Probiotics Potentials in Blood Cholesterol Levels Control and Heart Disease Risk Reducing

Cardiovascular disease is a leading cause of death, with 17.3 million deaths in 2008 and an estimated 23.3 million deaths expected globally by 2030 [1]. Heart disease alone consumed $108.9 billion in the United States and $23 billion in Canada [2]. Many factors contribute to heart disease, including daily nutrition and habits. Elevated blood cholesterol (hypercholesterolemia) and metabolic disorders are among the main causes leading to various heart diseases [3]. Increased blood cholesterol, especially high levels of low-density lipoprotein cholesterol (LDL-c), can lead to coronary artery disease [4]. Therefore, when doctors administer appropriate treatment measures, they can reduce the risk of disease and death related to heart disease. There are various methods to reduce cholesterol levels, and one of them is using probiotics, which have various benefits, particularly in lowering blood cholesterol in some patients.

Reducing Cholesterol Levels with Traditional Methods

Ayurveda is one of the oldest known medical systems globally. Ayurvedic methods are based on the patient’s diet to regulate behavior, patient care, detoxification, and rejuvenation. Herbs such as ginger, Guggul, and Arjuna are used to reduce blood cholesterol levels [5]. Red yeast rice extract is currently the most effective herbal remedy for lowering cholesterol. Studies have proven that it reduces LDL-c, improves endothelial function, and reduces arterial stiffness in heart disease.

Additionally, medical professionals have been using statins for several decades to improve heart health, specifically for treating high blood cholesterol. Studies have shown that statins reduce the rate of heart muscle infarction-related mortality by approximately 30% – 40% and decrease LDL-c levels by 25% – 40% [6]. However, statins are known to come with various side effects and symptoms, such as muscle inflammation, muscle atrophy, muscle tenderness, memory loss, liver damage, kidney disease, and colitis [7]. Due to the high cost of medication and potential side effects, the necessity of supplementing probiotics or combining probiotics with treatment forms an effective solution.

Establishing a healthy diet with the use of probiotics helps reduce blood cholesterol, thereby lowering the risk of heart disease.

Recent evaluations have focused on the dietary habits of patients using probiotics and have shown effectiveness in heart disease patients with elevated cholesterol levels. Although many aspects and different mechanisms, such as microbial strains in probiotics, medication dosage, treatment methods, and dietary changes, still need consideration in the process of lowering blood cholesterol.

Mechanism of Cholesterol Reduction by Probiotics

Probiotics are becoming a supplement in the diets of individuals with average/high blood cholesterol, significantly reducing the risk of heart disease. A 1% reduction in total cholesterol translates to a 2% reduction in the risk of heart disease, and a 1% reduction in LDL-C is associated with a 1% reduction in this risk. Therefore, the use of probiotics, prebiotics, and related metabolic compounds, such as nutritional supplements with cholesterol-lowering properties, can be a good alternative to prevent heart disease. In 2002, the World Health Organization (WHO) described probiotics as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host.” Some scientists from the International Scientific Association have officially approved definitions of probiotics and prebiotics [8]. Research trends show that probiotics demonstrate the ability to reduce LDL-C, improve the LDL/HDL ratio, lower blood pressure, reduce inflammatory cytokines, enhance insulin sensitivity, and decrease BMI [9,10].

The daily intake of cholesterol regulates the rate of cholesterol synthesis. The body controls cholesterol levels, maintaining it at 150-200 mg dL^-1, through new synthesis processes. The synthesis of steroid hormones, bile acids, and the formation of membranes using cholesterol as a fundamental component is involved [11]. The mechanism by which probiotics lower blood sugar is to enhance the metabolism of cholesterol and bile salts. Liver cells produce bile salts to enhance the transport of cholesterol and fats in the diet through the intestinal mucosa. Studies have shown that many Bifidobacterium and Lactobacillus species produce bile salt hydrolases that cut amide bonds [92]. Probiotics containing Bile Salt Hydrolase (BSH) genes work to increase bile salt production from cholesterol in their vicinity, thereby reducing cholesterol-related issues such as coronary heart disease.

On the other hand, researchers have also suggested that short-chain fatty acids (SCFAs) produced by the prebiotic metabolism of probiotics play a crucial role in cholesterol reduction. Researchers have reported that SCFAs act as ligands to activate peroxisome proliferator-activated receptor (PPAR) signaling. This regulates the fatty acid oxidation process in muscles and fat cells, leading to a reduction in stored fat [12].

Clinical Trials

In recent years, researchers have conducted several successful clinical trials on humans using probiotics to control lipid levels. Treating with probiotics has led to a reduction in LDL-cholesterol and improvement in total cholesterol, high-density lipoprotein cholesterol, and neutral fat levels [13]. Results from nutritional, genetic analysis of colonic biopsy specimens after probiotic use showed that Lactobacillus acidophilus reduced cholesterol levels in humans [14]. Using 4.2 × 10⁶ colony-forming units of Lactobacillus acidophilus L1 for 4 weeks significantly reduced total cholesterol and LDL-C [15].

Considering Lactobacillus, a type of probiotic as a supplement is an effective preventive measure of conditions of low blood lipids and intestinal infections. It is recommended to use probiotics as a supplement in the diet to treat digestive and urinary disorders. Bifidobacteria and Lactobacilli probiotics have been used as preventive factors or therapeutic approaches to reduce cholesterol and improve gut health and metabolic disorders in infants and adolescents [16]. Certain strains of Lactobacillus acidophilus, such as Lactobacillus plantarum and Lactococcus lactis, have reduced blood cholesterol levels by regulating bacterial concentrations in the blood.

Some studies have shown a correlation when using a probiotic product from Bifidobacterium longum, helping reduce blood lipids in adult males with moderately elevated cholesterol levels. The use of Bifidobacterium species is believed to be related to the treatment of lipid disorders in children with elevated blood cholesterol by improving lipid composition. Additionally, women who regularly consumed yogurt supplemented with Lactococcus acidophilus and Bifidobacterium for 6 months had higher HDL-c levels, and the LDL-c/HDL-c ratio also improved [17]. Therefore, probiotics are a natural alternative that may be beneficial for increasing lipid components and reducing the risk of heart disease without causing adverse reactions, unlike statin drugs.

Probiotics Potentials in Supporting Cholesterol Reduction

Thus, we can see that probiotics have the potential to be used as a therapeutic medication in reducing the risk of heart disease and various cardiovascular diseases by lowering blood cholesterol levels. Clinical data confirm the positive effects of using probiotics for elevated cholesterol. However, despite clear evidence of the effectiveness of probiotics, we need more specific evidence and additional time to investigate how probiotics with an appropriate microbial composition not only benefit cardiovascular health but also address common diseases while eliminating any potential negative health impacts.

References:

1. Yusuf, Salim, Steven Hawken, Stephanie Ôunpuu, Tony Dans, Alvaro Avezum, Fernando Lanas, Matthew McQueen et al. “Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study.” The lancet 364, no. 9438 (2004): 937-952.
2. Heidenreich, Paul A., Justin G. Trogdon, Olga A. Khavjou, Javed Butler, Kathleen Dracup, Michael D. Ezekowitz, Eric Andrew Finkelstein et al. “Forecasting the future of cardiovascular disease in the United States: a policy statement from the American Heart Association.” Circulation 123, no. 8 (2011): 933-944.
3. Santos, R. D., et al. “International Atherosclerosis Society Severe Familial Hypercholesterolemia Panel. Defining severe familial hypercholesterolaemia and the implications for clinical management: a consensus statement from the International Atherosclerosis Society Severe Familial Hypercholesterolemia Panel.” Lancet Diabetes Endocrinol 4.10 (2016): 850-61.
4. S Mannu, G., et al. “Evidence of lifestyle modification in the management of hypercholesterolemia.” Current cardiology reviews 9.1 (2013): 2-14.
5. Donato, Francesco, et al. “Guggulu and Triphala for the Treatment of Hypercholesterolaemia: A Placebo-Controlled, Double-Blind, Randomised Trial.” Complementary Medicine Research 28.3 (2021): 216-225.
6. Chauvin, Benoit, et al. “Drug–drug interactions between HMG-CoA reductase inhibitors (statins) and antiviral protease inhibitors.” Clinical pharmacokinetics 52.10 (2013): 815-831.
7. Selva-O’Callaghan, Albert, et al. “Statin-induced myalgia and myositis: an update on pathogenesis and clinical recommendations.” Expert review of clinical immunology 14.3 (2018): 215-224.
8. Gibson, Glenn R., et al. “Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics.” Nature reviews Gastroenterology & hepatology 14.8 (2017): 491-502.
9. Markowiak, Paulina, and Katarzyna Śliżewska. “Effects of probiotics, prebiotics, and synbiotics on human health.” Nutrients 9.9 (2017): 1021.
10. Kramer, A., et al. “Maintaining health by balancing microbial exposure and prevention of infection: the hygiene hypothesis versus the hypothesis of early immune challenge.” Journal of Hospital Infection 83 (2013): S29-S34.
11. Kumar, Manoj, Ravinder Nagpal, Rajesh Kumar, R. Hemalatha, Vinod Verma, Ashok Kumar, Chaitali Chakraborty et al. “Cholesterol-lowering probiotics as potential biotherapeutics for metabolic diseases.” Experimental diabetes research 2012 (2012).
12. Korecka, Agata, Tomas De Wouters, Antonietta Cultrone, Nicolas Lapaque, Sven Pettersson, Joël Doré, Hervé M. Blottière, and Velmurugesan Arulampalam. “ANGPTL4 expression induced by butyrate and rosiglitazone in human intestinal epithelial cells utilizes independent pathways.” American Journal of Physiology-Gastrointestinal and Liver Physiology 304, no. 11 (2013): G1025-G1037.
13. Guardamagna, Ornella, Alberto Amaretti, Paolo Emilio Puddu, Stefano Raimondi, Francesca Abello, Paola Cagliero, and Maddalena Rossi. “Bifidobacteria supplementation: effects on plasma lipid profiles in dyslipidemic children.” Nutrition 30, no. 7-8 (2014): 831-836.
14. van Baarlen, Peter, Freddy Troost, Cindy van der Meer, Guido Hooiveld, Mark Boekschoten, Robert JM Brummer, and Michiel Kleerebezem. “Human mucosal in vivo transcriptome responses to three lactobacilli indicate how probiotics may modulate human cellular pathways.” Proceedings of the National Academy of Sciences 108, no. supplement_1 (2011): 4562-4569.
15. Anderson, James W., and Stanley E. Gilliland. “Effect of fermented milk (yogurt) containing Lactobacillus acidophilus L1 on serum cholesterol in hypercholesterolemic humans.” Journal of the American College of Nutrition 18, no. 1 (1999): 43-50.
16. Marras, Luisa, et al. “The role of bifidobacteria in predictive and preventive medicine: a focus on eczema and hypercholesterolemia.” Microorganisms 9.4 (2021): 836.
17. Ataie-Jafari, Asal, et al. “Cholesterol-lowering effect of probiotic yogurt in comparison with ordinary yogurt in mildly to moderately hypercholesterolemic subjects.” Annals of Nutrition and Metabolism 54.1 (2009): 22-27.