The 11 Body Systems – The Circulatory System

Posted on |

Why is the circulatory system important?

Oxygen and nutrients are required to keep the cells of the body functioning. The circulatory system delivers these to cells and takes waste away both directly, and via the sub-system of the lymphatic system. The circulatory system also carries chemical messengers (hormones and neurotransmitters) that direct cells and ultimately, tissue and organs, to do what is required to keep the body healthy and in balance.

What is it made up of?

The circulatory or cardiovascular system is made up of the heart and blood vessels which deliver nutrients, oxygen, and messages to cells, including arteries à arterioles à capillaries, and take away deoxygenated blood in venules and veins.

How can I support circulatory health?

Cardiovascular health is most affected by the body’s ability to resist oxidative, glycation (sugar-related), and inflammatory damage. So, the health of the circulatory system is closely aligned with the of the entire body and especially how well we metabolise, transport, store, and excrete nutrients. The term ‘cardiometabolic’ is often used to describe this integration of systemic ‘metabolic’ health and the health of the cardiovascular system. Therefore, a nutrient-dense diet that helps to support a healthy metabolism and optimal partitioning of nutrients, along with reducing the effects of sugar-related damage, excessive oxidation and inflammation are essential to cardiovascular health.

Cardiovascular supporting ingredients in Good Green Stuff

Vitamin B1 – Thiamin

Thiamin deficiency is prevalent in heart failure patients and supplementation with this vitamin improves cardiac function, weight maintenance, and signs and symptoms of heart failure in patients. (1-3) Thiamin deficiency could be part of the complex aetiology (causation) of heart disease and supplementation might reduce the risk of future cardiovascular events. (4)

Vitamin B2 – Riboflavin

Riboflavin is a relatively under-recognised anti-oxidant that can help reduce oxidative stress to the body. (5) Cardiovascular disease patients with the MTHFR 677TT genotype and high blood pressure might experience significant reductions with riboflavin supplementation. (6)

Vitamin B3 – Niacin

Research suggests that niacin supplementation reduces cardiovascular disease events (7, 8) via its HDL-elevating, antioxidant and anti-inflammatory properties. (9) Niacin has been shown to significantly improve lipid abnormalities in people with type 2 diabetes mellitus but requires monitoring of glucose levels if used for long-term treatment. (10)

Vitamin B6 – Pyridoxines

There is a dose-dependent relationship between increased B6 intake and reduced cardiovascular risk. (11) Many people (~20% of the population) do not habitually consume enough B6 in their diets, (12) and due to the critical role of this vitamin, in concert with the other b-vitamins, supplementation is recommended.

Vitamin B9 – Folate

Folate supplementation helps to reduce homocysteine (a cardiovascular risk marker) and inflammation and might help improve glucose control (which in turn helps to reduce sugar-related damage to the tissues of the body). (13-15)

Vitamin C

Increased vitamin C intake, vitamin C supplementation, and higher concentrations of vitamin C are associated with lower blood pressure (16) and beneficial effects on endothelial function (the cells that line the interior of blood vessels), particularly in those with cardio-metabolic disorders. (17)

Vitamin E

Pooled data from randomised controlled trials show a significant, positive effect of vitamin E supplementation on endothelial function (the thin membrane that lines the inside of blood vessels, which when damaged is a contributor to heart disease). This effect is greatest for those with lower levels of vitamin E. (18) Supplementation with vitamin E also significantly reduces systolic blood pressure. (19)

Vitamin K

Research suggests that vitamin K supplementation significantly reduces vascular calcification, which is a marker for poor vascular health and is associated with cardiovascular events like heart attacks. (20) In addition, there is evidence to show that vitamin K may help manage insulin sensitivity and glucose tolerance, (21) and therefore might help to reduce sugar-related damage to the vascular system.  

Copper

The modern diet is assumed to provide enough copper but research has demonstrated that there might be a marginal (sub-clinical) deficiency in 38% of hyperlipidaemic patients (people with high blood triglyceride and cholesterol levels). Supplementation with copper at ~ 5 mg per day improved cholesterol, LDL, HDL, and especially triglycerides. (22, 23) Copper is also involved in antioxidant enzyme activities and supplementation in those with lower copper status improves levels of the important internal antioxidants; superoxide dismutase (SOD) and diamine oxidase (DAO). (24)

Magnesium

Magnesium status is important for preserving cardiac (heart) rhythm and supplements appear to reduce arrhythmia, (25) along with aiding endothelial function. (26) Magnesium is involved in blood glucose regulation and people with metabolic syndrome and diabetes might achieve positive changes in blood glucose, insulin levels, and HDL and LDL cholesterol, and triglycerides from magnesium supplementation. (27-30)

Potassium

High blood pressure is a risk factor for heart attack and stroke and research suggests that oral potassium supplementation can significantly and safely lower both systolic and diastolic blood pressure, with a greater magnitude in this blood pressure-lowering effect seen in those patients with hypertension, (31-33) those who consume high amounts of sodium, those not on hypertensive drug treatment, and those in the lowest category of potassium intake. (34)

Zinc

Zinc status is often low in those with metabolic syndrome and zinc has been shown to reduce fasting and post-meal glucose, fasting insulin, HbA1c, and c-reactive protein, (35) and improves insulin resistance in both men and women. (36) Zinc supplementation also significantly reduce triglycerides, cholesterol and LDL cholesterol. (37)

Flaxseed

Flaxseed supplementation is considered to be beneficial for the cardiovascular system. Systematic reviews and meta-analyses have shown significant reductions in blood pressure. (38, 39) Other research suggests that flaxseed supplementation might help people to reduce weight and improve body composition (lean vs fat mass). (40) Flaxseeds also help to regulate blood-sugar balance with reductions in blood glucose, insulin and insulin resistance models in those consuming supplemental flaxseed. (41)

Bioflavonoids

Foods high in bioflavonoids like citrus, tea, coffee, red wine, pomegranate, and chocolate, have been considered to be beneficial to health overall and these foods have also been shown to reduce inflammation and oxidation. (42) Reviews of observational studies suggest that increased bioflavonoid intake reduces the risk of cardiovascular disease, cardiovascular disease mortality, and all-cause mortality. (43-45)

Grapeseed

Grapeseed extracts contain antioxidants that increase the total antioxidant activity of the body, (46) with a range of purported health benefits. In a study of 150 and 300 mg of Grapeseed extract vs placebo, over 4 weeks, there was a significant reduction in blood pressure. (47) A meta-analysis of studies up to 2011 confirmed this, with consistent, significant reductions in systolic blood pressure and heart rate. (48) Grapeseed also improves blood flow and reduces oxidative damage to the cardiovascular system, (49) increases glutathione (a key antioxidant) concentration and reduce c-reactive protein (a marker of total body inflammation) in type 2 diabetics. (50)

Green Tea

Green tea catechins can help to reduce body-fat levels, and it has been hypothesised that this is due to synergistic effects including those of caffeine and green tea catechins on fat oxidation, (51-53) and there are also positive effects on blood glucose and insulin. (54) Green tea catechins also result in significant reductions in blood pressure, total cholesterol and LDL-cholesterol. (55-58) The antioxidant, chelating, and anti-inflammatory effects of green tea might also be able to help protect against the effects of environmental and lifestyle toxins. (59)

Cocoa

There are many purported benefits to overall health from the traditional use of Cocoa and Cocoa-containing foods and drinks for cardiovascular, neurological, oral, endocrine, immune, respiratory and reproductive systems, and these are beginning to be shown in modern, scientific studies. (60, 61) Reviews of the research have shown that Cocoa and its plant phenols can improve insulin function and sensitivity, blood pressure, and improve flow-mediated dilation, (62, 63) important for proper blood flow and overall health of the cardiovascular system. The benefits to blood pressure are greater than even drastic reductions in sodium. (64) Cocoa flavanols can also improve HDL (‘good’) cholesterol, and reduce triglycerides (fats in the blood) and insulin. (65) Additionally, improvements in inflammation have been seen in those with diabetes and metabolic syndrome. (66) Cocoa flavanols could benefit performance by improving mitochondrial efficiency, improving vascular function and reducing exercise-induced oxidative stress. (67)

Rosemary

the compound effects of antioxidant, anti-inflammatory, hypoglycaemic, hypolipidaemic, hypotensive, anti-atherosclerotic, anti-thrombotic, hepatoprotective, and hypocholesterolaemic actions of rosemary compounds have led to the suggestion that rosemary and rosemary extracts could be useful for cardiometabolic health. (68, 69)

Turmeric

Along with its other purported effects, it is likely that turmeric aids blood-glucose control, reduces cholesterol and blood lipids, and improves immune function, all of which help to improve cardiovascular health. (70)

Resveratrol

Human evidence shows that resveratrol supplementation can reduce triglyceride levels (one of the key markers for future cardiovascular risk). (71) A summary of randomised controlled trials found a significant reduction of body weight, BMI, and waist circumference, also markers of future health risk, from resveratrol supplementation. (72) Resveratrol, in addition to its antioxidant roles, increase nitric oxide and this is thought to be the mechanism by which it can reduce hypertension (high blood pressure), (73) an effect mostly seen with doses of > 300 mg per day and in those with diabetes. (74) In addition, resveratrol has been purported to be anti-inflammatory. In a review of 15 trials (n = 658), it was found to reduce C-reactive protein overall and also reduced tumour necrosis factor-α in young adults and those with obesity. (75)

Beta-glucans

Beta-glucans have demonstrated the ability to reduce blood glucose from either high doses (~ 6 g per day) or longer-term use of lower doses. (76) They can also reduce both total and LDL cholesterol, improving blood lipid profiles. (77, 78)

Co-enzyme Q10

CoQ10 has a relatively long history of use both for prevention of cardiovascular disease and as part of the supplemental regimen of those with heart disease, especially with statin use, which can reduce both production and availability of CoQ10 in the body. (79, 80) Meaningful reductions in blood pressure (up to 16 mm Hg reduction in systolic blood pressure) and improved mortality outcomes, and fewer cardiac events and complication for those with heart disease have been observed, (81-83) along with functional outcomes such as improved cardiac output and stroke volume. (82) CoQ10 has also resulted in meaningful reductions (~ 0.3 mmol/L) of triglycerides, a key marker for cardiovascular and cardiometabolic risk. (84) For those with existing coronary artery disease, CoQ10 can improve HDL and total cholesterol levels. (85) The most recent reviews of the evidence conclude that CoQ10 is a useful tool for managing heart disease. (86) In those with type 2 diabetes, CoQ10 might help to control blood glucose and improve triglyceride and HDL cholesterol concentration in the blood. (87)

Aloe Vera

Studies on oral use of Aloe vera extracts have shown reduced blood glucose, (88) cholesterol, triglycerides, LDL cholesterol, blood pressure, and improved HDL cholesterol. (89, 90)

Globe Artichoke

Globe artichoke appears to exhibit strong antioxidant activity, with increased superoxide dismutase, catalase, glutathione, and glutathione peroxidase levels. (91) At least one randomised controlled trial has demonstrated significant, modest reduction (~ -0.3 mmol/L) in total cholesterol resulting from globe artichoke supplementation. (92) An extract of globe artichoke has also resulted in improved blood glucose and insulin homeostasis in another randomised, double-blinded trial. (93)

Apple pectin

Apple pectin supplementation can reduce total cholesterol, LDL-cholesterol, triglycerides, and might have anti-obesity effects. (94, 95) Changes in the guts of laboratory animals from apple pectin supplementation have also been shown to increase the bioavailability of quercetin, an antioxidant bioflavonoid, (96, 97) with the suggestion that apple pectin may help improve overall nutriment and health.

Psyllium

Psyllium specifically is known to have cholesterol-lowering properties. (98) Reviews of the many studies that have been conducted on psyllium specifically show that it can help to reduce total and LDL cholesterol, apolipoprotein B, along with improve blood-sugar responses, and increases satiety. (99-101)

Milk Thistle

Milk thistle contains several flavonoids with antioxidant and anti-inflammatory properties. (102) It has also been found to have lipid-lowering, anti-diabetic, liver-protective and blood-pressure-lowering properties and it is hypothesised that it may improve cardiometabolic health. (103)

Bromelain

Bromelain is now being studied for a range of health effects. It is considered to inhibit platelet aggregation, be anti-inflammatory and anti-tumour, and improve immunity and digestive function. It may also enhance wound-healing and provide cardiovascular benefits. (104, 105)

Probiotics

Reviews of the scientific literature show a range of benefits from probiotic supplementation for weight- and fat-loss and reduced markers of diabetes and metabolic syndrome (106-110), reducing oxidation, (111, 112) inflammation and inflammation-related pain (113, 114), and improved cardiovascular markers (cholesterol and lipid profiles). (115)

Spirulina

Spirulina is thought to provide benefits for reducing oxidation (116) and improved cardiovascular and diabetic markers, (117) along with reduced inflammation. (118, 119) Reviews of the scientific literature show that spirulina might offer interesting, specific benefits to those with cardiovascular risk factors. It has been demonstrated to reduce total cholesterol and LDL-cholesterol and triglycerides, while increasing (‘good’) HDL-cholesterol. (120)

Hawthorn

Hawthorn has been mostly studied for its benefits in cardiovascular disease. A 2010 review of these studies concluded, current research to date suggests that hawthorn may potentially represent a safe, effective, nontoxic agent in the treatment of cardiovascular disease and ischemic heart disease. (121)

References

1.            Jain A, Mehta R, Al-Ani M, Hill JA, Winchester DE. Determining the Role of Thiamine Deficiency in Systolic Heart Failure: A Meta-Analysis and Systematic Review. Journal of Cardiac Failure. 2015;21(12):1000-7.
2.            DiNicolantonio JJ, Niazi AK, Lavie CJ, O’Keefe JH, Ventura HO. Thiamine Supplementation for the Treatment of Heart Failure: A Review of the Literature. Congestive Heart Failure. 2013;19(4):214-22.
3.            DiNicolantonio JJ, Lavie CJ, Niazi AK, Keefe JH, Hu T. Effects of Thiamine on Cardiac Function in Patients With Systolic Heart Failure: Systematic Review and Metaanalysis of Randomized, Double-Blind, Placebo-Controlled Trials. Ochsner Journal. 2013;13(4):495.
4.            DiNicolantonio JJ, Liu J, O’Keefe JH. Thiamine and Cardiovascular Disease: A Literature Review. Progress in Cardiovascular Diseases. 2018;61(1):27-32.
5.            Ashoori M, Saedisomeolia A. Riboflavin (vitamin B2) and oxidative stress: a review. British Journal of Nutrition. 2014;111(11):1985-91.
6.            Strain J, Hughes CF, McNulty H, Ward M. Riboflavin Lowers Blood Pressure: A Review of a Novel Gene-nutrient Interaction. Nutrition and Food Sciences Research. 2015;2(2):3-6.
7.            Lavigne PM KR. The current state of niacin in cardiovascular disease prevention. Journal of the American College of Cardiology. 2013;61(4).
8.            Yadav R FM, Younis N, Hama S, Ammori BJ, Kwok S, Soran H. Extended-release niacin with laropiprant: a review on efficacy, clinical effectiveness and safety. Expert Opinion on Pharmacotherapy. 2012;13(9):1345-62.
9.            A S. Effect of niacin on endothelial function: a systematic review and meta-analysis of randomized controlled trials. Vascular Medicine. 2014;19(1):54-66.
10.          Ding Y LY, Wen A. Effect of niacin on lipids and glucose in patients with type 2 diabetes: a meta-analysis of randomized, controlled clinical trials. Clinical Nutrition. 2015;34(5):838-44.
11.          Jayedi A, Zargar MS. Intake of vitamin B6, folate, and vitamin B12 and risk of coronary heart disease: a systematic review and dose-response meta-analysis of prospective cohort studies. Critical Reviews in Food Science and Nutrition. 2018:1-11.
12.          University of Otago and Ministry of Health. A Focus on Nutrition: Key findings of the 2008/09 New Zealand Adult Nutrition Survey. Wellington; 2011.
13.          Sudchada P, Saokaew S, Sridetch S, Incampa S, Jaiyen S, Khaithong W. Effect of folic acid supplementation on plasma total homocysteine levels and glycemic control in patients with type 2 diabetes: A systematic review and meta-analysis. Diabetes Research and Clinical Practice. 2012;98(1):151-8.
14.          Zhao JV, Schooling CM, Zhao JX. The effects of folate supplementation on glucose metabolism and risk of type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. Annals of Epidemiology. 2018;28(4):249-57.e1.
15.          Fatahi S, Pezeshki M, Mousavi SM, Teymouri A, Rahmani J, Kord Varkaneh H, et al. Effects of folic acid supplementation on C-reactive protein: A systematic review and meta-analysis of randomized controlled trials. Nutrition, Metabolism and Cardiovascular Diseases. 2018.
16.          Juraschek SP GE, Appel LJ, Miller ER. Effects of vitamin C supplementation on blood pressure: a meta-analysis of randomized controlled trials. The American Journal of Clinical Nutrition. 2012;95(5):1079-88.
17.          Ashor AW LJ, Mathers JC, Siervo M. Effect of vitamin C on endothelial function in health and disease: a systematic review and meta-analysis of randomised controlled trials. Atherosclerosis. 2015;235(1):9-20.
18.          Ashor AW, Siervo M, Lara J, Oggioni C, Afshar S, Mathers JC. Effect of vitamin C and vitamin E supplementation on endothelial function: a systematic review and meta-analysis of randomised controlled trials. British Journal of Nutrition. 2015;113(8):1182-94.
19.          Emami MR, Safabakhsh M, Alizadeh S, Asbaghi O, Khosroshahi MZ. Effect of vitamin E supplementation on blood pressure: a systematic review and meta-analysis. Journal of Human Hypertension. 2019.
20.          Lees JS CF, Witham MD, Jardine AG, Mark PB. Vitamin K status, supplementation and vascular disease: a systematic review and meta-analysis. Heart. 2018.
21.          Manna P KJ. Beneficial role of vitamin K supplementation on insulin sensitivty, glucose metabolism, and the reduced risk of type 2 diabetes: a review. Nutrition. 2016;32(7-8):732-39.
22.          Alarcón-Corredor OM, Guerrero Y, Ramírez de Fernández M, D’Jesús I, Burguera M, Burguera JL, et al. [Effect of copper supplementation on lipid profile of Venezuelan hyperlipemic patients]. Arch Latinoam Nutr. 2004;54(4):413-8.
23.          Hermann J, Chung H, Arquitt A, Goad C, Burns M, Chan B. Effects of Chromium or Copper Supplementation on Plasma Lipids, Plasma Glucose and Serum Insulin in Adults Over Age Fifty. Journal of Nutrition For the Elderly. 1999;18(1):27-45.
24.          Jones AA, DiSilvestro RA, Coleman M, Wagner TL. Copper supplementation of adult men: Effects on blood copper enzyme activities and indicators of cardiovascular disease risk. Metabolism. 1997;46(12):1380-3.
25.          Salaminia S, Sayehmiri F, Angha P, Sayehmiri K, Motedayen M. Evaluating the effect of magnesium supplementation and cardiac arrhythmias after acute coronary syndrome: a systematic review and meta-analysis. BMC Cardiovascular Disorders. 2018;18(1):129.
26.          Darooghegi Mofrad M, Djafarian K, Mozaffari H, Shab-Bidar S. Effect of magnesium supplementation on endothelial function: A systematic review and meta-analysis of randomized controlled trials. Atherosclerosis. 2018;273:98-105.
27.          Verma H, Garg R. Effect of magnesium supplementation on type 2 diabetes associated cardiovascular risk factors: a systematic review and meta-analysis. Journal of Human Nutrition and Dietetics. 2017;30(5):621-33.
28.          Morais JBS, Severo JS, de Alencar GRR, de Oliveira ARS, Cruz KJC, Marreiro DdN, et al. Effect of magnesium supplementation on insulin resistance in humans: A systematic review. Nutrition. 2017;38:54-60.
29.          Veronese N, Watutantrige-Fernando S, Luchini C, Solmi M, Sartore G, Sergi G, et al. Effect of magnesium supplementation on glucose metabolism in people with or at risk of diabetes: a systematic review and meta-analysis of double-blind randomized controlled trials. European Journal Of Clinical Nutrition. 2016;70:1354.
30.          Simental-Mendía LE, Sahebkar A, Rodríguez-Morán M, Guerrero-Romero F. A systematic review and meta-analysis of randomized controlled trials on the effects of magnesium supplementation on insulin sensitivity and glucose control. Pharmacological Research. 2016;111:272-82.
31.          Barri YM WC. The effects of potassium depletion and supplementation on blood pressure: a clinical review. The American Journal of the Medical Sciences. 1997;314(1):37-40.
32.          Cappuccio FP MG. Does potassium supplementation lower blood pressure? A meta-analysis of published trials. Journal of Hypertension. 1991;9(5):465-73.
33.          Poorolajal J ZF, Soltanian AR, Sheikh V, Hooshmand E, Maleki A. Oral potassium supplementation for management of essential hypertension: A meta-analysis of randomized controlled trials. PLOS ONE. 2017;12(4):e0174967.
34.          Filippini T FV, D’Amico R, Vinceti M. The effect of potassium supplementation on blood pressure in hypertensive subjects: a systematic review and meta-analysis. International Journal of Cardiology. 2017;230:127-35.
35.          Wang X, Wu W, Zheng W, Fang X, Chen L, Rink L, et al. Zinc supplementation improves glycemic control for diabetes prevention and management: a systematic review and meta-analysis of randomized controlled trials. The American Journal of Clinical Nutrition. 2019.
36.          Cruz KJC, Morais JBS, de Oliveira ARS, Severo JS, Marreiro DdN. The Effect of Zinc Supplementation on Insulin Resistance in Obese Subjects: a Systematic Review. Biological Trace Element Research. 2017;176(2):239-43.
37.          Ranasinghe P, Wathurapatha W, Ishara M, Jayawardana R, Galappatthy P, Katulanda P, et al. Effects of Zinc supplementation on serum lipids: a systematic review and meta-analysis. Nutrition & Metabolism. 2015;12(1):26.
38.          Khalesi S, Irwin C, Schubert M. Flaxseed Consumption May Reduce Blood Pressure: A Systematic Review and Meta-Analysis of Controlled Trials. The Journal of Nutrition. 2015;145(4):758-65.
39.          Ursoniu S, Sahebkar A, Andrica F, Serban C, Banach M. Effects of flaxseed supplements on blood pressure: A systematic review and meta-analysis of controlled clinical trial. Clinical Nutrition. 2016;35(3):615-25.
40.          Mohammadi‐Sartang M, Mazloom Z, Raeisi‐Dehkordi H, Barati‐Boldaji R, Bellissimo N, Totosy de Zepetnek J. The effect of flaxseed supplementation on body weight and body composition: a systematic review and meta‐analysis of 45 randomized placebo‐controlled trials. Obesity Reviews. 2017;18(9):1096-107.
41.          Mohammadi-Sartang M, Sohrabi Z, Barati-Boldaji R, Raeisi-Dehkordi H, Mazloom Z. Flaxseed supplementation on glucose control and insulin sensitivity: a systematic review and meta-analysis of 25 randomized, placebo-controlled trials. Nutrition reviews. 2017;76(2):125-39.
42.          Suen J, Thomas J, Kranz A, Vun S, Miller M. Effect of Flavonoids on Oxidative Stress and Inflammation in Adults at Risk of Cardiovascular Disease: A Systematic Review. Healthcare. 2016;4(3):69.
43.          Wang X, Ouyang YY, Liu J, Zhao G. Flavonoid intake and risk of CVD: a systematic review and meta-analysis of prospective cohort studies. British Journal of Nutrition. 2014;111(1):1-11.
44.          Grosso G, Sciacca S, Godos J, Micek A, Pajak A, Galvano F, et al. Dietary Flavonoid and Lignan Intake and Mortality in Prospective Cohort Studies: Systematic Review and Dose-Response Meta-Analysis. American Journal of Epidemiology. 2017;185(12):1304-16.
45.          Liu X-m, Liu Y-j, Huang Y, Yu H-j, Yuan S, Tang B-w, et al. Dietary total flavonoids intake and risk of mortality from all causes and cardiovascular disease in the general population: A systematic review and meta-analysis of cohort studies. Molecular Nutrition & Food Research. 2017;61(6):1601003.
46.          Nuttall SL, Kendall MJ, Bombardelli E, Morazzoni P. An evaluation of the antioxidant activity of a standardized grape seed extract, Leucoselect. Journal of clinical pharmacy and therapeutics. 1998;23(5):385-9.
47.          Sivaprakasapillai B, Edirisinghe I, Randolph J, Steinberg F, Kappagoda T. Effect of grape seed extract on blood pressure in subjects with the metabolic syndrome. Metabolism. 2009;58(12):1743-6.
48.          Feringa HH, Laskey DA, Dickson JE, Coleman CI. The effect of grape seed extract on cardiovascular risk markers: a meta-analysis of randomized controlled trials. J Am Diet Assoc. 2011;111(8):1173-81.
49.          Clifton PM. Effect of Grape Seed Extract and Quercetin on Cardiovascular and Endothelial Parameters in High-Risk Subjects. Journal of biomedicine & biotechnology. 2004;2004(5):272-8.
50.          Kar P, Laight D, Rooprai HK, Shaw KM, Cummings M. Effects of grape seed extract in Type 2 diabetic subjects at high cardiovascular risk: a double blind randomized placebo controlled trial examining metabolic markers, vascular tone, inflammation, oxidative stress and insulin sensitivity. Diabet Med. 2009;26(5):526-31.
51.          Rains TM, Agarwal S, Maki KC. Antiobesity effects of green tea catechins: a mechanistic review. The Journal of Nutritional Biochemistry. 2011;22(1):1-7.
52.          Thorne A, Matthews LJ, Lanosa M, Phung OJ, Baker WL, Coleman CI. Effect of green tea catechins with or without caffeine on anthropometric measures: a systematic review and meta-analysis. The American Journal of Clinical Nutrition. 2009;91(1):73-81.
53.          Thavanesan N. The putative effects of green tea on body fat: an evaluation of the evidence and a review of the potential mechanisms. British Journal of Nutrition. 2011;106(9):1297-309.
54.          Thielecke F, Boschmann M. The potential role of green tea catechins in the prevention of the metabolic syndrome – A review. Phytochemistry. 2009;70(1):11-24.
55.          Kim A, Chiu A, Barone MK, Avino D, Wang F, Coleman CI, et al. Green Tea Catechins Decrease Total and Low-Density Lipoprotein Cholesterol: A Systematic Review and Meta-Analysis. Journal of the American Dietetic Association. 2011;111(11):1720-9.
56.          Onakpoya I, Spencer E, Heneghan C, Thompson M. The effect of green tea on blood pressure and lipid profile: A systematic review and meta-analysis of randomized clinical trials. Nutrition, Metabolism and Cardiovascular Diseases. 2014;24(8):823-36.
57.          Khalesi S, Sun J, Buys N, Jamshidi A, Nikbakht-Nasrabadi E, Khosravi-Boroujeni H. Green tea catechins and blood pressure: a systematic review and meta-analysis of randomised controlled trials. Eur J Nutr. 2014;53(6):1299-311.
58.          Momose Y, Maeda-Yamamoto M, Nabetani H. Systematic review of green tea epigallocatechin gallate in reducing low-density lipoprotein cholesterol levels of humans. International journal of food sciences and nutrition. 2016;67(6):606-13.
59.          Rameshrad M, Razavi BM, Hosseinzadeh H. Protective effects of green tea and its main constituents against natural and chemical toxins: A comprehensive review. Food and Chemical Toxicology. 2017;100:115-37.
60.          Araujo QRD, Gattward JN, Almoosawi S, Parada Costa Silva MdGC, Dantas PADS, Araujo Júnior QRD. Cocoa and Human Health: From Head to Foot—A Review. Critical Reviews in Food Science and Nutrition. 2016;56(1):1-12.
61.          Martín MÁ, Ramos S. Health beneficial effects of cocoa phenolic compounds: a mini-review. Current Opinion in Food Science. 2017;14:20-5.
62.          Cassidy A, Abdelhamid A, Kay C, Rimm EB, Cohn JS, Kroon PA, et al. Effects of chocolate, cocoa, and flavan-3-ols on cardiovascular health: a systematic review and meta-analysis of randomized trials. The American Journal of Clinical Nutrition. 2012;95(3):740-51.
63.          Bauer SR, Ding EL, Smit LA. Cocoa Consumption, Cocoa Flavonoids, and Effects on Cardiovascular Risk Factors: An Evidence-Based Review. Current Cardiovascular Risk Reports. 2011;5(2):120-7.
64.          Kobler D, Schuler G, Thiele H, Eitel I, Schmidt J, Sareban M, et al. Effect of Cocoa Products on Blood Pressure: Systematic Review and Meta-Analysis. American Journal of Hypertension. 2010;23(1):97-103.
65.          Zhang I, Lin X, Liu S, Li A, Wang L, Sesso HD, et al. Cocoa Flavanol Intake and Biomarkers for Cardiometabolic Health: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. The Journal of Nutrition. 2016;146(11):2325-33.
66.          Ellinger S, Stehle P. Impact of cocoa consumption on inflammation processes—a critical review of randomized controlled trials. Nutrients. 2016;8(6):321.
67.          Decroix L, Soares DD, Meeusen R, Heyman E, Tonoli C. Cocoa Flavanol Supplementation and Exercise: A Systematic Review. Sports Medicine. 2018;48(4):867-92.
68.          Hassani FV, Shirani K, Hosseinzadeh H. Rosemary (Rosmarinus officinalis) as a potential therapeutic plant in metabolic syndrome: a review. Naunyn-Schmiedeberg’s Archives of Pharmacology. 2016;389(9):931-49.
69.          Sedighi R, Zhao Y, Yerke A, Sang S. Preventive and protective properties of rosemary (Rosmarinus officinalis L.) in obesity and diabetes mellitus of metabolic disorders: a brief review. Current Opinion in Food Science. 2015;2:58-70.
70.          Fallah Huseini H, Zahmatkash M, Haghighi M. A review on pharmacological effects of Curcuma longa L.(turmeric). Journal of Medicinal Plants. 2010;1(33):1-15.
71.          Zhao H, Song A, Zhang Y, Shu L, Song G, Ma H. Effect of Resveratrol on Blood Lipid Levels in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis. Obesity. 2019;27(1):94-102.
72.          Mousavi SM, Milajerdi A, Sheikhi A, Kord-Varkaneh H, Feinle-Bisset C, Larijani B, et al. Resveratrol supplementation significantly influences obesity measures: a systematic review and dose–response meta-analysis of randomized controlled trials. Obesity Reviews. 2019;20(3):487-98.
73.          Dorri Mashhadi F, Salari R, Ghorbanzadeh H. The effect of resveratrol dose and duration of treatment on blood pressure in patients with cardiovascular disorders: A systematic review. Curr Drug Discov Technol. 2019.
74.          Fogacci F, Tocci G, Presta V, Fratter A, Borghi C, Cicero AFG. Effect of resveratrol on blood pressure: A systematic review and meta-analysis of randomized, controlled, clinical trials. Critical Reviews in Food Science and Nutrition. 2018:1-14.
75.          Haghighatdoost F, Hariri M. Can resveratrol supplement change inflammatory mediators? A systematic review and meta-analysis on randomized clinical trials. European Journal of Clinical Nutrition. 2019;73(3):345-55.
76.          Andrade EF, Vieira Lobato R, Vasques de Araújo T, Zangerônimo MG, de Sousa RV, Pereira LJ. Effect of beta-glucans in the control of blood glucose levels of diabetic patients: a systematic review. Nutr Hosp. 2015;31(1).
77.          Pins J, Kaur H. A review of the effects of barley beta-glucan on cardiovascular and diabetic risk. Cereal Foods World. 2006;51(1):8.
78.          Ho HVT, Sievenpiper JL, Zurbau AL, Mejia SB, Jovanovski E, Yeung FA, et al. The Effect of Oat Beta-Glucan on Clinical Lipid Markers for Cardiovascular Disease Risk Reduction: A Systematic Review & Meta-Analysis of Randomized Controlled Trials. The FASEB Journal. 2016;30(1_supplement):289.5-.5.
79.          Sarter B. Coenzyme Q10 and Cardiovascular Disease: A Review. Journal of Cardiovascular Nursing. 2002;16(4):9-20.
80.          Banach M, Serban C, Ursoniu S, Rysz J, Muntner P, Toth PP, et al. Statin therapy and plasma coenzyme Q10 concentrations—A systematic review and meta-analysis of placebo-controlled trials. Pharmacological Research. 2015;99:329-36.
81.          Rosenfeldt F, Hilton D, Pepe S, Krum H. Systematic review of effect of coenzyme Q10 in physical exercise, hypertension and heart failure. BioFactors. 2003;18(1‐4):91-100.
82.          DiNicolantonio JJ, Bhutani J, McCarty MF, O’Keefe JH. Coenzyme Q10 for the treatment of heart failure: a review of the literature. Open Heart. 2015;2(1):e000326.
83.          Rabago G, Hernandez-Estefania R, de Frutos F, Gea A. Prophylactic treatment with coenzyme Q10 in patients undergoing cardiac surgery: could an antioxidant reduce complications? A systematic review and meta-analysis. Interactive CardioVascular and Thoracic Surgery. 2014;20(2):254-9.
84.          Suksomboon N, Poolsup N, Juanak N. Effects of coenzyme Q10 supplementation on metabolic profile in diabetes: a systematic review and meta-analysis. Journal of clinical pharmacy and therapeutics. 2015;40(4):413-8.
85.          Jorat MV, Tabrizi R, Mirhosseini N, Lankarani KB, Akbari M, Heydari ST, et al. The effects of coenzyme Q10 supplementation on lipid profiles among patients with coronary artery disease: a systematic review and meta-analysis of randomized controlled trials. Lipids in Health and Disease. 2018;17(1):230.
86.          Jafari M, Mousavi SM, Asgharzadeh A, Yazdani N. Coenzyme Q10 in the treatment of heart failure: A systematic review of systematic reviews. Indian Heart Journal. 2018;70:S111-S7.
87.          Zhang S-y, Yang K-l, Zeng L-t, Wu X-h, Huang H-y. Effectiveness of Coenzyme Q10 Supplementation for Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis. International Journal of Endocrinology. 2018;2018:11.
88.          Suksomboon N, Poolsup N, Punthanitisarn S. Effect of Aloe vera on glycaemic control in prediabetes and type 2 diabetes: a systematic review and meta-analysis. Journal of clinical pharmacy and therapeutics. 2016;41(2):180-8.
89.          Pothuraju R, Sharma RK, Onteru SK, Singh S, Hussain SA. Hypoglycemic and Hypolipidemic Effects of Aloe vera Extract Preparations: A Review. Phytotherapy Research. 2016;30(2):200-7.
90.          Zhang Y, Liu W, Liu D, Zhao T, Tian H. Efficacy of Aloe Vera Supplementation on Prediabetes and Early Non-Treated Diabetic Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients. 2016;8(7):388.
91.          Salekzamani S, Ebrahimi-Mameghani M, Rezazadeh K. The antioxidant activity of artichoke (Cynara scolymus): A systematic review and meta-analysis of animal studies. Phytotherapy Research. 2019;33(1):55-71.
92.          Bundy R, Walker AF, Middleton RW, Wallis C, Simpson HCR. Artichoke leaf extract (Cynara scolymus) reduces plasma cholesterol in otherwise healthy hypercholesterolemic adults: A randomized, double blind placebo controlled trial. Phytomedicine. 2008;15(9):668-75.
93.          Rondanelli M, Opizzi A, Faliva M, Sala P, Perna S, Riva A, et al. Metabolic Management in Overweight Subjects with Naive Impaired Fasting Glycaemia by Means of a Highly Standardized Extract From Cynara scolymus: A Double-blind, Placebo-controlled, Randomized Clinical Trial. Phytotherapy Research. 2014;28(1):33-41.
94.          Gonzalez M, Rivas C, Caride B, Lamas MA, Taboada MC. Effects of orange and apple pectin on cholesterol concentration in serum, liver and faeces. Journal of physiology and biochemistry. 1998;54(2):99-104.
95.          Samout N, Bouzenna H, Dhibi S, Ncib S, ElFeki A, Hfaiedh N. Therapeutic effect of apple pectin in obese rats. Biomedicine & Pharmacotherapy. 2016;83:1233-8.
96.          Nishijima T, Iwai K, Saito Y, Takida Y, Matsue H. Chronic Ingestion of Apple Pectin Can Enhance the Absorption of Quercetin. Journal of Agricultural and Food Chemistry. 2009;57(6):2583-7.
97.          Nishijima T, Takida Y, Saito Y, Ikeda T, Iwai K. Simultaneous ingestion of high-methoxy pectin from apple can enhance absorption of quercetin in human subjects. British Journal of Nutrition. 2015;113(10):1531-8.
98.          Naghdi Badi H, Dastpak A, Ziai S. A review of psyllium plant. Journal of Medicinal Plants. 2004;1(9):1-14.
99.          Jane M, McKay J, Pal S. Effects of daily consumption of psyllium, oat bran and polyGlycopleX on obesity-related disease risk factors: A critical review. Nutrition. 2019;57:84-91.
100.        Komishon A, Ho HVT, Sievenpiper J, Blanco Mejia S, Vuksan V, Zurbau A, et al. Effect of psyllium (Plantago ovata) fiber on LDL cholesterol and alternative lipid targets, non-HDL cholesterol and apolipoprotein B: a systematic review and meta-analysis of randomized controlled trials. The American Journal of Clinical Nutrition. 2018;108(5):922-32.
101.        Zurbau A, Ho HVT, Jovanvoski E, Mejia SB, Sievenpiper J, Jenkins A, et al. A systematic review and meta-analysis of RCTs on the effect of psyllium fiber on lipid targets for CVD risk reduction. The FASEB Journal. 2017;31(1_supplement):973.12-.12.
102.        Fallah Huseini H, Hemati A, Alavian S. A review of herbal medicine: Silybum marianum. Journal of Medicinal Plants. 2004;3(11):14-24.
103.        Tajmohammadi A, Razavi BM, Hosseinzadeh H. Silybum marianum (milk thistle) and its main constituent, silymarin, as a potential therapeutic plant in metabolic syndrome: A review. Phytotherapy Research. 2018;32(10):1933-49.
104.        Kelly GS, editor Bromelain: a literature review and discussion of its therapeutic applications. Alternative Medicine Review; 1996: Citeseer.
105.        Pavan R, Jain S, Shraddha, Kumar A. Properties and Therapeutic Application of Bromelain: A Review. Biotechnology Research International. 2012;2012:6.
106.        Saez-Lara MJ, Robles-Sanchez C, Ruiz-Ojeda FJ, Plaza-Diaz J, Gil A. Effects of Probiotics and Synbiotics on Obesity, Insulin Resistance Syndrome, Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease: A Review of Human Clinical Trials. Int J Mol Sci. 2016;17(6).
107.        Ejtahed H-S, Angoorani P, Soroush A-R, Atlasi R, Hasani-Ranjbar S, Mortazavian AM, et al. Probiotics supplementation for the obesity management; A systematic review of animal studies and clinical trials. Journal of Functional Foods. 2019;52:228-42.
108.        Borgeraas H, Johnson LK, Skattebu J, Hertel JK, Hjelmesæth J. Effects of probiotics on body weight, body mass index, fat mass and fat percentage in subjects with overweight or obesity: a systematic review and meta-analysis of randomized controlled trials. Obesity Reviews. 2018;19(2):219-32.
109.        Khalesi S, Johnson DW, Campbell K, Williams S, Fenning A, Saluja S, et al. Effect of probiotics and synbiotics consumption on serum concentrations of liver function test enzymes: a systematic review and meta-analysis. Eur J Nutr. 2018;57(6):2037-53.
110.        Barengolts E. GUT MICROBIOTA, PREBIOTICS, PROBIOTICS, AND SYNBIOTICS IN MANAGEMENT OF OBESITY AND PREDIABETES: REVIEW OF RANDOMIZED CONTROLLED TRIALS. Endocrine Practice. 2016;22(10):1224-34.
111.        Mishra V, Shah C, Mokashe N, Chavan R, Yadav H, Prajapati J. Probiotics as Potential Antioxidants: A Systematic Review. Journal of Agricultural and Food Chemistry. 2015;63(14):3615-26.
112.        Heshmati J, Farsi F, Shokri F, Rezaeinejad M, Almasi-Hashiani A, Vesali S, et al. A systematic review and meta-analysis of the probiotics and synbiotics effects on oxidative stress. Journal of Functional Foods. 2018;46:66-84.
113.        Pandey KR, Naik SR, Vakil BV. Probiotics, prebiotics and synbiotics- a review. Journal of Food Science and Technology. 2015;52(12):7577-87.
114.        Nazemian V, Shadnoush M, Manaheji H, Zaringhalam J. Probiotics and Inflammatory Pain: A Literature Review Study. Middle East J Rehabil Health Stud. 2016;3(2):e36087.
115.        Miremadi F, Sherkat F, Stojanovska L. Hypocholesterolaemic effect and anti-hypertensive properties of probiotics and prebiotics: A review. Journal of Functional Foods. 2016;25:497-510.
116.        Hernández ML, Wall-Medrano A, Juarez-Oropeza M, Ramos-Jimenez A, Hernandez-Torres RP. SPIRULINA AND ITS HYPOLIPIDEMIC AND ANTIOXIDANT EFFECTS IN HUMANS: A SYSTEMATIC REVIEW. Nutr Hosp. 2015;32(2):494-500.
117.        Yousefi R, Saidpour A, Mottaghi A. The effects of Spirulina supplementation on metabolic syndrome components, its liver manifestation and related inflammatory markers: A systematic review. Complementary Therapies in Medicine. 2019;42:137-44.
118.        Huijuan X, Guihua X. Review health effect of spirulina as function food. J Agric Sci. 2005;26:90-3.
119.        de la Jara A, Ruano-Rodriguez C, Polifrone M, Assunçao P, Brito-Casillas Y, Wägner AM, et al. Impact of dietary Arthrospira (Spirulina) biomass consumption on human health: main health targets and systematic review. Journal of Applied Phycology. 2018;30(4):2403-23.
120.        Serban M-C, Sahebkar A, Dragan S, Stoichescu-Hogea G, Ursoniu S, Andrica F, et al. A systematic review and meta-analysis of the impact of Spirulina supplementation on plasma lipid concentrations. Clinical Nutrition. 2016;35(4):842-51.
121.        Tassell M, Kingston R, Gilroy D, Lehane M, Furey A. Hawthorn (<i>Crataegus </i>spp.) in the treatment of cardiovascular disease. Pharmacognosy Reviews. 2010;4(7):32-41.