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September 21, 2010

Garlic Can Heal the Brain—and It Has Other Health Benefits

Sometime yesterday, Ramesh Bjonnes posted an article here at the Elephant entitled, “Why Garlic Is a Brain Toxin!” I eat a lot of garlic, and I regularly recommend it to my clients for controlling cholesterol, boosting the immune system, and even for increasing testosterone levels in aging men. So I figured I’d better read the post.

I did. And then I did a Google Scholar search for “sulphone hydroxyl ion,” which is the constituent the author said causes brain toxicity. Nothing came up – I mean, like, zero. That’s rare for anything that actually exists in the world. What this means is that no scholar or scholarly journal, magazine, or web site has ever mentioned this substance. In general, that would mean it does not exist.

So then I did a Google Scholar search for “garlic, brain, toxicity,” assuming that if garlic is in any way toxic to the brain, someone would have noticed that by now (garlic is a widely studied subject). I did not find anything that suggests garlic is toxic to the brain, but many articles have looked at the ways in which garlic can remove other toxins from the brain, and maybe even stop neuronal apoptosis (neuron death). In general, garlic (especially in very high doses, most commonly as an aged garlic supplement, which makes it more stable – beyond what one might get in the diet) is neuro-protective, anti-cancer (including its possible use to prevent Alzheimer’s Disease and other neuro-degenerative disorders), and may extend the life span of cells, and therefore, of us.

Each of the following is an open-source, academic, peer-reviewed study (you can read the whole study at the link):

Mechanisms of Inhibition of Chemical Toxicity and Carcinogenesis by Diallyl Sulfide (DAS) and Related Compounds from Garlic

Chung S. Yang, Saranjit K. Chhabra, Jun-Yan Hong and Theresa J. Smith

Laboratory for Cancer Research, College of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854-8020

ABSTRACT

Diallyl sulfide (DAS) is a flavor compound derived from garlicand is sequentially converted to diallyl sulfoxide (DASO) anddiallyl sulfone (DASO2) by cytochrome P450 2E1 (CYP2E1). These compoundshave been shown to reduce the incidence of a multitude of chemicallyinduced tumors in animal models. The impediment of phase I activationof these carcinogens is hypothesized to be accountable for thereduction in tumor incidence. Indeed, DAS, DASO and DASO2 arecompetitive inhibitors of CYP2E1. DASO2, in addition, is a suicideinhibitor of CYP2E1. These compounds have been shown to reducecarbon tetrachloride-, N-nitrosodimethylamine- and acetaminophen-induced toxicityin rodents. All three chemicals are substrates for CYP2E1. The protectiveeffect was observed when the organosulfur compounds were givenbefore, during or soon after chemical treatment. DAS and DASO2inhibited the bioactivation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone(NNK) and related lung tumorigenesis in A/J mice. Because CYP2E1does not play a key role in NNK activation, the inhibition ofother CYP enzymes active in NNK metabolism is likely. DAS alsohas been shown to induce other CYP and phase II enzymes as wellas decrease hepatic catalase activity. All of these effectsare observed at concentrations much higher than what is normallyingested by humans. The biological activities of garlic and itsrelated compounds at lower concentrations that mimic human consumptionremain to be studied further.

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Antioxidant Health Effects of Aged Garlic Extract

Carmia Borek

Department of Community Health and Family Medicine, Nutrition and Infectious Diseases Unit, Tufts University School of Medicine, Boston, MA 02111

ABSTRACT

Oxidative modification of DNA, proteins and lipids by reactiveoxygen species (ROS) plays a role in aging and disease, including cardiovascular,neurodegenerative and inflammatory diseases and cancer. Extractsof fresh garlic that are aged over a prolonged period to produceaged garlic extract (AGE) contain antioxidant phytochemicals thatprevent oxidant damage. These include unique water-soluble organosulfurcompounds, lipid-soluble organosulfur components and flavonoids,notably allixin and selenium. Long-term extraction of garlic(up to 20 mo) ages the extract, creating antioxidant properties bymodifying unstable molecules with antioxidant activity, suchas allicin, and increasing stable and highly bioavailable water-solubleorganosulfur compounds, such as S-allylcysteine and S-allylmercaptocysteine.AGE exerts antioxidant action by scavenging ROS, enhancing thecellular antioxidant enzymes superoxide dismutase, catalaseand glutathione peroxidase, and increasing glutathione in thecells. AGE inhibits lipid peroxidation, reducing ischemic/reperfusiondamage and inhibiting oxidative modification of LDL, thus protectingendothelial cells from the injury by the oxidized molecules,which contributes to atherosclerosis. AGE inhibits the activationof the oxidant-induced transcription factor, nuclear factor(NF)-B, which has clinical significance in human immunodeficiencyvirus gene expression and atherogenesis. AGE protects DNA againstfree radical–mediated damage and mutations, inhibits multistepcarcinogenesis and defends against ionizing radiation and UV-induceddamage, including protection against some forms of UV-inducedimmunosuppression. AGE may have a role in protecting againstloss of brain function in aging and possess other antiagingeffects, as suggested by its ability to increase cognitive functions,memory and longevity in a senescence-accelerated mouse model.AGE has been shown to protect against the cardiotoxic effectsof doxorubicin, an antineoplastic agent used in cancer therapyand against liver toxicity caused by carbon tetrachloride (anindustrial chemical) and acetaminophen, an analgesic. Substantialexperimental evidence shows the ability of AGE to protect againstoxidant-induced disease, acute damage from aging, radiationand chemical exposure, and long-term toxic damage. Althoughadditional observations are warranted in humans, compellingevidence supports the beneficial health effects attributed toAGE, i.e., reducing the risk of cardiovascular disease, stroke,cancer and aging, including the oxidant-mediated brain celldamage that is implicated in Alzheimer’s disease.

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For this next one, I’m posting the whole introduction since it covers so many of the research findings on the health benefits of garlic.

Garlic Reduces Dementia and Heart-Disease Risk

Carmia Borek

Department of Public Health and Family Medicine, Tufts University School of Medicine, Boston, MA 02111

ABSTRACT

Risk factors for cardiovascular disease, including high cholesterol,high homocysteine, hypertension and inflammation, increase therisk of dementia, including its most common form, Alzheimer’sdisease (AD). High cholesterol is also associated with elevatedß-amyloid (Abeta), the hallmark of AD. Oxidative damageis a major factor in cardiovascular disease and dementia, diseaseswhose risk increases with age. Garlic, extracted and aged toform antioxidant-rich aged garlic extract (AGE or Kyolic), mayhelp reduce the risk of these diseases. AGE scavenges oxidants,increases superoxide dismutase, catalase, glutathione peroxidase,and glutathione levels, and inhibits lipid peroxidation andinflammatory prostaglandins. AGE reduces cholesterol synthesisby inhibiting 3-hydroxy-3-methylglutaryl-CoA reductase and isadditive with statins in its action. Inhibition of cholesterol,LDL oxidation, and platelet aggregation by AGE, inhibits arterialplaque formation; AGE decreases homocysteine, lowers blood pressure,and increases microcirculation, which is important in diabetes,where microvascular changes increase heart disease and dementiarisks. AGE also may help prevent cognitive decline by protectingneurons from Abeta neurotoxicity and apoptosis, thereby preventingischemia- or reperfusion-related neuronal death and improvinglearning and memory retention. Although additional observationsare warranted in humans, compelling evidence supports the beneficialhealth effects attributed to AGE in helping prevent cardiovascularand cerebrovascular diseases and lowering the risk of dementiaand AD.

INTRODUCTION

Recent evidence suggests that midlife risk factors for cardiovasculardisease, such as high cholesterol, hypertension, high homocysteine,and inflammation, are important risk factors for dementia inlater years (15), with high cholesterol and hypertensionshowing a consistent association with increased risk of Alzheimer’sdisease (AD)4 and vascular dementia, pathological conditionswhose frequency increases with age.

High cholesterol levels promote the formation of atheroscleroticplaques that are risk factors for both heart attacks and stroke,in the latter case the resulting ischemia may result in neuronaldeath and lead to dementia. High cholesterol is also associatedwith increased levels of free-radical–producing ß-amyloidpeptides (Abeta), the hallmark of AD. Hypertension may contributeto cognitive decline seen in AD by causing cerebral small-vesselpathology and increasing the number of neurofibrilar tanglesand amyloid plaques. Small-vessel disease resulting from hypertensionmay be associated with the observed atrophy of the hippocampusand amygdala in AD (6).

Elevated plasma homocysteine (hyperhomocysteinemia) is an independentrisk factor for cardiovascular disease, stroke, and dementia,including AD (7,8). Studies on people 65 y and older and onyoung people ages 4–18 show that plasma levels of homocysteineincrease progressively with age, posing a serious threat forthese diseases in aging individuals. Hyperhomocysteinemia iscaused largely by deficiencies in vitamins B-6, B-12, and folate.The adverse vascular and neurotoxic effects of homocysteineare associated with oxidant stress; homocysteine impairs DNArepair in the hippocampus, sensitizing neurons to amyloid toxicity(9).

Reactive oxygen species. Reactive oxygen species and oxidant stress are implicated incardiovascular disease, cancer, and various forms of dementiaincluding AD (10). Oxidative damage to DNA, proteins, lipids,and other molecules rank high as a major cause in the onsetand development of these diseases. Reactive oxygen species,including free radicals, are by-products of normal metabolismand increase during infection and inflammation, hyperhomocysteinemia,and exposure to exogenous sources, including nitrous oxide metabolitepollutants, smoking, certain drugs (e.g., acetaminophen), andradiation.

Oxidative modification of LDL cholesterol increases the riskof atherosclerosis, cardiovascular, and cerebrovascular disease.Free radical–producing Abeta triggers neuronal apoptosis,increasing the risk of brain atrophy and dementia, includingAD, its most common form (11).

Garlic antioxidants. Garlic ranks highly among foods that help prevent disease, largelydue to its high content of organosulfur compounds and antioxidantactivity. Fresh garlic, however, may cause indigestion, andits pungent odor that lingers on the breath and skin can bea social deterrent. These disagreeable effects of fresh garlicare due to allicin, an oxidant released upon cutting or chewingthe clove.

Aged garlic extract. An alternative source of garlic that is odorless and rich inantioxidants is aged garlic extract (AGE) (12,13). The well-standardizedand highly bioavailable supplement is produced by prolongedextraction and aging of organic fresh garlic at room temperature.The process converts unstable compounds, such as allicin, tostable substances and produces high levels of water-solubleorganosulfur compounds that are powerful antioxidants. Theseinclude S-allylcysteine (SAC), AGE’s major component, and S-allylmercaptocysteine,unique to AGE. Among other compounds present are low amountsof oil-soluble organosulfur compounds, flavonoids, a phenol,allixin, selenium, and saponins.

AGE and cardiovascular disease. AGE has been shown to modulate cardiovascular risk factors inboth clinical and preclinical settings (1423). AGE hasbeen shown to reduce blood pressure, inhibit platelet aggregationand adhesion, lower LDL and elevate HDL cholesterol, reducesmoking-related oxidative damage, inhibit the production ofprostaglandins involved in inflammation, and lower homocysteine.SAC has been found to lower cholesterol by deactivating 3-hydroxy-3-methylglutaryl-CoAby as much as 41% (15). AGE efficacy in reducing cholesterolsynthesis is additive with statins, which inhibit 3-hydroxy-3-methylglutaryl-CoAreductase at a transcriptional level. Other possible contributorsto protection against cardiovascular disease and dementia arethe effects of AGE in increasing microcirculation (21) and protectingendothelial cells from oxidative damage, a factor most importantin diabetes where the microvasculature is damaged, and the riskof dementia is high. AGE can also temporarily increase, by 30–40%(23), the synthesis of constitutive nitric oxide, a protectivefactor against myocardial ischemic or reperfusion injury, riskfactors in cardiovascular disease and dementia following stroke(24). AGE has been found to inhibit the progression of coronary-arterycalcification (25), thus reducing the risk of a myocardial infarct.

AGE and the heart-dementia risk link: neuroprotective effects. The broad range of cardiovascular protection afforded by AGEmay be extended to a protective effect on the brain, helpingreduce the risk of dementia, including vascular dementia andAD. AGE has potential to protect the brain against neurodegenerativeconditions. Mechanisms include lowering cholesterol, inhibitinginflammation, reducing homocysteine, preventing oxidative braininjury following ischemia, protecting neuronal cells againstapoptosis (a programmed cell suicide triggered by oxidativestress) by inhibiting caspase 3, and preventing Abeta-inducedneurotoxicity.

Homocysteine. People with cardiovascular risk factors and a history of strokeshave an increased risk of both vascular dementia (arterioscleroticdementia), which can occur after a stroke, and AD, the mostcommon form of progressive dementia, accounting for over 70%of all cases.

Elevated homocysteine damages endothelial cells that line bloodvessels and induces thrombosis that can lead to heart attacksand stroke. Homocysteine produces breaks in DNA and inducesapoptosis, a major cause of neuronal death in dementia (79).The link between high levels of homocysteine and dementia, includingAD, has been observed in epidemiological studies and confirmedin case-control studies, where people with vascular dementiaand AD had higher levels of homocysteine than healthy people.A recent study (7) provided compelling evidence of a directlink between increased plasma homocysteine and loss of cognition,showing that in adults with intact cognition, an elevation inplasma homocysteine, over time, is associated with an increasedincidence of dementia, including AD.

Consumption of AGE has been shown to reduce homocysteine levels.In a preclinical study, levels of homocysteine in a 4-wk folate-deficientdiet containing AGE were compared with a folate-fortified dietcontaining AGE. Plasma homocysteine was 30% lower in the folate-deficientanimals that received AGE, but not in those with adequate folate.The results suggest that AGE may serve as an added treatmentin hyperhomocyteinemia (26). A clinical study, showing thatAGE inhibits the progression of coronary artery calcification,also showed a trend in lowering homocysteine levels (25).

Protection against ischemic or reperfusion adverse effects. Single ischemic or thromboembolic infarcts that occur in strategicareas of the brain hemispheres may cause a dementia-like syndrome;multiple temporally staggered small cerebral infarcts can giverise to progressive cognitive deficits and dementia. Areas ofthe brain supplied by small penetrating arterioles are especiallyprone to degenerative changes in patients with hypertensionand diabetes. Ischemia followed by reperfusion results in anincreased production of free radicals and oxidant stress thatmay lead to neuronal death by apoptosis and contribute to thedevelopment of dementia following stroke.

AGE has been shown to lower blood pressure and protect braincells from the deleterious effects of ischemia, increasing theirsurvival. The high antioxidant level in AGE helps prevent theoxidant damage that occurs during ischemia or reperfusion. Theprotective effects of AGE were observed in a preclinical studyof ischemia, and the findings showed that treatment with SACattenuated damaging reactive oxygen species and prevented braininjury, reducing infarct volume. None of the lipid-soluble compoundstested had a protective effect (27). SAC prevented neuronaldeath following ischemia and increased cell survival in thehippocampus, the memory region of the brain, by 30%, comparedwith controls (28).

Preventing neuronal apoptosis. The brain of an individual with AD exhibits extracellular plaquesof aggregated Abeta, intracellular neurofibrillary tangles thatcontain hyperphosphorylated tau protein and a loss of forebraincholinergic neurons that enervate the hippocampus and the neocortex.The accumulation of Abeta may trigger or contribute to neurodegeneration.Neuronal apoptosis, one of the characteristics of Alzheimer’sdisease, is associated with Abeta. Reactive oxygen species producedby Abeta are thought to play a role in the apoptotic mechanismof Abeta-mediated neurotoxicity.

Several routes lead to apoptotic cell death; a major route isthrough a mitochondrial- dependent pathway that results in therelease of cytochrome C, followed by the activation of caspases,with caspase-3 leading cells to their death (29). AGE and SAChave been shown in a number of in vitro studies to protect neuronalcells against Abeta toxicity and apoptosis (3034). Inone of the studies, PC12 cells exposed to Abeta showed a significantincrease in reactive oxygen species. Treatment with AGE andSAC suppressed the generation of reactive oxygen species andalso attenuated caspase-3 activation and DNA fragmentation,associated with apoptosis, and protected the cells against Abeta-inducedapoptosis. In another study AGE was found to inhibit caspase-3in a dose-dependent manner (33).

Caspase-3 catalyzes the formation of Abeta peptide (34) andis activated by Abeta (35). Their neurotoxic effects, however,appear to be independent; that is, in the presence of specificcaspase inhibitors, Abeta-induced neuronal death still occurredwith different morphological features (35). The findings thatAGE can inhibit Abeta toxicity, attenuate caspase-3 activation,and inhibit apoptosis enhances the potential of AGE as a neuroprotectoragainst AD.

Other anti-aging neuroprotective effects. Preclinical studies in models that are genetically prone toearly aging show that AGE has additional anti-aging effects(36,37). Treatment with AGE or SAC prevented the degenerationof the brain’s frontal lobe, improved learning and memory retention,and extended life span. Isolated neurons from the hippocampusarea, grown in the presence of AGE or SAC, showed an unusualability to grow and branch, which may be linked to the findingsthat AGE increases learning and cognition (37).

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Intake of Garlic and Its Bioactive Components

Harunobu Amagase, Brenda L. Petesch, Hiromichi Matsuura, Shigeo Kasuga and Yoichi Itakura

Department of Research and Development, Wakunaga of America Company, Mission Viejo, CA 92691 and; Institute for OTC Research, Wakunaga Pharmaceutical Company, Hiroshima 739-11, Japan

ABSTRACT

The health benefits of garlic likely arise from a wide varietyof components, possibly working synergistically. The complexchemistry of garlic makes it plausible that variations in processingcan yield quite different preparations. Highly unstable thiosulfinates,such as allicin, disappear during processing and are quicklytransformed into a variety of organosulfur components. The efficacyand safety of these preparations in preparing dietary supplementsbased on garlic are also contingent on the processing methodsemployed. Although there are many garlic supplements commerciallyavailable, they fall into one of four categories, i.e., dehydratedgarlic powder, garlic oil, garlic oil macerate and aged garlicextract (AGE). Garlic and garlic supplements are consumed inmany cultures for their hypolipidemic, antiplatelet and procirculatoryeffects. In addition to these proclaimed beneficial effects,some garlic preparations also appear to possess hepatoprotective,immune-enhancing, anticancer and chemopreventive activities.Some preparations appear to be antioxidative, whereas othersmay stimulate oxidation. These additional biological effects attributedto AGE may be due to compounds, such as S-allylcysteine, S-allylmercaptocysteine, N-fructosylarginine and others, formed during the extraction process. Althoughnot all of the active ingredients are known, ample researchsuggests that several bioavailable components likely contributeto the observed beneficial effects of garlic.

I did come across one article – Garlic as an antioxidant: the good, the bad and the ugly – that suggests whole garlic in high doses may have some toxicity for the liver, kidneys, and heart. Unfortunately, the article is not open-source [always lame when information is kept behind a pay-wall].

However, in following that rat trail, I did come across this article:

Clarifying the Real Bioactive Constituents of Garlic

Harunobu Amagase

Department of Research and Development, Wakunaga of America Co., Mission Viejo, CA 92691

ABSTRACT

Compounds in garlic work synergistically to produce variouseffects, but, because of garlic’s chemical complexity, processingmethods yield preparations with differing efficacy and safety.Although thiosulfinates such as allicin have been long misunderstoodto be active compounds due to their characteristic odor, itis not necessary for garlic preparations to contain such odorouscompounds to be effective, and they decompose and disappearduring any processing. Garlic exhibits hypolipidemic, antiplatelet,and procirculatory effects. It prevents cold and flu symptomsthrough immune enhancement and demonstrates anticancer and chemopreventiveactivities. In addition, aged garlic extract possesses hepatoprotective,neuroprotective, antioxidative activities, whereas other preparationsmay stimulate oxidation. Additional effects may be caused byS-allylcysteine, S-allyl mercaptocysteine), saponins, N-fructosylarginine, and other substances formed during a long-term extractionprocess. Although not all of active ingredients of garlic areknown, and allicin-like transient components are not directlyactive, ample research suggests that an allicin-free garlicpreparation that is standardized with a bioavailable componentsuch as S-allylcysteine, is active and various effects of garlicmay be attributed to it. Furthermore, various chemical constituentsin garlic products, including nonsulfur compounds such as saponins,may contribute to the essential biological activities of garlic.Further studies are needed to confirm their bioavailabilityand associated activities.

So, my advice? Get some whole garlic, press it, add it to some ground basil, and a little bit of extra virgin olive oil, with whatever other ingredients you like (maybe some Romano cheese), then slather some over the top of a grilled free-range chicken breast covered in melted Havarti cheese. Add some steamed asparagus, also covered with some pesto and grated cheese, and you have a really healthy dinner that is good for your heart, your immune system, and your brain.

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