Cardiora

SCIENTIFIC RESEARCH ON THE FOLLOWING INGREDIENTS:

Vitamin K2 – M-7

Highlighting The Substantial Body Of Evidence Confirming The Importance Of Vitamin K₂ As A Cardio-Support Nutrient, And How The Right K₂ Makes All The Difference

Abstract

In an ideal world, Vitamin K2 would have the same association with cardiovascular health that folic acid has with pregnancy. Optimal Vitamin K2 intake is crucial to avoid the calcium plaque buildup of atherosclerosis, thus keeping the risk and rate of calcification as low as possible.1-3

Matrix GLA protein (MGP)—found in the tissues of the heart, kidneys, and lungs—plays a dominant role in vascular calcium metabolism. Its production is stimulated by Vitamin D3, but it requires adequate Vitamin K2 intakes to be activated (similar to the bone-building protein osteocalcin). Once activated by Vitamin K2, MGP can bind calcium and escort it out of the areas where this mineral is destructive, namely arteries and soft tissues.1,4

No other productive mechanism for maintaining flexible blood vessels walls has been discovered, which makes MGP the only known and most potent existing inhibitor of cardiovascular calcification.

That is why Vitamin K2 is crucial as a cardiovascular health nutrient. Here we will endeavor to clear up considerable confusion about Vitamin K2, ensuring the right form is identified, as well as provide the substantial body of evidence confirming its role as a cardiovascular-support nutrient.

Source: Vik H. “Highlighting The Substantial Body Of Evidence Confirming The Importance Of Vitamin K2 As A Cardio-Support Nutrient, And How The Right K2 Makes All The Difference.” Integr Med (Encinitas). 2019 Dec;18(6):24-28. PMCID: PMC7238900, PMID: 32549853

Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study

Abstract

Vitamin K-dependent proteins, including matrix Gla-protein, have been shown to inhibit vascular calcification. Activation of these proteins via carboxylation depends on the availability of vitamin K. We examined whether dietary intake of phylloquinone (vitamin K-1) and menaquinone (vitamin K-2) were related to aortic calcification and coronary heart disease (CHD) in the population-based Rotterdam Study. The analysis included 4807 subjects with dietary data and no history of myocardial infarction at baseline (1990-1993) who were followed until January 1, 2000. The risk of incident CHD, all-cause mortality, and aortic atherosclerosis was studied in tertiles of energy-adjusted vitamin K intake after adjustment for age, gender, BMI, smoking, diabetes, education, and dietary factors. The relative risk (RR) of CHD mortality was reduced in the mid and upper tertiles of dietary menaquinone compared to the lower tertile [RR = 0.73 (95% CI: 0.45, 1.17) and 0.43 (0.24, 0.77), respectively]. Intake of menaquinone was also inversely related to all-cause mortality [RR = 0.91 (0.75, 1.09) and 0.74 (0.59, 0.92), respectively] and severe aortic calcification [odds ratio of 0.71 (0.50, 1.00) and 0.48 (0.32, 0.71), respectively]. Phylloquinone intake was not related to any of the outcomes. These findings suggest that an adequate intake of menaquinone could be important for CHD prevention.

Source: Geleijnse JM, Vermeer C, Grobbee DE, Schurgers LJ, Knapen MH, van der Meer IM, Hofman A, Witteman JC. “Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study.” J Nutr. 2004 Nov;134(11):3100-5. PMID: 15514282, DOI: 10.1093/jn/134.11.3100.

MK-7 and Its Effects on Bone Quality and Strength

Abstract

Vitamin K acts as a cofactor and is required for post-translational γ-carboxylation of vitamin K-dependent proteins (VKDP). The current recommended daily intake (RDI) of vitamin K in most countries has been established based on normal coagulation requirements. Vitamin K1 and menaquinone (MK)-4 has been shown to decrease osteocalcin (OC) γ-carboxylation at RDI levels. Among the several vitamin K homologs, only MK-7 (vitamin K2) can promote γ-carboxylation of extrahepatic VKDPs, OC, and the matrix Gla protein at a nutritional dose around RDI. MK-7 has higher efficacy due to its higher bioavailability and longer half-life than other vitamin K homologs. As vitamin K1, MK-4, and MK-7 have distinct bioactivities, their RDIs should be established based on their relative activities. MK-7 increases bone mineral density and promotes bone quality and strength. Collagen production, and thus, bone quality may be affected by MK-7 or MK-4 converted from MK-7. In this review, we comprehensively discuss the various properties of MK-7.

Source: Sato T, Inaba N, Yamashita T. “MK-7 and Its Effects on Bone Quality and Strength.” Nutrients. 2020 Mar 31;12(4):965. PMID: 32244313, PMCID: PMC7230802, DOI: 10.3390/nu12040965

Total Carbohydrate

Effect of carbohydrate on portal vein blood flow during exercise

Abstract

Effects of carbohydrate ingestion and exercise on portal vein blood flow were studied. Flow was measured by pulsed-electronic Doppler. Eight male subjects performed four tests after a standardised breakfast and 5 h fast. Beverages were CHO (10 % glucose, 30 mmol . l (-1) NaCl) and W (water, 30 mmol . l (-1) NaCl). Exercise experiments comprised a resting measurement, 10 min warm-up and 60 min 70 % VO(2)max cycling. Every 10 min subjects stopped cycling briefly (approximately 30 s) for measurements. Beverage was consumed after warm-up (500 ml) and at 20 and 40 min (250 ml). Similar tests were done at rest. Blood samples were taken concurrently with flow measurements for hormonal concentrations. Exercise decreased blood flow (repeated measures ANOVA, p < 0.0001) and carbohydrate ingestion increased flow (p = 0.015). At rest, flow was greater with CHO than with W at 20 (177 +/- 31; 101 +/- 25 %, resp.) (mean +/- SE), 30 (209 +/- 37; 120 +/- 20 %), 40 (188 +/- 32; 108 +/- 12 %), and 60 min (195 +/- 19; 112 +/- 12 %) (1-way ANOVA, Fisher's PLSD, p < 0.05). Flow was similar during exercise with CHO and W, with a tendency for CHO to maintain flow better, at 10 (124 +/- 27; 77 +/- 21 %), 20 (81 +/- 10; 60 +/- 13 %), 30 (106 +/- 26; 56 +/- 10 %), 40 (109 +/- 28; 54 +/- 8 %), 50 (85 +/- 17; 54 +/- 13 %), and 60 min (61 +/- 15; 47 +/- 7 %). A positive correlation between glucagon and flow and an inverse correlation between noradrenaline and flow were observed. Exercise reduces, and carbohydrate increases, portal vein flow. Changes in plasma concentrations suggest that noradrenaline and glucagon, respectively, may play a role in modulating flow.

Source: Rehrer NJ, Goes E, DuGardeyn C, Reynaert H, DeMeirleir K. Effect of carbohydrate on portal vein blood flow during exercise. 2005 Apr. PMID: 15776331, DOI: 10.1055/s-2004-820957

Vitamin A

Exploring the association between dietary vitamin A and coronary artery disease risk in men and women: findings from a US population study

Abstract

Introduction: Coronary artery disease (CAD) is an important public health problem with negative impacts on individual health and socioeconomics. Studies on the relationship of dietary vitamin A (DVA) to CAD are limited and conflicting. The purpose of this study was to investigate the relationship between DVA and the prevalence of CAD in U.S. adults, with particular interest in sex differences.

Methods: Data from 26,449 NHANES participants were used for analysis. The association of DVA with the prevalence of CAD was investigated utilizing multivariate logistic regression models and fitted smoothed curves, and interaction tests were performed to explore potential modifiers.

Results: This study included 12,748 males and 13,701 females aged 50.34 ± 17.54 years. Overall, adjusted DVA was linearly negatively correlated with CAD (per natural ln (DVA) increment: OR 0.91, 95% CI 0.83–0.99). Multivariate regression analysis showed that among female participants, each natural increment of ln DVA was associated with a 22% reduction in CAD prevalence (OR 0.78, 95% CI 0.68–0.89). However, there was no significant correlation in male participants (p for interaction <0.001).

Conclusion: DVA was negatively associated with the prevalence of CAD, and further analysis revealed an interaction between DVA and sex in terms of CAD prevalence.

Source: Wu Z, Yang W, Fang H, Chen Y, Wu Y, Gong R. Exploring the association between dietary vitamin A and coronary artery disease risk in men and women: findings from a US population study. 2024 Oct 15;11:1418159. DOI: 10.3389/fnut.2024.1418159, PMCID: PMC11518770, PMID: 39474454

Sodium

Clinical salt deficits

Abstract

Salt retention or salt deficit has a bearing on the body fluid volume. Both states are clinically difficult to recognize and quantitate. Salt deficit is particularly cumbersome in that regard since orthostatic blood pressure, heart rate changes, and simple physical inspection are inaccurate and unreliable. Salt deficit can be acute such as after hemorrhage or massive diarrhea, or more chronic as observed in Addison’s disease, failure of renal sodium chloride transporters, drug-related effects, or distal nephron disease. Molecular genetics has given us important new insights into salt deficit syndromes. Recent recognition of a novel sodium storage compartment involving sodium binding to proteoglycans adds to the overall complexity of these syndromes.

Source: Luft FC. Clinical salt deficits. 05 December 2014.

Potassium

Potassium disorders at intensive care unit admission and functional outcomes after cardiac arrest

Abstract

Background: Abnormal serum potassium levels are commonly found in the intensive care unit (ICU) population. We aimed to determine the prevalence of potassium disorders at ICU admission and its association with functional outcomes in comatose patients resuscitated from cardiac arrest.

Methods: We performed a post hoc analysis of pooled data from four randomised clinical trials involving comatose post-cardiac arrest patients admitted to ICU after return of spontaneous circulation (ROSC). Reference serum potassium levels were defined as between 3.0 and 4.9  mmol/L. An unfavourable functional outcome was defined as a cerebral performance category of 3 to 5 at 180 days. We compared potassium disturbances categorically in a mixed effects logistic regression model including initial rhythm, delay from collapse to return of spontaneous circulation, bystander cardiopulmonary resuscitation, lactate and urea at ICU admission, with normokalaemia set as the reference group.

Results: We included 1133 patients (557 from the HYPERION, 346 from the TTH48, 120 from the COMACARE, and 110 from the Xe-HYPOTHECA trials) with a median age of 64 years (interquartile range 55–72) and a predominance of males (72 %); a total of 712 (64 %) patients had unfavourable functional outcomes. On admission, 221 patients (19.5 %) experienced hyperkalaemia and 35 (3.1 %) patients experienced hypokalaemia. Fewer patients in the normokalaemia group (513/877, 58.5 %) had an unfavourable functional outcome compared to the hypokalaemia (24/35, 68.6 %) and hyperkalaemia groups (180/221, 81.4 %; p < 0.001). Hyperkalaemia was associated with higher odds for an unfavourable functional outcome (adjusted odds ratio (OR) 1.85, 95 % confidence interval (CI) 1.10–3.12, p = 0.02), while hypokalaemia was not (OR 1.36 95 % CI 0.51–3.60, p = 0.53). The associations were not significant in a subgroup analysis adjusted for the modified cardiac arrest hospital prognosis score in 833 patients (OR 1.74, 95 % CI 0.91–3.34, p = 0.10 for hyperkalaemia and OR 1.48, 95 % CI 0.40–5.44, p = 0.55 for hypokalaemia).

Conclusions: Of the comatose patients admitted to ICU after cardiac arrest, one in five experienced a potassium disorder on ICU admission. Hyperkalaemia was associated with unfavourable functional outcomes at 180 days, while hypokalaemia was not.

Source: Holma A, Lascarro JB, Cariou A, Reinikainen M, Laitio T, Kirkegaard H, Søreide E, Taccone FS, Lääperi M, Skrifvars MB. (2024). Potassium disorders at intensive care unit admission and functional outcomes after cardiac arrest.. Resuscitation, 110439 . DOI: 10.1016/j.resuscitation.2024.110439.

Apple Juice Powder

Effects of apple juice on risk factors of lipid profile, inflammation and coagulation, endothelial markers and atherosclerotic lesions in high cholesterolemic rabbits

Abstract

Background: Atherosclerosis which results from gradual deposition of lipids in medium and large arteries is a leading cause of mortality worldwide. The objective of this study was to determine the effect of apple juice on some risk factors of atherosclerosis and on the development of atherosclerosis in rabbits fed a high-cholesterol diet.

Methods: Thirty two male rabbits were randomly divided into four groups: normal diet, high cholesterol diet (%1 cholesterol), 1% cholesterol supplemented with 5 ml apple juice (low dose) and 1% cholesterol supplemented with 10 ml apple juice (high dose) for 2 month. The C-reactive protein (CRP), nitrite, nitrate, fibrinogen, total cholesterol(TC) and factor VII were measured before the experiment and by the end of period. At the end of study, fatty streak formation in right and left coronary arteries were determined using Chekanov method in all groups.

Results: Both doses of apple juice significantly were decreased TC, TG, CRP, fibrinogen, factor VII levels, atherosclerotic lesion in right and left coronary arteries and increased nitrite and nitrate compared to cholesterolemic diet. Also using 10 ml apple juice caused significant reduce in LDL-C and increase HDL-C, but 5 ml apple juice did not change these factors. Significant differences were observed between 5 and 10 ml apple juice groups by LDL-C. No significant difference was found between 5 and 10 ml apple juice groups with regard to CRP, nitrite, nitrate, fibrinogen, factor VII, TG, HDL-C and TC concentrations.

Conclusion: Apple juice can effectively prevent the progress of atherosclerosis. This is likely due to antioxidant and anti-inflammatory effect of apple juice.

Source: Setorki M, Asgary S, Eidi A, Haeri rohani A, Esmaeil N. Effects of apple juice on risk factors of lipid profile, inflammation and coagulation, endothelial markers and atherosclerotic lesions in high cholesterolemic rabbits. 2009 Oct 5. PMCID: PMC2761910, PMID: 19804641, DOI: 10.1186/1476-511X-8-39

Health Benefits of Apple Juice Consumption: A Review of Interventional Trials on Humans

Abstract

Although numerous studies have reported the benefits of apple consumption on cardiometabolic health parameters and chronic disease prevention, few have focused on the effects of apple juice specifically. Juice consumption may be a convenient way to take advantage of the health effects of the bioactive components present in apples. The present review aims to summarize the current literature on health benefits of apple juice as reported in clinical trials in humans. Of the 67 studies retained, 20 interventional studies on humans were reviewed. Overall, cloudy apple juice consumption was found to be associated with several markers of cardiovascular health that may ultimately be relevant for cancer and neurodegenerative diseases. Most of the documentation was found regarding oxidative stress, as well as observations with other parameters such as markers of inflammation, lipid profile, and diabetes. This review suggests that, in 20 studies, apple juice consumed in moderation exerts positive effects on markers of cardiovascular disease risk (particularly on oxidative stress).

Source: Vallée Marcotte B, Verheyde M, Pomerleau S, Doyen A, Couillard C. Health Benefits of Apple Juice Consumption: A Review of Interventional Trials on Humans. 2022 Feb 16. PMCID: PMC8879758, PMID: 35215471, DOI: 10.3390/nu14040821

Raspberry Juice Powder

Micronized Powder of Raspberry Pomace as a Source of Bioactive Compounds

Abstract

Red raspberries, which contain a variety of nutrients and phytochemicals that are beneficial for human health, can be utilized as a raw material in the creation of several supplements. This research suggests micronized powder of raspberry pomace production. The molecular characteristics (FTIR), sugar, and biological potential (phenolic compounds and antioxidant activity) of micronized raspberry powders were investigated. FTIR spectroscopy results revealed spectral changes in the ranges with maxima at ~1720, 1635, and 1326, as well as intensity changes in practically the entire spectral range analyzed. The discrepancies clearly indicate that the micronization of the raspberry byproduct samples cleaved the intramolecular hydrogen bonds in the polysaccharides present in the samples, thus increasing the respective content of simple saccharides. In comparison to the control powders, more glucose and fructose were recovered from the micronized samples of the raspberry powders. The study’s micronized powders were found to contain nine different types of phenolic compounds, including rutin, elagic acid derivatives, cyanidin-3-sophoroside, cyanidin-3-(2-glucosylrutinoside), cyanidin-3-rutinoside, pelargonidin-3-rutinoside, and elagic acid derivatives. Significantly higher concentrations of ellagic acid and ellagic acid derivatives and rutin were found in the micronized samples than in the control sample. The antioxidant potential assessed by ABTS and FRAP significantly increased following the micronization procedure.

Source: Różyło R, Amarowicz R, Janiak M, Domin M, Gawłowski S, Kulig R, Łysiak G, Rząd K, Matwijczuk A. Micronized Powder of Raspberry Pomace as a Source of Bioactive Compounds. 2023 Jun 20. PMCID: PMC10303312, PMID: 37375425, DOI: 10.3390/molecules28124871

Black Currant Powder

Anthocyanin-Rich New Zealand Blackcurrant Extract Supports the Maintenance of Forearm Blood-Flow During Prolonged Sedentary Sitting

Abstract

Objectives: We examined the acute effects of anthocyanin-rich New Zealand blackcurrant extract and a placebo on hemodynamics during 120 min of sedentary sitting in healthy males. Additionally, we investigated whether changes in resting hemodynamics altered repeated isometric hand-grip exercise performance and post exercise forearm blood flow (FBF).

Methods: Ten healthy males completed two trials during which they ingested either blackcurrant extract (1.87 mg total anthocyanins/kg bodyweight) or placebo powder. Heart rate, blood pressure and forearm blood flow were measured, and venous blood was sampled, prior to and 30, 60, 90 and 120 min-post ingestion. Participants remained seated for the duration of each trial. At 120 min post-ingestion participants completed as many repetitions of isometric hand-grip contractions as possible.

Results: Heart rate, blood pressure and mean arterial pressure changed over time (all p < 0.001) but did not differ between treatments. A treatment x time interaction for FBF (p = 0.025) and forearm vascular resistance (FVR) (p = 0.002) was found. No difference in the number of isometric hand-grip contractions was observed between treatments (p = 0.68) nor was there any treatment x time interaction in post-exercise FBF (p = 0.997). Plasma endothelin-1 (p = 0.023) and nitrate (p = 0.047) changed over time but did not differ between treatments (both p > 0.1). Plasma nitrite did not change over time (p = 0.732) or differ between treatments (p = 0.373).

Conclusion: This study demonstrated that acute ingestion of a single dose of blackcurrant extract maintained FBF and FVR during an extended period of sitting; however, this did not influence exercise performance during hand-grip exercise.

Source: Barnes MJ, Perry BG, Hurst RD, Lomiwes D. Anthocyanin-Rich New Zealand Blackcurrant Extract Supports the Maintenance of Forearm Blood-Flow During Prolonged Sedentary Sitting. 2020 May 27. PMCID: PMC7267005, PMID: 32537457, DOI: 10.3389/fnut.2020.00074

Application, emerging health benefits, and dosage effects of blackcurrant food formats

Abstract

Blackcurrant is rich in polyphenols, especially anthocyanins, and is regarded as an healthy food due to its various potential health benefits. The objectives of this review were to introduce five common types of blackcurrant food formats (blackcurrant juice concentrate/extract/powder/pomace/encapsulates) to summarize their practical applications in some real food matrices to produce blackcurrant containing functional food products. The emerging health benefits of these blackcurrant food formats that have been reported in the last three years were also clarified. Furthermore, the importance of their dose-dependent effects in practical applications was underlined. Encapsulation strategies are effective and protective manners to deliver blackcurrant concentrate or extract to various food matrices by the formation of encapsulates. Blackcurrant powder and blackcurrant pomace are natural vehicles for the delivery of blackcurrant bioactive components. Additionally, the dose-dependent effectiveness of these blackcurrant food formats towards various diseases needs to be investigated separately.

Source: Xue B, Hui X, Chen X, Luo S, Dilrukshi HNN, Wu G, Chen C. Application, emerging health benefits, and dosage effects of blackcurrant food formats. August 2022. DOI: 10.1016/j.jff.2022.105147

Tart Cherry Powder

Effects of Tart Cherry Juice on Biomarkers of Inflammation and Oxidative Stress in Older Adults

Abstract

Inflammation and oxidative stress are important factors in the development of cardiovascular disease and atherosclerosis. The findings of our previous study suggest that 12 weeks consumption of tart cherry juice lowers the levels of systolic blood pressure (BP) and low-density lipoprotein (LDL) cholesterol in older adults. The present study investigated the effects of tart cherry juice on blood biomarkers of inflammation and oxidative stress. In this randomized-controlled clinical trial, a total of 37 men and women between the ages of 65–80 were randomly assigned to consume 480 mL of tart cherry juice or control drink daily for 12 weeks. Several blood biomarkers of inflammation and oxidative stress were assessed at baseline and after 12 weeks intervention. After the 12 weeks intervention, tart cherry juice significantly increased the plasma levels of DNA repair activity of 8-oxoguanine glycosylase (p < 0.0001) and lowered (p = 0.03) the mean c-reactive protein (CRP) level compared to the control group. There was a significant group effect observed for plasma CRP (p = 0.03) and malondialdehyde (MDA) (p = 0.03), and a borderline significant group effect observed for plasma oxidized low-density lipoprotein (OxLDL) (p = 0.07). Within group analysis showed that the plasma levels of CRP, MDA, and OxLDL decreased numerically by 25%, 3%, and 11%, respectively after 12 weeks of tart cherry juice consumption compared with corresponding baseline values. The present study suggests that the ability of tart cherry juice to reduce systolic BP and LDL cholesterol, in part, may be due to its anti-oxidative and anti-inflammatory properties. Larger and longer follow-up studies are needed to confirm these findings.

Source: Chai SC, Davis K, Zhang Z, Zha L, Kirschner KF. Effects of Tart Cherry Juice on Biomarkers of Inflammation and Oxidative Stress in Older Adults. 2019 Jan 22. PMCID: PMC641315, PMID: 30678193, DOI: 10.3390/nu11020228

Dose-dependent effect of tart cherry on blood pressure and selected inflammation biomarkers: A GRADE-assessed systematic review and meta-analysis of randomized controlled trials

Abstract

Objectives: As a nutritious food, Tart cherries (Prunus cerasus L) benefit cardiovascular health. This study aims to clarify the effectiveness of Tart cherry in controlling blood pressure, heart rate, and inflammatory biomarkers, the appropriate dosage for this effect, and suggest directions for future studies.

Methods: PubMed, Scopus, and Web of Science were searched (up to May 2022), to identify eligible randomized controlled trials. It measured publication bias and was assessed for all outcomes. Evidence quality was evaluated using the Cochrane risk of bias tool and GRADE (Grades of Recommendations, Assessment, Development, and Evaluations).

Results: Regarding the 21 included trials, Tart cherry didn't affect blood pressure, heart rate, high-sensitive C-reactive protein, and interleukin-6 (P > 0.05). In contrast, with moderate certainty, it can reduce serum C-reactive protein (WMD: - 0.39 mg/l; 95% CI: - 0.74, - 0.05; P = 0.024) and with very low certainty can decrease tumor necrosis factor-alpha (WMD: - 0.14 pg/ml; 95% CI: - 0.27, - 0.02; P = 0.026). In addition, dose-response analysis implies that with each 30 ml elevation in dose, CRP reduces by 0.19 mg/l (95% CI: - 0.37, - 0.01).

Conclusions: Tart cherry can control inflammation by administering the proper dose. Even though tart cherry generally doesn't affect blood pressure and heart rate, further high-quality studies are needed to determine its effect.

Source: Norouzzadeh M, Hasan Rashedi M, Shahinfar H, Rahideh ST. Dose-dependent effect of tart cherry on blood pressure and selected inflammation biomarkers: A GRADE-assessed systematic review and meta-analysis of randomized controlled trials. September 2023. DOI: 10.1016/j.heliyon.2023.e19987

Billberry Powder

Effects of Bilberry Supplementation on Metabolic and Cardiovascular Disease Risk

Abstract

Metabolic syndrome is a cluster of interrelated conditions that is associated with an increased risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). Oxidative stress may impair normal physiological functions, leading to various illnesses. T2DM is considered to be associated with increased oxidative stress, inflammation, and dyslipidemia, which may play a significant role in the development of cardiovascular complications, cancer and vision loss through cataracts and retinopathy. While conventional therapies are a cornerstone for the management of the major risk factors of metabolic syndrome, increasing antioxidant defense by increasing intake of antioxidant-rich foods may improve long term prospects in CVD, obesity and T2DM. Bilberry (Vaccinium myrtillus L.) is one of the richest natural sources of anthocyanins which give berries their red/purple/blue coloration. Anthocyanins are powerful antioxidants and are reported to play an important role in the prevention of metabolic disease and CVD as well as cancer and other conditions. This review focuses on the potential effects of bilberry supplementation on metabolic and cardiovascular risk factors. Although there is evidence to support the use of bilberry supplementation as part of a healthy diet, the potential benefits from the use of bilberry supplementation in patients with T2DM or CVD needs to be clarified in large clinical trials.

Source: Chan SW, Tomlinson B. Effects of Bilberry Supplementation on Metabolic and Cardiovascular Disease Risk. 2020 Apr 3. PMCID: PMC7180827, PMID: 32260262, DOI: 10.3390/molecules25071653

Red Rice Yeast Extract

Safety and Efficacy of Red Yeast Rice (Monascus purpureus) as an Alternative Therapy for Hyperlipidemia

Abstract

Red yeast rice is a Chinese fermented rice product (Monascus purpureus) that some have claimed improves blood circulation by decreasing cholesterol and triglyceride levels in humans. The supplement contains naturally occurring monacolin K, the active ingredient found in Merck’s prescription agent lovastatin (Mevacor). Lovastatin is associated with various adverse effects such as myopathy and abnormal liver function test results, which can lead to serious problems if patients are not monitored and treated. The inclusion of lovastatin in red yeast rice and the lack of dietary supplement regulation by the FDA raise safety concerns for health care professionals as well as for patients. Studies have shown that red yeast rice products can be beneficial in lowering serum cholesterol levels, but they are not without risk. Furthermore, product uniformity, purity, labeling, and safety cannot be guaranteed.

Source: Klimek M, Wang S, Ogunkanmi A. Safety and Efficacy of Red Yeast Rice (Monascus purpureus) as an Alternative Therapy for Hyperlipidemia. 2009 Jun. PMCID: PMC2697909, PMID: 19572049.

Red Yeast Rice for Hypercholesterolemia

Abstract

The extract of red yeast rice (RYR) is the most effective cholesterol-lowering nutraceutical on the market. In particular, its effectiveness is directly related to the amount of monacolin K within the extract (up to 10 mg/day). Consuming monacolin K on a daily basis reduces low-density lipoprotein (LDL) cholesterol plasma levels between 15% and 25% within 6 to 8 weeks. Certainly, the decrease in LDL-cholesterol is accompanied by a similar reduction in total cholesterol, non–high-density lipoprotein cholesterol, plasma apolipoprotein B, matrix metalloproteinases 2 and 9, and high-sensitivity C-reactive protein. Furthermore, the RYR lipid-lowering effect is associated with significant improvements in pulse wave velocity and endothelial function, which are validated and reliable biomarker tools able to detect vascular aging. Although it has a mechanism of action similar to statins, a daily consumption of between 3 and 10 mg monacolin K has only minimal associated risks, and mild myalgias are seen only in the frailest patients (those who also cannot tolerate minimal dosages of statin). The monacolin K found in RYR is a safe and effective supplement for managing mild to moderate hypercholesterolemia in people with no additional cardiovascular risk factors.

Source: Cicero AFG, Fogacci F, Banach M. Red Yeast Rice for Hypercholesterolemia. 2019 Jul-Sep. PMCID: PMC6822657, PMID: 31687098, DOI: 10.14797/mdcj-15-3-192

Red Yeast Rice for the Improvement of Lipid Profiles in Mild-to-Moderate Hypercholesterolemia: A Narrative Review

Abstract

Reducing low-density lipoprotein cholesterol (LDL-C) levels is a key target for lowering cardiovascular risk and preventing atherosclerotic cardiovascular disease (ASCVD). Red yeast rice (RYR) is a nutraceutical widely used as a lipid-lowering dietary supplement. The main cholesterol-lowering components of RYR are monacolins, particularly monacolin K, which is structurally identical to lovastatin and targets the same key enzyme of cholesterol biosynthesis. RYR supplementation reduces LDL-C levels by approximately 15–34% versus placebo, with a similar effect to low-dose, first-generation statins in subjects with mild-to-moderate dyslipidemia. RYR has also demonstrated beneficial reductions of up to 45% versus placebo in the risk of ASCVD events in secondary prevention studies. RYR at a dose that provides about 3 mg/d of monacolin K is well tolerated, with an adverse event profile similar to that of low-dose statins. RYR is therefore a treatment option for lowering LDL-C levels and ASCVD risk for people with mild-to-moderate hypercholesterolemia who are ineligible for statin therapy, particularly those who are unable to implement lifestyle modifications, and also for people who are eligible for statin therapy but who are unwilling to take a pharmacologic therapy.

Source: Cicero AFG, Fogacci F, Stoian AP, Toth PP. Red Yeast Rice for the Improvement of Lipid Profiles in Mild-to-Moderate Hypercholesterolemia: A Narrative Review. 2023 May 12. PMCID: PMC10221652, PMID: 37242171, DOI: 10.3390/nu15102288

Beet Root Extract

Acute ingestion of beetroot juice increases exhaled nitric oxide in healthy individuals

Abstract

Background and objective: Nitric oxide (NO) plays an important role in the airways' innate immune response, and the fraction of exhaled NO at a flow rate of 50mL per second (FENO50) has been utilized to capture NO. Deficits in NO are linked to loss of bronchoprotective effects in airway challenges and predict symptoms of respiratory infection. While beetroot juice supplements have been proposed to enhance exercise performance by increasing dietary nitrate consumption, few studies have examined the impact of beetroot juice or nitrate supplementation on airway NO in contexts beyond an exercise challenge, which we know influences FENO50.

Methods: We therefore examined the influence of a beetroot juice supplement on FENO50 in healthy males and females (n = 38) during periods of rest and in normoxic conditions. FENO50, heart rate, blood pressure, and state affect were measured at baseline, 45 minutes, and 90 minutes following ingestion of 70ml beetroot juice (6.5 mmol nitrate). Identical procedures were followed with ingestion of 70ml of water on a control day.

Results: After beetroot consumption, average values of the natural log of FENO50 (lnFENO50) increased by 21.3% (Cohen's d = 1.54, p < .001) 45 minutes after consumption and by 20.3% (Cohen's d = 1.45, p < .001) 90 min after consumption. On the other hand, only very small increases in FENO50 were observed after consumption of the control liquid (less than 1% increase). A small subset (n = 4) of participants completed an extended protocol lasting over 3 hours, where elevated levels of FENO50 persisted. No significant changes in cardiovascular measures were observed with this small single dose of beetroot juice.

Conclusion: As NO serves a key role in innate immunity, future research is needed to explore the potential clinical utility of beetroot and dietary nitrate to elevate FENO50 and prevent respiratory infection.

Source: Kroll JL, Werchan CA, Rosenfield D, Ritz T. “Acute ingestion of beetroot juice increases exhaled nitric oxide in healthy individuals.” PLoS One. 2018 Jan 25;13(1). PMID: 29370244, PMCID: PMC5784918, DOI: 10.1371/journal.pone.0191030

Beetroot juice and exercise: pharmacodynamic and dose-response relationships

Abstract

Dietary supplementation with beetroot juice (BR), containing approximately 5-8 mmol inorganic nitrate (NO3(-)), increases plasma nitrite concentration ([NO2(-)]), reduces blood pressure, and may positively influence the physiological responses to exercise. However, the dose-response relationship between the volume of BR ingested and the physiological effects invoked has not been investigated. In a balanced crossover design, 10 healthy men ingested 70, 140, or 280 ml concentrated BR (containing 4.2, 8.4, and 16.8 mmol NO3(-), respectively) or no supplement to establish the effects of BR on resting plasma [NO3(-)] and [NO2(-)] over 24 h. Subsequently, on six separate occasions, 10 subjects completed moderate-intensity and severe-intensity cycle exercise tests, 2.5 h postingestion of 70, 140, and 280 ml BR or NO3(-)-depleted BR as placebo (PL). Following acute BR ingestion, plasma [NO2(-)] increased in a dose-dependent manner, with the peak changes occurring at approximately 2-3 h. Compared with PL, 70 ml BR did not alter the physiological responses to exercise. However, 140 and 280 ml BR reduced the steady-state oxygen (O2) uptake during moderate-intensity exercise by 1.7% (P = 0.06) and 3.0% (P < 0.05), whereas time-to-task failure was extended by 14% and 12% (both P < 0.05), respectively, compared with PL. The results indicate that whereas plasma [NO2(-)] and the O2 cost of moderate-intensity exercise are altered dose dependently with NO3(-)-rich BR, there is no additional improvement in exercise tolerance after ingesting BR containing 16.8 compared with 8.4 mmol NO3(-). These findings have important implications for the use of BR to enhance cardiovascular health and exercise performance in young adults.

Source: Wylie LJ, Kelly J, Bailey SJ, Blackwell JR, Skiba PF, Winyard PG, Jeukendrup AE, Vanhatalo A, Jones AM. “Beetroot juice and exercise: pharmacodynamic and dose-response relationships.” J Appl Physiol (1985). 2013 Aug 1;115(3):325-36. PMID: 23640589, DOI: 10.1152/japplphysiol.00372.2013

Elastin

Blood flow interplays with elastin: collagen and MMP: TIMP ratios to maintain healthy vascular structure and function

Abstract

Differential vascular remodeling is one of the major mechanisms of heterogeneity in atherosclerosis. The structural and functional heterogeneity between arteries and veins determines the degree of vascular remodeling. Matrix metalloproteases (MMPs) and their tissue inhibitors (TIMPs) play key roles in vascular structural and functional remodeling. We hypothesized that the level of blood flow in different arteries and veins caused structural and functional heterogeneity that ultimately determined potential vascular remodeling. To test this hypothesis, in vivo blood flow and blood pressure in the aorta, carotid, femoral artery, and femoral vein was measured in male Sprague-Dawley rats (weight 380–400 gm). Arterial and venous pressures were measured by PE-50 catheter cannulation. Blood flow was measured by a transonic ultrasound system. The aortic arch, femoral and carotid arteries, and abdominal vena cava were isolated to determine the expression of MMP-2, -9, -12, and -13 and TIMP-1, -3, and -4 by Western blot and in gelatin gel zymography. Masson trichrome and van Gieson stains were used to stain the histologic tissue sections. The results revealed that blood flow was higher in the aorta and carotid artery than the femoral artery and vein. MMP-9 and MMP-13 were higher in the carotid artery in comparison with the other blood vessels, while TIMP-3 showed higher expression in the aorta than the arteries. Further, the MMP-9 activity was significantly higher in the carotid artery than in the aorta and femoral artery. There was a higher degree of basement membrane collagen in the femoral artery and therefore a low elastin: collagen ratio, while in the carotid artery a higher level of elastin and, therefore, a high elastin: collagen ratio was found. The results suggested that medial thickness and elastin:collagen ratios had a threshold in blood flow in the range 0.6–2.5 mL/min, which increased robustly if blood flow increased to 2.7 mL/min. This pattern was inverted by the total MMP:TIMP ratio. We conclude that vascular remodeling is a function of rate of blood flow, which would in turn be determined by the amounts of MMPs and their inhibitors present. The study combined the endothelial and dynamic (blood flow/pressure) components that affect medial thickness and elastin: collagen ratios.

Source: Basu P, Sen U, Tyagi N, Tyagi SC. Blood flow interplays with elastin: collagen and MMP: TIMP ratios to maintain healthy vascular structure and function. 2010 Apr 15. PMCID: PMC2856577, PMID: 20407629, DOI: 10.2147/vhrm.s9472

Elastin, arterial mechanics, and cardiovascular disease

Abstract

Large, elastic arteries are composed of cells and a specialized extracellular matrix that provides reversible elasticity and strength. Elastin is the matrix protein responsible for this reversible elasticity that reduces the workload on the heart and dampens pulsatile flow in distal arteries. Here, we summarize the elastin protein biochemistry, self-association behavior, cross-linking process, and multistep elastic fiber assembly that provide large arteries with their unique mechanical properties. We present measures of passive arterial mechanics that depend on elastic fiber amounts and integrity such as the Windkessel effect, structural and material stiffness, and energy storage. We discuss supravalvular aortic stenosis and autosomal dominant cutis laxa-1, which are genetic disorders caused by mutations in the elastin gene. We present mouse models of supravalvular aortic stenosis, autosomal dominant cutis laxa-1, and graded elastin amounts that have been invaluable for understanding the role of elastin in arterial mechanics and cardiovascular disease. We summarize acquired diseases associated with elastic fiber defects, including hypertension and arterial stiffness, diabetes, obesity, atherosclerosis, calcification, and aneurysms and dissections. We mention animal models that have helped delineate the role of elastic fiber defects in these acquired diseases. We briefly summarize challenges and recent advances in generating functional elastic fibers in tissue-engineered arteries. We conclude with suggestions for future research and opportunities for therapeutic intervention in genetic and acquired elastinopathies.

Source: Cocciolone AJ, Hawes JZ, Staiculescu MC, Johnson EO, Murshed M, Wagenseil JE. Elastin, arterial mechanics, and cardiovascular disease. 2018 Apr 6. PMCID: PMC6139627, PMID: 29631368, DOI: 10.1152/ajpheart.00087.2018

Grape Seed Extract

Grape seed proanthocyanidins prevent plasma postprandial oxidative stress in humans

Abstract

Postprandial hyperlipemia is a well-defined risk factor for atherosclerosis. A reasonable contributing mechanism could involve the postprandial increase of plasma lipid hydroperoxides (LPO) affecting the oxidant/antioxidant balance and increasing the susceptibility of LDL to oxidation. Wine has been shown to prevent both these events. The present study was designed to investigate the effect of supplementing a meal with grape seed proanthocyanidins (the main phenolic antioxidant of red wine) on plasma postprandial oxidative stress. In two different sessions, 8 healthy volunteers consumed the same test meal rich in oxidized and oxidizable lipids without (control) or with 300 mg of a proanthocyanidin-rich grape seeds extract (GSE). Lipid hydroperoxide concentration, antioxidant status, and LDL resistance to oxidative modification were measured in postprandial plasma. The content of LPO in chylomicrons was 1.5-fold higher after the control meal than after the GSE-supplemented meal. Plasma LPO increased only after consumption of the control meal. The plasma antioxidant capacity increased in the postprandial phase only following the GSE supplemented meal. LDL isolated 3 h after the control meal tended to be more susceptible to oxidative modification (but the difference did not reach statistical significance). An opposite trend was observed following the GSE supplemented meal. In conclusion, the supplementation of a meal with GSE minimizes the postprandial oxidative stress by decreasing the oxidants and increasing the antioxidant levels in plasma, and, as a consequence, enhancing the resistance to oxidative modification of LDL.

Source: Natella F, Belelli F, Gentili V, Ursini F, Scaccini C. “Grape seed proanthocyanidins prevent plasma postprandial oxidative stress in humans.” J Agric Food Chem. 2002 Dec 18;50(26):7720-5. PMID: 12475295, DOI: 10.1021/jf020346o

Effect of Grape Seed Extract and Quercetin on Cardiovascular and Endothelial Parameters in High-Risk Subjects

Abstract

Grape seed extract (GSE) has in vitro antioxidant activity but whether or not it works in vivo is not clear. In a fully randomised, crossover trial with 4-week treatment periods on 36 men and women with above-average vascular risk, we aimed to demonstrate that 2 g/day of GSE (1 g of polyphenols) alone, or with 1 g/day of added quercetin in yoghurt, favourably alters vascular function, endothelial function, and degree of oxidative damage in comparison to a control yoghurt. GSE alone improved flow-mediated dilatation determined ultrasonically by an absolute 1.1% compared with control. There was no effect of the combination of GSE with quercetin. No other blood or urine measure was altered. Thus sufficient polyphenols from GSE appear to be absorbed to influence endothelial nitric oxide production, and GSE has the potential to favourably influence vascular function.

Source: Clifton PM. “Effect of Grape Seed Extract and Quercetin on Cardiovascular and Endothelial Parameters in High-Risk Subjects.” J Biomed Biotechnol. 2004;2004(5):272-278. PMID: 15577189, PMCID: PMC1082891, DOI: 10.1155/S1110724304403088

Policosanol (sugar cane wax)

Cuban Sugar Cane Wax Acid and Policosanol Showed Similar Atheroprotective Effects with Inhibition of LDL Oxidation and Cholesteryl Ester Transfer via Enhancement of High-Density Lipoproteins Functionality

Abstract

Background: Cuban sugarcane wax acids (SCWA) and policosanol (PCO) are mixtures of higher aliphatic acids and alcohols, respectively, purified from sugarcane wax with different chief components. Although it has been known that they have antioxidant and anti-inflammatory activities, physiological properties on molecular mechanism of SCWA have been less studied than PCO.

Methods: In this study, we compared antiatherogenic activities of SCWA and PCO via encapsulation with reconstituted high-density lipoproteins (rHDL).

Results: After reconstitution, SCWA-rHDL showed smaller particle size than PCO-rHDL with increase of content. PCO-rHDL or SCWA-rHDL showed distinct inhibition of glycation with similar extent in the presence of fructose. PCO-rHDL or SCWA-rHDL showed strong antioxidant activity against cupric ion-mediated oxidation of low-density lipoproteins (LDL), and inhibition of oxLDL uptake into macrophages. Although PCO-rHDL showed 1.2-fold stronger inhibition against cholesteryl ester transfer protein (CETP) activity than SCWA-rHDL, SCWA-rHDL enhanced 15% more brain cell (BV-2) growth and 23% more regeneration of tail fin in zebrafish.

Conclusion: PCO and SCWA both enhance the beneficial functions of HDL to maximize its antioxidant, antiglycation, and antiatherosclerotic activities and the inhibition of CETP. These enhancements of HDL functionality by PCO and SCWA could exert antiaging and rejuvenation activity.

Source: Cho KH, Bae MA, Kim JR. Cuban Sugar Cane Wax Acid and Policosanol Showed Similar Atheroprotective Effects with Inhibition of LDL Oxidation and Cholesteryl Ester Transfer via Enhancement of High-Density Lipoproteins Functionality. 2019 Feb 24. PMCID: PMC6739770, PMID: 31772618, DOI: 10.1155/2019/8496409

Policosanol: Clinical pharmacology and therapeutic significance of a new lipid-lowering agent

Abstract

Background: Policosanol is a mixture of higher primary aliphatic alcohols isolated from sugar cane wax, whose main component is octacosanol. The mixture has been shown to lower cholesterol in animal models, healthy volunteers, and patients with type II hypercholesterolemia.

Methods: We reviewed the literature on placebo-controlled lipid-lowering studies using policosanol published in peer-reviewed journals as well as studies investigating its mechanism of action and its clinical pharmacology.

Results: At doses of 10 to 20 mg per day, policosanol lowers total cholesterol by 17% to 21% and low-density lipoprotein (LDL) cholesterol by 21% to 29% and raises high-density lipoprotein cholesterol by 8% to 15%. Because higher doses have not been tested up to now, it cannot be excluded that effectiveness may be even greater. Daily doses of 10 mg of policosanol have been shown to be equally effective in lowering total or LDL cholesterol as the same dose of simvastatin or pravastatin. Triglyceride levels are not influenced by policosanol. At dosages of up to 20 mg per day, policosanol is safe and well tolerated, as studies of >3 years of therapy indicate. There is evidence from in vitro studies that policosanol may inhibit hepatic cholesterol synthesis at a step before mevalonate generation, but direct inhibition of the hydroxy-methylglutaryl–coenzyme A reductase is unlikely. Animal studies suggest that LDL catabolism may be enhanced, possibly through receptor-mediated mechanisms, but the precise mechanism of action is not understood yet. Policosanol has additional beneficial properties such as effects on smooth muscle cell proliferation, platelet aggregation, and LDL peroxidation. Data on efficacy determined by clinical end points such as rates of cardiac events or cardiac mortality are lacking.

Conclusions: Policosanol seems to be a very promising phytochemical alternative to classic lipid-lowering agents such as the statins and deserves further evaluation. (Am Heart J 2002;143:356-65.)

Source: Gouni-Berthold I, Berthold HK. Policosanol: Clinical pharmacology and therapeutic significance of a new lipid-lowering agent. February 2002. DOI: 10.1067/mhj.2002.119997

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