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Sci. Pharm. 2019, 87, 26; doi:10.3390/scipharm87040026 www.mdpi.com/journal/scipharm
Review
A Mini-Review of Human Studies on Cholesterol-
Lowering Properties of Probiotics
Bhagavathi Sundaram Sivamaruthi *, Periyanaina Kesika and Chaiyavat Chaiyasut *
Innovation Center for Holistic Health, Nutraceuticals, and Cosmeceuticals, Chiang Mai University,
Chiang Mai-50200, Thailand; p.kesika@gmail.com
* Correspondence: sivasgene@gmail.com (B.S.S.); chaiyavat@gmail.com (C.C.);
Tel.: +66-5394-4340 (B.S.S. & C.C.); Fax: +66-5389-4163 (B.S.S. & C.C.)
Received: 27 August 2019; Accepted: 25 September 2019; Published: 14 October 2019
Abstract: Cardiovascular diseases (CVD) are the major health issue of modernized society with a
high mortality rate. Lifestyle, genetic makeup, and diet are some of the major influencing factors
associated with CVD. The dyslipidemia is one such factor related to the development of several
CVD. Many studies proved that the consumption of probiotics confers several health benefits.
Several studies reported the evaluation of the cholesterol-lowering ability of probiotics (probiotics
that showed positive effect in vitro and in vivo studies) in human volunteers. The current review
summarizes the outcomes of human studies on the cholesterol-lowering property of probiotics.
Probiotic consumption significantly improved the health status of hypercholesteremic patients by
reducing the low-density lipoprotein cholesterol, total cholesterol, triglyceride levels, and increased
the high-density lipoprotein cholesterol. The probiotic supplementation improved the lipid profile
of diabetic patients, and obese people as well. However, not all probiotic interventions are effective
against dyslipidemia. The results are controversial and depend on several factors such as probiotic
strain, dose, duration of the treatment, lifestyle changes, etc. This literature survey indorses
additional studies on the cholesterol-lowering property of probiotics, which could help to reduce
the risk of CVD and other dyslipidemia associated health issues.
Keywords: probiotics; hypocholesteremia; cardiovascular diseases; cholesterol-lowering lipids;
microbiota
1. Introduction
Cardiovascular disease (CVD) is one of the major health issues with a high mortality rate (∼17.7
million deaths/year) [1]. The medical expenses to manage the CVDs are predicted to be tripled by
2030 [2]. Though genetics, microbiome, diet, lifestyle, and metabolic syndrome are the factors
associated with the development of CVD, dyslipidemic condition (characterized by the elevated level
of low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and the reduction in high-density
lipoprotein cholesterol (HDL-C) level), is one of the major risk factor related to CVD incidences [3].
The alteration of gut microbiota is closely associated with several ill-health conditions. High fat-
and sugar-containing diet, and low dietary fiber have a negative impact on the gastrointestinal system
[4]. Several studies revealed the link between gut microbiota and CVD incidences and progress [5,6].
Lower abundance of Bacteroidetes, higher abundance of Lactobacillales, Enterobacteriaceae,
Streptococcus spp., and increased Firmicutes/Bacteroidetes ratio are associated with CVD [6]. The
healthy dietary preference (rich in vegetables, fibers, and low consumption of meat and refined food
products) could improve gut health and reduce the risk of CVD.
Probiotics are live microbes that exhibit beneficial effect on human health when consumed in a
suitable amount [7]. Microbes that possess several health beneficial effects are termed as probiotics
after evaluating the safety and stability of the strain based on the standard regulations developed by
the Food and Agriculture Organization of the United Nations and the World Health Organization
Sci. Pharm. 2019, 87, 26 2 of 13
Expert Consultation on Evaluation of Health and Nutritional Properties of Probiotics [8–10]. The most
commonly used probiotics are Bifidobacteria and lactic acid bacteria. Other reported probiotics
include strains of Saccharomyces, Streptococcus, Pediococcus, Leuconostoc, Enterococcus, and Bacillus [11].
Probiotics are the potent players involved in the regulation of gut microbiota, thereby, it is
closely associated with human health and diseases state. Probiotics and probiotic-based fermented
foods are associated with the improvement of the health status of people who suffered from metabolic
disorders [12,13], inflammatory bowel diseases [11], antibiotic-associated diarrhea [14], menopausal
symptoms [15], and skin diseases [16]. The role of probiotics in mental health and cognitive
improvement [17] and the aging process [18] have been reported. The health benefits of probiotic
supplementation are attributed to their ability to maintain the equilibrium of gut microbiota and
immune system via the production of bacteriocins-like substances, short-chain fatty acids, and some
neurotransmitters like γ-aminobutyric acid [19,20].
Several in vitro and animal studies reported the cholesterol-lowering activity of probiotics [21–
23]. The current review focused on the outcomes of recent human studies concerning the cholesterol-
lowering property of probiotics. Studies based on the meta-analysis of probiotics supplementation
and lipid profile changes and non-significant outcome of clinical trials were also summarized. The
literature was collected from Scopus, PubMed, and Web of Science using the keywords “probiotics”
and “cholesterol” without any chronological restrictions. The relevant scientific papers were selected
based on the studies with human subjects and also published (at least abstract with clear content) in
the English language for the preparation of the manuscript.
Factors Affecting the Cholesterol Levels in Human
Age and gender play a role in affecting cholesterol levels. Cholesterol levels tend to increase in
older people. Total cholesterol and LDL-C levels may tend to increase in women after menopause
stage. Heredity may play a role in affecting cholesterol levels. Lack of physical activity is one of the
major causes of overweight and obesity, which affects the cholesterol level resulting increased total
cholesterol, LDL-C, TG, and decreased HDL-C levels. Therefore, weight management should be
focused on healthy lifestyle (healthy diet and physical activity) to manage the cholesterol levels and
to reduce the risk of CVDs. Consumption of probiotics may have a positive effect on managing the
cholesterol levels.
2. Impact of Probiotic Supplementation on the Lipid Profile of the Human Subjects
2.1. Hypercholesterolemic Subjects
Cavallini et al. [24] studied the effect of probiotics (Enterococcus faecium CRL 183 and Lactobacillus
helveticus 416) fermented soy product containing isoflavone on the lipid profile of moderately
hypercholesterolemic male subjects. The supplementation of soy product (equivalent of 1010 CFU of
probiotic strain) with 50 mg isoflavone per day for 42 days significantly improved the total cholesterol
(TC), LDL-C (low-density lipoprotein-cholesterol) and electronegative LDL content in the subjects
while the level of HDL-C (high-density lipoprotein-cholesterol) was unaffected and the level of
fibrinogen and C-reactive protein levels were not enhanced. The results suggested that the
consumption of probiotic soy product with isoflavone improved the cardiovascular risk factors in
hypercholesterolemic subjects [24].
A 12-week supplementation of a mixture of L. plantarum strains (CECT 7528, CECT 7529, CECT
7527; 1010 CFU/day) significantly increased the level of HDL-C and reduced LDL-C, TC, triglycerides
(TG), LDL-C/HDL-C ratio, and oxidized LDL levels in hypercholesterolemic subjects. The results
revealed that probiotics could be used for hypercholesterolemia treatment [25].
The dyslipidemic children were supplemented with a mixture of Bifidobacterium strains (B.
animalis lactis MB 2409, B. longum BL04, and B. bifidum MB 109B) for three months and their diet was
monitored. After the intervention, the changes in lipid profile were measured. The concentration of
serum level TC (222.8 ± 23.2 to 211.9 ± 27.3 mg/dL), HDL-C (55.8 ± 12.2 to 60.7 ± 14.2 mg/dL), TG (99.0
± 61.7 to 79.5 ± 34.5 mg/dL), and LDL-C (147.2 ± 21.9 to 135.3 ± 24.2 mg/dL) were significantly
Sci. Pharm. 2019, 87, 26 3 of 13
improved after three months of probiotic supplementation when compared to the baseline values.
The TC and LDL-C levels were notably reduced in the probiotic group compared to that of the
placebo. The results suggested that the supplementation of probiotics with dietary restriction help to
improve the lipid profile in dyslipidemic children [26].
The consumption of single probiotic strain (E. faecium M-74; 2 × 109 CFU/day) and selenium (50
μg) for one year did not alter the level of HDL-C and TG, while it significantly reduced the TC, and
LDL-C in elderly people compared to baseline and to that of the placebo. The study results
recommend that probiotics are promising therapeutic agents for several human ill-health conditions
[27].
The intervention of probiotic capsule containing L. acidophilus and B. bifidum (109 CFU/capsule;
three capsule/day) for six weeks significantly reduced the TC and LDL-C level in
hypercholesterolemic patients. There was no change in TG and blood sugar levels of the patients. The
level of HDL-C was significantly reduced during the study period. However, the probiotic
supplements improved the cholesterol profile, and the HDL-C content also reduced. The authors
claimed that L. acidophilus and B. bifidum have the potential to lower cholesterol in
hypercholesterolemic patients [28].
A significant level of reduction (15.5%) in remnant lipoprotein particle (RLP-P) content was
observed in the hypercholesterolemic patients, who had probiotic supplementation (Saccharomyces
cerevisiae var. boulardii CNCM I-1079) for eight weeks. The consumption of four probiotic capsules
(1.4 × 109 CFU/capsule) twice per day does not alter the TC, LDL-C, very low-density lipoprotein-
particle (VLDL-P), HDL-C, TG level, insulin, and representative cardiovascular markers,
significantly, but the notable level of RLP-P reduction was recorded after the experimental period.
The results suggested that CNCM I-1079 supplementation could be used as an adjuvant for
preventing and treating coronary artery disease [29].
2.2. Healthy Subjects
The supplementation of a milk-based fruit drink containing probiotic strain L. rhamnosus GG (6.2
× 107 CFU/ ml; 250 ml per day for three weeks) positively altered the global lipid profile in healthy
volunteers. Particularly, the level of sphingomyelins, lysophosphatidylcholines, and
glycerophosphatidylcholines were reduced after probiotic supplementation while triacylglycerols
content was increased when compared to baseline and to that of the placebo. The study also revealed
the association of inflammatory cytokines and lipid profile changes upon probiotic intervention. The
results proved that the intervention of L. rhamnosus GG improves the lipid profile in healthy subjects
[30].
The supplementation of 30 g of probiotic cheese containing L. acidophilus LA5 and B. lactis BB12
(each 5 × 106 CFU) with or without 30 g of chicory root extract significantly reduced the TC and LDL-
C and increased the HDL-C content in healthy volunteers in seven weeks of the experimental period.
The level of TG was reduced at a notable level in group supplemented with probiotics and chicory
root extract. There was no change in anthropometric measurements of the volunteers after the
experimental period when compared to baseline measurements. The study claimed that the use of
probiotic cheese containing LA5 and BB12 along with chicory root extract might be used to treat and
prevent the dyslipidemic condition [31].
2.3. Diabetes Patients
The consumption of probiotic yogurt (300 g per day) containing L. acidophilus La5 (∼4.14 × 106
CFU/g) and B. lactis Bb12 (∼3.61 × 106 CFU/g) for six weeks significantly improved the lipid profile of
type 2 diabetes mellitus (T2D) patients. Specifically, the level of TC, LDL-C, and ratio of LDL-C:HDL-
C and TC:HDL-C were reduced significantly when compared to baseline and to that of the placebo
control. There was no change in HDL-C and TG content in studied subjects. The results suggested
that the regular consumption of probiotic yogurt could improve the cholesterol level of T2D patients
[32].
Sci. Pharm. 2019, 87, 26 4 of 13
The supplementation of probiotic capsule containing L. acidophilus, L. casei, and B. bifidum (each
2 × 109 CFU/g) for six weeks reduced the TG and VLDL-C content in gestational diabetic (GD) patients
while no changes were observed in LDL-C, HDL-C, and TC. The probiotic supplementation
improved the serum insulin, plasma glucose level, homeostasis model assessment for insulin
resistance (HOMA-IR), and insulin sensitivity when compared to that of the placebo. The
consumption of a probiotic capsule enhanced the glycemic control and slightly improved the lipid
profile of GD patients [33].
The consumption of fermented milk containing B. animalis subsp. lactis BB-12 and L. acidophilus
La-5 (each 109 CFU; 120 g of fermented milk) for six weeks significantly reduced the LDL-C and TC
content in T2D patients. Additionally, the probiotic group showed reduced inflammatory cytokines
level and metabolic parameters such as HOMA-IR, HbA1c, fructosamine, and fasting blood glucose
(FBG). The study concluded that the probiotic consumption amended the glycemic control,
inflammatory system, and lipid profile in T2D subjects [34].
The daily consumption of 200 mL of fermented soymilk containing 2 × 107 CFU/mL of L.
plantarum A7 for eight weeks significantly reduced the TC, TG, LDL-C, and non-HDL-C in T2D
patients while HDL-C content was not altered when compared to baseline and to that of the control
group. The serum genistein and estimated glomerular filtration rate (eGFR) values were increased in
the probiotic soymilk-supplemented group when compared to the non-probiotic soymilk group. The
results suggested that L. plantarum A7 fermented soymilk showed a favorable impact on glomerular
function and lipid profile of T2D subjects [35].
The supplementation of 6 g/day of probiotic preparation made with L. acidophilus, B. bifidum, B.
lactis, and B. longum (each 1.5 × 109 CFU) for 24 weeks reduced the occurrence of low-HDL-C and
increased the HDL-C content when compared to the placebo control. The parameters associated with
hyperglycemia, hypertension, and metabolic syndrome have also been reduced significantly in the
probiotic group compared to that of the placebo control group [36].
The consumption of multi-species probiotic preparation (L. acidophilus ZT-L1, L. reuteri ZT-Lre,
L. fermentum ZT-L3, and B. bifidum ZT-B1; 2 × 109 CFU/day) for 12 weeks significantly reduced the TG,
TC:HDL-C ratio, and increased the HDL-C level in diabetic nephropathy (DN) patients compared to
that of the placebo control. The increase in insulin sensitivity and plasma total glutathione, and
decrease in FBG, HOMA-IR values, and malondialdehyde, high-sensitive C-reactive protein were
observed in the probiotic-treated group. The results suggested that probiotic consumption improved
the cardiovascular diseases risk factors in DN patients [37].
The supplementation of Ecologic®Barrier (multi-strain probiotic preparation containing B.
bifidum W23, B. lactis W51, B. lactis W52, L. acidophilus W37, L. brevis W63, L. casei W56, L. salivarius
W24, Lactococcus lactis W19, and Lactococcus lactis W58; dosage: two doses per day) for six months
reduced the TG, TC, LDL-C, and TC:HDL-C ratio values significantly when compared to the placebo
and baseline values. Ecologic®Barrier supplementation also reduced the FBG, insulin, HOMA-IR
values, and inflammatory cytokines level in T2D patients. The results suggested that multi-strain
probiotic preparation could be an adjuvant therapeutic agent to improve diabetic and cardiovascular-
associated metabolic parameters [38].
2.4. Other Subjects
The supplementation of Ecologic® Barrier (2.5 × 109 or 1 × 1010 CFU/day) for 12 weeks improved
the TG and LDL-C content and other metabolic and cardiovascular disease parameters in obese
postmenopausal women [39].
The supplementation of B. breve B-3 capsules (2 × 1010 CFU/day) for 12 weeks slightly reduced
the TG and improved the HDL-C content in pre-obese subjects, but the changes are not significant
when compared to baseline values. However, the probiotic supplementation reduced the body fat in
healthy pre-obese subjects; and the lipid profile was not improved significantly [40]. Similarly, L.
gasseri BNR17 supplementation (109 or 1010 CFU/day) for 12 weeks reduced the visceral fat mass in
obese subjects, but the changes in the TC, LDL-C, HDL-C, and TG were not significant when
compared to the placebo control [41]. The results have been summarized in Table 1.
Sci. Pharm. 2019, 87, 26 5 of 13
3. Meta-Analysis Studies
Several meta-analysis studies have been published based on the effect of probiotic
supplementation on the lipid profile of human subjects. The probiotic supplementation (both in the
form of freeze-dried powder, fermented products) significantly reduced TC and LDL-C in
hypercholesterolemic subjects while no significant changes were observed in TG and HDL-C content
[42–46]. The sub-group analysis of clinical trials suggested that the long-term consumption of
probiotic exhibited more beneficial effects on the lipid profile of the subjects [44]. A recent study
reported that intervention of probiotics significantly reduced the TC when compared to the TC of the
control group, and also stated that specific probiotic strains (B. lactis and L. acidophilus; L. plantarum)
significantly reduced the TC [47]. Another recent study suggested that the probiotic preparations
containing Lactobacillus and Bifidobacterium could reduce the LDL-C content in metabolic syndrome
patients without improving the TC and HDL-C content [48].
Probiotic consumption improved the TC and HDL-C content in non-alcoholic fatty liver disease
(NAFLD) subjects, but no changes were found to be observed in the level of LDL-C. The study
claimed that there were no sufficient studies on the impact of probiotic consumption on NAFLD to
confirm the beneficial role of probiotics [49].
The probiotic interventions significantly improved the lipid profile (reduced the TC, LDL-C, and
TG) of T2D patients along with the glucose homeostasis effectively [50–52].
Collectively, the results of meta-analysis revealed that the supplementation of probiotics might
improve the lipid profile of the human subjects. The efficiency of the probiotic intervention hinges on
several factors like dosage, duration of the treatment, combination of the probiotics strains, strain
quality, host metabolic activities, host-microbiome, etc. Thus, all the probiotic formulations are
effective in conferring the beneficial effects on the host system. The non-significant outcomes of
probiotic intervention studies are detailed in the following section.
4. Effect of Probiotics Supplementation on Lipid Profile: Non-Significant Outcomes
The consumption of L. acidophilus (9 × 1010 CFU/ day for six weeks), B. animalis subsp. lactis BB-
12® (3.16 × 109 CFU/day for four weeks), probiotic yogurt containing both L. acidophilus and BB-12®
(3.0 × 109 CFU/day for seven days), and L. acidophilus and B. longum (each 1010 CFU/ day for two
months) did not amend the lipid profile in healthy human subjects [53–56].
Recently, Culpepper et al. [57] reported that the supplementation of B. subtilis R0179 (2.5 × 109
CFU), B. animalis subsp. lactis B94 (5 × 109 CFU) for six weeks does not have any influential effect on
the lipid profile of healthy obese subjects.
A multi-genus and multi-species probiotic formula (L. acidophilus, L. casei, L. rhamnosus, L.
bulgaricus, B. breve, B. longum, and Streptococcus thermophilus) supplementation for eight weeks
showed no improvement in the lipid profile of T2D patients [58]. Mahboobi et al. [59] noticed that the
consumption of a multi-species probiotic capsule did not alter the TC, LDL-C, HDL-C, or TG values
in pre-diabetic subjects when compared to baseline and to that of the placebo control. Similarly, the
supplementation of probiotic (Lactobacillus spp., Bifidobacterium spp., S. thermophilus) or synbiotic
formulation (probiotics and fructo-oligosaccharide) did not amend the lipid profile of T2D patients
[60,61].
A multi-species probiotic preparation containing four Lactobacillus spp. (L. acidophilus, L.
bulgaricus, L. bifidum, and L. casei) did not improve the lipid profile in T2D patients. Only a non-
significant increase in HDL-C level was observed in the experimental subjects [62]. Similarly, 12
weeks of the randomized controlled clinical study suggested that the Ecologic®Barrier
supplementation did not improve the lipid profile in T2D patients [63].
5. Opinion on the Hypocholesterolemic Effect of Reviewed Probiotics
Based on the randomized, placebo-controlled, double-blind studies [24–41] reviewed in the
present article, the hypocholesterolemic effect of the probiotics was not significantly influenced by
the diet. Studies reported based on the intervention of single-strain probiotic (E. faecium M-74 along
Sci. Pharm. 2019, 87, 26 6 of 13
with selenium [27]; Saccharomyces cerevisiae var. boulardii CNCM I-1079 [29]; L. rhamnosus GG [30]; Soy
milk containing L. plantarum A7 [35]) preparation showed significant hypocholesterolemic effect
when compared to the study reported with the intervention of single-strain probiotics (B. breve B-3
[40]; Lactobacillus gasseri BNR17 [41]) preparation; whereas intervention of single-strain probiotics (L.
acidophilus [53]; B. animalis subsp. lactis BB-12 [54]) preparation exhibited no beneficial effect on the
lipid profile of the studied subjects. Therefore, the level of improving lipid profile is strain-specific
and might depend on the dosage and duration of the intervention.
Studies based on the intervention of multi-genus, multi-species, multi-strain (strains of same
species) probiotic preparation has been reported with positive effect on lipid profile [24–26,28,31–
34,36–39,47,48], while several studies reported no effect of multi-genus and multi-species probiotic
intervention on the lipid profile [55–63]. Even though intervention of Ecologic® Barrier (B. bifidum
W23, B. lactis W51, B. lactis W52, L. acidophilus W37, L. brevis W63, L. casei W56, L. salivarius W24,
Lactococcus lactis W19 and W58) exhibit hypocholesterolemic effect on different subjects (individuals
with T2D [38]; obese postmenopausal women [39]) with different intervention duration (six months
[38]; 12 weeks [39]), dosage of probiotic mixture does not influence the cholesterol-lowering ability
of the probiotic mixture.
The intervention of fermented milk with L. acidophilus LA-5 and B. animalis subsp. lactis BB-12
investigated in two studies [32,34] with the same intervention duration (six weeks) showed a
significant level of hypocholesterolemic effect in the individuals (almost similar age groups) with
T2D; whereas intervention of the same probiotic mixture along with chicory root extract [31] showed
significant hypocholesterolemic effect in the healthy subjects even with low dosage of probiotic
mixture [31] (when compared to the dosage of probiotic mixture in other studies [32,34]), which might
be due to the duration of intervention (seven weeks) or effect of chicory root extract or depend on the
healthy host. Hence, apart from dosage, the duration of intervention plays an important role in
influencing the curative effect of probiotics. Therefore, regular consumption of probiotic preparation
is required to retain health benefits in the needed host.
Sci. Pharm. 2019, 87, 26 7 of 13
Table 1. Impact of probiotic supplementation on lipid profile of human volunteers.
Study Subjects Diet Intervention Dosage Duration Findings
Ref.
RPCDB
Healthy male individuals
with moderate
hypercholesterolemia; n = 49;
Age = 37 to 57 years
No changes in the
usual diet
Fermented soy product
containing Enterococcus
faecium CRL 183, and
Lactobacillus helveticus 416
and isoflavone
200 ml per day (1010 CFU/
day) 42 days
• Improved the TC, LDL-
C and electronegative
LDL content
• Retained the HDL
[24]
RPCDB
Adults with
hypercholesterolemia; n = 60
(34 male, 26 female); Age = 18
to 65 years
No specific diet Lactobacillus plantarum (3
strains)
100 mg of the probiotic
mixture (1010 CFU during
production) per capsule; 1
capsule/ day
12 weeks
• ↓ LDL-C
• ↓ TC, TG
• ↓ LDL-C/HDL-C ratio
• ↓ Oxidized LDL
• ↑ HDL-C
[25]
RPCDB Dyslipidemic children; Age =
6 to 18 years
STEP 1 diet (normal
caloric diet)
Bifidobacterium animalis
subsp. lactis MB 2409, B.
bifidum MB 109B, and B.
longum BL04
3 strains (each 109 CFU)
within one capsule/ day 3 months
• ↓ LDL-C
• ↓ TC, TG
• ↑ HDL-C
[26]
RPCDB
Elderly people; n = 38 (7 male,
31 female); Age = 70 to 80
years
No specific diet E. faecium M-74 and
selenium
2 × 109 CFU of probiotic
and 50 µg selenium per
capsule/ day
1 year
• ↓ TC
• ↓ LDL-C
• No change in HDL-C,
and TG
[27]
RPCDB
Hypercholesterolemic
patients; n = 64 (male); Age =
40 to 60 years
Minimum calorie
diet with minimal
intake of lipid
L. acidophilus and B. bifidum
3 capsule/day;
Each strain 109
CFU/capsule
6 weeks
• ↓ TC
• ↓ LDL-C
• ↓ HDL-C
[28]
Single-
Arm,
Open-
Label
Study
Healthy adults with
hypercholesterolemia; n = 11
(10 male, 1 female); Age = 21
to 69 years
No changes in the
usual diet
Saccharomyces cerevisiae var.
boulardii CNCM I-1079
4 capsules twice a day;
1.4 × 1010 CFU/capsule 8 weeks • ↓ Remnant lipoprotein
particle
[29]
RPCDB
Healthy people; n = 26 (12
male, 14 female); Age = 23 to
55 years
No specific diet L. rhamnosus GG 250 ml probiotic drink/ day
(6.2 × 107 CFU/ ml) 3 weeks
• ↓
Lysophosphatidylcholi
nes
• ↓ Sphingomyelins
[30]
Sci. Pharm. 2019, 87, 26 8 of 13
• ↓
Glycerophosphatidylch
olines
• ↑ Triacylglycerols
RPCDB
Healthy people; n = 180 (90
male, 90 female); Age = 18 to
65 years
Consumption of
low-fat milk for a
week before the
trial begins
L. acidophilus LA5 and B.
lactis BB12 + chicory root
extract
30 g probiotic cheese (each
strain 5 × 106 CFU) and 30
g of chicory root extract
7 weeks
• ↓ TC
• ↓ LDL-C
• ↓ TG
• ↑ HDL-C
[31]
RPCDB
Individuals with T2D; n = 60
(23 male, 37 female); Age = 30
to 60 years
No changes in the
usual diet
Probiotic yogurt with L.
acidophilus,
La5 and B. lactis Bb12
300 g of yogurt per day 6 weeks
• ↓ TC
• ↓ LDL-C
• ↓ LDL-C:HDL-C ratio
• ↓ TC:HDL-C ratio
[32]
RPCDB Gestational diabetic patients;
n = 60; Age = 18 to 40 years
No changes in the
usual diet
L. acidophilus, L. casei and B.
bifidum
One capsule (Each strain 2
× 109 CFU/g) per day 6 weeks
• ↓ VLDL
• ↓ TG
• No change in HDL-C
[33]
RPCDB
Individuals with T2D; n = 45
(26 male, 19 female); Age = 35
to 60 years
No changes in the
usual diet
Fermented milk with L.
acidophilus La-5 and B.
animalis subsp. lactis BB-12
120 g of fermented milk
per day; (Each strain 109
CFU/day)
6 weeks • ↓ TC
• ↓ LDL-C
[34]
RPCDB
T2D patients; n = 40 (19 male,
21 female); Age = 40 to 70
years
Diet (consists of 0.8
g/kg protein, 2 g
potassium, 1.5 g
phosphorus, and 2
g sodium)
Soy milk containing L.
plantarum A7
200 ml of probiotic soy
milk/ day; 2 × 107 CFU/ml 8 weeks
• ↓ TC
• ↓ LDL-C
• ↓ non-HDL-C
• ↓ TG
• No change in HDL-C
[35]
RPCDB
Pre-diabetic subjects; n = 120
(50 male, 70 female); Age = 35
to 70 years
No changes in the
usual diet
L. acidophilus, B. bifidum, B.
lactis, and B. longum
6 g per day (Each strain 1.5
×109 CFU/day) 24 weeks • ↓ low HDL-C
• ↑ HDL-C
[36]
RPCDB
Diabetic nephropathy
patients; n = 60; Age = 45 to 85
years
No changes in the
usual diet
L. acidophilus ZT-L1, L. reuteri
ZT-Lre, L. fermentum ZT-L3
and B. bifidum ZT-B1
8 × 109 CFU/day (Each
strain 2 × 109 CFU/ day) 12 weeks
• ↓ TG
• ↓ TC:HDL-C ratio
• ↑ HDL-C
[37]
RPCDB
T2D patients; n = 61 (26 male,
35 female); Age = 35 to 70
years
No changes in the
usual diet
B. bifidum W23, B. lactis W51,
and W52, L. acidophilus W37,
L. brevis W63,
L. casei W56, L. salivarius
W24, Lactococcus lactis W19
and W58
2 g of the probiotic mixture
(2.5 × 109 CFU/g) per day 6 months
• ↓ TG
• ↓ TC
• ↓ LDL-C
• ↓ TC:HDL-C ratio
[38]
Sci. Pharm. 2019, 87, 26 9 of 13
RPCDB
Obese postmenopausal
women; n = 71; Age = 45 to 70
years
No changes in the
usual diet
B. bifidum W23, B. lactis W51,
and W52, L. acidophilus W37,
L. brevis W63, L. casei W56,
L. salivarius W24, Lactococcus
lactis W19 and W58
2 g of the probiotic mixture
(high dose: 1 × 1010 CFU;
low dose: 2.5 × 109 CFU)
per day
12 weeks
• In both High dose and
low dose group
• ↓ TG
• ↓ TC
• ↓ LDL-C
[39]
RPCDB
Healthy pre-obese adults; n =
80 (74 male, 6 female); Age =
35 to 56 years
No changes in usual
diet B. breve B-3 2 capsule per day;
10 × 109 CFU per capsule 12 weeks • ↓ TG
• Improved HDL
[40]
RPCDB
Obese adults; n = 90 (27 male,
63 female); Age = 20 to 75
years
As per dietitian
instruction, subjects
reduced 200 kcal
from their usual
diet every day
Lactobacillus gasseri BNR17
2 capsules (high dose: 1 ×
1010 CFU; low dose: 1 × 109
CFU) per day; 400 mg per
capsule
12 weeks • No significant changes
in TC, TG, and LDL-C
[41]
CDB: Randomized, placebo-controlled, double-blind study, TC: Total cholesterol, LDL-C: Low-density lipoprotein-cholesterol; HDL-C: High-density lipoprotein-
cholesterol; TG: Triglycerides; T2D: Type 2 diabetes mellitus; VLDL: Very low-density lipoprotein-cholesterol.
Sci. Pharm. 2019, 87, 26 10 of 13
5. Concluding Remarks
Several studies reported the effect of probiotics on lipid profiles such as TC, TG, LDL-C, and
HDL-C levels in different diseased conditions and in healthy volunteers as well, but the results are
not conclusive or consistent. The results of the studies suggested that the cholesterol-lowering ability
of probiotics is strain-specific, and depends on the host. Studies proposed that the
hypocholesterolemic effect of probiotics rely on the bile salt hydrolase activity, production of SCFAs,
binding of cholesterol to the cell surface of probiotic, co-precipitation of cholesterol and bile, and
conversion of cholesterol into coprostanol of probiotic strain [64].
Some of the human clinical studies have limitations such as probiotic formulations, dosage,
duration of the treatment and washout period, no proper follow-up study, etc. Most of the study
results conveyed that none of the probiotic supplements have the ability to improve all the desirable
parameters, except in some cases. Several probiotics exhibited hypocholesterolemic effect by
lowering the TC, LDL-C, and TG levels, and by improving the HDL-C levels in individuals with
hypercholesterolemia. The literature survey made in this study suggested that the cholesterol-
lowering ability of a probiotic formulation greatly influenced by the factors such as strains of the
same bacterial species showed different results, the combination of strains, dose, and duration. Intake
of probiotics in capsule form is considered to be more effective in exhibiting beneficial effects. Diet
does not significantly influence the cholesterol-lowering ability of the probiotics. Several meta-
analyses revealed that the supplementation of probiotic formulations improved the lipid profile.
Based on the meta-analysis studies, specific probiotic strains such as B. lactis and L. acidophilus, L.
plantarum significantly reduced the TC in adult patients [47], and Lactobacillus and Bifidobacterium
reduced LDL-C levels in metabolic syndrome patients [48]. Apart from dosage, the intervention
duration plays a role in impacting the curative effects of probiotics; thus, regular consumption of
probiotic is required to retain health benefits. Further studies are necessary to formulate the probiotic-
based therapeutic supplements to control dyslipidemia and to prevent the incidence of CVD.
Author Contributions: Conceptualization, B.S.S; methodology, B.S.S., and P.K.; writing—original draft
preparation, B.S.S.; writing—review and editing, B.S.S., P.K., and C.C.; supervision, B.S.S., and C.C.; project
administration, B.S.S., P.K., and C.C.; funding acquisition, C.C.
Funding: This research received no external funding.
Acknowledgments: The authors would like to acknowledge the financial support from Center of Excellence in
Medical Biotechnology (CEMB), The S&T Postgraduate Education and Research Development Office (PERDO),
The Commission on Higher Education (CHE), Thailand. Authors gratefully acknowledge Chiang Mai University
grant (CMU-grant) for the support.
Conflicts of Interest: The authors declare no conflict of interest.
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