A Perinatal Strategy For Preventing Adult Disease: The Role Of Long-Chain Polyunsaturated Fatty Acids

195 Pages·2002·5.251 MB·English

by  Undurti N. Das M.D., FAMS (auth.)

A Perinatal Strategy For Preventing
Adult Disease: The Role Of Long
Chain Polyunsaturated Fatty Acids
A Perinatal Strategy For Preventing
Adult Disease: The Role Of Long
Chain Polyunsaturated Fatty Acids
Undurti N. Das, M.D., FAMS
EFA Sciences LLC, Norwood, MA 02062, USA.
SPRINGER SCIENCE+BUSINESS MEDIA, LLC
Library of Congress Cataloging-in-Publication Data
A C.I.P. Catalogue record for this book is available
from the Library of Congress.
ISBN 978-1-4613-4638-8 ISBN 978-1-4419-8564-4 (eBook)
DOI 10.1007/978-1-4419-8564-4
Copyright © 2002 by Springer Science+Business Media New York
Origina1ly published by Kluwer Academic Publishers in 2002
Softcover reprint of the hardcover 1st edition 2002
AII rights reserved. No part of this work may be reproduced, stored in a retrieval
system, or transmitted in any form or by any means, electronic, mechanical,
photocopying, microfilming, recording, or otherwise, without the written permission
from the Publisher, with the exception of any material supplied specifically for the
purpose of being entered and executed on a computer system, for exclusive use by
the purchaser of the work.
Permission for books published in Europe: [email protected]!
Permissions for books published in the United Stales of America: [email protected]
Printed on acid-free paper.
The Publisher offers discounts on this book for course use and bulk purchases.
For further information, send email [email protected].
A Perinatal Strategy to Prevent Adult Diseases:
The Role ofLong-Chain Polyunsaturated Fatty Acids
Undurti N.Das,M.D., FAMS
Contents
Preface
Chapter 1 Introduction
Fetal/Perinatal imprinting onlater life 1
Chapter2 Perinatal origins ofadult disease
Obesity 5
Chapter 3 Perinatal origins ofadult disease
Insulin resistance and Diabetes mellitus 33
Chapter4 Perinatalorigins ofadult disease
Hypertension 49
Chapter5 Perinatal origins ofadult disease
Coronary heart disease 55
Chapter 6 MetabolicSyndrome X and low-gradesystemic
inflammation 61
Chapter7 Long-chain polyunsaturatedfatty acids in adult
diseases: A hypothesis 95
Chapter 8 Breast-feeding
Composition and benefits 113
Chapter 9 Long-chain polyunsaturatedfatty acids
Metabolism, physiologyand clinical significance 135
Chapter lOA perinatal strategy to preventadult diseases: The
Role oflong-chainpolyunsaturatedfatty acids
Clinical implicationsand testing the hypothesis 175
Index 189
Preface
Obesity, type 2 diabetes mellitus, hypertension, and coronary heart
disease are serious diseases affecting a significant number ofadults across
the globe. Insulin resistance, low-grade systemic inflammation, low-birth
weight, maternal protein malnutrition, neonatal high carbohydrate diet, and
high fat diet are associated with these diseases. On the other hand,
adequately breast-fed subjects are substantially at lower risk. Ifso, what is
the link between these various factors? One possibility is that human breast
milk contains factors that confer resistance to these modem diseases. Here I
present arguments that long-chain polyunsaturated fatty acids (LCPUFAs)
present in the breastmilkcouldbe responsible forthis beneficial action.
Though the entire class of LCPUFAs provided dunng perinatal
period is likely to have a role inthe prevention ofadultdiseases,itshouldbe
understood that each ofthese LCPUFAs exhibit a unique and in some cases
opposing bioactive properties. It is important to note that there is a close
interaction between (0-6 and (0-3 fatty acids. Human breast rmlk contains
almost twice (0.78 vs 0.43 %w/w) the amount of(0-6 LCPUFAs (gamma
linolenic acid, dihomo-gamma-linolenic acid and arachidonic acid)
compared to (0-3 LCPUFAs (eicosapentaenoic acid, docosapentaenoic acid,
and docosahexaenoic acid). Obviously, the best would be to mimic the
composition/concentrations in which these fatty acids are present in the
breast milk. The concept that LCPUFAs given during pennatal period (and
in adult life) is beneficial in preventing adult diseases certainlyneeds further
exploration. I am confident that some ofthe enterprising readers will delve
into the possibilitiessuggestedafterreadingthis book.
Undurti N. Das,M.D.,FAMS.
To
My Wife Lakshmi
and
My two eyes
Daughter Arundhati and Son Aditya
Chapter #1
Introduction
Fetal/Perinatal imprintingon later life
It is believed that stimuli or msults during critical or sensitive periods
inearly life can have lifetime consequences.This concept iswell established
in developmental biology and has been termed "programming". The
evidence for programming confirmed the critical period for imprinting in
animals, more so in birds'. Programming stimuli may be generated
endogenously, such as hormonal signals', or they may be environmental.
One importantenvironmental programmingstimulus is that inducedbyearly
nutrition. Animal studies have shown that nutrition in infancy or fetal life
induces lifetime effects on metabolism, growth, and neurodevelopment and
major disease processes such as atheroscelerosis, obesity, hypertension, and
diabetes mellitus'", Ifthis "programming" concept is applied in humans, it
suggests that fetal and/orearly life,i.e.perinatalperiodevents are at the root
of major adult diseases. In such an event, it would be a matter of major
publichealthand clinical importance.
This perinatal programming or "critical period" hypothesis suggests
that failure of a developing organism to progress in a coordinated manner
from one stage to the next within preset time limits leads to a permanent
deficit or disorder. In other words,insults induced during this critical period
of development may have lifetime consequences such that their impact IS
seen either immediately or at a later stage in life. This is supported by
several human observational studies reported that perinatal exposures can
lead to diseases in later life. For instance, exposure to radiation, nutritional
deficiencies, or viruses in utero or early childhood has been related to the
development of various diseases later in life7-11. Barker et al12 associated
small size at birth or infancy with adverse health outcomes in adulthood,
including abnormal lipid values, diabetes mellitus, hypertension, and death
2 Chapter#1
fromcoronaryheart disease (CHD).This led to thefetal origin hypothesis. It
isgenerally argued that small body size orbody shape atbirth isamarkerof
poor fetal nutrition resulting in fetal adaptations that program future
propensitytoadult disease.
In a study that originally examined cardiovascular mortality in men
born in Hertfordshire, England, in the early decades of the century, deaths
from CHD were indeed commoner in men who had been small at birth and
at 1 year". Other studies showed that lower birth weight is associated with
higher blood pressure in childhood and adult life. However this effect is
relatively small-not more than 2-3 mm Hg higher blood pressure for 1000 g
less of birth weight".This association ofadverse adult outcomes with lower
birth weight is strongest for blood pressure and impaired glucose tolerance
(IGT), and type 2 diabetes mellitus14. Though this association appears very
appealing, itisnot without controversies.Hence,amorecritical examination
of this fetal/perinatal programming of adult diseases is needed. It is
particularly important to know whether factors other than low birth weight
have a role in adult diseases. Obesity, atherosclerosis, hyperlipidemias,
essential hypertension, type 2 diabetes mellitus, stroke, and CHD are
considered as features ofMetabolic Syndrome X. One common thread that
runs in this group of diseases is insulin resistance and consequent
hypeinsulinemia. Other factors associated with this metabolic syndrome or
its consequences are hyperfibrinogenemia, increased plasminogen activator
inhibitor-l (PAl-I), low tissue plasminogen activator, nephropathy,
microalbuminuria, and hyperuricemia'". There is now evidence to suggest
that low-grade systemic inflammation occurs in these conditions.Thus, ifit
is true that CHD and other diseases have fetal/perinatal origin, it indirectly
suggests that low-grade systemic inflammation has its origins in the
fetal/perinatal period. In this context, it is interesting to note that breast-fed
infants have lower incidence of obesity, hypertension, type 2 diabetes
mellitus, and CHD suggesting that breast milk contains factor(s) that can
abrogate insulin resistance, low-grade systemic inflammation and thus, is
able to prevent these diseases. I suggest that the reason why breast-fed
infants have a lower incidence of features or diseases of Metabolic
Syndrome X is because breast milk is rich in long-chain polyunsaturated
fatty acids (LCPUFAs). I present arguments and suggest that adequate
supplementation of LCPUFAs from the second trimester of pregnancy till
adult life can suppress low-grade systemic inflammation, attenuate insulin
resistance, and preventthe onset ofadult diseases.
#1.Introduction 3
References:
I. Spalding DA. Instinct with original observation on young animals. Br J Animal
Behav1954;2:2-11.
2. AngelbeckIH,DuBTUIEF.Theeffectofneonataltestosteroneonspecificmaleand
female patterns of phosphorylated cytosohc proteins m the rat preoptic
hypothalamus,cortexandamygdala.Brain Res 1983;264:277-183.
3. McCanceRA. Food, growthandtime.Lancet1962;II' 271-272.
4. Hahn P.Effectoflittersize on plasmacholesterol and msulmand someliverand
adiposenssueenzymesinadult rodents JNutr 1984;114:1231-1234.
5. MottGE,LeWISDS,Mcfhll He. Programmmgofcholesterolmetabolismbybreast
or formula feedmg.In. Bock GR, Whelan I, eds Thechildhoodenvironment and
adult disease CIBAFoundationSymposium156 Chichester:Wiley, 1991:56-76.
6. DobbingI Nutntronalgrowthrestncuonand thenervoussystem.In:DavisonAN,
Thompson RHS, eds. The molecular baSISofneuropathology London: Edward
Arnold,1981:221-233.
7. StewartA,WebbI,Hewitt DA. Asurveyofchildhoodmalignancies.BMJ1958;i:
1445-1508.
8. MacMahon B.Prenatal X ray exposureand childhoodcancer.JNatl Cancerlnst
1962;28:1173-1191.
9. Otake M, Schull I.In utero exposure to A-bomb radiation:A reassessment. BrJ
Radlol1984;57:409-414.
10. Stem Z, Susser M, Saenger G, Marolla F. Famine and human development: the
Dutch hungerwinterof1944-45 New York;OxfordUniversityPress, 1975.
II. Chess S,Korn SI, FrenandezPB Psychtatncdisordersofchildren wuh congenual
rubella New York; Brunner-Mazel,1971.
12. Barker DIP,ed.FetalandInfantoriginsofadultdisease.London:BMIPublishing,
1992.
13. RobinsonR.The fetal originsofadult disease.BMJ2001;322:375-376.
14. Lithell HO,MckeiguePM,BerglundL,MohsenR,Lithell UB,Leon DA.Relation
ofsize atbirthtonon-insulmdependentdiabetes and msuhnconcentrationsmmen
aged 50-60years.BMJ1996;312:406-410.
15. HansenBe.The metabolicsyndromeX.Ann N YAcadScI 1999;892: 1-24.
Chapter #2
Perinatal origins ofadult disease
Obesity
The dramatic increase in the prevalence of obesity amongchildren and
adults has been attributed to increaseddietary intake of high-energy, high-fat
foods and reduced physical activity'. In the United States alone, the
estimated annual number of deaths attributable to obesity is about 280,0002•
In particular, obesity is associated with an increased risk of type diabetes
mellitus, coronary heart disease (CHD), an increased incidence of certain
forms of cancer, respiratory complications (obstructive sleep apnoea) and
osteoarthritis oflarge and small joints"4. Life-insurance and epidemiological
studies confirm that overweight and obesity are important predictors of
decreased logevity". The results of the Framingham study showed that the
risk of death within 26 years increased by 1% for each extra pound (0.45 kg)
increase in weight between the ages of 30 and 42 years, and by 2% between
the ages of 50 and 62 years".It is known that children who are obese tend to
become obese adults. Obese children and adults face health and
psychological challenges related to their obesity compared with their leaner
counterparts. In order to reduce the incidence of childhood obesity, it has
been recommended that children participate in 150 minutes of physical
activity every week (i.e. 30 min/day) from kindergarten through grade 12.
But, this is rarely implemented and followed? This is particularly troubling
because school based, high-quality, physical education or regular exercise
helps to promote healthier living and encourage a lifetime of active living.
Tremblay and Willms8 have confirmed recently, the increasing incidence of
childhood obesity. Increasing incidence of paediatric obesity increases the
risk of subsequent morbidities", Therefore, prevention of obesity in
childhood and effective treatmentofoverweightchildren are essential.