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Association Between Omega-3 Fatty Acid Intake and Dyslipidemia: A Continuous Dose-Response Meta-Analysis of Randomized Controlled Trials.
Wang, T, Zhang, X, Zhou, N, Shen, Y, Li, B, Chen, BE, Li, X
Journal of the American Heart Association. 2023;12(11):e029512
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Dyslipidaemia is considered to be a risk factor for cardiovascular disease (CVD) and the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are thought to confer benefits for both dyslipidaemia and CVD, although results from clinical trials and meta-analyses (studies pooling data from smaller studies to increase statistical power) are mixed. The aim of this meta-analysis, using a particular statistical method, was to evaluate whether dose-response relationships may be non-linear. This meta-analysis included 90 randomised controlled trials with 72,598 participants overall. Lipids evaluated were triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and non-HDL cholesterol. A near linear relationship was seen between intake of combined EPA and DHA and a decrease in TG and non-HDL, both overall and for the subgroups of patients with and without hyperlipidaemia and overweight. For LDL and HDL, J-shaped relationships were seen, with an increase followed by a decrease with increasing EPA + DHA intake, both overall and in the subgroups with and without hyperlipidaemia. The authors also pooled data from studies which used the red blood cell omega index (a measure of omega-3 status) and found that with increasing omega-3 status, TG and non-HDL declined whilst HDL increased in a near linear fashion, whilst there was still a J-shaped curve for LDL. The authors consider that a medium dose of EPA + DHA may be needed for the management of dyslipidaemia, and a high dose for people at high risk of developing CVD.
Abstract
Background Previous results provide supportive but not conclusive evidence for the use of omega-3 fatty acids to reduce blood lipids and prevent events of atherosclerotic cardiovascular disease, but the strength and shape of dose-response relationships remain elusive. Methods and Results This study included 90 randomized controlled trials, reported an overall sample size of 72 598 participants, and examined the association between omega-3 fatty acid (docosahexaenoic acid, eicosapentaenoic acid, or both) intake and blood lipid changes. Random-effects 1-stage cubic spline regression models were used to study the mean dose-response association between daily omega-3 fatty acid intake and changes in blood lipids. Nonlinear associations were found in general and in most subgroups, depicted as J-shaped dose-response curves for low-/high-density lipoprotein cholesterol. However, we found evidence of an approximately linear dose-response relationship for triglyceride and non-high-density lipoprotein cholesterol among the general population and more evidently in populations with hyperlipidemia and overweight/obesity who were given medium to high doses (>2 g/d). Conclusions This dose-response meta-analysis demonstrates that combined intake of omega-3 fatty acids near linearly lowers triglyceride and non-high-density lipoprotein cholesterol. Triglyceride-lowering effects might provide supportive evidence for omega-3 fatty acid intake to prevent cardiovascular events.
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Effect of sleep duration on dietary intake, desire to eat, measures of food intake and metabolic hormones: A systematic review of clinical trials.
Soltanieh, S, Solgi, S, Ansari, M, Santos, HO, Abbasi, B
Clinical nutrition ESPEN. 2021;45:55-65
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Adequate sleep is crucial to health. Yet, sleep disturbances have become very common in modern societies. A lack of sleep is linked to increased risk for several chronic diseases such as diabetes, high blood pressure, metabolic syndrome and cardiovascular disease. Furthermore, appetite-regulating hormones can be disrupted by sleep shortages, which is thought to drive chronic overeating, leading to weight gain, obesity and its associated health consequences. This review examined the relationship between sleep duration and food consumption and energy intake, whilst also monitoring changes in body weight and appetite-regulating hormones. The review encompassed 50 randomized controlled trials (RCTs) with 3387 participants, including 1079 children and adolescents and 2308 adults. The findings suggested that sleep shortages contribute to significant increases in calorie intake, fat intake, increased body weight, appetite, hunger, more frequent eating and bigger portion sizes. In this review lack of sleep did not change protein and carbohydrate intake. Nor did lack of sleep make people exert more or less energy overall, however, a variance amongst ethnic groups was observed here. There was not enough evidence for changes in metabolic rate, so the review assumed no significant effect. When viewed collectively, the appetite-regulating hormones of leptin and ghrelin, the stress hormone cortisol and the sugar-regulating hormone insulin were not significantly influenced by sleep duration. However, there seemed to be a wide variance of outcomes when looking at individual studies' results. In conclusion, the authors reiterated the importance of sleep for health maintenance, advocating for a minimum of 7 hours of sleep per day for adults and that, despite busy modern lifestyles, sleep optimisation strategies should be prioritised. Less than 6 hours of sleep per day increases the risk of health consequences, like weight gain and metabolic disorders and sleep management should be considered part of their treatment protocols.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Reduced sleep duration may serve as a mediator for weight gain in part due to increased appetite, increased fat intake and disruptions to energy balance.
- Enhancing sleep quality may serve to support weight loss protocols.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
Short sleep duration and disruptions to circadian rhythm have been associated with being overweight and obese. It has been suggested that sleep restriction may interfere with appetite regulating hormones leading to increased appetite and disrupted energy balance.
This study aimed to systematically review studies exploring the relationship between sleep duration and food consumption, energy intake, anthropometric characteristics and appetite-regulating hormones.
Methods
This systematic review included 50 randomised controlled trials including 3,387 participants.
Results
Energy intake
- 13 out of 30 the included studies found that short sleep conditions led to higher energy intake.
- 1 study identified that sleep restriction resulted in a 15.3% and 9.2% increase in energy intake in both women and men.
- 3 studies noted that prolonging sleep duration led to a reduction in energy intake.
- 1 study reported a reduction in energy intake after sleep restriction (P=0.031).
Fat consumption
- 9 studies out of 22 identified a significant association between short sleep and increased fat consumption.
- 7 studies did not identify a difference between groups.
- 3 studies noted a decrease in fat consumption following prolonged sleep (P<0.001, P<0.05, P=0.04).
Hunger and appetite
- 11 studies out of 17 observed that sleep restriction resulted in increased hunger ratings.
- 3 studies found an increase in appetite following sleep restriction (P<0.01) with 3 finding no difference..
- 1 study reported a decrease in appetite following sleep restriction.
- 2 studies noted that portion sizes increased as a result of sleep restriction (P<0.01).
- 1 study reported an increase in eating occasions following restricted sleep compared to habitual sleep (6.08 vs 4.96).
Body weight
- 6 studies out of 14 found no effect of sleep loss on body weight.
- 4 studies identified that sleep restriction led to weight gain (P<0.001, P<0.05, P=0.14, P=0.031).
- 2 studies reported weight loss following increased sleep duration (P<0.001).
Ghrelin and leptin
- Leptin and ghrelin levels were generally not found to be influenced by sleep duration, with the exception of a few studies.
Clinical practice applications:
Reduced sleep duration may promote weight gain by:
- Increasing energy intake.
- Increasing fat consumption.
- Increasing hunger and appetite.
- Increasing portion sizes and eating occasions.
Prolonging sleep duration may support weight loss by:
- Reducing energy intake.
- Reducing fat intake.
Considerations for future research:
- Mixed results on the influence of sleep restriction on appetite regulating hormones, leptin and ghrelin.
- Some studies noted the negative impact of sleep restriction on leptin and ghrelin concentrations, collectively shortened sleep duration did not appear to influence these hormones.
- Further sleep restriction studies exploring additional appetite regulating hormones and neuropeptides and the reward system may provide a more definitive understanding of the underlying mechanism for reduced sleep duration to disrupt the appetite and energy balance and promote weight gain.
Abstract
BACKGROUND AND AIMS Sleep, as well as diet and physical activity, plays a significant role in growth, maturation, health, and regulation of energy homeostasis. Recently, there is increasing evidence indicating a possible causal association between sleep duration and energy balance. We aimed to examine the relationship between sleep duration and food consumption, energy intake, anthropometric characteristics, and appetite-regulating hormones by randomized controlled trials (RCTs). METHODS Electronic literature searches were conducted on Medline, Web of Science, and Google Scholar until July 2020. The search was conducted with the following words: "Sleep Duration", "Circadian Rhythm", "Sleep Disorders" in combination with "Obesity", "Overweight", "Abdominal Obesity", "Physical Activity", "Energy Intake", "Body Mass Index", "Lipid Metabolism", "Caloric Restriction", Leptin, "Weight Gain", and "Appetite Regulation" using human studies.methods RESULTS After screening 708 abstracts, 50 RCTs (7 on children or adolescents and 43 on adults) were identified and met the inclusion criteria. In general, the findings suggested that sleep restriction may leads to a significant increment in energy intake, fat intake, body weight, appetite, hunger, eating occasions, and portion size, while protein and carbohydrate consumption, total energy expenditure, and respiratory quotient remained unaffected as a result of sleep restriction. Serum leptin, ghrelin, and cortisol concentrations were not influenced by sleep duration as well. CONCLUSION Insufficient sleep can be considered as a contributing factor for energy imbalance, weight gain, and metabolic disorders and it is suggested that to tackle disordered eating it may be necessary to pay more attention to sleep duration.
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The benefits and risks of beetroot juice consumption: a systematic review.
Zamani, H, de Joode, MEJR, Hossein, IJ, Henckens, NFT, Guggeis, MA, Berends, JE, de Kok, TMCM, van Breda, SGJ
Critical reviews in food science and nutrition. 2021;61(5):788-804
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This review examined the health benefits and risks associated with beetroot juice (BRJ) from 86 studies. The nitrate contained in high amounts in BRJ increases nitric oxide (NO) levels in the body. NO has vasodilatory effects and thus reduces blood pressure and helps oxygen- and nutrient delivery to organs and muscles. Hence there has been an interest in BRJ for sports performance improvement and the prevention and treatment of cardiovascular disease. The review collected evidence of the effect of BRJ on the cardiovascular system and sports performance according to gender, trained and untrained individuals. Whilst the authors also briefly mention other health benefits of BRJ. From wider research, it is known that excess nitrate can form carcinogenic N-nitroso compounds (NOCs) in the body. Yet little is known whether this could also be a potential risk with BRJ consumption since vegetable consumption and many plant compounds generally appear to reduce the risk of cancers and can block the formation of NOCs. Hence the authors concluded that more research is needed to ensure that currently suggested dosages for BRJ do not aid NOCs production. In summary, BRJ has a beneficial effect on nitric oxide levels, oxygen consumption, blood flow, platelet aggregation, heart rate, cardiac output, blood pressure, improves sports performance and endurance and could be valuable for the management of cardiovascular disease. Yet high levels of consumption may not come without risks and more studies are needed to assess safety.
Abstract
Beetroot juice (BRJ) has become increasingly popular amongst athletes aiming to improve sport performances. BRJ contains high concentrations of nitrate, which can be converted into nitric oxide (NO) after consumption. NO has various functions in the human body, including a vasodilatory effect, which reduces blood pressure and increases oxygen- and nutrient delivery to various organs. These effects indicate that BRJ may have relevant applications in prevention and treatment of cardiovascular disease. Furthermore, the consumption of BRJ also has an impact on oxygen delivery to skeletal muscles, muscle efficiency, tolerance and endurance and may thus have a positive impact on sports performances. Aside from the beneficial aspects of BRJ consumption, there may also be potential health risks. Drinking BRJ may easily increase nitrate intake above the acceptable daily intake, which is known to stimulate the endogenous formation of N-nitroso compounds (NOC's), a class of compounds that is known to be carcinogenic and that may also induce several other adverse effects. Compared to studies on the beneficial effects, the amount of data and literature on the negative effects of BRJ is rather limited, and should be increased in order to perform a balanced risk assessment.
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Effect of Hesperidin on Cardiovascular Disease Risk Factors: The Role of Intestinal Microbiota on Hesperidin Bioavailability.
Mas-Capdevila, A, Teichenne, J, Domenech-Coca, C, Caimari, A, Del Bas, JM, Escoté, X, Crescenti, A
Nutrients. 2020;12(5)
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Cardiovascular diseases (CVDs) cause around 31% of all deaths worldwide. Certain dietary patterns have been associated with a reduction in CVDs and so the use of natural-based products has gained importance as a preventive strategy. Hesperidin is a bioactive compound found in high levels in citrus fruits. The reported beneficial properties include antitumor, antioxidant, anti-inflammatory; cholesterol and glucose lowering effects. Many animal studies show multiple beneficial effects but are inconclusive in human studies. The aim of this review is to describe the effects of hesperidin on CVD factors and to highlight the individual differences in its bioavailability and effectiveness. The gut bacteria play an important role in this. Hesperidin is not broken down by the normal digestive process and reaches the colon largely intact. It is the job of the gut bacteria to break it down into bioavailable substances that can be absorbed and utilised. The discrepancies observed in some of the results from human clinical trials may be partly due to individual differences, including that of the gut bacteria. Further clinical trials should be considered as well as classifying individuals according to individual differences in metabotypes.
Abstract
Recently, hesperidin, a flavonone mainly present in citrus fruits, has emerged as a new potential therapeutic agent able to modulate several cardiovascular diseases (CVDs) risk factors. Animal and in vitro studies demonstrate beneficial effects of hesperidin and its derived compounds on CVD risk factors. Thus, hesperidin has shown glucose-lowering and anti-inflammatory properties in diabetic models, dyslipidemia-, atherosclerosis-, and obesity-preventing effects in CVDs and obese models, and antihypertensive and antioxidant effects in hypertensive models. However, there is still controversy about whether hesperidin could contribute to ameliorate glucose homeostasis, lipid profile, adiposity, and blood pressure in humans, as evidenced by several clinical trials reporting no effects of treatments with this flavanone or with orange juice on these cardiovascular parameters. In this review, we focus on hesperidin's beneficial effects on CVD risk factors, paying special attention to the high interindividual variability in response to hesperidin-based acute and chronic interventions, which can be partly attributed to differences in gut microbiota. Based on the current evidence, we suggest that some of hesperidin's contradictory effects in human trials are partly due to the interindividual hesperidin variability in its bioavailability, which in turn is highly dependent on the α-rhamnosidase activity and gut microbiota composition.
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Vitamin B12 Status Upon Short-Term Intervention with a Vegan Diet-A Randomized Controlled Trial in Healthy Participants.
Lederer, AK, Hannibal, L, Hettich, M, Behringer, S, Spiekerkoetter, U, Steinborn, C, Gründemann, C, Zimmermann-Klemd, AM, Müller, A, Simmet, T, et al
Nutrients. 2019;11(11)
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Veganism is growing in western societies and with it comes an increased risk of vitamin B12 deficiency which is principally found in animal products. Vitamin B12 is essential for multiple biological functions including DNA synthesis, digestive function and detoxification processes. It can take 2-5 years to exhaust natural stores of B12 within the body so deficiency risk is considered safe. This 2017 randomised control trial compared vitamin B12 status in 53 healthy omnivore subjects with 26 participants following an unsupplemented vegan diet for 4 weeks and the remaining 27 participants a meat-rich diet. The aim of the study was to answer two questions; (a) Do vitamin B12 markers respond to short-term dietary intervention with a meat-rich or a plant-based diet? and (b) Do meat-rich and vegan diets have an impact on plasma markers of inflammation and cardiovascular disease? Blood and urine samples were taken before and after the 4-week dietary protocol to also measure vitamin D status, Folate and Homocysteine levels as a marker for inflammation. The serum vitamin B12 levels (indicative of dietary B12) dropped significantly from 362.9 +/- 110.9 ng/mL to 296.1 +/- 94.1 ng/mL in the Vegan Diet group (p < 0.001) and remained stable in the Meat Diet group. Other markers measuring cellular B12 metabolism did not significantly vary. The short-term nature of the trial demonstrated rapid decrease in holo-TC, the bioactive form of vitamin B12 in plasma. The other blood and urinary markers demonstrated benefits to plant-based eating including reduced cholesterol intake and adequate profiles of nutrient and micronutrient status.
Abstract
Vegans are at an increased risk for certain micronutrient deficiencies, foremost of vitamin B12. Little is known about the short-term effects of dietary change to plant-based nutrition on vitamin B12 metabolism. Systemic biomarkers of vitamin B12 status, namely, serum vitamin B12 and holotranscobalamin, may respond quickly to a reduced intake of vitamin B12. To test this hypothesis, 53 healthy omnivore subjects were randomized to a controlled unsupplemented vegan diet (VD, n = 26) or meat-rich diet (MD, n = 27) for 4 weeks. Vitamin B12 status was examined by measurement of serum vitamin B12, holotranscobalamin (holo-TC), methylmalonic acid (MMA) and total plasma homocysteine (tHcy). Holo-TC decreased significantly in the VD compared to the MD group after four weeks of intervention, whereas metabolites MMA and tHcy were unaffected. Body weight remained stable in both groups. VD intervention led to a significant reduction of cholesterol intake, and adequate profiles of nutrient and micronutrient status. Lower intake of vitamin B12 was observed in VD, which was mirrored by a lower concentration of serum vitamin B12 and reduced holo-TC after 4 weeks. Plasma holo-TC may be a fast-responding biomarker to monitor adequate supply of vitamin B12 in plant-based individuals.
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Sorting out the Value of Cruciferous Sprouts as Sources of Bioactive Compounds for Nutrition and Health.
Abellán, Á, Domínguez-Perles, R, Moreno, DA, García-Viguera, C
Nutrients. 2019;11(2)
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Vegetable sprouts are naturally rich in nutrients and other beneficial compounds. The sprouts of cruciferous vegetables, such as broccoli, kale, radish and pak choi, stand out due to their high contents of glucosinolates and phenolic compounds. The aim of this review was to compile and update the available knowledge on the production, nutritional composition, and health benefits of cruciferous sprouts. A number of studies have found that compounds found in cruciferous sprouts have anti-cancer, anti-inflammatory, and antioxidant capacities. Consumption of cruciferous sprouts contributes to healthy glucose, insulin and fat levels in the blood, and may be beneficial for the treatment of some metabolic disorders, such as type 2 diabetes. There is evidence that compounds in cruciferous sprouts are a useful tool for enhancing phase II enzymes in the liver, and benefit levels of interleukine-6, C-reactive protein, and tumour necrosis factor-α, and inhibition of NF-κB, among others. The active compounds in these sprouts have an influence on several cardiovascular processes, potentially reducing the risk of several diseases. The lack of consistency between studies with regard to sampling schedules, doses, sample size, etc. means that it is not possible at this time to state the effective dose of sprouts or their active compounds needed in order to achieve health benefits. Further research is needed in this area.
Abstract
Edible sprouts with germinating seeds of a few days of age are naturally rich in nutrients and other bioactive compounds. Among them, the cruciferous (Brassicaceae) sprouts stand out due to their high contents of glucosinolates (GLSs) and phenolic compounds. In order to obtain sprouts enriched in these phytochemicals, elicitation is being increasing used as a sustainable practice. Besides, the evidence regarding the bioavailability and the biological activity of these compounds after their dietary intake has also attracted growing interest in recent years, supporting the intake of the natural food instead of enriched ingredients or extracts. Also, there is a growing interest regarding their uses, consumption, and applications for health and wellbeing, in different industrial sectors. In this context, the present review aims to compile and update the available knowledge on the fundamental aspects of production, enrichment in composition, and the benefits upon consumption of diverse edible cruciferous sprouts, which are sources of phenolic compounds and glucosinolates, as well as the evidence on their biological actions in diverse pathophysiological situations and the molecular pathways involved.
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Treatment of Obesity: Weight Loss and Bariatric Surgery.
Wolfe, BM, Kvach, E, Eckel, RH
Circulation research. 2016;118(11):1844-55
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Individuals with obesity who have been unable to lose weight through non-surgical means may be candidates for bariatric surgery. Criteria was established over 20 years ago and stated that individuals with a BMI >40 and individuals with a BMI >35-40 with other related conditions who have failed to achieve weight loss medically, are appropriate for surgery. However, individuals with less severe obesity who have type 2 diabetes have now been highlighted as possible candidates also, indicating that it is an evolving process. This review of 123 papers focused on the indications, safety and reasons for bariatric surgery and its role in the reduction of heart disease. The reason for bariatric surgery is to achieve weight loss and decrease an individual’s risk of death and conditions associated with obesity. Indications for surgery were discussed and the types of surgery that are available. Safety has improved due to a number of changes such as recognition of experience of surgeons and centres, the enactment of care protocols and a switch to minimally invasive procedures. However less invasive surgeries appear to accomplish considerably less weight loss. Benefits to body fat, blood fat levels, high blood pressure, diabetes, non-alcoholic fatty liver disease, inflammation, the ability of the blood vessels to dilate and sleep apnoea were all discussed. These were all used as evidence to support the argument that surgery improves an individual’s chances of survival compared to lifestyle interventions, as sufficiently designed trials to support this have not been performed. It was concluded that bariatric surgery has greater improved heart disease and death compared to lifestyle interventions due to the significantly higher weight loss that results.
Abstract
This review focuses on the mechanisms underlying, and indications for, bariatric surgery in the reduction of cardiovascular disease (CVD), as well as other expected benefits of this intervention. The fundamental basis for bariatric surgery for the purpose of accomplishing weight loss is the determination that severe obesity is a disease associated with multiple adverse effects on health, which can be reversed or improved by successful weight loss in patients who have been unable to sustain weight loss by nonsurgical means. An explanation of possible indications for weight loss surgery as well as specific bariatric surgical procedures is presented, along with review of the safety literature of such procedures. Procedures that are less invasive or those that involve less gastrointestinal rearrangement accomplish considerably less weight loss but have substantially lower perioperative and longer-term risk. The ultimate benefit of weight reduction relates to the reduction of the comorbidities, quality of life, and all-cause mortality. With weight loss being the underlying justification for bariatric surgery in ameliorating CVD risk, current evidence-based research is discussed concerning body fat distribution, dyslipidemia, hypertension, diabetes mellitus, inflammation, obstructive sleep apnea, and others. The rationale for bariatric surgery reducing CVD events is discussed and juxtaposed with impacts on all-cause mortalities. Given the improvement of established obesity-related CVD risk factors after weight loss, it is reasonable to expect a reduction of CVD events and related mortality after weight loss in populations with obesity. The quality of the current evidence is reviewed, and future research opportunities and summaries are stated.
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Garlic: a review of potential therapeutic effects.
Bayan, L, Koulivand, PH, Gorji, A
Avicenna journal of phytomedicine. 2014;4(1):1-14
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Garlic has been used throughout history, across many different cultures, for its therapeutic effects in supporting cardiovascular diseases, blood glucose dysregulation, and for anti-tumour and anti-microbial properties. Garlic (Allium sativum L.) use is thought to date as far back as the sixth century BC and has subsequently popped up in ancient Greek, Egyptian, Indian and Chinese medicines. This 2013 review looked at evidence to support the therapeutic effects of garlic, and its principal bioactive compound allicin. The authors reviewed clinical studies from the 1960’s through to 2012 and garlic was shown to reduce systolic blood pressure, prevent atherosclerosis, reduce serum cholesterol, LDL and triglycerides in doses ranging from 200 - 960 mg daily. The allylsulfide derivatives in garlic are attributed to its anti-cancer properties with studies showing garlic has a variety of anti-tumour effects, including tumour cell growth inhibition and chemopreventive effects. Garlic has also been shown to have therapeutic effect at reducing fasting blood glucose levels in diabetic patients. Garlic’s antimicrobial uses date back to Louis Pasteur when it was shown to be effective against multiple bacterial strains including Salmonella, Escherichia coli, Klebsiella, and Helicobacter as it is capable of inhibiting sulfhydryl enzymes. Garlic also displays some anti-fungal and anti-viral properties however there are few studies which explore these mechanisms. Anecdotal evidence suggests it reduces the duration of the common cold and aids respiration. The review offers little evidence of dosing or therapeutic efficacy.
Abstract
Throughout history, many different cultures have recognized the potential use of garlic for prevention and treatment of different diseases. Recent studies support the effects of garlic and its extracts in a wide range of applications. These studies raised the possibility of revival of garlic therapeutic values in different diseases. Different compounds in garlic are thought to reduce the risk for cardiovascular diseases, have anti-tumor and anti-microbial effects, and show benefit on high blood glucose concentration. However, the exact mechanism of all ingredients and their long-term effects are not fully understood. Further studies are needed to elucidate the pathophysiological mechanisms of action of garlic as well as its efficacy and safety in treatment of various diseases.