Help Please

[Guest guest]

( Moderator's Note: On the subject of fats, there are also files in our Files

section or in our archives called " The Oiling Of America " .

http://health.

 

Or for an indepth look go to this link from our links page:

Udo Erasmus on oils and fats. The author of the book: " Fats That Heal Fats that

Kill " http://www.udoerasmus.com./ )F.

 

 

 

Hey Ditzi ~

 

Glad to hear about your leg ulcer. Check this out...a VERY good read.

 

 

-

DitziSis

alternative_medicine_forum

Saturday, August 14, 2004 10:46 PM

help please

 

 

I'm just not having a very good few days right now.

Can someone please remind me what the nutrient is that ya need when your feet

burn...???

And what was it that was said about dog vaccinations? Tuxie is due for hers. I

live in the woods, so I think she probably needs a rabies shot without question.

Haven't heard of rabies in the basin in a few years...but those squirrels and

chickenmunkies are all around, as well as coyotes and bear. AND she's not an

especially social dog..she will bite. People think she's " OH SO CUTE " ...and she

is. Just not social. They will stick their hand into the car window, even tho I

tell them not to.

My mood tonight...I'm going to get a sign " Forget the dog, BEWARE OF ME! "

Thanks everyone.

Peace and good health,

MaryKaye

 

p.s. on a better, lighter note::

Leg ulcer is down to less than 3/4 " x 1/2 " ... using organic honey ONLY.

 

 

 

 

Omega 3:

Implications in Human Health and Disease

 

FORWARD

 

The study of omega 3 fatty acids is one of the fastest growing research areas in

nutritional and medical science today. As research interest in the topic has

increased, so has consumer and patient awareness. Ten years ago, less than 10%

of people polled recognized the term “omega 3,” but in 1999 an independent

survey reported that consumer awareness had grown to over 50%.1 Awareness and

interest among scientists and physicians have also grown, as evidenced by the

broad diversity of research projects currently examining the effects of omega 3

fatty acids. Many reports appearing in the scientific literature suggest that

simple modification of the diet with certain fatty acids can have a positive

impact on a broad range of diseases. These diseases include heart disease,

hypertension, cancer, diabetes, cystic fibrosis, asthma, arthritis,

dysmenorrhea, depression, schizophrenia, and attention deficit disorder.

 

INTRODUCTION

 

Fat is a hot topic! It is difficult to go anywhere without being reminded of it.

From media and health advisories related to dietary fat intake to the wide

availability of low-fat foods, fat has become a conscious part of our daily

living. People discuss their diet and cholesterol levels in the same casual way

they discuss weather and sports. For the most part, fat is regarded in a

negative fashion. Typically, it is considered in relation to excess energy

balance, obesity, and as a dietary factor in the development of cardiovascular

disease. However, the term fat is broad by definition; in contrast to popular

opinion that all fat is bad, there are “good” and “bad” fats, and fatty acid

nutrition must be considered in an educated context.

 

Under certain conditions, dietary fat may play a role in disease development.

What has not been emphasized is that certain types of fatty acids are essential;

that is, they must be obtained from the diet, are necessary for health, and

their absence from the diet can be detrimental.2 The “good” fats are the

essential fatty acids (EFAs) from the omega 3 and omega 6 fatty acid families.

Their significance in the diet is not based simply on the presence or absence of

one or the other, but rather their balance and the inclusion of short- and

long-chain EFAs. As such, both classes of fatty acids are recognized as playing

a significant role in health. Surprisingly, recommendations to eat more

polyunsaturated fat have typically considered only omega 6 while ignoring omega

3. This pattern has resulted in an American population that consumes excessive

amounts of omega 6 and very low levels of omega 3.

 

As far back as can be estimated, humans have relied on fat as a source of

calories and EFAs.3 Yet, only in the past two decades have we learned about the

life-giving role of fatty acids. This understanding began with the discovery of

the essential nature of dietary fat by George and Mildred Burr at the University

of Minnesota in 1929.4,5 The Burrs detailed the consequences of an essential

fatty acid deficiency in growing and developing animals. Clearly, the Burrs'

early work in the field defined the significance of EFAs, but science has

greatly expanded our knowledge of the relationship between fat and human health

over the past 70 years. Research has highlighted the significance of particular

types of fatty acids in the success or failure of our health. We are beginning

to understand what types of fat to feed people, as well as the consequences of

eating too much, not enough, or the wrong kind of fats. The message that is

beginning to unfold is not as simple as a consideration of “total dietary fat

intake,” but rather the composition of the diet with respect to specific fatty

acids and the relative balance between omega 6 and omega 3.6,7 For example, we

know that long-chain omega 3 polyunsaturated fatty acids (PUFAs) are important

for neural and visual development and the prevention of diseases such as

coronary artery disease.2 Indeed, just as it is becoming increasingly obvious

that the fatty acid composition of dietary fat will affect clinical outcomes,

omega 3 supplementation has shown potential value in the treatment of heart

disease, hypertension, cancer, diabetes, depression, schizophrenia, cystic

fibrosis, and arthritis.8-13

 

FATTY ACIDS AND LIPIDS: THE BASICS

 

Fatty Acids

 

Historically in Western societies, the term fat described a type of material

that was extracted from animals and plants and was equivalent to the terms lard,

tallow, or suet. This term was replaced with a broader one, lipid, to more

accurately identify a group of compounds with similar characteristics. By

definition, the term lipid collectively refers to a group of substances that are

insoluble in water and soluble in organic or nonpolar solvents such as hexane,

benzene, chloroform, and ether.14 Lipids are divided into three main classes,

simple (neutral), complex, and derived. Simple lipids are compounds in which the

fatty acids are esterified to a glycerol backbone like mono-, di-, and

triglycerides. Complex lipids, such as phospholipids, contain multiple

functional groups, such as a phosphate group, nitrogenous base, or sugar

moieties in addition to fatty acids and glycerol (Figure 1).

 

Fatty acids are derived from the hydrolysis of simple and complex lipids and are

broadly classified into saturated (containing no carbon-carbon double bonds) and

unsaturated (having one or more carbon-carbon double bonds). Unsaturated fatty

acids can be further classified into:

 

• Monounsaturated—one carbon-carbon double bond;

 

• Polyunsaturated (PUFA)—two or more carbon-carbon double bonds; and

 

• Highly unsaturated fatty acids (HUFA)—three or more carbon-carbon double

bonds.

 

NOTE: Fatty acids designated as HUFA are also PUFA but separate themselves from

PUFA in that they contain three or more carbon double bonds.

 

Structurally, fatty acids are made up of a straight chain of carbons that end in

a carboxylic acid terminus. In vertebrates, predominant chain lengths range from

2 to 26 carbons with as many as 6 carbon-carbon double bonds; however, longer

highly unsaturated acids have been described in relatively small amounts in

spermatozoa, retina, and brain cells.15 Common fatty acids are listed in Table

1.

 

The double bond structure of naturally occurring fatty acids assumes the cis

configuration, where the two hydrogens of the double bond are on the same side

of the double bond. Trans fatty acids have hydrogen molecules on opposite sides

of the double bond and are produced when PUFA are heated or hydrogenated, which

is the common process used to make margarine spreads from liquid vegetable oils.

Dietary trans fatty acids are absorbed and metabolized in a similar fashion to

the naturally occurring cis-configured fatty acids.16 Evidence suggests that

trans fatty acids may be associated with an increased health risk. Consumption

of diets high in trans fatty acids may be a significant risk factor in the

development of cardiovascular disease in a similar manner to diets high in

saturated fat.17

 

Fatty Acid Nomenclature

 

The nomenclature originally used to describe fatty acids was the “delta” system.

This system counted the position of double bonds in the fatty acid chain

starting from the carboxyl terminus. While accounting for every double bond,

this system proved cumbersome in light of the fact that the entire sequence

would change after elongation of the fatty acid. The “omega” () nomenclature

(synonymous with the “n” system) was introduced in the 1960s by Dr. Ralph Holman

to simplify the identification of polyunsaturated fatty acids.18 The general

scheme is detailed in Figure 2. In this system, a string of numbers and symbols

represents the fatty acid, whereby the first number of the sequence refers to

the total number of carbons in the fatty acid chain, the second refers to the

number of carbon-carbon double bonds, and the last or “omega” number refers to

the position of the first carbon-carbon double bond that occurs with respect to

the methyl end of the molecule. For example, -linolenic acid (18:33 or LNA) has

18 carbons, three carbon-carbon double bonds, and is an omega 3 fatty acid with

the first carbon-carbon double bond occurring three carbons from the methyl

terminus of the fatty acid, between the third and fourth carbons. As all

modifications of unsaturation and/or chain length in humans occur at the

carboxyl terminus or within nine carbons of the terminus, the “omega”

nomenclature classifies fatty acids into families whose terminal structure never

changes. Thus, the tail structure remains omega 3, omega 6, or omega 9

irrespective of chemical changes to the first nine carbons of the carboxyl

functional group. In addition, mammals, unlike plants, cannot interchange. Thus

mammals cannot change an omega 3 fatty acid into an omega 6 fatty acid and vice

versa.

 

Food Sources of Lipids

 

Predominant sources of lipid in the diet are triglycerides in vegetable oils and

meats.19,20 Structural lipids like phospholipid also provide a significant

source of fatty acid in animal-based food such as meat, poultry, fish, and eggs.

The most commonly occurring polyunsaturated fatty acids in nature are linoleic

acid (18:26 or LA) and -linolenic (18:33 or LNA) acids, which are predominantly

found in vegetable oils. Plants possess the necessary enzymatic machinery to

synthesize double bonds beyond the delta-9 carbon. Thus they can synthesize

omega 3 and -6 essential fatty acids. Long-chain PUFA, including tri-, tetra-,

penta-, and hexaenoic acids, are mainly found in marine and land animals.

Commonly occurring vegetable and plant oil omega 3 and omega 6 fatty acid

profiles are listed in Table 2. Significant dietary sources of LNA include

flaxseed, walnuts, perilla (Perilla species), purslane (Portulaca species),

canola, and soybean oils. Significant sources of LA include corn, sunflower,

cottonseed, safflower, canola, and soybean oils.

 

Among the long-chain omega 3 fatty acids, those predominantly found in food

sources include eicosapentaenoic (20:53 or EPA), docosapentaenoic (22:53 or

DPA), and docosahexaenoic (22:63 or DHA). Perhaps the most well known sources of

these fatty acids are cold-water fatty fish such as salmon.

 

Predominant dietary long-chain omega 6 fatty acids include

dihomo-gamma-linolenic acid (20:36 or DGLA) and arachidonic acid (20:46 or AA).

Long-chain omega 6 fatty acids are found in eggs, dairy products, and meats.

 

In the typical American diet, approximately 98% to 99% of dietary PUFA intake is

obtained from 18 carbon EFAs with long-chain omega 3 intake comprising about 150

mg per day out of 60 g to 100 g of daily fat intake. Long-chain omega 6 intake,

mainly as arachidonic acid, tends to vary but is estimated to be around 500 mg

per day.3

 

HISTORICAL PERSPECTIVES OF ESSENTIAL FATTY ACIDS

 

Essentiality of Fatty Acids

 

As stated earlier, the essential nature of fat was discovered by the Burrs.5

Their experiments documented that when young rats were fed an EFA-deficient

diet, they ceased to develop normally. The animals also developed dermatitis,

scaly tails, dry skin, thickened and brittle hair, kidney malfunction, and they

failed to reproduce. This condition was reversed when corn or flaxseed oil was

added to the diet. The main components of these oils, linoleic acid (18:26) and

a-linolenic acids (18:33), were determined to be the fatty acids responsible for

this recovery and thus were termed “essential.”

 

Subsequent studies have documented the unique requirements of PUFA in human and

animal nutrition.21 However, because flaxseed oil contains a small amount of

linoleic acid (6), the essential nature of omega 3 fatty acids was contested

until a classic case of -linolenic acid (3) deficiency was reported by Holman in

1982.22 LNA deficiency was described in a young girl injured by a gunshot. The

girl was maintained on a parenteral nutrition formula that included LA as the

sole EFA. Symptoms of an EFA deficiency (EFAD) developed that were related to

neurological function and included episodic paralysis, blurred vision, weakness,

and the inability to walk. Analysis of the patient's plasma lipid fatty acid

profile revealed near normal levels of omega 6 fatty acids and very low levels

of omega 3 fatty acids. The addition of LNA to the parenteral emulsion resolved

many of the patient's neurological symptoms.

 

A lack of EFA in the diet can result in EFAD. There is a correlation between the

extent and duration of EFA deprivation and the severity of symptoms. Extreme

deficits result in symptomatology similar to that originally described by the

Burrs; however, smaller deficits may not result in acute and overt

symptomatology, but rather may culminate in disease over a period of several

years or decades. In EFAD, the body deficient in PUFA attempts to replenish and

restore unsaturation by utilizing endogenous synthesis pathways (the omega 9

pathway) as a source of PUFA. This pathway terminates in the formation of a

triene, Mead's acid (20:39)—the body's best attempt at achieving unsaturation.

Mead's acid is produced in excess during EFAD. In 1960, Holman identified a

decrease of arachidonic acid and an increase of Mead's acid as a marker of EFAD

and referred to it as the triene:tetraene ratio.23 Today, however, more

revealing and detailed analyses of blood lipid profiles are available, and these

have facilitated more precise descriptions of the roles that omega 3 and omega 6

EFAs play in health (Table 3).146

 

By classical definition, true omega 3 deficiency is relatively rare, but a

relative insufficiency of omega 3 that may approach deficiency status is

considered prevalent.24,25 Experimentally, omega 3 deficiency has been studied

largely in rat and monkey models.26 In omega 3 deficient animals, brain and

tissue DHA (3) is replaced by DPA (6), the closest structural substitute for

DHA. In primates, this omega 3 deficiency resulted in visual as well as

neurological abnormalities that could be attenuated by the reintroduction of

omega 3 to the diet. Dietary DHA is very important for humans in the development

of brain and retinal tissue. Children who were breast fed or received long-chain

PUFA-supplemented formula reportedly perform better on visual and

problem-solving testing and intelligence quotients testing, compared to those

fed formula without long-chain PUFA. 27

 

METABOLISM OF OMEGA 3 AND OMEGA 6

 

Fatty Acid Metabolism

 

If LNA and LA are supplied by the diet, they can be desaturated and elongated to

long-chain highly unsaturated fatty acids, but the efficiency of this conversion

is reported to be low.28 Thus, it is recommended that long-chain PUFA also be

included in the diet.

 

It was not until 20 years after the discovery of EFAs that their metabolism was

elucidated.29-31 In 1950, Holman and Widmer reported that when LA was fed to

rats, a tetraene [arachidonic acid (20:46)] increased, and when LNA was fed, a

pentaene [eicosapentaenoic acid (20:53) or EPA] and a hexaene [docosahexaenoic

acid (22:63) or DHA] increased significantly in rat liver lipids.29 As more

definitive analytical techniques became available, Holman, Klenk and associates

found that the metabolism of LA resulted in the formation of omega 6 PUFA, and

the metabolism of LNA resulted in the formation of omega 3 PUFA.31,32 This

discovery led to the identification of the elongation and desaturation products

of the EFAs illustrated in Figure 3.

 

The preferred anabolic pathway for PUFA follows steps starting with 6

desaturation, elongation to 20 carbons, 5 desaturation, elongation to 22

carbons, 4 desaturation by and finally elongation to 24 carbons. The one

exception, docosahexaenoic acid (22:63), is now known to be formed by an

alternative pathway, referred to as the “Sprecher shunt,” which involves 6

desaturase instead of 4 desaturase.33

 

The three main fatty acid families, omega 3, omega 6, and omega 9, compete with

each other for the desaturase and elongase enzymes that regulate the conversion

of short-chain PUFAs into long-chain PUFAs based on 3>6>9. The competitive

nature of LNA and LA for these enzymes was established by Holman and Mohrhauer

and modeled mathematically by Lands and coworkers.34,35 Experimentally, when

rats were fed a constant amount of LNA (1% of energy) and increasing amounts of

LA (from 1% to 9% of energy), liver lipid content of omega 3 fatty acids

decreased significantly. Likewise, when LA was fed at a constant amount (0.6%

energy) and dietary LNA was increased, liver lipid composition of omega 6 fatty

acids decreased. From these early models, we know that diets high in the omega 6

LA—the typical American diet—suppress the metabolism and accretion of blood and

tissue omega 3 fatty acids.2,36,37

 

OMEGA 3 FATTY ACIDS IN HEALTH AND DISEASE

 

Eicosanoids

 

In 1930, two gynecologists reported that extracts of seminal fluid caused

uterine tissue to contract.38 Soon after this report, von Euler attributed the

uterine-stimulating characteristic of seminal fluid to lipid-like substances

originating in the prostate and collectively referred to these compounds as

“prostaglandins”.39

 

Prostaglandins (and leukotrienes) are eicosanoids, biologically active

substances that are produced by the direct enzymatic oxidation of 20- and

22-carbon PUFA, including AA, DGLA, EPA, and DHA, by the cyclooxygenase

(prostaglandin H synthase) and lipoxygenase (5-lipoxygenase) enzymes (Figure

4).40 Almost all cells in the human body are capable of producing eicosanoids

and, so far, over 100 eicosanoids have been identified.41 Eicosanoids are

essential for normal physiology and contribute to disease pathology, supporting

a wide variety of processes such as cardiovascular function, intestinal motility

and acid secretion, inflammation, and ischemia/reperfusion injury. During the

inflammatory cascade, eicosanoids influence the immune response by causing

vascular changes and edema, stimulating neutrophil chemotaxis, and stimulating

the production of cytokines. In this way, PUFA play an integral role in the

inflammatory process.42,43

 

AA, DGLA, EPA, and DHA predominate as substrate for the cyclooxygenase and

lipoxygenase enzyme systems. However, their eicosanoid products differ in

physiological potency or effect.

 

Eicosanoids can be arranged into three groups or series depending on their fatty

acid origin. Group 1 eicosanoids are derived from DGLA (6). Group 2 are derived

from AA (6) and are potent mediators of inflammation. Group 3 eicosanoids are

derived from EPA (3) and are of considerably lower potency as inflammatory

mediators than group 2 eicosanoids.41,44 For example, leukotriene B4 derived

from AA (Group 2) is 30 times more potent a chemotactic agent than EPA-derived

leukotriene B5. In addition, prostaglandin E2 (Group 2) elicits marked

vasoconstriction and edema, while prostaglandin E3 (Group 3) stimulates little

vasoactive activity (Figure 4).

 

Group 1 eicosanoids, such as prostaglandin E1 derived from DGLA, also possess

some anti-inflammatory properties, and thus dietary sources of gamma-linolenic

acid (18:36 or GLA) such as primrose and borage oil have also been investigated

in models of experimental and clinical inflammation.45

 

Anti-inflammatory Nature of Omega 3

 

Omega 3 fatty acids have a well-documented anti-inflammatory effect, the basis

of which relates to eicosanoid production.2,46 The inflammatory response relies

on dietary AA (6) and the subsequent production of group 2 eicosanoids; however,

dietary sources rich in omega 3 increase the cell membrane content of both EPA

and DHA.47,48 Increased proportions of membranous omega 3 at the expense of

arachidonic acid results in the competitive inhibition of pro-inflammatory group

2 eicosanoid production and increased production of anti-inflammatory group 3

eicosanoids.49

 

Experimentally, the competitive inhibition of group 2 synthesis by EPA and DHA

omega 3 fatty acids has been reported to have a rate constant similar to that of

ibuprofen.50 Lands et al were the first to identify that omega 3 fatty acids

could inhibit the formation of the highly inflammatory omega 6-derived

eicosanoids.50 It was noted that omega 3-derived analogs antagonized metabolism

of arachidonic acid by cyclooxygenase. Experimental models subsequently examined

the hypothesis that omega 3 fatty acids could attenuate injury by reducing the

inflammatory response.51,52 Fish oil supplementation reportedly decreased injury

severity in a feline model of cerebral ischemic injury as well as decreased

injury in experimentally-induced myocardial infarction in dogs. Other studies

have investigated the anti-inflammatory nature of fish oil for the treatment of

diseases including arthritis, cystic fibrosis, IgA nephropathy, diabetes,

ulcerative colitis, Crohn's disease, asthma, and sepsis, with apparent success

at improving outcomes.2,13,53-57 For example, in cystic fibrosis patients with

lung dysfunction, leukotriene B4 (LTB4) levels in bronchial lavage fluids were

reported to be significantly higher compared to unaffected controls.12 Fish oil

supplementation in this patient population resulted in reduced LTB4 production

and improved lung function, including increased tidal volume and sputum

generation. In inflammatory bowel disorders, fish oil supplementation resulted

in significant improvements in remission time and histological findings for

ulcerative colitis and Crohn's disease patients.57,58

 

Improvements in joint tenderness and morning stiffness have also been reported

in arthritic patients whose diets were supplemented with fish oil.13 In septic

patients, enteral formulas enriched with fish oil reduced infectious

complications by 70% and mean hospital stay length up to 29% compared to

patients on traditional formulas without long-chain omega 3.54

 

Experimentally, improved outcomes with supplemental omega 3 are attributed not

only to eicosanoid effects but also to eicosanoid-related events, including

cytokine production and second messenger cell signaling.59 Omega 3 fatty acids

have been reported to down-regulate the inflammatory response by decreasing the

production of inflammatory cytokines such as interleukin-1 (IL-1) and tumor

necrosis factor- (TNF). In humans, 300 g/day of fish or 18 g/day of fish oil for

3 months reportedly diminished production of IL-1 and TNF by up to 30% to 50% in

stimulated peripheral blood monocytes.61,62 In a septic rat model, fish oil

treatment reduced PgE2 production, calcium flux, inositol triphosphate

signaling, and mortality compared to corn oil treated animals.47,60

 

SUPPLEMENTAL FORMS OF OMEGA 3

 

Essential Fatty Acid Supplements

 

Several different types of EFA supplements exist in the marketplace today. The

vast majority are related to omega 3 fatty acids. Predominant sources of

supplemental omega 3 fatty acids include flaxseed, fish oil, and single cell

oils derived from algae. Flaxseed is rich in the short-chain omega 3, -linolenic

acid (LNA or 18:33), whereas fish oils are rich in long-chain omega 3 fatty

acids, EPA and DHA. The typical fatty acid profile of common fish oil is listed

in Table 4. Fish oil or fish body oils are a rich source of long-chain omega 3,

with typical concentrations of omega 3 in fish oil being around 30% or about 300

mg of EPA and DHA (180 mg EPA/120 mg DHA) per 1 g capsule.

 

Flax

 

Flaxseed and flaxseed oil products also comprise an abundance of the

supplemental fatty acid market. Flaxseed and its derived oil provide a rich

source of -linolenic acid, the parent omega 3 essential fatty acid. By weight,

flaxseed contains 40% to 45% oil, which on average contains ~55% LNA. Thus, the

overall weight percentage of LNA is ~22% of the whole flaxseed weight. Flaxseed

also has additional nutritional attributes including its high content of soluble

and insoluble fiber and lignans or phytosterols, both of which are thought to be

chemopreventive for certain types of cancers in animal studies.63 Flaxseed oil

(triglyceride) is derived by pressing seeds to expel their oil content and is

typically sold in liquid or capsular form. In supplemental form, whole flaxseed

is typically milled or ground to afford better digestion and integration into

physical mixtures. It is often the mainstay of many derived nutritional products

that manufacturers claim as omega 3 nutritional supplements.

 

It should be noted, however, that flaxseed or flaxseed oil does not contain EPA

or DHA. Thus flaxseed and fish oil are not interchangeable sources of omega 3

fatty acids per se. Before making a recommendation to consume “omega 3” fatty

acids, diligent care should be taken to discern the actual omega 3 constituents

of a product, and a survey of the literature conducted to define the actual

components (LNA, EPA, or DHA) used in clinical trials.

 

Purslane

 

Purslane (Portulaca oleracea) is one of the most highly undervalued food-plants,

partly because it is also one of the world's most common weeds. In England, it

was once cultivated in kitchen gardens and in the 17th century in Massachusetts

served as a salad vegetable. The protein content of purslane has been measured

at 19.9%. Purslane is also rich in antioxidants such as ascorbic acid,

-tocopherol, and glutathione. What few know is that this weed contains more LNA

than any other green leafy vegetable plant tested (4 mg/g fresh weight).

Purslane is grown in Europe as a pot herb and could be cultivated commercially

if there was enough demand.64-66

 

Fish Oil

 

Fish oil supplements have been around for decades. Cod liver oil has been used

for the promotion of health for many years as a source of vitamins A and D, but

it is now well known that this oil also contains significant amounts of omega 3

fatty acids. The classical publications by Bang and Dyerberg, and Dyerberg,

Bang, and Hjorne in the 1970s that ascribed the low incidence of heart disease

in Eskimos to dietary consumption of marine-related omega 3 were the initial

impetus for much of the supplemental fish oil industry development.67,68 Fish

oil is generally derived from oily or fatty fish rich in EPA and DHA. To produce

food-grade fish oil, a fairly complex process of extraction and purification is

performed. The process is designed to eliminate impurities such as free fatty

acids, protein residues, and oxidation products.69 The omega 3 fatty acid

content may also be concentrated by additional techniques such as molecular

distillation and urea precipitation, which separate long-chain polyunsaturates

rich in omega 3 from other fatty acids present in the oil. Highly concentrated

omega 3 preparations are also available as ethyl esters, but tend to be directed

toward more pharmaceutical type applications. Fish oil capsules typically

contain vitamin E, which is added to prevent oxidation.

 

Fish Oil Delivery Systems

 

Traditionally, fish oil delivery systems have either been simply liquid

triglycerides, like cod liver oil, or encapsulated products such as fish oil

capsules. Liquid fish oil, for obvious reasons of palatability, has for the most

part been abandoned. Fish oil capsules are still the predominant supplemental

form of omega 3, but while protecting from initial fishy flavors, side effects

from capsule consumption often include fish oil “burps” or reflux of fishy

flavors. This potential side effect raises compliance concerns in studies

examining supplementation. Newer products have attempted to eliminate fishy

reflux by integrating fish oil into more food-like matrices. Flavored fish oil

emulsions are emerging as a new delivery system that not only offer fish oil in

a palatable state but also may increase bioavailability or absorption of the

fish oil fatty acids, even when taken without food and on an empty stomach.70

Emulsion technology claims to eliminate gastric reflux or burping of fishy

flavors and improve bioavailability by reducing gastric and esophageal emptying

times and improving absorption based on its pre-emulsified state. Ease of use,

compliance, and the ability to consume fairly large dosages of fish oil

conveniently—as sometimes is required in clinical studies or as a part of a

therapeutic regimen—are all potentially positive characteristics of food-type

fish oil emulsions. Daily 10 g to 20 g doses of emulsified fish oil can be

consumed easily with a few spoonfuls, whereas ingesting 20 to 40 fish oil 500 mg

capsules requires a considerably greater effort, especially for children or

patients averse to or incapable of taking capsules.

 

Omega 3 Fatty Acid Enriched Products

 

Food products supplemented with omega 3 fatty acids include an experimental

spread,71 omega 3-enriched eggs from flaxseed-fed hens,72,73 and an omega

3-enriched partially-skimmed cow milk product.74 Research on these products is

still at the early stage, but the main clinical studies are briefly reviewed

below.75,76

 

Healthy male subjects (ages 25-44) maintaining a typical Western diet used a

spread rich in LNA and substituted flaxseed oil for cooking oil. After 4 weeks,

the regimen caused a 2.5-fold increase in plasma lipid concentrations of EPA

compared to controls (n=15) who maintained a diet low in LNA and high in LA. The

authors concluded that using LNA-rich vegetable oil products (the intake of LNA

amounted to 9 g/day) as part of a Western diet low in LA could help increase

levels of EPA.71

 

Male subjects consuming four omega 3-enriched eggs per day for 2 weeks showed a

significant decrease in the ratio of omega 6 to omega 3 in platelet

phospholipids, though without any significant change in their total cholesterol,

plasma triglycerides, or HDL-cholesterol.72 In hypercholesterolemic patients on

a low-fat (Step-1) diet, 12 omega 3-enriched eggs per week for 6 weeks resulted

in a 16% decrease in serum triglycerides; however, a subset of patients also

showed a significant increase in serum total cholesterol and LDL cholesterol.

(Three eggs provide about the same quantity of omega 3 fatty acids as 3 oz of

fish.73)

 

The development of an omega 3-enriched partially-skimmed milk product was based

on the fact that milk is the most efficient medium for fat absorption. In a

preliminary study, healthy, normolipidemic volunteers ingested the product for 6

weeks while maintaining their usual diet and not eating fish. The subjects

developed greatly increased plasma lipid levels of EPA (31%) and DHA (31%),

increased HDL-cholesterol levels (19%), and decreased triglyceride levels (19%)

compared to control subjects. The test product supplied 400 mg/day of omega 3

fatty acids (including 180 mg DHA and 120 mg/day EPA).74

 

A lipid-rich extract of the New Zealand green-lipped mussel (Perna canaliculus)

has been studied in the treatment of osteoarthritis and rheumatoid arthritis,

uses learned from folk medicine.77 Recent controlled clinical trials of

stabilized extract powders of the green-lipped mussel have resulted in

significant improvements in patients with either type of arthritis in morning

stiffness, joint tenderness, night pain, and the functional index.78 The

benefits of the extract are attributed to EPA, DHA, and other long-chain

PUFAs.77,78

 

Beware of Charlatans and Misinformation

 

Consumer and patient confusion regarding fatty acids abounds, often a direct

result of “ambiguous” marketing practices. Contributing to this confusion is the

trading off of studies by using the general term “omega 3” without specifying

LNA, EPA, or DHA content or application. For example, a sales ad or product

literature for a flaxseed or flaxseed oil product may cite that a study

confirmed treatment efficacy with “omega 3,” when in fact the study referenced

was conducted with a high dose of fish oil containing EPA and DHA. Whenever a

product makes a claim regarding composition and function, scientific principles

should be applied to discern fact from fiction.

 

SAFETY PROFILES OF OMEGA 3 FATTY ACIDS

 

Adverse Effects

 

A recent review on the safety of omega 3 fatty acids by the US Food and Drug

Administration concluded that a daily intake of EPA and DHA of up to 3 g is

“generally recognized as safe.”79 The safety profiles of supplemental fish oil

and flaxseed are also good. Dosages as high as 3 g to 8 g of omega 3 fatty acids

per day (10 g to 27 g fish oil) show virtually no significant adverse effects.80

The most common side effects observed with fish oil capsule consumption are

complaints of a fishy taste and belching of fish flavors. At relatively higher

doses, as with any oil, gastrointestinal complaints including loose stools have

been reported.

 

Bleeding

 

Increased bleeding times that are within the normal range have been reported

with very high intake of omega 3 fatty acids (ie, 7 g to 10 g omega 3 per day in

Greenland Eskimos), but this side effect is regarded as posing little threat

with supplemental doses under 5 g of omega 3 as EPA and DHA per day or the

equivalent of ~15 g of fish oil.2,81 However, owing to a lack of data and

because some individuals may be at potential risk of increased bleeding from

dosages of EPA and DHA of greater than 3 g/day, the FDA concluded that only

intake levels limited to 3 g/day are “generally recognized as safe.”79

 

Although there has never been a reported case of clinical bleeding attributed to

fish oil consumption even during surgery,82 obvious consideration should be

given to patients with bleeding disorders and patients taking blood thinners or

anticoagulants. In a prospective, randomized, controlled trial of a fish oil

concentrate (32% DHA, 51% EPA, and 3.7 mg vitamin E/g) in 511 patients

undergoing coronary bypass surgery, a dosage of 4 g/day for 9 months failed to

cause any episodes of excess bleeding compared to the control group not

receiving the fish oil, whether or not patients received 300 mg/day aspirin or

warfarin sufficient to maintain an INR of 2.5-4.2.83

 

Drug Interactions

 

Drug interactions of fish oil and digitalis require further research. In male

rats, a diet supplemented with fish oil concentrate (DHA 129 mg/g, EPA 180 mg/g)

at a dosage of 500 mg/kg/day for 60 days caused the response to digitalis to

increase twofold. The rats also showed a delayed response to a toxic dose of

digitalis. While this study suggests that fish oil might improve the efficacy of

digitalis,84 it also emphasizes the need to closely monitor patients taking

digitalis who are supplementing their diet with fish oil products.

 

Dosage

 

Therapeutic doses of 15 g fish oil per day (~5g EPA and DHA) or greater should

be administered under the supervision of a healthcare professional. In addition,

the type (short- or long-chain) and concentration (mg omega 3/supplement unit)

should be considered to accurately determine daily dosages.

 

NUTRITIONAL ATTRIBUTES OF OMEGA 3

 

Dietary Recommendations

 

Currently, no formal governmental recommendations exist for dietary omega 3

fatty acid intake in the United States, unlike other developed countries such as

Canada.19 Present US recommendations are to consume from 7% to 10% of energy as

PUFA and for LA, a minimum of 1% to 2% energy. Despite the lack of governmental

recommendations, a group of leading US physicians, biochemists, and

nutritionists have released guidelines for adequate intake of omega 3 fatty

acids (Table 5).85 The proposed adequate intake for EPA and DHA is 650 mg per

day (combined) with an LNA intake of 2.2 g per day. It has also been recommended

that the intake of LA be limited to 6.7 g per day from the present average

intake of 10-20 g per day. This recommendation, in effect, serves to reduce the

average dietary LA to LNA ratio from the present 10:1 to 2.3:1. This would

support greater conversion of LNA into long-chain omega 3, which is inhibited by

elevated intakes of LA and high ratios of LA to LNA.

 

Reduced dietary ratios of omega 6 to omega 3 have also been proposed by

countries like Sweden (5:1) and Japan (2 to 4:1) and by the World Health

Organization (5 to 10:1). However, these recommendations have been made under

the assumption that adequate intake levels of EPA and DHA could be met. Without

appreciable dietary amounts of EPA and DHA, the ratio of LA to LNA that supports

adequate conversion of LNA into EPA and DHA is estimated to be 1:1 to 4:1.25,35

 

Other countries, including Canada and the United Kingdom, have established

recommended daily intakes for omega 3 fatty acids.19 Canada recommends

consumption of 1.2 g to 1.6 g omega 3 per day, although the guidelines do not

specify which omega 3 should be consumed. The United Kingdom recommends LNA

consumption be 1% of energy and EPA and DHA should comprise 0.5% energy which,

based on a 2000 calorie diet, equates to 2.2 g of LNA and 1.1 g of EPA and DHA

per day.

 

The American Heart Association (AHA) has recently recommended increasing the

consumption of long-chain omega 3 for the prevention of primary and secondary

heart disease.86 For primary prevention, AHA recommends eating at least two

fatty fish meals per week, a dosage approximately equivalent to 300 mg EPA and

DHA per day. For secondary prevention, “consumption of one fatty fish meal per

day (or alternatively, a fish oil supplement) could result in an omega 3 fatty

acid intake (ie, EPA and DHA) of ~900 mg/d, an amount shown to beneficially

affect coronary heart disease mortality rates in patients with coronary artery

disease.”86,87 The consensus of this report recognizes that while some positive

data regarding consumption of dietary sources of LNA exist, primary benefit is

achieved from dietary sources of the long-chain omega 3 fatty acids EPA and DHA

in the prevention of primary and secondary heart disease.

 

Essential Fatty Acids in Pregnancy and Neonatal Nutrition

 

During pregnancy, EFAs play an important role in maternal health as well as the

health and development of the fetus and of the newborn infant.88,89 The mother

serves as a supply of EFAs for her developing fetus. Neurological tissues,

including the brain and retina, contain high concentrations of DHA. The human

brain is approximately 30% lipid with a gray matter DHA content of around 40%.

Brain DHA content increases three to five times during the last trimester of

pregnancy and again during the first 12 weeks of postnatal life. Coupled with

the observation that 70% of all brain cell division occurs prior to birth and

that a newborn's brain triples in size in the first year of life, the supply of

dietary DHA through the placenta, breast milk, or formula is paramount. It is

believed that humans cannot produce adequate amounts of DHA from LNA to meet the

requirements of brain growth and development, as breast-fed babies have

considerably higher amounts of brain DHA than infants fed formula containing

only LNA. Breast milk also differs in DHA composition depending on diet. In

general, populations consuming greater amounts of dietary omega 3 and lower

amounts of LA have higher levels of DHA in their breast milk. Dietary intake of

DHA in American women is around 35 mg to 50 mg per day, while Japanese women

consume nearly 600 mg of DHA. Thus Japanese women typically have considerably

higher levels of DHA in their breast milk compared to that of American mothers.

 

Crawford noted that human breast milk contained significant amounts of

arachidonic acid (20:46) as well as DHA, and so it was recommended that

artificial infant formula be fortified with long-chain omega 3 and 6 PUFA.90

However, American infant formulas, unlike most formulas in developed countries,

still do not contain long-chain omega 6 and omega 3 fatty acids. Recently,

however, the FDA has approved the use of AA and DHA in infant formulas.

 

Pregnancy is also a known stress on maternal stores of long-chain omega 3.

Significant decreases in omega 3 have been reported in pregnant women at 36

weeks gestation.91 When studied throughout pregnancy, maternal deficits of omega

3 corresponded to late-stage pregnancy, when fetal brain development is greatest

(Table 6). Deficits of omega 3 reportedly persisted 6 weeks postpartum and were

more pronounced in breastfeeding mothers than in non-breastfeeding mothers.

Omega 3 may also play a role in postpartum depression, as elevated fish

consumption correlates with a lower incidence of postpartum depression.92

 

Breastfeeding mothers whose diets were supplemented with DHA from high-DHA eggs,

low-EPA/high-DHA fish oil, or an algae-derived high-DHA triglyceride supplement,

all showed increased breast milk and plasma concentrations of DHA with the

result that their infants showed higher postpartum levels of DHA.93 While no

adverse effects have been found,94,95 there is debate over whether an increased

intake of DHA or omega 3 fatty acids will result in functional benefits to

either the mother or infant. Apart from the need for further investigations on

the mechanisms of long-chain PUFAs on the nervous system,96,97 proof of

functional benefits still require well-designed, randomized, controlled

trials.27,98,99

 

Studies on the potential benefits of omega 3 fatty acid supplementation in

mothers and infants have largely centered on neurological and visual functions.

Benefits to visual function of the newborn are predicated upon the high

concentration of omega 3 fatty acids in the human macula retinae and retina and

on research indicating that DHA plays an important role in retinal

functions.100,101 A systematic review of 12 empirical studies on PUFA intake and

visual acuity resolution in healthy full-term infants found that among

randomized studies, DHA-supplemented formula-fed infants at the age of 2 months

showed a significantly higher acuity compared to non-DHA-supplemented

formula-fed infants (P=0.0003). Among nonrandomized studies, the difference

between DHA-free formula-fed infants and human milk-fed infants was also

significant in favor of DHA supplementation at 2 months (P=0.000001), as well as

at 4 months (P=0.04). Beyond those ages, the lasting benefits of omega 3 fatty

acid supplementation to visual functions is as yet unknown,102,103 but Birch et

al showed benefit until 18 months.104

 

Based on the data available to date, authorities on the subject of omega 3 fatty

acids in infant development conclude that AA should be fed along with DHA in

infant formulas in order to achieve the rate of DHA accumulated in breast-fed

infants; that it appears likely that DHA should be provided to infants for the

first 6 months; and that further research is needed to determine whether the

amount of DHA provided in breast milk (60 mg/day) will be sufficient for infant

formulas.105 As for a dietary amount of DHA for mothers, an expert panel

recently recommended that during lactation and pregnancy women should ensure

that they receive a minimum of 300 mg/day.85

 

Normal Health and the American Diet

 

It is well recognized that omega 3 fatty acids are essential for normal growth

and development.2 It has also become increasingly apparent that adequate intakes

of omega 3 are required to prevent common diseases and that consuming diets rich

in omega 6 at the expense of omega 3 may actually promote the development of

disease. The diet of modern day people in Western cultures has changed

significantly over the past century. Changes in agriculture, food processing

practices, and consumer food preferences have not only resulted in increased fat

and saturated fat consumption but have also significantly altered the EFA

profile of the modern day diet, which is now high in LA and low in long-chain

omega 3.2,19,53 On average, our society consumes around 35% of its caloric

intake from fat, mainly as vegetable oil. The omega 6 LA comprises 7% to 9% of

our daily caloric intake, while the omega 3 LNA makes up about 0.7% of energy.

It is therefore estimated that the dietary ratio of LA to LNA ranges from 10 to

20:1, at which level the metabolism of LNA is strongly suppressed.2,25 Again,

this is far more than the recommended ratio of 2.3:1.

 

Once abundant, omega 3 and omega 6 HUFA currently make up only a very small

amount of the American diet. Omega 3 HUFA intake per day is estimated to be

below 200 mg while intake of omega 6 HUFA varies but in general is less than 600

mg per day.3,19,106 This results from changes in both food consumption patterns

and the composition of fatty acids in foods, mainly processed foods or foods

that contain vegetable oils. Food-consumption patterns have changed with the

increased intake of vegetable oil-containing foods such as processed foods, deep

fried foods, salad dressings, and spreadable margarines.107 Our reliance on

vegetable oil as a primary ingredient in food has grown, replacing vegetables,

fruits, fish, and lean meats—all potential sources of omega 3 fatty acids.

 

The fatty acid content of the animals that we raise for food—chickens, pigs, and

cattle—has also changed as a result of common animal feeding practices. Animals

once raised in a free-ranging environment, with a diet balanced in grasses and

grains, are now raised on feed lots with corn-based diets that contain high

ratios of omega 6 to omega 3, which suppress omega 3 metabolism. Reports as

early as 1968 recognized that range-fed animals contained higher amounts of

omega 3 fatty acids.108-111 Range-fed African cattle, for example, had a

polyunsaturated-to-saturated ratio of 0.7, compared to 0.1 for European

domesticated cattle. Striated muscle from the African cattle contained

significant amounts of HUFA, including DGLA (1%), AA (6%), EPA (3%), DPA-omega 3

(5%) and trace amounts of DHA, or 16% HUFA in tissue fatty acids. Today, the

amounts of these fatty acids in commercial beef are almost undetectable. The

difference between free-ranging and feed-lot animals is primarily due to the

fact that range-fed animals consume a low ratio of LA to LNA (nearly 1:1)

compared to corn-fed feed-lot animals, since corn has a very high LA to LNA

ratio, typically greater than 50:1.

 

The omega 3 content of vegetable oils has also changed. There has been a

substantial effort to reduce the LNA content of vegetable oils through plant

breeding programs to improve stability and shelf life of food products

incorporating vegetable oils.112 Commercially available soy oils now contain LNA

reduced to levels as low as 3%. The common “William's” variety that has been a

main supply of food grade soy oil has an LNA composition of 8%.19

 

The change in the fat and fatty acid content of our diet has occurred primarily

with the advent of industrialization. From an evolutionary perspective, a

significant change in the diet has occurred in a very short time. The diet of

our ancestors in the Paleolithic period (400,000 to 45,000 years ago) was lower

in fat and balanced in omega 6 and omega 3—a ratio of 1:1, or 10- to 20-fold

lower than today's standard.3 The Paleolithic diet was high in green leafy

vegetables, fruits, roots, fish, and free-ranging animals. Fat in the

Paleolithic diet came from wild animals and fish and from fruits and vegetables,

which contain small amounts of relatively LNA-rich fat.113 Wild animals also

contained appreciable amounts of long-chain omega 3, whereas domesticated

animals contain virtually none.108

 

Population studies confirm the consequence of a Western-type diet high in LA and

low in LNA and long-chain omega 3 on omega 3 status, compared to populations

that regularly consume fish. (Table 7, Figure 5).25 Figure 5 shows the omega 3

status of various healthy populations and confirms the competitive nature of

omega 6 and omega 3 fatty acids for the construction of phospholipid.25 For

example, populations with elevated levels of omega 6, like Americans, have low

levels of omega 3, and populations with high levels of omega 3, like the

Swedish, have low levels of omega 6. Additionally, this figure demonstrates that

Minnesotans are near the bottom with respect to omega 3 status. However,

fish-consuming populations, such as the Swedes and Kerala Indians, have high

omega 3 status. Populations that do not eat as much fish, but consume diets with

lower ratios of LA and LNA, such as Nigerians, also have a high omega 3 status

compared to Minnesotans.

 

Furthermore, there is growing evidence that diets high in LA and low in LNA

contribute to diseases including coronary artery disease and cancer (breast,

lung, and colon).114-116 For example, Israeli Jews, who have one of the highest

intakes of LA in the world (12% of calories), also have an unusually high

incidence of obesity, hypertension, diabetes, heart disease, and cancer. These

disease patterns, however, are not observed in non-Jewish populations in the

same region, who consume a traditional Mediterranean diet, rich in

monounsaturated fat.

 

Similar observations have been made in Japan following the advent of

industrialization and the influence of Western culture. Japan has gone from

having one of the highest long-chain omega 3 fatty acid intakes in the world to

a diet almost identical to that of the United States.114 During the past 40

years, the average intake of vegetable oil has increased nearly threefold in

Japan. The previously low omega 6 to omega 3 ratio increased from 2.8:1 in 1955

to 7:1 in 1994 as a result of the food preferences of Japanese youth. Younger

Japanese eat far higher quantities of food products containing vegetable oil and

lower amounts of fish and vegetables. Increases in the incidence of

cardiovascular disease, allergic hypersensitivities, and breast, lung, and colon

cancer have mirrored the changes in the Japanese diet. In animal models, diets

with a high ratio of omega 6 to omega 3 stimulate the formation of lung

cancer.116 In regard to experimental cancer models, it is generally observed

that diets high in LA promote carcinogenesis, while diets high in LNA, EPA, and

DHA, as well as inhibitors of eicosanoid synthesis such as aspirin, suppress

carcinogenesis.116 The incidence of other inflammatory diseases like Crohn's

disease has also risen dramatically in the past 35 years in Japan. From 1966 to

1982, the incidence of Crohn's disease in Japan rose from 10 to 155 cases per

10,000 persons.117

 

In order to bring the US population closer to a healthier fatty acid profile, it

has been recommended that DHA and EPA intake be increased from the present 100

to 200 mg/day to 650 mg/day. The recommended greater than fourfold increase in

DHA and EPA would require approximately the same increase in fish consumption

and a decrease in dietary LA from the current 11-16 g/day to 6.7 g/day. Even a

threefold increase is not presently possible because the United States imports

about 60% of its fish, and fish stocks, while recovering, are in many cases

still depleted. Therefore, in order to achieve the recommended intake of these

omega 3 fatty acids in the United States, the number of fish farms would have to

greatly increase.19 Special consideration would need to be given to the source

of fish in the diet. As a general rule, fish are a good source of omega 3 fatty

acids because their diets are rich in omega 3 fatty acids. However, farm-raised

fish may or may not be fed a omega 3 rich diet like their wild counterparts and

thus there may be variations in the omega 3 fatty acid content of farm-raised

fish.

 

Flaxseed oil has been proposed as a less expensive means of obtaining DHA and

EPA than dietary fish or fish oil supplements.71,118 LNA is the parent fatty

acid of DHA and EPA and occurs in flaxseed oil in high amounts (45% to 50%).

However, as a dietary source of EPA and DHA, LNA-rich vegetable oils such as

flaxseed oil have not proven to be reliable and the conversion rate of LNA to

long-chain omega 3 fatty acids remains to be established. The highest conversion

rate reported to date is 15%, but was not confirmed by others.118 A dietary

ratio of 4 to 1 of linoleic acid to -linolenic acid is needed to get a

conversion of LNA to EPA of 10-11 to 1.119

 

SUPPLEMENTAL OMEGA 3 IN THE TREATMENT OF DISEASE

 

Cardiovascular Disease

 

Epidemiological studies have correlated increased dietary intake of omega 3 with

reduced incidence in coronary heart disease and complications related to this

disease.120 Studies of Inuit populations of Greenland by Bang and Dyerberg, and

Dyerberg, Bang, and Hjorne in the 1970s are accredited with establishing the

cardioprotective effects of omega 3 from marine sources.67,68 These studies

found that the Inuit population had a very low incidence of cardiovascular

disease despite consuming a high-fat diet, which was known at the time to cause

heart disease. This seeming discrepancy between doctrine and experimental

observation was ultimately attributed to the Inuits' consumption of omega 3-rich

foods like whale blubber and fatty fish. Additional epidemiological studies have

reported that increased omega 3 and LNA consumption from fish is

cardioprotective.120 Subsequent to the Inuit study, the Chicago Western Electric

study found that fish consumption as low as 35+ grams per day, or about one

serving per week, significantly reduced the risk of myocardial infarction

(MI).121 Starting in 1958, this study followed over 1800 men ages 40 to 55 who

were free of known cardiovascular disease for a period of 30 years. The study

reported that fish consumption was significantly associated with a 30-year

reduced risk of MI. Multivariate relative risk of death for men consuming 35+

grams of fish per day from coronary artery disease, MI, and nonsudden MI were

0.62, 0.56, and 0.33 respectively, compared to nonfish consumers. Similar

findings were reported in the MRFIT and Honolulu Heart Program studies.120

 

In addition to protecting against the development of cardiovascular disease,

omega 3 fatty acids have also been shown to reduce the risk of dying from a

secondary heart attack after an initial heart attack.8,122 The GISSI heart study

reported results from over 11,000 Italian patients followed for 3.5 years who

were treated with fish oil and/or vitamin E shortly after an initial MI.

Patients randomly received either 850 mg of eicosapentaenoic acid and

docosahexaenoic acid/day at a ratio of 2:1 (equivalent to 100 g of fatty fish

per day), 300 mg vitamin E/day, both treatments, or no supplements (control).

Findings reported that treatment with 850 mg of long-chain omega 3 per day but

not vitamin E resulted in a significantly lower risk (10% to 15%) of primary

endpoints that included death, nonfatal MI, and stroke. Risk of death decreased

by 20% by four-way analysis and myocardial infarction decreased by 45%, as did

nonfatal stroke, nonfatal myocardial infarction, cardiovascular deaths, and

sudden deaths.123

 

Similar findings were reported in the DART study, which used dietary fish as a

source of omega 3 fatty acids.122 The DART study followed over 2000 men with a

previous history of MI. Men in the treatment group consumed two meals of fish

(about 300 g) per week. This study reported no significant differences in

myocardial infarction rate, but did find a 29% lower rate of sudden death in the

group consuming fish in patients followed for 2 years, suggesting that the

reduction in sudden death resulted from the anti-arrhythmic effect of omega 3.

 

The findings were similar in other observational studies, including the Health

Professional Study and the US Physicians' Health Study.120,124 This second study

reported a 52% lower risk of sudden cardiac death for men (n=20551, ages 40-84)

consuming one or more fish meals per week.

 

From the NHANES I Epidemiologic Follow-up Study, the Centers for Disease Control

and Prevention in the United States reported that although white males (ages

25-74) who ate fish once weekly showed only about 75% of the risk of death

compared to men who never ate fish, men who ate fish more frequently showed no

further risk reduction. The study, a 22-year follow-up involving 8825 US

Caucasian and African-American men and women, found no significant reduction in

the risk of cardiovascular death in white men and no significant reduction in

the risk of death from all causes in white women, black men or black women,

after controlling for multiple risk factors. However, the CDC noted the need for

further studies to confirm these results.125

 

A systematic review of 11 prospective cohort studies from 1966 to 1998 on the

association between congestive heart disease (CHD) and fish consumption

concluded that while the biochemical basis for the effect remains unknown, 40-60

g of fish/day versus no fish intake is found in association with a marked

reduction in CHD mortality of 40% to 60%, but only in those at higher risk of

CHD. Subjects at low risk of CHD who also maintained healthy life-styles

appeared to show no added reduction in the risk of CHD from the consumption of

fish. These conclusions are based largely upon two high-quality studies

involving a combined total of 2674 men compared to all other studies for the

period.123

 

Reducing relative ratios of LA to LNA has also demonstrated efficacy in

preventing death after an initial MI.126 The Lyon Diet Heart Study reported a

73% reduction in nonfatal MI for persons consuming a diet based on the diet of

Crete, Greece versus an American Heart Association diet. Subjects in this cohort

were advised to consume a diet rich in monounsaturated fat, while avoiding foods

rich in LA. In this study, dietary counseling of subjects resulted in a

significant decrease in their dietary ratio of LA to LNA—4.11 in treatment

versus 19.6 in control. Lower ratios like this support greater conversion of LNA

into long-chain omega 3, thus improving omega 3 status.

 

In the first year after coronary artery bypass grafting in CHD patients, vein

graft occlusion occurs in 15% to 30% of cases, largely due to atherosclerosis.

The possible benefits of supplementation with fish oil versus no fish oil was

studied in a randomized, controlled study of 610 subjects who received coronary

artery bypass grafting and either warfarin or daily aspirin. The fish oil

supplement was highly concentrated in DHA (32%) and EPA (51%) and contained 3.7

mg vitamin E/g as an antioxidant. In addition, patients were instructed to

reduce their intake of meat products, hard margarine, and milk products (all

sources of saturated fatty acids) and to avoid other fish oil products,

including cod liver oil. One year after surgery, the results showed that the

group taking the highly concentrated fish oil supplement developed significantly

fewer vein graft occlusions (p=0.05) compared to the control group, and an

inverse relationship was found between the frequency of occlusions and the serum

phospholipid levels of omega 3 fatty acids. Significant trends were also seen in

relation to increasing levels of DHA and EPA and decreasing numbers of vein

graft occlusions. The authors concluded that dietary supplementation with omega

3 fatty acids was positively associated with vein graft patency, suggesting that

patients undergoing coronary bypass surgery should be encouraged to maintain a

high intake of these fatty acids.127

 

Atherosclerosis—It is hypothesized that omega 3 fatty acid prevents

atherosclerosis through several mechanisms, including its lowering effects on

serum lipid levels and blood pressure, its anti-inflammatory and anti-thrombotic

properties, and its ability to prevent cardiac arrhythmias, including

ventricular tachycardia and fibrillation.128

 

Fish oil has also been used successfully to treat elevated triglycerides in

diseases such as diabetes. In a placebo controlled blinded trial in adult-onset

diabetes, Connor and coworkers reported that 6 g of EPA and DHA per day resulted

in a 43% reduction in fasting serum triglyceride levels with no significant

adverse effects on fasting serum glucose levels.129 In all of the above studies,

omega 3 lowered the death rate from sudden death and overall mortality without

lowering serum cholesterol levels, indicating the importance of anti-thrombotic,

anti-inflammatory, and anti-arrhythmic effects of omega 3, with secondary

prevention of CHD.

 

Hypertriglyceridemia—A substantial body of evidence supports the use of fish oil

in the treatment of hypertriglyceridemia.130 In normolipidemic subjects, daily

dosages of 2-25 g of omega 3 fatty acids produced decreases in triglyceride

concentrations of 20-60%. In patients with hypertriglyceridemia, decreases of up

to 81% have been reported.131-133 Recognizing the potential benefits of fish oil

against hypertriglyceridemia, the latest guidelines for the treatment of

dyslipidemia and prevention of atherogenesis from the American Association of

Clinical Endocrinologists prudently recommends that diets for patients with

dyslipidemia contain 2-4 g of fish oils/day.134 A recent review of clinical

studies on the effects of omega 3 fatty acids on lipoproteins by Harris found

that 29 parallel and 36 crossover design studies arrived at the same conclusion:

serum triglyceride levels are decreased by omega 3 fatty acids by 25-30% with

dosages of omega 3 fatty acids from fish oil of 3-4 g/day. Looking at the three

studies available on the effects of flaxseed oil on serum lipid concentrations,

Harris found that only “very large amounts” reached effects equivalent to fish

oil in lowering triglyceride concentrations.130

 

Hyperlipidemia—The majority of clinical studies on the consumption of omega 3

fatty acids have concluded that HDL cholesterol concentrations increase by 1-3%,

while LDL cholesterol concentrations increase by 5-10%.130 Since it was

demonstrated that omega 3 fatty acids reduce both the hepatic secretion and

synthesis of VLDL,132 fish oil supplementation has also been shown to lower

VLDL-cholesterol concentrations.135,136 A recent preliminary study in Spanish

women volunteers ages 24-34 who maintained a Mediterranean diet (high in

monounsaturated fatty acids and fats and low in omega 6 fatty acids) and aerobic

training 1-3 hours/week found evidence to suggest that this effect may occur

with short-term administration of fish oil in low dosages (6 capsules of fish

oil/day providing 252 mg DHA and 390 mg EPA); a significant decrease (p<0.05) in

VLDL cholesterol was evident after only 10 days.137

 

Fish Oil Plus HMG-CoA Reductase Inhibitors—Several studies suggest that omega 3

fatty acids may be beneficial to patients receiving HMG-CoA reductase

inhibitors.135,138,139 A placebo controlled, randomized study in 32 Australian

patients with primary mixed (type IIB) hyperlipidemia compared the hypolipidemic

effects of a fish oil supplement (3 g omega 3/day with EPA/DHA in a ratio of

2:1) and the fish oil supplement combined with pravastatin (40 mg/day) to a

placebo. After a treatment period of 12 weeks, results were compared to a 6-week

single-agent treatment period. Pravastatin alone failed to significantly change

VLDL or intermediate density lipoprotein (IDL) concentrations. Fish oil alone

failed to lower IDL concentrations, but significantly lowered the VLDL

concentration by 37% or more (p<0.05). When the two treatments were combined,

patients showed a significant (35% or more) reduction in concentrations of both

IDL and VLDL (both p<0.01). The authors noted that the short-term combination of

these agents appeared to be safe.135

 

In 14 Japanese patients with hyperlipidemia previously treated with HMG-CoA

reductase inhibitors (pravastatin or simvastatin) for 24-36 months, a

combination of EPA (900-1800 mg/day) for 3 months resulted in significant

reductions in serum concentrations of triglycerides and total cholesterol

compared to HMG-CoA reductase inhibitors alone (p<0.05 and p<0.01,

respectively), and serum HDL cholesterol concentrations showed a significant

increase (p<0.05).138

 

In a randomized, controlled, crossover design study, 10 patients with

heterozygous familial hypercholesterolemia were randomized to a group receiving

either lovastatin (20 mg twice daily) or a high dose of fish oil in capsules (27

g/day for 6 weeks). Patients followed a controlled-fat, low-cholesterol diet

from beginning to end which was supplemented with olive oil in capsules (27

g/day for 4 weeks). This was followed with a washout period of 4 weeks before

patients were crossed over and in the last period received fish oil (27 g/day)

plus lovastatin (20 mg twice daily) for 6 weeks. The results showed that on fish

oil alone there was a significant decrease in total cholesterol, no change in

LDL cholesterol, a significant increase in HDL cholesterol (9%), and a

significant decrease in triglyceride levels (43%). The combination of lovastatin

and fish oil showed more beneficial results than either fish oil or lovastatin

alone: total cholesterol decreased 39%, LDL cholesterol decreased 45%,

triglyceride levels decreased 51% (each p<0.01), and HDL cholesterol remained

the same. The authors concluded that lovastatin combined with fish oil had a

favorable additive effect on triglyceride levels and LDL cholesterol in these

patients.139

 

Diabetes

 

The majority of clinical studies on omega 3 fatty acids in the treatment of

patients with diabetes have been open trials of short duration (2-8 weeks) with

less than 20 patients. Their aim has primarily been to determine effects on

glucose tolerance and plasma lipoproteins, particularly triglyceride levels.

According to a recent meta-analysis of studies on fish oil in the treatment of

diabetes, triglyceride levels were lowered by close to 30%. The majority of

studies in patients with type 1 diabetes (n=12) showed significant decreases in

fasting glucose levels without significant adverse effects on glycemic control.

Of 14 studies on fish oil in the treatment of patients with type 2 diabetes, the

meta-analysis found that, although glycemic control was not adversely affected,

there was a tendency for fasting blood glucose levels to increase.140 Examples

of findings from among the placebo controlled trials on fish oil in diabetes are

reviewed in the following.

 

Type 1 Diabetes—A randomized, placebo controlled trial of fish oil (5 g three

times/day for 6 weeks) in 41 Caucasian patients with type 1 diabetes (ages

30-59) examined changes in thromboxane A2 levels produced by platelets, blood

lipids, platelet function, and albuminuria. Fish oil was tested because DHA and

EPA were shown to competitively inhibit the formation of thromboxane A2, a

mediator of platelet aggregation and vasoconstriction. Levels of thromboxane A2

were produced in greater amounts in the platelets of patients with diabetes

compared to those without the disease. The fish oil provided 1.9 g DHA plus 2.7

g EPA/day and a low dose of olive oil was used as the placebo. Patients were

excluded if they had known coagulation disorders or hyperlipidemia, and all

participants were instructed to eat a fat-free breakfast on those mornings when

blood samples were taken. Significant changes evident at the end of 6 weeks were

found in the fish oil group compared to placebo in a lowered production of

thromboxane and an increase in total cholesterol, probably due to increased LDL

cholesterol. Platelet aggregation showed no consistent change in rate or maximum

amount, but the lag time prior to when platelets aggregated was prolonged in the

fish oil group relative to the placebo group, which is consistent with a

partially inhibited production of thromboxane and changes in the fatty acid

composition of platelet membranes. No consistent change in the urinary excretion

of albumin was evident, nor was it entirely expected; the fish oil used was much

weaker than a specific thromboxane inhibitor and only a few of the patients had

microalbuminuria.141

 

Since it was noted that red blood cell membranes of patients with type 1

diabetes show decreased levels of omega 3 fatty acids in an inverse relation to

plasma glycosylated hemoglobin (HbA1c) levels, Stiefel and coworkers conducted a

prospective, randomized, controlled dietary intervention study on the effects of

low-dose omega 3 fatty acids (330 mg DHA plus 630 mg EPA/day) on these

parameters in 18 patients with type 1 diabetes. The control group maintained

their usual diet while the treatment group supplemented their usual diet with

omega 3 fatty acids. Those on the supplement showed a significant increase in

the omega 3 fatty acid content of membrane lipids and a significant decrease in

HbA1c, yet without significant changes in insulin requirements. Neural

conduction showed a slight but significant improvement. Stiefel and colleagues

concluded that dietary supplementation with a low dose of omega 3 fatty acids in

patients with type 1 diabetes appeared to change their cell membrane fatty acid

composition while it improved metabolic control and slightly improved neural

conduction.142

 

Type 2 Diabetes—Hendra and coworkers conducted one of the largest studies to

date on the effects of fish oil preparation on patients with type 2 diabetes

(n=80). Along with effects on hemostatic function, they evaluated patients'

fasting glucose and lipid levels. The prospective double blind, randomized,

placebo controlled study found that after 10 g of fish oil per day was

administered for 6 weeks, the EPA content of platelet membranes was

significantly increased (p<0.001) compared to the placebo (olive oil) and total

triglycerides were significantly decreased, yet no change in total cholesterol

was evident. After 3 weeks, but not after 6 weeks of treatment, fasting plasma

glucose levels were significantly increased (p<0.01). Whole blood platelet

spontaneous aggregation decreased after 6 weeks (p<0.02), yet without evidence

of changes in agonist-induced platelet aggregation, platelet factor IV levels,

or plasma -thromboglobulin levels, and platelet-rich plasma showed no

significant change in thromboxane generation. Hendra and colleagues concluded

that despite the benefit of lower triglyceride levels from the fish oil

preparation, a significant increase in clotting factor VII (p<0.02) and the

increase in fasting plasma glucose at 3 weeks (p<0.01) were deleterious effects

which suggested that the dosage used (10 g/day) was too high to be recommended

as a dietary aid to reduce the risk of cardiovascular disease in type 2

patients.143

 

The effects of a moderate intake of omega 3 fatty acids on glycemic control in

hypertriglyceridemic patients with diabetes was recently investigated by Sirtori

and colleagues in a large, multicenter, randomized, double blind placebo

controlled study conducted in Italy.144 The largest study of its kind, it

enrolled patients of both sexes (n=935; ages 45-80; 62% male) and included

hypertriglyceridemic patients without diabetes. Of the total, 55% were made up

of subjects with either type 2 diabetes or impaired glucose tolerance, and 21%

satisfied the criteria of syndrome X (arterial hypertension, impaired glucose

tolerance, hypertriglyceridemia, and low HDL cholesterol).

 

After a washout and run-in period of 4 weeks, patients received either placebo

(olive oil) or omega 3 fatty acids (1050 mg DHA plus 1530 mg EPA) three times

per day for 2 months, equivalent to the amount of DHA plus EPA found in

approximately 150 g of fresh salmon. This treatment period was followed by a

further 4 months with a reduced dosage of omega 3 fatty acids (one capsule taken

twice daily containing 700 mg DHA plus 1020 mg EPA). The supplements were taken

before main meals and patients maintained their body weight with an isoenergetic

diet along with instructions to reduce foods rich in AA (eggs, liver, heart, and

lungs) or to eat them no more than once per week. If insulin was required, the

patient was excluded from the study.

 

Treatment with omega 3 fatty acids had no significant effect on oral glucose

tolerance in either type 2 patients or those with impaired glucose tolerance,

and major glycemic indices (fasting glucose, insulinemia, and HbA1c) showed no

alterations. LDL cholesterol concentrations showed a significant difference

(p=0.048) between an increase of 3% in the placebo group and 6% in the group

receiving the omega 3 supplement, as did the comparative decrease in

triacylglycerol concentrations: -6.54% in the placebo group and -21.53% in the

omega 3 group (p<0.0001). However, those with impaired glucose tolerance showed

no significant difference in triacylglycerol concentrations compared to

normoglycemic patients. Although all groups showed a slight increase in HDL

concentrations (+5%) compared to their corresponding placebo group, those with

type 2 diabetes or glucose intolerance showed a significantly greater increase

(+8.31% versus 4.53% for placebo; p<0.05). The patients with traits conforming

to syndrome X showed no improvement in symptoms, except for lipoprotein

metabolism. The results indicated that omega 3 fatty acids, in a moderate daily

dose, “can provide a suitable option for the management of the middle-aged

population, including postmenopausal women, in whom hypertriglyceridemia may be

a major risk for cardiovascular death.”

 

Inflammatory disorders

 

Omega 3 fatty acids from fish oils have been extensively studied in inflammatory

diseases because of their anti-inflammatory properties. The inflammatory cascade

plays a significant role in the proper functioning of the immune response;

however, it is well recognized as a major cause of morbidity in inflammatory

disorders and diseases.145 Patients with inflammatory diseases such as

rheumatoid arthritis and inflammatory bowel disorder have elevated production of

group 2 eicosanoids including PGE2 and LTB4, and inflammatory cytokines

including IL-1 and TNF. Many pharmaceutical therapies are thus directed at

inhibiting the production of these mediators.

 

The role that eicosanoids and cytokines play in the development of disease is

multifactorial. Evidence presented herein suggests that diets elevated in omega

6 at the expense of omega 3 fatty acids result in eicosanoid precursor pools

dominated by AA. This imbalance results in an inflammatory mediator production

that favors group 2 eicosanoids and a pro-inflammatory state. Returning omega 3

fatty acids to the diet, either in the form of long-chain omega 3 (EPA and DHA)

or short chain omega 3 (LNA), begins to restore balance between omega 6 and

omega 3 fatty acids in the eicosanoid precursor pool. When a greater balance

between AA and EPA and DHA exists in the eicosanoid precursor pool, inflammatory

mediator production potential is reduced. Measuring fatty acid profiles of

plasma phospholipids determines levels of omega 3 and omega 6 fatty acids and

thus is a useful tool at estimating inflammatory potentials.146 The underlying

hypothesis is that an imbalance of dietary omega 6 and omega 3 fatty acids, and

subsequently tissue omega 6 and omega 3 fatty acids, contributes to disease and

disease morbidity, and that increasing the omega 3 fatty acid content of the

diet while decreasing omega 6 fatty acids serves to balance the cellular

eicosanoid precursor pool and subsequent inflammatory response.147

 

Inflammatory Bowel Disorders—The plasma fatty acid profiles of 47 patients with

chronic intestinal disorders, most of whom were diagnosed with Crohn's disease,

showed an increased ratio of omega 6 fatty acid precursors compared to those of

control and reference subjects (n=57), and over 25% showed evidence of EFA

deficiency including deficits in omega 3 fatty acids. This “EFA insufficiency”

is proposed to be a factor both contributing to the pathology of chronic

intestinal disease and a consequence of it. It has therefore been recommended

that in treating patients with chronic intestinal disease, imbalances and

deficiencies of EFAs be evaluated and their treatment include dietary

supplementation with fish oil and vegetable oils rich in EFAs, and, if

necessary, lipids administered intravenously.148

 

Lorenz and coworkers found no significant change in Crohn's disease patients and

a moderate but insignificant improvement in patients with ulcerative colitis in

a 7-month trial of fish oil in 39 men with inflammatory bowel disease. The fish

oil supplement provided 3.2 g of omega 3 fatty acids/day.149 However, in other

trials, larger doses of omega 3 fatty acids are reported to be beneficial in

both diseases.

 

Stenson reported significant improvements in disease activity in patients with

ulcerative colitis who were supplemented with 4.5 g of EPA and DHA (15 g fish

oil) after 8 weeks of treatment, and in a subsequent study he found similar

results in a larger placebo controlled trial, feeding 5.4 g EPA and DHA (18 g

fish oil) after 4 months.150 Fish oil treatment in this study resulted in

significant weight gain, reduced LTB4 production, and improved endoscopy score.

 

Steroid-sparing effects (reduced dosage of anti-inflammatory agents or

elimination of steroids) have also been reported in ulcerative colitis patients

treated with fish oil.151 Seventy-two percent of patients reported a

steroid-sparing effect after receiving 4.2 g of EPA and DHA for 3 months, and

56% of patients had a significantly improved disease activity score.151 In

Crohn's disease patients, Belluzzi reported increased remission percentages

after 1 year of 2.7 g of EPA and DHA (9 g of fish oil) versus placebo control.57

After 1 year of treatment, only 10% of the placebo patients remained in

remission, while 59% of the fish oil-treated patients remained in remission.

 

Arthritis—Fish oil supplementation has also demonstrated efficacy in the

treatment of rheumatoid arthritis.13,152 A preliminary investigation of the

omega 3 fatty acid profile of synovial fluid in rheumatoid arthritis patients in

Spain reported low levels compared to controls, significantly so for EPA and the

precursor LNA.153 Fish oil treatment reportedly resulted in decreased joint

tenderness and morning stiffness and improved grip strength and joint activity

indices for patients supplemented with 3 g to 6 g of EPA and DHA per day.

Generally, improvements in symptomatology began to occur 12 to 22 weeks after

initiation of fish oil treatment. Similar results were reported in a 12-week

trial of fish oil in rheumatoid arthritis which provided 3.6 g PUFA/day.154

 

It has also been reported that some arthritic patients administered a high dose

of fish oil were able to reduce their dosage of nonsteroidal anti-inflammatory

drugs (NSAIDs).155 Thus, fish oil therapy may be desirable for persons with

gastrointestinal complications related to chronic NSAID consumption.

 

The improvements seen in arthritic patients administered fish oil supplements

have generally been modest,13 though significant. A meta-analysis of seven

trials of fish oil in the treatment of rheumatoid arthritis (randomized, double

blind, placebo controlled, and either crossover or parallel in design)

demonstrated that 3 months of dietary supplementation with fish oil caused a

significant reduction in tender joints (p<0.001) compared to controls. After

re-analysis of a previous meta-analysis, improvements in morning stiffness were

less than statistically significant.156

 

Significant benefits from fish oil in the treatment of rheumatoid arthritis

continue to be reported from more recent trials.155,157 For example, Kremer and

colleagues examined the drug-sparing, cytokine-modulating, and clinical efficacy

of high-dose fish oil (130 mg/kg/day, eg, 9.75 g/75 kg/day) in 66 rheumatoid

arthritis patients who were allowed to continue taking diclofenac (75 mg twice

daily) and in 56 cases, various slow-acting antirheumatic agents. The 30-week,

double blind, placebo controlled (corn oil), prospective study found significant

improvements in the following: decreased IL-1 levels compared to baseline during

weeks 18-22; decreased number of painful joints compared to placebo at 8 weeks

(p=0.043); and no significant NSAID-sparing effect. It was noted that the

benefits found were no greater than those of other studies using 3-6 g fish

oil/day.

 

Geusens and colleagues conducted a 12-month, double blind, randomized study of

fish oil in 90 rheumatoid arthritis patients. They compared the effects of fish

oil in dosages of either 3 g/day (omega 3, 1.3 g/day) plus 3 g olive oil/day, 6

g fish oil/day (omega 3, 2.6 g/day), or olive oil at 6 g/day. Throughout the

trial, patients continued to take disease-modifying antirheumatic drugs (DMARDs)

and/or NSAIDs at stable dosages and received advice to eat fish once weekly. In

approximate amounts, the diet prescribed contained 30% fat, 50-58% carbohydrate,

and 12-15% protein. The amount of animal fat allowed was less than 100 g/day.

Sixty patients completed the study. At 12 months, the only group showing

significant overall improvement (20-25% from 3-12 months) was the highest dose

fish oil group (6 g/day). Compared to placebo, the 6 g/day group showed a

significant decrease in the use of NSAIDs and/or DMARDs (47% versus 15%,

p<0.05), and a significant increase in grip strength at 6 and 9 months (p<0.05).

The number of painful joints was significantly decreased in all treatment groups

compared to baseline, but not compared to each other, and no significant changes

in morning stiffness were found in any group. Gastric discomfort occurred in

6/30 patients on the 6 g/day dose of fish oil, 4/30 in the low dose group, and

2/30 on placebo.157

 

IgA Nephropathy—Fish oil treatment has also been used successfully to treat

patients with inflammatory disorders of the kidney. In 106 patients with IgA

nephropathy, Donadio reported that 12 g of fish oil per day resulted in a

significant reduction in death (p=0.006) and improved renal function compared to

placebo.55

 

Dysmenorrhea

 

PGE2 is a metabolic product of AA which is metabolized to produce PGF2. In

dysmenorrheic women, elevated plasma levels of PGF2 are associated with

menstrual pain which is treated with prostaglandin synthetase inhibitors such as

aspirin and indomethacin.158,159 Omega 3 fatty acids also produce a class of

prostaglandins (PGE3), but these are believed to be less active (“aggressive”)

than PGFs. Support for this hypothesis was found in an epidemiological study on

Danish women (n=181, ages 20-45). Self-administered questionnaires from the

subjects, none of who were pregnant or using oral contraceptives, revealed

highly significant correlations with menstrual pain and low intakes of fish and

vitamin B12. Menstrual pain was significantly higher among those with a low

intake of omega 3 fatty acids, which in turn significantly coincided with a low

ratio of omega 3/omega 6.159

 

Preliminary studies on the use of fish oil in the amelioration of symptoms of

dysmenorrhea have shown promising results.160,161 In a randomized, double blind,

placebo controlled, crossover design study in 37 American adolescents ages 15-18

with dysmenorrhea, a 2 month treatment with fish oil (capsules providing 720 mg

DHA, 1080 mg EPA plus 1.5 mg vitamin E/day) was reported to produce a

significant reduction in the Cox Menstrual Symptom Scale in the fish oil group

compared to the placebo group (p<0.004). Use of ibuprofen to control menstrual

pain was significantly less during consumption of fish oil compared to

placebo.160

 

In Denmark, a double blind, placebo controlled study was conducted to test the

hypothesis that menstrual cramps are mediated by prostaglandins. For 3 months or

a minimum of three menstrual periods, Danish women (n=70, ages 16-39) received

five capsules/day of placebo, fish oil, seal oil, or fish oil with vitamin B12.

Vitamin E (2.5 mg/capsule) was added to the marine oil preparations to inhibit

peroxidation. Before the dietary intervention, the ratio of omega 3/omega 6 in

the participants was low (0.096). When pain, interference with daily activities,

and other symptoms of dysmenorrhea were taken together, all three of the marine

oil preparations produced significant improvements; however, the best results

were found in the fish oil with vitamin B12 group. Unlike the others, they

showed a significant reduction in the visual analog pain score that persisted

during the washout period for a minimum of three menstrual periods. All groups

receiving marine oil supplementation reported reduced symptoms of dysmenorrhea,

but in the fish oil with B12 group, symptom reduction was over 50% higher. The

authors commented that the use of omega 3 fatty acids and B12 as a dietary

supplement in young women with dysmenorrhea might offer an alternative to

treatment with NSAIDS.161

 

Asthma

 

Epidemiological studies in Australia have suggested that children who eat fish

more often than once per week have a reduced risk of developing airway

hyper-responsiveness. A study was undertaken to investigate the association of

diet and asthma.162 Evidence was found suggesting that children who eat fresh,

oily fish containing greater than 2% fat have a significantly reduced risk of

both airway hyper-responsiveness and recent wheeze (current asthma). The

evidence for a reduced risk of asthma in adults in association with increased

fish consumption has largely been weak to negative.163,164 However, a recent

cross-sectional analysis of data in the United States derived from the National

Health and Nutrition Examination Survey found an increase in the forced

expiratory volume at 1 second (FEV1) of approximately 80 mL in adults, including

asthmatics, who consumed high amounts of fish compared to adults who consumed

low amounts.163

 

Clinical studies on the effects of fish oil in patients with asthma have been

relatively few and small, involving less than 40 patients. In a review of eight

randomized controlled trials (1986-1998) of fish oil in the treatment of asthma,

reviewers found a lack of consistent effect on outcomes of asthma symptoms,

FEV1, bronchial hyper-reactivity, use of asthma medication, and peak flow rate.

None of the studies reviewed reported exacerbation of asthma and no adverse

events were reported in association with fish oil supplementation.165

 

As for hay fever, a long-term, parallel, double blind, placebo controlled trial

of high-dose fish oil (providing DHA 2.2 g/day and EPA 3.2 g/day) found no

prevention of asthma and seasonal hay fever in pollen-sensitive, nonsmoking

asthmatics.12

 

Cystic Fibrosis

 

Leukotriene B4 (LTB4) has been proposed as a mediator of the inflammatory

response in the lungs of cystic fibrosis (CF) patients. Furthermore, it was

postulated that an overproduction of LTB4, if sustained, could lead to a

desensitization of neutrophils in the pulmonary circulation of CF patients

resulting in a chemotactic defect of circulating neutrophils. In these patients,

the chemotactic response of neutrophils to LTB4 was found to be significantly

less than that of healthy controls, suggesting that an increase in LTB4-induced

chemotaxis of neutrophils might be of benefit to cystic fibrosis patients.245

 

In a randomized, double blind, placebo controlled, crossover design trial, 16

cystic fibrosis patients (ages 12-26) with lung dysfunction received fish oil

supplementation (2.7 g EPA/day for 6 weeks) while maintaining their normal diet

and medications (antibiotics, pancreatic enzyme supplementation, and

bronchodilator therapy). Fish oil supplementation resulted in significantly

reduced LTB4 production and improved lung function, including increased tidal

volume and sputum generation. The chemotaxis of circulating neutrophils to LTB4,

which was significantly lower in all the subjects at baseline compared to

healthy volunteers (p<0.0001), showed a highly significant improvement (p<0.001)

with responses becoming nearly normal after the treatment with fish oil. No such

change was found in patients on placebo (olive oil). Treatment was well

tolerated and there were no reports of significant adverse effects. In order to

prevent steatorrhea, supplementation with pancreatic enzymes was increased by

the patients.12

 

Psychiatric Disorders

 

Depression—The investigation of the treatment of psychiatric disorders with

omega 3 fatty acids is a relatively new but potentially promising field of

research.11,92,167 Major depression has been characterized by deficits of plasma

and red blood cell omega 3 fatty acids, including EPA and DHA.168,169 Adams

reported that the severity of depression correlated clinically with the ratio of

AA to EPA in plasma phospholipids. Similarly, Peet reported significant

depletion of omega 3 fatty acids in red blood cells that was postulated to be

related to oxidative stress and/or elevated activity of phospholipase A2. Maes

has also reported that the exaggerated production of pro-inflammatory cytokines

and eicosanoids from external as well as internal stressors may be a

contributing factor in major depression.170

 

The level of fish consumption has also been noted to be predictive of major

depression and suicide. Hibbeln reported that persons consuming relatively

greater amounts of fish were less likely to suffer from major depression and

postpartum depression, and less likely to commit suicide.92 He also demonstrated

that plasma levels of PUFA essential fatty acids correlate with CNS metabolism

of dopamine and serotonin.175 It has been suggested that the remarkable increase

in depression during the past 85 years may be attributable to the sharp rise in

the ratio of omega 6 to omega 3 in the diet, which favors the production of

pro-inflammatory eicosanoids and cytokines.

 

Supporting this theory, a recent study found that in patients with major

depression, monosaturated fatty acids and omega 6 fatty acids in phospholipids

appear to show a compensatory increase with a concomitant deficiency of omega 3

fatty acids. The effect of antidepressants on the fatty acid profile of patients

was not significant. The results of the study suggested that in depression:

omega 3 fatty acids undergo abnormal metabolism; that their alterations show a

relation to inflammatory responses in depression; and that, regardless of a

successful treatment using antidepressants, fatty acid disorders may persist.

 

Serum zinc levels were also significantly lower in those with major depression

compared to those of healthy volunteers (p<0.0003). Compared to depressed

patients with normal levels of zinc, those with lower levels also showed lower

levels of DHA. Comparing the total omega 6 to total omega 3 fatty acid ratio and

the total omega 3 fatty acid levels between the three groups revealed

significant between-group differences. Patients with major depression who had

lower levels of zinc showed the largest deviations from normal.171 Metabolism,

utilization, and peroxidation of fatty acids depend on zinc and zinc plays a

fundamental role in controlling 6-desaturase activity, which catalyses the

conversion of LNA to EPA.172

 

In a related study, patients with major depression showed significantly lower

levels of omega 3 fatty acids in serum cholesteryl esters compared to patients

with minor depression and healthy controls.173 Bruinsma found that in healthy

middle-aged women, dietary long-chain omega 3 fatty acid intake was inversely

associated with depression. Significant associations were found with both the

severity of depression and greater levels of body dissatisfaction.174

 

Limited intervention data are available for the treatment of depression with

omega 3 fatty acids.167 In a pilot study, supplementation of long-chain omega 3

was reported to improve outcome in bipolar disorders. In 1999, Stoll, in a

placebo controlled, double blinded study in 30 patients with bipolar depression,

reported that 9.6 g/day of omega 3 as EPA (6.2 g) and DHA (3.4 g) resulted in

significant improvements in remission and outcome compared to placebo (olive

oil). The reductions in depressive and mania-related events in the omega 3

treatment group were so significant that the study was stopped after 4 months

and a larger multicenter study is in progress.

 

Schizophrenia—Membrane and fatty acid abnormalities have also been reported in

schizophrenic patients.176 The so-called “phospholipid membrane hypothesis” of

schizophrenia proposed by Horrobin suggests that schizophrenia may be a result

of an excess and/or deficit of prostaglandins related to omega 6 and omega 3

polyunsaturated fatty acids.177 Marked deficits of long-chain omega 3 and omega

6 have been reported in schizophrenic patients in several studies.11 However,

intervention with omega 6 fatty acids has yielded conflicting results, whereas

trials with omega 3 fatty acids have reported positive findings. In 20

schizophrenic patients, a 6-week trial of 10 g of fish oil per day resulted in a

17% improvement in the Positive and Negative Symptom Scale (PANSS), and a 40%

improvement in the Abnormal Involuntary Movement Scale (AIMS).177

 

Similar findings were reported in patients treated with an EPA-enriched oil.178

In a double blind placebo controlled trial, Peet reported that 45 schizophrenic

patients supplemented with 2 g per day EPA had a 24% improvement in PANSS

scoring after 3 months of treatment, but little effect was found in the

DHA-treated group. Collectively, adjunctive therapy with omega 3 fatty acids in

major depression and schizophrenia is a new but potentially promising area of

research that highlights not only the significance of adequate dietary intake of

omega 3 for normal health, but also its therapeutic potential.

 

Attention-Deficit Hyperactivity Disorder—Alterations in blood lipid EFAs have

been reported in children with attention-deficit hyperactivity disorder (ADHD).

In 53 ADHD patients, Burgess reported significant deficits of PUFA, including

EPA and DHA, in plasma and red blood cell lipids.179 Twenty-one of these

patients exhibited symptoms of EFA deficiency, including dry skin and hair

abnormalities, increased thirst and urination, and brittle nails. Subsets of the

ADHD population with lower compositions of blood lipid omega 3 had significantly

more behavioral problems (including temper tantrums) and learning, health, and

sleep-related problems than subjects with higher levels of omega 3. Clinical

trials are currently underway to determine the potential use of EFAs in the

treatment of ADHD.

 

Psychological Stress—Mice fed a diet deficient in DHA showed significantly

greater anxiety compared to mice fed a DHA-sufficient diet. Subsequently, a

double blind, placebo controlled study on psychological stress in medical

students was conducted prior to their undergoing exams. One group was given

capsules containing 3-3.6 g/day of a DHA-rich fish oil (49.3% DHA) for 3 months,

while the control group received capsules containing the same amount of soybean

oil plus a small amount of the DHA-rich fish oil (0.5% DHA). Medical students

receiving the DHA-rich supplement showed no change, whereas the control group

exhibited a significant increase in external aggression. Plasma concentrations

of DHA at baseline were 3% and rose to 6% after the supplementation period.180

Typical plasma DHA concentrations in Americans are 1% or less.175

 

Cancer

 

A growing body of in vitro, animal, epidemiological, and clinical studies is

producing evidence which supports the use of omega 3 fatty acids in the

prevention of colon and breast cancers and their use combined with

chemotherapy.181 Prostate cancer has also responded to dietary lipids in animal

models182 and is the subject of ongoing investigations.183,184 The proposed

chemopreventive mechanisms of omega 3 fatty acids in cancer of the breast and

colon are multiple and include the suppression of eicosanoid production

(produced by omega 6 fatty acid precursors), enhancement of apoptosis, increase

in anti-angiogenic activity, and inhibition of tumor cell growth.181 Evidence

from animal studies and more recent human studies suggests that a high intake of

omega 6 fatty acids increases the amount of free estrogen available for hormonal

catabolism and oxidative damage to DNA—mechanisms that can contribute to the

development of cancer of the colon and breast at several stages. Research in

animals and humans suggests that omega 3 fatty acids from fish oil can protect

against both kinds of cancer.185

 

Colon Cancer—In research on human large bowel cancer, particular attention is

being paid to dysregulation of AA metabolism which leads to over-expression of

cyclooxygenase-2 (COX-2), in turn resulting in an excess of prostaglandin

production, both of which have been shown to allow tumor self-promotion.

Similarly, NSAIDS have shown promise as chemopreventive agents with what appears

to be a similar mechanism: they inhibit prostaglandin biosynthesis at the level

of COX-2.186 A high level of dietary omega 6 fatty acids is again implicated,

with toxic effects on the epithelium of the colon, increased proliferation of

colon crypt cell formation, increased levels of secondary bile acids in the

colon, and increased levels of prostaglandin.

 

The deleterious effect of omega 6 fatty acids was recently demonstrated in a

study of male rats which compared diets containing a high amount of a high-fat

fish oil rich in omega 3 fatty acids and a diet containing high amounts of a

high-fat corn oil rich in omega 6 fatty acids. Striking changes were discovered

in the level of expression of ras-p21, a gene implicated in the development of

human colon cancer. For the induction of colon carcinogenesis, the rats received

a carcinogen (azoxymethane) subcutaneously. The corn oil-supplemented diet

resulted in enhanced ras-p21 expression induced by the carcinogen and an

increased incidence and multiplicity of visible colon tumors, whereas the fish

oil-supplemented rats showed the opposite: a lower multiplicity of colon tumors,

a decreased incidence of tumors, and interference with ras-p21, whereby the

amount of membrane-bound ras-p21 was decreased while its level in cytoplasm was

increased.187

 

Breast Cancer—Animal studies have repeatedly shown that mammary tumor

development is enhanced by dietary omega 6 fatty acids and inhibited by dietary

omega 3 fatty acids.188-190 Moreover, in one of the first studies to point this

out, rats fed a diet high in saturated fat from butter, coconut oil, and tallow

(20% w/w) showed close to half as many mammary tumors as rats fed diets high in

omega 6 fatty acids from equivalent amounts of sunflower oil, cottonseed oil, or

corn oil. A diet containing even a low amount of omega 6 fatty acid (0.5% corn

oil) produced nearly as many tumors as one containing 20% saturated fats.191

Rose and coworkers have shown that the growth and metastasis of human breast

cancer cells is stimulated in mice administered a diet rich in the omega 6, LA.

Conversely, a diet supplemented with DHA and EPA suppressed the growth and

metastasis of the tumors' cell line.189 In a further study, they administered a

high-fat diet to female mice which contained 8% LA and a week later implanted

human breast cancer cells. After the tumors grew, the mice either continued the

same diet or received diets containing 2%, 4%, or 8% DHA or EPA. After 8 weeks,

the groups receiving either DHA or EPA showed significantly less lung metastases

compared to mice fed the high-fat, 8% LA diet. In another experiment, mice

administered the DHA- or EPA-supplemented diets 7 days prior to surgery showed

dose-dependently and significantly less severe lung metastases at all three

dosages. Post-surgical feeding of DHA (2% and 4%), but not EPA, caused a

significant reduction in lung metastases.192

 

One of the possible chemoprotective mechanisms of omega 3 fatty acids is the

ability of unsaturated fatty acids to inhibit cancer cell adhesion, which is an

essential requirement of cancer cells before they can metastasize; only by

adhering to the subendothelial matrix are tumor cells able to invade secondary

organs. In vitro studies have shown that levels of EPA (5-10 mg/mL) found in

people who consume high amounts of fish oil can inhibit the adhesion of human

breast cancer cells to the subendothelial matrix at the level of the basement

membrane where metastasis occurs. The effect was also found from oleic acid (at

2.5 µg/mL).192

 

In a 32-country analysis of dietary components and the risk of breast cancer,

the caloric amount of fat in the diet showed the strongest association.

Mortality from breast cancer was also most strongly associated with dietary fat.

Of all the dietary components taken into account, only the percentage of

calories from fish significantly improved the association of fat with breast

cancer mortality and incidence. Supporting the assumption that fish oil may

protect against breast cancer, a study of 73 female breast cancer patients found

significantly lower dietary EPA and DHA compared to 55 women with benign breast

disease. Compared to postmenopausal women with benign breast disease,

phospholipids of breast adipose tissue from the postmenopausal breast cancer

patients showed a significantly lower percentage of DHA.193

 

Bagga et al demonstrated that breast adipose tissue levels of omega 3 fatty

acids of breast cancer patients can be changed by adding fish oil to a low-fat

diet. For 3 months, women with high-risk (stage II or III) localized breast

cancer consumed a very low-fat (15%), high-fiber diet. A daily fish oil

supplement (ten 1000 mg capsules/day) containing 12% DHA and 18% EPA was

administered in order to achieve an intake of omega 3 fatty acids of 3 g/day. At

the end of 3 months, omega 6 fatty acids in plasma were significantly reduced

and omega 3 fatty acids increased 3-fold. Biopsies revealed that compared to

baseline, breast fat showed a significant increase in omega 3 fatty acid

deposits, a higher level of total omega 3 fatty acids, and higher ratio of omega

3/omega 6.194

 

Shao and colleagues have shown that incorporating dietary fish oil may enhance

breast cancer therapy. Twenty days prior to tumor implantation (MX-1 human

mammary carcinoma), adult female athymic mice were fed either a diet high in

fish oil (25% plus 5% corn oil) or a control diet containing 5% corn oil. Ten

days later, half the mice in each group received chemotherapy with mitomycin C.

Compared to the mice on the corn oil diet, mice receiving the diet high in fish

oil showed significantly greater benefits from the chemotherapy, as evidenced by

the mean weight of their tumors (p<0.01). Their response to chemotherapy was

10-fold better than the mice on the low corn oil diet. Based on extensive tests,

researchers speculated that increased oxidative stress in the tumors (+300%

versus +25% in the corn oil group) resulted in a better response to treatment.

With chemotherapy, oxidative stress in the tumors increased 160% in the corn oil

group and 600% in the fish oil group. Tumors from the chemotherapy-treated mice

fed the diet high in fish oil showed a significant increase in xanthine oxidase

and DT-diaphorase, enzymes with proposed involvement in the antitumor activity

of mitomycin C. The authors of the study suggest that a dietary intervention

using a high dosage of fish oil may increase the therapeutic response to

pro-oxidant therapies for breast cancer.195

 

Prostate Cancer—There are indications that omega 3 fatty acids perform functions

in experimental prostate cancer progression similar to those described for

breast cancer.192 Prostate cancer risk was examined in a population-based,

case-control study involving 317 prostate cancer patients ages 40-80. Compared

to 480 age-matched controls, a significantly reduced risk of prostate cancer was

found in association with high levels of EPA and DHA in red blood cell

phosphatidylcholine. However, the association was not significant when daily DHA

and EPA from the diets of the patients were estimated. The results of this study

support the association of a reduced risk of prostate cancer with higher levels

of long-chain omega 3 fatty acids in red blood cells and the hypothesis that

eicosanoid processes are involved in the progression or initiation of prostate

cancer.183

 

A much smaller study of prostate cancer patients reported results that warrant a

considerably larger study. When the serum from 19 prostate cancer patients and

24 patients diagnosed with BPH (benign prostatic hyperplasia) were compared to

age-matched controls, levels of omega 3 fatty acids showed a significant

decrease in both groups of patients, while omega 6 fatty acid levels increased

only in the prostate cancer patients. The ratio of omega 3/omega 6 also

decreased in the prostate cancer patients, more so than those with BPH and less

so compared to the controls in either group of patients. A significant decrease

in omega 3 fatty acids in both types of patients and elevated levels of omega 6

fatty acids in the prostate cancer patients resulted in this decreased ratio.

The researchers proposed that the ratio of omega 3/omega 6 may be related to

both prostate cancer and BPH.184

 

Lung Cancer—An association between fish consumption and lung cancer risk has

been the subject of only a few studies with inconsistent results. The largest

study to date examined fish consumption and rates of lung cancer mortality in 36

countries for 10 periods from 1961 to 1994. When smoking and other confounding

factors were adjusted for, fish consumption was significantly associated with

lower rates of lung cancer mortality; however, the inverse relation was only

significant in those countries where smoking was above the median level of over

2437 cigarettes/year or where the population consumed a high level of animal fat

versus fish fat, and then only in men. For reasons unknown, no significant

relation between lung cancer mortality and fish consumption was evident in

women.196

 

Cancer Treatments—The use of omega-3 fatty acids in the treatment of cancer

continues to be studied in animals197 at the same time as progress is being

shown in human clinical trials.198 In the first veterinary investigation of its

kind, a double blind randomized study set out to determine the benefits of diets

supplemented with increasing levels of fish oil plus arginine on the survival

and quality of life of 32 client-owned dogs diagnosed with stage IIIa (n=28) or

stage IVa (n=4) lymphoma receiving chemotherapy with doxorubicin. Arginine was

added because of reports from human studies of lower levels in patients with

malignancies compared to healthy controls, and because elderly patients

receiving supplementation with the amino acid showed immunological benefits and

improved wound healing. No benefits were found in dogs with stage IV lymphoma,

but, compared to controls receiving a standard diet with chemotherapy, the dogs

with stage III lymphoma given the supplemented diet plus chemotherapy showed

longer survival times and disease-free interval scores. These improvements

showed a significant association with increasing serum levels of DHA. The

cumulative survival time for the experimental group was about 300 days longer

than the control group, which showed a cumulative survival time of only 410

days. Higher levels of EPA and DHA were significantly associated with lower

plasma lactic acid levels. In turn, lower levels of lactic acid were associated

with superior survival time and disease-free interval scores. The researcher

noted that lactic acidosis is found in association with various kinds of cancer

in humans and indicates a poor metabolic state.197

 

Increased survival time was reported in a study on the possible benefits of

omega-3 fatty acids (2.45 g EPA and DHA/day) plus an extract of milk thistle

(Silybum marianum, 200 mg/day) in 405 patients with brain metastases receiving

treatment with radiation. To avoid any interference with radiation treatment,

patients received the supplement for up to 20 weeks after their course of

radiotherapy. Patients treated with radiation alone showed a median survival of

54.1 weeks compared to 88.8 weeks for those receiving the supplement. The latter

group also showed a significant decrease in radionecroses, a common side-effect

of radiotherapy (14.1% versus 3.49% incidence, respectively).198

 

In a prospective randomized control study conducted in Greece, 60 patients

diagnosed with generalized solid tumors received either placebo or a fish oil

supplement (18 g providing 1020 mg EPA and 690 mg DHA), daily for 40 days. In

addition, the experimental group received 200 mg vitamin E daily to ameliorate

the oxidative activity of the fish oil. Immunomodulating or chemotherapeutic

treatments were not received by the patients during the 4 months preceding the

trial and no therapy with any “efficient or established” tumor treatment would

be available to them. Fifteen healthy subjects served as a control group and

each group of cancer patients held two subgroups of patients in a well-nourished

state and a malnourished state. The study set out to learn the effect of the

nutritional state on survival and immune response of the patients, plus the

effect of dietary supplementation with omega 3 fatty acids (fish oil) on

survival and immunomodulation, with emphasis on a subgroup mostly comprised of

severely malnourished, immunocompromised cancer patients.

 

Compared to the placebo group, the malnourished patients receiving omega 3 fatty

acids plus vitamin E supplementation showed a restoration of previously low

peripheral blood levels of the helper T/T cell ratio, significantly increased

helper T cell numbers both in the absolute and as a percentage, and

significantly decreased levels of suppressor T cells. The well-nourished group

also showed an increase in the helper T/T cell ratio, but the change failed to

reach a level of statistical significance. Serum cytokine production and levels

showed a significant increase only in TNF production in the peripheral blood

mononuclear cells of the malnourished subgroup of patients receiving omega 3

fatty acids plus vitamin E supplementation, which reached the same level as that

of the well-nourished subgroup. The malnourished group also showed a significant

increase in Karnofsky performance status. Compared to these patients, survival

was only significantly prolonged in the well-nourished group receiving omega 3

fatty acid supplementation plus vitamin E (mean survival 213 versus 481 days;

p<0.001). Nonetheless, when both groups of cancer patients were combined and

compared to the placebo group, survival was significantly prolonged in the

patients receiving omega 3 plus vitamin E (p<0.025).

 

Despite the high dosage of omega 3 plus vitamin E, no cases of serious toxicity

were found, with the exceptions of transient diarrhea and “mild abdominal

discomfort.” The authors concluded that omega 3 fatty acid supplementation

combined with vitamin E may provide palliative support to patients with

end-stage metastatic disease, especially to those in an undernourished state.

They add that the addition of vitamin E appears to have diminished the

immunosuppressive effect of fish oil on cell-mediated immunity and that the

survival increase may be the result of antitumor and anticachectic activity

through its immunomodulating and eicosanoid effects.199

 

Cancer Cachexia—Experiments in mice have shown that, despite a cachexia-inducing

tumor (MAC16), replacing part of the carbohydrate calories of the diet with fish

oil will inhibit loss of body weight.200,201 The effect was attributed to EPA

which was shown to directly inhibit tumor-induced lipolysis and to inhibit

protein degradation in skeletal muscles of the animals. This effect was due to

interference with catabolic factors produced by tumors; in this case, EPA

inhibited an increase in protein degradation by inhibiting the increased

production of PGE2 caused by a proteolytic factor produced by the tumor. EPA

also inhibited tumor growth, an effect that LA was shown to suppress, although

without affecting the anticachectic activity of EPA.201

 

Clinical studies of fish oil in the treatment of cancer cachexia are proving

fruitful ground for determining antitumor effects of omega 3 fatty acids in

addition to elucidating their nutritional and anticachectic role in cancer

patients. Recently, Burns et al conducted a phase I study to determine the

dose-limiting toxicity of encapsulated fish oil in cancer and leukemia patients

who had lost 2% of their body weight, thereby providing dosage information for

future clinical studies of fish oil in cancer patients. The maximum daily

tolerated dose was 300 mg/kg PO. Patients were able to tolerate up to 21 1000 mg

capsules/day, a dosage totaling 13.1 g of DHA plus EPA. The main side effect

from such a high dosage was diarrhea.202

 

Barber and colleagues, after two previous studies in pancreatic cancer patients

administered fish oil against cachexia,204,205 recently reported the results of

a further pilot study in 20 patients with advanced pancreatic cancer using a

canned fish oil-enriched supplement (providing 1.1 g EPA and 0.48 g DHA/can).

Median consumption of the supplement was 1.9 cans/day. At both 3 and 7 weeks,

most of the patients showed an increase in weight gain, a significant increase

in Karnofsky status, and significantly improved appetite and caloric intake,

whereas they had previously been losing weight at a median rate of 2.9 kg at

least monthly. A randomized controlled trial is now underway to determine

effects on survival and side effects, and to confirm the anticachectic effects

of fish oil.205

 

Vision

 

In adults aged 49 and over (n=3654) who consumed fish frequently (more than once

per week versus less than once monthly), an urban population-based study in

Australia recently found a significantly reduced risk of late age-related

maculopathy (ARM). However, it remains for future, larger studies to confirm

whether low dietary omega 3 fatty acids are a risk factor for ARM—currently the

most prevalent cause of blindness in the Western world.100

 

FATTY ACID PROFILE ASSESSMENT

 

Analytical tests are available to assess EFA profiles of patients. While not

prevalent in most clinical laboratories, many university and private

laboratories offer fatty acid profiling of plasma and red blood cell lipids.146

Analysis of plasma total phospholipid fatty acid profiles may provide an

accurate assessment of dietary intake of EFAs and correlate well with tissue

lipid composition. Similarly, red blood cell membrane fatty acid analysis

provides an index of long-term intake (about 3 months) that is less sensitive to

short-term changes in the diet since the red cell's life is 120 days. Baseline

fatty acid profiles serve to identify potential aberrations in nutritional and

physiological status, and analysis of nutritionally supplemented patients serves

to identify compliance and the effects of supplementation on fatty acid

profiles.

 

CONCLUSION

 

Omega 3 fatty acids play an important role in our health and well-being through

their roles in membrane lipids, as eicosanoid precursors, and through their

effects on gene expression. The American diet is clearly lacking in long-chain

omega 3 fatty acids while it is high in omega 6 fatty acids, mainly from our

reliance on vegetable oils, the absence of fish from our diet, and changes in

animal feeds which have produced meat and dairy products devoid of omega 3.

Consequences of this diet are multifactorial, but stem from relative imbalances

between omega 6 and omega 3 fatty acids in tissue lipids that have a direct

effect on normal cellular and immune system function. Restoring balance between

omega 6 and omega 3 fatty acids by changing the diet via changing the oils or by

supplementing it with fish oil has demonstrated promise in the treatment of

several diseases and is a testament to the fundamental importance of omega 3

fatty acids in the human body and to the importance of a balanced 6:3 ratio.

 

OMEGA 3 ESSENTIAL FATTY ACIDS

 

Fatty Acid Facts

 

* Omega 3 and omega 6 essential fatty acids are “good fats”

* They are “essential” because mammals cannot synthesize them and they must

be obtained from the diet and are necessary for health

* Alpha-linolenic acid (LNA) is the parent omega 3 essential fatty acid

* Linoleic acid (LA) is the parent omega 6 essential fatty acid

* Intake of omega 3 and omega 6 fatty acids in the diet should be in a

balanced ratio for good health

* The American diet has too much LA or omega 6, disrupting EFA balance and

promoting disease

* Supplementing the diet with omega 3 fatty acids can restore proper balance

that can be discerned by a fatty acid profile

 

Sources of Omega 3 Fatty Acid

Supplemental Forms of Omega 3 Foods Rich in Omega 3 Plant Oils Rich in Omega 3

Fish oil Salmon Flaxseed

Flaxseed Canned albacore tuna Canola

Algal oils Other cold water fish Hemp seed

 

Omega 3 Fatty Acid Deficiency

 

Reduced learning

Abnormal retinogram

Impaired vision

Polydipsia

 

Dietary Recommendations

 

United States:

 

* No current government recommendations for omega 3 fatty acids

* Government recommendation for LA is a minimum of 1-2% energy

* Government recommendations for PUFA intake is 7-10% energy

* Scientists and healthcare professionals proposed intakes are listed in

Table 5, and this serves to reduce the dietary ratio of LA to LNA from 10:1 to

2.3:1 and to increase the daily intake of EPA and DHA from less than 200 mg to

700 mg/day

* The American Heart Association recommends at least two fatty fish meals

per week for the primary prevention of heart disease and one fatty fish meal or

fish oil supplement per day for the secondary prevention of heart disease

 

Pregnant and Nursing Mothers:

 

* Pregnant women at 36 weeks gestation show significant decreases in omega 3

(see Table 6)

* Deficits of omega 3 persisted 6 weeks postpartum

* Deficits of omega 3 are more pronounced in breastfeeding mothers

* Omega 3 deficiencies may also play a role in postpartum depression

 

How Omega 3 Mediates Inflammation

 

* Certain omega 3 and omega 6 fatty acids are converted to eicosanoids such

as prostaglandins and leukotrienes

* Eicosanoids are important for normal physiology, disease pathology, and

the inflammatory response

* Eicosanoids differ in their physiological potency depending on their fatty

acid origin

* Elevated omega 6 at the expense of omega 3 results in a eicosanoid

precursor pool dominated by arachidonic acid, thus promoting the inflammatory

response

* Eicosanoids derived from omega 3 fatty acids EPA and DHA are weak

promoters of inflammation

* The greater the balance between arachidonic acid and EPA and DHA in the

eicosanoid precursor pool, the more balanced the inflammatory response

* Returning omega 3 fatty acids to the diet, either as long-chain omega 3

(EPA and DHA) or short chain omega 3 (LNA), improves omega 3 status and

attenuates the inflammatory response

 

Supplemental Omega 3 Used in the Treatment of Disease

 

Cardiovascular Diseases Inflammatory Diseases Psychiatric Disorders Cancers

Heart attacks Inflammatory bowel disease Depression Colon cancer

Coronary artery disease Arthritis Schizophrenia Breast cancer

Cardiac arrhythmia Cystic fibrosis ADHD Prostate cancer

IgA nephropathy Psychological stress Lung cancer

Cachexia

 

Toxicity and Contraindications

 

Safety

 

* Safety profile: excellent

* Doses as high as 3-8 g of omega 3 (EPA and DHA) per day (10-27 g fish oil)

show virtually no adverse effects

 

Side Effects

 

* Common complaints of fish oil capsules are fish taste and belching of

fishy flavors

* At higher doses, as with any oil, GI complaints include loose stools

 

Interactions

 

Increased bleeding times that are within normal ranges have been reported in

Greenland Eskimos with very high intakes of omega 3 (7-10 g EPA and DHA/day),

but this side effect is regarded as posing little threat with supplemental doses

of omega 3 (EPA and DHA) under 5 g per day, or the equivalent of 15 g of fish

oil per day. There has not been a clinical case of excessive bleeding reported

even after surgery. Obvious considerations should be provided for patients on

blood thinners and anticoagulants.

 

Animal studies suggest an increased response to digitalis with fish oil

consumption. This interaction requires further investigation. Monitor patients

receiving digitalis and fish oil supplements and adjust accordingly.

 

Safe Dosages

 

Typical supplemental fish oil doses in the range of 1 g to 15 g per day (0.3 to

5 g EPA and DHA) are considered safe, while therapeutic doses of 15 g or greater

should be taken only with the approval of a healthcare professional.

[Guest guest]

When my feet burn I take Vitamin B2

Margaret

-

DitziSis

alternative_medicine_forum

Sunday, August 15, 2004 6:46 AM

help please

 

 

I'm just not having a very good few days right now.

Can someone please remind me what the nutrient is that ya need when your feet

burn...???

And what was it that was said about dog vaccinations? Tuxie is due for hers. I

live in the woods, so I think she probably needs a rabies shot without question.

Haven't heard of rabies in the basin in a few years...but those squirrels and

chickenmunkies are all around, as well as coyotes and bear. AND she's not an

especially social dog..she will bite. People think she's " OH SO CUTE " ...and she

is. Just not social. They will stick their hand into the car window, even tho I

tell them not to.

My mood tonight...I'm going to get a sign " Forget the dog, BEWARE OF ME! "

Thanks everyone.

Peace and good health,

MaryKaye

 

p.s. on a better, lighter note::

Leg ulcer is down to less than 3/4 " x 1/2 " ... using organic honey ONLY.

 

 

http://pets.care2.com/

 

http://www.theanimalrescuesite.com

 

WAITING

 

 

 

 

 

[Guest guest]

Thanks Frank and Catherine!

I knew there had to be a response...but some how it got lost in my

inbox. Not hard to get lost in there...so I came up here looking.

I've forwarded it to myself and will get down to biz on it. Looks

like I'll have to buy some additional supplements, which won't happen

til the end of the month.

I really, REALLY thank you both for your response!

 

, " Catherine Coy "

<catherinecoy@c...> wrote:

> ( Moderator's Note: On the subject of fats, there are also files in

our Files section or in our archives called " The Oiling Of America " .

>

http://health.

>

> Or for an indepth look go to this link from our links page:

> Udo Erasmus on oils and fats. The author of the book: " Fats That

Heal Fats that Kill " http://www.udoerasmus.com./ )F.

>

>

>

> Hey Ditzi ~

>

> Glad to hear about your leg ulcer. Check this out...a VERY good

read.

>

>

> -

> DitziSis

> alternative_medicine_forum

> Saturday, August 14, 2004 10:46 PM

> help please

>

>

> I'm just not having a very good few days right now.

> Can someone please remind me what the nutrient is that ya need

when your feet burn...???

> And what was it that was said about dog vaccinations? Tuxie is

due for hers. I live in the woods, so I think she probably needs a

rabies shot without question. Haven't heard of rabies in the basin in

a few years...but those squirrels and chickenmunkies are all around,

as well as coyotes and bear. AND she's not an especially social

dog..she will bite. People think she's " OH SO CUTE " ...and she is.

Just not social. They will stick their hand into the car window, even

tho I tell them not to.

> My mood tonight...I'm going to get a sign " Forget the dog, BEWARE

OF ME! "

> Thanks everyone.

> Peace and good health,

> MaryKaye

>

> p.s. on a better, lighter note::

> Leg ulcer is down to less than 3/4 " x 1/2 " ... using organic

honey ONLY.

>

>

>

>

> Omega 3:

> Implications in Human Health and Disease

>

> FORWARD

>

> The study of omega 3 fatty acids is one of the fastest growing

research areas in nutritional and medical science today. As research

interest in the topic has increased, so has consumer and patient

awareness. Ten years ago, less than 10% of people polled recognized

the term " omega 3, " but in 1999 an independent survey reported that

consumer awareness had grown to over 50%.1 Awareness and interest

among scientists and physicians have also grown, as evidenced by the

broad diversity of research projects currently examining the effects

of omega 3 fatty acids. Many reports appearing in the scientific

literature suggest that simple modification of the diet with certain

fatty acids can have a positive impact on a broad range of diseases.

These diseases include heart disease, hypertension, cancer, diabetes,

cystic fibrosis, asthma, arthritis, dysmenorrhea, depression,

schizophrenia, and attention deficit disorder.

>

[Guest guest]

Thanks Margaret...

I've upped my Bcomplex til I can also add the oils. Should be taking

more Bcompx anyway!

 

 

, " Margaret "

<me.chalkley@b...> wrote:

> When my feet burn I take Vitamin B2

> Margaret

> -

> DitziSis

> alternative_medicine_forum

> Sunday, August 15, 2004 6:46 AM

> help please

>

>

> I'm just not having a very good few days right now.

> Can someone please remind me what the nutrient is that ya need

when your feet burn...???

> And what was it that was said about dog vaccinations? Tuxie is

due for hers. I live in the woods, so I think she probably needs a

rabies shot without question. Haven't heard of rabies in the basin in

a few years...but those squirrels and chickenmunkies are all around,

as well as coyotes and bear. AND she's not an especially social

dog..she will bite. People think she's " OH SO CUTE " ...and she is.

Just not social. They will stick their hand into the car window, even

tho I tell them not to.

> My mood tonight...I'm going to get a sign " Forget the dog, BEWARE

OF ME! "

> Thanks everyone.

> Peace and good health,

> MaryKaye

>

> p.s. on a better, lighter note::

> Leg ulcer is down to less than 3/4 " x 1/2 " ... using organic

honey ONLY.

[Guest guest]

I am not sure if the group moderator will alow this reply but here

goes...

 

I receive messages in digest form too. and sometimes I forward useful

information to my family members.

 

All I do is highlight the portion that I would like to forward

( click press left button of mouse and drag till end of text I want to

highlight) then right click on the highlighted section---> popup menu -

---> select copy...go to email.....righ click ....popupmenu ---> paste

 

 

Text is same font size as text in digest. BTW I Use IE and Windowns

XP, I am not sure if MAC would behave differently..

 

regards

 

, " orphan1948 "

<orphan1948> wrote:

> Okay call me computer illiterate but......Heres the delema not

> everyone I know has a computer so I often copy articles I find and

> send them via snail mail. I'm currently using Mozilla Firefox

browser

> and for the life of me can't figure out how to get the articles in

the

> digest to print in a readable size everything comes out miniaturized.

> I've tried fit to page, zoom,printable area. usually going to the

> article link works okay but not all articles have a direct link. Any

> suggestions advice concerning this irritating matter would be greatly

> appreciated.

>

> Best R's,

>

> O.

[Guest guest]

Hi, I would like to ask for Light or prayers for my hubby who has to deal with a

prostate problem that has to be checked out for cancer. I am so numbed with this

news and so I am hoping that others could help with their prayers. Right now it

is very hard to focus at all . We are sort of frozen with this news. I thank you

for all you can do. The biopsy will take place on March 23 and I am so hoping

that there will be no signs of cancer. Thanks, Judy

[Guest guest]

HEALING & PRAYERS ARE ON ITS WAY TO YOUR HUSBAND FOR HIS HIGHEST GOOD.COULD YOU

BE ABLE TO MENTION HIS NAME PLEASE?

 

LOVE & LIGHT,

SUREKHA

 

Vivek & Surekha Joshi

619-50 Mississauga Valley Blvd.

Mississauga L5A 3S2 ON

Canada

Tel: +1 905 897 8516

Cell:+1 647 408 8516

 

--- On Sat, 3/7/09, Judy <songyn wrote:

 

Judy <songyn

[CrystalHW] Help Please

 

Received: Saturday, March 7, 2009, 1:12 AM

 

 

 

 

 

 

Hi, I would like to ask for Light or prayers for my hubby who has to deal with a

prostate problem that has to be checked out for cancer. I am so numbed with this

news and so I am hoping that others could help with their prayers. Right now it

is very hard to focus at all . We are sort of frozen with this news. I thank you

for all you can do. The biopsy will take place on March 23 and I am so hoping

that there will be no signs of cancer. Thanks, Judy

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

[Guest guest]

Judy

 

I will light a candle for your husband and you.? What is his name?? I'ld like to

send prayers

and Reiki to ease the nerves and replenish any energy that may have been lost

through stressing.?

Please let us know how he is doing.

 

Blessings

Dawn

 

 

 

 

 

 

 

 

Judy <songyn

 

Fri, 6 Mar 2009 8:12 pm

[CrystalHW] Help Please

 

 

 

 

 

 

 

 

 

 

Hi, I would like to ask for Light or prayers for my hubby who has to deal with a

prostate problem that has to be checked out for cancer. I am so numbed with this

news and so I am hoping that others could help with their prayers. Right now it

is very hard to focus at all . We are sort of frozen with this news. I thank you

for all you can do. The biopsy will take place on March 23 and I am so hoping

that there will be no signs of cancer. Thanks, Judy

 

 

 

---

 

The Crystal healing workshop files are online at

http://pjentoft.com/0crystal-healing.html

some files, photos, and message archives can also be found At:

 

[Guest guest]

I said a prayer for you and your husband Judy. Keep us posted

 

Love & Light

Kay

 

leopardgoose wrote:

 

Judy

 

I will light a candle for your husband and you.? What is his name?? I'ld like to

send prayers

and Reiki to ease the nerves and replenish any energy that may have been lost

through stressing.?

Please let us know how he is doing.

 

Blessings

Dawn

 

 

 

 

 

 

 

 

Judy

 

Fri, 6 Mar 2009 8:12 pm

[CrystalHW] Help Please

 

 

 

 

 

 

 

 

 

 

Hi, I would like to ask for Light or prayers for my hubby who has to deal with a

prostate problem that has to be checked out for cancer. I am so numbed with this

news and so I am hoping that others could help with their prayers. Right now it

is very hard to focus at all . We are sort of frozen with this news. I thank you

for all you can do. The biopsy will take place on March 23 and I am so hoping

that there will be no signs of cancer. Thanks, Judy

 

 

 

---

 

The Crystal healing workshop files are online at

http://pjentoft.com/0crystal-healing.html

some files, photos, and message archives can also be found At:

 

[Guest guest]

dear Judy,

 Reiki prayers ,blessings are on the way for your husband. May you also have the

strength to support him.God is great and let not worries take charge of you.

Love.

krishna

 

--- On Sat, 3/7/09, Judy <songyn wrote:

 

Judy <songyn

[CrystalHW] Help Please

 

Saturday, March 7, 2009, 6:42 AM

 

 

 

 

 

 

Hi, I would like to ask for Light or prayers for my hubby who has to deal with a

prostate problem that has to be checked out for cancer. I am so numbed with this

news and so I am hoping that others could help with their prayers. Right now it

is very hard to focus at all . We are sort of frozen with this news. I thank you

for all you can do. The biopsy will take place on March 23 and I am so hoping

that there will be no signs of cancer. Thanks, Judy

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

[Guest guest]

Prayers have been sent.

 

--- On Sat, 3/7/09, Judy <songyn wrote:

 

 

Judy <songyn

[CrystalHW] Help Please

 

Saturday, March 7, 2009, 1:12 AM

 

 

 

 

 

 

Hi, I would like to ask for Light or prayers for my hubby who has to deal with a

prostate problem that has to be checked out for cancer. I am so numbed with this

news and so I am hoping that others could help with their prayers. Right now it

is very hard to focus at all . We are sort of frozen with this news. I thank you

for all you can do. The biopsy will take place on March 23 and I am so hoping

that there will be no signs of cancer. Thanks, Judy

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

[Guest guest]

~~~Judy <songyn

I would like to ask for Light or prayers for my hubby who has to deal with a

prostate problem that has to be checked out for cancer. ~~~~

Greetings Judy and All,

 

I just want to reiterate something the I believe it was Peggy our list Owner who

posted quite a while back. While I do not usually post to the list in response

to healing requests, I DO immediately start sending healing energies for the

better good of all who are involved/effected. I know there are other who also

work this way. SO anyone who does post healing requests but does not get many

actual replies, do not feel that you are being slighted in anyway. I for one

would rather put my energies towards the healing then towards a reply to the

request.

 

I would like to recommend some rose quartz and lepidolite for love and calming

energies and smokey quartz for the prostate. Reiki and crystal healing energies

started being sent before I even started typing this email.

 

Blessings to your weekend all.

ReNau

 

 

" Codail, suaimhnigh i nge/aga nadragain "

" Sleep, rest in the arms of the Dragon "

 

 

 

 

[Guest guest]

Positive thoughts and prayers are sent to you and your husband~

 

, Debbie Bowes <flowerlady6

wrote:

>

> Prayers have been sent.

>

> --- On Sat, 3/7/09, Judy <songyn wrote:

>

>

> Judy <songyn

> [CrystalHW] Help Please

>

> Saturday, March 7, 2009, 1:12 AM

Hi, I would like to ask for Light or prayers for my hubby who has to deal with

a prostate problem that has to be checked out for cancer. I am so numbed with

this news and so I am hoping that others could help with their prayers. Right

now it is very hard to focus at all . We are sort of frozen with this news. I

thank you for all you can do. The biopsy will take place on March 23 and I am so

hoping that there will be no signs of cancer. Thanks, Judy

>

>

>

>

>

>

>

>

>

>

>

>

>

 

[Guest guest]

energy and prayer sent

http://www.youtube.com/watch?v=ujBaa13bdgI

look into the ana bekoach

 

MitchelL Gibson speaks about its incredible healing miracles in many videos on

you-tube

, " Judy " <songyn wrote:

>

> Hi, I would like to ask for Light or prayers for my hubby who has to deal with

a prostate problem that has to be checked out for cancer. I am so numbed with

this news and so I am hoping that others could help with their prayers. Right

now it is very hard to focus at all . We are sort of frozen with this news. I

thank you for all you can do. The biopsy will take place on March 23 and I am so

hoping that there will be no signs of cancer. Thanks, Judy

>