No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Cellular effects of garlic supplements and antioxidant vitamins in lowering marginally high blood pressure in humans: pilot study
Abstract
The present investigation was carried out to determine the in vivo effects of garlic and antioxidants on marginally high blood pressure in human subjects as well as the in vitro effects on human endothelial cell (EC) nitric oxide (NO) production. The antioxidant vitamin C alone (2.0 g/d), garlic alone (2.5 g/d), or a combination was administered for 10 days in human subjects with marginally high blood pressure. Furthermore, the effect of garlic extract, garlic ingredients (including alliin, allyl disulfide, diallyl trisulfide), or antioxidants (vitamin C, vitamin E, and vitamins C + E), and combinations on human EC NO formation were examined. Vitamin C alone did not result in any changes in systolic or diastolic blood pressure. In contrast, garlic resulted in a significant lowering (P < .05) of mean systolic but not diastolic blood pressure. In contrast, garlic plus vitamin C resulted in a distinct lowering of mean systolic and diastolic blood pressures to reference ranges. At the cellular level, the various garlic ingredients resulted in significant (P < .01) increase in EC NO production by about 2-fold above control. In contrast, vitamin C, E, or both resulted in slight but not statistically significant increase in EC NO production. However, combinations of the garlic ingredients with antioxidant vitamins resulted in enhanced (P < .01) EC NO production by about 3-fold. The effect of garlic ingredients or garlic ingredients and antioxidants on EC NO production might explain the effects of garlic and vitamin C in lowering marginally high blood pressure.
... Garlic's multi-fold therapeutic effects have been recognized for thousands of years amongst different cultures around the world, and continues to attract interest from pharmacologists and health practitioners (Frishman et al., 2009;Qidwai and Ashfaq, 2013; Table 2). This herb is not only known for its hypotensive capacity, but is also characterized by antiinflammatory, antioxidant, antibacterial, hypocholesteremic, and anti-cancer properties (Banerjee et al., 2002;Mousa and Mousa, 2007;Frishman et al., 2009;Qidwai and Ashfaq, 2013). For health benefits, garlic can be consumed in different forms, such as raw, aged, an aqueous extract, oil, and in powder form (Banerjee et al., 2002;Frishman et al., 2009;Ried et al., 2013). ...
... Many hypertensive patients use garlic to lower their blood pressure (Qidwai and Ashfaq, 2013). The reported effects vary from significant reduction in mean arterial pressure, drop in either SBP or DBP only, to no alteration in blood pressure at all (Banerjee et al., 2002;Mousa and Mousa, 2007;Frishman et al., 2009;Yang et al., 2011;Augusti et al., 2012). However, most studies confirm the induction of hypotensive effects by garlic and its constituents. ...
... The endogenous signaling gases, NO and H 2 S, are recognized as mediators of garlic's antihypertensive properties (Banerjee et al., 2002;Mousa and Mousa, 2007;Ried et al., 2013). In a clinical trial performed by Mousa and Mousa (2007) on stage 1 hypertensive subjects (≥140 mmHg), who consumed a daily dose of 2600 mg of garlic (one tablet comprising of 650 mg of garlic bulb-Allium sativum-powder) for a period of 10 days, the authors reported a significant reduction of 17 mmHg in SBP, but the DBP remained unchanged (Mousa and Mousa, 2007; Table 6). ...
The use of herbal therapies for treatment and management of cardiovascular diseases is increasing. Plants contain a bounty of phytochemicals that have proven to be protective by reducing the risk of various ailments and diseases. Indeed, accumulating literature provides the scientific evidence and hence reason d’etre for the application of herbal therapy in relation to cardiovascular diseases. Slowly, but absolutely, herbal remedies are being entrenched into evidence-based medical practice. This is partly due to the supporting clinical trials and epidemiological studies. The rationale for this expanding interest and use of plant based treatments being that a significant proportion of hypertensive patients do not respond to Modern therapeutic medication. Other elements to this equation are the cost of medication, side-effects, accessibility and availability of drugs. Therefore, we believe it is pertinent to review the literature on the beneficial effects of herbs and their isolated compounds as medication for treatment of hypertension, a prevalent risk factor for cardiovascular diseases. Our search utilized the PubMed and ScienceDirect databases, and the criterion for inclusion was based on the following keywords and phrases: hypertension, high blood pressure, herbal medicine, complementary and alternative medicine, nitric oxide, vascular smooth muscle cell proliferation, hydrogen sulfide, nuclear factor kappa-B, oxidative stress and epigenetics/epigenomics. Each of the aforementioned keywords was co-joined with plant or herb in question, and where possible with its constituent molecule(s). In this first of a two-part review, we provide a brief introduction of hypertension, followed by a discussion of the molecular and cellular mechanisms. We then present and discuss the plants that are most commonly used in the treatment and management of hypertension.
... In a pilot study, hypertensive subjects who had taken a dosage of 2.5 g/day garlic for 10 days significantly lowered (p < .05) mean SBP, yet the DBP stayed unaltered (Mousa & Mousa, 2007). ...
The use of food products and functional foods to manage and treat several health conditions is expanding globally. Garlic (Allium sativum) consumption is commonly used
for its potential therapeutic functions in numerous cardiometabolic disorders, including hypertension. The proposed blood pressure–reducing effects of garlic after its
consumption influence several metabolic pathways, resulting in potentially beneficial health outcomes. The first postulated mechanism is nitric oxide (NO) activation, leading to vasodilation. Furthermore, garlic consumption was also shown to promote vasodilation by suppressing the renin–angiotensin–aldosterone system (RAAS) and the formation of prostaglandins, suppressing angiotensin-converting enzyme activity. The mechanism of garlic-related vasodilation is related to its high sulfur-containing content associated with forming hydrogen sulfides (H2S). The H2S binds to and activates vascular ATP-sensitive potassium channels (kATP), leading to hyperpolarization, which induces vasodilation. This review summarizes garlic’s features and the mechanical paths that could contribute to blood pressure control.
... normotensive rats fed 10% and 20% A. sativum diets (Groups 5 and 6) showed a downregulation of the ICAM-1 gene expression and plasma TNF-alpha levels which was lower than that observed for normotensive rats fed basal diet (Group 1). It has been previously reported that A. sativum possesses anti-inflammatory activity [33] which forms parts of the reasons for its medicinal uses. ...
This study assessed the short term effect of Allium sativum-based diets on mRNA expression of Calmodulin (CaM), Inositol Trisphosphate receptor (IP 3 R) and Intracellular adhesion molecule (ICAM-1) in the heart and aorta of cyclosporin-induced prehypertensive rats. Plasma levels of Ca 2+ and Tumor Necrosis Factor-alpha (TNF-alpha) were also determined. The experimental rats used for this study were randomly allocated into 7 groups (n=4): normotensive control rats (fed basal diet); untreated prehypertensive rats (fed basal diet); prehypertensive rats (fed 10% and 20% Allium sativum based diets respectively); normotensive rats (fed 10% and 20% Allium sativum based diets respectively); prehypertensive rats treated with 10mg/kg captopril respectively for 7 days. Induction of hypertension with cyclosporin caused significant increase (p ˂ 0.05) in mRNA expression of CaM, IP 3 R and ICAM-1, accompanied by increased (p ˂ 0.05) systolic and diastolic blood pressures, plasma Tumor Necrosis Factor-alpha (TNF-alpha) and Ca 2+ levels. These effects were considerably reversed by Allium sativum-based diets fed to the prehypertensive rats. These findings provide evidence which suggest that CaM, IP3R, and ICAM-1 are also upregulated in prehypertension, but are modulated by short term dietary intervention with garlic.
... Copious studies have indicated that supplementation of various nutrients (micronutrients and macronutrients) along with various nutraceuticals and functional foods like dietary fibers, probiotics, Coenzyme Q10 (CoQ10), fish oil, garlic, green tea, grape seed polyphenols, and arginine are shown to be safe and effective against mild or moderatehypertensive subjects [2,130,131]. Even though this review article focuses on the importance of only micronutrients, it is not necessary that these micronutrients alone be beneficial against HT and its related abnormalities. ...
Hypertension (HT) is one of the pivotal risk factors for various detrimental diseases like cardiovascular diseases (CVDs), cerebrovascular disease, and renal dysfunction. Currently, many researchers are paying immense attention to various diet formula (dietary approach) with a special focus on micro and macronutrients along with modified lifestyle and standard anti-hypertensive drugs. Micronutrients (minerals/vitamins) play a central role in the regulation of blood pressure (BP) as they aid the function of macronutrients and also improve the anti-hypertensive functions of some anti-hypertensive agents. Even though several studies have demonstrated the beneficial effects of micronutrients on controlling BP, still some ambiguity exists among the nutritionists/doctors, which combination or individual mineral (dietary approach) contributes to better BP regulation. Therefore, this critical review article was attempted to delineate the underlying role of micronutrients (minerals and vitamins) for the management and prevention or delaying of HT and their related complications with strong affirmation from clinical trials as well as its mechanism of controlling BP. Moreover, the major source and recommended daily allowance (RDA) of various micronutrients are included in this review for guiding common readers (especially HT subjects) and dieticians to choose/recommend a better micronutrient and their combinations (other nutrients and standard anti-hypertensive drugs) for lowering the risk of HT and its related co-morbid conditions like CVDs.
... Mata analysis interpretation confirmed that AGE produces a dependable lowering of blood pressure (both SBP and DBP) compared to other forms of A. Sativum [33]. [34,35]. Benavides et al. reported that garlic provides polysulfides to red blood cells to boost H 2 S production and synthesis results vasorelaxation [36]. ...
Hypertension is a critical health problem and worse other cardiovascular diseases. It is mainly of two types: Primary or essential hypertension and Secondary hypertension. Hypertension is the primary possibility feature for coronary heart disease, stroke and renal vascular disease. Herbal medicines have been used for millions of years for the management and treatment of hypertension with minimum side effects. Over aim to write this review is to collect information on the anti-hypertensive effects of natural herbs in animal studies and human involvement as well as to recapitulate the underlying mechanisms, from the bottom of cell culture and ex-vivo tissue data. According to WHO, natural herbs/shrubs are widely used in increasing order to treat almost all the ailments of the human body. Plants are the regular industrial units for the invention of chemical constituents, they used as immunity booster to enhance the natural capacity of the body to fight against different health problems as well as herbal medicines and food products also. Eighty percent population of the world (around 5.6 billion people) consume medicines from natural plants for major health concerns. This review provides a bird's eye analysis primarily on the traditional utilization, phytochemical constituents and pharmacological values of medicinal herbs used to normalize hypertension i.e.
... Mata analysis interpretation confirmed that AGE produces a dependable lowering of blood pressure (both SBP and DBP) compared to other forms of A. Sativum [33]. [34,35]. Benavides et al. reported that garlic provides polysulfides to red blood cells to boost H 2 S production and synthesis results vasorelaxation [36]. ...
Hypertension is a critical health problem and worse other cardiovascular diseases. It is mainly of two types: Primary or essential hypertension and Secondary hypertension. Hypertension is the primary possibility feature for coronary heart disease, stroke and renal vascular disease. Herbal medicines have been used for millions of years for the management and treatment of hypertension with minimum side effects. Over aim to write this review is to collect information on the anti-hypertensive effects of natural herbs in animal studies and human involvement as well as to recapitulate the underlying mechanisms, from the bottom of cell culture and ex-vivo tissue data. According to WHO, natural herbs/shrubs are widely used in increasing order to treat almost all the ailments of the human body. Plants are the regular industrial units for the invention of chemical constituents, they used as immunity booster to enhance the natural capacity of the body to fight against different health problems as well as herbal medicines and food products also. Eighty percent population of the world (around 5.6 billion people) consume medicines from natural plants for major health concerns. This review provides a bird’s eye analysis primarily on the traditional utilization, phytochemical constituents and pharmacological values of medicinal herbs used to normalize hypertension i.e. Hibiscus sabdariffa , Allium sativum, Andrographis paniculata, Apium graveolens, Bidenspilosa, Camellia sinensis, Coptis chinensis, Coriandrum sativum, Crataegus spp., Crocus sativus, Cymbopogon citrates, Nigella sativa, Panax ginseng,Salviaemiltiorrhizae, Zingiber officinale, Tribulus terrestris, Rauwolfiaserpentina, Terminalia arjuna etc.
Graphic Abstract
... Recently, S-1-propenylcysteine, but not S-allylcysteine, was shown significantly to decrease systolic BP of spontaneously hypertensive rats (Ushijima et al., 2018). Garlic ingredients, such as alliin, allyl disulphide and diallyl trisulfide result in significant increase of human endothelial cell NO production (Mousa and Mousa, 2007). Lastly, seven dipeptides with ACE inhibitory properties were isolated from garlic aqueous extracts and tested for ACE inhibition, finding that Phe-Tyr was the most potent one (Suetsuna, 1998). ...
Hypertension has become the leading risk factor for worldwide cardiovascular diseases. Conventional pharmacological treatment, after both dietary and lifestyle changes, is generally proposed. In this review, we present the antihypertensive properties of phytocomplexes from thirteen plants, long ago widely employed in ethnomedicines and, in recent years, increasingly evaluated for their activity in vitro and in vivo, also in humans, in comparison with synthetic drugs acting on the same systems. Here, we focus on the demonstrated or proposed mechanisms of action of such phytocomplexes and of their constituents proven to exert cardiovascular effects. Almost seventy phytochemicals are described and scientifically sound pertinent literature, published up to now, is summarized. The review emphasizes the therapeutic potential of these natural substances in the treatment of the 'high normal blood pressure' or 'stage 1 hypertension', so-named according to the most recent European and U.S. guidelines, and as a supplementation in more advanced stages of hypertension, however needing further validation by clinical trial intensification.
... arterial BP lowering. [16] The results of the present study are compatible with the results of others [17] who stated that garlic can lower elevated BP to a normal level. ...
Background: Essential hypertension is a global major health problem
... The electrochemical reduction of radical is manifested in square wave volatammetry by a defined peak at around -0.6 V. The addition of the antioxidant sample to the solution containing the free radical causes the decrease in the current density of this peak [14][15][16][17][18]. ...
Cyclic voltametry (CV) and Square wave voltametry (SWV) were used to study the electrochemical behavior
and evaluate the antioxidant capacity of virgin olive oil. Firstly, in this work we illustrate the electrochemical methods based on the preparation and characterization of H2O2 amperometric sensor, then the antioxidant capacity of the virgin olive oil was evaluated by measuring of the of virgin olive oil effect on the H2
O2 reduction.
... 26 De posse desses dados, busca-se compreender os mecanismos moleculares que sublinham o estresse redox e propor medicamentos ou alternativas nutricionais (alimentos ou nutrientes específicos) que possam diminuir a ação deletéria dessas espécies reativas sobre a saúde da população humana. [27][28][29][30] Em termos alimentares, a deterioração de óleos e gorduras é responsável pelos odores e sabores rançosos, com consequente decréscimo da qualidade e segurança nutricionais, causado pela formação de produtos secundários, potencialmente tóxicos. Assim, a adição de antioxidantes é requerida para preservar sabor e odor, além de evitar a destruição de vitaminas. ...
Growing knowledge on the health-promoting impact of antioxidants in everyday foods, combined with the assumption that a number of common synthetic preservatives may have hazardous side effects has led to increased investigations in the field of natural antioxidants, principally those found in plants. Food industries normally discard plant residues that could benefit the human health and diminish undesirable environmental impact. Once estimated the content of antioxidants in these residues, advantageous economical and social alternatives to the discard are possible, for example, their use for preparation of nutraceuticals to be offered to low-income populations. We present here a broad, although not complete, account of the continuously growing knowledge on the antioxidant capacity of whole fruits, seeds and peels, cereals, vegetal oils and aromatic plants, at several physical forms, as well as a description of the usual methods for evaluating their antioxidant capacity and examples of agroindustrial processes that could be harnessed for the production of antioxidant supplement food, along with research perspectives in the area.
... Benefits Ali et al. (2000) stated in their report that there is some inconsistency regarding the effectiveness of garlic against hypertension. Conversely, a study by Mousa and Mousa (2007) stated that when garlic is taken together with vitamin C, it brings down marginally high blood pressure. ...
This study was designed to investigate the possible neuroprotective effects of garlic oil on histopa-thological and biochemical changes induced by Acrylamide in rats. Forty-eight rats were randomly divided into three experimental groups: control, acrylamide, and acrylamide co-treated with garlic oil. After recording the neurological symptoms, four rats at 7, 14, 21, 28 days from each group were decapitated and nervous tissues were excised for gross and histopathologic evaluation and biochemical assessment. In Acrylamide intoxicated group, rats showed ataxia and weakness in their hind limb after 2 weeks followed by hind limb paralysis then quadric paralysis at the end of experiment. Co-treatment of rats with garlic oil in this study resulted in mild improvement in the recorded clinical signs. Acrylamide neurotoxicity increase Lipid peroxidation and Nitric oxide levels, Superoxide Dismutase, Acetylcholine esterase activities and reduced Glutathione contents. Histopathologically, Acrylamide toxicity developed congestion, hemorrhage, and thrombosis in the vasculature. Malacia in the grey and white matter, demyelination, Lewy like bodies and mast cells were observed. Neu-ronal degeneration was seen in Purkinje cell layer, hippocampal neurons, mitral cell layer, and motor neurons in the brain stem and spinal cord. Transmission electron microscopy revealed degenera-tion of Purkinje neurons, vacuolation of glia cell processes and perivascular edema in cerebellum and demyelination of myelin sheath, degeneration of Schwann cells and increment of the collagen content in the interstitium of sciatic nerve. Co-treatment with garlic oil caused biochemical and morphological improvement on central nervous system and prephral nervous system. We postulate that the neuroprotective effects of garlic oil could attributed to its direct and indirect antioxidant actions.
Background:
Garlic is widely used by patients for its blood pressure lowering effects. A meta-analysis published in 2008 concluded that garlic consumption lowers blood pressure in hypertensive and normotensive patients. Therefore, it is important to review the currently available evidence to determine whether garlic may also have a beneficial role in the reduction of cardiovascular events and mortality rates in patients with hypertension.
Objectives:
To determine whether the use of garlic as monotherapy, in hypertensive patients, lowers the risk of cardiovascular morbidity and mortality compared to placebo.
Search methods:
A systematic search for trials was conducted in the Cochrane Hypertension Group Specialised Register, CENTRAL, MEDLINE, EMBASE, AGRICOLA, AMED, and CINAHL up to November 2011. A hand search of reference lists of identified reviews was conducted. Experts in the area were also contacted to identify trials not found in the electronic search. Clinicaltrials.gov was searched for ongoing trials.
Selection criteria:
Randomized, placebo-controlled trials of any garlic preparation versus placebo for the treatment of hypertension were included.
Data collection and analysis:
Two reviewers independently extracted data and assessed trial quality using the risk of bias tool. Data synthesis and analysis was performed using RevMan 5.
Main results:
The search identified two randomized controlled trials for inclusion. One trial included 47 hypertensive patients and showed that garlic significantly reduces mean supine systolic blood pressure by 12 mmHg (95% CI 0.56 to 23.44 mmHg, p=0.04) and mean supine diastolic blood pressure by 9 mmHg (95% CI 2.49 to 15.51 mmHg, p=0.007) versus placebo. The authors state that garlic was "free from side effects" and that no serious side effects were reported. There were 3 cases "where a slight smell of garlic was noted."The second trial could not be meta-analysed as they did not report the number of people randomized to each treatment group. They did report that 200 mg of garlic powder given three times daily, in addition to hydrochlorothiazide-triamterene baseline therapy, produced a mean reduction of systolic blood pressure by 10-11 mmHg and of diastolic blood pressure by 6-8 mmHg versus placebo.Neither trial reported clinical outcomes and insufficient data was provided on adverse events.
Authors' conclusions:
There is insufficient evidence to determine if garlic provides a therapeutic advantage versus placebo in terms of reducing the risk of mortality and cardiovascular morbidity in patients diagnosed with hypertension. There is also insufficient evidence to determine the difference in withdrawals due to adverse events between patients treated with garlic or placebo.Based on 2 trials in 87 hypertensive patients, it appears that garlic reduces mean supine systolic and diastolic blood pressure by approximately 10-12 mmHg and 6-9 mmHg, respectively, over and above the effect of placebo but the confidence intervals for these effect estimates are not precise and this difference in blood pressure reduction falls within the known variability in blood pressure measurements. This makes it difficult to determine the true impact of garlic on lowering blood pressure.
The aim of the present study was to develop an oil-free o/w microemulsion, Cremophor EL:ethanol-propylene glycol:saline, for diallyl trisulfide (DATS) for intravenous (i.v.) administration to modify the safety and pharmacokinetics of DATS. The ternary diagram was constructed to identify the regions of dilutable microemulsions, and the optimal composition of microemulsion was determined by evaluation of injection safety such as hemolysis, intravenous stimulation and injection anaphylaxis compared to commercial formulation Chentian(®). Promising microemulsion with modified injection safety was developed that could incorporate 100 mg/g of DATS. The droplet size of the microemulsion was about 26 nm in diameter with narrow distribution (polydispersity index: 0.14). Acute toxicity test showed that median lethal dose (LD(50)) of DATS microemulsion was 1.69-fold higher than that of Chentian(®). Pharmacokinetics was assessed by comparing with the commercial injection after intravenous administration to rats at a dose of 30 mg/kg. The developed microemulsion showed significant higher area under the drug concentration-time curve and lower clearance and distribution volume than those of Chentian(®) (p<0.05). This helped DATS to reach higher level in vessel, and circulate in the blood stream for a longer time resulting in better therapeutic effect. In conclusion, microemulsion would be a promising intravenous delivery system for DATS.
Early trials of garlic preparations on blood lipids mainly supported a lipid-lowering effect, whereas later well-designed garlic tablet trials were mainly entirely null. However, enteric simulation tests suggest that this discordance may result from ineffective delivery of bioactive agents from the brands of garlic powder (GP) and cyclodextrin-bound garlic oil (GO) tablets tested in some recent negative trials. In contrast, enteric simulation tests show that the preformed bioactive agents present in "traditional" gelatin capsules of GO are efficiently released, although such capsules have rarely been investigated in lipid-lowering trials. It was hypothesized that gelatin capsules of GO given to normal subjects would improve specified coronary heart disease risk factors. Effects of a GP preparation were also investigated. Subjects (n = 51; men and women, mean age 27 y) were randomly assigned to receive either 8.2 mg/d of GO (allyl sulfides) or placebo for 11 wk. Another 27 subjects received garlic powder (GP) of similar biopotential (7.8 mg allicin/d). Outcome measures were 95% confidence intervals (CI) between GO and placebo groups for differences between baseline and subsequent sample times. Men and women combined showed no significant differences save for an improved total antioxidant capacity at 6 wk (P = 0.01). Hence, no benefit from GO after 11 wk is one plausible conclusion. However, there were significant differences in effect of GO between men and women for HDL cholesterol (HDL-C) (P = 0.004) and total cholesterol (TC)/HDL-C (P = 0.003). Women showed favorable effects in terms of CHD risk factors (i.e., increases in HDL-C and reductions in TC/HDL-C), whereas men had small adverse effects. There was a significant difference in the GO effect for glucose (P = 0.006), with a reduction seen for men and an increase for women. The gender effects were unexpected and such analyses were not planned in advance. Confirmation of these findings with larger numbers of subjects would have importance for the use of garlic against CHD and for the design of future garlic studies.
The vascular endothelial cell (EC) plays an essential role in the pathogenesis of inflammation, transplant rejection and tumour metastasis. Most research on vascular ECs uses human umbilical vein endothelial cells (HUVECs). However, HUVECs are derived from immune-naive foetal tissue, and show significant functional differences from adult vascular endothelium. In this paper, we characterise an alternative model based on human saphenous vein ECs (HSVECs), describe their culture conditions and provide a detailed functional comparison with HUVECs. Compared with HUVECs, HSVECs show an increased sensitivity to ox-LDL and a reduced response to cytokines, as indicated by adhesion molecule expression as well as leukocyte adhesion and transmigration. With respect to their ability to present antigen, HSVECs have a higher level of HLA-DR, CD40 and ICOS-L following cytokine stimulation. In addition, HSVECs upregulate the costimulatory ligand CD80 (B7.1) following CD40 ligation, and support allogeneic T cell proliferation, while HUVECs fail to express CD80. Due to differential expression of adhesion molecules, poorly differentiated tumour cell lines also showed more adhesion to HSVECs than to HUVECs. These results indicate that HSVECs have advantages over HUVECs for studying adult vascular endothelial pathology in vitro.
Epidemiologic studies show an inverse correlation between garlic consumption and progression of cardiovascular disease. Cardiovascular disease is associated with multiple factors such as raised serum total cholesterol, raised LDL and an increase in LDL oxidation, increased platelet aggregation, hypertension, and smoking. Numerous in vitro studies have confirmed the ability of garlic to reduce these parameters. Thus, garlic has been shown to inhibit enzymes involved in lipid synthesis, decrease platelet aggregation, prevent lipid peroxidation of oxidized erythrocytes and LDL, increase antioxidant status, and inhibit angiotension-converting enzyme. These findings have also been addressed in clinical trials. The studies point to the fact that garlic reduces cholesterol, inhibits platelet aggregation, reduces blood pressure, and increases antioxidant status. Since 1993, 44% of clinical trials have indicated a reduction in total cholesterol, and the most profound effect has been observed in garlic's ability to reduce the ability of platelets to aggregate. Mixed results have been obtained in the area of blood pressure and oxidative-stress reduction. The findings are limited because very few trials have addressed these issues. The negative results obtained in some clinical trials may also have resulted from usage of different garlic preparations, unknown active constituents and their bioavalability, inadequate randomization, selection of inappropriate subjects, and short duration of trials. This review analyzes in vitro and in vivo studies published since 1993 and concludes that although garlic appears to hold promise in reducing parameters associated with cardiovascular disease, more in-depth and appropriate studies are required.
A variety of different spectrophotometric methods have been developed to quantify nitric oxide (NO)-derived metabolites such as nitrate and nitrite. Some of these methods measure the formation of colored complexes such as azo dyes (e.g., Griess reaction), whereas other methods measure the formation of fluorometric compounds. Virtually all of these methods require the rapid and spontaneous decomposition of NO in the presence of molecular oxygen to yield potent N-nitrosating agents which ultimately N-nitrosate the various detector compounds. The N-nitrosation of 2,3-diaminonaphthalene (DAN) to yield the highly fluorescent 2,3-naphthotriazole offers the advantages of specificity, sensitivity, and versatility. This assay is capable of detecting as little as 10–30 nM (10–30 picomol/ml) of NO and may be used to quantify NO generated in a physiologically relevant environment (e.g., neutral pH) with minimal interference due to nitrite decomposition. The trapping efficiency of DAN for NO is approximately 80% and the enhanced sensitivity of this assay provides a valuable method for the determination of small amounts of NO. This chapter details the spectrofluorometric methods used in our laboratory to quantity NO generated by several different NO-releasing compounds and by a variety of different cell types in culture. In addition, we describe how this method may be modified to quantify nitrite and nitrate, the stable decomposition products of NO oxidation in aqueous solution.
It is surprising that nearly 100 years after it was first discovered, and the subsequent recognition of its limited accuracy, the Korotkoff technique for measuring BP has continued to be used without any substantial improvement. The brachial artery is occluded by a cuff placed around the upper arm and inflated to above systolic pressure. As it is gradually deflated pulsatile blood flow is reestablished and accompanied by sounds that can be detected by a stethoscope held over the brachial artery just below the cuff. The onset of phase I of the Korotkoff sounds (tapping sounds corresponding to the appearance of a palpable pulse) corresponds to systolic pressure, but tends to underestimate the systolic pressure recorded by direct intra-arterial measurement.12 The disappearance of sounds (phase V) corresponds to diastolic pressure, but tends to occur before diastolic pressure determined by direct intraarterial measurement.12 The fifth phase should be used, except in situations in which the disappearance of sounds cannot reliably be determined because sounds are audible even after complete deflation of the cuff, for example, in pregnant women, in which case the fourth phase (muffling) may be used.13
To undertake a systematic review, including meta-analysis, of published and unpublished randomized controlled trials of garlic preparations to determine the effect of garlic on blood pressure relative to placebo and other antihypertensive agents.
Studies were identified by a search of Medline and the Alternative Medicine electronic databases, from references listed in primary and review articles, and through direct contact with garlic manufacturers.
Only randomized controlled trials of garlic preparations that were at least 4 weeks in duration were deemed eligible for inclusion in the review.
Data were extracted from the published reports by the two authors independently, with disagreements resolved by discussion.
Eight trials were identified (all using the same dried garlic powder preparation (Kwai) with data from 415 subjects included in the analyses. Only three of the trials were specifically conducted in hypertensive subjects, and many had other methodological shortcomings. Of the seven trials that compared the effect of garlic with that of placebo, three showed a significant reduction in systolic blood pressure (SBP) and four in diastolic blood pressure (DBP). The overall pooled mean difference in the absolute change (from baseline to final measurement) of SBP was greater in the subjects who were treated with garlic then in those treated with placebo. For DBP the corresponding reduction in the garlic-treated subjects was slightly smaller.
The results suggest that this garlic powder preparation may be of some clinical use in subjects with mild hypertension. However, there is still insufficient evidence to recommend it as a routine clinical therapy for the treatment of hypertensive subjects. More-rigorously designed and analysed trials are needed.
The endothelium plays a critical role in maintaining vascular tone by releasing vasoconstrictor and vasodilator substances. Endothelium - derived nitric oxide (NO) is a vasodilator rapidly inactivated by superoxide (O2-) found in significant quantities. The porphyrinic sensor (0.5-8 microm diameter) and chemiluminescence methods were used to measure NO and (O2-) respectively. Effects of hypertension, low density lipoprotein (LDL), and heart preservation on the release of NO and O2- were delineated. In the single endothelial cell (rat aorta) NO concentration was the highest in the cell membrane decreasing exponentially with distance from cell, and becoming undetectable beyond 50 microm and 25 microm for normotensive (WKY) and hypertensive (SHR) rats respectively. The endothelium of SHR released 40% less NO (300+/-25 nmol L(-1)) than that of normotensive rats (500+20 nmol L(-1)), due to the higher production of O2- in SHR rats. An exponentially decreasing NO production (from 1.20 +/- 0.15 to 0.16 +/- 0.05 micromol (L-1)) and concomitant increase of O2- generation (from 10 +/- 0.3 to 300 +/- 25 nmol L(-1) were observed in left ventricle of stored (eight hours) rabbit heart. Native and oxidized low density lipoproteins (nLDL and oxLDL) inhibited NO generation and increased O2- production. The local depletion of the L-arginine substrate may disarrange the nitric oxide synthase, leading to production of O2- from oxygen.
Angiogenesis is a complex process involving endothelial cell migration, proliferation, invasion, and tube formation. Inhibition of these processes might have implications in various angiogenesis-mediated disorders. Because nitric oxide (NO) is known to play a key role in various vascular diseases, the present study was undertaken to determine the role of NO in angiogenesis-mediated processes using the NO donor, S-nitroso N-acetyl penicillamine (SNAP) and S-nitroso N-acetyl glutathione (SNAG). The antiangiogenic efficacy of these NO donors was examined using in vivo and in vitro model systems. The in vitro studies demonstrated the ability of SNAP to inhibit cytokine fibroblast growth factor (FGF2)-stimulated tube formation and serum-induced cell proliferation. The inhibitory effect on cell proliferation by SNAP concentrations above the millimolar range was associated with significant shifts in the concentration of NO metabolites. Furthermore, using the mouse Matrigel implant model and the chick chorioallantoic membrane (CAM) models, SNAP demonstrated maximal inhibitory efficacy (85-95% inhibition) of cytokine (FGF2)-induced neovascularization in both in vivo models. SNAP and SNAG resulted in 85% inhibition of FGF2-induced neovascularization in the mouse Matrigel model when given at 5 mg/kg/day infusion in minipumps during 14 days and 87% inhibition of angiogenesis induced by FGF2 in the CAM when administered a single dose of 50 microg. Thus, NO donors might be a useful tool for the inhibition of angiogenesis associated with human tumor growth, or neovascular, ocular, and inflammatory diseases.
The effect of dietary composition on blood pressure is a subject of public health importance. We studied the effect of different levels of dietary sodium, in conjunction with the Dietary Approaches to Stop Hypertension (DASH) diet, which is rich in vegetables, fruits, and low-fat dairy products, in persons with and in those without hypertension.
A total of 412 participants were randomly assigned to eat either a control diet typical of intake in the United States or the DASH diet. Within the assigned diet, participants ate foods with high, intermediate, and low levels of sodium for 30 consecutive days each, in random order.
Reducing the sodium intake from the high to the intermediate level reduced the systolic blood pressure by 2.1 mm Hg (P<0.001) during the control diet and by 1.3 mm Hg (P=0.03) during the DASH diet. Reducing the sodium intake from the intermediate to the low level caused additional reductions of 4.6 mm Hg during the control diet (P<0.001) and 1.7 mm Hg during the DASH diet (P<0.01). The effects of sodium were observed in participants with and in those without hypertension, blacks and those of other races, and women and men. The DASH diet was associated with a significantly lower systolic blood pressure at each sodium level; and the difference was greater with high sodium levels than with low ones. As compared with the control diet with a high sodium level, the DASH diet with a low sodium level led to a mean systolic blood pressure that was 7.1 mm Hg lower in participants without hypertension, and 11.5 mm Hg lower in participants with hypertension.
The reduction of sodium intake to levels below the current recommendation of 100 mmol per day and the DASH diet both lower blood pressure substantially, with greater effects in combination than singly. Long-term health benefits will depend on the ability of people to make long-lasting dietary changes and the increased availability of lower-sodium foods.
In a double-blinded randomized controlled trial, we investigated the long-term effect of vitamin C supplementation on blood pressure. A total of 439 Japanese subjects with atrophic gastritis initially participated in the trial using vitamin C and beta-carotene to prevent gastric cancer. Before and on early termination of beta-carotene supplementation, 134 subjects dropped out of this trial, whereas 120 and 124 subjects took the vitamin C supplement daily at either 50 mg or 500 mg, respectively, for 5 years. Before supplementation, neither systolic nor diastolic blood pressure was significantly related with the serum vitamin C concentration. This relationship was unchanged after adjustment for age, body mass index, and alcohol intake or after stratification by gender. After 5 years, systolic blood pressure significantly increased in groups, regardless of vitamin C dose, compared with baseline. Systolic blood pressure in the high-dose group (500 mg daily) increased from 125.4 to 131.7 mm Hg (5.88 mm Hg increase; 95% confidence interval [CI], 3.11 to 8.65). This value was similar with that of the low-dose group (5.73 mm Hg increase; 95% CI, 2.62 to 8.83) and of the dropout group (4.52 mm Hg increase; 95% CI, 1.26 to 7.77). There was no difference in change of diastolic blood pressure among the 3 groups. In conclusion, we observed no reduction in blood pressure with long-term moderate doses (500 mg/day) of vitamin C supplementation in a high-risk population for stomach cancer and stroke.
Heart failure and pathological overgrowth of the heart often occur hand in hand. New data on a biomechanical sensor challenge the viewpoint that cardiac hypertrophy causes heart failure (pages 68–75).
Nitric oxide (NO) and the mitogenic peptide angiotensin II (Ang II) have been implicated in endothelial cell growth. However, the putative relationship between these two opposing agents with respect to endothelial cell growth remains unknown. In this study, proliferating and confluent rat coronary microvascular endothelial cells (CMEC) were treated with different doses of Ang II, Ca2+ ionophore A23187, or valsartan (an Ang II type 1 (AT1) receptor inhibitor) alone or in combination for 24 h before measuring the nitrite levels as an index of NO generation. NO production and endothelial NO synthase (eNOS) mRNA/protein expression were found to be 3-fold greater in proliferating vs. quiescent CMEC. Treatments of CMEC with Ang II or Ca2+ ionophore A23187 equally increased NO production without altering the fold-difference in the basal release of NO from proliferating vs. confluent CMEC. Valsartan abolished NO production in CMEC treated with Ang II but not Ca2+ ionophore A23187. Treatments of endothelium-intact vascular rings with Ang II (1 nmol/l to 10 micromol/l) plus valsartan or PD-123319, an Ang II type 2 (AT2) receptor inhibitor, attenuated vascular responses to acetylcholine in an Ang II dose-dependent manner. In these rings, phenylephrine produced significant increases in contractile responses only at nmol/l concentrations of Ang II. In contrast, pharmacological and mechanical inactivation of endothelium enhanced contractile responses to phenylephrine at micromol/I concentrations of Ang II. These data demonstrate that Ang II stimulates NO production in CMEC in both an AT1- and an AT2 receptor-regulated manner, and that this stimulation of NO may be beneficial in counterbalancing the direct vasoconstrictor effect of Ang II on underlying smooth muscle cells.
Nitric oxide (NO), produced by endothelial nitric oxide synthase (eNOS), is a key signaling molecule in vascular homeostasis. Loss of NO bioavailability due to reduced synthesis and increased scavenging by reactive oxygen species is a cardinal feature of endothelial dysfunction in vascular disease states. The pteridine cofactor tetrahydrobiopterin (BH4) has emerged as a critical determinant of eNOS activity: when BH4 availability is limiting, eNOS no longer produces NO but instead generates superoxide. In vascular disease states, there is oxidative degradation of BH4 by reactive oxygen species. However, augmentation of BH4 concentrations in vascular disease by pharmacological supplementation, by enhancement of its rate of de novo biosynthesis or by measures to reduce its oxidation, has been shown in experimental studies to enhance NO bioavailability. Thus, BH4 represents a potential therapeutic target in the regulation of eNOS function in vascular disease.
Emotional stress acutely and repetitively causing blood pressure increase or aggravating existing hypertension is usually not reflected by norepinephrine and epinephrine increase but by a sudden rise of dopamine, the third "defensive" catecholamine coping with the damaging neuropsychological and cardiovascular actions of the first two. This double-edged sympathetic response to emotional stress evolves during human lifespan and long-term evolution of hypertension. In the course of philogenesis it carries a potential mismatch between the normal physiology of the human dopaminergic system and current environmental (emotional particularly) conditions in industrialized countries. This offers a rational support to a mental stress-cardiovascular diseases relationship proposed 40 years ago in a WHO report which followed a memorable 1960 Prague Hypertension Meeting.
Endothelium-dependent vasodilation is impaired and predicts the risk of a coronary event in patients with coronary artery disease (CAD). Oxidant stress and increased systemic inflammation may contribute to this endothelial dysfunction. Aged garlic extract (AGE) contains antioxidant compounds and increases nitric oxide production and decreases the output of inflammatory cytokines from cultured cells. The aim of this study was to test the effect of treatment with AGE on brachial artery flow mediated endothelium-dependent dilation (FMD) and circulating markers of oxidative stress and systemic inflammation. The trial included 15 men with angiographically proven CAD in a randomized, placebo-controlled, cross-over design with 2-week treatment and washout periods. During AGE supplementation, FMD increased (44%) significantly (p = 0.04) from the baseline and mainly in men with lower baseline FMD. Levels of FMD at the end of AGE treatment were significantly (p = 0.03) higher compared with the corresponding levels at the end of placebo treatment when the variation in baseline body weight was taken into account. Markers of oxidant stress (plasma oxidized low density lipoprotein and peroxides), systemic inflammation (plasma C-reactive protein ad interleukin-6) and endothelial activation (VCAM-1) did not change significantly during the study. These data suggest that short-term treatment with AGE may improve impaired endothelial function in men with CAD treated with aspirin and a statin. Whether improvement in endothelial function decreases the risk of future cardiovascular events remains to be determined.
Oxygen-free radicals and other oxygen/nitrogen species are constantly generated in the human body. Most are intercepted by antioxidant defences and perform useful metabolic roles, whereas others escape to damage biomolecules like DNA, lipids and proteins. Garlic has been shown to contain antioxidant phytochemicals that prevent oxidative damage. These include unique water-soluble organosulphur compounds, lipid-soluble organosulphur compounds and flavonoids. Therefore, in the present study, we have tried to explore the antioxidant effect of garlic supplementation on oxidative stress-induced DNA damage, nitric oxide (NO) and superoxide generation and on the total antioxidant status (TAS) in patients of essential hypertension (EH). Twenty patients of EH as diagnosed by JNC VI criteria (Group I) and 20 age and sex-matched normotensive controls (Group II) were enrolled in the study. Both groups were given garlic pearls (GP) in a dose of 250 mg per day for 2 months. Baseline samples were taken at the start of the study, i.e. 0 day, and thereafter 2 months follow-up. 8-Hydroxy-2'-deoxyguanosine (8-OHdG), lipids, lipid peroxidation (MDA), NO and antioxidant vitamins A, E and C were determined. A moderate decline in blood pressure (BP) and a significant reduction in 8-OHdG, NO levels and lipid peroxidation were observed in Group I subjects with GP supplementation. Further, a significant increase in vitamin levels and TAS was also observed in this group as compared to the control subjects. These findings point out the beneficial effects of garlic supplementation in reducing blood pressure and counteracting oxidative stress, and thereby, offering cardioprotection in essential hypertensives.
Alliin, a compound derived from garlic, demonstrated dose-dependent inhibition of fibroblast growth factor-2 (FGF2)-induced human endothelial cell (EC) tube formation and angiogenesis in the chick chorioallantoic membrane (CAM) model. Additionally, alliin demonstrated potent inhibition of vascular endothelial growth factor (VEGF)-induced angiogenesis in the CAM model. The antioxidant vitamins C and E significantly (P < 0.001) enhanced the inhibitory efficacy of alliin on FGF2-induced EC tube formation and angiogenesis. Alliin significantly increased (P < 0.01) nitric oxide (NO) release into the CAM fluid, which was further enhanced by vitamins C and E. The NO synthesis inhibitor nitro-L-arginine methyl ester (L-NAME) reversed the anti-angiogenesis efficacy of alliin in the CAM model. Vitamins C and E significantly enhanced the anticancer efficacy of alliin in inhibiting colon and fibrosarcoma tumor growth. Alliin significantly inhibited both FGF2 and VEGF secretion from human fibrosarcoma cells in a concentration-dependent manner. Additionally, alliin up-regulated the p53 production in FGF2-stimulated EC. These data indicated a synergistic effect of antioxidants on the anti-angiogenesis and anticancer efficacy of alliin. These data also suggest the implication of cellular NO and p53 as mediators of anti-angiogenesis and anticancer effects of alliin.
Foods and nutrients play a vital role in normal functioning of the body. They are helpful in maintaining the health of the individual and in reducing the risk of various diseases. Worldwide acceptance of this fact formed a recognition link between "nutrition" and "health" and the concept of "nutraceuticals" was evolved. Nutraceuticals are medicinal foods that play a role in maintaining well being, enhancing health, modulating immunity and thereby preventing as well as treating specific diseases. Thus the field of nutraceuticals can be envisioned as one of the missing blocks in the health benefit of an individual. More than any other disease, the etiology of cardiovascular disease reveals many risk factors that are amenable to nutraceutical intervention. The scientific literature shows that several ingredients marketed for use in dietary supplements address each of these. The ability of nutraceuticals to positively influence cardiovascular risk factors should be recognized as an enormous opportunity in the treatment of a highly prevalent disease. Nutraceuticals hold promise in clinical therapy as they have the potential to significantly reduce the risk of side effects associated with chemotherapy along with reducing the global health care cost. In this review, an attempt has been made to summarize some of the recent research findings on garlic, omega-3-fatty acids, soy products, dietary fibres, vitamins, antioxidants, plant sterols, flavonoids, prebiotics and probiotics that have beneficial effects on the heart, in order to update the practising clinician on the benefit of using nutraceuticals for the management of cardiovascular diseases.
Epidemiologic studies show an inverse correlation between garlic consumption and progression of cardiovascular disease. Cardiovascular disease is associated with multiple factors such as raised serum total cholesterol, raised LDL and an increase in LDL oxidation, increased platelet aggregation, hypertension, and smoking. Numerous in vitro studies have confirmed the ability of garlic to reduce these parameters. Thus, garlic has been shown to inhibit enzymes involved in lipid synthesis, decrease platelet aggregation, prevent lipid peroxidation of oxidized erythrocytes and LDL, increase antioxidant status, and inhibit angiotension-converting enzyme. These findings have also been addressed in clinical trials. The studies point to the fact that garlic reduces cholesterol, inhibits platelet aggregation, reduces blood pressure, and increases antioxidant status. Since 1993, 44% of clinical trials have indicated a reduction in total cholesterol, and the most profound effect has been observed in garlic's ability to reduce the ability of platelets to aggregate. Mixed results have been obtained in the area of blood pressure and oxidative-stress reduction. The findings are limited because very few trials have addressed these issues. The negative results obtained in some clinical trials may also have resulted from usage of different garlic preparations, unknown active constituents and their bioavalability, inadequate randomization, selection of inappropriate subjects, and short duration of trials. This review analyzes in vitro and in vivo studies published since 1993 and concludes that although garlic appears to hold promise in reducing parameters associated with cardiovascular disease, more in-depth and appropriate studies are required.
Previous studies have suggested that patients with chronic medical conditions use complementary and alternative medicine (CAM) at a higher rate than the general population. Despite recent interest in CAM for cardiovascular disease, few data are available regarding patterns of use in patients with cardiovascular disease in the United States. This study used the 2002 National Health Interview Survey and analyzed data on CAM use in 10,572 respondents with cardiovascular disease. Among those with cardiovascular disease, 36% had used CAM (excluding prayer) in the previous 12 months. The most commonly used therapies were herbal products (18%) and mind-body therapies (17%). Among herbs, echinacea, garlic, ginseng, ginkgo biloba, and glucosamine with or without chondroitin were most commonly used. Among mind-body therapies, deep-breathing exercises and meditation were most commonly used. Overall, CAM was used most frequently for musculoskeletal complaints (24% of respondents who used mind-body therapies, 22% who used herbs, 45% who used any CAM). Mind-body therapies were also used for anxiety or depression (23%) and stress or emotional health and wellness (16%). Herbs were commonly used for head and chest colds (22%). Fewer respondents (10%) used CAM specifically for their cardiovascular conditions (5% for hypertension, 2% for coronary disease, 3% for vascular insufficiency, < 1% for heart failure or stroke). Most, however, who used CAM for their cardiovascular condition perceived the therapies to be helpful (80% for herbs, 94% for mind-body therapies). CAM use was more common in younger respondents, women, Asians, and those with more education and greater incomes. In conclusion, CAM use, particularly herbs and mind-body therapies, is common in the United States in patients with cardiovascular disease and mirrors use in the general population. CAM use specifically to treat cardiovascular conditions, however, is less common.
Antiangiogenesis efficacy of nitric oxide donors
- Powell