Omega-3 Fish Oils: The Greatest Nutritional Health Discovery Since Vitamins:

An Interview with Professor Jørn Dyerberg, M.D. By Richard A. Passwater, Ph.D.

http://www.drpasswater.com/nutrition_library/dyerberg.html
© 2010 Whole Foods Magazine and Richard A. Passwater, Ph.D.

Part One; The Discovery

Reduce your chance of dying a sudden death by 45% (1, 2)! Reduce your risk of dying from sudden cardiac death by 90% (3). Reduce your chance of developing Alzheimer’s disease by 45–50% (4). Stay younger longer (5, 6)! Reduce the inflammation and pain of rheumatoid arthritis and the pain of osteoarthritis arthritis and other inflammatory diseases (7, 8). The litany of health benefits from omega-3’s goes on, but hopefully, these are enough to get your attention so that you will read on about this miraculous dietary supplement. We will discuss the details of these studies in a later installment of this series.

Recently, a low level of long-chain omega-3 fatty acids had been purposed as a risk factor for heart disease. The new risk factor is based on measuring the fatty acids in red blood cells, and is expressed as a percentage of EPA + DHA of total fatty acids. An omega-3 index of >8% is associated with 90% less risk for sudden cardiac death, as compared to an omega-3 index of <4%.

Admittedly, to some, omega-3s are starting to sound a bit old. What could be new about them? Plenty! And, of course, since everyone knows about them now, it’s hard to envision that it took a small handful of brilliant and dedicated scientists to discover their importance to human health.

Modern mankind is deficient in the omega-3 fatty acid nutrients. In recent years, the biologically functional omega-3 fatty acids in fish oil, eicosapentaenoic acid (EPA) and docosahexaenoic acid ( DHA), have been the second-most important dietary supplement, ranking just behind general purpose multis (multivitamins and minerals). Now, it seems that in a couple of market segments, fish oil supplements have become the leading supplement.

The Nielsen Company, a market research firm, reports that sales of omega-3 products showed a 42% growth in 2009 (9). ConsumerLab.com reported in February that fish oil/omega-3 supplements were used by 74% of respondents of their survey (up from 71.6% in 2008), followed in popularity by multivitamins, which were used by 72% (down from 73.8% in the prior year) (10).

The popularity of fish oils is largely due to their health benefits and convenience of supplemental form. Fish are important in the diet, but difficult to include often enough for maximum benefit. Also, the purity of refined fish oils allows more of the important omega-3s to be consumed without the burden of the impurities of whole fish, which include mercury and PCBs.

Nearly everyone in the civilized world knows of at least some of the health benefits of these marine lipids. EPA and DHA are primarily found in cold-water fish, but it seems that few people, aside from scientists, know of the primary discoverer of these health benefits, Jørn Dyerberg, M.D. The story has been more than 40 years in the making and he had to go to nearly the end of the earth to uncover it. His complete research is well-deserving of a Nobel Prize.

Several billions of people live and have lived on this planet and yet relatively few have ventured deep into the Arctic Circle. Nor have they made a major health study that betters the health of millions of people. Dr. Dyerberg has done both.

Dr. Dyerberg, professor and Dr. Med.Sc., has made several discoveries that elucidate many of the health benefits of omega-3 fish oils. Dr. Dyerberg made five scientific expeditions to Northwest Greenland examining the association between fish oil intake and coronary heart diseases in Eskimos. Dr. Dyerberg, who is Danish, hypothesized that the rarity of coronary heart disease among the Inuit population could be due to the omega-3 fatty acids in their diet consisting largely of seal and cold-water oily fish. Together with his fellow researchers, he went on to elucidate the unique physiological effects of these fatty acids. His research opened new fields leading to thousands of health studies by many. His own research encompasses more than 350 scientific publications primarily concerning blood lipids, atherosclerosis, the blood coagulation system, omega-3 polyunsaturated fatty acids, trans-fatty acids and pro­staglandins.

In 2007, Dr. Dyerberg was honored by the American Heart Association in “Recognition of Outstanding Scientific Contribution for the Advancement of Heart Health Worldwide.” In 2008, he received the American Dietetic Association Foundation’s Edna and Robert Langholtz International Nutrition Award. Hopefully, the Nobel Prize committees are studying his research.

Dr. Dyerberg has served as chief physician and head at the Aalborg hospital. He has been a professor in Copenhagen since 2001 and is currently a medical and scientific advisor to Napro-Pharma Ltd. (Norway) and Unilabs Ltd. (Denmark).

Passwater: Dr. Dyerberg, I first learned of your research in 1981 thanks to a visit to my laboratory by Dr. Tom Sanders of Queen Elizabeth College in London. He was aware of my writings questioning the prevalent thinking that heart disease was simply a matter of eating too much cholesterol and he thought that I would be interested in your seminal findings. He told me about your forays to Greenland and showed me your 1971 to 1981 publications. This meeting led to my writing of the first book on fish oils in 1982, called EPA—Marine Lipids (11).

 The first thought that went through my mind was, “What in the world were you doing in the cold, cold Arctic when you could be working in a nice warm clinic or laboratory.” I could envision you and your colleagues riding dog sleds and trying to convince the Inuits to give you blood samples.

So, let’s start at the beginning. Dr. Dyerberg, why did you want to become a physician in the first place?

Dyerberg: I have never had any other idea for my professional life than to be a doctor. During my studies and the first two to three years after, I aimed at becoming a specialist in medicine (internist). In the course of that, I was appointed to Dr. H.O. Bang’s laboratory in Aalborg Denmark, where I was fascinated by the research possibilities that position offered. After a period at the pediatric and neurological departments, I returned to the clinical-chemical specialty with Dr. Bang, a decision I have never regretted, and I have spent the whole of my professional career in that specialty.

Passwater: Okay, then why did you travel to the end of the earth to study the health of the Greenland Inuits?

Dyerberg: It started in 1968 when an editorial appeared in the Danish Medical Society’s weekly journal, pointing at the unusual pattern of diseases among our Danish co-citizens in Greenland, the Eskimos or Inuits as they are called today. The anonymous author stated that it was an obligation for Danish researchers to study this issue “before it was too late,” meaning before westernization of the Inuit society took over.

Passwater: Even though Greenland is some distance from Denmark—actually being in North America while Denmark is in Europe—Greenland had been an “autonomous country” within the Kingdom of Denmark and thus many Danes had settled there.

Dyerberg: Yes. Among the many differences between the Greenland Eskimos’ disease pattern and the Danes’ disease pattern (including Eskimos who moved to Denmark) were that the Greenland Eskimos had a surprisingly low death rate from heart diseases, in spite of the fact that their traditional diet was based on seal and fish and consequently rather high in animal fat. Animal fat is considered by many to be a risk factor for coronary heart disease due to the increase in blood cholesterol. The Eskimo findings appeared to be paradoxical.

Passwater: You say surprisingly low. Wasn’t it only about a tenth—just 10%—of the U.S. rate of heart disease?

Dyerberg: Yes, we computed the death rates from coronary heart disease and found that the age standardized death rate for males aged 45–65 years in Greenland at that time was 5.3% compared to 40.4% in the United States. At that time, I was a resident physician in Dr. Bang’s laboratory. Dr. Bang had visited Greenland in the 1950s during a measles epidemic, and suggested that we should go to Greenland to examine the Eskimo’s blood lipids using an analytical method I had developed for my Ph.D. thesis for measuring lipoproteins in blood, a method that could be performed under field conditions (12). We managed to collect a modest sum of money to finance the trip, and together with a laboratory technician, we made our first Greenland expedition in 1970.

Passwater: A strong analytical background is important to scientific discovery. I have had the opportunity as a director of an analytical research laboratory to help many scientists, even Nobel Prize winners, use advanced analytical tools to help elucidate their discoveries.

You used the word, “expedition.” I doubt that in 1970 you could just go out with a load of scientific equipment and catch a plane to a remote Eskimo village. In 1981, when I first read your research papers, I envisioned you traveling by dogsled. Am I right?

Dyerberg: Yes, as you can see by these photos from our later expedition in 1976. The first (see Figure 1) shows a view from the sled as we were sledding 100 miles on the sea ice to Igdlorssuit. The name of the village translates to “The Big Houses.” Perhaps you recognize the word “igloo” in it. Igdlorssuit was a settlement with 100 inhabitants and approximately 800 dogs.

Passwater: It seems that everyone needs eight huskies to power their sled. The photo makes me feel cold just looking at it. It also reminds me of the old motivational expression that “the view changes only for the lead dog.”

I would guess that the only “experience” most of our North American readers have with dog sledding is from seeing TV news reports of the Great Iditarod Sled Race. We may have some readers in the northern states and Canada who have actually taken joyrides on dogsleds for short distances for recreation near where they live. However, very few of our readers have taken a real dogsled expedition across the frozen tundra and frozen sea. What most of our readers they normally see on the news is a bunch of excited dogs barking happily at the start of the race.

Dyerberg: The experience of dog sledding all depends on the weather! We were happy to do the two long tours on sea ice from the main city Uummannaq to the settlement Igdlorssuit (now called Illorsuit) about 100 kilometers to the north. Uummannaq is a town of 1,500 people today and is the northernmost ferry point. Igdlorssuit is directly north over the sea ice of the Uummannaq Fjord. We had blue skies during the days of the midnight sun during our travel. The temperature ranged from about –10 to –20 degrees Celsius (minus four to plus 14 degrees Fahrenheit) and low wind. That makes such the experience perfect. In harsh weather, it can be quite the opposite. At that time, dog sledding was the only transportation available in winter time. Now, I believe they have snow scooters.

Passwater: Wise planning! The only time I was above the Arctic Circle was in North Finland in October 1993 and I was not so fortunate. I was there during the period when it was mostly dark and very much colder than I like. My hosts from the University of Jyvaeskylae took us north on a side-trip and we had a long and happy celebration to help us deal with the darkness and weather.

How about the dogs?

Dyerberg: When you start out the dogs are eager and barking, but they quiet down as they have to do hard work for a long time—the tour took 10–12 hours, with two to three stops for making tea and feeding the dogs. The behavior of the dogs depends solely on the driver. We had experienced Eskimos as drivers, but of course we also tried to run the pack, but in vain. You have to know the commands and to use the whip to direct the dogs, and both are plain impossible. It is rather slow driving, the dogs cannot run fast with a heavy sled (we brought a lot of gear) and you are asked to run along with the sled now and then to ease the dogs’ burden. This is not easy as we were in a dress that does not invite running, as you can see from my photos. You do not stop for fishing; the sea ice was 1.5 meters when we sledded the approximately 100 km each way on it. There are some unpleasant issues as well, but there was no other way of getting the research done.

One of the dogs in each pack is the boss, which he rather often has to state, so both while sledding and resting there are often fights, which often leaves the lines entangled and “soiled.” It can be quite a job for the driver to disentangle them with his bare hands and often with the help of his teeth!

We were hungry when we reached our destination and glad to enjoy some Eskimo food.

Passwater: Well, maybe it wasn’t as “glamorous” as I envisioned. This second photo (Figure 2) shows that at least you could stop to rest occasionally. That must be you on the right.

Figure 2: Melting snow to make tea while the dogs rest. Dr. Jørn Dyerberg is on the right. Reprinted with the permission of copyright owner, Dr. Jørn Dyerberg.

Dyerberg: Yes, here we are taking a rest for both the dogs and the people. Yes, I am on the right on the sled having a cup of warm tea sitting next to our technician. That is a primus stove at our feet for melting snow and boiling water for our tea.

Passwater: I guess it is either water or tea made from melting the snow. Any other drinks would be too heavy and bulky to carry by dogsled.

Dyerberg: Right. In this April 1976 expedition, we were collecting food items in winter time from the Eskimos. There were eight of us on eight dogsleds. There were Dr. Bang, myself, two technicians for preparing the samples, a practical guy, a dietician for doing food interviews, Dr. Hugh Sinclair from England and an expedition leader Ivars Silis—a later well-known arctic photographer—and 88 huskies.

We stayed and worked at Igdlorssuit for about four weeks and returned to Uummannaq the same way. From there, we took a boat down to Srd. Stromfiord and flew back to Denmark.

Passwater: At the time, did you sense you were on an adventure or just working?

Dyerberg: We knew that we had data that had never been collected before, but we had at that time no idea of the magnitude of our findings. The omega-3 concept was still some years ahead of us.

Passwater: Studying a people’s diet is one thing, but you started with blood samples. What were you looking for?

Dyerberg: We collected blood from 130 Eskimos in a fasting state, returned to Denmark, analyzed their blood lipids and lipoproteins and published the results in The Lancet in April 1971 (13).

Passwater: Even though the word “omega-3” was not mentioned in that seminal paper, it was the birth of the omega-3 story, and the study has since been classified as a “Nutrition Classic.”

Dyerberg: We found, in spite of their high-fat diet, that the Eskimos had favorable blood lipid levels. Yes, their cholesterol levels were lower than what we found in Danes, however their blood cholesterol levels were not low enough to explain the marked difference in heart attacks compared with Danes and Americans, thus we had to look for further explanations.

Since we realized that it was unlikely anyone would ever be able to reach these people again before their diet and lifestyle were altered due to the changes being brought about by modern travel and accessibility improvements, we felt it was our duty to analyzes and publish as much as we could before it was too late. We used everything at our disposal including an old gas chromatograph in our lab. At least in the future, others would be able to know as much about 1970-era Eskimo blood lipid profiles as we could determine with our 130 blood samples.

Passwater: If it was already an old chromatograph in the early 1970s, it must have been a single-column instrument without temperature programming and without capillary columns. That would have really been a difficult analysis. So, you expanded beyond gel electrophoresis and your procedure for lipoproteins. In the 1970s, gas chromatographs and other analytical instruments were not as sophisticated or as fast as they are today. What could you hope to find other than the most basic blood evaluations?

Dyerberg: We were just testing for everything we knew about, but we did notice a couple of extra peaks in the fatty acid analysis of the blood samples—peaks that we had never seen before.

Passwater: Aha! Mystery compounds X and Y. Very interesting. If you didn’t happen to have the proper separation column and instrument settings, you may never have detected those extra peaks.

For our readers not familiar with gas chromatography, the different peaks represent the presence of different compounds as they elute from the separation column over time. So, here you were finding an indication of compounds never seen in human blood samples before. They were in the blood of Eskimos currently living in Greenland, but not in Eskimos who had moved to Denmark.

Dyerberg: Yes, we didn’t know what compounds they indicated, but it was reasonable to believe that they were fatty acids.

Passwater: But, you had to know just what these mystery compounds were for sure. Where did they come from? Could they be related to heart disease? If so, how?

Let’s take a pause and resume our chat next month. Stay tuned, readers, to learn how Dr. Dyerberg solved these riddles. WF

References

1. Dietary Supplementation With N-3 Polyunsaturated Fatty Acids And Vitamin E After Myocardial Infarction: Results Of The GISSI-Prevenzione Trial. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico.
2. C.M.Albert,et al., “Blood Levels of Long-Chain N-3 Fatty Acids and the Risk of Sudden Death,” N. Engl. J. Med. 346 (15), 1113–1118 (2002).
3. H.Leon,et al., “Effect of Fish Oil on Arrhythmias and Mortality: Systematic Review,” BMJ 337, a2931 (2008).
4. E.J.Schaefer,et al., “Plasma Phosphatidylcholine Docosahexaenoic Acid Content and Risk of Dementia and Alzheimer Disease: The Framingham Heart Study,” Arch. Neurol. 63 (11), 1545-1550 (2006).
5. R. Farzaneh-Far,et al., “Association of Marine Omega-3 Fatty Acid Levels with Telomeric Aging in Patients with Coronary Heart Disease,” JAMA 303 (3), 250–257.
6. R. Farzaneh-Far,et al.,“Telomere Length Trajectory and its Determinants in Persons with Coronary Artery Disease: Longitudinal Findings from the Heart and Soul Study,” PLoS One 5 (1), e8612.
7. B.Galarraga, et al., “Cod Liver Oil (N-3 Fatty Acids) as a Non-Steroidal Anti-Inflammatory Drug Sparing Agent in Rheumatoid Arthritis,” Rheumatol (Oxford) 47, 665–669 (2008).
8. D.Fritsch, et al., “A Multicenter Study of the Effect of Dietary Supplementation with Fish Oil Omega-3 Fatty Acids on Carprofen Dosage in Dogs with Osteoarthritis,”J. Amer. Veterinary Medical Assoc. 236 (5), 535–539 (2010).
9. S. Starling, “Nielsen: Omega-3 Sales Grow 42 Percent,”www.nutraingredients-usa.com/content/view/print/275814,accessed Feb. 1, 2010.
10. ConsumerLab.com Newsletter Feb. 1, 2010,http://view.email.consumerlab.com/?j=fe54177877610d757611&m=fef61d78716705&ls=fde910737d6103747010717d&l=fe651670746d067f7613&s=fe2e107576600d7f711670&jb=ffcf14&ju=fe2c1670766601787c1d70&r=0
11. R.A.Passwater, EPA—Marine Lipids (New Canaan, CT, Keats Publishing, 1982).
12. J.Dyerberg and N. Hjorne, “Quantitation of the Lipoprotein Complex by Agarose Gel Electrophoresis,”Clin Chim Acta 33 (2), 458–461 (1971).
13. H.O.Bang,et al., “Plasma Lipid and Lipoprotein Pattern in Greenlandic West-Coast Eskimos,” Lancet 1 (7710), 1143–1145 (1971).

Part Two: Solving the Riddle

Last month, we chatted with Dr. Jørn Dyerberg about his major health discovery of omega-3 fatty acids in human health. While that part of the interview with Dr. Dyerberg was in press, another major confirming study was published that should be noted. In a large multi-year study, Dutch researchers reported a 62% lower risk of fatal heart attack in people consuming a modest amount of EPA and DHA (approximately 230 mg/day) from fish as compared with those consuming small amounts (approximately 40 mg/day of EPA and DHA) (1).

Getting back to our main story, last month Dr. Dyerberg recounted his expedition into Greenland to discover why these remote-living Eskimos had about only one-tenth the heart disease incidence of many western countries including the United States and Denmark. The sojourns were hard physical work, and now comes the difficult detective work of solving this scientific riddle.

Jørn Dyerberg, M.D., professor and Dr. Med. Sc., has made several discoveries that elucidate many of the health benefits of omega-3 fish oils. He made five scientific expeditions to northwest Greenland examining the association between fish oil intake and coronary heart diseases in Eskimos. Dr. Dyerberg, who is Danish, hypothesized that the rarity of coronary heart disease among the Inuit could be due to the omega-3 fatty acids in their diet consisting largely of seal and cold-water oily fish.

Together with his fellow researchers, he went on to elucidate the unique physiological effects of these fatty acids. His research opened new fields leading to thousands of health studies by many. His own research encompasses more than 350 scientific publications primarily concerning blood lipids, atherosclerosis, the blood coagulation system, omega-3 polyunsaturated fatty acids, trans-fatty acids and prostaglandins.

In 2007, Dr. Dyerberg was honored by American Heart Association in “Recognition of Outstanding Scientific Contribution for the Advancement of Heart Health Worldwide.” In 2008, he received the American Dietetic Association Foundation’s Edna and Robert Langholtz International Nutrition Award.

Passwater: Dr. Dyerberg, when we left off, you were telling us about how you had discovered two before-unknown peaks in your gas chromatographic analysis of the blood samples from the Greenland Eskimos. You had reason to believe that these peaks were due to unknown fatty acid compounds in the blood.

Dyerberg: Yes, and if they were fatty acids, I would have to learn more about determining which ones they might be. So, I sought help in the interpretation of our results from Dr. Ralph Holman at the Hormel Institute at the University of Minnesota, who was the leading fatty acid analyst of the time.

Judging by the position of the peaks, Dr. Holman postulated that we had found omega-3 fatty acids in blood, quite possibly EPA and DHA.

Figure 1: Chromatogram shows two previously unexplained peaks. A chromatogram produced by a gas chromatograph plots the concentration of the components in a sample against time. Larger compounds in terms of molecular weight take longer to elute from the separation column. Dr. Jørn Dyerberg’s analysis of blood lipids from the Eskimos showed two later eluding peaks than observed before. Since the two peaks eluted later, this indicated that they were larger molecular weight compounds than the fatty acids normally observed previously.

Passwater: As I see the omega-3 story, you are the defining scientist, and your detection of these two unknown compounds in the blood of the Eskimos was the defining event that has led to an advance in nutrition that can favorably impact everyone’s health. These early chromatograms should be in a scientific museum such as the Smithsonian.

EPA and DHA hitherto were neither recognized as essential nutrients nor reported as constituents of human blood or tissue, and their function was completely unknown. Well, trying to find the answer to your question of why the Inuits had dramatically less heart disease has taken you to the end of the earth and now back to the United States where you had studied earlier.

Now that we are speaking about identifying the presence of omega-3 fatty acids, let’s just take a moment and review some basic biochemistry terminology for our readers. The omega-3 family of fatty acids is defined as fatty acids that have their first “unsaturated” carbon as the third carbon from the “omega” end of the molecule. Fatty acids are components of fats similar to how amino acids are building blocks of proteins. A fatty acid has several carbon atoms strung together like a chain with an “acid” functional group [COOH] at its beginning carbon atom. The “acid” group is easily identified because it is the only group in fatty acids that contains oxygen atoms. Not surprisingly, this first carbon atom in the fatty acid “backbone” or “chain” is designated as the “alpha” carbon.

The end of the fatty acid farthest from the acid group is called the “omega” end, which is sometimes called the “methyl end.” This carbon atom is said to contain the terminal methyl group (CH₃) (see Figure 2). If a carbon atom is not fully saturated with hydrogen, it is said to be “unsaturated” and is linked to a neighboring carbon atom, which is also unsaturated by a double bond. The location of the first double bond counted from the omega end denotes whether a fatty acid belongs to the omega-6, omega-3 or other omega family. Humans cannot interconvert omega-3 and omega-6 fatty acids to each other, nor can they make either of these fatty acids from scratch. Additionally, as we will discuss in the next installment, all omega-3s do not function in the same way, and importantly, not all omega-3 fatty acids are biologically equal. Humans cannot readily convert significant amounts of shorter omega-3 members to EPA and DHA.

Dr. Dyerberg, in your analysis, you found compounds that were very long-chain fatty acids (based on the time it took for them to elute from the separation column of the gas chromatograph) and omega-3 or whatever, this was new information.

Figure 2: The two ends of a fatty acid are usually designated “alpha” and “omega.” Here, this “stick and ball” Kekulé system molecular model is of butyric acid. The “balls” represent atoms and the “sticks” linking the atoms represent the “bonds” which are a sharing of electron paths that act as a force to hold the atoms together. Butyric acid—a simple saturated (only single bonds) fatty acid having a chain length of four carbon atoms (carbon atoms shown in red, hydrogen atoms are shown in grey)—is shown. The alpha end is the end having the acid group, which has two oxygen atoms (shown in blue). The omega end contains the terminal methyl group (CH3) and also is called the “methyl end.”

Dyerberg: Yes, I even had to learn the names of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Dr. Holman knew them from basic fatty acid chemistry outside of the body, but as far as I know, no one had studied them in human blood before or knew that they existed in the body.

Nothing at all was known about the effects of EPA and DHA in human biology at that time! It was known that a deficiency in the omega-3 fatty acid alpha-linolenic acid (ALA), with 18 carbon atoms and three double bonds, caused skin problems in rats, but nothing on the effect of the long-chained omega-3 fatty acids. At that time, polyunsaturated fatty acids meant omega-6 fatty acids from vegetable oils.

Figure 3 shows the chemical structures of these three omega-3 fatty acids.

Figure 3: Here, we switch from the “stick and ball” model of molecular structures to the “shorthand” molecular system to better focus on the differences between the chemical structures of three important omega-3 fatty acids, ALA, EPA and DHA. In these models, the atoms are not represented as balls. Carbon atoms are not labeled and are merely shown as bends in the structure. Hydrogen atoms are not labeled unless they are part of a radical group. Oxygen atoms are labels as “O.”

Passwater: As I mentioned, we will discuss the biochemistry of various omega-3 family members in the next installment of this series. This is important to understand why the biological functions of EPA and DHA are different from ALA and why humans can transform only a very small amount of ALA into EPA and DHA. Therefore, all omega-3s are not of equal importance to our health.

How did you confirm that they were indeed EPA and DHA?

Dyerberg: Dr. Holman gave me some pure EPA and DHA samples. I returned to Denmark and used these pure compounds as standards in the analysis. The chromatographic peaks that we observed were confirmed to be EPA and DHA. The Eskimos indeed had appreciable amounts of EPA and DHA in their blood.

Passwater: Could you tell if the EPA and DHA were present in their blood as free fatty acids or were they present primarily as components of triglycerides? As information for our non-chemist readers, fatty acids normally occur in nature as components of a larger unit commonly called a triglyceride, which is composed of three fatty acids on a glycerol backbone. Biochemists prefer to call triglycerides by the more descriptive name, triacylglycerols (TGA).

Were the fatty acid peaks due their being liberated from triglycerides during the sample preparation for fatty acid analysis by gas chromatography?

Dyerberg: We found EPA and DHA in all plasma lipid classes, free fatty acids, triglycerides, cholesterol esters and phospholipids. In looking for them, we also found them in plasma from Danes, but to a much lesser extent (2).

Passwater: Did you have any idea at this time how EPA and/or DHA could be relevant to heart disease?

Dyerberg: No, but we also noticed that the Eskimos’ blood samples were lower in another fatty acid, called arachidonic acid (AA). At that time, there were new scientific discoveries coming out of Sweden and England showing that blood clotting, among many other things, was regulated by components called prostaglandins.

Passwater: Prostaglandins are now recognized as members of a larger family of oxygenated fatty acids called eicosanoids. In the 1930s, a compound that originated in the prostate that caused a reaction in the uterus was discovered. But, it wasn’t until about 1973 that Hamberg and Samuelson discovered that compounds with similar structures affected platelet aggregation and, in turn, platelet stickiness and blood clotting.

Dyerberg: Yes, prostaglandins were synthesized in the body from AA. AA is an omega-6 polyunsaturated fatty acid found in meat. It has a chain length of 20 carbon atoms, the same number as EPA; but AA has only four double bonds, while EPA has five. The important difference, though, is that EPA has its first double bond in the omega-3 position and AA has its first double bond in the omega-6 position (see Figure 4).

Figure 4: A comparison of the chemical structure of the omega-6 fatty acid, ALA, to that of the omega-3 fatty acid, EPA. The double lines represent double bonds between carbon atoms. Counting from the omega end, the first double bond in arachidonic acid is at the sixth carbon, thus, it is called an omega-6 fatty acid. Omega-6 is sometimes written as Ω-6, n-6 or w-6.

We then hypothesized that the shift in Eskimo blood from AA to EPA and/or its 22 carbon omega-3 cousin, DHA could “tune” their blood clotting into a less active state by changing the prostaglandin formation to components generated from EPA and/or DHA, thereby diminishing the risk for clots in their arteries and consequently their risk of heart attacks.

Passwater: This is where I found your research to be extremely exciting. Up until this point, I found your research very enlightening, but with this information, I found it to be compelling. So, I set about writing the first book on omega-3s nearly 30 years ago in 1981 based on your research. The book became one of the first of the Good Health series by Keats Publishing (3). The role of platelet aggregation and blood viscosity in heart disease made a lot of sense to me. You just don’t have a myocardial infarction unless and until you have a blood clot. Keeping the blood slippery and free from clotting will reduce the probability of having the common heart attack called an acute myocardial infarction (AMI or MI). We can discuss that later in Part 3, but for now, let’s continue with the detective story.

Your search for the answers took you from Denmark to Greenland to the United States. What did you do next?

Dyerberg: In Dr. Hans Olaf Bang’s lab, we investigated whether EPA could give rise to the formation of prostaglandins with an effect on blood clotting. This we found, and it fitted with our hypothesis of an “anti-clotting” effect of EPA.  Then, we went back to Greenland to study the Eskimos’ blood and diets again.

Passwater: The journeys—scientific and physical—add up in years and distance. Physically, you have gone from Denmark to Greenland to Denmark to United States to Denmark and now back to Greenland.

What additional factors did you study on this trip?

Dyerberg: We then confirmed that EPA and DHA affected the clotting time of the Eskimos’ blood. This could be studied by measuring the Eskimos’ bleeding tendency. We examined this during new expeditions to northern Greenland, finding that the Eskimos actually had a longer cutaneous bleeding time. In 1979, again in The Lancet, we reported our results in a paper entitled “Haemostatic Function and Platelet Polyunsaturated Fatty Acids in Eskimos” (4). This paper also became a “nutritional classic.”

Passwater: Your findings at this point certainly were fascinating. Humans certainly don’t produce many long-chain omega-3s in their bodies, so then you had to answer where did the EPA and DHA come from. Polyunsaturated fatty acids are associated with plant foods, not animals. The snow- and ice-covered Arctic with their long periods of darkness is not conducive to growing plants, so isolated villages depended mostly on fishing and whatever else they could find hunting for food. The classical “Food Pyramid” for United States citizens has fats, oils and sweets in the smallest section with the recommendation to use them sparingly. I used to make jokes about the Eskimo food pyramid being composed of their main food groups of raw blubber, boiled blubber, fried blubber, baked blubber and roasted blubber. It was only a joke, but it made a point.

How did you connect Omega-3 fatty acids in the blood to Omega-3 fatty acids in the diet?

Dyerberg: As you know, not much was known at that time about EPA and DHA. What we found was that although fish and seals don’t make EPA and DHA themselves, they consume and concentrate these omega-3 fatty acids from the foods they eat. EPA and DHA are synthesized in the biosphere in the sea by algae. They then pass up the food chain via bigger and bigger organisms and finally via fish or, as for the Eskimos, seals that live on fish, into humans.

When we returned to Greenland, we collected food from the Eskimos using the cumbersome double portion technique, homogenized the food and froze it for transportation to analysis in Denmark. We found that the Eskimos ate approximately 14 grams of EPA and DHA per day! (5)

Passwater: Wow! Fourteen grams of EPA and DHA a day! And, most recommendations today are for at least one gram of EPA and DHA a day.

Getting back to your detective story, the next question then became whether the positive effects on the heart of omega-3 fatty acids from fish and fish oils that you found in the Eskimos could be transferred to our society by supplementing our diet with omega-3 fatty acids from fish oils?

Dyerberg: That’s a question that today, after nearly 40 years of research and after the undertaking numerous studies in volunteers and in patients with heart diseases, can be answered with an unambiguous “yes.” A 2009 survey of the preventable causes of deaths in the United States concludes that 84,000 deaths per year are attributable to low dietary omega-3 fatty acid intake (6)!

Furthermore, we have today obtained in-depth insight into how this beneficial effect is brought about. The studies have found that omega-3 fatty acids from fish oils have several positive effects; these effects work in combination, thereby lowering the risk of heart attacks. The same is true for patients already suffering from heart disease.

Passwater: How exciting. Let’s take another pause and pick up again here next month to discuss some of these effects of omega-3s and the clinical results that have been found. It is staggering to realize how much benefit has come from your pioneering discoveries. WF

References

1. J. de Goede and J.M. Geleijnse,et al.,“Marine (n-3) Fatty Acids, Fish Consumption, and the 10-Year Risk of Fatal and Nonfatal Coronary Heart Disease in a Large Population of Dutch Adults with Low Fish Intake,” J. Nutr. 140 (5), 1023–1028 (2010).
2. J. Dyerberg,et al.,“Fatty Acid Composition of the Plasma Lipids in Greenland Eskimos,” Am. J. Clin. Nutr. 28 (9), 958–966 (1975).
3. R.A. Passwater,EPA—Marine Lipids(New Canaan, CT, Keats Publishing, 1982).
4. J. Dyerberg and H. O. Bang, “Haemostatic Function and Platelet Polyunsaturated Fatty Acids in Eskimos,”Lancet2 (8140), 433–435 (1979).
5. H.O. Bang,et al.,“The Composition of the Eskimo Food in Northwestern Greenland,” Am. J. Clin. Nutr. 33 (12), 2657–2661 (1980).
6. G.M. Danaei,et al.,“The Preventable Causes of Death in the United States: Comparative Risk Assessment of Dietary, Lifestyle, and Metabolic Risk Factors,” PLoS Med. 6 (4), e1000058 (2009).

Part Three – The Basics of How EPA and DHA Bring Health Benefits

Do all omega-3 fatty acids provide heart benefits? Does the ratio of EPA to DHA matter? Is EPA good for the heart while DHA is good for the brain? Does it matter if EPA and DHA are present as free fatty acids, triglycerides or ethyl esters? Several misconceptions have arisen over the years and some readers may be surprised at the answers to these questions.

We have been chatting with Dr. Jørn Dyerberg regarding his major discovery of omega-3 fatty acids in human health. In the June 2010 issue, Dr. Dyerberg recounted his expedition into Greenland to discover why these remote-living Eskimos had about only one-tenth the heart disease incidence of many Western Countries including the USA and Denmark. Last month, we discussed the detective work required to solve the scientific riddle. In this session, we will discuss how EPA and DHA function and clarify several issues concerning omega-3 fatty acids in general.

 Jørn Dyerberg, M.D., professor and Dr. Med. Sc., has made several discoveries that elucidate many of the health benefits of omega-3 fish oils. Dr. Dyerberg made five scientific expeditions to Northwest Greenland in the 1970s examining the association between fish oil intake and coronary heart diseases in Eskimos. Dr. Dyerberg, who is Danish, hypothesized that the rarity of coronary heart disease among the Inuit could be due to the omega-3 fatty acids in their diet consisting largely of seal and cold-water oily fish. Together with his fellow researchers, he went on to elucidate the unique physiological effects of these fatty acids. His research opened new fields leading to thousands of health studies by many. His own research encompasses more than 350 scientific publications primarily concerning blood ­lipids, atherosclerosis, the blood coagulation system, omega-3 polyunsaturated fatty acids, trans-fatty acids, and pro­staglandins.

 In 2007, Dr. Dyerberg was honored by the American Heart Association in “Recognition of Outstanding Scientific Contribution for the Advancement of Heart Health Worldwide.” In 2008, he received the American Dietetic Association Foundation’s Edna and Robert Langholtz International Nutrition Award.

Passwater: Usually in science, when one question is answered, other questions are raised. You sought to uncover why Eskimos had only a fraction of the heart disease normally observed in Western Nations. You found a difference in EPA and DHA content between the blood of Eskimos and that of Danes and North Americans. This raised the question: From where did these fats come? You were able to trace their origin to diet. This raised the question: What biochemical effects did they have? You verified that EPA and DHA had effects on cardiovascular health in terms of improved (longer) blood clotting times, improved blood lipid (triglycerides, cholesterol, etc.) levels and a better balance of prostaglandin (PG ) formation. This raised several other questions. Is either EPA or DHA more important? Can other omega-3 fatty acids have similar biochemical effects? Can other fatty acids be converted into EPA and DHA in the body or are EPA and DHA themselves essential fatty acids?

Let’s start with the very basics of the concept that some types of fats are essential to life. At one time, fats were considered merely unessential sources of calories. Now, we understand that fats are important components of every cell and the many compounds made from fats are involved in controlling thousands of functions. We now recognize that a balance of omega-3 and omega-6 fats that is close to the balance of fats of the Paleolithic diets to which man has been exposed for many thousands of years is a better fit for our genetic makeup than the more recent agricultural diets and the modern fast-food diets.

The concepts of “vitamin F” and “essential fatty acids” were developed decades ago, but no one knew much else about the biochemistry of fatty acids. Drs. H.M. Evans (the discoverer of vitamin E in 1925) and George O. Burr demonstrated that fat-free diets impaired the growth and reproduction of laboratory animals in 1927 (1). They viewed this as a vital factor in fats along the lines of a vitamin and called this factor “vitamin F” at first. Drs. George O. Burr and Mildred M. Burr introduced the concept of essential fatty acids (EFAs) during the next two years (2). Specifically, linoleic acid (LA)—a C18: 2 omega-6 fatty acid that cannot be made in the body—was involved. The deficiency symptoms noted were basically scaly skin and an increased consumption of water. These symptoms were eliminated when LA was added to the fat-free diet. It wasn’t until about 1970 that it was realized that EFA were critical to the retina. Now, EFA are recognized as being essential to normal growth reproduction and good health.

Dr. Dyerberg, wasn’t that basically all that was known about essential fats when you found appreciable amounts of EPA and DHA in the blood of the Greenland Eskimos?

Dyerberg: Yes, at the time we made our original observations in Inuits, the essentiality of (omega-6) fatty acids was related only to these basic issues, and the focus was on linoleic acid. The omega-3 series was not considered and the discovery of derived products (as the prostaglandins) was in its initial state, and the relation of EPA and DHA deficiencies to increased Ischemic Heart Disease (IHD) was unknown. IHD is the medical term for reduced blood flow to the heart. Over the years, interest in the health benefits of consuming omega-3 fatty acids EPA and DHA has also been aimed at the intake of the EFA alpha-linolenic acid (ALA, 18: 3 n-3), which in other mammals can be converted into EPA and DHA. In man, however, it can only be converted to a small extent.

The focus of interest has in that respect been twofold: whether ALA has health benefits of its own and whether the conversion of ALA to longer chained omega-3 fatty acids in humans is sufficient to produce desirable tissue levels of EPA and DHA.

The concept of “essential” polyunsaturated fatty acids (PUFAs) is a bit odd in a way, in that very few essential functions are known of the prime essential PUFAs linoleic acid (18: 2 n-6) and linolenic acid (18: 3n-3). Linoleic acid has a function in the water barrier of the skin, but no essential functions are known related to linolenic acid. Their longer-chained derivatives, arachidonic acid (AA) (20: 4 n-6), EPA (20: 5 n-3) and DHA (22: 6 n-3), are truly the “essential” fatty acids when it comes to their function and effects in the body.

Passwater: The Institute of Medicine states, “ALA is not known to have any specific functions other than to serve as a precursor for synthesis of EPA and DHA” (3). Heart health involves more than the old concept of EFAs. What is important to heart health goes beyond growth and maintenance and the classical symptoms of EFA deficiency of scaly skin and thirst. Cardiovascular optimization involves the two long-chain omega-3 fatty acids EPA and DHA, and their intermediary docosapentaenoic acid (DPA) (22: 5n-3). The only fatty acids for cardiovascular optimization are EPA and DHA. Let’s look at the basics of EPA and DHA.

We have mentioned earlier that the body is very inefficient in producing either EPA or DHA from the more common plant-based omega-3s such as ALA from flaxseed oils and a similar C18 omega-3 fatty acid from other plant oils and certain fish, stearidonic acid (SDA).

Animals do have enzymes that can add double bonds and lengthen the fatty acid (desaturation and elongation) in polyunsaturated fatty acids, but not after the omega-9 position in the fatty acid. (Plants can introduce new double bonds between an existing double bond and the terminal methyl group.) Animals can increase unsaturation to a very limited extent, but can’t change an omega 6 into an omega-3, nor can they make omega 6 or omega 3 fatty acids.

Dr. Dyerberg. Please elaborate on the ability for humans to make EPA and DHA and how does this relate to heart health?

Dyerberg: The body can form a small amount of EPA and DHA from ALA. However, this is inadequate for best cardiovascular health.

Omega-3 prostaglandins (PGs) and other essential metabolites such as protectins (complementary regulatory proteins that protect cell membranes; also called CD59 or MIRL) can be made only from EPA and DHA. A small amount of omega-3 PGs can result from ALA after the body converts it to EPA or DHA. ALA contributes only a little to the heart health benefits attributed to EPA and DHA since only about 1–5 % of ingested ALA becomes EPA and next to nothing DHA.

Passwater:   Billy Shakespeare pointed out that a rose by any other name is still a rose and the famous quote; “a rose is a rose is a rose” was soon born. Dr. Dyerberg, is an omega-3 an omega-3 an omega-3 (suggesting that all omega-3s are equal) or are there major health differences between the omega-3 fatty acids?

Dyerberg: Consumers should be aware that just having “omega-3” on a product label doesn’t mean that it is necessarily heart healthy. The consumer should be interested in how much EPA and DHA are present. If the omega-3 is from ALA, then little of it will be converted into the form of omega-3 that produces heart benefits which is EPA and DHA.

It can be concluded that to obtain desirable levels of plasma and tissue long- chained omega-3 fatty acids by supplementation, far lower and dietary acceptable doses are effective when supplementing with the preformed fatty acids such as fish oil-based supplements, than by giving the precursor ALA. To obtain desirable heart health benefits with ALA intake, this cannot be achieved by supplementation, but necessitates substantial dietary alterations.

The effect of ALA intake on cardiovascular risk markers is comparable to that of linoleic and oleic acid, and dietary changes reducing the intake of saturated fat and increasing the ALA intake are consequently advisable.

With regard to supplementation, ALA (often derived from flaxseed oil) has only minor effects on cardiovascular risk, probably due to the low conversion rate to long-chained omega-3 fatty acids.

Passwater: Is this conversion dependent on the rest of the diet?

Dyerberg: Yes, as an example, excessive omega-6 fatty acids such as the amount present in typical western diets can reduce the already meager amount of conversion of ALA to EPA.

Passwater: Please allow me add some background information here. The conversion of ALA to long-chain EPA is influenced by diet as well as genetics. The high levels of linoleic acid (LA) in western diets inhibit the low rate of ALA conversion further. If one consumes very high amounts of ALA and very little LA, the conversion of ALA to EPA can be enhanced, but it still falls short of what is required for optimization of heart health. This is why the diet of the Eskimos was protective against heart disease and the diets in western nations were not. This is the “why Eskimos don’t get heart attacks” story of Dr. Dyerberg’s research in Greenland is what we are discussing.

If one wishes to focus on preventing IHD, then one should focus on EPA and DHA. Our focus is on optimization and not merely deficiency. The state of knowledge and consensus of experts in the field is that ALA conversion to EPA is too inefficient to rely on for optimum heart health. Most scientists in the field agree and note the most recent studies confirm the lower range of conversion (more towards 1% than 5%) among those consuming standard western diets (4). A 2001 study using radioisotopes to follow the conversion found that “Only about 0.2% of the plasma ALA was destined for synthesis of EPA.” (5)

Even if the conversion is many times higher in some, whatever the figure is, it isn’t enough to produce the heart benefits produced by EPA and DHA. One percent or ten % is not 100%. If ALA did produce sufficient conversion to EPA and DHA, there would have been no need for Dr. Dyerberg to go to Greenland and find EPA in the blood of the Eskimos. There would have been ample EPA in most peoples’ blood from ALA present in these diets and people would have only ten percent of the IHD…

This is not to say that ALA is of little value or that it produces no benefit. It is an essential fatty acid and has multiple health benefits including benefits to overall cardiovascular health, as well as many benefits that we have yet to elucidate. Whole flaxseed also has merit because it supplies fiber and ALA. ALA is good and should be in everyone’s diet, but, ALA does not significantly contribute to the strong heart benefits of EPA and DHA which are due to the eicosanoids (derivatives of C20 fatty acids) that have been the focus of this discussion.

This point was the focus of a 2006 systematic review entitled “Omega-3 Fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies” was published in the American Journal of Clinical Nutrition. (6)

Earlier that year in the same journal, Dr. L. Arterburn and colleagues concluded, “A large proportion of dietary alpha-linolenic acid (ALA) is oxidized, and because of limited interconversion of n-3 fatty acids in humans, ALA supplementation does not result in appreciable accumulation of long-chain n-3 fatty acids in plasma.” (7)

Not only do we do highly inefficiently convert ALA to EPA, but adult humans do not make DHA from ALA. Adults cannot meet the needs of DHA for the developing fetus for neuro and brain development without dietary DHA. In infants, very high amountsof ALA did result in some increase in blood DHA in two studies. (8.9)

The International Society for the Study of Fatty Acids and Lipids (ISSFAL) published their official statement on ALA supplementation and conversion to long-chain polyunsaturated fatty acids in humans in 2009 in the peer-reviewed journal for experts in this field, Prostaglandins, Leukotrienes and Essential Fatty Acids. (10) The ISSFAL is a body of over 500 lipid scientists.The meta analysis and review was conducted by Dr. J. Thomas Brenna of Cornell University, Dr. Norman Salem, Jr. of Martek Biosciences, Dr. Andrew J. Sinclair of Deukin University (Australia) and Dr. Stephen C. Cunnane of the University of Sherbrooke (Canada). The ISSFAL statement concludes, “With no other changes in diet, improvement of blood DHA status can be achieved with dietary supplements of preformed DHA, but not with supplementation of ALA, EPA, or other precursors.” The statements of the ISSFAL can be also viewed at www.issfal.org.uk/lipid-matters/issfal-policy-statements/ official-policy-statement-number-5.html.

ALA supplementation can increase EPA slightly, but not optimally. However, the evidence clearly shows that precursor supplementation does not increase blood levels of DHA whether the supplement is ALA, EPA or stearidonic acid. The only known means to increase blood DHA by supplementation in adults is through the consumption of preformed DHA. Dietary DHA and blood/breast milk DHA has a remarkably tight dose-response relationship. (11)

A point of confusion in studies regarding fatty acids is whether the study involves supplementation or replacement. As Dr. Brenna points out, “In considering dietary interventions, seemingly conflicting results can be reconciled by attention to two concepts: supplementation versus replacement. Supplementation is the addition of a dietary nutrient with no other change in the diet. Replacement is the substitution of one food for another. In the case of ALA, supplementation is achieved by the addition of an oil rich in ALA, such as flax or perilla oil, to an otherwise unchanged diet. The major change in the diet is an increase in ALA, with insignificant changes in other fatty acids. Replacement would be achieved by substituting an ALA-rich cooking oil such as canola for ALA-poor oils such as corn, safflower, sunflower and peanut. Importantly, replacement also significantly alters the dietary proportion of the omega-6 PUFA, linoleic acid, a factor that is often overlooked in the interpretation of such studies. Linoleic acid competes with ALA for conversion to long-chain PUFAs and influences the answer. (12)

Two studies out of the 21 studies reviewed by the ISSFAL showed that conversion of ALA can be improved, but not to optimal EPA or DHA levels) In one study, DHA increased by an impressive 21%, when high-ALA perilla oil was used as cooking oil in place of moderate-ALA soy oil over 10 months. Perilla oil has about 15% linoleic acid, compared to more than 50% linoleic acid in soy oil, and thus linoleic acid was reduced to less than a third of pre-intervention levels. (13) In the second study, the researcher instructed the participants to avoid foods high in linoleic acid, in addition to the supplementation with ALA. (14) Good luck with that.

The Food and Drug Administration (FDA) has examined this question and  announced on September 8, 2004 the availability of a qualified health claim for reduced risk of coronary heart disease (CHD) on conventional foods that contain eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) omega-3 fatty acids. (15) The qualified health claim does not apply to ALA.

Passwater: Now, let’s resume our chat with Dr. Dyerberg. Dr. Dyerberg, are vegetarians usually sub-optimally nourished in terms of EPA and DHA even if they eat ample ALA say from flaxseed sources? Are vegetarian diets overly rich in omega-6 fats as well?

Dyerberg: My answer is yes. It should, however, be stressed as I mentioned before, that if the diet is altered substantially, as the vegetarians’ and even more so the vegans’ are, the conversion of the 18 carbon PUFAs to their longer derivatives is enhanced. As the vegetarian diet generally is very rich in omega-6 fatty acids, I would recommend a supplementation with EPA and DHA.

Passwater: Would vegetarians be better off taking DHA derived from microorganisms or ALA?

Dyerberg: As mentioned, I would recommend that vegetarians—and especially vegans—do add an EPA/DHA supplement to their diet. Whether this supplementation is based on fish oil or on algae is, in my opinion, of no importance. It is the fatty acids that work and your body does not differ between their origins.

Passwater: As our long-term readers realize, I often ask the same question in a couple of different ways as a means of emphasis and clarity just to be sure that everyone understands the issue. Let me repeat. So, in order to get the heart benefits, now so widely attributed to omega-3s, we need specific omega-3s—the long-chain EPA and DHA. Are EPA and DHA of equal value to the body? Can the body interconvert EPA and DHA?

Dyerberg: Both EPA and DHA have essential functions in the body. We do not know in detail all these metabolic processes. EPA and DHA can be inter-converted in the body to a certain extent, but especially the conversion of EPA to DHA is modest. Both fatty acids are present in marine food, and I see no reason to spend a lot of money in producing and supplementing with “stand alone) substances such as EPA (alone) and DHA (alone). The human biology has developed with foods containing EPA and DHA (and AA!), and it is for me not a meaningful nutritional issue to search for the pure substances.

Passwater: At first, your research centered on PG formation from EPA and DHA. You linked the presence of EPA and DHA in the diet of Eskimos to a better balance of PG. Specifically, you found that EPA and DHA balanced the production of the PGs responsible for increased clotting time, blood platelet protection and vascular function to reduce blood platelet aggregation.

Now, research has moved to include membrane function and phospholipids. Your research has expanded into the role of EPA and DHA in forming better membrane phospholipids, which result in more fluid and thereby healthier membranes. The result is better health throughout the body in all systems. Thus, we can understand the better health that EPA and DHA produce beyond heart benefits. They affect every cell in the body via their important role in every cell membrane.

Evidence has emerged describing the biological essentiality of DHA for vision and the brain, its function and behavior. Most of the dry weight of the brain is lipid (fat) because brain activity depends greatly upon the functions provided by lipid membranes. The brain is 60% fat, and DHA is the most abundant fatty acid in the brain, comprising 25–35%. DHA is found in even greater concentrations—50–60%—in the retina.

Drs. Michael Crawford and Andrew Sinclair have shown that the brain needs DHA for its structure, growth and function. Drs. Gene Anderson and Nicholas Bazan have shown that vision requires docosahexaenoic acid (DHA). Dr. Claudio Galli has shown that DHA is important in learning.

We have discussed EPA and DHA in regards to eicosanoid balance. Is the association of DHA with brain health due to its relationship with membrane fluidity and neurotransmitters? Is this an oversimplification or is there scientific basis for such an association? Is EPA needed just as much as DHA for brain function?

Dyerberg: DHA has both structural and functional effects in the brain, and so have its derivatives, the protectins. But, EPA also seems to have essential roles related to brain function. A recent metaanalysis of randomized, controlled trials actually finds that EPA, but not DHA, appears to be responsible for the efficacy of omega-3 long-chain PUFA supplementation in depressed individuals (16).

Passwater: On May 26, you were a featured speaker at the opening session of “A Celebration of DHA: Discovery, Achievement and Challenges for Global Health 40 Years On” at the Royal Academy of Medicine in London. A goal of the conference was to call for a new focus to be placed on brain disorders and ill mental health; they will be the top two burdens of ill health worldwide by 2020 and are the greatest threat to humankind today.

Do you see an important role for fish oils in reversing this trend?

Dyerberg: One of the most interesting nutritional findings in recent decades has been the effect of dietary factors on modifying age-related cognitive decline (dementia).

Several studies have found a negative association between intake of long-chained omega-3 fatty acids and the risk of dementia. In the Framingham Heart Study, the top quartile of plasma DHA levels was associated with a significant 47% reduction in the risk of developing dementia (17). I find these positive results in dementia, especially Alzheimer’s one of the most promising fields of research in the huge area of omega-3 science.

Passwater: With attention being given to DHA for brain function, when did we realize that mothers’ milk contained DHA?

Dyerberg: In recent decades it has been realized that mothers’ milk contains both EPA and DHA, however in varied amounts dependent on the omega-3 intake of the mothers (18). The DHA/EPA ratio is generally from 2: 1 to 1: 1, but in Italy, mother’s milk contained more EPA than DHA (0.17 and 0.12 wt% respectively) (19). Consequently, DHA and EPA as well as AA are essential for newborns as the content of mothers’ milk is considered the “gold standard” for the composition of food to the newborn.

Passwater: Forgive the redundant question, but I want to make this point clear. Does it matter what is the ratio of EPA to DHA in the diet? Does a higher ratio of DHA mean more goes to the brain? Are supplements having more DHA than EPA more suited for brain health and are supplements with more EPA than DHA better for heart health?

Dyerberg: Again, to me it is a nutritional issue. Marine food sources contain EPA as well as DHA in various amounts and in various relative amounts. As long as you get enough of both, either from food or from supplements, it is fine. This means 200–300 milligrams of each of these fatty acids per day.

Passwater: EPA and DHA are best known for their heart and brain benefits. However, a dazzling amount of research involving EPA and DHA is increasingly being associated with reduced inflammation, which has an impact on many conditions from arthritis to athletic recovery to heart health to cancer. Does this property of fish oil involve the PG-3 family of prostaglandins?

Dyerberg: A steady and increasing number of scientific publications have appeared, now reaching tens of thousands, broadening into areas we were not aware of when the omega-3 arena was opened by us. This includes: anti-inflammatory effects in rheumatic disorders, possible effects in mood and psychiatric ailments, and positive influence on the development of the brain and nervous system in newborns.  All the above results relate to the long-chained omega-3 fatty acids EPA and DHA.

Several studies have demonstrated that omega-3 fatty acid supplementation attenuates the inflammatory process in chronic inflammatory disorders (e.g., rheumatoid arthritis) (20). This effect has been used in the treatment of various autoimmune disorders and lends support to the notion of an anti-inflammatory effect of omega-3 fatty acids in IHD prevention. It also supports the explanation for the benefit of low doses of omega-3 fatty acids in coronary heart disease.

The anti-inflammatory effect of long-chained omega-3 fatty acids was first noticed when examining the chemo-tactic potency of leukotrienes generated from EPA compared to the leukotrienes formed from AA. Leukotrienes are proinflammatory agents synthesized in the white blood cells (leukocytes). Leukotrienes derived from AA exhibit 10- to 30-fold greater potency than the EPA-derived leukotrienes.

New families of locally acting anti-inflammatory substances generated from omega-3 fatty acids, termed resolvins, protectins and isoprostanes have recently been identified. These components control the duration and magnitude of inflammation. Given the potent actions of leukotrienes, lipoxins, adhesion molecules, resolvins and protectins in human disease, the intake of EPA and DHA may attenuate the development of atherosclerotic diseases.

Passwater: EPA and DHA affect the risk of heart disease in many ways ranging from the anti-clotting effect that you elucidated in the 1970s to rhythm-normalization of the heart beat to triglyceride level affects, and as we are now finding, also to anti-inflammation affects.

I like to look at the anti-inflammatory effect as just as important as any other risk factor in heart disease. Omega-6s produce the chemical messengers of inflammation. Chronically, this leads to silent inflammation and the smoldering fires in the arteries and heart that lead to many diseases. Omega-3s lead to the chemical messengers that produce the opposite effect. A balance of both is needed.

In addition to the omega-3 and omega-6 fatty acids we have been discussing, there are also omega-7 and omega-9 fatty acids. Omega-9 fatty acids are generally the monounsaturated fatty acids such as oleic acid common in the Mediterranean diet.

Omega-7 fatty acids generally seem to behave worse than saturated fatty acids. Omega-7 fats behave like saturated fats, not the monounsaturated fats that they are. Omega-7 fats raise LDL and lower HDL. There is no known role in the body for omega-7 fatty acids.

Are omega-9 fatty acids of value, and if so, what role do they play in the body?

Dyerberg: Omega-9 fatty acids such as oleic acid have good organoleptic qualities as a constituent of olive oil. The omega-9 monounsaturated fatty acids do not share the cholesterol-increasing properties as saturated fats, and are therefore recommended to constitute 10% of our daily energy intake.

Passwater: Why COLD water fatty fish? Would fatty fish from the tropics also have EPA and DHA? Why are cold water fish usually cited for their EPA and DHA content? Is it because they need more body fat to survive the cold and thus have more stored EPA and DHA? Or is their diet different?

Dyerberg: The content of EPA and DHA is higher in cold water than in tropical marine fish. The reason may be that EPA and DHA have low melting points, thereby keeping the cells in the body of cold water fish in a flexible state in spite of the low sea temperature.

Passwater: Most fats in foods are in the form of triglycerides. Triglycerides are the most compact and calorie-dense compounds that can be converted into energy in the body.

During digestion, the fatty acids are stripped off of the glycerol backbone of the triglycerides? They are reassembled later in the lymph and via the veins that reach the liver. They can then be burned for energy, used to make phospholipids and eicosanoids or converted back into TG for storage in fat cells.

Today, fish oil supplements are available in various forms. Regarding supplements, does it make much practical difference which form the fish oil is in (triglyceride, phospholipids, ethyl ester, free fatty acid or whatever)?

My preference is the basic triglyceride form that is produced merely by rendering. However, there are products that have been concentrated after further distillation and even available as highly purified ethyl esters. The latest research that I have seen suggests that all are about equally absorbed. The triglyceride forms enter the lymph and bloodstream earlier than the ethyl esters, but in the long-term, all are about equally absorbed, though at different rates at different periods of time. Again, I prefer the more natural distribution of EPA and DHA on the middle carbon of the glycerol backbone of the triglyceride, rather than the more randomize distribution of EPA and DHA on all three carbons that occurs during heavy distillation and the reformation during condensation of the distillate in the second position.

Is there any meaningful difference?

Dyerberg: Generally, the various fatty acid formulations (triglycerides, ethyl esters, free fatty acids, phospholipids) are well absorbed, especially when taken along with a meal. We have earlier found that triglycerides compared to ethyl esters, are somewhat better absorbed. At the recent International Society for the Study of Fatty Acids and Lipids meeting in Maastricht, a study was presented finding exactly the same results.

Regarding the stereochemistry of the fatty acid position in the triglyceride molecule, several studies have documented that this has no effect on the bioavailability of the fatty acids.

Passwater: How much EPA/DHA do you recommend daily?

Dyerberg: The average intake of marine omega-3 fatty acids in Americans is low (approximately 200 mg/day), and for many it is zero! It is far below what today is considered for a target intake in the United States, namely, 400–500 mg/d of EPA + DHA. For pregnant females, we recommend a daily intake of DHA on 200–300 mg, due to the special need of DHA for the fetus’ brain development.

Passwater: Thank you, Dr. Dyerberg. Let’s pause once again and resume our chat with a look at some of the research with fish oil that documents the health benefits with which we began this conversation. WF

References

1. H.M. Evans and G.O. Burr, “Increased Efficacy of Subcutaneous when Compared with Intraperitoneal Administration of the Ovarian Hormone,”Am. J. Physiol.77 (3), 518–210 (1926); H.M. Evans and G.O. Burr, “A New Dietary Deficiency with Highly Purified Diets,” Proc. Soc. Exp. Biol. Med., 24, 740–740 (1927).
2. G.O. Burr and M.M. Burr, “A New Deficiency Disease Produced by the Rigid Exclusion of Fat from the Diet,”J. Biol. Chem.82 (2), 345–367 (1929).
3. Food and Nutrition Board, Institute of Medicine of the National Academies, Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (The National Academies Press, Washington, D.C., 2002).
4. Fats of Life Newsletter, ”Fat Basics” www.fatsoflife.com/fat-basics.php, accessed June 24, 2010.
5. Pawlosky RJ, Hibbeln JR, Novotny JA, et al. Physiological compartmental analysis of alpha-linolenic acid metabolism in adult humans.J Lipid Res.2001; 42: 1257–1265.
6. Wang, C., W. S. Harris, et al. (2006). “n-3 Fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review.”Am J Clin Nutr84(1): 5-17.
7. Arterburn, L. M., E. B. Hall, et al. (2006). “Distribution, interconversion, and dose response of n-3 fatty acids in humans.”Am J Clin Nutr83(6 Suppl): 1467S-1476S.
8. Clark KJ, Makrides M, Neumann MA, et al.J Pediatr1992;120(4 Pt 2):S151-S158.
9. Jensen CL, Chen H, Fraley JK, et al.Lipids1996;31:107-113.
10. Brenna, J. T., N. Salem, Jr., et al. (2009). “alpha-Linolenic acid supplementation and conversion to n-3 long-chain polyunsaturated fatty acids in humans.”Prostaglandins Leukot Essent Fatty Acids80(2-3): 85-91.
11. Gibson RA, Neumann MA, Makrides M.Eur J Clin Nutr1997;51:578-584
12. http://www.fatsoflife.com/article.php?nid=1&edition=arch&id=1670&issueid=72

13. Ezaki O, Takahashi M, Shigematsue T, et al.J Nutr Sci Vitaminol (Tokyo) 1999;45:759-772.
14. Mantzioris E, James MJ, Gibson RA, et al.Am J Clin Nutr1995;61:320-324.
15. http://www.fda.gov/SiteIndex/ucm108351.htm
16. J.G.Martins, “EPA but not DHA Appears to be Responsible for the Efficacy of Omega-3 Long Chain Polyunsaturated Fatty Acid Supplementation in Depression: Evidence from a Meta-Analysis of Randomized Controlled Trials,”J. Am. Coll. Nutr. 28 (5), 525–542 (2009).
17. E.J.Schaefer,et al., “Plasma Phosphatidylcholine Docosahexaenoic Acid Content and Risk of Dementia and Alzheimer Disease: The Framingham Heart Study,” Arch. Neurol. 63 (11), 1545–1550 (2006).
18. P.Guesnet,et al., “Blood Lipid Concentrations of Docosahexaenoic and Arachidonic Acids at Birth Determine their Relative Postnatal Changes in Term Infants Fed Breast milk or Formula,” Am. J. Clin. Nutr. 70 (2): 292–298 (1999).
19. G.Serra,et al., “Fatty Acid Composition of Human Milk in Italy,” Biol. Neonate 72 (1), 1–8 (1997).
20. R.J.Goldberg and J. Katz, “A Meta-Analysis of the Analgesic Effects of Omega-3 Polyunsaturated Fatty Acid Supplementation for Inflammatory Joint Pain,”Pain 129 (1-2), 210–223.

Part 4: The Major Studies

In the introduction to our chat with Jørn Dyerberg, M.D., I briefly mentioned a few of the reasons why readers should be interested in learning more about fish oil. Dr. Dyerberg’s discoveries led to our understanding of why the long-chain omega-3 fatty acids, EPA and DHA, are so important to our health.

In Part One, I called your attention to the following: “Reduce your chance of dying a sudden death by 45% (1, 2)! Reduce your risk of dying from sudden cardiac death by 90% (3). Reduce your chance of developing Alzheimer’s disease by 45–50% (4). Stay younger longer (5, 6)! Reduce the inflammation and pain of rheumatoid arthritis and the pain of osteoarthritis arthritis and other inflammatory diseases (7, 8). The litany of health benefits from omega-3s goes on, but hopefully, these are enough to get your attention so that you will read on about this miraculous dietary supplement. We will discuss the details of these studies in a later installment of this series.

“Recently, a low level of long-chain omega-3 fatty acids had been purposed as a risk factor for heart disease. The new risk factor is based on measuring the fatty acids in red blood cells, and is expressed as a percentage of EPA + DHA of total fatty acids. An omega-3 index of >8% is associated with 90% less risk for sudden cardiac death, as compared to an omega-3 index of <4% (9).”

In Part 2, I noted another important large multi-year study in which Dutch researchers reported a 62% lower risk of fatal heart attack in people consuming a modest amount of EPA and DHA (approximately 230 mg/day) from fish as compared with those consuming small amounts (approximately 40 mg/day of EPA and DHA) (10).

This month we will chat with Dr. Dyerberg about the details and meaning of these studies.

Jørn Dyerberg, M.D., professor and Dr. Med. Sc., has made several discoveries that elucidate many of the health benefits of omega-3 fish oils. Dr. Dyerberg made five scientific expeditions to Northwest Greenland in the 1970s examining the association between fish oil intake and coronary heart diseases in Eskimos. Dr. Dyerberg, who is Danish, hypothesized that the rarity of coronary heart disease among the Inuit could be due to the omega-3 fatty acids in their diet consisting largely of seal and cold-water oily fish. Together with his fellow researchers, he went on to elucidate the unique physiological effects of these fatty acids. His research opened new fields leading to thousands of health studies by many. His own research encompasses more than 350 scientific publications primarily concerning blood lipids, atherosclerosis, the blood coagulation system, omega-3 polyunsaturated fatty acids, trans-fatty acids and prostaglandins.

 In 2007, Dr. Dyerberg was honored by the American Heart Association in “Recognition of Outstanding Scientific Contribution for the Advancement of Heart Health Worldwide.” In 2008, he received the American Dietetic Association Foundation’s Edna and Robert Langholtz International Nutrition Award.

Passwater: Dr. Dyerberg, there are so many important studies that show the health benefits of fish oil. It’s hard to pick just a few to chat about, but let’s start with one of my favorites: The 1999 GISSI Study (1). This study caught the attention of many clinical researchers and influenced the thinking of “official” organizations that make dietary recommendations. The GISSI study used supplements of 850 mg/day of total EPA and DHA.

Dr. Dyerberg, what is important about the GISSI Study? What is the take home message for us?

Dyerberg: The GISSI study was the second large clinical trial examining the effect of an increased intake of EPA and DHA on coronary heart disease. The first was the Diet and Reinfarction Trial (DART) (11). The DART study (published in 1989) involved 2,033 men recovering from myocardial infarction. They were randomly allocated to receive advice or to receive no advice on each of three dietary factors: an increase in fatty fish intake, a reduction in intake of certain fats (saturated fat) with an increase in others (polyunsaturated fatty acids, PUFAs) or an increased intake of cereal fiber. The men advised to eat more fatty fish had 29% lower two-year all-cause mortality; the other forms of advice did not have any significant effects (12).

The Italian GISSI-Prevenzione trial (published in 1999) was even bigger, involving 11,300 persons! The trial showed that three-year treatment with low-dose omega-3 PUFAs (850 mg/day) was associated with a significant total mortality reduction of 21% in patients who survived a recent myocardial infarction or heart attack (starting treatment within three months from symptom onset). An analysis of the causes of death showed that among all cardiac causes, sudden cardiac death was the most affected by n-3 PUFA, which was reduced by 45%!

Passwater: I like to use slides based on three studies in my lectures. The most important message that I see in these studies is that those persons in the highest quartile of EPA and DHA combined intake have only about 10% of the cardiac risks of persons in the lowest quartile of EPA and DHA intake. The data from Dr. D.S. Siscovick and colleagues looked at a patient cohort nested within the famous Physicians Health Study and found that those persons in the highest quartile of EPA and DHA intake had only 10% of the risk of sudden cardiac death of normal people (90% reduction in risk of sudden cardiac death) (14). We haven’t even discussed the importance of EPA and DHA in normalizing heart rhythm and preventing abnormal heart rhythms that can lead to sudden heart death (3).

Figures 1–3 are based on these three studies and I think they present compelling graphics that should get everyone’s attention.

Dr. Dyerberg, these three studies add considerably to the body of science that shows that EPA and DHA reduce the risk of death from cardiovascular disease. We owe you a lot for your pioneering research and further elucidation of the science that has led to these studies. What should people conclude from these and similar studies?

Figure 1: The odds ratio (relative risk) of having an acute coronary syndrome is inversely associated with the combined EPA and DHA content of the blood. Acute coronary syndrome is an umbrella term used to cover any group of clinical symptoms compatible with acute myocardial ischemia. Acute myocardial ischemia is chest pain due to insufficient blood supply to the heart muscle that results from coronary artery disease (also called coronary heart disease). This content can be conveniently expressed as the percentage of EPA and DHA in the total blood cell membrane fatty acids. This percentage is referred to by Dr. W.S. Harris et al. as the “Omega-3 Index.” Figure 1 charts the EPA and DHA intake as three groupings: low (<4%), intermediate (4–8%) and high (>8%). The odds ratios were calculated to include possible confounding factors including age, race, sex, diabetes, hypertension, family history and various serum lipids. Data are from R.C. Block et al. (13).

Figure 2: Relationship between total EPA and DHA content (expressed as the Omega-3 Index) and the risk for primary cardiac death. Primary cardiac death is the sudden cessation of heartbeat and cardiac function, resulting in the loss of effective circulation. It is also called primary cardiac arrest or sudden cardiac death. Data are from Dr. D.S. Siscovick and colleagues (14).

Figure 3: Relationship between the total EPA and DHA (expressed as the Omega-3 Index) and sudden cardiac death. Data are from Dr. C.M. Albert and colleagues (2).

Dyerberg: There are several conclusions, but to me the most obvious is that we are in a nutritional deficiency of long- chained omega-3 fatty acids. In the United States, the average daily intake of EPA plus DHA is 100–200 mg. In 20% of U.S. citizens, the intake is close to zero! The recommended intake is 400–600 mg/day, and in pregnancy and lactation, women should consume 300 mg of DHA/day.

Passwater: Wow! The intake of EPA and DHA is close to zero in 20% of U.S. citizens! Holy smoke! And, the U. S. Daily average is about 100–200 mg, instead of the recommended 400–600 mg! On average, U.S. citizens are getting only a third to a sixth of the recommended amounts, and I feel that the 600 mg recommendation should be higher. We seek optimal health, not average health. I personally lean more toward the 1,000-mg level for healthy persons and more for those with health problems. This is still far short of the 14,000 mg you found in the Eskimo diet (15).

Let’s turn to another critical health problem. Dementia and Alzheimer’s disease may become the most important health problem as the population ages. There have been studies showing that EPA and DHA may become more important to counter these problems. I mentioned the study by Dr. E.J. Schaefer and colleagues in the introduction (4).

Dr. Dyerberg, what does this study suggest to you?

Dyerberg: That the field of long-chained omega-3 fatty acids in human nutrition is broadening rapidly. The necessity of a sufficient daily intake of EPA plus DHA is maybe even more convincing when considering brain health, that with respect to heart health! Several studies have reported that the risk of developing dementia—as Alzheimer’s disease—is inversely related to the intake of long-chain omega-3 fatty acids. This is maybe most convincingly shown in the Framingham study finding that a mean DHA intake of 180 mg/d was associated with a significant 47% reduction in the risk of developing all-cause dementia (4). Studies from the Netherlands, France and Italy find the same relations.

In one study, researchers examined omega-3 fatty acid erythrocyte membrane content and cognitive variation in late adulthood (16). Dr. L.J. Whalley and colleagues found that total omega-3 PUFA and DHA concentrations in erythrocytes were associated with benefits for cognition in persons aged 64 to 68 years.

There are 5.2 million people in the United States living with Alzheimer’s. Alzheimer’s is the seventh-leading cause of death. The direct and indirect costs of Alzheimer’s and other dementias amount to more than $148 billion each year.

Passwater: Our goal is to help people not just live longer, but to live better longer. I mentioned two studies that may impact on just this very idea—living better longer. In the studies that I mentioned in the introduction to this series, it was found that fish oils protected telomeres from shortening. A telomere is a region of repetitive DNA at the end of a chromosome that protects the chromosome from deterioration. Leukocyte telomere length, an emerging marker of biological age, has been shown to predict cardiovascular morbidity and mortality.

Dr. Dyerberg, do you see fish oil as improving our general health beyond reducing the risk of overt diseases, but also in helping us live better longer?

Dyerberg: Results from New Zealand illustrates that an increased intake of long-chained omega-3 fatty acids may help us not just to live longer, but to live better longer. In the New Zealand Adolescents and Adults study of 2,416 persons above 15 years of age, researchers found that there was a significant positive trend in mental well-being across the quintiles of the ratio of EPA to AA in serum phospholipids (17). The longevity issue is convincingly illustrated by the findings that those in the highest quartile of omega-3 fatty acid blood levels experienced the slowest rate of telomere shortening. But, other studies have also found similar relations.

In a Norwegian randomized clinical trial on n-3 polyunsaturated fatty acids supplementation and all-cause mortality in elderly men at high cardiovascular risk, they observed a tendency toward reduction in all-cause mortality in the n-3 PUFA groups that, despite a low number of participants, reached borderline statistical significance (18).

In The Heart and Soul Study, blood n-3 FA levels were inversely associated with total mortality independent of standard and emerging risk factors, suggesting that reduced tissue n-3 FA levels may adversely impact metabolism (19).

Passwater: Research soon took us from primarily cardiovascular studies to protection against the inflammatory diseases. I mentioned two studies related to arthritis in the introduction (7, 8).

Dr. Dyerberg, how do you see the role of EPA and DHA in reducing inflammation?

Dyerberg: The omega-3 polyunsaturated fatty acids possess potent anti-inflammatory activities. Some of the effects of omega-3 PUFAs are brought about by a modulation in the amount and types of eicosanoids made, and other effects are elicited by eicosanoid-independent mechanisms, including actions upon intracellular signaling pathways, transcription factor activity and gene expression. Animal experiments and clinical intervention studies indicate that omega-3 fatty acids have anti-inflammatory properties and, therefore, might be useful in the management of inflammatory and autoimmune diseases.

Passwater: Well, your pioneering research certainly has extended into many areas of health for all people. It seems as if there are new studies about the benefits of EPA and DHA being published nearly every week. They extend the role of these long-chain omega-3 fatty acids from artery health (20) to cancer prevention (21–26). Dr. Emily White and her colleagues at the Fred Hutchinson Cancer Research Center studies 35,016 postmenopausal women who did not have a history of breast cancer for six years and found those who regularly used fish oil supplements had a 32% reduced risk of ductal breast cancer. They concluded, “Fish oil may be inversely associated with breast cancer risk.”(26)

There are so many thousands of research articles published now that I bet it is difficult for even you to keep track of all of the published articles.

Dyerberg:  The number of scientific publications on the health effects of EPA and DHA has increased enormously since our original publications in the 1970s, and the number of human studies is now above 9,000! This is of course nearly impossible to keep check on—my own database has now reached number 2,846 and is still growing. I consider myself privileged to have been a co-initiator of such an important science.

Passwater: On behalf of myself and our thousands of readers, I thank you for your time and patience in chatting with us over these past four months. It’s been a remarkable and truly enjoyable experience. Your explanations as well as your research will help countless millions of people. WF

References

1. Dietary Supplementation With N-3 Polyunsaturated Fatty Acids And Vitamin E After Myocardial Infarction: Results Of The GISSI-Prevenzione Trial. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico (1999).
2. C.M.Albert,et al., “Blood Levels of Long-Chain N-3 Fatty Acids and the Risk of Sudden Death,” N. Engl. J. Med. 346 (15), 1113–1118 (2002).
3. H.Leon,et al., “Effect of Fish Oil on Arrhythmias and Mortality: Systematic Review,” BMJ 337, a2931 (2008).
4. E.J.Schaefer,et al., “Plasma Phosphatidylcholine Docosahexaenoic Acid Content and Risk of Dementia and Alzheimer Disease: The Framingham Heart Study,” Arch. Neurol. 63 (11), 1545-1550 (2006).
5. R. Farzaneh-Far,et al., “Association of Marine Omega-3 Fatty Acid Levels with Telomeric Aging in Patients with Coronary Heart Disease,” JAMA 303 (3), 250–257.
6. R. Farzaneh-Far,et al.,“Telomere Length Trajectory and its Determinants in Persons with Coronary Artery Disease: Longitudinal Findings from the Heart and Soul Study,” PLoS One 5 (1), e8612.
7. B.Galarraga, et al., “Cod Liver Oil (N-3 Fatty Acids) as a Non-Steroidal Anti-Inflammatory Drug Sparing Agent in Rheumatoid Arthritis,” Rheumatol (Oxford) 47, 665–669 (2008).
8. D.Fritsch,et al., “A Multicenter Study of the Effect of Dietary Supplementation with Fish Oil Omega-3 Fatty Acids on Carprofen Dosage in Dogs with Osteoarthritis,” J. Amer. Veterinary Medical Assoc. 236 (5), 535–539 (2010).
9. W.S.Harris, “The Omega-3 Index as a Risk Factor for Coronary Heart Disease,”Am. J. Clin. Nutr. 87 (6), 1997S–2002S (2008).
10. J. de Goede and J.M. Geleijnse,et al.,“Marine (n-3) Fatty Acids, Fish Consumption, and the 10-Year Risk of Fatal and Nonfatal Coronary Heart Disease in a Large Population of Dutch Adults with Low Fish Intake,” J. Nutr. 140 (5), 1023–1028 (2010).
11. M.L. Burr,et al., “Diet and Reinfarction Trial (DART): Design, Recruitment, and Compliance,”Eur. Heart J. 10 (6), 558–567 (1989).
12. M.L. Burr,et al.,“Effects of Changes in Fat, Fish, and Fibre Intakes on Death and Myocardial Reinfarction: Diet and Reinfarction Trial (DART),” The Lancet, 2 (8666), 757–761 (1989).
13. R.C. Block,et al., “EPA and DHA in Blood Cell Membranes from Acute Coronary Syndrome Patients and controls,”Atherosclerosis 197 (2), 821–828 (2008).
14. D.S.Siscovick,et al., ”Dietary Intake and Cell Membrane Levels of Long-Chain n-3 Polyunsaturated Fatty Acids and the Risk of Primary Cardiac Arrest,” JAMA 274 (17), 1363-1367 (1995).
15. L.K.Whalley,et al., “n-3 Fatty Acid Erythrocyte Membrane Content, APOE Varepsilon4, and Cognitive Variation: An Observational Follow-Up Study in Late Adulthood,” Am. J. Clin. Nutr. 87 (2), 449–454 2008).
16. F.L. Crowe,et al., “Serum Phospholipid n 3 Long-Chain Polyunsaturated Fatty Acids and Physical and Mental Health in a Population-Based Survey of New Zealand Adolescents and Adults,” Am. J. Clin. Nutr. 86 (5), 1278–1285 (2007).
17. G. Einvik,et al.,  “A Randomized Clinical Trial on n-3 Polyunsaturated Fatty Acids Supplementation and All-Cause Mortality in Elderly Men at High Cardiovascular Risk,” Eur. J. Cardiovasc. Prev. Rehabil. 2010 Apr 10. [Epub ahead of print].
18. J.V. Pottala,et al.,“Blood Eicosapentaenoic and Docosahexaenoic Acids Predict All-Cause Mortality in Patients With Stable Coronary Heart Disease: The Heart and Soul Study,” Circ. Cardiovasc. Qual. Outcomes 2010 Jun 15. [Epub ahead of print].
19. C.A. Fahs,et al.,“The Effect of Acute Fish Oil Supplementation on Endothelial Function and Arterial Stiffness Following a High-Fat Meal,” Appl. Physiol. Nutr. Metab. 35(3), 294–302 (2010).
20. M. Ligo, T. Nakagawa and Y. Iwahori, “Inhibitory Effects of Docosahexaenoic Acid on Colon Carcinoma Metastasis to the Lung,”Br. J. Cancer75 (5), 650–655 (1997).
21. J. Kim,et al.,“Fatty Fish and Fish Omega-3 Fatty Acid Intakes Decrease the Breast Cancer Risk: A Case-Control Study,” BMC Cancer 9, 216 (2009).
22. E.J. Ramos,et al.,“Effects of Omega-3 Fatty Acid Supplementation on Tumor-Bearing Rats,” J. Am. Coll. Surg. 199 (5), 716–723 (2004).
23. H. Toriyama-Baba,et al.,“Organotropic Chemoprevention Effects of n-3 Unsaturated Fatty Acids in a Rat Multi-Organ Carcinogenesis Model,” Jpn. J. Cancer Res. 92 (11), 1175–1183 (2001).
24. A. Wolk,et al.,“Long-Term Fatty Fish Consumption and Renal Cell Carcinoma Incidence in Women,” JAMA 296 (11) 1371–1376 (2006).
25. Brasky, T. M., Lampe, J. W., Potter, J. D., et al. Specialty Supplements and Breast Cancer Risk in the VITamins And Lifestyle (VITAL) Cohort. Cancer Epidemiol Biomarkers Prev 19(7); 1696-1708 (2010).

© 2010 Whole Foods Magazine and Richard A. Passwater, Ph.D.

Potassium-to-Sodium Ratio Affects Overall Health

An Interview with Herb Boynton by Richard A. Passwater, Ph.D.

http://www.drpasswater.com/nutrition_library/potassium_sodium.html

Part 1: Innovative Supplements Have Helped Millions

When most people think of salt and health, they think of blood pressure. Many, if not most people, are not “salt sensitive” meaning that they can eat salted French fries or potato chips and not notice a rise in blood pressure. So they may reason, “If I’m not salt-sensitive, then I don’t have to worry about my salt intake. That’s for the salt-sensitive people to worry about.”

Wrong! Salt intake, particularly the ratio of potassium to sodium in our diet, affects the functioning of every cell in our bodies!

So, even if your blood pressure doesn’t rise with increased salt intake, your rate of ageing is increasing, your arteries are stiffening, your bones are weakening, your nerve impulses are slowing, your memory is declining, your risk of kidney stones is increasing, your ability to fight against cancer is impaired and the ability to nourish every cell in your body is decreased. There is overwhelming evidence that an excess of dietary salt, coupled with a deficiency in potassium, is perhaps the single largest contributor to health problems in the U. S.

Salt can cause diseases having nothing to do with blood pressure. One could say that, to a large extent, your health depends on the balance of potassium to sodium (salt) in one’s body. By improving your potassium-to-sodium balance, you can lower your risk of heart attack, stroke, osteoporosis, asthma, ulcers, stomach cancer, hypertension and other salt-linked killer diseases. The good news is that increasing the amount of potassium in your diet can counterbalance the effects of high salt intakes.

Bringing this information to the public has been a passion of a longtime friend of mine, Herb Boynton. Herb and his colleagues-Richard Moore, M.D., Ph.D., a pioneer in potassium and sodium biochemistry, and Mark McCarty, a health researcher have written a book, The Salt Solution, that should be read by everyone. I repeat-everyone-not just those interested in health, not just those who have high blood pressure, but everyone!

There is no commercial interest in this passion of Herb Boynton. It is just that Herb developed high blood pressure at an early age, and he knew what a devastating effect that could have on his health and longevity. So, as a “labor of love,” he has researched the subject for several decades and now, in the book, in this column and in subsequent interviews with his co-authors, we are able to benefit from his experience.

Herb also is a student of the Paleolithic (Stone Age) and present-day primitive diets. One of the many good fortunes of knowing Herb for more than a quarter of a century is that there have been countless times that he has bent my ear about studies of one primitive diet or another and its health benefits. Herb has been a major contributor to the field of applied nutrition, and yet many people today may not know about his contributions, nor the research that he sponsored at various laboratories around the world. Among other accomplishments, as founder of Nutrition 21, Herb developed and introduced the first-ever selenium and chromium supplements. These nutritional products have improved the health of millions of people around the world.

Herb is “retired” now, which means that he may find more time for writing. He was one of the first to write about selenium and other trace elements in nutrition magazines. His vocabulary and elegant style are legendary, and his early (mid-1970s) articles in Let’s Live and Bestways were classics. Please join me for a chat with Herb about his important role in the natural products industry, both past and present.

Passwater: Herb, tell us about the origin of Nutrition 21?

Boynton: About 45 years ago I contracted polio. I was young and in peak physical condition; it was the last thing I expected to happen. I wondered how a vital young guy like me could get a terrible disease like that. It triggered an interest in nutrition that persists to this day. That was the primary reason I founded Nutrition 21. The year was 1973, and I was 49 years old. Nutrition 21 was founded to be a nutrition research firm, and thus began a 25-year intensive course in applied nutrition.

Passwater: You attribute your interest in trace elements to your friend Dr. Klaus Schwarz. As you know, I dedicated my 1980 book, Selenium as Food & Medicine, to Klaus. How did your friendship with Klaus come about?

Boynton: In 1972, 1 read a fascinating article in Scientific American entitled “The Elements of Life.” It discussed the manner in which Klaus had invented trace element “isolators” which could restrict the dietary content of a trace element. With the aid of these controlled diets and laboratory animals, he had been able to demonstrate the nutritional essentiality for seven or eight elements that formerly were thought to be unimportant or even toxic. These trace elements included selenium, chromium, silicon, vanadium, nickel, tin and others.

This was an utterly remarkable achievement on Dr. Schwarz’s part, and in my view he should have received a Nobel Prize. In any case, he was interested in what I was doing, and together we were able to develop an organic selenium product and later an organic chromium product, both of which Nutrition 21 introduced into the marketplace.

Passwater: Why did you choose selenized yeast to be your organic selenium compound?

Boynton: We didn’t think that inorganic forms of selenium were good choices nutritionally. We jointly decided to see if we could grow a yeast product. Yeast already is in the food supply, of course, and it normally contains significant amounts of selenium. We thought that we might be able to increase the amount of selenium normally found in yeast.

We contacted Dr. Henry Peppler at Universal Foods Corporation in Milwaukee, and he agreed to run a series of tests to see if that would be possible. The first few tests were failures, but after about five or six months, we were able to grow a yeast that contained approximately 1,000 parts per million of selenium, and it was indeed organic. A large percentage of the organically bound selenium was in the form of selenomethionine, but it also contained several selenium-peptides. We introduced that into the marketplace about 1975. Anyway, it was just in time for your 1975 book Supernutrition: Megavitamin Revolution, which told the public about your research and the health benefits of selenium.

Passwater: Well, our friendship goes back to that time. You introduced yourself to me after one of my lectures, and I had already known about you from your writings. By the way, we have more sophisticated analyses of selenium yeast now. The best that we could determine before was that selenium yeast contained largely selenomethionine, selenocystine and seleno-peptides. Now, thanks to more sophisticated techniques using high performance liquid chromatography-inductively coupled plasma-mass spectrometry (HPLC-ICP-MS). we know that selenomethionine accounts for no more than about 20% of all selenium-containing compounds. Another group of selenium-containing compounds include selenocystine (which 1 used in any earlier research), seleno-methylselenocysteine and selenoethionine. There also is another group of compounds, mostly unidentified al this time, that make up a about 40% to 50% of all the selenium compounds in yeast. These unidentified compounds may include selenophosphates, triphenyl phosphine selenide, diselenides, triselenides and other very interesting organic selenium compounds.

Later, you introduced selenomethionine, but your next innovative product was GTF-Chromium. Before you introduced it, you permitted me to test it on diabetic mice in my laboratory. The effectiveness of GTF-Chromium was readily apparent in the diabetic mice. Diabetic mice fed the RDA of all nutrients including chromium in the form of chromium chloride grew to be obese, pear-shaped, had high blood sugar levels and were short-lived. Diabetic mice fed the same diet, except that an equal amount of chromium as GTF-Chromium replaced the chromium chloride, grew normally, were normal in shape, did not become obese, had normal blood sugar levels and had normal lifespans.

Chromium is a very important supplement and I enjoyed researching with it and writing about it in my 1982 booklet, GTF Chromium (Glucose Tolerance Factor). How did the discovery of GTF chromium come about?

Boynton: Glucose Tolerance Factor (GTF) was the description for the organic form of chromium that helped insulin function to transport the blood sugar glucose through cell membranes. It was Dr. Schwarz’s suggestion that we try to do the same thing for chromium that we did for selenium, and grow yeast with more organically bound chromium than normal. We tried to do this at the same time that we were developing selenized yeast, but-where as it took us only a few months to get a successful method of growing selenium yeast-it took us over a year to achieve a chromium yeast with organically bound chromium. GTF-Chromium was introduced into the marketplace about a year or two later than selenium yeast.

Passwater: Much of what has been reported in the scientific literature about GTF is associated with Dr. Walter Mertz. Wasn’t Dr. Mertz a colleague of Dr. Schwarz’?

Boynton: This is true. Dr. Schwarz introduced me to Dr. Mertz and I have had intermittent conversations with Dr. Mertz over the years. As you know, these two scientists were mutually responsible for determining the nutritional essentiality of chromium. I last saw Dr. Mertz about two years ago at a chromium symposium in Boston; he is now enjoying a well-deserved retirement.

We were never able to determine the precise chemical constituents of our chromium yeast, and we still haven’t. With regard to the chromium yeast, we know that the chromium is organically bound, but we were never able to elucidate the precise formula of that product. Just as you mentioned that other organic selenium compounds have been identified in selenium yeast, I am sure that there are several interesting organic chromium compounds in GTF yeast.

Later, of course, we became aware of Dr. Gary Evans’ patent on chromium picolinate, and our initial tests convinced us that this was a better form of chromium than our GTF-chromium yeast. So we licensed the patent for chromium picolinate from the U.S. government.

Passwater: That was another exciting development! I wrote a series of Vitamin Connection columns on chromium picolinate between February and June of 1989. It also became the focus of my 1992 booklet, Chromium Picolinate, and my 1993 book, The Longevity Factor. This nutrient is so important to insulin function. Also, it helps prevent damage to the body that may result from even only slightly elevated blood sugar levels. The things to watch for are glycation and the formation of Advanced Glycosylation End-products (AGEs) .

You sponsored several clinical studies and research with these compounds, particularly chromium picolinate.

Boynton: Yes, we did. The most important of these was the one that we did with Dr. Richard Anderson of the U.S. Department of Agriculture and Dr. Nancy Cheng. This research started about 10 years ago in Beijing. It first was reported at the annual meeting of the American Diabetes Association in San Francisco in June 1996 and was published in 1997 in the journal Diabetes. The paper was titled “Elevated intakes of supplemental chromium improve glucose and insulin variables in individuals with type 2 diabetes.” That study was particularly important because it demonstrated that, at both the 200 mcg and 1,000 mcg dosages, chromium picolinate had very impressive salutary effects on the blood sugar levels of nun-insulin-dependent diabetics. Moreover, benefits were observed at both fasting blood levels and levels of glycosylated hemoglobin. We were extremely pleased with the results of that test.

I might say in passing that the reason we did this in China was that no one was willing to use 1,000 mcg of chromium in the United States, despite the fact chromium is remarkably safe even at gigantic dosages. It was an irrational fear. Nevertheless, we were unable to obtain permission to do this test in the U.S. We were very grateful for Dr. Nancy Cheng for making the Beijing hospital available to us.

Passwater: Somewhere between the work on the two chromium supplements, you introduced L-selenomethionine. I believe that all of the human clinical tests with selenium have been with selenium yeast. What was the story behind selenomethionine?

Boynton: In the early 1980s, there was a scare about yeast products. Although brewer’s yeast and baker’s yeast had long been staples in health food stores, the public was misled into thinking that nutritional yeasts were related to Candida and that people should be on yeast-free diets. The truth is that nutritional yeasts are totally dead cells. There are a few strains of pernicious yeast, but these have live cells. I recall that you wrote about this ungrounded fear in this column a year or so ago. (Author’s Note: There were two columns, both appearing under the overall title “Nutritional Yeasts and Yeastophobia,” The first was published in June 1999 and featured Dr. Seymour Pomper, and the second, published in July 1999, spotlighted Dr. Jack Sobel.)

Since many people stopped taking their selenium yeast supplements, I didn’t want them to miss the health benefits of selenium, so, with time and effort, we developed L-selenomethionine supplements.

Passwater: Why did you become so passionately interested in potassium and sodium?

Boynton: In 1942, before I’d reached 18, I tried to enlist in the Navy. To my great dismay, I flunked the physical; they told me my blood pressure was too high. I did pass the Army physical, which was more lenient, and I spent the next three years in World War II.

Over the ensuing decades, my blood pressure remained high-too high to even qualify for life insurance. The fact that Nutrition 21 was a research firm immersed me in the scientific research on diet and health. One of the most important facts I learned was that correcting my potassium/sodium balance might reduce my blood pressure and my risk of heart disease as well as other diseases.

As a result, I reduced my salt intake. I began by giving up potato chips (which 1 dearly love) and ate more fresh fruits and vegetables. Changes didn’t occur overnight, but after a few months, my blood pressure dropped into the normal ranges. Now I’m in my mid-70s, and my blood pressure hovers around 115 over 75-lower than the blood pressure of many adults decades younger. I no longer worry that I might die of a stroke, as my mother, my sister and my favorite aunt did.

I do, however, continue to watch my salt and potassium intake very carefully. It’s the smallest of dietary sacrifices, and the rewards are incalculably rich.

Passwater: What you seem to have mastered so well and for so long gives many others immeasurable difficulty. There are countless numbers of people who need help in adjusting their taste to less salt in their food or in easily increasing their potassium intake. Your book addresses both concerns and we’ll chat about them later, but your mention of the word “rich” reminds me that salt was once a measure of wealth. In my 1983 book, Trace Elements, Hair Analysis and Nutrition, I point out that salt was once used as payment for goods. In fact, the word salary is derived from this practice. Then there is the phrase “not worth his salt.” Salt has been regarded very highly in the past.

Boynton: Salt is more than a seasoning, and salt craving is almost universal. Several countries even have taxed salt. In India, Mahatma Gandhi led a “salt march” in 1930 to protest the British policy of monopolizing the production, sale and taxation of salt. In 18th-century France, where salt was very expensive and heavily taxed, 10,000 people a year were arrested for smuggling salt-and 300 a year were hanged.

Salt is indeed an essential nutrient, and it used to be scarce. For about 99.5% of human history, salt was so scarce that our bodies learned how to hoard it. It used to be that we had far more potassium in our diet than sodium. Paleolithic diets had about 16 times more potassium than sodium, whereas modern “civilized” diets have about 1.6 times more sodium than potassium.

Through the millennia, our- bodies learned how to hang on tenaciously to sodium and squander potassium. Because sodium has been so scarce in diets until modern times, our bodies developed mechanisms to hang onto every morsel of sodium it could. The sodium-potassium pumps in the kidneys are different than those in other tissues and they function to return sodium back into the bloodstream. Now our diets consist largely of processed foods instead of whole foods. Food processors refine foods in such a way as to reduce potassium and then they add salt to satisfy our cravings and taste preferences. The result is that millions of Americans suffer from a silent but deadly deficiency of potassium, while consuming massive amounts of salt. We eat more than a week’s worth of salt every day-while eating only two-thirds as much potassium as we should.

Passwater: As far as I am concerned, the most important finding in your book is that an unbalanced, upside-down ratio between potassium and sodium can affect every cell in the body and greatly affect health and longevity. This is not just a blood pressure thing. Please elaborate.

Boynton: Our bodies have trillions of cells, and each and every cell is dependent on the balance between potassium and sodium. These two electrolytes power the cell membranes to move many biochemical compounds in and out of the cells. Potassium and sodium, using energy produced from food “burned” by the cell in the form of adenosine triphosphate (ATP), act as a pump to move compounds through the cell membranes. This is commonly called the “sodium-potassium pump.” The sodium-potassium pump is essential to every cell in your body, and it is a component within all cells of almost all animals on earth-even one-celled animals.

Passwater: That’s an important point. When students learn about the sodium-potassium pump, they are told of its importance in nerve, muscle, gastric or kidney cells, but few appreciate the fact that the sodium-potassium pump is critical to every cell. In fact, the energy used by all of these tiny sodium-potassium pumps amounts to one-fourth of the calories consumed by people in calorie balance. Our bodies wouldn’t spend this much energy on one function unless there was a very important reason. Just what are these pumps doing and why?

Boynton: The pumps actually are proteins in the cell membranes that pull potassium into the cell interiors and push sodium out. Because the pumps move more sodium out than potassium in, they generate a voltage between the inside and the outside of the cell.

Passwater: The passive transport via diffusion would allow the sodium and potassium to equilibrate on both sides of the cell membrane, and thus there would be no electrical charge. However, the active transport of the pump, which requires energy, concentrates potassium inside the sell and sodium outside the cell.

Boynton: Yes, the pump moves three sodium ions out of the cell for every two potassium ions it brings in. Since both sodium and potassium ions have a positive charge of one (valence), the result is that there is a net transfer of positive charges out of the cell.

Passwater: The pumping action against the gradient is brought about by a protein commonly called “sodium, potassium ATPase,” which functions by conformational changes that can attract or repel one of the ions or the other. The conformation change by the protein requires energy from ATP But we still haven’t explained why building up this charge, a voltage across the cell membrane, is so important.

Boynton: Well, the electrical potential, the voltage, is like a battery and is capable of doing work. This is called the “sodium battery.” One of the key things that this sodium battery does is to drive electrical signals along nerves. It also determines the tension and relaxation of muscle cells by its effect on the calcium pump. And cells couldn’t make the proteins they need without the amino acids that are transported through the membrane with the help of the sodium battery. It also enables glucose to enter the cell against the gradient and to become fuel for the energy of the cell to perform all of its functions.

Passwater: OK, I think that our readers get the idea that the potassium-to-sodium balance is indeed critical to the functioning of every cell in our bodies. It appears that if the potassium-to-sodium balance is not right, then the sodium battery does not become fully charged and the electrical potential of the cell membrane is diminished. This, at first, has the effect of stiffening the membrane and decreasing the flow of nutrients into the cell. In essence, the membranes function like aged membranes. The body is aging biochemically. If the voltage further decreases, channels and pores in the membrane may malfunction. Eventually, various illnesses develop. We’ll talk more about the calcium pump later on when we talk about why an imbalance of potassium and sodium may be more to blame for osteoporosis than a lack of calcium.

Now that we have given a simplified explanation of the sodium-potassium pump and its importance to overall health, we should point out to our readers that one of your co-authors, Richard D. Moore, M.D., Ph.D., is a pioneer in researching the sodium-potassium pump. How and when did you meet Dr. Moore?

Boynton: Dick and I have been friends for about 20 years. He is now professor emeritus of biophysics, State University of New York. His 1986 book, “The K Factor” was the seminal book for the public on the importance of the potassium-to-sodium ratio. He also wrote a second book, The High Blood Pressure Solution, which is similar to The K Factor but uses language that is easier for the average person to understand. Both books, I thought, were excellent, and it bears saying that Dr. Moore probably knows more about potassium-sodium relationships and the sodium-potassium pump and its relation to general health than anybody else. We were extremely fortunate to secure his assistance as a co-author.

Meanwhile, it should be pointed out that our book is not a technical book. We don’t dwell on the science of the sodium-potassium pump. Rather, we concentrate on practical aspects and teach readers how easy it is to make the dietary changes that will improve their health.

Passwater: I found the book very clear and reader-friendly, with lots of practical advice. Your other co-author is Mark McCarty, who formerly was your research director at Nutrition 21. How did you meet Mark?

Boynton: When I started Nutrition 21, I hired medical students from the University of California in San Diego to do research for me. There was a succession of five or six very bright kids who helped me out in the early years. I couldn’t afford to hire anybody full time. The brightest of them all was Mark. He was a third- year medical student at the time, and he became extremely interested in nutrition, eventually deciding he would rather be a research biochemist than a medical doctor. So we hired him full time, and he has been enormously important to Nutrition 21. Mark is an extremely bright young man.

Passwater: Well, when a Mensa-qualified person like you calls someone else bright, that is saying a lot. So, as I see it, you have blended your experience as both a supplier of nutrients and a patient who had to learn to balance sodium and potassium, Dr. Moore’s experience with the sodium-potassium pump and Mark McCarty’s medical research experience, and you have written The Salt Solution. What other diseases besides hypertension do you discuss in the book?

Boynton: Initially, we were interested primarily in the high blood pressure/stroke situation, but the more research we did the more it became evident that potassium-sodium imbalance is linked to a number of other diseases, and among these is osteoporosis. In a metaphorical sense, excess salt simply sucks calcium out of the bones. I would say that a high-salt diet probably is a greater hazard for osteoporosis than a low-calcium diet. By merely reducing salt consumption to rational levels, the problem of osteoporosis can be greatly ameliorated.

Passwater: This is due to the effect of the sodium-potassium pump on the calcium pump. Please elaborate a little on the calcium pump.

Boynton: Earlier, we talked about how the sodium-potassium pump uses the energy from food to make a “sodium battery.” The calcium pump removes calcium from cell interiors by letting some of the sodium back in. In effect, the sodium is trying to get back into the cell, drawn by the charge differential. Remember, the cell interior has a negative charge that attracts ions such as sodium. The membrane protein, calcium ATPase, could be called the calcium pump. It is like a wheel that loads up three sodium ions on one side and one calcium ion on the other. This “wheel” also is powered by ATP. Since calcium has a charge of plus two (valence), the net effect is that the negative charge on the cell interior is reduced and calcium is removed…

Passwater: …from the cell. So the imbalance of potassium and sodium results in calcium being forced out of cells. Oops, I seem to have interrupted you. You were discussing other salt-related diseases.

Boynton: We also found a relationship to asthma and clear relationships to gastric cancer, ulcers and, surprisingly, to age-related cognitive memory decline. The data there are very, very impressive. It seems absolutely true that sustained isolated systolic blood pressure is a factor in dementia and in memory decline in older people and, possibly, even in younger people as well.

Passwater: OK, we have introduced all three authors and set the stage. In Part 2, planned for the June issue, we will discuss more specifically the benefits of improving the potassium-to-sodium ratio and the consequences of not doing so. Plus, we will zero in on some easy and practical tricks to improve one’s potassium-to-sodium balance. WF

Part 2: Imbalance Often Leads to Hypertension

In April, we discussed how modern diets, high in processed foods, cause an imbalance between sodium (salt) and potassium that affects every cell in the body and can lead to more than 10 diseases. We interviewed Herb Boynton, co-author of The Salt Solution (along with Richard D. Moore, M.D., Ph.D., and Mark McCarty), and learned how this potassium-sodium imbalance is the cause of high blood pressure (essential hypertension), the main cause of stroke, and contributes to heart disease, memory decline, osteoporosis, asthma, ulcers, stomach cancer, kidney stones, and cataracts, and possibly be involved with erectile dysfunction and rheumatoid arthritis. Clearly, the best way to get potassium and sodium back into satisfactory balance is to eat whole foods. When you eat whole, unprocessed foods, you are not going to get very much sodium, but you are going to get very large amounts of potassium. For 90 persons out of 100, that would be an immense improvement in their overall diets.

Dr. Richard D. Moore is our guest for this column. He received his medical degree from the Indiana School of Medicine and his doctorate in biophysics from Purdue University. He is professor emeritus, State University of New York at Plattsburgh.

Passwater: When people say, “I am not concerned about salt because I am not salt-sensitive” or “I can eat all the potato chips I want, and my blood pressure doesn’t change; therefore, salt is no problem for me,” are they missing the boat?

Moore: Absolutely. It is not simply a question of blood pressure. People can have normal blood pressure and still have serious metabolic problems that result from this potassium-sodium imbalance. In turn, these metabolic problems can lead to any of more than 10 diseases, including osteoporosis, asthma, kidney disease, kidney stones, mental decline, stomach cancer, ulcers and others.

Passwater: To help people recognize foods and diets that cause potassium/sodium imbalances, you have devised the “K Factor” to simplify the potassium-to-sodium ratio concept. Instead of having to mentally juggle and compare the two large numbers for potassium and sodium levels, the K Factor is one number that is easier to handle for comparisons.

Moore: “K” is the chemical symbol for potassium, derived from the Latin word kalium. The higher the K Factor, the better the food or diet. Soybeans have a K Factor of 340. Corned beef hash has a K Factor of about 0.37. Selecting mostly foods with a high K Factor will allow you to include some foods with poorer K Factors. The K Factor of the total diet is the important number.

Passwater: You recommend that diets have a K Factor of at least four. Why?

Moore: When I looked at all the published data for both potassium and sodium in the diet — or in the urine which reflects the diet-and then looked at the incidence of hypertension, I could see that, as the K Factor got above one or two, there was significantly less hypertension (high blood pressure). I chose a K Factor of four because of all the diets where there was any significant occurrence of high blood pressure, the K Factor was less than three. Actually a diet with a K Factor of three or above is not bad, but, for practical purposes, I think a K Factor above four is a better goal. Of course, even higher than that would be better in terms of general health. I say this based upon the fact that our ancestors had a K Factor of about 16 to 1 and we evolved having a K Factor something like that.

Passwater: You’re saying that modern diets have a poorer K Factor than diets based mostly on whole, unprocessed food?

Moore: Let me give you a very interesting statistic. In 1985, The New England Journal of Medicine published an article titled “Paleolithic Nutrition.” The authors, who had credentials as anthropologists specializing in the Paleolithic era, determined that, on average, our caveman forebears got around 11,000 mg of potassium daily and about 700 mg of sodium. This, by the way, is about the same ratio that modern-day hunter / gatherers have. It works out to a dietary K Factor of 15.7.

Today, in the United States, that 11,000 mg has shrunk to 2,500 mg of potassium. Meanwhile, the sodium intake has increased from 700 mg to 4,000 mg. This is a K Factor of 0.6. You would not expect that any animal species, human or otherwise, could live for several million years with a huge potassium intake and rather modest amounts of sodium and then suddenly flip-flop this ratio with impunity. The scientific literature supports our conclusions.

There is absolutely no doubt that the imbalance thereby produced influences at least ten serious diseases and very probably several others. This is why we think The Salt Solution is an extremely important book, and we hope that people will read it. It will enable them to correct this huge dietary error. A daily ration of 2,500 mg of potassium is far too little. And, of course, as virtually everyone should know, 4,000 mg of sodium is at least ten times as much sodium as people need.

Passwater: What about the diets of the remaining “primitive” peoples of today?

Moore: One factor that was a big influence on us in writing our book was the work done by Drs. Dennis Burkitt and Hugh Trowell. They wrote the book Western Diseases and Refined Carbohydrate and Disease, as well as several others. In Western Diseases, Dr. Trowell states, “Ethnic groups who do not add common salt to their food have lifelong low blood pressure; no exception to this generalization has been traced.” That really made an impression on me. The Yamomano Indians in Brazil have excellent blood pressure and they also — hear this! — get less than 100 mg of sodium daily versus the 4,000 mg that the average person in the United States consumes.

Passwater: At least our readers understand the value of eating whole foods and holding back on their intake of heavily processed foods.

Moore: You’ve hit on something that I really would like to emphasize; if you take any unprocessed fruit or vegetable, in 99% of all cases, such foods will have 20 to 100 times as much potassium as sodium. Unprocessed foods have a high K Factor, that is, much more potassium than sodium. This is because the sodium-potassium pumps in their cells work to keep potassium in.

If you take foods like meat, fish, fowl, eggs and dairy products, 99% will have at least three, four or five times as much potassium as sodium. The key factor is to eat whole unprocessed foods. If people ate only whole, unprocessed foods and used salt modestly, there would be no problem with potassium-sodium imbalance. Nevertheless, The Salt Solution and The High Blood Pressure Solution list foods that are particularly high in potassium and also list the major sodium villains.

Passwater: Are we engaged in a hopeless battle? As we know, for some reason, people tend to prefer the convenience or the taste of processed foods. It has just gotten out of hand.

Moore: The statistics show that 80% of the calories consumed by Americans today come from processed foods. Most of these processed foods not only have huge amounts of salt added, but in a great many cases, large amounts of potassium have been depleted. Typical of this is polished rice; three-fourths of the potassium in polished rice disappears. It is about the same with wheat. About three-quarters of the potassium is removed from the wheat berry by reducing it to white flour. We have a double whammy here, with huge amounts of salt being added, and, in a great many cases, potassium being removed.

The shame of it is that it is so easy to increase potassium. As I mentioned, just about any whole food that has not been processed is loaded with potassium. This includes bananas, oranges, apples, rutabagas and cabbage. Potatoes are one of the richest sources of this mineral. A big baked potato, for example, will have about twice as much potassium as a banana but a lot of people will add salt to their baked potato in some form or another, and that is counterproductive

Passwater: What about cow’s milk?

Moore: Cow’s milk has a K Factor of 2.8. It also is true that even though ocean fish live in a high-salt environment, they still have three to five times as much potassium in the flesh as sodium. So don’t rule out salmon, tuna, sardines or any marine fish, because they all are quite high in potassium and quite low in sodium. If you eat the canned variety of these fish, however, you have to be careful they are not loaded with salt.

Passwater: Is there a good way to supplement diets to improve the potassium content? How about salt substitutes?

Moore: The Finnish people developed a product that they call “PanSalt,” which is known in the United States as Solgar Heart Salt or Cardia Salt. Most people can’t tell it from ordinary salt, yet it has far less sodium than ordinary salt. It also has quite a lot of potassium in it. Over in Finland, the results have been utterly remarkable. Substitution of this flavoring alternative has caused an astonishing 60% drop over the past 20 years in premature deaths from stroke and heart disease, and a drop of 10 points in average diastolic (bottom number) blood pressure. I must add that these people are also admonished to eat high potassium foods and keep their sodium consumption down in general. Whatever the reason, there has been an astonishing reduction in both high pressure and stroke in Finland, where consumer acceptance of PanSalt has been so strong that there are now more than 1,000 processed foods seasoned with the product. This is a significant step.

Passwater: Tell us more about this salt substitute and the studies done with it.

Moore: Solgar Heart Salt/Cardia Salt contains 54% less sodium (by volume) than regular table salt and also contains 176 milligrams of potassium and 13 milligrams of magnesium in each quarter-teaspoon serving. An important factor is that it doesn’t taste bitter as many other salt substitutes do that contain potassium. A taste test conducted by Tuft’s University Health & Nutrition Newsletter (May 1997), found “most tasters found Solgar Heart Salt/Cardia Salt more palatable – and more like salt – than the other salt replacers they tried.”

We report in The Salt Solution a clinical study of 24 patients being treated for high blood pressure where Solgar Heart Salt/Cardia Salt was substituted for regular salt, in combination with patient education and lifestyle modification, significantly reduced their systolic by pressure by 8.8 points, on average, and their diastolic blood pressure by 7.1 points. The researchers remarked, “The significant decrease in blood pressure was seen in patients who were taking stable doses of antihypertensive medications, despite constant weight and no measurable increase in exercise.” (Phillips, 1998)

Another clinical trial that we report involves 233 hypertensive patients who substituted Solgar Heart Salt/Cardia Salt for table salt for six weeks significantly reduced their systolic blood pressure by 4.2 points and their diastolic blood pressure by 2.7 points. The researchers concluded, “Solgar Heart Salt/Cardia Salt tastes like regular salt and provides a practical means to help patients achieve a diet lower in sodium and higher in potassium.” (Whelton, 1997)

Still another clinical trial of 30 subjects found that the substitution of Solgar Heart Salt/Cardia Salt for regular table salt significantly lowered systolic pressure by 7.4 points and diastolic pressure by 3.6 points in just five weeks. (Kawasaki and Itoh, 1996)

Passwater: The blood pressure decreases may seem relatively small, but we should keep in mind that these studies are short and that the differences can be significant over the long term. As shown by the Finnish studies, the effect on stroke was quite dramatic.

Moore: Readers of The High Blood Pressure Solution report very dramatic decreases to below 120/80, even if starting the program over 160/110.

Passwater: A health claim recently has been approved that says, more or less, that food labels can mention potassium in relation to stroke.

Moore: It is a big step forward. The Tropicana Orange Juice people are advertising this fact, which is very much to their credit. But it bears emphasizing that this is not true of just orange juice, but is true of almost all whole fruits and vegetables. Most fruits, vegetables and legumes are loaded with potassium, and most of them have very little sodium. The only vegetable that I can think of that has fairly heavy amounts of sodium is celery, and it doesn’t have all that much. It still is very favorable in terms of potassium content.

Passwater: Average citizens, if they know about potassium at all, frequently come to this knowledge only after a doctor has prescribed a diuretic (to reduce excess retained water) and then told them to eat bananas to replace the potassium that has gone out with the water. The thinking appears to be that high blood pressure and too much water retention are not a good combination. So let’s get rid of the water. But, in the process, minerals such as potassium also are depleted.

Moore: First of all, The Salt Solution is not anti-drug. However, many people can restore their blood pressure to normal limits simply by increasing potassium and by reducing sodium from this ridiculously high 4,000 mg a day to somewhere between 500 and 1,000 mg a day.

Passwater: OK, I believe that we have established the practical benefits illuminated by your findings. Now, let’s chat about the details of the work itself, which, in my opinion, is Nobel Prize stuff on a level with the discoveries of the structure of DNA and the Krebs Cycle. You’ve helped elucidate one of the cell’s basic mechanisms, and, along the way, you seem to have proven the connection between potassium-salt balance and blood pressure. What got you started?

Moore: I got into this not because I was interested in any particular disease, but because I was interested in basic physical mechanisms of how the cell works and how the sodium/potassium pump is involved. When I was a graduate student at Purdue’s Physics Department in 1958, I decided to work on that mechanism. I had heard Professor Lorin Mullins, head of the Department of Biophysics at the University of Maryland, refer to calculations that indicated that the sodium pump in a resting cell used almost a quarter of all the energy available. Any mechanism that uses that much energy has got to be important. If you looked at the power distribution in a city and you found one operation in the city was using a quarter of all the electricity, you would think it was an awfully important operation.

When I did some of my early studies about the functioning of the sodium/potassium pump, I uncovered some clues that led me to think that insulin might be affecting it. Later, my group-and also that of Dr. Torben Clausen in Denmark-demonstrated that insulin does indeed regulate the sodium/potassium pump. That is pretty well established now. Additionally, with the help of research by Dr. Ken Zierler at Johns Hopkins University, we know that the action of insulin on this pump occurs at concentrations even lower than those required to affect glucose uptake in cells. This is another clue that insulin action on the pump is awfully important.

Then some theoretical analysis suggested that insulin might be raising the pH (measure of acidity or alkalinity) inside cells, thus making the cell interiors more alkaline. We did experiments in that area, and we were the first to show that is indeed the case. People used to think pH inside cells was constant. Before we did the experiments, I made a habit of asking any biologist or biochemist I would meet at a scientific conference-at least three dozen, I would estimate-“Is the pH inside the cell variable or constant?” The answer invariably was that it had to be a constant. “Why,” I would ask. “Because every enzyme is affected by pH,” they would invariably answer. It is true that every enzyme is affected by pH, and everyone was assuming — as I had originally — that the pH in the cell was therefore constant.

Of course, the corollary hypothesis is that there is a pattern to the enzyme pH profile, which is indeed the way it turns out. The pH is not constant, but is a physiological variable. The pH level is involved with regulation of glycolysis, and to some extent, cell division.

Three or four people besides myself had begun working on regulation of pH. Before long, a couple of the others showed that one way to accomplish this regulation is via the sodium/hydrogen exchange pump, whereby sodium leaks back into the cell due to a difference in its energy gradient. Technically, the electrochemical potential — or free-energy gradient — provides the energy to move a proton, which is acid or a hydrogen ion (H+) out of the cell.

That was a possible way to explain our observation of insulin-increased pH. So we undertook experiments that confirmed our theory. Those experiments, incidentally, were very gratifying because they were based on a thermodynamic mathematical analysis that makes predictions which we verified, namely, that at a certain calculable value of extracellular sodium, if the sodium is lowered by replacing it with magnesium or sucrose, the sodium/hydrogen exchange pump no longer works. Further, if the sodium is lowered below that point where the insulin stimulated it, it should make the pH more acidic. And that’s what actually happens. This is neat: just by changing the sodium outside the cell, you can convert the action of insulin on glycolysis from stimulation to inhibition.

Passwater: In other words, the pH would go down (more acidic) instead of going up (more alkaline), which is what it normally does.

Moore: Indeed, that is the case. Our work was pretty decisive, but the finding has been ignored by most researchers. But a lot of our other findings on insulin and pH haven’t been ignored. In fact, there are a lot of researchers following up on this now. What’s disappointing is how few of them are referring back to the original papers written by our group.

Parenthetically, we showed this is the way that insulin affects and stimulates glycolosis: if we lowered the sodium outside the cell below this particular value that can be calculated, we found that insulin-instead of stimulating glycolosis-inhibits it. All this without adding any foreign chemicals. This is a pretty convincing conclusion.

In the process, other people with whom I had worked, including my former major professor, showed that besides the sodium/hydrogen exchange pump, there is a sodium/ calcium exchange pump. This sodium/ calcium exchange pump moves three sodium ions into the cell in exchange for one calcium ion going out.

Passwater: Let’s remind our readers that calcium ions have a charge of “plus two,” whereas potassium ions and sodium ions each have a charge of “plus one.”

Moore: Yes, and now this is a stociometric ratio of 3 to 2 in terms of charges and 3 to 1 in terms of ions. This is opposed to the sodium/potassium exchange pump which is not stociometric.

Passwater: For our non-chemist readers, stociometric merely means a constant proportion is involved. Chemists use this term to describe relationships in which the proportion of the elements involved follow the Law of Constant Proportions.

Moore: The sodium/potassium pump does not have a fixed ratio of sodium to potassium ratio, although textbooks find it convenient to say it is a 3 to 2 ratio.

The sodium/calcium exchange is electrically not neutral, so, therefore, the membrane potential affects that. A higher membrane potential will tend to make that pump move calcium out. At each cycle, that pump moves a positive charge in. The other thing that will make it move calcium out is lowering the sodium inside the cell.

About the time all this was worked out, a researcher called me about an article that I had written about a compound that could stimulate the sodium pump. In the paper, I had mentioned that this compound acted like a “super potassium ion.” He was interested in that, and I wondered why. It turned out that he was doing experiments on high blood pressure and he, as well as others, had found a substance in the blood of people with high blood pressure that tends to inhibit the sodium potassium pump.

That was when the proverbial light bulb came on in my brain. I realized that if you inhibit the sodium/potassium pump, of course sodium is going to build up inside the cell. Inhibition of the sodium/potassium pump also causes the plasma membrane (the outermost of the cell’s “skin”) potential to decrease.

Both of these effects are going to affect the sodium calcium exchange pump in a way that will make it work less actively. Therefore, you are also getting an increase of calcium inside the cell. It is possible, in fact, to calculate exactly what the limits of that increase would be. I believe it was Dr. Mordecai Blaustein, head of the Department of Physiology at the university of Maryland, who showed something like a 5% increase in sodium inside the cell. And this, he said, results in about a 150/cr20% increase in calcium in the cell. It is something like that order of magnitude. Drs. Blaustein and Mullins were both at the University of Maryland, and their groups, as well as a group at Cambridge, had worked out this sodium/calcium exchange pump.

So we now know that this mechanism, the sodium/ calcium pump, is very sensitive to a slowdown of the sodium/potassium pump. Therefore, calcium is going up in all the cells of the body, because we know that a decrease in the potassium and an increase in the sodium in people with high blood pressure is occurring in all the cells of the body-not just the arterial wall cells. But, if one thinks for just a moment-as this researcher who called was thinking: the smooth muscle cells around the small arteries or arterioles control blood pressure. Add to this the fact that the trigger for causing muscle contractions is calcium, and it becomes obvious. It was one of those things where two and two were sitting there in front of me and I hadn’t bothered to add them together.

What suddenly came to me was the recognition that as calcium goes up in those muscle cells, the muscles are stimulated to contract and constantly constrict the blood vessels. This, of course, raises blood pressure. Dietary sodium can be the cause of the increased calcium in these cells and the resultant constricted blood vessels. Potassium would, of course, stimulate the sodium/potassium pump and, thus, indirectly, through the resulting increase in sodium-calcium exchange, decrease the intracellular calcium and allow the muscles in the blood vessel walls to relax.

It immediately hit me-why would anyone want to use this so-called “super potassium” instead of using potassium itself? After all, the compound that I had reported on as a “super potassium” presented problems. I had reported in the article that this so-called “super potassium” punches holes in cell membranes over time. I wouldn’t go near it, It was bound to be extremely toxic.

Of course, potassium ions are natural things and can’t be patented. However, new compounds can be patented and used as drugs. So I tried to speak to the people at the Hypertension Society about the benefits of the natural compounds of potassium over the synthetic drugs, but they didn’t want to talk with me or any of my group or the other researchers that I mentioned. That’s why I wrote my first book with Dr. George D. Webb — The K Factor: Reversing and Preventing High Blood Pressure without Drugs(Macmillan, 1986) Why deal with possible dangerous drugs when simple natural substances can do better and more safely?

I wanted this information out in the physicians’ and public’s hands.

The idea for writing The K Factor wasn’t mine. The other researchers also were perturbed because no one would listen to the basic truths we were unearthing. Dr. Mullins especially was annoyed because he had had a similar experience. He couldn’t get the cardiologists to listen to the thesis that sodium-calcium exchange is involved with the action of digitalis-increased strength of contraction even though the facts were published in the scientific literature. So he wrote a book about it, We knew we weren’t going to get the Hypertension Society to pay attention, so we decided to leapfrog them and go directly to the practitioners and public. I also took the message to the radio and TV airwaves.

Initially. I thought that supplemental potassium alone would be enough to lower blood pressure. But, as I got into it further and really thought it out, I could see it is a lot more than that. A low ratio of potassium to sodium may be the cause of high blood pressure, but blood pressure is not the whole problem. It’s very much like dealing with a fever that is caused by an infection.

The elevated body temperature, if it gets high enough, can cause damage, but treating the fever without treating the infection is not the total answer. We try to bring this out in The Salt Solution and in The High Blood Pressure Solution. This potassium-sodium imbalance is a big, big health problem. But, it has been hard to get people to pay attention to it, Now, we are finding that physicians who treat stroke patients are becoming interested. It seems that treating strokes is one of the most discouraging things you can do in medicine.

As I indicated, this potassium/ sodium imbalance is present in every cell in the body. We now have very strong evidence-not totally conclusive, but very strong evidence-that this potassium/ sodium imbalance also is a cause of insulin resistance. Furthermore, this potassium/sodium imbalance, which contributes to insulin resistance also is associated with an abnormal metabolism of carbohydrates and fatty acids, and may contribute to causing Type 2 diabetes. I just mentioned that the Hypertension Society people did not want to listen to us. Well, we had the same experience with the Diabetes Society when Dr. Ken Zierler and I tried to show them the link between sodium and insulin resistance.

I predicted in 1986 in The K Factor, that this potassium/sodium imbalance would be causing other disease states and I mentioned it again briefly in my 1993 book, The High Blood Pressure Solution: Natural Prevention and Cure with the K Factor. (Healing Arts Press) Now, The Salt Solution documents the fact that there are indeed quite a few other disease states caused by this potassium/ sodium imbalance. These relationships all have been discovered in the past five to seven years, and my guess is that we will find even more.

Passwater: I understand that you have updated The High Blood Pressure Solution and that the revision is in press now.

Moore: Correct. There are a couple of things worth noting with regard to high blood pressure. One is that vegetarians almost never get high blood pressure. That simple fact should say to people in flashing neon lights that hypertension is obviously something about diet. First, we know, from other lines of evidence, that there is a potassium/ sodium ratio which is extremely high in that kind of diet, and you don’t have to be a vegetarian to get that kind of ratio.

What I did was rank diets of various groups of peoples by the ratio of potassium to sodium in the diets. I found that when you have people with diets better than three-to-one potassium over sodium, you don’t see any significant incidence of hypertension. When the diets get down to two-to-one, you begin to see a noticeable incidence of hypertension and when they get down below a one-to-one ratio, there is a lot of hypertension. I chose four-to-one to allow for a margin of error. Of course, we evolved on a much higher ratio than that, about 16-to-0ne. Even relatively recently in history, before food processing, except for the peoples using salt to cure things, the ratio was above four-to-one, closer to ten-to-one. Even meat has a ratio of a little over three-to-one. Kosher meat is probably higher because most of the sodium is in the blood, which is eliminated.

The experience in Finland shows what can be accomplished by just going part way — by using a salt substitute that replaces 28% of the sodium with potassium and another 12% of the sodium with magnesium (a total of 40% of the sodium replaced, and with significant amounts of the “good guys” added). The Finnish experience doesn’t come anywhere near a 4 to 1 ratio — it’s not even up to a 1 to 1 ratio — yet it was enough to reduce strokes and heart attacks by 60% throughout the nation.

The population of Finland is over five million, and this certainly is larger than the number of participants in any of the drug studies. The biggest drug study on hypertension involved only 17,000 people. The fact that this was done in a whole country and they succeeded in getting this salt-substitute used instead of table salt in food processing, in fast food restaurants etc., as well as at home, shows what can be done. It’s simply amazing that few in this country seem to be aware of this even though the information was published in 1996.

Passwater: How about the DASH (Dietary Approaches to Stop Hypertension) diet studies?

Moore: The DASH diet is a step in the right direction, but it doesn’t go far enough. It is very frustrating to me because it is entirely based on empiricism and “group think.” Those responsible for the DASH diet just looked at evidence showing that there is a little bit of help to be derived from potassium, a little bit of help from sodium and so on. They put the DASH diet and clinical studies together without an understanding of the fundamental relationship between sodium and potassium. That is, they didn’t understand the very important point that, because of osmotic equilibrium, the sum of the sodium and potassium inside the cell is very close to constant (within about 2%).

Therefore, it is virtually impossible — not just because of the sodium/potassium exchange pump and all these things in the body which tend to move sodium in one direction and potassium in the other direction, but just because of physical reasons (the laws of physics) — to lower sodium inside the cell without the involvement of potassium. Potassium has such an important role in the body. You can’t lower the sodium without replacing it with potassium. That is the key: there is just no sense in talking about either sodium or potassium alone! This is so awfully important. It is one point that I would love to get across to the medical profession, but up until now most practitioners have failed to get it.

Therefore, the vast majority of those studies that have been done with dietary sodium were very poorly designed, scientifically. They didn’t take into account that this is not a one variable situation. There are two variables that must be taken into account together! The two are linked, and you have to look at them together if you are going to see a pattern.

Passwater: Everyone in clinical studies is trained to look at one variable at a time, no wonder that synergistic effects are missed.

Moore: Not in physics-that’s where my background is.

Passwater: It’s a shame that more biochemists don’t know a little about biophysics.

Moore: In medical school, this idea of trying to change one variable at a time has become a religion. But the only way you can do that is with drugs. You can change an intake of a drug, i. e. one variable, but once you look at what is going on inside the body, you discover that everything is interlinked. Thus, it is impossible to change one variable without all the others also shifting.

Passwater: I call that polypharmacy, and it’s just too complex for the scientific method that people have been trained to use. All the nutrients seem to have interactions, and you just can’t study them individually.

Moore: That’s right. Nutritionists are still talking about sodium requirements. It depends on the potassium levels in the diet, too.

Passwater: It goes on and on. We try to get the message across. Eventually, clinical researchers will design clinical studies to look at more than one variable at a time. In the meantime, I guess we’ll have to put up with some frustration.

Thank you Dr. Moore for chatting with us about potassium-sodium ratios and hypertension. Next month, we’ll be joined by your Salt Solution co-author, Mark McCarty. WF

Part 3: Old News That Bears Repeating

Over the past few issues, we have been talking with the co-authors of The Salt Solution about the ways in which too much salt and not enough potassium in the diet-common for modern processed-food diets-causes an imbalance between sodium (salt) and potassium that affects every cell in the body and can lead to more than 10 different diseases.

A major part of the problem is that salt is a hidden component of much processed food. In fact, processed food accounts for up to 75% of the salt intake in a typical American diet. In general, it can be said, only 15% of salt intake comes from the saltshaker. It is easy to consume an extra teaspoon of salt (about 2,500 mg) from processed food without even being aware of it Another part of the problem is that food processing removes potassium.

In April, Herb Boynton explained how this potassium/ sodium imbalance affects every cell in the body and can lead to a slew of ailments, ranging from hypertension to cataracts and possibly even erectile dysfunction. In June, Dr. Richard Moore elaborated on how the ratio of these nutrients, which he calls the “K Factor,” keeps the arteries under constant constriction, raising the pressure needed to pump blood through them.

In this month’s installment, co-author Mark McCarty tells us about the link between a low K Factor diet and high blood pressure, stroke, osteoporosis, kidney stones, asthma, stomach cancer and ulcers. Mark absconded from the third year of medical school some years ago to devote himself to applied nutrition, a field that he felt was grievously neglected by the medical establishment. For many years, he was research director for Nutrition 21; where Herb Boynton, a co-author of The Salt Solution, was the founder and president. In that setting, they worked together to develop, test, and market some important cutting-edge supplements, most notably organic selenium and chromium picolinate. Mark is currently president of NutriGuard Research, a supplement company he helped to found, and he also holds consulting positions with Pantox Laboratories, Nutrition 21, and Natural Alternatives. To date, he has authored over 100 publications in the refereed biomedical literature, most of which have appeared in the journal Medical Hypotheses.

Passwater: Mark, let’s review some of the more obvious relationships of the sodium-potassium imbalance to overall health. May we begin with high blood pressure?

McCarty: The link between too much dietary salt and high blood pressure certainly is very old news, but the fact that poor potassium nutrition plays an equally important role in the genesis of high blood pressure and stroke, has, until recently, largely been ignored. The ratio of these two nutrients affects the efficiency of the sodium-potassium pumps in all of the cells in the body-including key vascular tissues such as smooth muscle cells and the endothelial inner lining of the blood vessels. These pumps are vigorously effective if one’s diet is high in potassium and low in salt-which is the way that mankind evolved. But if you reverse that ratio, as modern diets typically do, these pumps function less efficiently. This pump failure can impair the ability of the endothelium to release protective nitric oxide-the hormone-like factor that helps to prevent blood clots, keep blood vessels properly dilated, and ward off the inflammatory process of atherosclerosis. Another consequence is that the level of unbound calcium in vascular smooth muscle cells tends to increase, causing these cells to contract, and thus raising blood pressure by increasing the resistance to blood flow.

Passwater: It also is old news that high blood pressure is a major risk factor for stroke. Aren’t there studies that show that stroke risk increases with salt intake?

McCarty: Salt intakes appear to have a greater impact on risk for stroke than on risk for high blood pressure. This finding emerged from a study in which average urinary sodium levels in various regions in Europe were correlated with the average blood pressure and the incidence of stroke in these regions. The correlations between urinary sodium and stroke risk turned out to be much tighter than those between sodium and blood pressure! Likewise, in certain types of rodent, salt intake has a greater impact on the incidence of stroke than on blood pressure. Another important thing to realize is that, although high blood pressure greatly increases risk for a stroke, the majority of Strokes occur in elderly people whose blood pressure is considered to be Anormal.@ The implication of these findings is that, even if one’s blood pressure isn’t notablyelevated on one’s current intake of salt the, salt in one’s diet may nonetheless be increasing one’s stroke risk!

Passwater: How about salt’s effect on osteoporosis?

McCarty: The more salt one eats, the more calcium the body loses in urine. The calcium level of an individual’s blood is tightly regulated because the level of blood calcium has a major impact on the heart’s electrical rhythm and other vital physiological processes. When a lot of salt is eaten, the immediate impact of the resulting urinary loss of calcium is a transient drop in blood calcium that has to be immediately corrected. The hormone that is produced to return the blood calcium to optimal levels, parathyroid hormone, aids the efficiency of calcium absorption from the diet, but it also has the unfortunate effect of leaching calcium from the bone mineral. On the other hand, potassium rich diets are protective in two ways: the increased potassium intake helps the kidneys to excrete salt more efficiently, so that salt can’t promote as much calcium loss in the urine. Plus, if one’s potassium comes from natural foods, the negatively charged organic molecule associated with that potassium can be metabolized to release bicarbonate, which has an alkalinizing flirt on the body that protects bone from the adverse impact of acid-generating proteins. hitting it simply, if you cat a low salt diet that is high in potassium-rich foods anal in moderate in protein, your bone health should benefit greatly.

Passwater: This might also of affect the risk for kidney stones.

McCarty: Yes, the increased amount of calcium excreted in the urine when one eats a salty, potassium-depleted diet means that there is more opportunity for calcium kidney stones to form. Surprisingly, unless the diet is extremely high in calcium, reducing dietary calcium doesn’t have much impact on the amount of calcium in the urine-and a low-calcium diet actually can make matters worse by increasing the intestinal absorption of the dietary compound oxalate.

This may lead to the formation of calcium oxalate kidney stones. One study has determined that people whose diets have low dietary potassium-to-sodium ratios are three times more likely to form kidney stones than those with high potassium-to-sodium ratios.

Passwater: What’s the connection between a poor K Factor (potassium-to-sodium ratio) and asthma?

McCarty: Several scientists have proposed and in some measure confirmed a link between salty diets and asthma; we discuss their findings in The Salt Solution. Salty diets seem to exacerbate asthma primarily in males. Why females seem to be at leis risk in this regard isn’t clear. A recent study shows that salty diets can make exercise-induced asthma worse. There is suggestive evidence that inefficient function of the sodium-potassium pumps can make the bronchial tubes more sensitive to bronchoconstrictors such as those released by exposure to allergens.

Passwater: What about stomach cancer and ulcers?

McCarty: The highest rates of gastric cancer and gastric ulcers are seen in countries where diets are high in heavily salted foods. Heavy salting of foods is practiced to prevent microbial contamination of food in societies that lack refrigeration; salt is not very efficient for this purpose, however, and, as a result, molds or bacteria frequently generate mutagens in salt-preserved food. This isn’t the fault of salt per se, but rather of lack of refrigeration.

On the other hand, there is some reason to believe that high-salt diets can be directly damaging to the stomach lining, that they increase the ability of the bacterium most responsible for gastric diseases-Helicobacter pylori-to colonize the stomach lining and do its dirty work. What is clear is that, when societies gain access to refrigeration, the use of salt preservation goes down and rates of gastric ulcer and gastric cancer plunge. This was true throughout the world during the 20th century. Today, gastric cancer is one of the less common cancers in the U.S., but it was one of our major cancer killers in the 19th century. Unfortunately, there is still a lot of horrible poverty throughout the world, and gastric cancer is second only to lung cancer as the chief cause of cancer mortality worldwide.

Passwater: You discuss other conditions in The Salt Solution, as well as a practical plan to improve one’s dietary K Factor. Some of these links between salt and illness are well-known, but some are new. You have written extensively about your research over the years. What do you offer that is new in The Salt Solution?

McCarty: I think perhaps the most interesting novel contribution I made to the book deals with senile dementia and the rarity of this disorder among the indigenous people of the tiny island of Kitava of f the coast of Papua New Guinea. 1 encountered the work of Dr. Staffan Lindeberg in the process of doing library research for the book. Dr. Lindeberg is a Swedish cardiologist who has a considerable interest in preventive medicine. He has an avid interest in the impact of dietary factors on health and on the relative immunity of certain third-world peoples to many of the diseases that are prominent killers in Western society. In particular, he has long been interested in the association between dietary salt and hypertension. It is well-documented that all peoples whose traditional diets have not included added salt are essentially immune to essential hypertension. I don’t know of any exception to this generalization.

Passwater: How about vegetarian diets?

McCarty: Vegetarian diets-especially if they feature potassium-rich whole foods-often tend to decrease blood pressure for a variety of reasons. If they are heavily salted, however, they don’t provide absolute protection from hypertension. For example, people in rural China typically eat a quasi-vegetarian diet, but are highly susceptible to stroke and hypertension because their diet has an outrageous salt-to-potassium ratio. The fact that white rice is a very lousy source of potassium doesn’t help. They get about three times as much sodium as potassium. I think that as they incorporate more fatty meats and become overweight, the problem is likely to get worse.

I certainly am in favor of a vegetarian diet. I am a vegan myself, because I think that that’s the type of diet that will provide the best overall health protection. However, a vegan diet is not inherently low in salt, so I have to make a special effort to keep my salt intake relatively low. A lot of vegetarians make up for the lack of animal products and grease in their diet with an increased intake of salty condiments. This is a big mistake; they may just be exchanging a Western way of premature death-heart attack-for an Eastern way-stroke! A lot of health-food-store products that brag about how organic and vegetarian and low in fat they are, are awash in salt. There is just too little awareness on this crucial point-which is why we needed to write our book.

Passwater: Mark, thanks for going over some of this with us. I think we are now in a better position to appreciate your new data on how a sodium-potassium imbalance may be implicated in the development of senile dementia and even, possibly, Alzheimer’s disease. In our next issue we’ll return with you and go into more detail on this novel insight. WF

Part 4: Potassium, Sodium and Dementia

This segment concludes our four-part interview with the three authors of The Salt Solution a landmark book that outlines what is perhaps the greatest danger in the American diet – too much salt and too little potassium.

In this month’s installment, co-author Mark McCarty tells us about the link between a low K Factor diet and dementia. As you may recall, Mark was a medical school “dropout” some years ago, who then devoted his career to applied nutrition. He has long been a colleague of Herb Boynton, the founder of Nutrition 21 and another of the co-authors (along with Richard D. Moore, M.D., Ph.D.) on The Salt Solution. Mark is currently president of NutriGuard Research, a supplement company he helped to found, and he also holds consulting positions with Pantox Laboratories, Nutrition 21 and Natural Alternatives. To date, he has authored over 100 publications in the refereed biomedical literature, most of which have appeared in the journal Medical Hypotheses.

Passwater: In the July issue, we left off with a discussion of Dr. Staffan Lindeberg and some fascinating discoveries he made about the indigenous people of the tiny island of Kitava off the coast of Papua New Guinea. Specifically, you said that he claimed to have found no evidence of senile dementia among this population. May we get back to Dr. Lindeberg and his discoveries?

McCarty: Sure. Naturally, Dr. Lindeberg is fully aware of the evidence that essential hypertension, as well as the age-related rise of blood pressure, are virtually absent in low-salt societies. But he thought it would be interesting to see whether he could carry this inquiry further and determine whether avoiding salt and hypertension would have a correspondingly favorable impact on risk for stroke. Actually, some recent epidemiology suggests that salt intakes have a more impressive impact on stroke risk than on hypertension risk or on blood pressure. In other words, salt increases your risk for stroke in ways that have nothing to do with blood pressure-implying that a salty diet may be dangerous for one’s cerebrovascular health even when blood pressure is considered normal. And everyone should be aware that, whereas high blood pressure can greatly increase the risk of a stroke, the majority of elderly people who have strokes in fact have “normal” blood pressure!

Dr. Lindeberg became aware of an island off the coast of Papua New Guinea called Kitava where the residents have never added refined salt to their food. In fact, there are very few aspects of Western civilization that have caught on there with the exception of tobacco smoking. Most of the adults are tobacco addicts, and they import cigarettes from the West. But aside from that, they incorporate Western foods only to a trivial extent and, in particular, they have never imported salt or added refined salt to foods. They do cook in seawater to some extent, so that their diet is by no means salt-free, but Dr. Lindeberg was able to estimate that they probably don’t get much more than 1,000 mg of sodium a day, which means their salt intake is probably about a quarter of what it averages among people in the United States.

Dr. Lindeberg realized that Kitava offered us a priceless-and probably fleeting-opportunity to examine the impact of unsalted diets on risk for stroke and other vascular disorders. So he organized a Swedish scientific expedition to Kitava and spent a number of months getting to know the Kitavan people and conducting extensive clinical examinations in an effort to determine what proportion of elderly Kitavans had suffered a stroke or had heart disease. ‘There are about 2,500 people on the island, a fair percentage of whom are over 70, so he had plenty of people to examine. Lindeberg had an excellent translator with him, and the Kitavans were very helpful and articulate. But they initially were wary about the drawing of blood. One of the big heroes of the whole project was a very old Kitavan man who, after having his blood drawn, walked around the whole rim of the island just to demonstrate to his colleagues that blood drawing doesn’t harm you!

Dr. Lindeberg conducted physical examinations on a large number of elderly Kitavans, with the intent of eliciting any evidence that they may previously have suffered a stroke or heart attack, or had coronary heart disease. But he also supplemented this information by asking the whole tribe whether they were aware of any person in the tribe who had experienced symptoms suggestive of a heart attack or stroke. The bottom line is that he was unable to unearth any evidence that anyone on the island had ever suffered a stroke or heart attack! Obviously, he wasn’t able to completely rule out that possibility, but it was quite clear that if these disorders existed at all on Kitava, they were extremely rare. The closest he came to a suggestive episode was a story he heard independently from several different people about a man in his 70’s who was walking on the beach and fell over dead for no apparent reason.

This incident occurred in the late 19th century! This should give you an idea of how well the Kitavans hang on to their history! In any case, Lindeberg was completely successful in confirming his suspicion that lifelong consumption of a low-salt diet confers almost total immunity from stroke. Back during the early 20th century, there were reports that stroke was extremely rare among black Africans whose diets were low in salt and who seemed immune to high blood pressure-but Lindeberg’s study provides even more convincing documentation of this point.

Passwater: Please tell us more about their diet.

McCarty: It is quite interesting. They get the majority of their calories from tropical tubers, namely yams and sweet potatoes, which are of low caloric density and extremely high in potassium per calorie. They have no cereal products in their diet, except for a bit of corn in the autumn. Grain products, even whole grain products, usually are not very high in potassium. Fruit, coconuts, greens, wild beans, and a small amount of fish-about 5% of calories-round out their diet, which thus is “pesco-vegetarian.” I have estimated, based on the food consumption data that Dr. Lindeberg published, that these people are getting around 8,000 mg of potassium a day, which is about triple what we get in the United States. All in all, I think their potassium-to-sodium ratio is about 12 times higher than ours, so that is a very major shift-virtually replicating a Paleolithic level of potassium and salt intake.

One interesting aspect of the Kitavans’ diet is that it contains a fair amount of saturated fat. In fact, about 18% of their calories come from saturated fat because they eat a lot of coconuts. However, their diet also provides a meaningful amount of protective omega-3 fats owing to their fish intake, whereas their omega-6 intake is quite low, inasmuch as their diet is quite low in grain products. So the omega-3/omega-6 balance favors omega-3. Another factor likely to be relevant to their excellent vascular health is that they are greyhound-lean throughout life. Their body mass index (BMI) is around 20 to 21, and their insulin levels actually decrease as a function of age, which is, of course, the inverse of what we see in the West. This implies excellent insulin-sensitivity. In fact, not a hint of diabetes is seen among these people.

Passwater: The BMI is an individual’s body weight in kilograms divided by his/her height in meters squared. A BMI of 25 is considered overweight and a BMI of 30 is considered obese.

McCarty: I think the main things the Kitavans have going for them from the standpoint of vascular health are lifelong leanness, insulin-sensitivity, a meaningful amount of omega-3 in their diet, and a whole-food, near-vegan diet that has a remarkably high potassium-to-sodium ratio. In addition, Dr. Lindeberg found that their blood contained a low level of the clot-promotion factor called PAI-1. He noted that this particular component was only about half as high in Kitavans as in Swedes. It would seem that their excellent insulin sensitivity contributes to this, but it also is possible that the Kitavans have some genetic advantage in this regard. You have to balance these protective factors against the fact that they have a high saturated fat intake, As a result, their blood cholesterol levels are not notably low. I recall that they average about 180 in the men and 220 in the women. Also, about 80% of the adults are tobacco addicts. You can bet that the coronary care units in the U.S. are filled with people who smoke and have cholesterol levels in the 180-220 range- yet the Kitavans display no sign of heart disease at all!

Passwater: That is so intriguing. And, of course, Lindeberg also had been unable to find any evidence of stroke among these people.

McCarty: Quite right! This is particularly interesting when compared to the experience in many other Third World cultures, where heart attack has been rare, but stroke usually is quite common. Meanwhile, a careful reading of one of Dr. Lindeberg’s papers brought up a point that I found of exceptional interest. He devoted just a couple of sentences to the observation that he saw no evidence of senile dementia on Kitava, and that all the elderly seemed to be mentally well-preserved.

Passwater: Let me first clarify a point. We haven’t spoken of life span. Is there a significant number of elderly Kitavans?

McCarty: Yes. Proportionally, there are many people in their 70s, 80s and even a few in their 90s.

Passwater: I just wanted to make sure that none of the readers draws the conclusion that Kitavans all die relatively young. If they did, that would, of course, cut down the chances of developing strokes or dementia

McCarty: There is a misimpression that, because the average life span in a lot of Third World countries may be relatively low compared to ours, there would be a paucity of elderly people in these societies. In fact, the average diet confers almost total immunity life span usually is skewed by infant or childhood mortality. I recall call reading that the average 40-year old Bolivian Indian with virtually no access to medical care has a longer life expectancy than a 40-year old resident of the U.S. In other words, if people in these cultures manage to make it through infancy and childhood without succumbing to infection, they have quite a decent chance to become elderly.

The chief causes of death in Kitava are infection and trauma. Also, there are a few very elderly Kitavans who have died in their sleep for no apparent reason, without symptoms suggestive of a heart attack or stroke. Perhaps their aging heart muscles just wore out and they had an arrhythmia. Aside from ovarian cancer-10 cases of which have been documented-cancer seems to be rare (although without autopsies, it is difficult to be sure). There is only one known case of a breast cancer that eroded the overlying skin. The fact that the Kitavan diet consists of low-glycemic index whole foods, and is vegan aside from a modest intake of fish that provides cancer-preventive omega-3, suggests that they should be at low risk for cancer-in part because this diet keeps them very lean and insulin-sensitive. The only fatality that occurred while Dr. Lindeberg was there was that of a 70-year-old man who fell out of a palm tree. We don’t have too many 70-year-old people in the U.S. shinnying up to the tops of palm trees, but I suppose if we did, we would have a fair number of palm tree fatalities!

May I make one other comment about Kitava? It is rather peculiar that these people do not have low cholesterol levels, and most of them smoke-yet there is zero evidence of coronary heart disease in Kitava! That suggests to me that if you eat an unsalted diet and stay lean and insulin-sensitive all your life, this may have a profoundly protective impact that overrides the impact of LDL cholesterol and even smoking. Perhaps salted diets are a permissive factor for heart disease. Do we know of any society eating an unsalted diet that has a significant incidence of coronary disease? I am not sure we do. Of course, the problem is that, as people adopt Westernized diets, salt consumption goes hand in hand with all of the other poor dietary habits that promote vascular disease. I’m not aware of any Third World society that adopted diets high in fatty animal products and refined grains, that didn’t simultaneously become addicted to salt. So we can’t tell whether avoiding salt would have protected them from the other aspects of this diet. The Kitavans are unique in that their relatively high cholesterol levels stem from the use of coconuts, not from any fatty animal products.

Passwater: How about the physical activity of these people? I know they are not couch potatoes, but, I would assume, neither are they marathon runners.

McCarty: Not at all. They probably would laugh at us for doing aerobic exercise. Obviously, there is a certain effort involved in gathering their food, but the impression that I get from Dr. Lindeberg’s work is that while they are probably somewhat more active than the average American, they may get less exertion than a lot of blue collar workers in the U.S. They certainly are not the Oceanic equivalent of the Tarahumara Indians of Mexico (who tend to view marathons as sprints!). Clearly, exercise is not the chief reason why the Kitavans have superb vascular health.

Passwater: In any case-getting back to your comment about dementia-I think there is a sufficient number of elderly people in Kitava to judge whether senile dementia or heart disease would be a significant problem.

McCarty: Yes. And you don’t need to have vast numbers of elderly to encounter dementia. I think I’ve read that about half of Americans over 85 suffer from dementia!

Passwater. That is scary.

McCarty: You bet it is. What’s the point of taking elaborate measures to try to stay healthy into old age if your only reward is to live your last days in a totally dependent state of imbecility? It’s so incredibly important to figure out how to prevent this outcome!

As I was saying, I was fascinated by the brief comment in Dr. Lindeberg’s paper about dementia, and so I got his email address and wrote to him. I asked, “When you say you didn’t see evidence for senile dementia, did this mean that you yourself didn’t encounter any demented elderly people-or did you make some efforts to determine whether anybody on the island had ever heard of anyone who had become senile as a function of age?” He indicated it was the latter. He had attempted to determine whether anybody on the island had known about anyone else on the island who had become demented when they became old-and he learned that senile dementia was a totally foreign concept to the Kitavans!

Full-blown senile dementia in general is not a subtle disease. If a person cannot recognize his own children or the other members of his tribe, you would think that everybody would know that. Bear in mind that in Kitava, no one is distracted by a lot of information overload as we are in modern civilization. There, everyone’s chief concern is about the other members of the tribe. That is what everyone knows more about than anything else. So, if a member of the tribe were to become severely demented, one would think that everyone would know about it. The bottom line is that no one in Kitava had ever heard of an elderly person becoming demented with age-which is quite a striking observation on an island which has about 2,500 residents and a fair proportion of the elderly, and where people can tell you about medical events that transpired a century ago!

I might add that, in response to his inquiries, the Kitavans introduced Lindeberg to a couple of mentally retarded people who were relatively young. This is not germane to senile dementia, but it shows that the Kitavans were trying to cooperate with his investigation.

When I learned about the evident rarity of dementia in Kitava, it jogged something in my memory, and I plowed back into the writings of Dr. Hugh Trowell. Dr. Trowell was a brilliant physician who worked in British East Africa during the middle decades of the 20th century. He wrote several books and monographs documenting the rarity of many “Western” diseases in Africa during the early decades of that century, when well trained British physicians had begun to serve the populace, but Western eating habits were only beginning to catch on among black Africans. Several of his later books were written in collaboration with Dr. Denis Burkitt. Many of our readers will remember them as the Burkitt and Trowell who popularized the health benefits of high-fiber diets.

In any case, my old friend and mentor Herb Boynton loaned me several of Dr. Trowell’s books-large portions of which I had read some years previously and I scanned their indexes for “senile dementia.” I thus found a relevant passage in which Dr. Trowell cited the work of a British psychiatrist who had been practicing at the psychiatric ward of a Nairobi hospital back in the 1930s. From other portions of Dr. Trowell’s book, I had learned that salt use was still uncommon among all but the most socially exalted black East Africans at the time. Further, I learned that stroke was considered extremely rare-rather like the situation that still prevails in Kitava. This psychiatrist wrote that on his psychiatric ward, he observed the full spectrum of psychiatric disorders that one would expect to encounter in Britain or the U.S.-with the exception that “senile dementia was a notable absentee.”

So here, again, we have the correlation between a virtually unsalted diet, a virtual absence of stroke, and a virtual absence of senile dementia!

I am emboldened to suggest that if one keeps his or her cerebral vasculature so healthy as to be virtually immune from stroke, that individual also will be nearly immune from senile dementia-not just the so-called vascular dementia that results from small strokes, but from Alzheimer’s disease as well. In effect, I am proposing that senile dementia is a disease of civilization made possible by salted diets!

Passwater: Tell us more about why you believe that this is the case.

McCarty: There is a lot of epidemiological evidence indicating that risk factors for stroke are very similar to risk factors for Alzheimer’s. I am not the only scientist to have suggested that a healthy cerebrovascular endothelium may act in various ways to prevent the chronic inflammatory process that manifests as Alzheimer’s disease, or to protect neurons from this process. One possibility, supported by some evidence, is that small strokes somehow act as a co-factor that makes Alzheimer’s possible. If this is so, then preventing strokes also would tend to prevent Alzheimer’s. Conversely, it is conceivable that vigorous cerebral blood flow is somehow protective.

Another possibility that I particularly like is that the nitric oxide produced by a healthy microvascular endothelium may have an anti-inflammatory impact on the brain -much as it does in preventing atherosclerosis in large arteries. Bear in mind that both Alzheimer’s and atherosclerosis are low-grade chronic inflammatory disorders.

Additionally, in moderate physiological concentrations, nitric oxide might act to protect neurons from the pro-inflammatory factors that damage and kill them in Alzheimer’s disease. Conversely, it is now known that the toxic amyloid peptides that seem to induce much of the neural damage in Alzheimer’s, also attack the cerebrovascular endothelium and effectively block its production of nitric oxide. This suggests that, once the inflammatory process of Alzheimer’s disease gains a firm foothold, there may be no going back, because the cerebrovascular endothelium won’t be able to recover its healthful protective function. This further suggests that some measures which help to prevent Alzheimer’s may not be of much use for treating it. In other words, don’t wait until the horse is already out of the barn before shutting the barn door!

I probably should mention that some scientists speculate that excess nitric oxide production contributes to inflammatory damage in Alzheimer’s-and I’m not sure they’re wrong! You need to take a subtle look at this issue. In the modest concentrations produced by the healthy vasculature, and in the relative absence of the free radical superoxide, nitric oxide appears to have a number of protective properties, including an anti-inflammatory effect. On the other hand, in many inflammatory disorders, certain immune cells generate large amounts of nitric oxide in conjunction with large amounts of superoxide. These two compounds interact rapidly in a reaction that destroys the nitric oxide and converts it to a really vicious chemical known as peroxynitrite. So whether nitric oxide is helpful or harmful really depends on the context.

In any event, in light of my speculation that vascular nitric oxide might help to prevent dementia, I was particularly intrigued to encounter recent reports that people who use statin drugs to control their cholesterol levels appear to be at greatly reduced risk for Alzheimer’s. A remarkable 70% reduction in risk has been suggested by two studies. Here is the relevance: there is now a lot of evidence that statin therapy lowers stroke risk fairly markedly. This initially seemed a little odd, because LDL cholesterol does not appear to be a strong risk factor for stroke. However, recent studies show that statins can act directly on the vascular endothelium to boost endothelial production of nitric oxide! Actually, there is both an increase in nitric oxide synthesis and a suppression of superoxide production.

As I just stated, superoxide is a potent free radical that can destroy nitric oxide, converting it to dangerous peroxynitrite. Increased effective production of nitric oxide offers a satisfying explanation for the ability of statins to prevent stroke but I suggest that this also may be the mechanism whereby they prevent Alzheimer’s as well. Of course, I can’t rule out the possibility that statins have some direct protective impact on brain tissue, but at least these findings are quite consistent with the possibility that the nitric oxide produced by healthy endothelium helps to prevent dementia.

Another measure which has been shown to boost the ability of vascular endothelium to produce nitric oxide is estrogen. This finding fits very nicely with the fact that there is considerable epidemiological evidence that women who use long-term postmenopausal estrogen replacement are at substantially lower risk for Alzheimer’s!

However, the overriding determinant of cerebrovascular health may be dietary salt and potassium status. In other words, if you eat an unsalted, potassium-rich diet throughout life, chances are that you will have a healthy cerebral vasculature into ripe old age, and this will help you prevent not only stroke but, most likely, Alzheimer’s disease. I realize that this is such an audacious proposition, it probably will be many years before we know just how accurate it is. It may be that the leanness and insulin-sensitivity of the Kitavans contribute importantly to their protection, too-as well as their intake of omega-3. Omega-3 has anti-inflammatory properties, and Alzheimer’s is a type of inflammation.

Passwater: For the readers who may not have read part one of this series of columns, let’s talk about why a potassium-rich sodium-reduced diet would result in the healthy endothelium that you were just speaking of.

McCarty: There is experimental evidence from laboratory rat studies that, in fact, salted diets tend to impair vascular nitric oxide production. Conversely, we know from rabbit studies that a modest increase in blood potassium levels-as can be achieved by eating more potassium tends to aid endothelial nitric oxide function by suppressing endothelial superoxide generation. This is much like what the statin drugs recently have been shown to do. One of the major determinants of these effects is the membrane potential of the vascular endothelial cells. When the membrane potential of endothelial cells is high, this tends to promote nitric oxide synthesis by boosting calcium uptake by the cells, while at the same time inhibiting the mechanisms that generate superoxide. More synthesis of nitric oxide and less of superoxide translates into a considerable boos in the protective activity of nitric oxide.

Passwater: But I thought that an increase in membrane potential helped to keep calcium out of cells!

McCarty: That is true in vascular smooth muscle and many other tissues but you see precisely the opposite effect in endothelial cells, for reasons that are a little too complex to discuss here. In endothelial cells, an increase in intracellular calcium levels is the signal that turns on nitric oxide production.

In any case, the salt and potassium contents of your diet influence the membrane potential of vascular endothelium and other cells by regulating the activity of the sodium-potassium pumps we mentioned earlier. When these pumps are vigorously active, membrane potential tends to increase, whereas you see the opposite effect if they are inhibited. A salted diet in susceptible people causes the body to make inhibitors of these pumps. This in turn helps the kidneys rid the body of excess salt, but at the cost of inhibiting the sodium-potassium pump in many other tissues.

Conversely, an increase in blood potassium levels directly stimulates the activity of these pumps- while helping the kidney to harmlessly rid the body of salt. The net effect is that membrane potentials tend to be high if one eats a low salt, high-potassium diet, whereas they are more likely to be low in the context of a salty, potassium-depleted diet. In torn, with a high membrane potential, the ability of nitric oxide to ward off blood clots, lower blood pressure, and quell inflammation and atherosclerosis is optimized, whereas a low membrane potential means that these benefits are substantially lost.

Note that the modulating effects of salt and potassium on cerebrovascular endothelial function don’t necessarily correlate with blood pressure. In other words, if a salted diet doesn’t raise an individual’s blood pressure, that doesn’t necessarily mean that it isn’t impairing the healthful function of the cerebral circulation and increasing the risk for stroke. Conversely, getting more dietary potassium may protect one’s brain even when it doesn’t evidently improve his or her blood pressure.

By the way, one reason I think that leanness and excellent insulin-sensitivity might play a role in the protection from stroke and dementia enjoyed by the Kitavans is that the excessive fat exposure involved in insulin resistance syndrome can impair vascular nitric oxide function. This correlates nicely with the fact that insulin resistance syndrome increases risk for stroke.

I recently published a technical paper proposing that the key to avoiding strokes is to optimize the nitric oxide production of the cerebrovascular endothelium. I suspect that more and more factors that protect us from stroke-like statins, estrogen, a low-salt/high-potassium diet, leanness, and exercise-are going to be shown to have a favorable effect in this regard.

I also should mention that exercise training can boost endothelial nitric oxide production-as well as reduce stroke risk-while elevated homocysteine, associated with increased risk for both stroke and Alzheimer’s, can impair endothelial function. There is a definite pattern here!

Passwater: One final question about the Kitavans. How can you be sure that these islanders don’t just have some marvelous genetic inheritance that protects them from stroke and dementia? Could you be over-interpreting one rather anomalous observation?

McCarty: I can’t know for sure, but I doubt that good genes alone are primarily responsible. Dr. Lindeberg met one Kitavan who had left the island as a young man and had lived a more Westernized lifestyle for a number of years. This individual, it turned out was both fat and hypertensive! Scientists repeatedly have noted that Oceanic cultures tend to be lean and relatively free of “Western” diseases while they maintain their traditional lifestyles, but that they rapidly become susceptible to obesity, hypertension, diabetes, and vascular disorders when they adopt a Westernized diet. Indeed, some of these cultures prove to be much more susceptible to these disorders than EuroAmericans are-particularly diabetes. The other reason I doubt it’s purely a genetic issue is the admittedly thin evidence that senile dementia was very rare in Kenyans when they also were eating unsalted diets and were virtually free of hypertension and stroke.

I readily admit that my proposal that Alzheimer’s may be substantially preventable by simple natural nutritional measures seems audacious, and this certainly will not be an easy proposition to prove. But my view is that you have nothing to lose by trying this strategy. Eating and exercising in a way that will keep blood pressure low and minimize risk for stroke, may or may not prevent Alzheimer’s. But preventing stroke, vascular dementia, and other potentially devastating consequences of hypertension is no small benefit in itself! And the recent revelations about the apparent ability of statins, estrogen, and aspirin-like drugs (NSAIDS) to reduce Alzheimer’s risk encourage the view that this disorder is indeed highly susceptible to prevention. If drugs have a protective effect, should we expect less of optimal nutrition?

By the way, I should note, in concluding, that Dr. Lindeberg has been very gracious and helpful to me, and I am particularly grateful for the fact that he sent me a copy of his fascinating Ph.D. thesis summarizing his research on Kitava. I hope that someday he will find the time to write his own book describing his experiences there.

Passwater: We thank you, and your co-authors, for bringing out this information about the importance of the dietary K Factor-the potassium-to-sodium ratio in the diet. You are making a significant contribution to overall health, as well as to the reduction of risk factors for the specific diseases that we have discussed. As I said at the start of this series, The Salt Solution is “must” reading for everyone. The book not only presents the scientific evidence, but provides a practical, easy-to-follow, nine-step nutritional program to improve eating habits and reverse the effects of typical high-salt diets. WF

http://www.drpasswater.com/nutrition_library/potassium_sodium.html

Cheating a little here, buying cajun chicken and cauli rice from Aldi..  😉

Ingredients

• 1 pack ready to cook cajun chicken fillets https://www.aldi.co.uk/ready-to-cook-cajun-chicken-fillets/p/069344039299500
• 1 pack cauliflower rice
• 1 1/2 tbsp olive oil
• 1/4 tsp turmeric
• 1/4 tsp ginger
• 1/4 tsp curry powder
• 1/4 tsp chopped garlic
• Piri piri salt
• 1 cup baby spinach
• 1/4 cup greek yoghurt
• 1/4 cup chopped cucumber
• 1/4 tsp chopped mint

Directions

1. Grill Cajun Chicken – 6 minutes each side, until crispy

Whilst chicken is grilling:

1. Fry cauli rice in olive oil – whislt frying rice
2. Add turmeric, garlic, ginger, curry powder – mix well
3. 1 minute before rice is ready (after about 8 minutes) add chopped baby spinach
4. Mix chopped cucumber into yoghurt, add chopped mint
5. Serve hot chicken on a bed of cauli rice, with a side of minty cucumber yoghurt

This actually makes a big cake – suitable for 2 people, or 1 if hungry..

Ingredients

• 1 egg
• 1/2 tsp baking powder
• 1/4 cup almond milk
• 1 tbsp coconut flour
• 1 tbsp almond flour (ground almonds)
• 1 heaped tsp cocoa powder
• 2 tsp stevia (or sugar free sweetener – to taste)
• 1 tsp double cream
• 1 1/2 heaped tsp peanut butter
• 1/2 tsp cinnamon
• 1/4 tsp vanilla essence
• 1/4 tsp almond essence
• 1/4 tsp orange essence

Directions

1. Mix ingredients well in a bowl or big mug – until light and full of air bubbles.
2. Microwave for 2 mins or until all liquid has solidified (I actually do 2:45 @ 800W).
3. Sprinkle with a little extra stevia and cinnamon to taste.
4. Cover with creme-fraiche.

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