effective at lowering cholesterol and improving lipid parameters. But what happens when it is combined with statin drugs? This was investigated in a 12-week observational, prospective, multicenter and open label study15 in which 381 men and women (18-75 years old, LDL cholesterol levels > 115 mg/dL or total cholesterol > 200 mg/dL) received one capsule with 1.2 billion CFU/day of the same three Lactobacillus plantarum strains (Floradapt Cardio) with or without additional statin treatment. Results showed a statistically significant and robust decrease in LDL-C, TC and TG values after probiotic supplementation when compared to baseline in the whole population. Furthermore, analysis of probiotic-only treated subpopulations also presented a significant LDL, TC and TG reduction. HDL concentration was significantly enhanced in the whole cohort, while there was a trend toward improved HDL values in probiotic-only treated subpopulations. Interestingly, LDL levels at baseline and statin potency did have an impact on LDL decrease. In addition, the incidence of adverse events was low, and neither the drop-out range nor the concomitant medication had an impact on adverse events. Such outcomes provide evidence of the safe and well tolerated profile of the L. plantarum blend as well as the fact that it can be safely used in combination with additional treatments.
2021 Human Clinical Study: In Combination With Red Yeast Rice
The last study examined the use of the L. plantarum blend with or without statin drugs. This 12-week randomized, double-blind, placebo-controlled clinical study16 examined the effects of 1 billion CFU/day of the L. plantarum blend in combination with red yeast rice (containing 10 mg/day of monacolin K) or placebo in 39 adult patients with total cholesterol (TC) ≥200 mg/dL and being statin-naïve or having recently stopped statin treatment because of intolerance. Results were that study groups were comparable at baseline, except for history of recent hypercholesterolemia treatment (81 percent in active vs. 22 percent in placebo). Changes in LDL cholesterol and TC became significant compared to placebo (mean difference between groups = 23.6 ± 1.5 mg/dL, p = 0.023 and 31.4 ± 1.9 mg/dL, p = 0.011, respectively). No adverse effects were noted during the study. In conclusion, this combination of 10 mg of monacolin K and L. plantarum strains was well tolerated and achieved a statistically significant greater reduction in LDL-C and TC in the intervention group compared to the placebo.
Conclusion
CVD is the No. 1 cause of death globally, and LDL-C a major target for CVD risk reduction. As a result, there has been significant interest in the use of dietary supplements to help lower LDL-C levels, and a combination of three Lactobacillus plantarum strains, collectively called Floradapt Cardio, has shown particular promise in multiple human clinical studies. These studies include the use of the L. plantarum blend alone or in combination with statins or red yeast rice. In all of these scenarios, the L. plantarum blend demonstrated efficacy and safety in significantly lowering LDL-C levels and improving other lipid parameters. VR
References:
1 World-Health-Organization. WHO Media Centre: Cardiovascular Diseases. Availabe online: www.who.int/nmh/publications/fact_sheet_cardiovascular_en.pdf (accessed on 6 March 2021).
2 Ference BA, Ginsberg HN, Graham I, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur. Heart J. 2017; 38, 2459–2472.
3 Silverman MG, Ference BA, Im K, et al. Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions: A Systematic Review and Meta-analysis. JAMA. 2016; 316: 1289–1297.
4 Grundy, S.M.; Stone, N.J.; Bailey, A.L.; Beam, C.; Birtcher, K.K.; Blumenthal, R.S.; Braun, L.T.; de Ferranti, S.; Faiella-Tommasino J, Forman DE, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019; 73: e285–e350.
5 Mach F, Baigent C, Catapano A, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS). Eur Heart J. 2019: 41: 111–188.
6 Ward NC, Pang J, Ryan JDM, Watts GF. Nutraceuticals in the management of patients with statin-associated muscle symptoms, with a note on real-world experience. Clin Cardiol. 2018; 41: 159–165.
7 Ward NC, Pang J, Ryan JDM, Watts GF. Nutraceuticals in the management of patients with statin-associated muscle symptoms, with a note on real-world experience. Clin Cardiol. 2018; 41: 159–165.
8 Bianconi V, Mannarino MR, Sahebkar A, et al. Cholesterol-Lowering Nutraceuticals Affecting Vascular Function and Cardiovascular Disease Risk. Curr Cardiol Rep. 2018; 20: 53.
9 Le Roy T, Lecuyer E, Chassaing B, et al. The intestinal microbiota regulates host cholesterol homeostasis. BMC Biol. 2019; 17: 94.
10 Molinero N, Ruiz L, Sanchez B, et al. Intestinal Bacteria Interplay With Bile and Cholesterol Metabolism: Implications on Host Physiology. Front Physiol. 2019; 10: 185.
11 Choi S-B, Lew L-C, Yeo S-K, et al. Probiotics and the BSH-related cholesterol lowering mechanism: a Jekyll and Hyde scenario. Crit Rev Biotechnol. 2015;35(3):392-401.
12 Bosch M, Fuentes MC, Audivert S, et al. Lactobacillus plantarum CECT 7527, 7528 and 7529: Probiotic candidates to reduce cholesterol levels. J Sci Food Agric. 2014; 94: 803–809.
13 Fuentes MC, Lajo TL, Carrión JM, Cuñé J. Cholesterol-lowering efficacy of Lactobacillus plantarum CECT 7527, 7528 and 7529 in hypercholesterolaemic adults. Br J Nutr. 2013 May 28;109(10):1866-72.
14 Fuentes MC, Lajo T, Carrión JM, Cuñé J. A randomized clinical trial evaluating a proprietary mixture of Lactobacillus plantarum strains for lowering cholesterol. Med J Nutrition Metab. 2016; 9:125–135.
15 Jumangit J, Paz J. An observational, multicenter and open-label study to determinate the efficacy and safety of AB-LIFE® alone or adjunct with statins to lower cholesterol level. AB-Biotics Internal Clinical Study Report. December 2019; 50 pgs.
16 Guerrero-Bonmatty R, Gil-Fernández G, Rodríguez-Velasco FJ, Espadaler-Mazo J. 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. Nutrients. 2021 Apr 6;13(4):1206.
Gene Bruno, MS, MHS, the dean of academics for Huntington University of Health Sciences, is a nutritionist, herbalist, writer and educator. For more than 30 years he has educated and trained natural product retailers and health care professionals, has researched and formulated natural products for dozens of dietary supplement companies, and has written articles on nutrition, herbal medicine, nutraceuticals and integrative health issues for trade, consumer magazines and peer-reviewed publications. He can be reached at gbruno@hchs.edu.
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