diet and nutrition therapy in dyslipidemia management

In:Dyslipidemia:Causes,Diagnosis and Treatment Editors: Miroslava Karapetrovie, Zlatko Aeimovie

©Copyright 2011 Novapublishers Co.

Chapter 1

DIET AND NUTRITION THERAPY IN DYSLIPIDEMIA MANAGEMENT Rakesh Sharma1 and Robert J Moffatt2 1

Amity Institute of Nanotechnology, Amity University Uttar Pradesh, NOIDA, India 2 Department of Exercise, Food and Nutrition, Florida State university, Tallahassee, FL 32304

ABSTRACT Abnormal blood lipids is a condition of elevated cholesterol, low-density lipoproteins, triglycerides or low high density lipoproteins leading to hypercholesterolemia with risk of atherosclerosis or diabetes. Status of dyslipidemia changes in different age groups and ethnicities in different life styles. Dietary low fat intake or nutrition supplementation is the key of lowering blood lipids as art for keeping dyslipidemia in control and manageable. Use of wild and traditional foods is less known in keeping good health at low risk of dyslipidemia or cardiac diseases. Ancient view of low fat, vegan dietary intake, exercise and active life style puts forth evidence of long life expectancy at low risk of cardiovascular disease as observed among tribals in present times. Extensive clinical trials suggest ambiguous state of strictly medical treatment of dyslipidemia to completely cure the disease while it causes more side effects. Recent clinical trials show clear benefits of dietary and nutrition therapy in lipid lowering and management of dyslipidemia in order to keep cholesterol in normal range. New guidelines suggest the search of new more sensitive biomarkers of dyslipidemia or cardiovascular disease to assess the disease growth, need of active life style, better knowledge of lipoprotein metabolic control to fine tune the dosage and selection of drugs combined with dietary or nutraceutical regimens under medical supervision. Ancient traditional ways of active life style suggest benefits of ‘spiritual acceptance’ or no affluence, no use of processed foods or discipline of regular fasts to keep low fat diet and good health with high life expectancy.

Keywords: dietary management, dyslipidemia, cholesterol, nutrition, lipid.

R.Sharma and RJ Moffatt

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1. INTRODUCTION Dyslipidemia is an abnormal amount of lipids (e.g. cholesterol lipid, lipoprotein, or apolipoprotein levels) in the blood. The word ‘dyslipidemia’ was coined way back in 1965 by Fredrickson as major seven classes of elevated lipids in the body [1]. Lipid disease initiates if dyslipidemia goes uncontrolled at biochemical level with result of increased glucose (diabetes) or lipid and lipoprotein deposits (obesity and hypercholesterolemia). It is believed that continuous lipid profile monitoring at regular intervals and timely effective intervention (exercise, dietary, nutrition supplements, lipid lowering foods and behavioral counseling) keeps dyslipidemia in control and it is manageable for longer life expectancy when pharmacological medication fails or shows side effects. In last decade, management of dyslipidemia has remained a major controversy to meet target levels of LDL-C, triglycerides and keeping up HDL-C in blood for long time by antihypertensive therapy, statins, niacin, fibrates, omega-3 fatty acids, and dietary management especially in children, adolescents and elderly population [2]. With all these factors in consideration, present chapter focuses on dyslipidemia in following sections including definition, lipids lipoproteins, concepts of lipid disorder and lipid lowering, ancient and modern views of low fat diets, nutrition therapy in clinical trials, less known low fat risk tribal life styles, guidelines and futuristic prospects of dyslipidemia management. Our ultimate message is “Effective dyslipidemia management by ‘non-drug therapy and effective intervention’ prevents person from cardiovascular disease”. The present chapter puts forth evidence of traditional non-affluent and ancient life styles as favorable to keep good health.

Definition of Dyslipidemia Dietary fat-intake and elevated blood lipids are considered as risk of dyslipidemia and development of atherosclerosis and diabetes. The elevated cholesterol and lipoproteins are the main lipids to cause dyslipidemia. The elevated lipids are known as triglycerides (TC), lipoproteins (LDL-C), apolipoproteins (apo-B), non-HDL-C, and TG and low HDL-C and apo A-I in the blood. The lipid disorders are classified into seven dyslipidemia profiles [1].       

elevated LDL-C (type IIa) elevated LDL-C combined with high triglyceride (TG) (type IIb) elevated TG (type IV) low HDL-C (hypo- ), elevated LDL-C type IIa, type IIb, or type IV accompanied by low HDL-C; hyper-apobetalipoproteinemia (hyper-apoB), i.e. elevated apolipoprotein B (apoB) but normal LDL-C Inherited lipoprotein disorders that often present in youth at high risk of future CVD include familial hypercholesterolemia (FH), familial combined hyperlipidemia

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(FCHL), hyper-apoB, familial hypoalphalipoproteinemia, apolipoprotein A-I mutations, common and rare variants in ABCA1 including Tangier disease, lecithin cholesterol acyl transferase (LCAT) deficiency, and hyper-TG associated with lipoprotein lipase deficiency and defective apoC-II. The disorder of cholesteryl ester transfer protein deficiency, often presents as high HDL-C, but its increased or reduced risk of CVD is not resolved [2].

Lipids and Lipoproteins in Dyslipidemia In blood, lipids are transported in almost all organs and remain in circulation to compensate the energy demands. By density gradient centrifugation of plasma, different lipid fractions can be separated out in chloroform-methanol organic phase as shown in Figure 1 [1].

Source: Sharma et al. How doctor evaluates the carotid artery disease http://www.scribd.com/doc/24292286/Evaluation-of-Carotid-Artery-Disease.

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Figure 1. A set of lipids is shown after centrifugal separation into VLDL, IDL, HDL. The measurement of different lipids can measure Cholesterol: HDL and IDL fractions to confirm the dyslipidemia. The elevated lipids predict a first guideline of disease progress evaluation and response of drug therapy.

Different lipid fractions and lipoproteins can be measured to evaluate the dyslipidemia and possibility of cardiovascular risk. Both hypercholesterolemia and metabolic syndrome are associated with atherogenic and diabetes related dyslipidemia, which is characterized by high TG, elevated small dense LDL-C and low HDL-C. Such dyslipidemia poses a high risk of CHD on patients. According to NCEP ATPIII, elevated TG is measured as very LDL (VLDL) as marker for atherogenic remnant lipoproteins or non-HDL-C6. Furthermore, NCEP III guidelines state that non-HDL-C is calculated by subtracting HDL-C from total cholesterol and should be a secondary target if TG is >200 mg/dL. Atherogenic dyslipidemia (LDL-C, HDL-C, and TG) are interrelated and each component predicts CHD risk.

Low-Density Lipoprotein Cholesterol


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LDL-C is a combination of lipoprotein (LDL) and lipid-like cholesterol. Cholesterol is circulated in blood as free or cholesterol esters along with bound form with lipoproteins in the form of LDL-C. LDL-C can be small dense LDL particles can be more in number than blood cholesterol. However, LDL-C value measurement in a standard lipid profile does not provide any information about the size of LDL particles [5].

High-Density Lipoprotein Cholesterol HDL is a high-density lipoprotein to transport cholesterol back to liver. HDL-C consists HDL particle with cholesterol ester inside. Low HDL-C is risk factor for CHD (golden rule is that every 1 mg/dL increase in HDL decreases 2% to 3% risk of CHD). Although the mechanism is not clear, it is believed that the anti-atherogenic effect of HDL-C may be a result of reverse cholesterol transport (RCT), and anti-oxidant and anti-inflammatory properties as shown in Table 1. However, small size of HDL-C particles and action of CETP (cholesterol ester transfer protein from liver) play an important role to make small HDL-C particles by exchanging more TG from VLDL particle and cholesterol esters from HDL-C. Smaller HDL-C particles are readily excreted out from the kidneys resulting in lower LDL-C particles [6]. Table 1. The multiple anti-atherogenic protective actions of high-density lipoprotein cholesterol

In following section, we describe individual lipoproteins.

Triglycerides Triglycerides are small lipid molecules. They are circulated in blood in exchange with VLDL particles and constitute the lipoproteins. The relationship of LDL and TG to composite endpoints of CHD was assessed in Pravastatin or Atorvastatin Evaluation and Infectious Therapy-Thrombolysis in Myocardial infarction (PROVE IT-TIMI)-22 trial[7]. TG < 150 mg/dL was associated with lower CHD risk in ACS patients.

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Apart from lipoproteins, other factors such as homocyst(e)ine, C-reactive protein, genetic risks and hormone replacement therapy also influence cardiovascular disease risk.

What Is Lipid Lowering? The elevated blood lipids are the result of lipid disorder(s) in the body mainly due to interralated lipid metabolic changes in liver, intestine, adipose tissue at the cellular level of membrane, mitochondria and macrophages as shown in Figure 2. The central regulatory pathway is cholesterol biosynthesis and its breakdown into bile acids. The first regulatory enzyme segment includes 3-Hydroxy-3-Methylglutaryl Coenzyme A (HMG-CoA) reductase (HMG-CoAR for cholesterol synthesis) and Cholesterol-7α Hydroxylase (CHOL-H for cholesterol breakdown) to precursors. The ratio of HMGCoAR:CHOL-H plays a significant role in control of lipids in the body. The ‘lipid lowering’ or cutting down cholesterol is the measure of bring back the elevated blood lipids to normal lipid levels in the body by using the choice of HMG-CoAR inhibitors (mainly statins) or CHOL-H stimulators (mainly bile acid sequesterants). The lipid lowering may also include dietary low fat intake or synthetic diets to keep low supply of lipids by utilizing the stored lipids and fats (Step I and Step II diets). However, broadly success in lipid lowering by use of diets or drugs also depends on several other body constitutional, age, heredity, socio-economic, and environmental factors. How Severe Is Dyslipidemia to Cause Lipid Disorders? The elevated lipids, lipoprotein, and apo-B levels are common in primary dyslipidemias associated with premature CAD and CVD. FH is an autosomal dominant disorder due to defects in the LDL receptor (LDLR) gene (see Figure 1). FCHL and hyper-apo-B result from overproduction of VLDL, IDL, and LDL (see Figure 1). The expression of FCHL can be delayed or associated with type IIa, IIb, or IV lipoprotein profiles or isolated high apoB with premature CAD. The apoB and apoA-I apolipoprotein levels were stronger predictors of parental CVD than LDL-C and HDL-C. National Health and Nutrition Education Survey (NHANES) in collaboration with NCEP and AHA have set guidelines on use of lipid profiles in evaluation of dyslipidemia. The lipid profile includes the following lipids including TC, TG, LDL-C, HDL-C, and non-HDL-C. Each lipid is measured by following calculations:      

LDL-C = TC – (HDL-C + TG/5). TG = (VLDL)-C. For TG = 400 mg/dl, a direct LDL-C is measured. TC, HDL-C, and non-HDL-C are measured by clinical chemistry on nonfasting condition. apoB and apoA-I are mesured by immunochemical methods Non-HDL-C = TC - HDL-C. It includes apoB-containing lipoproteins [VLDL, intermediate-density lipoprotein (IDL), LDL, and lipoprotein(a)]. VLDL, LDL, and HDL subclasses by nuclear magnetic resonance spectroscopy or vertical-spin density-gradient ultracentrifugation.

Another set guideline on dyslipidemia management and cardioprotection highlights global risk and several factors influencing risk based on LDL-C (mmol/L) and total

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colesterol:HDL-C ratio target levels in different risk catagories (