The Effect of Farlong® NotoGinseng™ (Ginseng Plus®) on Cholesterol and Blood Pressure

A Randomized, Placebo-controlled, Double-blind, Parallel Study to Determine the Effect of Farlong® NotoGinseng™ (Farlong® Ginseng Plus®) on Cholesterol and Blood Pressure

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04069715

Enrollment

Registered

2019-08-28

Start date

2016-07-20

Completion date

2019-06-01

Last updated

2021-05-17

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hyperlipidemias, Hypertension

Keywords

LDL-C, Blood pressure, triglycerides, HDL-C, total cholesterol, endothelial vasodilation, Hyperlipidemias, Hypertension

Brief summary

In this randomized, placebo-controlled, double-blind parallel study in human participants with elevated LDL-C and elevated BP described here, the clinical benefits of Farlong NotoGinseng™ (Farlong Ginseng Plus® Panax Notoginseng extract), a product made of highly concentrated pharmaceutical grade notoginseng root extract, and containing high potency bioactive components, notoginsenoside, ginsenoside Rb1 and ginsenoside Rg1, will be investigated for its efficacy on LDL-C and blood pressure.

Detailed description

Health statistics include data on health disparities, global impact of cardiovascular diseases (CVDs) and risk factors including smoking, physical activity, body weight, cholesterol, blood sugar and blood pressure (BP) (1). Based on this, it is estimated that 33% of US adults had high blood pressure in 2009-2012 and during the same period, 43% of Americans had total cholesterol of 200 mg/dL or higher (2). Chronic, elevated BP, defined as systolic BP (SBP) greater than 140 mmHg and diastolic BP (DBP) greater than 90 mmHg is clinically known as hypertension (3). Notably, hypertension is a strong, consistent, and independent risk factor for CVD and renal disease, including stroke, coronary heart disease, and kidney failure (4). Epidemiological evidence indicates that there is a log-linear relationship between elevated bad cholesterol, or low density lipoprotein-cholesterol (LDL-C) concentration, and relative risk of CVD (5). Lifestyle factors known to modify BP and cholesterol levels, including a balanced diet and exercise are not always met, highlighting the potential for nutritional supplementation. The use of nutritional supplements, which might be effective in the reduction of high BP (hypertension) and hypercholesterolemia, is rapidly growing. However, most of the products available on the market have not been clinically evaluated for their effectiveness. Common ingredients found in cholesterol-lowering supplements include plant sterols. Plant sterols have been shown to reduce hypercholesterolemia in numerous experimental studies and in clinical trials, and are associated with lowering LDL-C by 10-15% (6;7). It has been estimated that consumption of at least 1.3 g of plant sterols/day may help to reduce the risk of heart disease by lowering blood cholesterol (8). Previous pre-clinical work reported that in addition to reduced cholesterol, supplementation with plant sterols can lower BP in hypertensive animals, although studies in humans are in early phases of development (9). Plant sterol supplementation may also improve vascular function, as one human trial found an association with sterol intake and lower levels of carotid wall thickness in older Amish participants (10). Traditional Chinese Medicine has been used to treat cardiovascular diseases for thousands of years and species of the genus Panax plant are widely used in China and all over the world. Panax notoginseng (Burk.) F.H. Chen, is one of about 12 species in the Panax genus of the Araliaceae. Due to its sensitivity to light, P notoginseng is restricted to narrow geographic regions growing at an altitude of 1200-2000 m, primarily in the Wenshan mountains of Yunnan province in the People's Republic of China. The plant grows to a height of 30-60 cm and has dark green leaves branching from the stem where it typically bears a cluster of berries in the middle (11). The root of P notoginseng has a 400-year old history as a tonic and hemostatic drug; over 200 compounds have been isolated from this plant, exhibiting a variety of pharmacological effects, and appropriately enough the genus name Panax is derived from the Greek word (Pan = all + axos = medicine) meaning 'cure all' (12). Historically, Chinese medicine ascribes Panax ginseng C.A. Meyer to tonifying qi, while P notoginseng nourishes the blood by dissipating blood stasis, inhibiting bleeding, enhancing circulation and alleviating pain. While the radix and rhizome of P notoginseng are used for bleeding disorders, the flower of this plant has been noted for several properties, including but not limited to, treating hypertension, and rejuvenating the liver (11). In the literature, extracts from P notoginseng have been referred to as Sanchitongshu, Xueshuantong, Sanqi or Tianqi and these ginsenosides from P notoginseng have collectively been referred to as Panax Notoginsenoside Saponins. The primary bioactive ingredients in notoginseng plants are saponins, of which more than 60 have been identified (13). Saponins from notoginseng plant exert angiogenic effects by activating vascular endothelial growth factor and its receptor in downstream signaling pathways (14;15). Further, ginsenoside Rg5, a compound newly synthesized during the steaming process of notoginseng was found to promote angiogenesis and improve hypertension in animal models without adverse effects in the blood vasculature (16). Rg5 specifically increased phosphorylation of insulin-like growth factor-1 receptor (IGF-1R) resulting in stimulation of nitric oxide pathways to enhance angiogenesis (16). These studies suggest that notoginseng may have beneficial clinical applications in the management of CVD. Currently, there is a lack of well-controlled trials evaluating the doses and effects of notoginseng (17). In this context, it is imperative to conduct well-controlled clinical trials that may unravel the mechanism (s) of action as well as evaluate the clinical potential of notoginseng as a natural health product and dietary supplement. In this randomized, placebo-controlled, double-blind parallel study in human participants with elevated LDL-C and elevated BP described here, the clinical benefits of Farlong NotoGinseng™ (Farlong Ginseng Plus® Panax Notoginseng extract), a product made of highly concentrated pharmaceutical grade notoginseng root extract, and containing high potency bioactive components, notoginsenoside, ginsenoside Rb1 and ginsenoside Rg1, will be investigated for its efficacy on LDL-C and BP.

Interventions

DIETARY_SUPPLEMENTFarlong NotoGinseng™ (Farlong Ginseng Plus® Panax Notoginseng extract)

A product made of highly concentrated pharmaceutical grade notoginseng root extract, and containing high potency bioactive components, notoginsenoside, ginsenoside Rb1, Rg1, Rd, Re and Rb2.

OTHERPlacebo

Turmeric 0.4%, Rice Flour 76.6%, Magnesium stearate 23%, capsule shell (gelatin) 61 mg

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

SUPPORTIVE_CARE

Masking

DOUBLE (Subject, Investigator)

Intervention model description

This was a randomized, placebo-controlled, double-blind, parallel study with a 4-week therapeutic lifestyle change diet (TLC) run-in period and a 12-week supplementation period.

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

Yes

Inclusion criteria

1. Male and females age 18-75 years (inclusive) 2. BMI 23.0 to 32.5 kg/m2 3. Participants with LDL-C ≥2.6 mmol/L and \<3.8 mmol/L (≥ 100 mg/dL and \< 150 mg/dL) 4. Participants with pre-hypertension (systolic blood pressure of greater than or equal to 100 and less than 140 mmHg) 5. Participants agree to follow a therapeutic lifestyle changes (TLC) diet 6. If female, participant is not of child bearing potential, which is defined as females who have had a hysterectomy or oophorectomy, bilateral tubal ligation or are post-menopausal (natural or surgically with \> 1 year since last menstruation) OR Females of childbearing potential must agree to use a medically approved method of birth control and have a negative urine pregnancy test result. Acceptable methods of birth control include: * Hormonal contraceptives including oral contraceptives, hormone birth control patch (Ortho Evra), vaginal contraceptive ring (NuvaRing), injectable contraceptives (DepoProvera, Lunelle), or hormone implant (Norplant System) * Double-barrier method (condoms with spermicide or diaphragm with spermicide) * Intrauterine devices * Vasectomy of partner (shown successful as per appropriate follow-up) * Non-heterosexual lifestyle or agrees to use contraception if planning on changing to heterosexual partner(s) 7. Willing to maintain current physical activity patterns throughout the study 8. Willingness to complete questionnaires, records, and diaries associated with the study and to complete all clinic visits 9. Healthy as determined by laboratory results, medical history, and physical exam 10. Has given voluntary, written, informed consent to participate in the study

Exclusion criteria

1. History of allergic reaction or hypersensitivity to any of the study supplement components 2. Pregnant, breastfeeding, or planning to become pregnant during the course of the trial. 3. Use of cholesterol-lowering or blood pressure lowering prescription drugs within the last 6 months prior to randomization 4. LDL-C ≥ 3.37 mmol/L (130 mg/dL), if the 10-year risk of cardiovascular event is ≥ 20% as estimated by the Framingham risk score 5. LDL-C \> 3.5 mmol/L (135.34 mg/dL) OR if the total cholesterol vs. HDL-C ratio is \> 5.0 OR hs-CRP \> 2 mg/L in males \> 50 years and females \> 60 years, and if the 10-year Framingham risk score is 10-19% 6. Total cholesterol vs. HDL-C ratio \> 6.0, if the 10-year Framingham risk score is \< 10% 7. Use of ginseng-based drinks or products 8. Health supplements that affect blood pressure and cholesterol levels other than vitamins and minerals, such as plant sterols, omega-3, fish oil, soy protein, soluble oat fiber, psyllium seed husk, licorice or other blood pressure and cholesterol lowering nonprescription supplements within 1 month of enrollment and during the study 9. Persons on medications listed in section 4.3 10. BMI \> 32.5 kg/m2 11. Individuals with a history of coronary artery disease, previous myocardial infarction, peripheral vascular disease, atherosclerosis, diabetic men \> 45 years old, and diabetic women \> 50 years 12. Use of medicinal marijuana 13. History of chronic use of alcohol (\> 2 drinks/day) over the past 6 months 14. Currently smoking ≥ 20 cigarettes/day 15. Use of systemic antibiotics, corticosteroids, androgens, or phenytoin, and HRT (HRTs are allowed if participant has been on a stable dose for at least 3 months and intends to maintain their dosage regimen). 16. Significant or untreated medical disorders including uncontrolled diabetes, recent myocardial ischemia or infarction, unstable angina, peripheral vascular diseases/bruits, uncontrolled thyroid dysfunction, renal failure and serious renal diseases, chronic active hepatitis, acute hepatitis, cirrhosis of liver, AIDS, malignancy, recent cerebrovascular disease and neurological disorders or significant psychiatric illness 17. Unstable medical conditions 18. History of angina, congestive heart failure, inflammatory bowel disease, pancreatitis, gastrointestinal, renal, pulmonary, hepatic or biliary disease, autoimmune disorders or cancer (evidence of active lesions, chemotherapy or surgery in the past year) 19. Anticoagulant/ antiplatelet medications; see section 4.3 for concomitant medications that are exclusionary 20. Immunocompromised individuals 21. History of hemoglobinopathies such as sickle cell anemia, thalassemia, or sideroblastic anemia 22. Individuals who have followed the Therapeutic Lifestyle Changes (TLC) diet within 12 weeks of screening 23. Recent surgery or will be undergoing surgery that may have an effect on the study in the opinion of the Qualified Investigator 24. Participation in a clinical research trial within 30 days prior to randomization. 25. History of eating disorders. 26. Clinically significant abnormal laboratory results at screening 27. Exercise greater than 24 km (15 miles)/week or 4,000 kcal/week 28. Cognitively impaired and/or who are unable to give informed consent 29. Plan to donate blood during the study or within 30 days of completing the study 30. Any additional underlying medical or psychiatric condition, clinical disorder or laboratory finding, which in the opinion of the Qualified Investigator may interfere with study objectives

Design outcomes

Primary

Measure	Time frame	Description
The Difference in Serum LDL-C From Baseline to Week 12 Between Farlong NotoGinseng™ (Farlong Ginseng Plus® Panax Notoginseng Extract) and Placebo After 12 Weeks of Supplementation.	12 weeks	The difference in serum LDL-C (mmol/L) from baseline to week 12 between Farlong NotoGinseng™ (Farlong Ginseng Plus® Panax Notoginseng extract) and placebo after 12 weeks of supplementation.

Secondary

Measure	Time frame	Description
2. The Difference in Blood Pressure From Baseline to Week 8 Between Farlong Notoginseng and Placebo	8 weeks	2\. The difference in blood pressure (mmHg) from baseline to week 8 between Farlong Notoginseng and placebo
3. The Difference in Blood Pressure From Baseline to Week 12 Between Farlong Notoginseng and Placebo	12 weeks	3\. The difference in blood pressure (mmHg) from baseline to week 12 between Farlong Notoginseng and placebo
4. The Difference in Triglycerides From Baseline to Week 8 Between Farlong Notoginseng and Placebo	8 weeks	4\. The difference in triglycerides (mmol/L) from baseline to week 8 between Farlong Notoginseng and placebo
5. The Difference in Triglycerides From Baseline to Week 12 Between Farlong Notoginseng and Placebo	12 weeks	5\. The difference in triglycerides (mmol/L) from baseline to week 12 between Farlong Notoginseng and placebo
6. The Difference in HDL-C From Baseline to Week 8 Between Farlong Notoginseng and Placebo	8 weeks	6\. The difference in HDL-C (mmol/L) from baseline to week 8 between Farlong Notoginseng and placebo
1. The Difference in Serum LDL-C From Baseline to Week 8 Between Farlong Notoginseng and Placebo	8 weeks	1\. The difference in serum LDL-C (mmol/L) from baseline to week 8 between Farlong Notoginseng and placebo
8. The Difference in Total Cholesterol From Baseline to Week 8 Between Farlong Notoginseng and Placebo	8 weeks	8\. The difference in total cholesterol from baseline to week 8 between Farlong Notoginseng and placebo
9. The Difference in Total Cholesterol From Baseline to Week 12 Between Farlong Notoginseng and Placebo	12 weeks	9\. The difference in total cholesterol from baseline to week 12 between Farlong Notoginseng and placebo
10. The Difference in Endothelial Vasodilation, as Measured by the EndoPAT, From Baseline to Week 8 Between Farlong Notoginseng and Placebo	8 weeks	10\. The difference in endothelial vasodilation (LnRHI), as measured by the EndoPAT, from baseline to week 8 between Farlong Notoginseng and placebo. The reactive hyperemia index (RHI) is a measure of endothelial function and LnRHI is a similar index after natural log transformation (Normal: LnRHI \> 0.51 Abnormal: LnRHI ≤ 0.51). An increase in LnRHI is indicative of improvement in endothelial function.
11. The Difference in Endothelial Vasodilation, as Measured by the EndoPAT, From Baseline to Week 12 Between Farlong Notoginseng and Placebo	12 weeks	11\. The difference in endothelial vasodilation (LnRHI), as measured by the EndoPAT, from baseline to week 12 between Farlong Notoginseng and placebo. The reactive hyperemia index (RHI) is a measure of endothelial function and LnRHI is a similar index after natural log transformation (Normal: LnRHI \> 0.51 Abnormal: LnRHI ≤ 0.51). An increase in LnRHI is indicative of improvement in endothelial function.
7. The Difference in HDL-C From Baseline to Week 12 Between Farlong Notoginseng and Placebo	12 weeks	7\. The difference in HDL-C (mmol/L) from baseline to week 12 between Farlong Notoginseng and placebo

Participant flow

Participants by arm

Arm	Count
Farlong NotoGinseng™ Farlong NotoGinseng™ (Treatment Group)	47
Placebo Placebo Group	48
Total	95

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Lost to Follow-up	1	1
Overall Study	Physician Decision	1	1
Overall Study	Withdrawal by Subject	3	3

Baseline characteristics

Characteristic	Farlong NotoGinseng™	Placebo	Total
Age, Continuous	50.83 years STANDARD_DEVIATION 12.65	49.96 years STANDARD_DEVIATION 11.85	50.39 years STANDARD_DEVIATION 12.19
Race/Ethnicity, Customized Central American	3 Participants	0 Participants	3 Participants
Race/Ethnicity, Customized Eastern European White	4 Participants	2 Participants	6 Participants
Race/Ethnicity, Customized Middle Eastern	2 Participants	1 Participants	3 Participants
Race/Ethnicity, Customized South American	1 Participants	3 Participants	4 Participants
Race/Ethnicity, Customized South Asian	1 Participants	0 Participants	1 Participants
Race/Ethnicity, Customized Western European White	36 Participants	42 Participants	78 Participants
Region of Enrollment Canada	47 participants	48 participants	95 participants
Sex: Female, Male Female	35 Participants	32 Participants	67 Participants
Sex: Female, Male Male	12 Participants	16 Participants	28 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 47	0 / 48
other Total, other adverse events	23 / 47	20 / 48
serious Total, serious adverse events	0 / 47	0 / 48

Outcome results

Primary

The Difference in Serum LDL-C From Baseline to Week 12 Between Farlong NotoGinseng™ (Farlong Ginseng Plus® Panax Notoginseng Extract) and Placebo After 12 Weeks of Supplementation.

The difference in serum LDL-C (mmol/L) from baseline to week 12 between Farlong NotoGinseng™ (Farlong Ginseng Plus® Panax Notoginseng extract) and placebo after 12 weeks of supplementation.

Time frame: 12 weeks