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Supplements to Address Circulatory Health

By Yousry Naguib, Ph.D.
Vitamin Retailer magazine, March  2005

The circulatory system is made up of the heart, blood, and blood vessels. The heart is a muscular organ that pumps blood through the body, supplying cells and tissues with oxygen and nutrients through an intricate network of blood vessels. In order to meet the body’s energy demands, the heart must beat more than 100,000 times per day. The blood is the transport system by which oxygen and nutrients reach every cell in the body, and carbon dioxide and other waste materials are carried away for removal from the body. Blood also carries hormones, which control body vital processes, and antibodies to fight infections.
Blood vessels are small tubes that carry blood to and from all parts of the body. The human circulatory system is composed of three types of vessels (arteries, veins, and capillaries) that total approximately 60,000 miles in length, which is enough to circle the earth more than twice!. Although the average adult body contains less than 1.5 gal. of blood, the heart pumps 2,000 gal. of blood each day through the blood vessels. Arteries carry oxygen-rich blood away from the heart and branch into smaller vessels in order to facilitate its delivery to the organs and other tissues; and veins carry oxygen-poor blood back to the heart.
Circulatory problems usually come as a consequence of multiple risk factors. The incidence of poor circulation rises with age, as hardening of the arteries becomes more common. Gender also seems to play a role in determining who gets certain circulatory problems. Women, for example, are more likely than men to develop varicose veins.
Disorders of the circulatory system generally result in diminished flow of blood and diminished oxygen exchange of the tissues. Blood supply is impeded in such conditions as high blood pressure (hypertension), and atherosclerosis, which can affect any artery of the body.
Blood pressure (BP) refers to the pressure of blood against the walls of arteries and is measured in millimeters of mercury (mm Hg). It is measured by two numbers: systolic BP, the pressure in the arteries after the heart contracts; and diastolic BP, the pressure in the arteries when the heart relaxes. Untreated high BP can damage the delicate lining of the blood vessels, leading to the buildup of fatty deposit or “plaque” along the artery wall. The blood vessel becomes narrowed and stiff, a condition known as atherosclerosis, and blood flow through the blood vessel is reduced. Inadequate blood flow to certain organs in the body can lead to certain diseases, including stroke, heart disease, eye damage (retinopathy), and peripheral arterial disease of the legs.
Strokes occur when the blood supply to the brain is cut off, or when a blood vessel in the brain bursts and spills blood into an area of the brain, causing damage to brain cells.
Coronary artery disease (CAD) is the most common cause of heart failure in the US. CAD is a manifestation of atherosclerosis. Deposits of fats, calcium and dead cells, called atherosclerotic plaques, form on the inner walls of the coronary arteries and interfere with the flow of blood. Blood flow to the heart muscle may even stop if a thrombus, or clot, forms in a coronary vessel, which may cause a heart attack. In a heart attack (also known as a myaocardial infarction), the heart muscle becomes damaged by lack of oxygen, and unless blood flow returns within minutes, muscle damage increases, and the heart’s ability to pump blood is compromised. If the clot can be dissolved within a few hours, damage to the heart can be reduced.
In peripheral vascular disease of the legs, not enough blood flows to the legs. The condition usually is caused by fatty deposits that build up along the walls of blood vessels. The most common symptom is intermittent claudication, a cramping in the legs or tired feeling in the muscles of the leg during exercise or walking that goes away by rest. Most commonly, the pain occurs in the calf, but it can also occur in the thigh, hip, or buttock. The risk factors for getting peripheral vascular disease are the same as the risk factors for coronary heart disease.
Supplements that are known to help improve circulation include: l- arginine, garlic, ginkgo, horse chestnut, butcher’s broom, hawthorn berry, essential fatty acids, bioactive peptides, and coenzyme Q10.

Arginine relaxes the arteries, including coronary arteries that supply blood to the heart, helping to maintain healthy BP and blood flow.1 Arginine also assists in promoting healthy blood flow to the organs necessary for sexual function.2
L-arginine is used by the body to produce nitric oxide, or NO. NO causes blood vessels to relax and widen, which in turn results in greater blood flow and oxygen to the heart.  In the presence of the enzyme nitric oxide synthase, L-arginine induces NO formation from the endothelial cells to improve circulation. Being a free radical with vasodilator properties, NO exerts dual effects on tissues and cells in various biological systems. At low concentrations NO can dilate the blood vessels and improve the circulation, but at high concentrations it can cause circulatory shock and induce cell death.
The discovery of how NO works has led to better sexual performance for many older men. Insight into the function of NO brought about the development of Viagra, a medication for the treatment of impotence. It causes the smooth muscle cells in the blood vessels of the penis to relax and thus dilate.
The dietary supplement L-citrulline is a new activator of the NO pathway. L-citrulline is recycled by the body into L-arginine. L-citrulline is an amino acid found in melons; it stimulates the body to produce more L-arginine, which in turn produces more nitric oxide.

Garlic has strong antioxidant properties and it has been suggested that garlic can prevent cardiovascular disease, inhibit platelet aggregation and thrombus formation, and improve blood circulation.
It is hypothesized that garlic supplementation increases tissue blood flow and this is mediated by the vasodilator actions of interleukin-6 (IL-6). In one study, 13 young healthy female volunteers received 600 mg of garlic tablets, and 13 female volunteers received placebo (control) once daily for seven days. In the garlic-group, calf blood flow and plasma IL-6 concentrations increased significantly. In the control-group, calf blood flow and plasma levels of IL-6 remained unchanged. These data suggest that garlic supplementation increases resting tissue blood flow and this may be mediated by IL-6.3

Ginkgo tree is one of the oldest trees, with a long history of use in traditional Chinese medicine. The beneficial effects of ginkgo biloba include improvement of memory, and increased blood circulation.
Ginkgo is thought to be helpful for preventing or treating dementia because it improves blood flow in the brain. A review of studies on ginkgo and mild memory impairment (dementia) found that ginkgo was significantly more effective than placebo in enhancing memory and cognitive function.4
Ginkgo has also been studied in people with intermittent claudication. An analysis of eight published studies revealed that people taking ginkgo tend to walk roughly 34 m farther than those taking placebo.5

Bioactive Peptides
Bioactive peptides that inhibit angiotensin I converting enzyme (ACE) in the cardiovascular system can contribute to the prevention and treatment of hypertension. These peptides are produced in the enzymatic hydrolysate of food material such as milk, animal and fish meat, maize, wheat, and soybeans, and also from microbe-fermented products. ACE plays a dual role in the regulation of hypertension: It catalyzes the production of the vasoconstrictor angiotensin II and it activates the vasodilator bradykinin. By inhibiting these processes, ACE inhibitors have antihypertensive effects.
In a recent study, researchers at the National Public Health Institute in Finland reported that ingestion of a new sour milk containing the tripeptides isoleucyl-prolyl-proline (Ile-Pro-Pro) and valyl-prolyl-proline (Val-Pro-Pro) produced by fermentation with Lactobacillus helveticus bacteria seems to lower BP modestly. Subjects with hypertension were given 150 ml per day a placebo (regular sour milk) or a fermented sour milk containing 2.4-2.7 mg of Ile-Pro-Pro and 2.4-2.7 mg of Val-Pro-Pro per 150 ml. Systolic BP fell on average 2.6 mmHg more than on the fermented product compared to the placebo product. The difference in diastolic BP (1.0 mmHg) between the two products was not significant.6
Peptides derived from sardine protein hydrolysates were also found to exhibit anti-hypertensive effect. In a randomized double-blind placebo-controlled study, subjects with mild hypertension or high-normal BP received either 195 g of vegetable drink containing 0.5 g of sardine peptides with 0.4 mg of the dipeptide – valyl-tyrosine (test group) or a vegetable drink without sardine peptides (control group) once daily for 13 weeks. Subjects in the test group showed a significant decrease in systolic BP, from 142 mmHg to 134.4 mmHg, and a decrease in diastolic BP from 88 mmHg to 83.5 mmHg. No change in systolic BP (140.8 mmHg) and diastolic BP (90.5 mmHg) were observed in the control group.7
Katsuobushi oligo-peptide from the bonito fish, a member of the tuna family, has been shown in a double-blind, randomized, cross-over study to lower BP in 61 borderline and mildly hypertensive subjects at a dose of 1.5 g per day.8

Researchers at the University of Pennsylvania reported that the hydrolysate of bovine milk protein, either alone or combined with algenic acid, significantly reduced daytime BP, by 9.2 mmHg in systolic BP and 6.0 mmHg in diastolic BP.9

Hawthorn Berry
The berries and flowers of hawthorn (Crataegus oxycantha) are widely used as a cardiac tonic, and recommended as a treatment option for congestive heart failure (a disease in which the heart does not adequately maintain circulation). Clinical studies have confirmed that hawthorn leaf and flower extracts are beneficial for people with New York Heart Association (NYHA) class II (an early stage characterized by a reduced cardiac output with medium effort) chronic heart failure.10
People with congestive heart failure taking 160-900 mg of hawthorn extract per day for eight weeks showed improved quality of life including greater ability to exercise without shortness of breath and exhaustion.11
In a recent meta-analysis study, involving 632 patients with chronic heart failure (NYHA class II), patients received hawthorn extract experienced more beneficial maximal work load, assessed using bicycle exercise testing, than placebo. Hawthorn treatment also reduced BP-heart rate product, and significantly improved fatigue as compared to placebo. Based on the findings of this meta-analysis, hawthorn extract can be recommended as an adjunctive therapy to improve the physical performance and ameliorate symptoms of patients with chronic heart failure.12, 13

Horse Chestnut Seed
Horse chestnut (Aesculus hippocastanum) seed extract is widely used for the management of chronic venous insufficiency (CVI), a condition where blood pools in the veins of the lower legs. It occurs when the valves that keep blood flowing up from the legs become damaged by varicose veins, or by a blockage in a vein, such as a blood clot. Symptoms of CVI include ankle and leg swelling.
In an open study, patients with CVI who took 50 mg horse chestnut tablet twice daily rated efficacy of the supplement to provide symptom relief as “very good” or “good,” some patients reported no effects by the end of the study.14
A 2004 review study found that horse chestnut seed extract significantly improves leg pain, and leg volume, but suggested that larger randomized trials are needed to establish conclusively this supplement’s efficacy.15

Butcher’s Broom Extract
Butcher’s broom contains chemicals that help to strengthen certain blood vessels, which help keep blood circulating throughout the body. Clinical trial demonstrated an improvement in venous insufficiency symptoms such as ankle diameter, tension of the leg, and cramping.
In one multi-center, double-blind, randomized, placebo-controlled trial, women suffering from CVI who received a butcher’s broom extract (Ruscus aculeatus L. extract) for 12 weeks showed a significant improvements in the leg volume, and ankle and leg circumferences as compared to the placebo. The study concluded that butcher’s broom extract in the daily recommended dosage is a safe and effective treatment for patients suffering from CVI.16

Ginseng is one of the most popular herbal remedies, and is commonly included in herbals used for the treatment of sexual dysfunction. Panax ginseng has been shown to relax blood vessels by enhancing nitric oxide synthesis in the endothelium of many organs, including the corpora cavernosa. Ginseng contains the active components ginsengosides, which in animal studies have been shown to promote nitric oxide release in endothelial cells, and induce relaxation in rabbit corpus cavernosum tissue, effects which may account for the aphrodisiac property of Panax ginseng .17
The efficacy of Panax ginseng for erectile dysfunction was demonstrated in a recent double-blind, placebo-controlled study. Forty-five men with erectile dysfunction were given either 900 mg Panax ginseng or placebo three times daily for eight weeks, followed by 2 weeks washout period, after which patients received crossover treatment of placebo or Panax ginseng for another eight weeks. Mean International Index of Erectile Function scores were significantly higher in patients treated with Korean red ginseng than those who received placebo.18

Coenzyme Q10
Coenzyme Q10 (CoQ10) is found in virtually all cells of human body, including the heart, liver, and skeletal muscles. CoQ10 can be synthesized in the body, and functions as a carrier to transfer electrons across the membrane of mitochondria (the energy generator in the body’s cells) to drive the production of adenosine triphosphate (ATP), the fuel that energizes cells in our body.
Research in patients with hypertension indicates that treatment with coQ10 decreases BP, possibly by decreasing oxidative stress. In one study, 26 patients with essential hypertension were treated with oral coQ10, 50 mg twice daily for 10 weeks. At the end of the treatment, plasma coQ10 values increased from 0.64 microgram/ml to 1.61 microgram/ml, systolic BP decreased from 164.5 to 146.7 mmHg, and diastolic BP decreased from 98.1 mmHg to 86.1 mmHg.19
Similar reduction, 17.8 mmHg, in systolic BP was reported in a randomized, double-blind, placebo-controlled trial on 46 men and women with systolic hypertension who received 60 mg of coQ10 twice daily.20

Essential Fatty Acids
Dietary supplementation with long-chain polyunsaturated fatty acids has become an attractive possibility to prevent cardiovascular diseases. In one study, four groups of eight subjects with essential hypertension received either 10 ml or 50 ml of fish oil, 50 ml of safflower oil, or 50 ml of a mixture of oils that approximated the types of fat present in the American diet, daily for four weeks. BP decreased in the men who received the high dose of fish oil..21
In a recent meta-analysis of 36 clinical trials of fish oil and blood pressure, intake of fish oil at a median dose of 3.7 g per day reduced systolic BP by 1.7 mmHg and diastolic BP by 1.5 mmHg. The study concluded that high intake of fish oil may lower BP, especially in older and hypertensive subjects.22

Cholesterol lowering supplements, such as red yeast rice, phytosterols, policosanol, guggul, polymethoxylated flavones, and tocotrienols, help prevent atherosclerosis and associated diseases. Too much cholesterol in the bloodstream leads to narrowing and blockage of the arteries that greatly increases the risk of stroke, coronary heart disease, and heart attacks.
Additionally, vitamins C and E, niacin, and grape seed extract, all of which are believed to have a dilating effect on blood vessels, may help to get the blood flowing. Certain niacin forms may cause uncomfortable flushing. Magnesium supplements may help dilate vessels and alleviate arterial spasms.

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[2] Zorgniotti AW, Lizza EF. Effect of large doses of nitric oxide precursor, L-Arginine, on erectile dysfunction. International Journal of Impotence Research  1994; 6
[3] Anim-Nyame N et al. Garlic supplementation increases peripheral blood flow: a role for interleukin-6. J Nutr Biochem. 2004; 15:30
[4] Ernst E, Pittler MH. Ginkgo biloba for dementia: a systematic review of double-blind, placebo-controlled trials. Clin Drug Invest 1999; 17:301
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[7] Kawasaki T et al. Antihypertensive effect and safety evaluation of vegetable drink with peptides derived from sardine protein hydrolysates on mild hypertensive, high-normal and normal blood pressure subjects. Fukuoka Igaku Zasshi. 2002; 93:208
[8] Fujita H et al. Effect of an ace-inhibitory agent, katsuobushi oligopeptide, in the spontaneously hypertensive rat and in borderline and mildly hypertensive subjects. Nutrition  Research 2001; 21:1149
[9] Townsend RR et al. A randomized, double-blind, placebo-controlled trial of casein protein hydrolysate (C12 peptide) in human essential hypertension. Am J Hypertens 2004; 17:1056
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[14] Dickson S et al. An open study to assess the safety and efficacy of Aesculus hippocastanum tablets (Aesculaforce 50mg) in the treatment of chronic venous insufficiency. J Herb Pharmcother 2004; 4:19
[15] Pittler MH, Ernst. Horse chestnut seed extract for chronic venous insufficiency. Cochrane Database Syst Rev 2004; 2:CD003230
[16] Vanscheidt W et al. Efficacy and safety of a Butcher’s broom preparation (Ruscus aculeatus L. extract) compared to placebo in patients suffering from chronic venous insufficiency. Arzneimittelforschung 2002; 52:243
[17] Chen X, Lee TJ. Ginsenosides-induced nitric oxide-mediated relaxation of the rabbit corpus cavernosum. Br J Pharmacol 1995; 115:15
[18] Hong B et al. A double-blind crossover study evaluating the efficacy of Korean red ginseng in patients with erectile dysfunction: a preliminary report. J Urol 2002; 168:2070
[19] Digiesi V et al. Coenzyme Q10 in essential hypertension. Mol Aspects Med 1994; 15 Suppl:S265
[20] Burke BE et al. Randomized, double-blind, placebo-controlled trial of coenzyme Q10 in isolated systolic hypertension. South Med J 2001; 94:1112
[21] Knapp HR, Fitzgerald GA. The antihypertensive effectsd of fish oil. A controlled study of polyunsaturated fatty acid supplements in essential hypertension. N Engl J Med. 1989; 320:1037

[22] Geleijnse JM et al. Blood pressure response to fish oil supplementation: metaregression analysis of randomized trials. J Hypertens. 2002; 20:1493