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NUTRITION Metabolic Syndrome, Inflammation, and the Aging Process by Barry Sears, Ph.D. M UCH OF ANTI-AGING MEDlCtNE IS currently focused on hormonal replacement, especially those hormones that decrease with aging. How- ever, relatively little attention is placed on reducing the levels of honnones that increase with aging. In particular, the hor- mones associated with increased systemic inflammation are elevated levels of insulin and eieosanoids. The primary cause ofthe rise of these hormones is due to a condi- tion known as metabolic syndrome that is ultimately caused by the diet. Thus, a more appropriate description of anti-ag- ing medicine would be anti-inflammatory medieine and, therefore, frontline therapy for anti-aging becomes diet. Description of Metabolic Syndrome Metabolic syndrome is a cluster of chronic conditions associated with hyper- insulinemia. These include obesity, type 2 diabetes, heart disease, and hypertension. Sinee hyperinsulinemia is caused by in- sulin resistance, a better choice of terms to describe metabolic syndrome might be insulin resistance syndrome. Description of Insuiin Resitance Insulin resistance occurs when insulin is unable to transmit its hormonal signal to the interior of the cell. This occurs when the insulin binds to its receptor on the cell surface; but the transmission of biochemical signals that normally result from insulin's binding to its receptor is now degraded. The result is that there is a decreased ability to remove excess blood glucose from the bloodstream. The signal to release insulin from the pancreas is elevated blood glucose; the in- ability to reduce blood glucose levels due to insulin resistance forces the pancreas to secrete ever-higher levels of insulin creating hyperinsulinemia. Since insulin receptors are found in the liver, smooth muscle, and adipose tissues, the conse- quence of abnormal insulin signaling can have widespread negative metabolic consequences. Although the exact cause of insulin re- sistance remains to be elucidated, the most likely candidate is cellular inflammation and the resulting intracellular production of inflammatory cytokines such tumor necrosis factor (TNF). TNF primarily comes from immune cells sueh as macro- phages that infiltrate into inflamed tissues. And here is the irony; Inflammation is not only the underlying cause of insulin resis- tance, but the resulting hyperinsulinemia causes further increases in inflammatory mediators known as eieosanoids, and the cycle is amplifled. Effect of Hyperinsulinemia on Siient inflammation The type of inflammation that causes insulin resistance is below the threshold of perceived pain; hence the term silent inflammation. Sinee there is no pain as- sociated with silent inflammation, it can linger for years, if not decades, causing a continuing immunological assault on organs, until enough damage has been done to result in chronic disease. The primary diseases that are accelerated by silent inflammation include obesity, type 2 diabetes, heart disease, and hypertension. These are exactly the same conditions that cluster together in metabolic syndrome, and accelerate the aging process. Measuring Silent inflammation The first clinical marker discovered for silent inflammation was high sensitivity C-reactive protein (hs-CRP). However this particular marker is relatively crude and is easily increased by infection. A much more precise, and much earlier marker of the presence of silent inflam- mation is the ratio of two fatty acids in the bloodstream. One is arachidonic acid (AA) and the other is eicosapentaenoic acid (EPA). AA is an omega-6 fatty acid that is a building block for pro-inflam- matory eieosanoids, whereas EPA is an omega-3 fatty acid that is the building block for anti-inflammatory eieosanoids. The ratio of A A/EPA in the blood is in- dicative ofthe inflammatory potential of each ofthe 100 trillion cells in the body. The higher the AA/EPA ratio, the more systemic silent inflammation is taking plaee through the body, and the faster you age. System Consequences of Siient infiammation Now that silent inflammation can be measured, it becomes the best pos- sible early warning signal that aging is accelerating in the body. Since silent inflammation is systemic, this means that every organ of the body is under potential inflammatory assault and this leads to recruitment of macrophages into such inflamed organs. One ofthe conse- quences of this maerophage infiltration is EiCOSanoidS (eye.kah.sa.noids) were the first hormones developed by living organisms and are produced by every cell in your body. Although they might be considered to be primitive hormones, they control everything from your immune system to your brain to your heart. There are two kinds of eieosanoids, those that promote inflammation (pro-inflammatory) and tissue destruction and those that stop inflammation (anti-inflammatory) and promote healing. You need to have both kinds in the proper balance in order to be in a state of wellness. 50 The Atnerican Chiropractor A PRIL 2006 •n-ww.amchiropractor.com

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Page 1: Metabolic Syndrome, Inflammation, and the Aging Process Syndrome, Inflammation, and the... · Metabolic Syndrome, Inflammation, and the Aging Process by Barry Sears, Ph.D. M UCH OF

NUTRITION

Metabolic Syndrome, Inflammation,and the Aging Processby Barry Sears, Ph.D.

M UCH OF ANTI-AGING MEDlCtNE IS

currently focused on hormonalreplacement, especially those

hormones that decrease with aging. How-ever, relatively little attention is placedon reducing the levels of honnones thatincrease with aging. In particular, the hor-mones associated with increased systemicinflammation are elevated levels of insulinand eieosanoids. The primary cause oftherise of these hormones is due to a condi-tion known as metabolic syndrome thatis ultimately caused by the diet. Thus, amore appropriate description of anti-ag-ing medicine would be anti-inflammatorymedieine and, therefore, frontline therapyfor anti-aging becomes diet.

Description of MetabolicSyndrome

Metabolic syndrome is a cluster ofchronic conditions associated with hyper-insulinemia. These include obesity, type 2diabetes, heart disease, and hypertension.Sinee hyperinsulinemia is caused by in-sulin resistance, a better choice of termsto describe metabolic syndrome might beinsulin resistance syndrome.

Description of Insuiin ResitanceInsulin resistance occurs when insulin

is unable to transmit its hormonal signalto the interior of the cell. This occurswhen the insulin binds to its receptor onthe cell surface; but the transmission ofbiochemical signals that normally resultfrom insulin's binding to its receptor isnow degraded. The result is that there isa decreased ability to remove excess bloodglucose from the bloodstream.

The signal to release insulin from thepancreas is elevated blood glucose; the in-ability to reduce blood glucose levels dueto insulin resistance forces the pancreasto secrete ever-higher levels of insulincreating hyperinsulinemia. Since insulinreceptors are found in the liver, smoothmuscle, and adipose tissues, the conse-quence of abnormal insulin signalingcan have widespread negative metabolicconsequences.

Although the exact cause of insulin re-sistance remains to be elucidated, the mostlikely candidate is cellular inflammationand the resulting intracellular productionof inflammatory cytokines such tumornecrosis factor (TNF). TNF primarilycomes from immune cells sueh as macro-phages that infiltrate into inflamed tissues.And here is the irony; Inflammation is notonly the underlying cause of insulin resis-tance, but the resulting hyperinsulinemiacauses further increases in inflammatorymediators known as eieosanoids, and thecycle is amplifled.

Effect of Hyperinsulinemia onSiient inflammation

The type of inflammation that causesinsulin resistance is below the thresholdof perceived pain; hence the term silentinflammation. Sinee there is no pain as-sociated with silent inflammation, it canlinger for years, if not decades, causinga continuing immunological assault onorgans, until enough damage has beendone to result in chronic disease. Theprimary diseases that are accelerated bysilent inflammation include obesity, type 2diabetes, heart disease, and hypertension.

These are exactly the same conditions thatcluster together in metabolic syndrome,and accelerate the aging process.

Measuring Silent inflammationThe first clinical marker discovered for

silent inflammation was high sensitivityC-reactive protein (hs-CRP). Howeverthis particular marker is relatively crudeand is easily increased by infection. Amuch more precise, and much earliermarker of the presence of silent inflam-mation is the ratio of two fatty acids inthe bloodstream. One is arachidonic acid(AA) and the other is eicosapentaenoicacid (EPA). AA is an omega-6 fatty acidthat is a building block for pro-inflam-matory eieosanoids, whereas EPA is anomega-3 fatty acid that is the buildingblock for anti-inflammatory eieosanoids.The ratio of A A/EPA in the blood is in-dicative ofthe inflammatory potential ofeach ofthe 100 trillion cells in the body.The higher the AA/EPA ratio, the moresystemic silent inflammation is takingplaee through the body, and the fasteryou age.

System Consequences of Siientinfiammation

Now that silent inflammation canbe measured, it becomes the best pos-sible early warning signal that aging isaccelerating in the body. Since silentinflammation is systemic, this meansthat every organ of the body is underpotential inflammatory assault and thisleads to recruitment of macrophages intosuch inflamed organs. One ofthe conse-quences of this maerophage infiltration is

EiCOSanoidS (eye.kah.sa.noids) were the first hormones developed by living organisms and are produced by every cell inyour body. Although they might be considered to be primitive hormones, they control everything from your immune system toyour brain to your heart. There are two kinds of eieosanoids, those that promote inflammation (pro-inflammatory) and tissuedestruction and those that stop inflammation (anti-inflammatory) and promote healing. You need to have both kinds in theproper balance in order to be in a state of wellness.

50 The Atnerican Chiropractor • A PRIL 2006 •n-ww.amchiropractor.com

Page 2: Metabolic Syndrome, Inflammation, and the Aging Process Syndrome, Inflammation, and the... · Metabolic Syndrome, Inflammation, and the Aging Process by Barry Sears, Ph.D. M UCH OF

the eontinuing release of inflammatoryeytokines that include TNF and cor-responding increase in insulin resistance atthe cellular level.

One of the flrst organs to be affected by '•'•.macrophage infiltration is the adipose tissue. Asthe inflammation in the adipose inereases. so doesthe resulting insulin resistanee. Although a primarygoal of insulin is to drive down excess blood glucoselevels, it has another important rote toplay: to inhibit the release of excessfi'ee fatty acids fi'om the adipose tissue.As insulin resistanee develops in theadipose tissue, there is a release of freefatty aeids that can cause Hpotoxicityin other organs. Lipotoxicity resultswhen lipid droplets begin to fonn incells where excess fat should be absent. If the formation of theselipid droplets is in the liver, the result is fatty liver. If it's in the

There is no drug that canreduce the earliest stages of

silent inflammation. However,anti-inflammatory diets can.

ofthe glycemie load ofthe diet by adecreased intake of grains and starches

and increased intake of fruits and non-starchy vegetables. Tbe result is a significant

reduction of tbe glycemie load ofthe diet andeorresponding reduction in the amount of insulin

that is secreted to reduce the post-prandial bloodglucose levels. The second component is adequate

protein intake to stimulate the bormone glueagon.Glucagon helps maintain stable bloodglucose levels, so that satiety is ef-fectively maintained. The third factoris calorie restrietion. This is tbe onlyproven dietary factor tbat can reversetbe aging process. However, to besuccessful, you have to have the ap-propriate balance ofthe glycemie load

from carbohydrates and protein to maintain satiety in the faceof redueed calorie intake. The last factor is a reduced intake of

smooth muscle, there is more insulin resistance with less ability inflammatory omega-6 fatty aeids sueh as vegetable oils; replaceto remove glucose from the circulation. If there is lipotoxicityin heart muscle cells, it results in lipid accumulation that givesrise to atherosclerotic lesions. And, finally, if lipotoxicity takesplace in the panereas, it leads to the reduetion of insulin secretion,itself, with the rapid development of type 2 diabetes.

TreatmentThere is no drug that ean reduee the earliest stages of silent

inflammation. However, anti-inflammatory diets can. Tbereare several components to such a diet. The first is reduetion

them with monounsaturated fats such as olive oil. By redueingomega-6 fatty aeids, you effeetively reduee the body's ability tomake excess AA, thus decreasing inflammation. These are tbehallmarks ofthe anti-inflammatory Zone Diet that was designedto keep insulin within a :?one, thus decreasing the likelihood ofdeveloping insulin resistance.

To maximize the benefits of such an anti-inflammatory diet,there are two final components for an anti-inflammatory lifestyle.The first is to supplement the diet with adequate levels of fisboils rich in EPA.

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Page 3: Metabolic Syndrome, Inflammation, and the Aging Process Syndrome, Inflammation, and the... · Metabolic Syndrome, Inflammation, and the Aging Process by Barry Sears, Ph.D. M UCH OF

The EPA supplies the necessary build-ing blocks for the production of anti-in-flammatory eicosanoids that effectivelyquell the flames of silent inflammation.Finally, there is consistent, moderateexereise to reduee any accumulated lipiddroplets in the smooth museles, thus re-ducing insulin resistance.

SummaryAging ean be viewed as a contitiuous

inflammatory attack on the body that ishormotially driven. By treating food asif it were a drug and following an anti-inflammatory lifestyle, you have the idealstrategy to reverse insulin resistance andits associated inflammation. But, the doorswings both ways. If you ignore the hor-monal consequences of the diet, then otheranti-aging strategies, such as hormonalreplacement, will be highly attenuated, ifnot severely eompromised. Bottom line:Reduce the hormones that increase withage, before you increase the ones thatdecrease with age, if you truly want topractice anti-aging medicine.

Dr, Barry Sears is a leading authority on thedietary control of hormonal response, and theauthor of the #/ best seller on the New YorkTimes, book list. The Zone. A former researchscientist at the Boston University School ofMedicine and the Massachusetts Instituteof Technology, Dr, Sears has dedicated hisresearch efforts over the past 30 years to thestudy of lipids. He holds 13 U.S. Patents inthe areas of intravenous drug delivery systemsand hormonal regulation for the treatment ofcardiovascular disease\

To Learn more about The Zone Anti- Inflammatory Lifestyle Managementprogram call 1-800-404-8171 or visitwww.drsearszonefast.com. To find outmore about the AA/EPA blood test, visitwww.omega3testing.conv'physician.html.

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Page 4: Metabolic Syndrome, Inflammation, and the Aging Process Syndrome, Inflammation, and the... · Metabolic Syndrome, Inflammation, and the Aging Process by Barry Sears, Ph.D. M UCH OF