article no. plef.1999.0061 evolutionary aspects of omega-3 fatty … · pmstag/andins, leukotfimes...

Pmstag/andins, Leukotfimes and Essential Fatty Acids (1999) @0(5&s), 421-429 (0 1999 Harwurl Brace 8 Co. Ltd Article no. plef.1999.0061

Evolutionary aspects fatty acids in the food supply

of omega-3

A. P. Simopoulos

The Center for Genetics, Nutrition and Health, 2001 S Street, NW, Suite 530, Washington, DC 20009, USA

Summary Information from archaeological findings and studies from modern day hunter-gatherers suggest that the Paleolithic diet is the diet we evolved on and for which our genetic profile was programmed. The Paleolithic diet is characterized by lower fat and lower saturated fat intake than Western diets; a balanced intake of omega-6 and omega-3 essential fatty acids; small amounts of trans fatty acids, contributing less than 2% of dietary energy; more green leafy vegetables and fruits providing higher levels of vitamin E and vitamin C and other antioxidants than today’s diet and higher amounts of calcium and potassium but lower sodium intake. Studies on the traditional Greek diet (diet of Crete) indicate an omega-6/omega-3 ratio of about l/l. The importance of a balanced ratio of omega8:omega9, a lower saturated fatty acid and lower total fat intake (30-33%) along with higher intakes of fruits and vegetables leading to increases in vitamin E and C, was tested in the Lyon Heart study. The Lyon study, based on a modified diet of Crete, confirmed the importance of omega-3 fatty acids from marine and terrestrial sources, and vitamin E and vitamin C, in the secondary prevention of coronary heart disease, and cancer mortality.

INTRODUCTION

The interaction of genetics and environment, nature and nurture is the foundation for all health and disease. This concept, based on molecular biology and genetics, was originally defined by Hippocrates. In 480 BC Hippocrates stated the concept of positive health as follows:

Positive health requires a knowledge of man’s primary constitution (which today we call genetics) and of the powers of vaxious foods, both those natural to them and those resulting from human skill (today’s processed food). But eating alone is not enough for health. There must also be exercise, of which the effects must likewise be known. The combination of these two things makes regimen, when proper attention is given to the season of the year, the changes of the winds, the age of the individual and the situation of his home. If there is any deficiency in food or exercise the body will fall sick.

In the last decade, using the techniques of molecular biology, it has been shown that genetic factors determine susceptibility to disease and environmental factors determine which genetically susceptible individuals will be affected.’ Nutrition is an environmental factor of major importance. Whereas major changes have taken place in

Corres~&nce to: A. P. Simopoulos. Tel.: +l 202 462 5062;

Fax: +I 202 462 5241; E-mail;[email protected]

our diet over the past 10 000 years, since the beginning of the Agricultural Revolution, our genes have not changed. The spontaneous mutation rate for nuclear DNA is estimated at 0.5% per million years. Therefore, over the past 10 000 years there has been time for very little change in our genes, perhaps 0.005%. In fact, our genes today are very similar to the genes of our ancestors during the Paleolithic period 40 000 years ago at which time our genetic profde was established.2 Genetically speaking, humans today live in a nutritional environment that differs from that for which our genetic constitution was selected. Studies on the evolutionary aspects of diet indicate that major changes have taken place in our diet (Table 1) and particularly in the type and amount of essential fatty acids, and in the antioxidant content.2-4 Using the tools of molecular biology and genetics, research is defining the mechanisms by which genes influence nutrient absorption, metabolism and excretion, taste perception, and degree of satiation; and the mechanisms by which nutrients influence gene expression.

Whereas evolutionary maladaptation leads to repro- ductive restriction (or differential fertility), the rapid changes in our diet, particularly the last 150 years, are potent promoters of chronic diseases such as atheroscle- rosis, essential hypertension, obesity, diabetes and many cancers. In addition to diet, sedentary life styles and expo-

421

422 Simopoulos

Table 1 Characteristics of Hunter-gatherer and Western diet and lifestyles

Characteristic Diet and lifestyle

Hunter-gathemr western

Physical activity level

Diet Energy-density Enerov intake Protein

animal vegetable

Carbohydrate

Fibre Fat

vegetable animal

~61~3 ratio linoleic and

linolenic acids long chain w6 and

w3 PUFA

low moderate high high very low low-moderate (slowly absorbed) high low very low low polyunsaturated low (2.4)

low (3.3)

high (2.3)

Vitamins Paleolithic period Riboflavin, mglday 6.49 Folate, mg/day 0.357 Thiamin, mg/day 3.91 Ascorbate, mglday 604.00 Carotene, mglday 5.56

(retinol equivalent) (927.00) Vitamin A, mg/day 17.2

(retinol equivalent) (2870.00) Vitamin E, mg/day 32.8

High Low

high high low-moderate low-moderate low-moderate moderate (rapidly absorbed) low high moderate to high high saturated high (12)

high (12.3)

low (0.2)

Current US Intake 1.34-2.08 0.149-0.205 1.08-l .75

77-l 09 2.06-2.57

7.02-8.48 (1170-429)

7-l 0

From Simopoulos.4

sure to noxious substances interact with genetically controlled biochemical processes leading to chronic disease. This paper discusses evolutionary aspects of diet with emphasis on the balance of omega-6:omega-3 fatty acids and their health implications in coronary heart disease and cancer.

EVOLUTIONARY ASPECTS OF DIET

The foods that were commonly available to pre-agricultural humans (lean meat, fish, green leafy vegetables, fruits, nuts, berries and honey) were the foods that shaped modern human’s genetic nutritional requirements. Cereal grains as a staple food are a relatively recent addition to the human diet and represent a dramatic depar- ture from those foods to which we are genetically programmed and adapted.

Cereals became part of our food supply only very recently, 10 000 years ago, with the advent of the Agri- cultural Revolution. Prior to the Agricultural Revolution humans ate an enomnous variety of wild plants, whereas today about 17% of plant species provide 90% of the world’s food supply, with the greatest percentage con-

tributed by cereal grains.5 Three cereals: wheat, maize and rice, together account for 75% of the worlds grain production. Human beings have become entirely depen- dent upon cereal grains for the greater portion of their food supply. The nutritional implications of such a high grain consumption upon human health are enormous. And yet, for the 99.9% of mankind’s presence on this planet, humans rarely or ever consumed cereal grains, as it is only in the last 10 000 years that humans have consumed cereals. Up to that time, humans were non-cereal eating hunter-gatherers since the emergence of Homo erectus 1.7 million years ago. There is no evolutionary precedent in our species for grass seed consumption.* Therefore, there is little time (< 500 generations) since the beginning of the Agricultural Revolution 10 000 years ago to adapt to a food type which now represents human- ity’s major source of both calories and protein. Cereal grains are high in carbohydrates and omega-6 fatty acids, but low in omega-3 fatty acids and in antioxidants. Recent studies show that low fat/high carbohydrate diets increase insulin resistance and hyperinsulinemia, conditions that increase the risk for coronary heart disease, diabetes and obesity.6-8

A number of anthropological, nutritional and genetic studies indicate that human’s overall diet, including energy intake and energy expenditure, has changed over the past 10 000 years with major changes occurring during the last 150 years in the type and amount of fat and in vitamins C and E intake (Table 1, Fig. 1).2~4~5~q-”

Eaton and Konner’ have estimated higher intakes for protein, calcium, potassium and ascorbic acid and lower sodium intakes for the diet of the late paleolithic period than the current USA and Western diet. Most of our food is calorically concentrated in comparison with wild game and the uncultivated fruits and vegetables of the Paleo- lithic diet. Paleolithic man consumed fewer calories and drank water, whereas today most drinks to quench thirst contain calories. Today industrialized societies are characterized by (1) an increase in energy intake and decrease in energy expenditure; (2) an increase in saturated fat, omega-6 fatty acids and trans fatty acids, and a decrease in omega-3 fatty acid intake; (3) a decrease in complex carbohydrates and fibre; (4) an increase in cereal grains and a decrease in fruits and vegetables; and (5) a decrease in protein, antioxidants and calcium intake (Tables 12). 2.4,11,12

EIIQBWTiAL FATTY Ac=IDS AND l-NE oMIQA=S/ OMEUA=8 mAimAWE

Large-scale production of vegetable ok

The increased consumption of omega-6 fatty acids in the last 100 years is due to the development of technology at

Prostaglandins, Leukotrienes and Essential Fatty Acids (1999) 60(5&6), 421429 0 7999 Harcourt Brace & Co. Ltd

Evolutionary aspects of omega-3 fatty acids in the food supply 423

Hunter gatherer I Agricultural I Industrlal

Vitamin C

Saturated

600

-10 ooo 1800 l!Joo zoo0 Years

Fig. 1 Hypothetical scheme of fat, fatty acid (w-3, w-6 trans and total) intake (as percent of calories from fat) and intake of vitamins E and C (mg/d). Data were extrapolated from cross-sectional analyses of contemporary hunter-gatherer populations and from longitudinal observations and their putative changes during the preceding 100 years.“‘,”

Table 2 Late Paleolithic and currently recommended nutrient composition for Americans

Late Current Paleolithic recommendations

Total dietary energy, (%) Protein Carbohydrate Fat Alcohol

P:S ratio Cholesterol (mg) Fiber (g) Sodium (mg) Calcium (mg) Ascorbic acid (mg)

33 46 21

-0 1.41

520 100-l 50 690

1500-2000 440

12 58 30 - 1.00

300 30-60

1100-3300 800-l 600

60

Modified from Eaton et al.” P:S = polyunsaturated to saturated fat.

the turn of the century that marked the beginning of the modem vegetable oil industry, and to modem agriculture with the emphasis on grain feeds for domestic livestock (grains are rich in omega-6 fatty acids).13 The invention of the continuous screw press, named expeller by V.D. Anderson, and the steam-vacuum deodorization process by D. Wesson, allowed the industrial production of cotton- seed oil and other vegetable oils for cooking.‘3 Solvent extraction of oilseeds came into increased use after World War One and the large scale production of vegetable oils became more efficient and more economic. Subsequently, hydrogenation was applied to oils to solidify them. The

partial selective hydrogenation of soybean oil reduced the alpha-linolenic acid (INA) content of the oil while leaving a high concentration of linoleic acid (LA). LNA content was reduced because LNA in soybean oil caused many organoleptic problems. It is now well known that the hydrogenation process and particularly the for- mation of tram fatty acids has led to increases in serum cholesterol concentrations whereas IA in its regular state in oil is associated with a reduced serum cholesterol concentration.14f’5

Since the 195Os, research on the effects of omega-6 PUPAS in lowering serum cholesterol concentrations has dominated the research support on the role of PUPAS in lipid metabolism. Although a number of investigators contributed extensively, the paper by Ahrens et al. in 1 95416 and subsequent work by Keys et alI7 firmly established the omega-6 fatty acids as the important fatty acids in the field of cardiovascular disease. The availability of methods for the production of vegetable oils and their use in lowering serum cholesterol concentration led to an increase in both the fat content of the diet and the greater increase in vegetable oils rich in omega-6 fatty acids.

Agribusiness and modern agriculture

Agribusiness further contributed to the decrease in omega-3 fatty acids in animal carcasses. Wild animals and birds who feed on wild plants are very lean, with a carcass

0 7999 Harcourt Brace & Co. Ltd Prostaglandins, Leukotrienes and Essential Fatty Acids (1999) 60(5&S), 421-429

424 Simopoulos

Table 3 Fatty acid content of plants*

Fatty acid

Red Butter- leaf crunch

Pursiane Spinach lettuce lettuce Mustard

mgig of wet weight 14:o 0.16 0.03 0.03 0.01 0.02 16:0 0.81 0.16 0.10 0.07 0.13 18:0 0.20 0.01 0.01 0.02 0.02 18:lw-9 0.43 0.04 0.01 0.03 0.01 18:2 w-6 0.89 0.14 0.12 0.10 0.12 18:3 w-3 4.05 0.89 0.31 0.26 0.48 205 w-3 0.01 0.00 0.00 0.00 0.00 22:6 w-3 0.00 0.00 0.002 0.001 0.001

Other 1.95 0.43 0.12 0.11 0.32

Total fatty acid content 8.50 1.70 0.702 0.60 1.101

*Adapted from Reference 22.

fat content of only 3.9%,18 and contain about five times more PUPAS per gram than is found in domestic livestock.1g,20 Most importantly, 4% of the fat of wild animals contcains eicosapentaenoic acid (EPA). Domestic beef contains very small or undetectable amounts of LNA because cattle are fed grains rich in omega-6 fatty acids and poor in omega-3 fatty acids” whereas deer that forage on ferns and mosses contain more omega-3 fatty acids (LNA) in their meat.

Modern agriculture with its emphasis on production has decreased the omega-3 fatty acid content in many foods: green leafy vegetables, animal meats, eggs, and even fish.22-25 Foods from edible wild plants contain a good balance of omega-6 and omega-3 fatty acids. Table 3 shows purslane, a wild plant, and compares it to spinach, red leaf lettuce, buttercrunch lettuce and mustard greens.

Purslane has eight times more alpha-linolenic acid than the cultivated plants.

Modern aquaculture produces fEh that contain less omega-3 fatty acid than do fish grown naturally in the ocean, rivers and lakes (Table 4).23

As can be seen from Table 5 comparing the fatty acid composition of egg yolk from free-ranging chicken and the standard US Department of Agriculture (USDA) egg, the former has an omega-6:omega-3 ratio of 1.3 whereas the USDA egg has an omega-6:omega-3 ratio of 1 9.9.24 By enriching the chicken feed with fishmeal or flax, the ratio of omega_6:omega-3 decreased to 6.6 and 1.6 respectively.24

Imbalance of omega4omega-3

It is evident that food technology and agribusiness provided the economic stimulus that dominated the changes in the food supply. From per capita quantities of foods available for consumption in the US national food supply in 1985, the amount of EPA is reported to be about 50 mg per capita/day and the amount of DHA is 80 mg per capita/day. The two main sources are fish and p0ultry.2~

It has been estimated that the present western diet is ‘deficient’ in omega-3 fatty acids with a ratio of omega-6 to omega-3 of ZO-25:1, instead of 1:l 0 is the case with wild animals and presumably human beings.21-26

Before the 1940s cod liver oil was ingested mainly by children as a source of vitamin A and D with the usual dose being a teaspoon. Once these vitamins were syn- thesized consumption of cod-liver oil was drastically decreased. Thus an absolute and relative change of omega-6:omega-3 in the food supply of Western societies has occurred over the last 100 years (Fig. 1).2,4*10-‘2 A balance existed between omega- 6 and omega-3 for millions

Table 4 Fat content and fatty acid composition of wild and cultured trout, eil, and salmona

Trout (saimo gairdneri Eel (Anguiiia Salmon and Saimo trutta fario) anguiiia) (Saimo saiar) Wild cuitured Wild Cuitured Wild cuitured @=2) (n=9) (n=4) (n=4) (n=2) (~3)

Fat (g/l OOg) 5*3 6il 21i6 30*2 lO*O.l 16*0.6

Fatty acids (g/l OOg fatty acid) 18:3 w-3 3i2 1 iO.3” 2i2 1*0.3 1iO.l l*O.l 20:5 w-3 74.6 4ilc 4i2 3kO.6 5*0.2 5LkO.l 22:6 w-3 15*2 13*lb 4i2 6kO.4 10*2 7*0.1 b Other ~-3~ 5kO.6 2zto.7” 3*1 2*o.2b 3*0.5 4&l 18:2 w-6 4i3 9*2” 2*2 5zto.3C l*O.l 3*0.1 Other ~-6~ 1 io.4 0.6~.lc 2kO.3 0.4*0.1” 0.2iO.l 0.5*0.1 Sum of w-3 3OkO.2 2Oi3” 14*3 12il 20*2 17iO.2 Sum of w-6 5*3 9G? 3il 6iO.3’ 2LtO.l 3*0.1C w3:w-6 7*5 2eO.6’ 5*2 2~tO.3~ 11*2 6i0.1b

Reproduced from van Viiet T., Katan M. B.= x * S. D. n, number of lots; each lot consisted of about six. trout or eel or one or two salmon. b.C Significantly different from wild: b = Pd.05 compared with wild fish; c = PcO.01 compared with wild fish. d 18:4 w-3 + 20:3 w-3 + 22:5 w-3. ’ 2014 w-6 + 22~4 w-6

Prostaglandins, Leukotrienes and Essential Fatty Acids (1999) 60(5&S), 421-429 Q 7999 Hatcourt Brace & Co. Ltd

Table 5 Fatty acid levels in chicken egg yolksa~b~c fats leads to increases in IL-l, prostaglandins and leuko-

Fatty acid Greek Supermarket Flshmeal Flax trienes, is not consistent with human evolution and may

egg egg egg egg lead to maladaptation in those genetically predisposed.

mg/g yolk Saturates HEALTH IMPLICATIONS: THE DIET OF CRETE

14:o 1.1 0.7 1.0 0.6 150 0.1 0.3 0.2

AND ITS RELATION TO CARDIOVASCULAR 16:0 77.6 56.7 67.8 58.9 DISEASE AND CANCER 17:o 0.7 0.3 0.8 0.5 18:0 21.3 22.9 23.0 26.7 Over the past 15 years a number of animal experiments,

Total 100.7 80.7 92.9 86.9 epidemiological investigations and double blind con- Monounsaturates trolled clinical trials have confirmed the hypotriglyceri-

16:l w-7 21.7 4.7 5.1 4.4 18:l 120.5 110.0 102.8 94.2

demic, anti-inflammatory and antithrombotic aspects of

2O:l w-9 0.6 0.7 0.9 0.5 omega-3 fatty acids3!jd3 and the essentiality of omega-3 24:l w-9 0.1 __ fatty acids, particularly docosahexaenoic acid (IX-IA) for

Total 142.8 115.4 108.9 99.1 the development of retina and brain in the premature Omega-6 polyunsaturates

18:2 w-6 16.0 26.1 67.8 42.4 infant. It therefore became important to investigate the

1813 w-6 0.3 0.2 omega-3 fatty acid composition of diets that have been

20:2 w-6 0.2 0.4 ::: 0.4 shown to be associated with a decreased rate of cardio- 20:3 w-6 0.5 0.5 0.5 0.4 20:4 w-6 5.4 5.0 4.4 2.6

vascular disease and cancer. Such an opportunity

22:4 w-6 0.7 0.4 0.3 - presented itself in the diet of Crete.44

22:5 w-6 0.3 1.2 0.2 The population of Crete was one of the populations par- Total 23.1 33.9 74.1 46.0 ticipating in the Seven Countries Study.45 The others were Omega-3 polyunsaturates the populations of the former Yugoslavia, Italy, Holland

18:3 w-3 6.9 0.5 4.1 21.3 20:3 w-3 0.2 0.1 0.4

(Zutphen), Finland, USA and Japan. The results of the - 20:5 w-3 1.2 0.2 0.5 Seven Countries Study are interesting because they show 22:5 w-3 2.8 0.1 0.4 0.7 that the population of Crete had the lowest rate of cardio- 22:6 w-3 6.6 1.1 6.5 5.1

Total 17.7 1.7 11.3 28.0 vascular disease and cancer, followed by the population

Polyunsaturates: 0.4 0.4 0.9 0.9 of Japan. The investigators concluded that the reason

saturates must be the high olive oil intake and the low saturated fat Monounsaturates: 1.4 1.4 1.2 1.1 intake of the ‘Mediterranean diet’. The fact that Crete

saturates Ratio of w-6: w-3 1.3 19.9 6.6 1.6

had a high fat diet, 37% of energy from fat, and Japan had a low fat diet, 11% of energy from fat, was not very much

‘Modified from Simopouios A. P., Salem Jr N.24 bThe eggs were discussed nor were any other fatty acids considered, hard-boiled and their fatty acid composition and lipid content were assessed as described elsewhere. “Greek eggs, free-ranging

despite the fact that the people of Crete ate 30 times more

chickens; Supermarket eggs, standard US Department of fish than the US population. Furthermore, the people of Agriculture eggs found in US supermarkets; fish meal eggs, main Crete ate plenty of vegetables, fruits, nuts and legumes, source of fatty acids provided by fish meal and whole soybeans; flax eggs, main source of fatty acids provided by flax flour.

all rich sources of folate, calcium, vitamins and minerals. In addition, since the meat came from animals that grazed, rather than being grainfed, it contained omega-3

of years during the long evolutionary history of the genus polyunsaturated fatty acids as did the milk and milk Homo, and genetic changes occurred partly in response products, such as cheese (Table 6). The population of to these dietary influences.’ During evolution, omega-3 Crete eats snails about three times per week throughout fatty acids were found in all foods consumed: meat, fish, the year. Renaud has shown that the snails of Crete wild plants, nuts and berries.2,“,‘g-34 Recent studies by and Greece contain more omega-3 fatty acids and less Cordain et a1.35 on wild animals confirm the original omega-6 fatty acids than the snails of France (personal observations of Crawford and Sinclair et al. (Fig. 1).1g.36 communication). However, rapid dietary changes over short periods of The traditional Greek diet, including the diet of Crete, time as have occurred over the past 100-l 50 years is a includes wild plants. Wild plants are rich socrces of totally new phenomenon in human evolution. omega-3 fatty acids and antioxidants.Z2~27~30 A commonly

A balance between the omega-6 and omega-3 fatty eaten plant is purslane (Table 3). Purslane is rich in LNA acids is a more physiologic state in terms of gene expres- (400 mg/l 00 g) as well as in vitamin E (12 mg/ 100 g), vita- .sion,3’ prostaglandin and leukotriene metabolism and min C (27 mg/ 100 g) and glutathione ( 15-20 mg/ 100 g)F7 interleukin-1 (IL-l) production? The current recommen- In Crete and Greece, purslane is eaten fresh in salads, in dation to substitute vegetable oils (omega-6) for saturated soups and omelettes, or cooked with poultry, and during


Q 1999 Harcowi Brace & Co. Ltd Prostaglandins, Leukotrienes and Essential Fatty Acids (1999) 60(5&S), 421-429

426 Simopoulos

Table 6 Fatty acid content of various cheeses (per 1 OOg edible portion)

2% Milk Cheddar American Swine GreekMyztthra Greek feta

Total Saturated Fat, g 12:o g 14: g 16: g 18:0 g

Total Monounsaturated Fat, g

Total Polyunsaturated, g Fat, g 18:2, g 18:3, g

Arachidonic acid, mg Eicosapentaenoic acid, mg Docosapentaenoic acid, mg Docosahexaenoic acid, mg

1.2 cl Cl <l Cl

1

21 .oo 19.89 16.04 0.54 0.48 0.57 3.33 3.21 2.70 9.80 9.10 7.19 4.70 3.00 2.80

7.20

9.99 8.95 7.05

9.30

1.90 5.40 2.00

3.90

1.60 3.90 1.70

3.00

0.07 0.94 0.99 0.62 0.04 0.58 0.81 0.34 0.03 0.36 0.38 0.28

0.80 0.58 0.38 0.29 0.30 0.20

14 10 18 14 31 23

5.5 5.1

Total Fat, g 2.27 31.93 29.83 23.71 14.00 10.78

Milk, Cheddar, American and Swiss from US Department of Agriculture Handbook #8; Greek Myzithra and Greek Feta from National institute on Alcohol Abuse Alcoholism analyses. From Reference 4.

the winter months the dried purslane is used in soups, vegetable pies, and as a tea for sore throats and earaches. It is highly recommended for pregnant and lactating women and for patients with diabetes.

The purslane study was just the beginning in our involvement in a series of studies that investigated the omega-3 fatty acids in the Greek diet under conditions similar to those prior to 1 960.22,2427*30 In the Greek country- side, chickens wander in the farm, eat grass, purslane, insects, worms, and dried figs, all good sources of omega- 3 fatty acids. Table 5 shows the composition of the Ampelistra (Greek) egg. It has a ratio of omega-6/omega-3 fatty acids of 1.3 whereas the USDA egg has a ratio of 19.4.

Similarly, Greek cheeses contain omega-3 fatty acids, whereas American cheeses do not (Table 6). Noodles made with milk and eggs in Greece also contain omega-3 fatty acids. Thus a pattern began to unfold. The diet of Greece, including Crete prior to 1960, contained omega-3 fatty acids in every meal -breakfast, lunch, dinner and snacks. Figs stuffed with walnuts are a favorite snack. ~0th figs and walnuts contain omega-3 fatty acids. Contrast this snack with a chocolate chip cookie which contains trans fatty acids and omega-6 fatty acids from the partially hydrogenated oils used in preparation.33 While these studies were carried out between 1984 to 1986, further analyses of blood specimens from the Seven Countries Study were published in 1993 by Sandker et al.“6 indicating that the serum cholesteryl esters of the population in Crete had three-fold the amount of LNA than the population of Zutphen (Table 7). Similar data indicated that the Japanese population also had higher concentrations of omega-3 fatty acids than

those of Zutphen. Here then was the missing link. It was the higher concentrations of omega-3 fatty acids that added protection for cardiovascular disease not only the olive oil, wine, fruits and vegetables of the ‘typical Mediterranean diet’.

The two populations with the lowest coronary heart disease in the Seven Countries Study participants had a higher intake of LNA. The Japanese obtained it from canola oil and soybean oil and the population of Crete from purslane, other wild plants, walnuts and figs. Additional studies showed that the population of Crete not only had higher serum cholesteryl ester levels of LNA but also lower linoleic acid (IA, 18:2 w-6) (Table 7).46

Renaud had been working with LNA and shown that it decreases platelet aggregation!’ Everything seems now to fall into place in terms of defining the characteristics of the diet of the population of Crete. Their diet was very

Table 7 Mean fatty acid composition of cholesteryl esters in serum of 92 elderly men from Crete and 97 elderly men from Zutphen

Fatty acid % methylesters P value

Crete Zutphen

16:0 11.1il.O 11.9i1.3 co.oo1 18:l 3.2*1 .l 2.9i1.6 <0.213 18:0 0.7*0.3 1.1*0.5 <O.OOl 18:l 31 .Ozt2.7 21.4i3.9 <O.OOl 18:2 w-6 41.9i3.7 53.1 i6.5 <O.OOl 18:3 w-3 0.9&X5 0.3*0.4 co.OO1 20:4 w-6 6.5*1.6 4.5*1.5 co.oo1 Others 4.6k3.3 4.7i3.7 0.891

Ratio 18:2/18:1 1.37iO.20 2.80i0.75 <O.OOl

Results are expressed as mean % (by weight) methyesters*SD. From Reference 48.

Prostaglandins, Leukotrienes and Essential Fatty Acids (1999) 60(5&S), 421429 0 1999 Hamurt Brace & Co. Ltd

similar to the Paleolithic diet in composition. It was low in mendations for a prudent diet low in fat and high in saturated fat, balanced in the essential fatty acids (omega- carbohydrates are not appropriate. The American Heart 6 and omega-3), very low in truns fatty acids, and high in Association does not distinguish between omega-6 fatty vitamins E and C. This diet formed the basis of the diet acids and omega-3 fatty acids, and ignores the detrimen- used by de Lorgeril and Renaud in their now famous Lyon tal effects of bans fatty acids in coronary heart disease.31 study.44~47-4p The Lyon study is a pxospective randomized Dietary recommendations need to be changed and be single blinded secondary prevention trial that compared consistent with the Paleolithic diet containing equal the effects of a modified Crete diet enriched with LNA to amounts of omega-6 and omega-3 fatty acids and plenty those of a Step I American Heart Association diet. A total of fruits and vegetables. of 605 patients were divided into two groups, 302 in the The diet of Crete or the traditional diet of Greece experimental group were fed the modified diet of Crete, resembles the Paleolithic diet in terms of antioxidants, including 2 g of LNA per day and 303 in the control group saturated fat, monounsaturated fat and in the omega- which followed the Step I American Heart Association 6/omega-3 ratio. The Lyon Heart Study and subsequently diet. Plasma levels of vitamins C and E (FK.05) and the Singh et al. studf3 support the importance of having omega-3 fatty acids (P<.OOl), measured 2 months after a diet consistent with human evolution. Western diets randomization, were higher and those of omega-6 fatty today deviate from the Paleolithic diet and are associated acids were lower (FKOOJ) in experimental subjects. The with high rates of cardiovascular disease, diabetes, obesity ratio of omega-6 to omega-3 fatty acids was 4/l. After a and cancer. Although the health of the individual and the mean follow-up of 27 months, there were 16 cardiac population in general is the result of the interaction deaths in the control group and three in the experimental between the genetic profile and the environment, nutri- group; 17 non-fatal myocardial infarctions in the control tion is one of the most important environmental factors.54 and five in the experimental group. A risk ratio for these two main end points combined of 0.27 (95% CI 0.12-0.59, P=O.OOl) after adjustment for prognostic variables.

CONCLUSION

Overall mortality was 20 in the control, eight in the exper- Studies on Paleolithic diet suggest that omega-3 fatty imental group, an adjusted risk ratio of 0.30 (95% CI acids were present in practically all foods that humans 0.1 l-0.82, Jw.02). ate, and in equal amounts to omega-6 fatty acids. The study showed a decrease in death rate by 70% The depletion of the omega-3 fatty acids in Western

in the experimental group and clearly showed that a diets is the result of agribusiness, modern agriculture and

modified Crete diet low in butter and meats such as deli aquaculture. The high ratio of omega-6 to omega-3 fatty products, but high in fish and fruits and vegetables, and acids (20/l instead of l/l) is the result of excessive pro- enriched with LNA is more efficient than the American duction of vegetable oils and the indiscriminate recom-

Heart Association or similar prudent diets in the second- mendation to substitute saturated fat and butter with oils

ary prevention of coronary events and death. The same high in omega-6 fatty acids in order to lower serum subjects were followed for 5 years. At 4 years of follow-up, cholesterol levels without taking into consideration their de Lorgeril et a150 reported the reduction of risk in the adverse effect on overall human metabolism. experimental subjects compared with control subjects The results of the Seven Countries Studies and the was 56% (P=.O3) for total deaths, and 61% (P=.O5) for Lyon Heart Study based on a modified diet of Crete, indi- cancers, indicating that a modified diet of Crete is asso- cate that a Paleolithic type diet such as the traditional ciated with lower risk for coronary heart disease and Greek diet balanced in omega-6 and omega-3 fatty acids cancer. and rich in vitamins C and E (fruits and vegetables) is

Rosamond et a15’ reported that although there is a associated with decreased rates of heart disease and decline in mortality from coronary heart disease, largely cancer more so than any other diet or drug intervention. due to improvements of treatment and secondary prevention of myocardial infarction from 1987 to 1994, there REFERENCES has been a stable or slight increase in incidence of hospi- talization for myocardial infarction. Levy and Thom5’

1. Simopoulos A. P., Childs B. (Eds). Genetic Variation and

state, ‘A more puzzling paradox is the fact that no decline Nutrition. World Rev Nutr Diet, Vol. 63. Karger: Basel, 1990.

2. Eaton S. B., Konner M. Paleolithic nutrition. A consideration of in the incidence of myocardial infarction was observed in the ARIC sample during a period when the prevalence of causal risk factors was reduced.’ It is not puzzling; it is simply that the ‘causal risk factors’ of the study were not the most important risk factors. This study indicates that

its nature and current implications. New En& JMed 1985; 312: 283-289.

3. Simopoulos A. P. Omega-3 fatty acids in health and disease and in growth and development. AmJ clin Nutr 1991; 54: 438-463.

4. .Simopoulos A. P. Genetic variation and evolutionary aspects of diet. In: Papas A. (Ed). Antioxidants in Nutrition and Health,

the current American Heart Association dietary recom- CRC Press: Boca Raton, 1999; 65-88.

Q 1999 Harcoutt Brace & Co. Ltd Ptvstaglandins, Leukotrienes and Essential Fatty Acids (1999) 60(5&S), 421-429


428 Simopoulos

5. Simopoulos A. P. (Ed). Plants in Human Nutrition. World Rev Nutr Diet, Vol. 77. Karqer: Basel, 1995.

6. Fanaian M., Szilasi J., Storlien L., Calvert G. D. The effect of modified fat diet on insulin resistance and metabolic parameters in type II diabetes. Diubetologia 1996; 39(suppll): A7.

7. Simopoulos A. P. Is insulhr resistance influenced by dietary linoleic acid and tram fatty acids? Free Rad Biol 6 Med 1994; 17: 367-372.

8. Simopoulos A. P. Fatty acid composition of skeletal muscle membrane phospholipids, insulin resistance and obesity. Nuti To& 1994; 2: 12-16.

9. Leaf A., Weber P. C. A new era for science in nutrition. Am J CZin Nuti 1987; 45: 1048-1053.

10. Simopoulos A. P. The Mediterranean diet: Greek column rather than an Egyptian pyramid. Nutr Today 1995; 30: 54-6 1.

11. Simopoulos A. P. Overview of evolutionary aspects of w3 fatty acids in the diet. In: Simopoulos A. P. (Ed). The Return of w-3 Fatty Acids into the Food Supply. I. Land-Based Animal Food Products and Their Health Effects. World Rev Nutr Diet Basel: Karger, 1998; l-l 1.

12. Eaton S. B., Konner M., Shostak M. Stone agers in the fast lane: chronic degenerative diseases in evolutionary perspective. Am JMed 1988; 84: 739-749.

13. Kirshenbauer H. G. Fats and Oils. 2nd Edition. New York: Reinhold Publishing, 1960.

14. Emken E. A. Nutrition and biochemistry of tram and positional fatty acid isomers in hydrogenated oils. Annu Rev Nutr 1984; 4: 339-376.

15. Troisi R, Willett W. C., Weiss S. T. Tram-fatty acid intake in relation to serum lipid concentrations in adult men. Am J Clin Nutr 1992; 56: 1019-1024.

18. Ledger H. P. Body composition as a basis for a comparative study of some East African mammals. Symp Zoo2 Sot London 1968; 21: 289-310.

16. Ahrens E. H., Blankenhom D. H., T&as T. T. Effect on human serum lipids of substituting plant for animal fat in the diet. Proc Sot Exp Biol Med 1954; 86: 872-878.

17. Keys A., Anderson J. T., Grande F. Serum cholesterol response to dietary fat. Lancet 1957; 1: 787.

19. Crawford M. A. Fatty acid ratios in free-living and domestic animals. Lancet 1968; 1: 1329-1333.

20. Wo C. K. W., Draper H. H. Vitamin E status of Alaskan Eskimos. Am J Clin Nutr 1975; 28: 808-813.

21. Crawford M. A., Gale M. M., Woodford M. H. Linoleic acid and linolenic acid elongation products in muscle tissue of Syncerus caffer and other ruminant species. Biochem J 1969; 115: 25-27.

22. Simopoulos A. P., Salem N., Jr. Purslane: a terrestrial source of omega-3 fatty acids. N Engl J Med 1986; 315: 833.

23. van Vliet T., Katan M. B. Lower ratio of n-3 to n-6 fatty acids in cultured than in wild ftsh. Am J Clin N&Y 1990; 51: l-2.

24. Simopoulos A. P., Salem N., Jr. Egg yolk as a source of long- chain polyunsaturated fatty acids in infant feeding. Am J Clin Nutr 1992; 59: 41 I-414.

25. Raper N. R, Cronin F. J., Exler J. Omega-3 fatty acid content of the US food supply. J Am College Nuk 1992; 11: 304.

26. Hunter J. E. Omega-3 fatty acids from vegetable oils, in Dietary w3 and w6 Fatty Acids: Biological Effects and Nutritional Essentiality, Series A: Life Sciences, Vol. 171. Galli C., Simopoulos A. P., Eds., Plenum Press, New York, 1989: 43-55.

27. Simopoulos A. P., Norman H. A., Gillaspy J. E., Duke J. A. Common purslane: a source of omega-3 fatty acids and antioxidants. JAm College N&r 1992; 11: 374-382.

28. Simopoulos A. P. Nutrition and fitness, JAMA 1989; 261: 2862-2863.

29. Simopoulos A. P., Salem N Jr. n-3 fatty acids in eggs from range-fed Greek chickens. N Engl J Med 1989; 321: 14 12.

30. Simopoulos AP, Norman HA, Gillaspy JE. Purslane in human nutrition and its potential for world agriculture. World Rev Nutr Diet, Volume 77. Basel, Switzerland: Karger, 1995: 7-74.

3 1. Simopoulos A. P. Trans fatty acids. In: Spiller G. A. Handbook of Lipids in Human Nutrition Florida: CRC Press 1995: 91-99.

32. DuPont J., White P. J., Feldman E. B: Saturated and hydrogenated fats in food in relation to health. J Am Colkge Nuf 1991; 10: 577-592.

42. Galli C., Simopoulos A. P., Tremoli E. @is): Fatty Acids and Lipids: Biological Aspects. World Rev Nutr Diet. Basel, Karger, vol. 75, 1994.

33. Litin L., Sacks F. Tram-fatty-acid content of common foods, NEngl JMed 1993; 329: 1969-1970.

34. Guil J. L., Torija M. E., Gimenez J. J., Rodriguez I. Identification of fatty acids in edible wild plants by gas chromatography. J Chromutog A 1996; 719: 229-235.

35. Cot&in L., Martin C., Florant G., Watkins B. A. The fatty acid composition of muscle, brain, marrow and adipose tissue in elk: evolutionary implications for human dietary lipid requirements. Worth Rev Nuk Diet 1998; 83: 225-226.

36. Sinclair A. J., Slattery W. J., O’Dea. The analysis of polyunsaturated fatty acids in meat by capillary gas-liquid chromatogramphy. J Food Sci Ag?ic 1982; 33: 771-776.

37. Simopoulos A. P. The role of fatty acids in gene expression: health implications. Ann Nutr Metub 1996; 40: 303-3 11.

38. Simopoulos A. P., Kifer R E., Martin R R (Ed). Health Effects of Polyunsaturated Fatty Acids in Seafoods, Proceedings from the Conference, June 1985. Academic Press, Orlando, 1986.

39. Galli C., Simopoulos A. P. (Eds). Dietary w3 and w6 Fatty Acids: Biological Effeots and Nutritional Essentiality. New York: Plenum Publishing Corporation, 1989.

40. Simopoulos A. P., Kifer R R, Martin R E. and Barlow S. M. (Eds). Health Effects of w3 Polyunsaturated Fatty Acirds in Seafoods. World Rev Nutr Diet. Basel, Karger, vol. 66, 1991.

4 1. Galli C., Simopoulos A. P., Tremoli E. @Is). Effects of Fatty Acids and Lipids in Health and Disease. World Rev Nutr Diet. Basel: Kargex, vol. 76, 1994.

43. Salem N. Jr, Simopoulos A. P., Galli C., Iagarde M., Knapp H. (Eds). Proceedings of the 2nd Congress of ISSFAL on Fatty Acids and Lipids from Cell Biology to Human Disease. Lipids, Volume 3 1 (Supplement) S-l-S326, 1996.

44. Simopoulos A. P., Robinson J. The Omega Plan. The Medically Proven Diet that Gives You the Essential Nutrients You Need. New York: Macmillan, 1998.

45. Keys A. Coronary heart disease in seven coutries. Circulation 1970; Ql(supp1): l-211.

46. Sandker G. W., Kromhout D., Aravanis C. et al. Serum lipids in elderly men in Crete and The Netherlands. Eur J CZin NuEr 1993; 47: 201-208.

47. Renaud S., Godsey F., Dumont E., Thevenon C., Ortchanian E., Martin J. L. Iniluence of long-term diet modification on platelet function and composition in Moselle farmers. Am J C%n Nutr 1986; 43: 136-150.

48. De Lorgetil M., Renaud S., Mamelle N., et al. Mediterranean alpha-linolenic acid rich-diet in the secondary prevention of coronary heart disease. Z.uncet 1994; 513: 1454-1459.

49. Renaud S., de Lorgetil M., Delaye J. et al. Cretan Mediterranean diet for prevention of coronary heart disease. Am J Clin Nutr 1995; 6l(suppl): 136OS-1367s.

50. de Lorgeril M., Salen P., Martin J.-L. et al. Mediterranean dietary pattern in a randomized trial. Prolonged survival and possible reduced cancer rate. Arch Intern Med 1998; 158: 1181-l 187.

Prostaglandins, Leukotrienes and Essential Fatty Acids (1999) 60(5&S), 421-429 0 7999 Harcouri Brace & Co. Ltd


51. Rosamond W. D., Chambless L. E., Folsom A. R. et al. Trends in the incidence of myocardial infarction and in mortality due to coronary heart disease, 1987 to 1994. N Engl J Med 1998; 339: 86 l-867.

52. Levy D., Thorn T. J. Death rates from coronary disease-progress and a puzzling paradox. N En@ .J Med 1998; 339: 9 15-917.

53. Singh R B., Niaz M. A., Sharma J. P. et al. Randomized, double- blind, placebo-controlled trial of fish oil and mustard oil in

patients with suspected acute myocardial infarction: The Indian Experiment of Infarct Survival 4. Cardimasc Drugs Thr 1997; 11: 485-91.

54. Simopoulos A. P., Herbert V., Jacobson B. The Healing Diet: How to Reduce Your Risks and Live a Longer and Healthier Life If You Have a Family History of Cancer, Heart Disease, Hypertension, Diabetes, Alcoholism, Obesity, Food Allergies. New York Macmillan Publisheql995.

0 7999 Harcourt Brace & Co. Ltd Prostaglandins, Leukotrienes and Essential fatty Acids (1999) 60(5&6), 421-429

article no. plef.1999.0061 evolutionary aspects of omega-3 fatty … · pmstag/andins, leukotfimes...

Documents