I wrote this book for several reasons.

First, I have been teaching a course called Nutrition and Health for almost 25 years and I have taught the material in this book many times. Over this period of time I have adjusted my teaching so that the students could maximally learn the important concepts underlying fat and lipoprotein metabolism so that they could use this information in later classes.

Second, I have been asked by many people about cholesterol and why it is so important or so bad for them, and I finally decided to write a book that would finally explain the functions of this mystery substance in a way that my friends and family could understand. In fact, I have encountered some doctors who had no idea what cholesterol was and what it did in the body. So this book is for them, too.

Third, I recently was asked to teach the department’s obesity course and although I am not an obesity researcher, I gave it a try. For twenty five years I had taught about obesity in my general nutrition class, but this only takes about two lectures as there is so much other material in the course. I thought I knew everything I needed to know about obesity, but in teaching the obesity course for two semesters, I was surprised to learn that, in fact, I knew very little about obesity and its causes.

And in fact, when I combined what I learned in teaching the obesity class and what I had been teaching in Nutrition and Health for twenty five years, I realized that I had a powerful message to make available to a wider audience.

And finally, one day I started to look through Ancel Keys’ “Seven Countries” book that I had on my book shelf in my office. I kept on reading it through the afternoon, and by the next day, I had read the book cover to cover. And the thought that immediately came to my mind was that everything that I had heard about Ancel Keys in my graduate school classes and in basic scientific discussions was not accurate. I had heard that he had been a dominant and divisive figure in the history of CHD research, but this was not the Ancel Keys that came across so eloquently in the book. The book was carefully written and was open minded; Ancel Keys did not use bombastic language that indicated he was the ultimate source of knowledge; and most importantly, several times in the book he acknowledged that he did not understand his findings. I found a man who was a true scientist, and not someone who used science for his own purposes and advancement.

And if one searchers for Ancel Keys on the internet, it is immediately apparent that there are many people who consider him the devil because of his scientific findings. They dispute the cholesterol hypothesis with very little understanding how complex lipid metabolism is and with little sense of how work it required to make even elementary discoveries. In fact, they reminded me of the global warming science deniers that are so prevalent today.   So another reason I wrote this book was to set the record straight concerning Ancel Keys’ research accomplishments, and also the research accomplishments of the many scientists who have struggled to make sense of the cholesterol and fat fields. And as he does in his scientific research articles, Dr. Keys gives credit to other scientists and their research studies in his book, “Seven Countries.”

As I indicated earlier, I am not an obesity researcher. But I am a lipids researcher and I understand lipid metabolism to the extent that I can explain it and relate it to our current obesity crisis. It is quite possible that at times I made lipid metabolism too simple. If I have done so, I recommend that you read a biochemistry text! The fact that I am not an obesity researcher may be an important facet of what I bring to the table because I think it helped me sort through the great quantities of articles and information that has accumulated in the obesity field of study. Also, not being an obesity researcher may have caused me to leave out some important aspects of the obesity problem. If I have done so, then I apologize for these omissions.




When Dr. Ancel Keys wrote the “Seven Countries” book (published in in 1980), he seemed to follow the strategy of writing ”Just the facts” from his multi-country study and interpreting the data as best he could without exaggerated speculation. However, the exciting and much more interesting human story of how he came upon his theory that diet and blood cholesterol were responsible for the high rates of CHD in some populations is not in “Seven Countries.”   In fact, the interesting story of how he developed his ideas and how he discovered the “Mediterranean diet” were presented in the first few chapters of the cookbook that he and his wife, Margaret, wrote, “How to Eat Well and Stay Well the Mediterranean Way,” first published in 1969 and then again published in 1975.

This book is rather hard to find now a days. I could not find it in either the Rutgers University or New York Public Library Systems. When I tried to buy it on Amazon and other sites, it was listed at over $300 for a used copy. However, if you find this book in a used book store, buy it, because it is surely a gem of a book. I finally found it in a local library in New Jersey that seems to specialize in cook books!

In the Authors’ Preface, Dr. Keys and Margaret give the background for the book and graciously thank all the scientists, physicians and friends who were involved in the work and who helped them in their travels around the globe in search for the causes of CHD. They write that the book was the result of 25 years of research by them with the help of hundreds of co-workers and friends. No where is it stated that their endeavor was a singular enterprise. They give ample credit to many others who contributed to their story.

In 1962 Dr. Keys and his family moved, part-time, to Pioppi, Italy, south of the city of Naples. The house they finally settled in is on the Cilento coast and overlooks the Mediterranean sea, and Dr. Keys named it “Minnelea”, from the first letters of Minnesota and the ancient Greek Elea.   Quite remarkably, the house he lived in can be rented during the summer months.

Screen shot 2014-06-15 at 10.31.39 PM

Screen shot 2014-06-15 at 10.32.10 PM

In chapter 1, “Introduction-Why and How,” Dr. Keys and Margaret explain, in a relatively short chapter of 24 pages, how the idea about diet being an important component of the onset of CHD was hatched, how it progressed slowly at first, and then, how the concept was formerly presented and studied under the well planned structure of the “Seven Countries” study. Anyone who has heard the invectives that claim that the diet-cholesterol-CHD theory was a conspiracy put forth by Dr. Ancel Keys can’t possibly believe this claim after reading the story of how the ideas coalesced among Dr. Keys and his colleagues.

“How to Eat Well and Stay well the Mediterranean Way,” which is a combination “Who done it mystery” and health/cookbook, was written before there was any controversy concerning the fat and cholesterol hypothesis, and therefore, the detailed descriptions of how their ideas were made more concrete was written without any sense of defending a core idea. In fact, what comes across in this chapter is a sense of wonder how a meandering course led to one of the most important discoveries in modern medicine. And it is hard for us to realize that at the beginning of their journey, no one had any idea concerning what caused CHD, or that simple changes in life style could protect against CHD, or enhance its ghastly effects.

Although Dr. Keys had been a successful and well known scientist since the 1930s, and he had been involved in a variety of studies, including measuring cholesterol in blood in several smaller studies, the current story really begins in February 1952, when the Keys traveled to Naples, Italy, to study the role of diet in CHD. They had been living in England as part of a Fulbright Fellowship, and they had been invited to the University of Naples by Professor Gino Bergami.

Quite amazingly, they wrote about a singular observation that had stimulated their thinking, “A totally obscure Dutch language publication stated that natives of Java lived on a diet very low in fat, had remarkably low cholesterol levels, and almost never suffered heart attacks.”

Concerning their work in Naples, they were going to follow-up on the dual observations made by local physicians that the local Neapolitan diet was low in fat and that there were few cases of CHD among the common people of the city. They did, in fact, find this to be true, and found that the men they studied in Naples had an average cholesterol of 165 compared to the 230 that was the average Dr. Keys usually observed in Minnesota, USA. Later on that year, they visited Spain for the purpose of observing the eating habits of the people in several villages there. They observed a similar situation concerning the foods eaten and the good health of the people living in these villages. The Keys’ trips to these two Mediterranean countries were fairly casual, but the observations they made had a great impact on them, that the diet consumed in these communities, at the time, appeared to be protective against CHD.

In the spring of 1954, the year I was born, the Keys returned to Naples to continue their studies. They brought with them several other investigators, including the prestigious American cardiologists, Joseph T Doyle of New York and Paul Dudley White, who was President Eisenhower’s cardiologist. They extended their studies to several other sites in Italy, including Cagliari, on the island of Sardinia, and the northern city of Bologna, known for having a richer cuisine than the other locations in Italy. Their findings concerning the fat content of the diet and blood cholesterol concentrations held up in these locations.

The year 1954 also saw the beginning of a collaboration with Dr. Noboru Kimura, a young heart doctor from Japan. By 1956 a fair size study was underway in Fukuoka, Japan, a city with surrounding farming villages and also a nearby US military base.

A month long visit to Japan by Dr. Keys and his team confirmed the widely reported but unsubstantiated claims that Japanese men, who were fairly heavy smokers, had very low rates of CHD.

Studies also commenced in Hawaii, where white men who consumed a fairly American diet could be compared to men of Japanese ancestry, who still followed a basically Japanese diet.

The results were startling, the Japanese in Fukuoka, Japan and in Hawaii, had blood cholesterols of about 160, but the white Americans in Hawaii had cholesterol levels similar to the white men Ancel Keys studied in Minnesota. This led to an interesting yet unique conclusion at the time. This conclusion was that high cholesterol and high rates of CHD were not related to climate! Sounds funny now, but this really was considered a possibility at the time.

In 1956 Dr. Keys was afforded the the opportunity to collaborate with Professor MarttiKarvonen of the Institute of Occupational Health in Helsinki, Finland. The first village they sampled was Karelia and they found very high rates of CHD among the men. The average blood cholesterol concentration was a shocking 260, compared to the 230 Dr. Keys had consistently measured in Minnesota. When he saw what they ate, however, it became apparent what was the cause of the high cholesterols. Dr. Keys states that he, “…watched in disbelief to see some of them take slabs of cheese the size of slices of sandwich bread, smear them a quarter of an inch deep with butter and eat them, with a beer, as an after-sauna snack.”

Earlier I wrote how the CHD rates in Finland were cut in half by a combination of decreasing fat intake, decreasing blood pressure, and lowering smoking.

In 1957 Dr. Keys and a team of scientists next surveyed the village of Nicotera, near the toe of the Italian boot, and several villages on the island of Crete. The blood cholesterol levels were very low (160) in Nicotera because of the extremely low fat intake of its inhabitants. Crete was especially interesting because the fat intake was relatively high there. But because most of the fat consumed was olive oil, the cholesterol concentrations in the blood of the men of Crete were below 200. At this time, in the 1950s, the foods on Crete were served usually drenched in olive oil. Butter and milk were not used. Meat was only consumed once or twice per week. Some farmers had the habit of drinking wine glasses of pure olive oil for breakfast! Although roughly 1/3 of the calories consumed on Crete were from fat, the rates of CHD were extremely low. This was an early sign that it was the type of fat that was important in influencing the cholesterol levels of blood, and not fat per se.

All of what had gone on before was sort of a feasibility study for a much larger study. There were critics who thought the small studies carried out by Dr. Keys and his team were too haphazardly designed and performed.   So the plans went forward to start a well designed study that would measure blood cholesterols and rates of CHD in different populations throughout the world, and to measure in precise ways (using dietitians and analyzing samples of diets) the dietary intakes of subjects in the different regions. This was the start of the “Seven Countries” study. It eventually would study about 13,000 men in seven countries, with some countries providing several distinct geographical locations to be studied.

One must remember that the “Seven Countries” study was started before statins had been discovered. Therefore, there was a great deal of emphasis on stopping the progression of any CHD that was already a scourge of Western populations. As discussed in other chapters, in Finland, dietary recommendations changed the diet of many Finns such that there was a large decrease in CHD. But changes occurred in the other direction, too. As Europe recovered from the drastic effects of World War II, the diet of many began to become richer in terms of meat and dairy products. This had the effect of slowly increasing CHD where before there had been almost none. The Mediterranean diet was becoming less “Mediterranean” in several of the cohorts while the follow-ups to the “Seven Countries” study were underway.

What was the Mediterranean Diet as Dr. Keys Observed it?

Chapter 2   The Mediterranean World.

In Chapter 2 Dr. Keys and Margaret wrote about the foods they found in the Mediterranean diet and the Mediterranean life style they observed in their travels.   They make the comment in the beginning of the Chapter that they are specifically talking about the countries of Greece, Italy, the Mediterranean portion of France, and Spain. Each had their own special dishes and customs. The location they knew best was southern Italy, because they decided to move to a house in southern Italy for at least six months of the year while Dr. Keys was still working, and for the full year after they retired in 1972.

What was the Mediterranean diet they observed and experienced?

Vegetables and fruits.

The availability of vegetables and fruits depended upon the season. Early in the spring there were cauliflower, artichokes, and lettuce available. Later there were fava beans and a dozen different wild greens in the markets. Later still came spinach, green beans, and zucchini. Late spring brought cherries, kumquots and mushrooms.

Summer brought figs, tomatoes, eggplants, peppers and onions. At the end of summer, wine was prepared during the grape harvest.   All sorts of melons were available in the early fall.  From their own property they harvested apples, pears and a whole family of citrus fruits.  Late fall saw the production of persimmons, pomegranates, and finally olives. In the end, one senses that there was a cornucopia of fresh vegetables and fruits that were brought in from the local farms and hillsides the year round.


Olives pressed early in the season were the source of virgin olive oil. A small percentage of olives were prepared for whole storage to be used as table olives during the year. The largest per capita consumption of olive oil occurred on Crete, where it provided 30% of the total caloric intake. In other areas of the Mediterranean, olive oil provided from 15% to 20% of total calories. French cooking used more butter and therefore was not as healthy as the cuisine of Greece and Italy.


Freshly baked bread provided a considerable amount of calories for Mediterranean peoples. In Greece, it could provide up to 38% of the total calories consumed. In other countries it was less, but it still was a significant percent of the total calories consumed. On average, at the time of Dr. Keys’ investigations, three times more bread was eaten in the Mediterranean areas compared to what was eaten in the USA.


Fruit was the main dessert served in Mediterranean households. Sweet desserts were reserved for holidays. Peoples of the Mediterranean region ate, on average, 150% more fruit than Americans.

Garlic and onions

These were used in cooking, stews and salads. Garlic soup is a specialty of the Spanish whereas the French are known for their onion soup. The Italians are known for their bruschetto, which is a slice of hot toast brushed with olive oil and raw garlic.

Tomatoes and garden greens.

The Mediterranean peoples harvested tomatoes and prepared tomato sauce every August. Bottled tomato sauce was used throughout the year in stews and with pastas. Also eaten all year round was a vast array of leafy greens that come from the garden or from the roadside. The Mediterranean people ate a much wider variety of greens than do Americans.

Dr. Keys wrote in a later article, “Near our second home in southern Italy. all kinds of leaves are an important part of the everyday diet. There are many kinds of lettuce, spinach, Swiss chard, purslane. and plants I cannot identify with an English name such as lettuga, barbabietole, scarola, and rape. Some are perennials.  The climate permits replanting annuals several times a year so leaves to eat are always at hand.  No main meal in the Mediterranean countries is replete without lots of dure (greens).  Mangiafoglia is the Italian word for “to eat leaves” and that is a key part of the good Mediterranean diet.”

Seafood and Meat

Mediterranean people were strong consumers of anchovies, octopus, mackerel, dried codfish from northern seas, and a vast array of ocean fish.

Americans were eating four times more meat than what was consumed in Greece and Spain. In Mediterranean countries more veal than beef was consumed, except in France. Only about half the eggs Americans ate were consumed by Mediterraneans. The French ate more butter than Americans, but the other Mediterranean countries consumed only about one third to one half the butter Americans did at the time.


The consumption of wine was much greater in Mediterranean countries, but it was usually consumed with main meals. For men, the amount of wine consumed possibly amounted to about 10% of total caloric intake coming from alcohol. There was very little consumption of hard liquor except on special occasions.

The Mediterranean people are known to drink strong and freshly made coffee, often using an “espresso” machine. In fact, coffee with added hot milk was a common breakfast for Mediterranean people. Spain was the one country where people also drank a considerable amount of hot cocoa. Other drinks that were popular were lemonade, cola drinks, and mineral water. Cola drinks were not consumed at the level observed at the time in the United States

The Intangibles

Mediterranean people were more likely to take an evening stroll than Americans.  They were also likely to eat a wider variety of foods, especially fresh seafood and vegetables.  Because of the southern sun, they received more sunlight on a yearly basis, spread across the year round, than in northern regions where there are periods of little sun followed by intense sun exposure during the summer.

At the time Dr. Ancel Keys and Margaret wrote their Mediterranean cookbook, they commented that although the expenditures of the Mediterranean countries on health care were much less than that expended in the US, the Mediterranean peoples’ “overall health and longevity are impressive, both in the vital statistics and in our own many years of scientific observations.”

The main difference in health was that there was much lower rate of CHD in Mediterranean countries compared to the US. Dr. Keys specifically commented that the difference was not explained by climate, genes, nor the way disease was diagnosed nor how statistics were kept. And another plus was that deaths from all causes were lower in the the Mediterranean countries than in the US.

The remainder of the book, “How to Eat Well and Stay well the Mediterranean Way,” is chock full of recipes of all types, and as stated by the Keys in the Authors’ Preface, all were tested first in their kitchens, sometimes in Pioppi, Italy, sometimes in Minnesota, before they were entered into their cook book.

Their book was the first one to promote the Mediterranean diet.   Combined with the early chapters on diet and health, it represents an additional major triumph in the life of this extraordinary scientist and his companion spouse.

Ancel and Margaret Keys had three children, a boy and two girls. He retired from the University of Minnesota in 1972. Due to many factors (genetics, personal traits, diet) that can’t possibly be known for any particular individual, but one would like to think that the Mediterranean diet played an important role, Ancel Keys lived to be a hundred years old. He died in Minneapolis on November 20, 2004, two months short of his 101st birthday. Margaret died in 2006 at the age of 97. It is safe to say that Ancel and Margaret had a long and productive partnership, and that they were giants in the fields of Nutrition and Medicine.

There are thousands of books that have diets as their entire subject. I have dedicated just one chapter to diets because all diet books, and all popular diets, are derivatives of a very few number of diet possibilities.   The diet possibilities are:

1) Extreme macronutrient distribution diets

2) Inclusion or exclusion diets

3) Very low calorie diets

4) Diets with external psychological and/or structural support (usually diets that one pays for)

5) Diets that use eccentric or no preparation techniques (example: The Paleo diet)

Because all diets are based on a few very simple variations of the basic average American diet, the diets that have been recently popularized have actually been around for 50 years or more and every so often they have renewed popularity. An excellent review of an amazing variety of diets was presented in the book, “Rating the Diets,” by Theodore Berland and the Editors of Consumer Guide, published by Consumer Guide (Stokie, Illinois), Volume 77, April 1975. This guide reviews, in detail, many popular diets, including Dr. Atkin’s, Dr. Stillman’s, Mayo, Prudent, Zen, Simeons, Kennedy Hormone Diet Program, Cellulite Diet, Boston Police Diet, and many other diets. This review by the Chicago Tribune health columnist, Theodore Berland, is extremely well written and comprehensive.  It is also extensively referenced with early scientific articles describing studies of many of these diets.  Many of these articles have been forgotten, but they are still relevant and scientifically pertinent.

In my opinion, all diets are viable if they are healthy – for both the short-term and the long-term. People are different and they tend to gravitate to diets that fit their life style and basic tendencies.  I will only address the diets that are made up of different macronutrient contents, as these are the ones that are most often written about in books and in magazine articles.

In Chapter 7, I discussed the “Dietary Goals for the United States” that was released by Senator George McGovern’s committee, and the subsequent Dietary Guidelines released a few years later.  I included a table that presented the macronutrient breakdown of diets from a wide range of human societies.   This table illustrated the point that human groups were and are highly adaptable to different dietary macronutrient mixtures.

In the next table, I have compared the different main diets that rely on variations in macronutrient content that are popular today. In the left most column is the typical American diet as described by the USDA. In the second column is the low carbohydrate diet that is also called the Atkins Diet. In the middle column is the Zone high protein diet that many students in my class who are weight training adhere to. The fourth column is the very low fat diet, which is essentially a high unprocessed carbohydrate diet. And the fifth diet is the Mediterranean diet, which was first proposed and written about by Ancel Keys.

table diets for Ancel Keys obesity book

The typical American diet shown is an amalgam of many diets consumed in the United States. This diet is also called the “Western Diet.”

The Very Low Carbohydrate Diet

The low carbohydrate diet has been around for many years but has recently become popular again. It is predicated on the concept that high intakes of carbohydrates are obesogenic because they lead to an increased insulin level, which supports energy storage over utilization, and extremely low carbohydrate consumption prevents this. This is a complex metabolic issue and I will not discuss it right now.  A very important distinction here is that I am talking about the very low carbohydrate diet, where carbohydrate intake is at first set at 20 grams per day, which computes to just 80 kcal out of entire intake of 2000 kcal, or less than 5% of the total kcal intake.  And when intake is increased gradually to 50 grams of carbohydrate, carbohydrate intake is only increased to about 10% of total kcal intake.  This compares to the 50% of total kcal intake that carbohydrates provide in the typical American diet.  Because carbohydrates are so low in the diet, the very low carbohydrate diet is actually a high fat diet!  But most nutritionists feel that very low carbohydrate diets actually work, to some extent, because most kcal in our diet are supplied by carbohydrates, and when you eliminate carbohydrates, you eliminate total kcal from the diet. Therefore, lower energy intake occurs on this diet.  I have known several colleagues who like and prefer the very low carbohydrate diet and have used it to lose weight. They will follow the low carbohydrate diet for a month or two and then cycle back onto their regular diet.  Therefore, if the low carbohydrate diet appeals to someone, I applaud their use of this diet.

Several well known nutritionists have written negative reviews of the very low carbohydrate diet.

Dr. John Yudan, M.D., who was a Professor of Nutrition at the University of London, and who was a proponent of removing as much sugar from the diet as possible, commented in 1960, “We now also understand why this diet can lead to loss of weight in the obese. It is low in Calories, and it is this which causes loss of weight, and not some peculiarity in carbohydrates metabolism.”

Yudan, J and Carey, M. The treatment of obesity by the High-fat diet – the inevitability of calories. Lancet (Oct 29, 1960) pp. 939-941.

The negatives and positives of the very low carbohydrate diet are listed on the table.

Zone, High Protein Diet

The high protein diet provides at least 30% of kcal from protein and if possible more. Consuming 30% of kcal from protein sounds reasonable, but in reality it is difficult to obtain this much protein in the diet due to the naturally low content of protein in most foods. Another difficulty is that there are a limited number of protein rich foods, which leads to boredom when eating this diet. Also, a protein supplement often needs to be consumed to reach enough protein. The biggest plus of the classic high protein diet is that there are ample carbohydrate kcal in the diet that can be used for energy and to restock glycogen stores.

Very low fat/high carbohydrate diet

The very low fat/high carbohydrate diet is supported by several well respected medical authorities for the treatment and prevention of cardiovascular diseases such as CHD. Because this diet only contains about 10% of kcal from fat, the majority of kcal must be provided by carbohydrates. Therefore, the low fat diet is, in fact, a high carbohydrate diet. But the carbohydrates are derived from whole grain products. Also, there is a high intake of fruits and vegetables, so this diet also contains high fiber. Because of the composition of the diet, it is nutrient dense. The main problem with the low fat/high carbohydrate diet is that it provides low satiety due to the low fat content in the diet. Therefore, although there is no doubt that it is heart healthy diet, it is difficult for many people to stay on the very low fat/high carbohydrate diet. However, there are certain people who enjoy this diet and remain on it for their entire adult lives.

The Mediterranean Diet

The Mediterranean diet is in the far right column in the table, and this diet was first promoted in Ancel and Margaret Keys’ cookbook, “How to Eat Well and Stay Well the Mediterranean Way” (Doubleday, 1975). I will discuss the Mediterranean Diet in detail in the last chapter of this book. But if you look through the table, you will see that the Mediterranean diet maintains the approximate macro nutrient percentages of the typical American diet, but the ingredients and methods of food preparation are totally different. An important aspect of the Mediterranean diet is that it is a high fiber diet. Also, a recently published clinical trial confirmed that the Mediterranean diet was protective against diseases of the heart. I will discuss the Mediterranean diet in detail in the last chapter.

Since the diets presented in the table are based upon different variations in macronutrient content, I would like to discuss each of the macronutrients individually.


What Fats Should Americans Eat?

As discussed in an earlier chapter, there are over 10,000 different lipid species inside a cell. Therefore, a logical overriding strategy would be that humans should consume as wide a variety of fats from a wide range of foods as possible.  In previous chapters I discussed the most important functions of fats and cholesterol, but I was unable to cover every function they serve in the body. I also did not provide structures for the various lipid groups.  It is not the purpose of this book to cover every aspect of lipid metabolism.  In order to be exposed to a wider explanation of the functions of lipids and see their drawn structures, a recent book by Dr. Glen Lawrence would be a good place to start.

The Fats of Life: Essential Fatty Acids in Health and Disease [Paperback] by Professor Glen D. Lawrence, Rutgers University Press, 2013.

The next figure illustrates that humans should obtain nutrients, including fats, from many food sources.  The figure also shows why certain foods have a particular fatty acid composition.

Food Sources for Lipids

The algae on the left are one of the main sources of food for fish and other marine life. Algae are photosynthetic organisms and use photons from the sun to incorporate CO2 into cell molecules including lipids. Many different fatty acids are synthesized in algae but a large percentage are PUFA, including the omega 3 fatty acids EPA and DHA. Since ocean algae live their whole lives in the very cold ocean, it is important for their membranes to remain fluid and not to harden and freeze up. For this reason, algae incorporate EPA and DHA into the phospholipids of their cell membranes. When fish consume algae they receive high amounts of omega 3 fatty acids. Since fish cannot make their own omega 3 fatty acids, they utilize the omega 3 fatty acids from the algae for their own membranes. This allows the fish, too, to live in the cold ocean. Therefore, the fatty acid composition of fish resembles the fatty acid composition of the algae they eat.  Also, this is the reason why fish caught in the ocean are healthier than fish that are farm raised and fed grains as food.

Terrestrial plants also live exposed to harsh environmental conditions (temperatures vary from -40 °F to 110 ° F ). As with algae, plants use photosynthesis to synthesize fatty acids from CO2.   Most plants have the enzymes necessary to synthesize PUFA, especially omega 6 fatty acids. However, different from algae, plants have limited capacity to synthesize large amounts of omega 3 fatty acids. Therefore, although plants are good sources of PUFA, they are not good concentrated sources of omega 3 fatty acids. In the figure the overall content of PUFA falls from about 70% in algae to about 30% in plants, although this depends upon the specific plant studied.

When humans consume meat they consume the fatty acid pattern that is found in the animals from where the meat was derived from. In general, the fatty acid composition can vary based upon what the farm animals were fed. However, the fatty acid content of meat is usually more saturated and contains smaller amounts of PUFA. The monounsaturated fat content of the fat can vary considerably. Quite interestingly, the fatty acid content of animals that are free living and hunted by hunter-gathers often contains higher levels of PUFA than animals raised on a farm.

Finally, the fatty acid composition of cow’s milk is the most saturated of any other common food. The reason for this is that milk contains higher levels of saturated medium chain fatty acids, which may be better for digestion and utilization in young animals, including humans.

Since omega 3 fatty acids are so important for the brain, it is probably an excellent strategy to get a considerable amount of our dietary fats from sources on the left side of the figure. These sea foods are rich in PUFA including omega 3 fatty acids. However, there are other foods available that supply PUFA, and these are the land based plants. Early humans also relied upon whole grains and these should be included in the diet for both their fiber and PUFA. From what we know of Ancel Keys’ “Seven Countries” study, it is probably reasonable to obtain fat from the sources on the right side of the figure less frequently, although they can certainly remain in the diet at lower levels.

Because of the composition of fat in the foods presented in the figure, an intelligent goal for consuming these foods is to follow the recommendations shown in tan color on the slide. Recommendations for the main meals during the week would be:

Algae   – May become an important food source of omega fatty acids for humans some day! Who knows?

Fish and seafood – Eat twice a week as a main course

Plant foods and whole grains/legumes –   Eat at least 3 times a week as a main course

Meat – Eat as a condiment and maybe as a main source occasionally– Eat no more than 2 times a weeks as a main course. White meats are better than red. Chicken can be used as a main course.

Dairy – Eat sparingly – especially butter, which is concentrated milk fat; Eggs are a great sources of protein (6 grams per egg) – if you eat 2 eggs, only eat one yolk!

As long as you follow the above simple rules, you will not need to count the grams of fat that you are eating in your diet.

Conclusions on Fat

The above figure presents an improved way of looking at fat. We need to stop talking about Low Fat/High Fat in the diet. It is the type of fat that will either protect you, or lead to, after decades, to a multitude of chronic disease conditions!  If foods from all of the sources shown in the figure are eaten, then a wide range of different fatty acids and lipids will be consumed.


Since most of us consume enough protein, I have decided not to have an extensive protein section. Nutritionists believe that it a sensible to boost protein intake up to about 20% of total calorie intake (up from about 16%) to help maintain body weight. For most of us this involves boosting our protein intake by 25 grams per day! This is not as easy as it sounds, as protein rich foods tend to be more expensive. Reasonably priced protein bars (some providing 10 grams of protein per bar) can be used for a quick high protein snack. Consuming the Zone or High Protein diet is another story completely.  Boosting dietary protein kcal even further, up to 30% of total calorie intake from protein, is difficult and takes planning and determination. Most people following this strategy must use protein supplements or the consistent consumption of high protein sources such as meat and fish.

For example, on a 2500 kcal diet, providing 30 % of total kcal intake from protein means that a person on the high protein diet would need to consume 750 kcal from protein, which calculates to 188 grams of protein per day.  In order to eat 188 grams of protein one would have eat the following:

Food needed for 188 grams of protein

In order to understand how much protein this is compared to what is normally eaten, below is a short review of how much protein our body needs, how much is recommended, and how much most Americans consume per day.

Average protein requirement- Average amount of protein we need per day to survive

For a 70 kg man:  0.35 grams x 70 = 24.5 grams (Requirement)

For a 60 kg woman: 0.35 grams x 60 = 21 grams (Requirement)

RDA for protein- What is recommended to maintain health in almost all healthy people

Man: 70 kg x 0.8 g protein = 56 g protein   (RDA)

Woman: 60 kg x 0.8 g protein = 48 g protein (RDA)

NHANES III actual protein intake (average grams/day)- What we actually consume (average) per day

Man 19-30: 103 g/day (Actual Consumption)

Woman 19-30: 70.4 g/day (Actual Consumption)


Certainly it is possible to eat the high protein foods listed on a daily basis, but it may be difficult to keep this diet up for more than a couple of months due to the monotonous nature of eating similar foods every day.  However, there are people who like to eat a high protein diet, and when designed properly, the high protein diet may be effective for weight loss because total calories will decrease as one becomes disenchanted with consistently consuming high protein.


The intake of carbohydrates has increased during the period that obesity rates have increased. Earlier I showed that per capita consumption of corn sweeteners increased 4 fold from 1970 to 1997. Consumption of carbonated soft drinks also increased during this time.

Let’s take a closer look at carbohydrate intake during the increase in obesity rates.

Change in Carb intake AJCN

Total Carbs vs Fiber Intake AJCN 2004

Carb and BMI Figure AJCN

Total energy intake remained fairly constant until 1980 (data not shown). After 1980 total energy intake gradually increased until it reached approximately 500 kcal/day. Increased consumption of carbohydrate was the main contributor (428 kcal; about 80% of the increase). The remaining increases came from protein (12%) and fat (8%). During a 20 year period, the increase in consumption of dietary carbohydrates went from 48% to 54% of total energy intake while dietary fat fell from 41% to 37% of total energy intake.

Lee S Gross, Li Li, Earl S Ford, and Simin Liu. Increased consumption of refined carbohydrates and the epidemic of type 2 diabetes in the United States: an ecologic assessment. Am J Clin Nutr 2004;79: 774–9.


Conclusions on Carbohydrates

The data from Gross and colleagues above certainly point a powerful suspicion on the increased intake of simple sugars as an important contributor to the obesity epidemic.  As we discussed in an earlier chapter, many changes were occurring during this period of time.  As Michael Moss described so eloquently in his book, “Salt Sugar Fat: How the Food Giants Hooked Us,” published in 2013 by Random House, food companies started to add sugar and other sweeteners to their products in order to improve their bliss point, where the food becomes highly desirable.  Also described by Mr. Moss, food companies used the strategy of expanding product lines in order to provide a wide array of super palatable foods that fit every niche and are absolutely irresistible.  Certainly staying away from sugar and other sweeteners such as high fructose corn syrup would decrease the total kcal consumed.

A study investigated which diet was best for losing weight

Let’s discuss a study that tested several important diets.

Michael L. Dansinger, Joi Augustin Gleason, John L. Griffith, Harry P. Selker, Ernst J. Schaefer. Comparison of the Atkins, Ornish, Weight Watchers, and Zone Diets for Weight Loss and Heart Disease Risk Reduction  A Randomized Trial  JAMA, Vol 293, 43-53, January 5, 2005

Here are 3 out of the 4 diets Dansinger and colleagues tested:

Atkins diet – Start with less than 20 g of carbohydrate daily, with a gradual increase towards 50 g daily. (Also called Very Low Carb Diet!)

Zone diet – 40-30-30 balance of percentage calories from carbohydrate, fat, and protein. (Also called the High Protein Diet!)

Dean Ornish diet- Vegetarian diet developed by Dr. Dean Ornish containing 10% of calories from fat. (Also called the Low Fat/High Carb (Complex) Diet!)

Study Design.  The study was a 1-year randomized trial of the dietary components of the Atkins, Zone, and Ornish diets. Participants (160 individuals, about 50:50 men:women) were enrolled in the study conducted in Boston, MA. Each group contained about 40 individuals. Enrollees were adults of any age who were overweight or obese with a body mass index between 27 and 42. Each participant had to have at least 1 metabolic cardiac risk factor in order to provide motivation.

The participants were taught the diets through 1 hour meetings on 4 occasions during the first 2 months of the study. A dietitian and physician described the diets and gave general advice on how to adhere to each diet. Written materials and an official diet cookbook were given to each participant.  During the course of the study, food intake was monitored using 3-day food records at baseline, 1, 2, 6, and 12 months.

Results of the Study

After a year in the study, the mean weight loss was similar across all the diets. At 1 year, weight loss averaged about 2-3 Kg per person, or only a mean weight loss of about 2-3%. Also, the 1 year discontinuation rates were: Atkins, 48% stopped; Ornish, 50% stopped; and Zone diet, 35% stopped. So the Atkins and Ornish diets appeared harder to stay on, and more people adhered to the Zone high protein diet.  The above weight loss figures were means for the groups.  However, individuals did have successes.  Three individuals on the Ornish diet and 1 person on the Zone diet lost more than 20 Kg of body weight, whereas no one on the Atkin’s diet lost this much weight after one year in the study.

Conclusions from the study by Dansinger and colleagues (JAMA. 2005; 293:43-53):

“Our findings challenge the concept that 1 type of diet is best for everybody and that alternative diets can be disregarded.”

“…our findings do not support the notion that very low carbohydrate diets are better than standard diets, despite recent evidence to the contrary.”

“…poor sustainability and adherence rates resulted in modest weight loss and cardiac risk factor reductions for each diet group…”


Unless one adheres to a diet, the diet will not succeed, no matter which diet it is.

Therefore, one must conclude that rather than following a prescribed diet, one might be more successful following a healthy lifestyle! This was the exact conclusion that Ancel Keys came to and what he and his wife, Margaret, wrote about in their book, “How to eat well and stay well the Mediterranean way,” published by Doubleday in 1975.


Earlier in Chapter 12 I discussed the systematic analysis of 232 studies with almost 1 million children performed by Tremblay and colleagues. The authors stated,

“Qualitative analysis of all studies revealed a dose-response relation between increased sedentary behaviour and unfavourable health outcomes. Watching TV for more than 2 hours per day was associated with unfavourable body composition, decreased fitness, lowered scores for self-esteem and pro-social behaviour and decreased academic achievement.”

The authors also indicated that the above negative changes could be reversed if children watched less than 2 hours of television per day.

Mark S Tremblay, Allana G LeBlanc, Michelle E Kho, Travis J Saunders, Richard Larouche, Rachel C Colley, Gary Goldfield and Sarah Connor Gorber. Systematic review of sedentary behaviour and health indicators in school-aged children and youth.

Online open access:   http://www.ijbnpa.org/content/8/1/98

I repeat the above observations because it is interesting that the two-hour time point seems to be an important time mark for causing physiological changes in children. But what is just as interesting is that the two to 2.5 hour time point appears to be important in causing physiological changes in adults, too.

In my nutrition and health class, students always ask about the role of structured exercise (done in a gym or at home on a treadmill, etc.) in treating obesity. I let them figure it out for themselves. I give them an assignment where they calculate their daily energy expenditure and I have them list their favorite activities/exercise and list the kilocalories (kcal) expended per hour during each activity. Then I have the students list their favorite snacks with the kcal each one has. The reaction to this assignment has been consistent every year for the past ten years: “I can’t believe how long I need to exercise to burn off the kcal in my favorite snack!” It is just too easy in today’s environment to eat excess kcal! The take home message from this assignment is that structured exercise is not a way to treat or prevent obesity, unless you have enormous amounts of time to spend in the gym (say 3-4 hours per day). I haven’t met anybody with that kind of time yet!

What I teach in my class is that structured exercise is important and necessary for the following reasons:

1) keep coronary artery smooth muscle cells healthy so that they can dilate when your heart is called upon to pump extra blood;

2) keep ligaments and connective tissue strong and flexible so that you do not have injuries;

3) put stress on your bones to keep them dense and strong, and

4) keep skeletal muscles from dissolving away with age.

But exercise is very important in helping us maintain a healthy body weight. Dr. James A. Levine of the Mayo Clinic has spent a good part of his career researching and promoting the role of Non-Exercise Activity Thermogenesis (NEAT) in influencing a person’s body weight.

Dr. James A. Levine, Mayo Clinic

What is NEAT? NEAT is the energy we expend each day in every day activities such as walking, standing, cleaning the house, taking public transportation to work, walking the dog, standing instead of sitting, taking the stairs, and playing with the kids. Dr. Levine has used state of the art measuring devices in his studies of people’s everyday activities, and he has determined that people who are able to maintain a healthy body weight expend approximately 2.5 hours more NEAT per day than people who have difficultly maintaining their weight.

Dr. Levine has commented, “Thus, the obesity epidemic may reflect the emergence of a chair-enticing environment to which those with an innate tendency to sit, did so, and became obese. To reverse obesity, we need to develop individual strategies to promote standing and ambulating time by 2.5 hours per day and also re-engineer our work, school, and home environments to render active living the option of choice.”

Levine JA, Vander Weg MW, Hill JO, Klesges RC. Non-exercise activity thermogenesis: the crouching tiger hidden dragon of societal weight gain. Arteriosclerosis, Thrombosis and Vascular Biology 2006: 26: 729-736.


Why is NEAT more helpful in maintaining weight than structured exercise? Because we do NEAT more often! This is shown in the following figure.

NEAT example plus swimming

In the figure, several examples of energy expenditure are given for the same sized man. The blue-collar worker expends more energy per day than the worker who sits at a desk all day. Even adding 1 hour of swimming per day to the desk worker’s total energy expenditure does not bring the total kcal expended for the desk worker up to that expended by the blue-collar worker.

Most people who perform structured exercise regularly do so only about 4 hours per week or less. People who perform greater than average NEAT do so every day/7 days a week! On average, a person who expends a large amount of kcal in everyday activities will burn 500 more kcal per day than a person with a similar body type who does little NEAT per day. The reason for our lower levels of NEAT today are due to many reasons- jobs where we sit all day in front of a computer, no need to hand wash the clothes and hang them out to dry, driving to the supermarket instead of walking or having to hitch the horse to the buggy. The reasons are numerous because of all the work saving devices that have been introduced into modern day society. And then there was the introduction into the home of the two major digital systems in the late 1900s: cable TV, large screen televisions, VCRs, and the remote control devices that led to longer hours of inactivity, and easy to use and more powerful desk top computers that also nailed people’s rear ends to chairs.

Dr. James Levine, in a series of brilliant studies, documented the role of NEAT (i.e., the lack of it) in the obesity epidemic in the US. See his articles through the links below!

How do we increase NEAT in our everyday lives?

It’s easy but hard. By this I mean all we have to do is to reverse what we have done to decrease NEAT in the past 45 years. But giving up our digital devices and other work savers requires a conscious decision not to benefit from all of these modern conveniences. Here are some suggestions. The first thing is to throw out the television set. There is nothing that causes you to sit and not move more than watching television. If you do not wish to part with your TV, then an alternate would be to throw out the couch and replace it with a treadmill. However, most people do not use their treadmill no matter what! Another way to increase NEAT is to walk to work and/or use public transportation. This will provide 30 to 90 min per day of exercise depending upon your commute circumstances. If it is impossible to commute from where you live – move! And the act of moving will boost your activity level right there and then! Another way to increase NEAT is to get a job where you need to walk around. Again, you need to be committed in order to get that NEAT! If you do not want to change jobs, consider installing a treadmill desk in your office. In fact, there are directions on how to build your own treadmill desk on the Internet! And you can get exercise in the building process! There are numerous ways to increase NEAT in your life!

What is structured exercise good for? Is it important?

Yes, it is amazingly important because you still need the four health benefits that I wrote about earlier in this chapter. Most important, you need to perform 4 hours of strenuous exercise per week, in addition to the increased NEAT, to keep your heart muscles and coronary artery smooth muscle cells in good shape! Please see a few of the many publications by Dr. James Levine by clicking on the links below:





In the last chapter I discussed how fatty acids (the body’s gasoline) are mobilized from adipose in order to be used for energy by tissues like the heart. But it turns out that fatty acids and other lipid species are used in cells for many other purposes than just energy.

Just like all the different pieces that one finds in a box of Lego® bricks, all the different lipids in the cell can be used in intertwining ways to build any structure needed. One of my favorite lipids is found in the inner membrane of the mitochondrion. This membrane contains a relatively large quantity of an interesting lipid called cardiolipin, which is not enriched in any other membrane. The inner mitochondrial membrane is involved in producing ATP for the cell and it needs to be impermeable to hydrogen ions. Therefore, cardiolipin is what I call the electrical tape of the inner mitochondrial membrane. It is highly stable molecule that deflects both hydrogen ions and electrons well. Of course, biology would develop such a useful building block by utilizing the perfect lipid for this specific function.

If proteins are the houses and factories of the cell, and cholesterol is what makes membranes much stronger, then lipids are the stones that make up the walls and roadways of the cell, like the stones used in the following picture.

Rock Wall and Path 6-2014


A more conventional picture of how lipids form the cell membrane and surround a cell completely is shown in the following figure.

Screen shot 2014-06-03 at 3.52.52 PM

The diversity and utility of lipids

Scientists who study lipidomics, a specific field in lipid metabolism that relates to the vast diversity of lipids in biological systems, have discovered that there are over 10,000 distinct lipid species within a cell. But it is quite possible that there are many more lipid species than this. The fact that there are so many different lipids in cells leads to the basic concept that the more types of lipids that are present in the diet the better, because the lipids in our food, especially a large cornucopia of fatty acids, can be used in many different ways.

Therefore, in addition to providing energy, a wide variety of lipids are used for Structure and Communication.

The Backdrop

Omega 3 and Omega 6 Fatty Acids, Structural Components of the Brain, Role in Brain Development

There are a wide variety of lipids that probably contributed to human development. Valuable information about who we are today, and what kind of diet may be most suited for optimal health and maintenance of body weight, can be obtained from studies of the development of early humans.

Research performed in the last 10-15 years has documented that all humans living today are descendants from a small group of humans who lived and developed in Africa.   This particular group of modern humans possibly lived on the coast of southern Africa 190,000 to 100,000 years ago.

In an article in Scientific American, Curtis Marean, a professor at the School of Human Evolution and Social Change at Arizona State University, addressed the observation that modern humans display very low genetic diversity compared to other species, a fact that suggests that there was a population “crash in early H. sapiens.”   In 1991 Dr. Marean began to investigate caves that may have supported early H. sapiens during a long glacial period that lasted until about 120,000 years ago.

Curtis Marean, “When the Sea Saved Humanity,” Scientific American, August 2010, pages 53 – 61

Scientific Am Cover

Dr. Marean discovered an interesting cave, called PP13B, near Mossel Bay, South Africa. He found evidence that this cave was used by Homo sapiens from between 164,000 and 35,000 years ago. While other small groups of Homo sapiens may have died out in other parts of Africa due to the cold and adverse conditions brought about by the return of cold weather and glaciers between 195,000 and 123,000 years ago, this group of humans obviously survived. One advantage this group of humans had was that they had quick access to rich seafood because the cave looked out over the ocean. Also, they lived close to a diverse population of plants, including those that contain tubers, bulbs and corms with rich stores of carbohydrates. In the sediments of the cave, Dr. Marean discovered a diverse group of shells from shellfish harvested from the ocean. He also discovered a multitude of stone tools.

Cave in South Africa 6-2014

Dr. Marean has proposed that the genetic, fossil and archaeological data indicate that this cave, and other caves near by, may have been the site where modern humans survived the return of the glaciers and developed before leaving Africa around 50,000 years ago. Also, because these humans consumed seafood as a major source of high quality protein, they also consumed omega 3 fatty acids that are present in seafood. Over this entire period of time, it is quite possible that the brains of these early humans were developing and becoming more capable of advanced thought.

The development of the human brain in a geographical location that provided a source of rich high quality protein and omega 3 fatty acids may explain the fatty acid composition of our brains today.

The following table displays the fatty acid composition of human newborn adipose tissue and compares it to the fatty acid composition of human newborn brain. The differences in fatty acid content are startling!

The human brain has greatly increased concentrations of arachidonic (omega 6) and docosahexaenoic (omega 3) acids compared to adipose and other tissues such as liver and muscle. These are fatty acids that are highly unsaturated (contain multiple double bonds each). Obviously, as the brain is greatly enriched in these fatty acids over adipose tissue, there must be an important reason for this enrichment, and there also must be a mechanism that directs the enrichment of these fatty acids in brain.

Table adipose vs brain

Because to the best of our knowledge, omega 3 fatty acids were high in the diet when the human brain was developing and improving, there is a major hypothesis that a sufficient content of omega 3 fatty acids is required in our diet today in order to have the optimal mixture of fatty acids for brain development.

Benefits due to consumption of adequate amounts of omega 3 fatty acids

We can only speculate right now that because our brains have a very high content of arachidonic and docosahexaenoic acids, that these fatty acids play a special function in the brain. But if there was evidence that a deficiency of these fatty acids causes some kind of detrimental situation, and that increased consumption causes a positive effect, then this would strengthen arguments indicating that these fatty acids play an important role in brain. And in fact, there are now very strong epidemiological data that PUFA, especially those that are found in fish oils, are highly beneficial to human health in several important ways.

Omega 3 Fatty Acids and Depression

The health benefits of omega 3 fatty acids has been the subject of hundreds of articles in the scientific literature.   One interesting area studied is the effects of omega 3 intake on depression in different populations based upon easy access to fresh seafood. Studies have suggested that the consumption of fish on a regular basis is protective against depression.

A meta-analysis of 47 clinical research trials testing the efficacy of treating patients with various brain related disorders with different omega 3 fatty acid administration protocols was published in 2014. In the studies that specifically tested omega 3 fatty acids on clinically defined depression (11 studies), and in less rigorously defined depression (8 studies), a significant improvement in symptoms was noted in patients who consumed additional EPA compared to patients who received the placebo or DHA alone. This meta-analysis was more positive than the previous meta-analysis that was published. The authors stated that their study took advantage of several very recently conducted clinical trials that increased the total number of patients enrolled in the overall analysis.

The observation that treatment with EPA was effective whereas DHA was not effective is difficult to understand at this time as the biochemistry indicates that DHA is present in the brain at much higher concentrations than EPA. The authors of this meta-analysis suggested that it may be the anti-inflammatory properties of EPA that are protective, and not the role of omega 3 fatty acids as structural molecules in neurons. Also, the time of life when increased omega 3 fatty acid intake is required by humans may also be an important factor. DHA is known to be especially important for brain development during gestation and during the first several years of life.

Grosso G, Pajak A, Marventano S, Castellano S, Galvano F, Bucolo C, Drago F, Caraci F.  Role of omega-3 Fatty acids in the treatment of depressive disorders: a comprehensive meta-analysis of randomized clinical trials. PLoS One. 2014 May 7;9(5):e96905.


Summary: Omega 3 Fatty Acids and Depression

We are getting to the point where the data on the positive contributions of omega 3 fatty acid consumption to overall health is fairly convincing. There are areas where omega 3s are not as helpful as originally proposed, but certainly the studies that show improvement in depression show there are other areas where omega 3 fatty acids are required for specific physiological functions. With the availability of pharmacological omega 3 fatty acid products, we will soon have more information on the efficacy of omega 3 fatty acids.

Not All is Rosy Concerning Omega 3s. No Effects of Omega 3 Supplements on CHD

Whereas increased omega 3 intake was shown to be beneficial in depression, positive effects of omega 3s have not been observed with coronary heart disease (CHD). The most recent meta-analysis study showed that neither omega 3 intake, nor supplementation with omega 3 fatty acids, provided protection against CHD. In the same meta-analysis study, intake of saturated fat and monounsaturated fat were also not associated with CHD. This study suggests that there are other factors in the diet, beside fat content, that are responsible for the protection afforded against CHD by certain diets including the Mediterranean Diet.

The results indicating that fats did not influence the rates and outcomes of CHD at first are surprising, but we have to remember that most, if not all, of these epidemiological studies were performed after very, very high intakes of fat, such as those that occurred in Finland, had already come down!

ChowdhuryR, Warnakula S, Kunutsor S, Crowe F, Ward HA, Johnson L, Franco OH, Butterworth AS, Forouhi NG, Thompson SG, Khaw KT, Mozaffarian D, Danesh J, Di Angelantonio E. Association of dietary, circulating, and supplement fatty acids with coronary risk: a systematic review and meta-analysis. Ann Intern Med. 2014 Mar 18;160(6):398-406. doi: 10.7326/M13-1788.



Fatty Acids and Cell to Cell Communication – The Endocannabinoids

The endocannabinoids are lipid molecules that are used in the body to send signals from one cell to another.   In the brain, endocannabinoids usually transmit a chemical signal from one post-synaptic neuron to a near by pre-synaptic neuron.   Endocannabinoids are a family of molecules that are derivatives of fatty acids. The major endocannabinoids, N-arachidonoyl ethanolamine (anandamide) and 2-arachidonoyl glycerol (2-AG) have the polyunsaturated fatty acid, arachidonic acid, as a central part of their structures.

The story how the endocannabinoids were discovered is mind blowing.

Marijuana is one of the names given to the Cannabis sativa plant, which has been used for its mind altering properties. The physicochemical properties of marijuana include euphoria, heightened sensory perception, and increased appetite. The active ingredient in marijuana is tetrahydrocannabinol or THC. The many effects caused by marijuana and, THC, caused scientists to ask how it worked on so many systems. Biochemical studies found a membrane receptor (called CB1) on the surface of cells in the brain that THC tightly bound to after marijuana use. The scientists asked the question, if THC, an external substance, enters the brain and binds to CB1 receptors, which then causes many of its physicochemical effects, are there naturally occurring, endogenous compounds that normally bind to the CB1 receptor?

After about 20 years of looking for a needle in a haystack, scientists reported that they discovered the endogenous compounds that bind to the CB1 receptor, and they called these compounds, endocannabinoids. The following figure shows the structure of tetrahydrocannabinol (THC) and the structure of the endocannabinoid, N-arachidonoyl ethanolamine (anandamide).

THC Endocannabinoids Figure

The Brain reward system first occurs in the Arcuate nucleus, where signals (especially those related to food) from different areas of the body are received (See following Figure). Then signals are sent from the Arcuate nucleus to the Nucleus accumbens, where positive neurotransmitters like dopamine are secreted. Soon afterwards, other signals may be sent to the prefrontal cortex, where conscious actions are initiated (for example- go get another slice of pizza).

Originally (in early evolution) the brain reward system was used to give pleasurable feedback for when something nutritious was being eaten or when something good happened in everyday activities. Later on in evolution, this system was co-opted and is now involved in addictions and other negative activities.

Brain Reward Center NEJM 2008

How Lipids Signal From One Cell To Another Cell

The following Figure shows how endocannabinoid molecules, which are lipids, are transferred from one cell membrane to another cell membrane in order to continue a signal down a nerve tract. Anandamide or 2-AG are synthesized using arachidonic acid molecules that are part of the phospholipids that make up the cell membrane of neurons. When the endocannabinoids are released from the post-synaptic neuron into the space between the two neurons, they bind to the endocannabinoid receptors that are on the pre-synaptic neuron. Next, the receptors initiate signals within the cytoplasm and the pre-synaptic neuron continues moving the signal down the nerve.

Endocannabinoid Signaling at Membrane

So What Fats Should Americans Eat?

The answer to this question will be found in the chapter where the Mediterranean diet is discussed. A recent study has been published that has shown that the Mediterranean diet can be protective against CHD. Of course, Ancel Keys discovered this in the “Seven Countries” study, and wrote about it. Ancel Keys and his biochemist wife, Margaret, wrote the cook book, “Eat Well and Stay Well the Mediterranean Way,” which was published in 1975. Later, Dr. Keys and his wife moved to southern Italy and practiced the Mediterranean diet up close and personnel. In several articles written after his retirement to Italy, Dr. Keys provided insights into the Mediterranean diet and how it was changing as European countries were recovering their wealth in the period after World War II. But this part of the story will be presented in a later chapter.




« Newer Posts - Older Posts »