The Effect of a Dietary Supplement Containing Rhamnan Sulfate from Monostroma nitidum on Carotid Atherosclerotic Plaque: A Case Series

Abstract

We report on 6 patients in our care who were harboring atherosclerotic plaque in the carotid arteries. This condition poses a risk of acute ischemic stroke and indicates potential atherosclerosis elsewhere in the vascular system. The plaque was revealed by routine ultrasound measurement of carotid intima-medial thickness (CIMT) defined as the distance between the lumen-intima interface and the media-adventitia interface. Recent improvements in image resolution and edge detection algorithms have resulted in improved reliability and clinical usefulness of the technology.

The patients were enrolled in a systems-based functional medicine program of cardiology prevention to address root causes. The program provided personalized interventions that included drug therapy, dietary supplements, and lifestyle modification. The 6 patients followed the integrative regimen, which successfully managed existing cardiovascular symptoms and risk factors while keeping various biomarkers under control. However, they continued to exhibit carotid plaque with no improvement.

A novel dietary supplement that targets endothelial glycocalyx regeneration was added to the personalized intervention programs. The supplement contains a proprietary extract of rhamnan sulfate from the green seaweed Monostroma nitidum. The 6 participants consumed the supplement daily, and their plaque burden was measured after 6 months using the same CIMT technology. In every case, the total plaque burden was reduced, with an average reduction in the 6 patients of 5.55 mm, which is statistically significant. Significant reductions in maximum carotid plaque thickness were also observed at the end of the 6 months. The study suggests that rhamnan sulfate from Monostroma nitidum may provide a safe and effective intervention for reducing atherosclerotic plaque, and should be evaluated as an adjunct therapy for prevention and treatment of cardiovascular disease.

Introduction

Cardiovascular disease (CVD), the single leading cause of death in the United States,¹ continues to pose a major challenge to healthcare practitioners. Labor income loss attributed to heart disease in the United States in 2018 was over $200 billion, with stroke contributing another $63.6 billion.² The origins of most heart disease and strokes can be traced to atherosclerosis, a systemic condition characterized by the accumulation of lipid-laden plaques within arterial walls.³

As these plaques evolve, they can either harden and narrow the arteries or become vulnerable or unstable plaques. The vulnerable plaques, characterized by a lipid-rich core with a thin fibrous cap, pose the greatest risk, as their rupture can lead to thrombus or clot formation and sudden arterial occlusion.⁴ In the carotid arteries, which supply oxygenated blood to the brain, plaque accumulation poses a specific risk of stroke. Carotid arteries can also provide an accessible window into the condition of the vascular system as a whole. Correlations have been established between plaque in the carotid arteries and plaque in the coronary arteries.^5,6 Intima-media thickness (IMT) of the carotid arteries has been associated with a variety of cardiovascular risk factors and shown to be predictive of pathologies including cerebrovascular disease, coronary artery disease, and endothelial dysfunction.⁷

Carotid plaque burden can be measured using a non-invasive ultrasound-based technique known as carotid intima-media thickness (CIMT) test. This measurement can provide important insights into an individual’s overall cardiovascular health and risk profile.⁸ CIMT measures the thickness of the intima and media, the innermost two layers of the arterial wall, serving as a surrogate marker for atherosclerosis. An increased CIMT suggests a higher burden of atherosclerosis and, consequently, a higher risk of cardiovascular events. CIMT enjoys many advantages as an imaging modality, being portable, safe, and economic compared to other alternatives such as CT angiography and MRI imaging. At the same time, it retains sensitivity and robustness thanks to the development of automated edge-detection algorithms for image analysis.⁷ As a result, CIMT has become a standard tool in both clinical and research settings for assessing vascular health.

Once plaque has been identified in the vascular system, healthcare practitioners face the question of what interventions are possible that may reduce the plaque burden and mitigate cardiovascular risk. In spite of the progress made on pharmaceutical therapies that target different risk factors and mechanisms, events, and deaths from CVD continue to occur and even increase in certain areas.⁹ There is an urgent need to identify novel targets to address the significant residual risk.

In recent years, marine-derived sulfated polysaccharides, such as rhamnan sulfate (RS) from the green seaweed Monostroma nitidum, have gained attention for their specific benefits to vascular health. RS has been shown to possess anticoagulant, antioxidative, anti-obesity, anti-diabetes, anti-inflammatory, and lipid-lowering properties, which are valuable in maintaining endothelial structure and function.^10,11 Most importantly, RS has been shown to protect and regenerate the endothelial glycocalyx (EGX).¹² The EGX is a micro-thin, gel-like layer of different glycans that covers the luminal surface of vascular endothelium. It is considered the first line of defense against endothelial damage that leads to the development of atherosclerotic plaque. Since endothelial damage starts with a compromised EGX, the EGX could potentially serve as a novel therapeutic target for managing atherosclerotic plaque.¹³

Taking note of the relevant research, we included an RS-containing dietary supplement in our cardiology prevention program. This case series aims to clinically explore the effect of this EGX-regeneration therapy on carotid arterial plaque that had not responded to a personalized integrative intervention program. CIMT was used to monitor changes of carotid plaques in 6 patients before and after consumption of the dietary supplement for 6 months. We believe this is the first time that real-world human clinical data for the effect of an EGX-regeneration therapy on atherosclerotic plaque are reported. It is our hope that the data reported here will generate more interest in future clinical research on this promising new therapeutic approach.

Materials And Methods

Study Participants

The 6 participants presented in the final analysis were existing patients at the True Health Center for Functional Medicine (Folsom, CA). This multi-disciplinary practice delivers personalized primary care with a proprietary data-driven wellness plan that has successfully prevented any heart attacks from occurring among its patients for over a decade. The study participants had a high risk for cardiovascular events with a significant presence of plaque in their carotid arteries as diagnosed by CIMT (at least one individual plaque > 1.0 mm thickness).

Patients were enrolled in a cardiology prevention program that uses a systems-based functional medicine approach to address root causes individually with pharmaceuticals, dietary supplements, and lifestyle modification. Unlike many others, these 6 patients did not experience any improvement on the measurements of carotid plaque burden, although their biomarkers and risk factors had also improved significantly. Therefore, subjects were chosen for the study because they fit the profile of having so-called “stubborn plaque.” They had followed an integrative treatment regimen that managed existing cardiovascular symptoms and risk factors while keeping various biomarkers under control, yet continued to exhibit carotid plaque with no improvement.

Dietary Supplement Formulation

The intervention for this case series is a proprietary dietary supplement, Arterosil HP^®, from Calroy Health Sciences LLC (Scottsdale, AZ). The main ingredient in Arterosil HP is MonitumRS™, a proprietary extract of rhamnan sulfate, one of the best studied endothelial glycocalyx regenerating compounds, from the green seaweed Monostroma nitidum. It also contains a powdered blend of 22 fruits and vegetables that are rich in antioxidants and polyphenols known to improve endothelial function and reduce the risk of CVD.¹⁴

Study Design

Study participants continued their cardiology program while adding Arterosil HP^®, 1 capsule twice per day for 6 months, to their existing drug and supplement regimens. Patients were instructed to maintain their body weight as well as exercise and diet with no changes during the intervention period. Patient compliance to the program was checked via standard follow-up phone calls and at each visit.

The study spanned a total of 8 months, from June 2020 to February 2021. At the beginning and end of the 6-month intervention period for each subject, CIMT was performed, and carotid plaque burden was analyzed by Vasolabs (Cross, UT) to evaluate the effect of the intervention. We calculated the total carotid plaque burden by summation of the maximum thickness of all identified carotid plaques for each participant. Each participant also had a blood draw during the 2 visits. Blood and urine samples were sent to Cleveland HeartLab (Cleveland, OH) for inflammation panel testing. The 7 inflammatory biomarkers in the panel are implicated in the development of atherosclerosis and have been used for risk evaluation of CVD.

Statistical Analysis

Paired t tests were conducted after testing normality of samples to determine changes in study outcomes before and after Arterosil HP intervention. The defined significance level is 0.05. Data analyses were performed using R Statistical Software (v4.3.2; R Core Team 2023) in conjunction with Microsoft Excel.

Results

Total Carotid Plaque Burden

All 6 participants saw a reduction in total carotid plaque burden. Of those 6, the maximum reduction in total plaque burden was 8.08 mm, the minimum 2.49 mm, and the mean reduction 5.55 mm (Table 1). The participant with the least identifiable carotid plaque at baseline saw her total carotid plaque burden reduced to 0 mm.

Table 1.

Total carotid plaque burden of subjects at baseline and 6 months after intervention

Participant	Age	Sex	Total Plaque Burden (Baseline)	Total Plaque Burden (Endpoint)	Change
1	50	M	8.91	3.83	-5.09
2	70	M	10.46	2.52	-7.95
3	71	F	4.82	1.31	-3.51
4	62	M	12.52	4.44	-8.08
5	71	F	11.33	5.13	-6.20
6	52	F	2.49	0.00	-2.49

A paired sample t test was conducted to compare the total carotid plaque burden of the participants at baseline and at the end of the intervention period (Figure 1). The results show the change on average of the 6 participants is statistically significant (P = .0019). A Shapiro-Wilk test was completed to validate the assumption of normality for the participant’s total plaque burden at baseline (W = 0.90975, P = .4347) and endpoint (W = 0.99541, P = .7838), revealing no significant departure from normality in the samples. The same test was repeated for subsequent samples analyzed by t test.

Figure 1.

Total carotid plaque burden as measured by ultrasound at baseline and 6 months after intervention. The results are shown as means of the 6 participants, and the reduction is statistically significant.

RCA and LCA Plaque Thickness

Additionally, individual measurements were recorded for the maximum plaque thickness on the left carotid artery (LCA) and right carotid artery (RCA). A statistically significant reduction of mean maximum plaque thickness of 0.89 mm (P = .048) was observed in the right carotid and 1.11 mm (P = .0034) in the left (Figure 2).

Figure 2.

RCA (Panel A) and LCA (Panel B) maximum plaque thickness as measured by ultrasound at baseline and 6 months after intervention. The results are shown as means of the 6 participants, and the reductions are statistically significant.

Other Measurements

Participants completed an inflammation panel testing by Cleveland HeartLab and were evaluated for blood pressure at the beginning and end of the study. The biomarkers in the inflammation panel included F₂-isoprostanes, oxidized LDL (OxLDL), asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), microalbumin, high sensitivity CRP (hsCRP), lipoprotein-associated phospholipase A2 (Lp-PLA2) activity, creatinine, and myeloperoxidase (MPO). This inflammation testing measures risk for CVD beyond the cholesterol level. It also provides an insight into the mechanism of changes for therapeutical interventions.

Table 2 shows the averages of these biomarkers for the 6 participants before and after intervention. At the beginning of the study, these biomarkers were generally under control. No significant changes were observed for any of these measurements. Due to missing lab results and also results reported as a range (i.e., below a specific level), no statistical analysis was performed for F₂-isoprostanes, microalbumin, and hsCRP.

Table 2.

Biomarker test results at the baseline and 6 months after intervention.

Biomarker	Mean at Time 0	Mean at 6 Months	P value
F2-Isoprostane (ng/mg creatinine)	0.39a	0.43a	N/A
OxLDL (U/L)	42.83	46.17	.15
ADMA (ng/mL)	112.17	102.17	.10
SDMA (ng/mL)	114	100	.06
Microalbumin (mg/g creatinine)	9.85b	6.2b	N/A
hsCRP (mg/L)	1.45c	1.30c	N/A
Lp-PLA2 (nmol/min/mL)	95.33	93.3	.89
MPO (pmol/L)	298.80	263.80	.40
Creatinine (mg/dL)	106.4	115.17	.78

^aMean of 3 participants. One participant had undetectable results. One participant had a result of less than 0.21. The other participants had results of less than 0.51 and 0.40. No statistical analysis was performed.

^bMean of 2 participants. Three other participants had results of less than 3.0. One participant has a missing data point. No statistical analysis was performed.

^cMean of 4 participants. One participant had a missing data point, and the other had a result of less than 0.3. No statistical analysis was performed.

Upon further examination, the incomplete microalbumin data exhibit the greatest change of 37% among all the tests. Microalbumin measures kidney function as a risk for CVD. The presence of small amounts of albumin in the urine indicates microvascular endothelial dysfunction and has been associated with the loss of EGX.^15,16 Although microalbumin < 30 mg/g is generally considered normal, lower levels at and above 3.9 mg/g for men or 7.5 mg/g for women were associated with an almost 3 fold risk of CVD in the Framingham Heart Study.¹⁷ Our limited data indicate the intervention had a potential to lower microalbumin when it is above the optimal levels, i.e., 3.9 mg/g for men or 7.5 mg/g for women.

There was also no significant change in the average blood pressure of the 6 participants during the invention period (Table 3). The average systolic blood pressure was slightly elevated and remained stable during the intervention. Overall, blood pressure is well controlled for this group of participants with our cardiology prevent program. There was no additional intervention implemented to lower systolic blood pressure during the study.

Table 3.

Participant blood pressure pre- and post-intervention. The results are shown as means of the 6 participants, and no statistically significant changes are observed.

Blood Pressure	Mean at Time 0	Mean at 6 Months	P value
Systolic	122.2	129.0	.44
Diastolic	72.3	68.2	.36

Adverse Reactions

Supplementation was well tolerated and no adverse reactions were reported during the duration of the study. Arterosil HP contains food-grade ingredients in a non-animal hard capsule and is manufactured under the Code of Federal Regulations, Title 21, Part 111 (21 CFR Part 111). The dietary supplement is shown to be safe and well tolerated in this study.

Discussion

Although rapid advancement of medical technology has resulted in a significant decrease of mortality, CVD remains the leading cause of death in the United States and a heavy economic burden to society. Atherosclerosis is a multifactorial and complex condition that leads to heart disease and many other health problems. The development and progression of atherosclerosis involve interaction of many genetic and environmental factors encompassing the commonly known risk factors such as dyslipidemia, hypertension, hyperglycemia, obesity, hyperuricemia, etc.

Given the complexity, an integrative functional medicine approach is well suited for the management of atherosclerosis. We have developed and successfully implemented an integrative cardiology prevention program in our clinical practice. Here we report a case series of “stubborn” plaque patients to evaluate the safety and efficacy of Arterosil HP, a novel proprietary formulation designed to restore the EGX.

Atherosclerosis, characterized by the progressive development of lipid-laden plaques in the arterial walls, is the major underlying pathology of most cardiovascular diseases, including myocardial infarction. The standard treatment of atherosclerosis aims at the risk factors with lipid-lowering, anti-platelet/coagulation, hypotensive, and hypoglycemic drugs.¹⁸ Despite the development of clinical tools for diagnosis and treatment, including statins, thrombolytic medicines, PCSK9 inhibitors, etc., adverse cardiovascular events are still prevalent. New treatment options for atherosclerosis deserve to be examined for use alongside existing best practices.

Functional medicine takes a systems-based approach to address the root causes of cardiovascular disease with individualized plans. Various strategies to stabilize and reverse atherosclerotic plaque include interventions to regulate metabolism, oxidative stress, inflammation, immune response, cellular death mechanisms, vessel wall remodeling, neovascularization, etc.¹⁹ Our practice uses a functional medicine approach centered on managing inflammation to treat atherosclerotic plaque. The integrative program normally combines drug therapy, dietary supplementation, and lifestyle modification to reduce patients’ risk of heart attack and stroke. Results of this program have been encouraging, with no cases of myocardial infarction occurring in any patients over a period of more than ten years.

Despite current advances in treating atherosclerosis, we are still far from conquering the disease. One of the major reasons is the complex underlying pathology that is not yet fully understood. Much recent work on the pathogenesis of atherosclerosis has focused on the “response to injury theory”. The theory holds that atherosclerosis may be understood as an inflammatory response to insults occurring to the endothelium.²⁰ When the endothelium is damaged by atherogenic risk factor(s), LDL follows adhered monocytes and penetrates the endothelium into the intima. Oxidation and accumulation of LDL in the subendothelial space trigger the formation of foam cells from monocyte-derived macrophages. The development of atherosclerotic plaques ensue with the exacerbation of inflammatory and immune response, proliferation and migration of vascular smooth muscle cells, and remodeling of the extracellular matrix.²¹

A novel insight that adds to our understanding of atherogenesis is the role of EGX.²² The EGX is a micro-thin, gel-like layer consisting of glycoproteins, proteoglycans, glycosaminoglycans, and glycolipids, which coats the entire luminal surface of the vascular endothelium. It is a selectively permeable barrier and a signal transducer with antioxidant, anticoagulant, antiadhesive, and anti-inflammatory properties.²³ The endothelial glycocalyx is a delicate structure and can be damaged by several common mechanisms involved in the pathogenesis of atherosclerosis. These include high blood glucose, oxidative stress, and inflammation. It is a fact that atherosclerotic lesions tend to occur at very specific locations, such as branches, bifurcation, and curvatures of arteries. These locations are characterized by disturbed blood flow patterns, including reversed, oscillatory, and turbulent flows associated with lower shear stress. Coincidentally, the EGX dimension is significantly reduced at these atheroprone locations.²⁴ The carotid artery is one of those locations that is prone to atherosclerotic plaque development.

Given the vital role the EGX plays in the pathology of cardiovascular diseases, it has increasingly become a target for therapeutic intervention.²⁵ In our patients with “stubborn plaque”, we decided to test Arterosil HP, a dietary supplement containing RS, which has been shown to regenerate EGX.¹² EGX is the first line of defense against endothelial damage and dysfunction. Arterosil HP is the first commercial product specifically designed for EGX regeneration.²⁶ We hypothesized adding EGX as a new target in our cardiology prevention program would allow us to address atherosclerotic plaque more effectively. After 6 months of intervention, the 6 participants with “stubborn plaque” saw a substantial reduction of their total carotid plaque burden. Their RCA and LCA maximum plaque thickness also decreased significantly. We found that the supplement is safe to use and well tolerated.

The findings of this case series of 6 participants suggest that daily supplementation with an RS-based dietary supplement may positively influence carotid plaque burden. Carotid atherosclerosis often presents asymptomatically yet is a well-established risk factor for ischemic stroke. It is also known to be associated with other common cardiovascular risk factors such as total cholesterol, smoking, and HDL to total cholesterol ratio.²⁷ CIMT, as measured by ultrasound, has been validated as a surrogate marker for atherosclerosis and is clinically used as a tool for clarifying cardiovascular disease risk.²⁸ Additionally, total carotid plaque burden may be a more sensitive marker of cardiovascular risk than intima-media thickness.⁷

RS isolated from Monostroma nitidum is a natural glycan ranging in molecular weight from the thousands up to one million.²⁹ Its chemical structure, specifically glycosyl linkages and monosaccharide composition, may vary depending on geographical location and environmental conditions. It was first studied extensively for its anticoagulant activity due to its structural similarity to heparin and was found to promote cardiovascular health.^30-32 Later, oral RS was found not to impact coagulation pathways to thin blood in an animal study while preventing thrombosis. The animals also showed no internal or external bleeding.³³ It is, therefore, believed that proper dosing of RS improves EGX integrity, making the endothelial wall more thromboresistant.

Blood coagulation is known to be activated in response to vascular injury and may contribute to plaque development.³⁴ In advanced atherosclerosis, high-risk plaques become prone to erode and/or rupture. The resulting thrombi superimposed on eroded or ruptured plaques may obstruct blood flow which leads to acute ischemic syndrome.³⁵ As such, anticoagulant and antithrombotic therapies are widely used in the prevention and treatment of atherosclerosis and atherothrombosis.³⁶ The potential of RS to keep the endothelium thromboresistant may have played a role in the observed antiatherogenic effect in the study and deserves further research.

It has been reported that RS enhances EGX and decreases the LDL permeability of human coronary artery endothelial cells.³⁷ The finding was recently validated by another study.³⁸ This new study also demonstrated that orally administered RS reduced vascular inflammation and inhibited proliferation and migration of smooth muscle cells. Specifically, RS inhibited NF-ĸB activation induced by TNF-α in human endothelial cells. In ApoE knockout female mice fed with a high fat diet, RS significantly reduced vascular inflammation as demonstrated by a decrease of macrophages in the aortic root and phosphorylation of NF-ĸB p65. In addition, there was an increase of endothelial nitric oxide production in these mice. More importantly, RS treatment significantly decreased plaque deposition on, and also stenosis of, the aorta and thoracic aorta. The same study conducted ultrasound imaging of the aortic root and found decreased lipid deposition as well as decreased stenosis in the mice. The study clearly demonstrated that RS has potent anti-inflammatory properties and reduces atherosclerosis in a relevant animal model for atherosclerosis.

Regulating access of circulating blood cholesterol to the endothelium may serve as a major mechanism for Arterosil HP, the RS-containing supplement, to reduce carotid plaque. Elevated LDL cholesterol has long been recognized as a major risk factor for atherosclerosis. However, it is also known that a significant number of CVD events occur with normal blood cholesterol. One study shows 56.4% of 55 539 patients hospitalized with CAS had optimal LDL cholesterol level of < 100 mg/dL.³⁹ Another study revealed that 37.8% of 740 middle-aged individuals with normal blood cholesterol levels of < 200 mg/dL and other modifiable risk factors (i.e., blood pressure, fast blood glucose, A1C, and smoking) in the optimal ranges had subclinical atherosclerosis as defined by the presence of atherosclerotic plaques.⁴⁰

One explanation to the risk beyond the LDL cholesterol level is the LDL particle size. Small, dense LDL particle are more atherogenic than large, buoyant LDL particles because they have increased oxidizability, longer circulating time, better penetration through the endothelium, and enhanced binding to the extracellular matrix in the subendothelial space after penetration.⁴¹ In fact, it is believed the retention of apolipoprotein B (apoB) -containing lipoprotein such as LDL in the subendothelial space initiates atherosclerosis.⁴² Decreasing LDL passage through the endothelium by mechanism of a robust EGX is, therefore, a novel strategy to reverse atherosclerotic plaques. It is expected to complement current cholesterol-lowering strategies to stabilize and reverse atherosclerotic plaque.

In this case study, the addition of Arterosil HP to our cardiology prevention program significantly reduced carotid plaques in 6 months. The limited data on the reduction of microalbumin indicate an improved microvascular barrier function related to EGX. Half of the 6 participants were on statins during the study. Their cholesterol levels were in normal ranges before the study, so lipid panels were not scheduled at the end of the study. Although the effect of statins on the plaque regression cannot be completely ruled out, it is unlikely statins by themselves would cause such a dramatic improvement for two reasons. First, research has demonstrated statin therapy only causes small reduction of carotid plaque by ultrasound over a longer period time of a year or more.⁴³ Second, previous treatment with statins did not cause any regression of carotid plaques in the participants of this study.

Since inflammation drives development of atherosclerotic lesions, anti-inflammatory therapy can play an important role in reversing the process. It is believed that reducing local inflammation allows some foam cells to emigrate out of the intima and incoming phagocytes to remove components of the plaque via efferocytosis.^44,45 It is well established that NF-ĸB plays an important role in the cellular regulation of inflammatory response. Activation of NF-ĸB is reported in the key cellular components of atherosclerotic plaques at different stages.^46,47 RS inhibited NF-ĸB signaling in the aorta and reduced macrophages in atherosclerotic mice.³⁸ It is plausible that the RS-containing supplement induced plaque shrinkage by enhancing phagocyte-mediated efferocytosis via its anti-inflammatory activity.

Anti-inflammation is a major component of our cardiology prevention program. We use an inflammation panel testing to monitor patients’ progress. The 6 participants in this study saw no significant changes in the major inflammation biomarkers of hsCRP, Lp-PLA2, and MPO in the panel. This points to the importance of EGX in anti-atherosclerotic therapy. Evidence suggests that oral supplementation of RS can be incorporated into EGX.^33,38 As such, RS not only is positioned close to its target but also enhances the anti-inflammatory property of the EGX. To further study such an effect, we need better clinical tools to evaluate EGX directly and inflammation at the atherosclerotic lesions.^26,48,49

We have successfully implemented a systems-based cardiology prevention program at our practice. The program takes an integrative approach to the root causes by combining different therapies including pharmaceuticals, nutraceuticals, diet, and exercise. We use a variety of cardiometabolic biomarkers to assess and monitor the pathophysiology that drives the disease processes. These include lipid profiles, blood sugar and glycosylated hemoglobin, inflammation biomarkers, oxidative stress, uric acid, homocysteine, nitric oxide, etc. We incorporate CIMT in the program to detect subclinical atherosclerosis at an early stage for prevention. The program is effective to bring biomarkers under control and prevent major adverse cardiac events. However, we were unable to stop or reverse the progress of carotid plaques in some patients until we introduced Arterosil HP, a dietary supplement containing a glycocalyx regenerating compound, in the program.

Endothelial dysfunction is at the center of atherosclerosis. It starts at EGX disruption and dysfunction. Targeting EGX addresses a critical step that initiates and drives atherogenic process. This is a new tool complementing the existing therapies for a multifactorial disease. The results of this case series indicate that an RS-containing dietary supplement Arterosil HP has the potential to stabilize and reverse atherosclerotic plaque in humans. It can be incorporated into clinical practice easily and safely as an adjunct therapy of any integrative program for the management and treatment of atherosclerosis.

Limitations

Common limitations noted in randomized clinical trials using CIMT as an endpoint include the reproducibility of measurements and differences in expected progression rates of CIMT.⁵⁰ Here we include total plaque burden and maximal RCA/LCA plaque burden as measures, which are known to have a high level of reproducibility. Additionally, selected subjects in this retrospective case series generally presented with modest or no reduction of carotid plaque burden in the preceding 2-3 years. Nevertheless, alternative plaque imaging technologies such as CT angiography and MRI have the potential to present more precise measurements of plaque composition as well as plaque morphology. The data here are obtained retrospectively from a small population without a control group. Although the fast reduction of carotid plaque is impressive, there were potential interactions with other interventions used by individual participants in the program. Additionally, subjects presented in this study maintained various blood markers associated with cardiovascular disease within safe levels. More work needs to be done to show that the results can be generalized to the wider population of CVD risk patients. Future research should include larger, more diverse populations and control groups. Despite these limitations, the data generated remain compelling and clearly indicate a need for further study, including randomized clinical trials of RS-based treatments for atherosclerosis.

Biographies

Dr. Kristine Burke is certified in family medicine and sports medicine and fully certified in functional medicine. She is the Chief Medical Officer for Diabetes Reversal Group LLC and has practiced the full spectrum of family medicine in the Folsom and El Dorado Hills areas since 1997. Dr. Burke believes that the best medical care requires time, a trusting relationship, and a collaborative approach to achieve the most successful personal outcomes: good health, longevity, and superior quality of life. She truly enjoys caring for her patients and strives to guide them to wellness and prevention, as well as carefully managing their illnesses and medical conditions. Kristine Burke is a member of Calroy’s Science and Medical Advisory Board.

Ian G. Jennings is an M.D. candidate at the University of California, San Diego, School of Medicine, having graduated Summa Cum Laude from California Polytechnic State University with a B.A. in Business Administration. He previously studied microbiome genomics at the Davidson Lab in San Luis Obispo and later served as a clinical research coordinator and lead medical scribe at True Health Center for Functional Medicine in Folsom, California. His research interests include holistic, integrative health, innovative chronic disease management approaches, and the convergence of clinical medicine and biomedical sciences.