Effects of S-Allylcysteine-Rich Garlic Extract and Dietary Inorganic Nitrate Formula on Blood Pressure and Salivary Nitric Oxide: An Open-Label Clinical Trial Among Hypertensive Subjects.

INTRODUCTION:  The conversion of dietary inorganic nitrate (NO3-) to nitric oxide (NO) is a non-canonical pathway that plays an important role in NO biology, especially under pathological conditions. Inorganic NO3- supplementation is a proven method for controlling mild hypertension. Recent reports have suggested that another gaseous transmitter, hydrogen sulfide (H2S), influences NO biosynthesis and metabolism. Here, data are presented from an open-label clinical trial examining the effect of an encapsulated formulation (Vascanox® HP) that combines dietary sources of inorganic NO3- and S-allylcysteine (SAC), a source of H2S from garlic, on NO bioavailability and blood pressure in subjects experiencing elevated blood pressure or mild hypertension. METHODS:  An open-label clinical trial was conducted among patients with hypertension. Participants took Vascanox® for four weeks. Blood pressure was measured at baseline, two weeks, and four weeks. Salivary nitrite (NO2-), a surrogate of NO bioavailability, and NO3- were assessed prior to and two, six, and 24 hours after dosing on the first day of the study and prior to and two hours after dosing at subsequent study visits using saliva NO test strips. Changes in study outcomes over time were evaluated via analysis of variance (ANOVA) and paired t-tests. RESULTS:  Twelve participants completed the clinical trial. Vascanox® HP decreased systolic blood pressure by ~11 mmHg (p < 0.001) at two weeks and persisted beyond four weeks with daily supplementation. It also decreased the diastolic blood pressure of hypertensive subjects but not normotensive ones. The magnitude of the decrease was 11 mmHg (p < 0.01) at four weeks of study. Measurements of salivary concentrations of NO2- revealed high peak levels (743 uM) at two hours post-administration and a slow decay to elevated levels (348 uM) at 24 hours. NO2- salivary concentrations, a surrogate biomarker of NO bioavailability, remained above baseline for the duration of the study. CONCLUSIONS:  Vascanox® HP was shown to be a safe, effective, quick-acting, and long-lasting dietary supplement for controlling mild hypertension.

The role of noninvasive cardiovascular testing, applied clinical nutrition and nutritional supplements in the prevention and treatment of coronary heart disease.

Numerous clinical trials suggest that we have reached a limit in our ability to decrease the incidence of coronary heart disease (CHD) and cardiovascular disease (CVD) utilizing the traditional diagnostic evaluation, prevention and treatment strategies for the top five cardiovascular risk factors of hypertension, diabetes mellitus, dyslipidemia, obesity and smoking. About 80% of heart disease (heart attacks, angina, coronary heart disease and congestive heart failure) can be prevented by optimal nutrition, optimal exercise, optimal weight and body composition, mild alcohol intake and avoiding smoking. Statistics show that approximately 50% of patients continue to have CHD or myocardial infarction (MI) despite presently defined 'normal' levels of the five risk factors listed above. This is often referred to as the 'CHD gap'. Novel and more accurate definitions and evaluations of these top five risk factors are required, such as 24 h ambulatory blood pressure (ABM) results, advanced lipid profiles, redefined fasting and 2 h dysglycemia parameters, a focus on visceral obesity and body composition and the effects of adipokines on cardiovascular risk. There are numerous traumatic insults from the environment that damage the cardiovascular system but there are only three finite vascular endothelial responses, which are inflammation, oxidative stress and immune vascular dysfunction. In addition, the concept of translational cardiovascular medicine is mandatory in order to correlate the myriad of CHD risk factors to the presence or absence of functional or structural damage to the vascular system, preclinical and clinical CHD. This can be accomplished by utilizing advanced and updated CV risk scoring systems, new and redefined CV risk factors and biomarkers, micronutrient testing, cardiovascular genetics, nutrigenomics, metabolomics, genetic expression testing and noninvasive cardiovascular testing.

Recent Science and Clinical Application of Nutrition to Coronary Heart Disease.

One of the greatest threats to mortality in industrialized societies continues to be coronary heart disease (CHD). Moreover, the ability to decrease the incidence of CHD has reached a limit utilizing traditional diagnostic evaluations and prevention and treatment strategies for the top five cardiovascular risk factors (hypertension, diabetes mellitus, dyslipidemia, obesity, and smoking). It is well known that about 80% of CHD can be prevented with optimal nutrition, coupled with exercise, weight management, mild alcohol intake, and smoking cessation. Among all of these factors, optimal nutrition provides the basic foundation for prevention and treatment of CHD. Numerous prospective nutrition clinical trials have shown dramatic reductions in the incidence of CHD. As nutritional science and nutrigenomics research continues, our ability to adjust the best nutrition with an individualized approach is emerging. This article reviews the role of nutrition in the prevention and treatment of CHD and myocardial infarction (MI).

Acute effects of an oral nitric oxide supplement on blood pressure, endothelial function, and vascular compliance in hypertensive patients.

This blinded placebo-controlled crossover study evaluated the acute effects of an orally disintegrating lozenge that generates nitric oxide (NO) in the oral cavity on blood pressure (BP) response, endothelial function, and vascular compliance in unmedicated hypertensive patients. Thirty patients with clinical hypertension were recruited and enrolled in a blinded placebo-controlled clinical trial in an outpatient setting. Average baseline BP in 30 patients was 144±3/91±1 mm Hg. NO supplementation resulted in a significant decrease of 4 mm Hg in resting systolic BP (P<.003) and a significant decrease of 5 mm Hg in diastolic BP (P<.002) from baseline and placebo after 20 minutes. In addition, there was a further statistically significant reduction by 6 mm Hg in both systolic and diastolic pressure after 60 minutes (P<.0001 vs baseline). After a half hour of a single dose, there was a significant improvement in vascular compliance as measured by augmentation index and, after 4 hours, a statistically significant improvement in endothelial function as measured by the EndoPAT (Itamar Medical, Franklin, MA). A single administration of an oral active NO supplement appears to acutely lower BP, improve vascular compliance, and restore endothelial function in patients with hypertension.

The role of nutrition and nutraceutical supplements in the treatment of hypertension.

Vascular biology, endothelial and vascular smooth muscle and cardiac dysfunction play a primary role in the initiation and perpetuation of hypertension, cardiovascular disease and target organ damage. Nutrient-gene interactions and epigenetics are predominant factors in promoting beneficial or detrimental effects in cardiovascular health and hypertension. Macronutrients and micronutrients can prevent, control and treat hypertension through numerous mechanisms related to vascular biology. Oxidative stress, inflammation and autoimmune dysfunction initiate and propagate hypertension and cardiovascular disease. There is a role for the selected use of single and component nutraceutical supplements, vitamins, antioxidants and minerals in the treatment of hypertension based on scientifically controlled studies which complement optimal nutrition, coupled with other lifestyle modifications.

Nutrition and nutraceutical supplements for the treatment of hypertension: part III.

Vascular biology, endothelial and vascular smooth muscle, and cardiac dysfunction play a primary role in the initiation and perpetuation of hypertension, cardiovascular disease, and target organ damage. Nutrient-gene interactions and epigenetics are predominant factors in promoting beneficial or detrimental effects in cardiovascular health and hypertension. Macronutrients and micronutrients can prevent, control, and treat hypertension through numerous mechanisms related to vascular biology. Oxidative stress, inflammation, and autoimmune dysfunction initiate and propagate hypertension and cardiovascular disease. There is a role for the selected use of single and component nutraceutical supplements, vitamins, antioxidants, and minerals in the treatment of hypertension based on scientifically controlled studies that complement optimal nutrition, coupled with other lifestyle modifications.

Nutrition and nutraceutical supplements for the treatment of hypertension: part II.

Vascular biology, endothelial and vascular smooth muscle, and cardiac dysfunction play a primary role in the initiation and perpetuation of hypertension, cardiovascular disease, and target organ damage. Nutrient-gene interactions and epigenetics are predominant factors in promoting beneficial or detrimental effects in cardiovascular health and hypertension. Macronutrients and micronutrients can prevent, control, and treat hypertension through numerous mechanisms related to vascular biology. Oxidative stress, inflammation, and autoimmune dysfunction initiate and propagate hypertension and cardiovascular disease. There is a role for the select use of single and component nutraceutical supplements, vitamins, antioxidants, and minerals in the treatment of hypertension based on scientifically controlled studies, which complement optimal nutrition, coupled with other lifestyle modifications.

Nutrition and nutraceutical supplements for the treatment of hypertension: part I.

Vascular biology, endothelial and vascular smooth muscle, and cardiac dysfunction play a primary role in the initiation and perpetuation of hypertension, cardiovascular disease, and target organ damage. Nutrient-gene interactions and epigenetics are predominant factors in promoting beneficial or detrimental effects in cardiovascular health and hypertension. Macronutrients and micronutrients may be able to prevent, control, or treat hypertension through numerous mechanisms related to vascular biology or other mechanisms. Oxidative stress, inflammation, and autoimmune dysfunction are some of the primary factors that initiate and propagate hypertension and cardiovascular disease. The literature suggests that there may be a complementary role of single and component nutraceutical supplements, vitamins, antioxidants, and minerals in the treatment of hypertension when combined with optimal nutrition and other lifestyle modifications. However, many of these studies are small and do not have long-term follow-up for efficacy and safety. The role of these nutrition and nutraceutical supplements will require careful review and additional studies to determine their exact role in the management of hypertension.

The role of nutrition, nutraceuticals, vitamins, antioxidants, and minerals in the prevention and treatment of hypertension.

Macronutrient and micronutrient deficiencies are very common in the general population and may be even more common in patients with hypertension and cardiovascular disease due to genetic or environmental causes and prescription drug use. These deficiencies will have an enormous impact on present and future cardiovascular health and outcomes, such as hypertension, myocardial infarction, stroke and renal disease, and on overall health costs. The diagnosis and treatment of these nutrient deficiencies can reduce blood pressure; improve vascular health, endothelial dysfunction, and vascular biology; and decrease cardiovascular events. Vascular biology assumes a pivotal role in the initiation and perpetuation of hypertension and target organ damage (TOD). Endothelial activation, oxidative stress, inflammation, autoimmune vascular dysfunction, and vascular smooth-muscle dysfunction are initial events in hypertension. Nutrient gene interactions determine a broad array of phenotypic consequences, such as vascular problems and hypertension. In addition to other lifestyle modifications, optimal nutrition, nutraceutical supplements, vitamins, antioxidants, minerals, weight loss, exercise, smoking cessation, and moderate restriction of alcohol and caffeine can prevent and control hypertension in many patients. An integrative approach combining these lifestyle suggestions with the correct pharmacologic treatment will best achieve new goals for blood pressure levels, reduce cardiovascular risk factors, improve vascular biology and vascular health, reduce cardiovascular TOD, and reduce health care expenditures. In this article, the expanded scientific role for nutraceutical supplements in the treatment of essential hypertension will be discussed. It is the purpose of this article to review only the hypertension clinical trials that have evaluated the clinical use and efficacy of nutrition, weight loss, exercise, and nutritional supplements, vitamins, minerals, and antioxidants.

The role of nutraceutical supplements in the treatment of dyslipidemia.

The combination of a lipid-lowering diet and scientifically proven nutraceutical supplements has the ability to significantly reduce low-density lipoprotein (LDL) cholesterol, increase LDL particle size, decrease LDL particle number, lower trigylcerides and very LDL levels, and increase total and high-density lipoprotein 2b cholesterol. In addition, inflammation, oxidative stress, and immune responses are decreased. In several prospective clinical trials, coronary heart disease and cardiovascular disease have been reduced with many nutraceutical supplements. This nutritional and nutraceutical supplement treatment is a valid alternative for patients who are intolerant to statins, cannot take other drugs for the treatment of dyslipidemia, or prefer alternative treatments. This new approach to lipid management to decrease vascular disease utilizes a functional medicine approach with a broader treatment program that will address the multitude of steps involved in lipid-induced vascular damage.

The role of magnesium in hypertension and cardiovascular disease.

Magnesium intake of 500 mg/d to 1000 mg/d may reduce blood pressure (BP) as much as 5.6/2.8 mm Hg. However, clinical studies have a wide range of BP reduction, with some showing no change in BP. The combination of increased intake of magnesium and potassium coupled with reduced sodium intake is more effective in reducing BP than single mineral intake and is often as effective as one antihypertensive drug in treating hypertension. Reducing intracellular sodium and calcium while increasing intracellular magnesium and potassium improves BP response. Magnesium also increases the effectiveness of all antihypertensive drug classes. It remains to be conclusively proven that cardiovascular disease such as coronary heart disease, ischemic stroke, and cardiac arrhythmias can be prevented or treated with magnesium intake. Preliminary evidence suggests that insulin sensitivity, hyperglycemia, diabetes mellitus, left ventricular hypertrophy, and dyslipidemia may be improved with increased magnesium intake. Various genetic defects in magnesium transport are associated with hypertension and possibly with cardiovascular disease. Oral magnesium acts as a natural calcium channel blocker, increases nitric oxide, improves endothelial dysfunction, and induces direct and indirect vasodilation.

Role of mercury toxicity in hypertension, cardiovascular disease, and stroke.

Mercury has a high affinity for sulfhydryl groups, inactivating numerous enzymatic reactions, amino acids, and sulfur-containing antioxidants (N-acetyl-L-cysteine, alpha-lipoic acid, L-glutathione), with subsequent decreased oxidant defense and increased oxidative stress. Mercury binds to metallothionein and substitute for zinc, copper, and other trace metals, reducing the effectiveness of metalloenzymes. Mercury induces mitochondrial dysfunction with reduction in adenosine triphosphate, depletion of glutathione, and increased lipid peroxidation. Increased oxidative stress and reduced oxidative defense are common. Selenium and fish containing omega-3 fatty acids antagonize mercury toxicity. The overall vascular effects of mercury include increased oxidative stress and inflammation, reduced oxidative defense, thrombosis, vascular smooth muscle dysfunction, endothelial dysfunction, dyslipidemia, and immune and mitochondrial dysfunction. The clinical consequences of mercury toxicity include hypertension, coronary heart disease, myocardial infarction, cardiac arrhythmias, reduced heart rate variability, increased carotid intima-media thickness and carotid artery obstruction, cerebrovascular accident, generalized atherosclerosis, and renal dysfunction, insufficiency, and proteinuria. Pathological, biochemical, and functional medicine correlations are significant and logical. Mercury diminishes the protective effect of fish and omega-3 fatty acids. Mercury inactivates catecholaminei-0-methyl transferase, which increases serum and urinary epinephrine, norepinephrine, and dopamine. This effect will increase blood pressure and may be a clinical clue to mercury-induced heavy metal toxicity. Mercury toxicity should be evaluated in any patient with hypertension, coronary heart disease, cerebral vascular disease, cerebrovascular accident, or other vascular disease. Specific testing for acute and chronic toxicity and total body burden using hair, toenail, urine, and serum should be performed.

The importance of potassium in managing hypertension.

Dietary potassium intake has been demonstrated to significantly lower blood pressure (BP) in a dose-responsive manner in both hypertensive and nonhypertensive patients in observational studies, clinical trials, and several meta-analyses. In hypertensive patients, the linear dose-response relationship is a 1.0 mm Hg reduction in systolic BP and a 0.52 mm Hg reduction in diastolic BP per 0.6 g per day increase in dietary potassium intake that is independent of baseline potassium deficiency. The average reduction in BP with 4.7 g (120 mmol) of dietary potassium per day is 8.0/4.1 mm Hg, depending race and on the relative intakes of other minerals such as sodium, magnesium, and calcium. If the dietary sodium chloride intake is high, there is a greater BP reduction with an increased intake of dietary potassium. Blacks have a greater decrease in BP than Caucasians with an equal potassium intake. Potassium-induced reduction in BP significantly lowers the incidence of stroke (cerebrovascular accident, CVA), coronary heart disease, myocardial infarction, and other cardiovascular events. However, potassium also reduces the risk of CVA independent of BP reductions. Increasing consumption of potassium to 4.7 g per day predicts lower event rates for future cardiovascular disease, with estimated decreases of 8% to 15% in CVA and 6% to 11% in myocardial infarction.

Nutrition and nutraceutical supplements in the treatment of hypertension.

Macronutrient and micronutrient deficiencies are very common in the general population, and may be even more common in patients with hypertension and cardiovascular disease due to genetic and environmental causes, and prescription drug use. Vascular biology assumes a pivotal role in the initiation and perpetuation of hypertension and target organ damage sequelae. Endothelial activation, oxidative stress and vascular smooth muscle dysfunction (hypertrophy, hyperplasia and remodeling) are initial events that initiate hypertension. Nutrient-gene interactions determine a broad array of phenotypic consequences such as vascular problems and hypertension. Optimal nutrition, nutraceuticals, vitamins, antioxidants, minerals, weight loss, exercise, smoking cessation, and moderate restriction of alcohol and caffeine, in addition to other lifestyle modifications, can prevent, delay the onset, reduce the severity, treat and control hypertension in many patients. An integrative approach combining these lifestyle suggestions with the correct pharmacologic treatment will best achieve new goal blood pressure levels, reduce cardiovascular risk factors, improve vascular health, reduce target organ damage, including coronary heart disease, stroke, congestive heart failure and renal disease, and reduce healthcare expenditure. The expanded scientific roles for nutraceutical supplements will be discussed in relation to the prevention and treatment of essential hypertension and cardiovascular diseases.