Lipid Lowering Effects of Herbal Supplements: A Review

 

Elizabeth Tan1,2, Erwin Faller1,3

1Centro Escolar University, Manila, Philippines.

2University of San Carlos, Cebu City,Cebu, Philippines.

3San Pedro College, Davao City, Davao del Sur, Philippines.

*Corresponding Author E-mail: Philippines eytan@usc.edu.ph

 

ABSTRACT:

As cardiovascular diseases are still a major cause of death in most countries, it is still relevant to look into treatment of such diseases.  Dyslipidemia is one of the important identified risk factors for cardiovascular diseases. As this is largely driven by lifestyle and diet, it may be difficult to control it with lifestyle modifications alone. Currently, Statins remains to be the mainstay therapy for dyslipidemia but this is also met by problems within certain patient population.  The drug may be contraindicated in certain patient groups; some patients tend to not respond to Statins; while certain patients may not tolerate the adverse events. This study looked into available literature on studies done on dyslipidemia using plant-based formulations using randomized clinical trial.  Based on the review conducted, there are several plant-based formations with potential to be similar in efficacy to Statins.  Some of the plants used are abundant or may be easily sourced.  With the increasing popularity of food supplements or nutraceuticals, exploration on the potential of plant-based products is attractive.  Despite the promising results of some studies, these will need further investigations and targeting a larger population size.  Formulation options may need to be explored also focused on its stability. 

 

KEYWORDS: Lipid-lowering, Plant formulations, Cholesterol, Dyslipidemia, Hypolipidemic.

 

 


INTRODUCTION:

Cardiovascular diseases are a leading cause of mortality and morbidity in the world. There is a dearth of epidemiological data showing that sedentary habits and lifestyle contributes to such.  Countries have made efforts to disseminate such information discouraging this behavior1. As the management of cardiovascular diseases does not solely depend on addressing one symptom, nor is it simplified by just giving a drug. There are many other diseases that can aggravate cardiovascular conditions. This paper looks into the existing issue on dyslipidemia and other conditions that may be affected by it.  Statins are the mainstay therapy for where lipid-lowering is required.  Despite its lauded efficacy, there is still a continuous search for alternatives due to its pronounced side effects. 

 

In the current days, patients are more inclined to take food supplements and nutraceuticals.  The aim of this paper is to present some studies done on these alternatives and to look at their potential to be used either alongside Statins or as independent therapy.  Studies included were only those done on human subjects and had randomized design.

 

LITERATURE REVIEW:

Dyslipidemia and Its Management:

Dyslipidemia is one of those risk factors for cardiovascular diseases. It is a chronic, metabolic disease characterized by increased total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) levels or decreased high-density lipoprotein cholesterol (HDL-C)2. It increases the risk of the development of severe outcomes from COVID-19 infections3 and can potentially increase mortality and severity of COVID-19 and the association is stronger in patient with older age, male, and has hypertension4. At the height of COVID-19 pandemic, patients should have their co-morbidities managed appropriately to stay as health as possible to avoid complications.

 

Links have been observed between cardiovascular diseases and groups of population. Cross-sectional studies indicate that children and adolescents with severe obesity are at greater risk for dyslipidemia than those with mild obesity, among others5. Women with PCOS (polycystic ovarian syndrome) are at increased risk of cardiometabolic disease. In this population, higher serum concentration of total cholesterol, lower serum concentration of high density lipoprotein cholesterol, and increased risks of non-fatal cerebrovascular disease events have been noted 6.

 

More and more people are becoming aware of the implication of diet on cholesterol. A study on the knowledge of adults in Bangalore, India on consuming fatty diet and blood cholesterol shows moderate level7. There are studies looking at high cholesterol levels with hypertension such as on done in Chennai8 and one that looked into the relationship of serum lipids with body mass index9.  Obesity is recognized as a hazard in cardiovascular disease risk which also calls for cholesterol lowering among obese patients10. Another study looked at the association of height with blood total cholesterol (TC) level in young adults and the potential use of the two parameters in combination as an indicator of coronary heart disease (CHD) risk in adulthood11.  A study went to the extent of investigating the alterations and clinical significance of serum lipid profile, Hb (gm%), blood sugar and blood urea 12.

 

Strengthening the proof that dyslipedemia is indeed a worldwide concern, several studies have documented this.  Time trends and levels of mean total cholesterol and lipid functions, and dyslipidemia prevalence in Latin America and the Carribean had results to strengthen programs for dyslipidemia prevention and management13. Dyslipidemia is identified as a health problem in northern China. Age-standardized prevalence was 31.2% overall with higher prevalence in men than women. Postmenopausal women had higher prevalence of dyslipidemia. The student respondents were of Han and Mongol ethnicity with the former being at higher risk for dyslipidemia14. In northeast China, patients with dyslipidemia showed high cardiovascular burden with low control rates and high prevalence of co-existing risk factors.  Among the surveyed population, only 2.9% had their dyslipidemia controlled5. A study on ethnic groups in Indonesia revealed that older group of Minangkabau ethnic women have higher risk toward dyslipidemia as they have higher plasma total and LDL cholesterol while the younger group of Sudanese ethnic men have higher risk based on HDL levels as this is lowest in this ethnic group16. Some Southeast Asian refugees were screened in a primary care clinic and a striking finding was low HDL-C values posing a risk for hypercholesterolemia. This justified the routine screening requirement for this group17. High blood cholesterol level used to be a problem of wealthy western countries. However, dietary and behavioral determinants are changing rapidly around the world.  Looking at the global perspective of change in total cholesterol or non-HDL cholesterol levels, not much has changed due to the fact that wealthy nations are achieving better dyslipidemia control but low and middle income countries, especially the east and southeast Asia are seeing an increase in dyslipidemia.  In 2017, high non- HDL cholesterol was responsible for an estimated 3.9 million worldwide deaths, half of which happened in Asia18. As dyslipidemia is on the rise in Asian nations, awareness to have lipid levels checked may not be routine.  This was seen in a small study involving adult Vietnamese volunteers that had high total cholesterol and triglycerides; half of them stated that they did not see a doctor annually or at least on a regular basis19. In countries where medical services are still out-of-pocket, physician visits are just limited to when it is absolutely urgent. 

 

The condition of hyperlipidemia can be described as high cholesterol in the blood (hypercholesterolemia), high triglycerides in the blood (hypertriglyceridemia) or it could be both20. This form of condition can lead to atherosclerosis due to accumulation of cholesterol in blood vessels thereby increasing the risk for cardiovascular diseases21.

 

Statins are compounds of natural origin that are biosynthesized as secondary metabolites of filamentous fungi and act as competitive inhibitors of HMGR22.  Emerging evidence suggest that statins exert other mechanism of action called Pleiotropic effects; which are plaque stability, endothelial function modification, thrombus formation etc23. Statins are the most common drugs administered for patients with cardiovascular disease24. Effective lipid-lowering therapy could decrease the blood LDL-C levels25. More intensive LDL-C lowering was associated with a greater reduction in risk of cardiovascular mortality in patients with higher baseline LDL-C levels than less intensive methods26. Prescription with lipid lowering medications decrease the risk of micro and macro cardiovascular complications related to dyslipidemia however, adherence remains a challenge worldwide27. Adverse effects associated with its use lead to discontinuation of therapy. Statin-induced myotoxicity (SIM) is one of the common adverse effects seen across all ages, gender, and ethnicities.  A higher risk for SIM is seen in patients with a polymorphism in the SLC01B1 gene28. Discovery of anti-HMGCR antibodies is another barrier to adherence in therapy.  Documented neuromuscular side effects include asymptomatic elevation of muscle enzymes, mild to moderate myalgia and cramps, toxic and immune-mediated severe necrotizing myopathy, and rare cases of rhabdomyolysis29. A study indicated that GATM polymorphism may be a pharmacogenomics biomarker for predicting incidence of SIM which may be a useful information on Statin adherence30. In high risk Asian patients with hypercholesterolemia, Atorvastatin 20 mg was both efficacious in reducing LDL-C and cost-effective compared to Atorvastatin 10 mg31. It may be good to note that high-intensity Atorvastatin compared with Rosuvastatin is associated with an increased incidence of ADR32.  High-intensity Statins were associated with better persistence and adherence to treatment but overall long-term persistence and adherence remain a challenge33. A small case summary documented a 44-year old Caucasian male experiencing bilateral foot pain, weakness, and soreness while taking Atorvastatin 20 mg daily. Pain subsided within weeks after discontinuation of therapy but returned years later after the initiation of Rosuvastatin34.  Recent “life-long’ analysis conducted on young familial hypercholesterolemia patients, elderly hypercholesterolemia subjects, and from a 20-year follow up randomized clinical trial have been published confirming that cardiovascular benefits of Statin therapy in patients for whom it is recommended by current guidelines, greatly outweigh the risks of side effects35. Extensive research has established the benefits and safety of Statins but majority of the patients are not adequately treated and do not achieve the low-density lipoprotein cholesterol target levels due to poor adherence brought about by dangerous and sometimes, fatal outcomes36.  Adults with primary non adherence to Statins describe seeking alternatives, avoiding perceived risks to the drug, poor acceptance and understanding of cardiovascular disease risk estimates, and doubts about the benefits of Statins. Many patients do not disclose their decisions to providers, including the decision to stop therapy37.

 

The use of medicinal herbs continue to be an alternative treatment approach for several diseases38. The International Lipid Expert Panel (ILEP) said that nutraceutical therapies containing herbal monomers and derivatives seem to be very safe and well tolerated39 and made recommendation to use them as a lipid-lowering option to Statins for intolerant populations40. Food-derived bioactive compounds like Resveratrol are continuously explored for their protective effects against metabolic complications41. Herbal medicine use prevalence was found to be at 68% in a study done in Indonesia. A good 40% of surveyed respondents admitted to self-medicating with herbal medicine42.  Any decrease in serum LDL-C concentrations is associated with a decreased cardiovascular disease risk, and this benefit is similar to a comparable LDL-C reduction after drug treatment and dietary intervention. Life-long reductions in serum LDL-C levels have a large impact on cardiovascular disease risk and a long-term dietary enrichment with functional foods or supplements with proven LDL-lowering efficacy is a feasible and efficient approach to decrease future cardiovascular disease risk.  As the practice of use of functional foods is widely practiced among patients, a shared decision between medical doctors and dietitians with patients to ensure proper empowerment and better adherence to management approaches43. In the efforts to search for options for lipid-lowering agents, several studies are continuously being conducted. Water extract from Lentinula edodes showed HMG-CoA reductase inhibitory activity but contained no statins.  This showed possible potential as a hypolipidemic extract if dose-dependent studies could be carried out44.  Green coffee bean extract supplementation led to significant reductions in total cholesterol, HDL-C, and LDL-C levels45. Supplementation with Spirulina showed reduction in plasma concentrations of total cholesterol, LDL-C, triglycerides, and elevating those of HDL-C46.  In a study involving quercetin, it showed that an 8-week consumption of it will significantly lower levels of triglycerides and HDL-C47.  Lactobacillus species are even being explored for its potential as lipid-lowering agent48 in the hope to search for more alternatives. While acceptability of Statins is high, the side-effects associated with then are the limitations.  Recent studies also reveal genetic influence in successful management with Statins. As with any drug, possible contraindications may also prevent physicians from prescribing patients with the drug.  For these reasons, there is continuous quest to look for alternatives to Statins.

 

METHODOLOGY:

A search for literature was done in PubMed to look at existing studies done on the topic and its management using plant-based or food supplements.  The criteria used was “Hypolipidemic Agents” [Mesh] AND (“Plant Preparations” [Mesh] OR “Phytotherapy” [Mesh].  Additional references were searched in Science Direct using keywords such as lipid lowering, plant-sourced, hypolipidemic agents, formulations from plants. 

 

The articles chosen met the following inclusion criteria: (i) articles are done or focused in Asia; (ii) published in English; (iii) published from 1999-2021; (iv) has abstract and/or free full text available, (v) uses plant-based to food-based formulations.

 

 

 

Search Strategy:

 

“Hypolipidemic Agents” [Mesh] AND (“Plant Preparations” [Mesh] OR “Phytotherapy” [Mesh]

 

Keywords: lipid lowering, plant-sourced, hypolipidemic agents, formulations from plants

 

Search Results:

 

PubMed: 30 (with free full text), 174 (abstracts)

 

Science Direct: 78

 

 

Articles included. met the following conditions (n=63):

 i.  articles done or focused in Asia;

ii.  published in English

iii.  published from 1999-2021

iv.  has abstract and/or free full text available;

v.  uses plan-based or food-based formulations.

Figure 1.  Identification and Inclusion of Research Articles

 

RESULTS AND DISCUSSION:

Alternatives to Statins:

A study by Berthold et al (2011) was done on malleable protein matrix (MPM) to look at the potential lipid lowering effects.  The study had 161 subjects with hypercholesterolemia and randomized to receive MPM (30g per day given as 2 doses) or matching placebo for 12 weeks.  Triglycerides decreased at about 9.8% from baseline and a slight decrease in LDL-C was also observed. MPM contains Lactoferrin and immunoglobulin49.  Another study done on MPM involved 197 patients randomized to receive either MPM supplement with low-fat yoghurt or a matching placebo yoghurt identical in protein content (15 g per day).  Patients were given such for 3 months with two daily servings of 150 g yoghurt.  Results were compared with baseline data.  The group receiving treatment showed significant reduction of triglycerides by a wide margin compared to placebo. For patients with elevated triglycerides at baseline, the lowering was much more pronounced50. A meta-analysis on whey supplementation was done by Zhang et al in 2016 and showed that its whey’s effects on lipids are modest with more lowering evident in triglycerides but no effect on TC, LDL-C and HDL-C 51. There are studies focusing on triglyceride lowering as its benefit on cardiovascular disease reduction is more evident.  Drugs are even being developed to lower triglycerides 52

 

Two-month consumption of 30g each day of soy protein isolate lowered total cholesterol and triglycerides and increased HDL-C.  This study was done on 28 Russians and soy protein isolate was given in cookies form53. Apart from soy protein, there are other components of soy which are non-protein components but may contribute to lipid-lowering by a different mechanism.  According to a study by Ramdath et al in 2017, there are evidences that non-protein components improve markers of cardiovascular health although more studies have to be conducted to better understand the mechanism of the constituents 54. Triglyceride lowering potential is a good agent to explore to reduce over-all cardiovascular disease risk. Angelica gigas Nakai, which has been explored for several medicinal uses was assessed for its activity on triglycerides.  The study was a 12-week, randomized, double-blind, placebo-controlled clinical trial. Treatment group received the plant extract at 200 mg per day in capsule form.  At the end of the trial period, triglycerides and VLDL-C concentrations and triglyceride/HDL-C ratio in the test group were significantly reduced compared to the placebo group 55. In a double-blind randomized, placebo-controlled, parallel trial with 84 subjects, the effects of Cynanchuan wilfordii ethanol extract on blood cholesterol levels evaluated.  After 8 weeks, LDL-C and triglycerides levels were lower than in placebo.  In a subgroup where the participants has LDL-C > 150 mg/dL, there was a significant decrease in total cholesterol, apolipoprotein B, and cholesteryl ester transfer protein 56. Plant-derived compounds which have been purified and characterized may be tested pre-clinically to discover its lipid lowering ability.  Clinical studies may then follow should pre-clinical studies be promising. 

 

Another study done on 358 subjects with hypertriglyceridemia where they were randomly assigned to receive 2,700 mg of xuezhitong (XZT), 1200 mg of xuezhikang (XZK), or placebo.  XZT is an extract of Allium macrostemon Bunge and is said to have lipid-lowering properties. This plant has constituents similar to garlic oil. After 12 weeks, triglyceride levels were reduced from baseline data but the groups who receive XZT and XZK had a significantly lower reduction than placebo.  Treatment with XZT showed superior results compared with placebo in terms of lipid control, triglycerides, LDL-C, and HDL-C.  Daily use of XZT for 12 weeks showed high HDL-C compared to placebo and XZK57. XZT is used in traditional Chinese medicine. This field has its science and basis which can be explored among non-traditional medicine users.  As this population likely uses Western medicine, there may be risks for potential interactions hence it is prudent to have studies to evaluate their compatibility. 

 

Cinnamon (Cinnamomum verium, Cinnamomum zcylanicum) is a popular condiment.  It has been investigated for its medicinal properties. This condiment contains Type-A procynanidin polyphenols. A study by Anderson, et al in 2016 on 137 patients assigned to placebo or treatment groups, treatment being 500 mg of water extract of cinnamon for two weeks showed total cholesterol decrease. LDL-cholesterol was also lowered58. A randomized, open-label, clinical trial looked into Heracleum persicum extract given as an adjunctive therapy for dyslipidemia.  One hundred subjects were randomized to receive 500mg per day of the supplement with 10 mg of Atorvastatin for 8 weeks.  The other group received Atorvastatin 20 mg only.  Out of 100 patients only 52 completed the study.  There were significant reductions in total cholesterol and LDL-C in both groups but the extent of the reduction was higher in the group with H. persicum supplementation59. Curcuma zedoaria contains active chemical components like terpenoids, flavonoids, phenylpropanoids, and sesquiterpenes.  Different doses of the dried powder dissolved in boiling water for 5 minutes were given to 30 mild hypercholesterolemia male volunteers for 2 consecutive months.  The higher the dose of Curcuma the higher the decrease in total cholesterol and LDL-C while a greater increase in HDL-C was observed60.  Another randomized, double-blind, placebo controlled, multi center clinical trial assessed the efficacy and safety of Emblica officinalis (amla) extract in patients with dyslipidemia.  500 mg was administered twice daily for 12 weeks while the other group got placebo.  There was a total of 98 patients. Results looked promising as lowering was seen in total cholesterol


 

Table 1 Summary of Studies Referenced

Active Compound

Source

Formulation

Efficacy

Reference

Type A procyanidin polyphenol

Cinnamomum aromaticum

CinSulin

Decreased total cholestero and LDL-cholesterol

39

Flavonoids

Rhus coriara L.

Capsule

Decreased triglycerides.t otal cholesterol, and LDL-C.  Increased HDL-C.

40

Whey protein hydrolysate containing lactoferrin and immunoglobulin

MPM

(malleable protein matrix)

Powder

Decreased triglycerides.

41

Soy protein isolate

__________

Cookies

Decreased total cholesterol and triglycerides.  Increased HDL-C.

43

Flavonoids

Heracleum persicum

Capsule

Decreased total cholesterol and LDL-C.

44

Chitin gluten fiber

Aspergillus niger

Capsule

Decreased total cholesterol and triglycerides. 

45

Propionic acid

Cabbage kimchi

As food

Decreased triglyceride, total cholesterol, and LDL-C.  Increase in HDL-C.

46

Monacolin K

Red yeast and olive extract

Capsule

Decreased LDL, total cholesterol, and triglycerides.

47

Flavonoids

Curcuma zedoaria Roscoe

Tea

Decreased total cholesterol, LDL-C, and triglycerides.

48

Polyphenol

Annurca apple

Capsule

Decreased total cholesterol and LDL-C.  Increased HDL-C.

49

Polyphenol

Emblica officinalis

Capsule

Decreased triglycerides, total cholesterol, and LDL-C.

50

Cynandione A

Cynanchum wilfordii

Tablet

Decreased total cholesterol and LDL-C.

52

Coumarin derivatoves

Angelica gigas

Capsule

Decreased triglycerides.

53

Saponins

Allium macrostemon Bunge

Capsule

Decreased total cholesterol, and LDL-C. Increased HDL-C.

54

Flavonoids

Hibiscus sabdoriffa

Capsule

Decreased total cholesterol.

55

Monacolin K

Berberis aristata+Silybum marianum+monacolin K and KA

Capsule

Decreased total cholesterol, triglycerides, and LDL-C.

56

Flavonoids

Morus alba

LopiGLIK

Decreased total cholesterol, LDL-C, and triglycerides.  Increased HDL-C.

57

Plant sterol/stanol

——————

Capsule

Decreased LDL-C, total cholesterol, and triglycerides.

58

 


Triglycerides, LDL-C, and VLDL-C in the treatment group compared to placebo61. These plant-based compounds if prepared as appropriate dosage forms for administration to patients will increase convenience and better quantification of dose.  A study on stability may make it possible for commercial manufacture. In order to provide more information as to the active compound responsible for lipid-lowering activity, further studies may be conducted.

 

A formulation of polyphenolic extract from Annurca apple showed that 2 capsules a dat of the product taken for a month have an LDL-C lowering equivalent to 40 mg of Simvastatin or 10 mg of Atorvastatin.  It also showed an increase in HDL-C62.  This study is randomized by design and was conducted on 250 patients. With promising results, an expansion of the population and inclusion of patients with higher baseline LDL-C and total cholesterol may also be included to see the extent of the action of Annurca apple.

 

A two-arm, double-blind-placebo-controlled randomized clinical trial, using a parallel design with 80 primary hyperlipidemic patients given Rhus coriara 500 mg capsules or placebo for 6 weeks.  This plant contains flavonoids as one of its constituents. Results reported significant increase in mean serum HDL-C ad Apo-A1 levels compared to placebo.  No significant difference was observed though in both groups when it comes to reductions in total cholesterol, LDL-C and triglyceride levels.  It was said that a greater reduction was observed among obese patients63.  Bilberries (Vaccinium myrtillus) is known to have high content of phenolic compounds.  Its freeze-dried form containing 40g/day or 480g fresh bilberries equivalent was given to patients who had percutaneous coronary intervention in an 8-week trial period. There were no difference in total cholesterol or LDL-C between study groups but significant reduction in both total and LDL-C were found from the baseline to after 8 weeks of intervention in the bilberry group64. Hibiscus sabdariffa leaves are used in folk medicine and was explored for its hypolipidemic effect.  The study was a double-blind, placebo control, randomized trial on 60 subjects.  The experimental group were given 1 gram of extract for 90 days.  Serum LDL-C and triglycerides decreased in both groups but there were no significant differences between the experimental and placebo groups65. Black cumin (Nigella sativa) seeds were tested on 30 health male volunteers for 4 weeks.  It was only in the treated group where a significant correlation between total cholesterol change after treatment and its baseline level, and between LDL-C change after treatment and its baseline.  No correlations were found for HDL-C and triglycerides66. The population where these studies were conducted may be too small to make a generalization.  While the results between study groups may show little to no significance, there is reduction seen when compared to baseline.  An increase in the dose may be done. 

 

A commercially available product containing red yeast rice and olive extract was given to 50 patients in a double-blind, placebo-controlled randomized trial for 8 weeks.  The commercial product’s constituents were identified as monacolins and hydroxytyrosol. LDL-C was lowered by 24%; total cholesterol, apolipoprotein B, and triglycerides were also reduced.  Oxidized LDL was decreased by 20% 67.

 

Combination formulations have also been explored for lipid lowering activity. One study is the combination of Berberis aristata, Silybum morianum, and monacolin K and KA.  In a double-blind, randomized, placebo-controlled trial with 143 patients.  The product was given once a day at dinner for 3 months.  There was a significant decrease in total cholesterol, triglycerides, and LDL-C compared to placebo68.  Another study done as a cross-over, randomized, double-blind trial used two combination sets of nutraceuticals.  Combination A has policosanol, red yeast rice (Monacolin K 3mg), Berberine 500 mg, astaxantine, folic acid, and coenzyme Q10 while Combination B has red yeast rice (Monacolin K 3.3 mg), Berberine 531.25 mg and leaf extract of Morus alba.  One group was on combination A while the other was on B for four weeks then the groups switched combination.  Combination B reduced LDL-C below 130 mg/dL in 56.6% of the patients while it was only 21.7% of them in combination A.  Both treatments reduced plasma levels of triglycerides, total cholesterol, and LDL-C and increased HDL-C. In patients taking combination B, total cholesterol, and LDL-C reductions were more pronounced69.  Monacolin K is similar to Lovastatin, a cholesterol-lowering compound.  A scientific opinion on monacolin K in red yeast published in 2018 in EFSA Journal concluded that since the compound is identical to lovastatin, the side effects associated with the latter may be seen in the former.  The Panel mentioned that there had been reports of severe adverse reactions at 3 mg/day of monacolin K. On the basis of the information available and several uncertainties highlighted in this opinion, the Panel was unable to identify a dietary intake of monacolins from red yeast rice that does not give rise to concerns about harmful effects to health, for the general population, and as appropriate, for vulnerable subgroups of the population70.  Considering that it is chemical identify to Lovastatin, reduction of daily dose to lower than 3 mg/day may be explored to see if there if it will still cause lipid-lowering but without the adverse reactions. 

 

A dietary supplement in soft gel form was evaluated for its lipid effects.  The randomized cross over study had one group taking esterified sterol/stanol soft gel capsules and the other taking placebo that had soybean oil and medium-chain triacylglycerols from coconut oil.  After 6 weeks the groups swapped treatments.  This was done in combination with Therapeutic Lifestyle Changes (TLC) diet.  Results showed that inclusion of soft gel capsules providing esterified plant sterols/sanols at 1.8 g per day into the TLC diet can have favorable changes in lipoprotein cholesterol levels in patients with hypercholesterolemia71.

 

Bays et al (2013) looked into effects of chitin-glucan fiber on oxidized LDL (OxLDL).  The study was conducted for 6-weeks, randomized, double-blind, placebo-controlled on 130 subjects who were assigned to receive various amounts of chitin-glucan per day.  The 4.5 per day dose significantly reduced OxLDL compared to placebo.  LDL-C had significant lowering at 1.8 g per day dose.  The chitin-glucan did not affect HDL-C or triglycerides72.

 

A study on fermented vegetable, kimchi, showed to improve serum lipid levels in healthy young adults.  This was done on 100 volunteers assigned to two groups with different amounts of kimchi in their daily diet.  After 7 days total cholesterol and LDL-C significantly decreased most especially among volunteers with higher levels at baseline73. Kinchi is consumed across different cultures hence it may be good to explore the specific ingredients to point out which one is responsible for lipid-lowering.  The extent of lowering effect may also be verified.  As consumption of highly spicy dish may also have its side-effects which may be unwanted, it will be important to establish that the quantity consumed is reasonable yet effective in terms of lipid-lowering.

 

The growing concern on how to better manage non-communicable diseases such as those related to cardiovascular system is evident.  Lipid profile is an important factor to determine risk for cardiovascular-related conditions.  More studies related to this should be conducted in low- and middle-income countries to pave the way for studies on how to better manage patients.  The availability of drugs used to manage dyslipidemia, one of the contributing factors for cardiovascular diseases, should be evaluated for acceptability and appropriateness for use of certain patient population.  The interest to find for alternatives to these lipid-lowering agents should be pursued.  There are already studies on some alternatives and conducting it with a bigger population may allow for more generalizability of data collected.  This will afford for a stronger conclusion.  With these alternatives being studied, a look into its manufacture as an appropriate dosage form for better quantification of dose and stability studies to support its feasibility to be marketed.  These alternatives may either replace current options, especially for populations who cannot be prescribed with them, or they may be supportive therapy for current options.

 

CONCLUSION:

The availability of alternatives to Statins are supported by pre-clinical studies and even randomized controlled studies on human subjects.  A study on these promising alternatives on bigger population may allow for more supporting date to be made available.  Looking into the possibility of manufacturing these available alternatives as a dosage form may also be worthy citing convenience of administration, better quantification of dose, and stability.  These potentials may remain as alternatives or may be options for patients where Statins are contraindicated.  With the increasing popularity of food supplements or nutraceuticals, these may find favor among those who need lipid-lowering agents.

 

CONFLICT OF INTEREST:

The authors have no conflicts of interest.

 

ACKNOWLEDGEMENT:

The researcher thanks her adviser on this paper and co-author, Dr. Erwin Faller, for his expertise, guidance and support.  Special thanks to Centro Escolar University and University of San Carlos.

 

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Received on 18.05.2021            Modified on 13.06.2021

Accepted on 05.07.2021           © RJPT All right reserved

Research J. Pharm. and Tech 2022; 15(1):270-278.

DOI: 10.52711/0974-360X.2022.00044