Cardiovascular Health Clinical Evidence

COENZYME Q10

Southern Medical Journal
Burke BE, R Neuenschwander, RD Olson. Randomized, double-blind, placebo-controlled trial of coenzyme Q10 in isolated systolic hypertension. 2001 Nov; 94(11):111217.

 Topic:
Is CoQ10 a safe and effective treatment for hypertension?

Background:
Hypertension is widespread, affecting more than 50 million adults, and is a common risk factor for heart disease.

Study Type:
Human clinical intervention trial

Study Design:
Double-blind, placebo-controlled. Subjects took CoQ10 or a placebo. Blood samples and blood pressure readings were taken.

Dosage:
60 mg/twice daily for 12 weeks

Subjects:
46 men and 37 women with isolated systolic hypertension (meaning the maximum, or top number, is elevated while the minimum, or bottom number, is not)

Results:
Systolic blood pressure was reduced by an average of 17.8 ± 7.3 mm Hg.

Conclusions:
“Our results suggest CoQ10 may be safely offered to hypertensive patients as an alternative option.”

 Journal of Human Hypertension

 Singh RB et al. Effect of hydrosoluble coenzyme Q10 on blood pressures and insulin resistance in hypertensive patients with coronary artery disease. 1999 Mar; 13(3):203–8.

 Topic:
What is the effect of CoQ10 on blood pressure and insulin resistance in subjects with hypertension and coronary artery disease?

Background:
Heart disease and insulin resistance seem to be intertwined, with insulin-resistant patients suffering higher rates of heart failure. Is there a treatment that can address both issues?

Study Type:
Human clinical intervention trial

Study Design:
Randomized, double-blind. Subjects took either CoQ10 or vitamin B. After 8 weeks, researchers recorded their blood pressure, insulin levels (fasting and 2 hours after eating), blood sugar, triglycerides, and several markers of oxidative stress.

Dosage:
60 mg/twice daily for 8 weeks

Subjects:
59 patients taking blood pressure medication

Results:
In the treatment group, HDL (good) cholesterol and antioxidants such as vitamins A, C, E, and beta-carotene all rose. In the vitamin B group, only vitamin C and beta-carotene rose.

Conclusions:
“These findings indicate that treatment with coenzyme Q10 decreases blood pressure, possibly by decreasing oxidative stress and insulin response in patients with known hypertension receiving conventional antihypertensive drugs.”

Molecular Aspects of Medicine
Digiesi V et al. Coenzyme Q10 in essential hypertension. 1994; 15 Suppl:s257–63.

Topic:
What is the effect of CoQ10 on blood pressure and cholesterol levels?

Background:
Blood pressure and cholesterol levels are both well-known risk factors for cardiovascular disease.

Study Type:
Human clinical intervention trial

Study Design:
Subjects took CoQ10. Researchers measured blood levels of CoQ10, total and HDL (good) cholesterol, and blood pressure at base line and at 10 weeks.

Dosage:
50 mg/twice daily for 10 weeks

Subjects:
26 patients with high blood pressure

Results:
Over the course of the study, CoQ10 levels rose with supplementation. Systolic blood pressure (the upper reading) decreased from 164.5 ± 3.1 to 146.7 ± 4.1 mm Hg and diastolic blood pressure (the lower reading) decreased from 98.1 ± 1.7 to 86.1 ± 1.3 mm Hg. Total cholesterol fell and HDL cholesterol rose{cke_protected_1}[MT1]{cke_protected_2} .

 

Mechanism of Action
CoQ10 improves heart health by dilating blood vessels, inhibiting LDL oxidation (slowing the progression of atherosclerosis), decreasing inflammatory cytokines, and decreasing blood viscosity. CoQ10 is also an antioxidant that inhibits superoxide, a free radical, either by scavenging it, or by interfering with its synthesis in blood vessels and vascular muscle. MicroActive® CoQ10 is 3 times better absorbed than standard CoQ10 because it is encapsulated in a molecular carrier of beta-cyclodextrin, a compound made of sugar molecules that increases the solubility of CoQ10.

PHYTOSTEROLS

Asia Pacific Journal of Clinical Nutrition

Wu T et al. The effects of phytosterols/stanols on blood lipid profiles: a systematic review with meta-analysis. 2009; 18(2):179–86.

Topic:
Are phytosterols/stanols effective at lowering cholesterol?

Background:
Phytosterols and stanols are cholesterol-like molecules found in plants. They are thought to lower cholesterol levels, possibly by competing with cholesterol for absorption.

Study Type:
Review paper

Summary:
Researchers screened 76 studies and found 20 of sufficiently high methodological quality to consider.  Analyzing the data from these trials, they found phytosterols/stanols can significantly decrease LDL (bad) cholesterol and triglycerides.

Conclusions:
“Foods enriched with 2.0 g of phytosterols/stanols per day had a significant cholesterol-lowering effect.”

 Journal of the American College of Nutrition

Zhao HL et al. Action of plant sterol intervention on sterol kinetics in hypercholesterolemic men with high versus low basal circulatory plant sterol concentrations. 2011 Apr; 30(2):155–65.

 Topic:
How does supplementation with plant sterols (PS) affect subjects with high and low levels of PS at base line?

Background:
The relationship between PS absorption and cholesterol absorption and synthesis is not well understood.

Study Type:
Human clinical intervention trial

Study Design:
Subjects consumed a spread enriched with PS or one without PS. Their levels of campesterol and beta-sitosterol (two kinds of PS) as well as their cholesterol concentrations and rates of cholesterol synthesis were measured.

Dosage:
2 g/day for two 4-week periods, separated by a 4-week washout period

Subjects:
82 men with high cholesterol

Results:
Consumption of PS-enriched products reduced cholesterol by 34.3% ± 1.9%, although cholesterol synthesis also increased in this group. The cholesterol-lowering effect of PS was strongest among subjects who were in the 50th–75th percentile of PS concentrations at base line.

Conclusions:
“These data suggest that basal PS concentrations indicate not only sterol absorption efficiency but also the extent of PS-induced cholesterol reduction and thus might be clinically useful to predict the extent of cholesterol response to PS intervention within a given individual.”

The American Journal of Clinical Nutrition
Devaraj S, BC Autret, I Jiala. Reduced-calorie orange juice beverage with plant sterols lowers C-reactive protein concentrations and improves the lipid profile in human volunteers. 2006 Oct; 84(4):756–61.

Topic:
What is the effect of supplementing with plant sterols (PS) on C-reactive protein (CRP) and cholesterol levels?

Background:
Plant sterols have been shown to reduce LDL cholesterol. Can they also reduce inflammation, which is a factor in atherosclerosis (hardening of the arteries)?

Study Type:
Human clinical intervention trial

Study Design:
Randomized, placebo-controlled. Subjects drank beverages with or without PS. Fasting blood samples were taken at base line and at 8 weeks.

Dosage:
1 g/twice daily for 8 weeks

Subjects:
72 healthy subjects

Results:
Supplementing with PS significantly reduced total cholesterol and LDL cholesterol. There was also a significant reduction in levels of CRP, a marker of inflammation. There were no significant changes in triglycerides, glucose, liver function, or levels of vitamin E and carotenoids (plant pigments the body can convert to vitamin A).

Conclusions:
“Supplementing with a reduced-calorie orange juice beverage containing plant sterols is effective in reducing CRP and LDL cholesterol and could be incorporated into the dietary portion of therapeutic lifestyle changes.”

European Journal of Clinical Nutrition
Korpela, R., et al. Safety aspects and cholesterol-lowering efficacy of low fat dairy products containing plant sterols. 2006 May; 60(5):633–42.

Topic:
What is the effect of supplementing with plant sterols (PS) on cholesterol levels and on levels of fat-soluble vitamins?

Background:
Some vitamins are transported and stored in water-based body fluids and others in fat. If plant sterols successfully lower cholesterol levels, might levels of fat-soluble vitamins also decrease?

Study Type:
Human clinical intervention trial

Study Design:
Parallel, double-blind. Subjects consumed PS-enriched low-fat dairy products. Researchers measured their levels of cholesterol and fat-soluble vitamins.

Dosage:
2 g/day for 6 weeks

Subjects:
164 subjects with mildly to moderately elevated cholesterol

Results:
Subjects consuming the PS-enriched dairy products saw their PS blood levels rise and experienced a 6.5% reduction in their total cholesterol levels, while there was no change in the control group. In addition, LDL (bad) cholesterol fell by 10.4% in the sterol group and by only 0.6% in the control group. There was no change in either group in HDL (good) cholesterol or triglycerides, but because the LDL levels fell among members of the treatment group, their HDL/LDL ratio rose by 16.3%, while in the control group, this ratio rose by only 4.3%. Levels of fat-soluble vitamins did not decrease when total levels of cholesterol were considered.

Conclusions:
“Yogurt, low-fat hard cheese and low-fat fresh cheese enriched with a plant sterol mixture reduced serum cholesterol in hypercholesterolemic subjects and no adverse effects were noted in the dietary control of hypercholesterolemia.”

 European Journal of Clinical Nutrition

 Thomsen AB et al. Effect of free plant sterols in low-fat milk on serum lipid profile in hypercholesterolemic subjects. 2004 Jun; 58(6):860–70.

Topic:
What is the effect of supplementing with plant sterols (PS) on subjects with mildly elevated cholesterol? What is the optimal dose?

Background:
Plant sterols are thought to reduce levels of LDL (bad) cholesterol. Is this treatment effective?

Study Type:
Human clinical intervention trial

Study Design:
Double-blind, randomized, placebo-controlled, three-arm crossover study. Subjects all took a placebo, a low dose of PS, and a higher dose of PS in different phases of the study. Researchers measured their LDL cholesterol levels.

Dosage:
1.2 g or 1.6 g/day for 4 weeks each

Subjects:
138 subjects with mildly elevated cholesterol screened, 81 participated, 71 completed

Results:
In the low-dose group, LDL cholesterol was lowered by an average of 7.13 ± 12.32%, and in the high-dose group by 9.59 ± 12.44%. The difference between the two doses was not statistically significant. There were no significant changes in vitamin E or carotenoid levels after supplementation.

Conclusions:
“The present study shows for the first time a substantial reduction in LDL cholesterol with a new, partly vegetable-oil-filled 1.2% low-fat milk product, containing nonesterified (unsaturated) plant sterols from soybean oil, in a randomized, placebo-controlled trial. This result encourages further development of novel low-fat dairy products containing free plant sterols for future use in cholesterol-lowering initiatives.”

European Journal of Nutrition

Christiansen LI et al. Cholesterol-lowering effect of spreads enriched with microcrystalline plant sterols in hypercholesterolemic subjects. 2001 Apr; 40(2):66–73.

Topic:
How does a new, microcrystallized form of plant sterols (PS) perform in lowering cholesterol?

Background:
Previous research has shown PS can lower cholesterol levels.  The effectiveness of the sterols depends on their form, however.

Study Type:
Human clinical intervention trial

Study Design:
Double-blind, randomized, placebo-controlled. Subjects consumed a rapeseed oil–based spread for 6 weeks before the PS was introduced. Then the subjects were divided into 3 groups, a control group that continued to consume the rapeseed oil spread, a group that consumed a low dose of PS, and one that consumed a higher dose. There were no other dietary or lifestyle changes. Researchers then measured their total and LDL (bad) and HDL (good) cholesterol levels.

Dosage:
1.5 g or 3 g/day for 6 weeks

Subjects:
155 subjects with high cholesterol

Results:
Total cholesterol levels and LDL cholesterol levels were significantly decreased by 7.5%–11.6% in the treatment group. The effect was similar in the low- and high-dose groups. There was no change in HDL cholesterol or triglycerides and no negative side effects.  Levels of fat-soluble vitamins did not decrease.

Conclusions:
“Microcrystalline plant sterols are effective in lowering serum total- and LDL-cholesterol concentrations without obvious side effects. The daily dose of 1.5 g plant sterols is enough to reach the maximum effect.”

 

Mechanism of Action
Plant sterols inhibit the uptake of cholesterol, possibly by decreasing the solubility of cholesterol and by displacing it from the sites that absorb it. Sterols activate liver X receptor, which regulates cholesterol, and increase the expression of ATP-binding cassette G transporters (ABCG), proteins that transport substances across cellular membranes. ABCG then redirects absorbed PS back into the intestines.

 RESVERATROL

 Clinical Hemorheology and Microcirculation

 Magyar K et al. Cardioprotection by resveratrol: A human clinical trial in patients with stable coronary artery disease. 2012; 50(3):179–87.

Topic:
Can resveratrol improve cardiovascular function in patients with stable heart disease?

Background:
Resveratrol is an antioxidant in grape skins and red wine.  Several benefits of this substance have already been identified, particularly for heart health.

Study Type:
Human clinical intervention trial

Study Design:
Double-blind, placebo-controlled. Subjects took resveratrol or a placebo and researchers measured various parameters of heart health.

Dosage:
10 mg/day for 3 months

Subjects:
40 white subjects who’d recently had a heart attack

Results:
There was significant improvement in the function of the left ventricle and blood vessels. Ejection fraction (the ratio of blood flowing through the left ventricle) was improved. Resveratrol also lowered LDL (bad) cholesterol and reduced platelet aggregation, as compared with the control group.

Conclusions:
“Our results show that resveratrol improved left ventricle diastolic function, endothelial function, lowered LDL-cholesterol level, and protected against unfavorable hemorheological changes measured in patients with coronary artery disease (CAD).”

Nutrition, Metabolism and Cardiovascular Disease

Wong RH et al. Acute resveratrol supplementation improves flow-mediated dilation in overweight/obese individuals with mildly elevated blood pressure. 2011 Nov; 21(11):851–6.

Topic:
Can resveratrol improve blood vessel function in overweight and obese subjects with mildly elevated blood pressure?

Background:
Flow-mediated dilation (FMD) is a measure of blood vessel function. Reduced FMD is associated with obesity and high blood pressure. Previous research has shown that polyphenols can improve FMD. Does the polyphenol resveratrol have this effect and is it dose-dependent?

Study Type:
Human clinical intervention trial

Study Design:
Double-blind, randomized crossover. Subjects took a low, medium, or high dose of resveratrol or a placebo. Researchers measured blood levels of resveratrol and FMD 1 hour after consumption.

Dosage:
A single dose of 30, 90, or 270 mg

Subjects:
14 men and 5 postmenopausal women, all overweight or obese with untreated borderline high blood pressure, mean age 55 ± 2 years

Results:
Supplementation increased blood levels of resveratrol and FMD. The effect was dose-dependent. FMD was also linearly related to resveratrol levels.

Conclusions:
“A cute resveratrol consumption increased plasma resveratrol concentrations and FMD in a dose-dependent manner. This effect may contribute to the purported cardiovascular health benefits of grapes and red wine.”

 

Mechanism of Action
Resveratrol decreases cholesterol in three ways: it activates AMP-activated protein kinase, which inhibits cholesterol synthesis; it decreases the activity of HMG-CoA, an enzyme in the metabolic pathway that produces cholesterol; and it up-regulates CERP, which transports cholesterol. 

 Resveratrol also induces the expression of PON1, an enzyme in HDL that has an anti-atherosclerotic effect. Finally, resveratrol activates endothelial nitric oxide synthase, an enzyme that relaxes blood vessels and inhibits platelet aggregation in the blood vessels.

 ARJUNA BARK

Journal of the Association of Physicians of IndiaGupta R et al. Antioxidant and hypocholesterolaemic effects of Terminalia arjuna tree-bark powder: a randomised placebo-controlled trial. 2001 Feb; 49:231–5.

Topic:
How does arjuna bark powder compare with vitamin E as an antioxidant and cholesterol-lowering treatment?

Background:
Arjuna bark is used in traditional Indian medicine to support heart health.

Study Type:
Human clinical intervention trial

Study Design:
Randomized, controlled. Subjects stopped taking any vitamin supplements 1 month before the trial began, and all subjects received dietary advice from the American Heart Association. Base line levels of cholesterol, triglycerides, HDL (good) and LDL (bad) cholesterol, and byproducts of oxidative stress were measured. Subjects took arjuna bark powder, vitamin E, or a placebo.

Dosage:
500 mg/day for 30 days

Subjects:
105 subjects not taking cholesterol-lowering drugs or vitamin supplements

Results:
There were no significant changes in total, HDL, or LDL cholesterol, or triglycerides in the vitamin E or control group, but in the arjuna group, there were significant decreases in total and LDL cholesterol. Oxidative stress decreased significantly in both the vitamin E and arjuna groups. The effect was more pronounced in the vitamin E group (a 36.4 ± 17.7% decrease for vitamin E versus a 29.3 ± 18.9% decrease for arjuna).

Conclusions:
Terminalia arjuna bark powder has significant antioxidant action that is comparable to vitamin E. In addition, it also has a significant hypocholesterolaemic effect.”

International Journal of Cardiology
Dwivedi S et al. Role of Terminalia arjuna in ischaemic mitral regurgitation. 2005 Apr 28; 100(3):507–8.

Topic:
Can arjuna bark powder help treat ischemic mitral regurgitation?

Background:
Ischemic mitral regurgitation (IMR) is a complication following a heart attack, in which the mitral valve does not function properly. Previous research has shown arjuna bark powder has cardiovascular benefits and cholesterol-lowering effects. Can it treat this problem?

Study Type:
Human clinical intervention

Study Design:
Placebo-controlled. Subjects took arjuna bark or placebo and their heart health was assessed at 1 and 3 months.

Dosage:
500 mg/day for 3 months in addition to anti-ischemic treatment

Subjects:
40 patients with a recent heart attack and IMR

Results:
Subjects in the treatment group showed a significant decrease in IMR, an improvement in the E/A ratio (the pattern with which the ventricles fill with blood), and reduction in angina (chest pain).

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Indian Heart Journal
Bharani A et al. Efficacy of Terminalia arjuna in chronic stable angina: a double-blind, placebo-controlled crossover study comparing Terminalia arjuna with isosorbide mononitrate. 2002 Mar-Apr; 54(2):170–5.

Topic:
How does arjuna bark extract compare with isosorbide mononitrate as a treatment for stable angina (chest pain)?

Background:
Preliminary research has shown cardiovascular benefits for arjuna bark extract, but there has not yet been a double-blind, randomized, placebo-controlled study with adequate sample size.

Study Type:
Human clinical intervention trial

Study Design:
Randomized, double-blind, placebo-controlled crossover. Subjects took arjuna bark extract for 1 week, isosorbide mononitrate for 1 week, and a placebo for 1 week, with a washout period of 3 or more days in between. Subjects were examined and took treadmill tests at the end of each treatment period. 

Dosage:
500 mg every 8 hours for 1 week

Subjects:
58 men with chronic, stable chest pain and evidence of probable ischemia (restriction of blood flow to the heart)

Results:
When subjects took the arjuna bark powder they experienced significantly less chest pain and needed to take less isosorbide dinitrate for the pain (5.69 ± 6/91 mg/week during the arjuna week versus 18.22 mg ± 9.29 mg during the placebo week). They were also able to exercise longer on the treadmill test (6.14 ± 2.51 minutes versus 4.76 ± 2.38 minutes). Other exercise parameters improved as well. Improvements in clinical and treadmill tests were similar during the isosorbide mononitrate and arjuna weeks, when compared with placebo. There were no significant side effects.

Conclusions:
Terminalia arjuna bark extract, 500 mg 8 hourly, given to patients with stable angina with provocable ischemia on treadmill exercise, led to improvement in clinical and treadmill exercise parameters as compared to placebo therapy. These benefits are similar to those observed with isosorbide mononitrate (40 mg/day) therapy and the extract was well tolerated.”

Indian Heart Journal
Bharani A, LK Ahirwa, N Jain. Terminalia arjuna reverses impaired endothelial function in chronic smokers. 2004 Mar-Apr; 56(2):123–8.

Topic:
Can Terminalia arjuna improve blood vessel function in smokers?

Background:
Smoking increases oxidative stress and causes blood vessel dysfunction, which can lead to atherosclerosis (hardening of the arteries). But improvement is possible through smoking cessation and antioxidant supplementation. Can arjuna, a medicinal plant from India with antioxidant action, help?

Study Type:
Human clinical intervention trial

Study Design:
Double-blind, placebo-controlled crossover. The smokers’ and nonsmokers’ brachial artery function was compared at base line. Smoking subjects then took arjuna or a placebo for 2 weeks each and their brachial artery function was assessed again.

Dosage:
500 mg every 8 hours for 2 weeks

Subjects:
18 healthy male smokers, mean age 28.16 ± 9.45 years, and 18 age-matched nonsmoking controls

Results:
Flow-mediated dilation, a measure of blood vessel function, improved after arjuna treatment but not after placebo.

Conclusions:
“Smokers have impaired endothelium-dependent but normal vasodilation as determined by brachial artery reactivity studies. Further, Terminalia arjuna therapy for two weeks leads to significant regression of this endothelial abnormality amongst smokers.”

Mechanism of Action
Arjuna bark’s cardio-protective action comes from several of its constituents, such as glycosides, which strengthen contractions of heart muscle, and flavonoids, which have antioxidant, anti-inflammatory, and cholesterol-lowering effects. Arjuna bark decreases chest pain, increases coronary artery flow, decreases blood pressure, and increases ejection fraction (the ratio of blood flowing through the left ventricle).