1. Do you frequently experience brain fog and find it hard to focus?
2. Is your blood sugar count higher than it should be?
3. Do you frequently suffer from digestive problems if you eat high-protein foods?
4. Do you feel sleepy from time to time, especially after meals?
5. Have you gained weight—especially around the middle?
6. Have your blood triglyceride levels gone up?
7. Do you have high blood pressure?
8. Have you noticed a loss of muscle over the last few years?
9. Is your LDL cholesterol higher than it should be?
10. Do you take a statin drug?
11. Have you been told that you have low albumin or hematocrit levels in your blood?
12. Has your doctor told to cut back on the amount of cholesterol in your diet?
13. Have you been told you that you have reduced kidney function?
14. Is your vision as sharp as it once was?
15. Do you have any concerns about the health of your heart and blood vessels?
The supermarket has a plentiful supply of food, but your cupboards at home are bare. How do you solve this problem if you are hungry? Simple: you go to the store; carry the food home via your trusty means of transport—your car or bike or feet; prepare it; and consume it. Problem solved.
Our cells are hungry too. They need nourishment to keep on doing the jobs they do, and they too rely on a transport system that brings essential nutrition from where it’s stored into and through the bloodstream, which is the highway of the transport system, right to the door of the cells, so the cells can take in the nutrition they need to support your body’s health functioning.
In fact, all three categories of essential nutrients required by our cells—fats, carbohydrates, and proteins—have their own separate carriers, their own particular transport systems. As you will guess, each of these carriers is also genetically unique to the individual and naturally is influenced by that individual’s lifestyle, diet, and environment.
How do these carriers operate? The carrier for fats essentially has to mask its fat “personality” in order to do its job. This is because fats are not soluble and therefore do not dissolve in the blood, which is principally made up of water. These carriers are called lipoproteins; you know them as forms of cholesterol—very-low-density lipoproteins, or VLDL; low-density lipoproteins, or LDL; and high-density lipoproteins, or HDL.
Carbohydrates, by contrast, can be transported into the blood directly as glucose, a soluble carrier. Once the glucose gets to the cell, however, its transport into it is controlled by a complex regulatory system of hormones, of which the most important is insulin.
The carriers for protein, needed by all cells in the body to maintain cellular structure and function, are amino acids and the blood protein albumin, which, like cholesterol, is made in the liver.
Vitamins and minerals have their own carriers as well. Vitamins A, D, E, and K, which are fat-soluble vitamins, are carried by the same lipoproteins that carry fat. Other vitamins, which are water-soluble, are carried by a range of different protein transporters.
These transport carrier systems are all tightly controlled; they need to be if they’re going to get the right nutrients, not to mention all those communicating hormones and signaling substances, to the right cells needed for the maintenance of health—and to all the cells that need to get the nutrients. Any sort of glitch in any of these carriers anywhere along the route of transport can produce a state of malnourishment in the cells the carrier serves. Such a glitch works like any standard traffic jam on any road or highway: as the line of traffic slows and then comes to a halt, there’s too much of a buildup at the end of the line, in the storage tissues. Obviously, that means that not enough of the substance is getting to the cells of the tissues and organs where it is needed.
In an automobile traffic jam, the cars get there eventually—if they don’t turn around and go home. In your body, there are damaging consequences when not enough nutrients get to your cells. In due course, the deficiency produces a change in the function of the body for which the cells are responsible. Over time, if not corrected, that alteration constitutes a damaging defect that can lead to conditions of chronic illness. Defects in fat transport have been associated with heart disease and stroke, defects in the carbohydrate transport process with diabetes and dementia, defects in the protein transport process with muscle loss, and defects in the transport of vitamins and minerals with such nutrient-related diseases as osteoporosis and various forms of anemia.
What is particularly notable about glitches in the body’s transport process, however, is the extent to which the chronic illnesses they lead to can be prevented and reversed through changes in diet and lifestyle. That’s particularly lucky, because some of the standard drugs that treat these illnesses can cause adverse reactions along with their benefits. A case in point is the class of drugs widely used today to combat the heart disease that too often results from an imbalance in the fat transport system.
FAT TRANSPORT AND HEART DISEASE
I’m pretty sure you know what plaque is. It’s a deposit of fat clinging to an artery wall and clogging the artery. But did you know that its discovery goes back to the late nineteenth century, when Dr. Rudolf Virchow in Germany noted the connection between such deposits and heart disease, a health problem that was far less common at that time? Confirmation of the connection came later when the Russian physiologist Nikolai Anitschkow produced this same type of plaque in rabbits by feeding them diets high in fat and cholesterol.
The connection—fat and cholesterol, cholesterol and plaque, plaque and heart disease—was explored further in 1948, when the Framingham Heart Study got under way in Massachusetts. The aim was to evaluate the behavior and habits of people in the town of Framingham—some 5,000 of them at first—to see if there was a relationship between the incidence of heart disease caused by plaque in the arteries and Framinghamers’ diet and daily habits. As I write this, the Framingham study is in its third generation. Much has been learned, and among the results the study has yielded is the famous list of cardiac risk factors—among them, the substance fingered as the cause of plaque, elevated levels of cholesterol in the blood.
Actually, only about 10 percent of the cholesterol in blood comes directly from the cholesterol in animal products in the diet; most of the cholesterol in the blood is made in the liver and is not a result of direct consumption of food. It is transported by the lipoproteins from the liver through the bloodstream to the arteries. The Framingham study found that if the cholesterol was carried by low-density or very-low-density lipoproteins—LDL or VLDL—there was an increased incidence of heart disease, but if the cholesterol was carried by the high-density HDL, the incidence was reduced.
Why would one form of cholesterol be a risk for heart disease and another form act as protection from the very same disease? The answer is not in the cholesterol, although we popularly speak of “good” cholesterol and “bad” cholesterol—erroneously and inaccurately. Rather, the answer is all in the transport experience.
The first thing to understand in this regard is that cholesterol is very important to the proper functioning of the body—when it is available in the right form in the right place. It performs three essential functions. First, cholesterol is used by all cells of the body in the construction of the membrane that keeps each cell intact. Second, it serves as the source material from which testosterone, estrogen, and the steroid hormones like cortisol are made. Finally, cholesterol is used to make the bile salts that are necessary in the digestion and assimilation of fats. If there isn’t enough cholesterol available, then these important functions can be compromised. The result? Numerous health problems like low libido, poor tolerance of stress, and even altered immunity.
LDL, the so-called bad cholesterol, is transported from the liver on a specific protein carrier whose job is to deliver it to the artery wall, where it can then be used by cells within a range of different tissues. HDL, or good cholesterol, however, is transported by a different protein carrier whose particular task is to pick up the cholesterol from the artery wall and take it back to the liver to be broken down and excreted. The balance between the cholesterol influx into the artery wall and the cholesterol efflux out of the artery wall determines how this cholesterol influences health and disease.
So in this as in just about everything having to do with our health, balance is everything. If the transport tilts too much toward the to-the-artery side, our LDL will be too high and our HDL too low, leading to a definite risk of heart disease. But it’s all too easy to surmise that the exact opposite—a tilt to the lowest LDL cholesterol levels—would equate with peak health. It does not. Peak health comes with the proper balance between LDL and HDL levels; both transporters are needed, but in the correct proportional relationship.
LDL cholesterol, for example, is found in neurosteroids that are critical in regulating brain function and mood, so too low a level of LDL is not healthy for the brain. Studies show a correlation of very low cholesterol levels with depression and even with suicidal thoughts and behaviors. So not enough of it is not good for happiness in general and perhaps for survival in particular. Deficiencies of LDL can also mean insufficient protection by the fat-soluble vitamins A, D, E, and K, which means deficiency in needed nutrients, and away the system goes—like a dog chasing its tail in a loop of increasing health risks.
There’s another factor that should probably be mentioned here, and that’s stress, a major agent of cholesterol imbalance. I saw this up close one day some years ago when a patient who had just had a blood test left our lab, got into her car, and promptly backed right into a tree in the parking lot. She was uninjured but in mild shock when she came back into the laboratory. We took her blood again. She had certainly not consumed any food or drink between blood draws, yet her LDL cholesterol level had shot up nearly 30 percent post-accident.
Studies on competitive athletes confirm this effect of stress on LDL level. I’m told that the elite Formula One drivers at the twenty-four-hour Le Mans auto race experience elevated levels of LDL during the race despite the fact that they do not take in any food. In fact, their LDL levels stay high for some time after the race. It’s only when their bodies have had a chance to adjust to the absence of competition and danger and the accompanying stresses that the cholesterol levels of these typically very fit athletes come back into balance.
What happens in these cases? There is now evidence that stress hormones mobilize cholesterol from the body and bring it into the blood to elevate LDL cholesterol. The cholesterol is in a sense an alarm chemical; when your physiology is under stress, your LDL cholesterol spikes in the blood as a signal of that stress.
STATINS
But now fast-forward from the Framingham study to the early 1970s, and travel across the globe to the research laboratory of microbiologist Akira Endo at the Sankyo Company in Japan. Endo, who had grown up on a farm, had been fascinated as a boy by Alexander Fleming’s discovery of penicillin from mold. His desire was to follow in his idol’s footsteps, and at Sankyo, he was being tasked to do pretty much that; his job was to find substances of industrial value in fungi. At the time of this story, Endo was looking at specific enzymes made by fungi that could be used to process fruit juice, but his interests were much broader than that. And indeed, in screening the effects of various types of fungi, Endo came across one species, Penicillium citrinum, which produced something that prevented animals from making cholesterol. From this unlikely discovery, the family of statin drugs was born.
At the Merck Research Laboratories, Dr. Alfred Alberts picked up on Endo’s discovery to develop the first FDA-approved statin drug for the treatment of high levels of cholesterol in the blood, lovastatin (Mevacor). From that, the most widely prescribed drug in the world, the statin Lipitor, was developed by Dr. Roger Newton, a colleague and good friend of mine, and his atherosclerosis research team at what was then Warner-Lambert/Parke-Davis.
As is well known, statins block the manufacture of cholesterol in the liver. That obviously means less LDL is being delivered to the artery wall. Often, there is an accompanying decrease in the amount of HDL picking up cholesterol from the artery wall as well, but the impact of the reduced rate of delivery to the artery wall is greater than the effect of the lowered rate of removal from it—a slight tip in the balance. This means that blood cholesterol levels go down, and so does the risk of heart disease.
But hold on. A reduction in blood cholesterol is associated with a lower incidence of heart disease: Does that necessarily mean that cholesterol causes heart disease? No. Not necessarily. Association does not prove causality.
And now the story of statins and cholesterol gets quite interesting. Yes, medical studies confirm that people who have had a heart attack can prevent a second by taking statin drugs. And yes, studies find that men with elevated LDL blood cholesterol levels may prevent a first heart attack by taking statins; the benefit is small but definable and occurs only in men. In women, who suffer a different type of heart disease from men, there is no general first-heart-attack prevention benefit in taking statins. In fact, there is some evidence that postmenopausal women taking statins have a greater risk of type 2 diabetes from taking the drug.
What these varied responses to statins tell us is that the activity of statins seems to be more than just a matter of inhibiting cholesterol synthesis; rather, the statins serve as agents that block inflammation at the artery wall. And since such inflammation normally causes damage to the LDL carrier of cholesterol, literally oxidizing it, what statins effectively end up doing by blocking the inflammation is preventing injury to the artery wall.* This is a finding that takes us back to the future, for Rudolf Virchow, the discoverer of plaque, first proposed in 1879 that atherosclerosis was due to an injury—his word exactly—to the artery wall. Now here we are in the early twenty-first century finding that Virchow’s model is in fact correct. The inflammation triggers an immune response that leaves the fatty deposit behind. That fatty deposit in turn triggers more immune responses, and more plaque builds up, degrading the artery wall further. So the injury to the artery is caused by inflammation—in part, anyway—and statins seem to be uniquely able to prevent the type of inflammation that causes that arterial injury.
Statins may also produce adverse side effects, however; one in particular is that in blocking the production of coenzyme Q10, statin use can lead to muscle pain, often serious.
Some time ago, I was introduced to the high-powered senior executive of a major insurance company—let’s call him Doug. He was a very fit, healthy-looking guy, a man of disciplined habits—nonsmoker, exercised regularly, healthy diet—but a definite type A personality. Whatever he did, he went above and beyond what was required and what was expected. That was probably why his cardiologist, noting that Doug’s LDL cholesterol level was a “little too high” at 110 milligrams per deciliter, put him on a statin drug; the doctor wanted Doug’s cholesterol count to be under 100. The statin worked: Doug’s LDL went down to 85. At his next cardiology appointment, however, the doctor announced that the new LDL standard for optimal health was to get the level below 60, and he increased the dose of the statin.
When Doug and I met, some months thereafter, he told me how little energy he had; he felt his memory had become spongy and he was losing his male vigor. Doug wondered if all of it—and especially the erectile dysfunction—could have anything to do with the statin he was taking. Perhaps not the statin itself, I suggested, but rather the dose; it could well be causing an imbalance in his transporters, resulting in a cellular cholesterol deficiency.
That was indeed the case. Doug asked his cardiologist to adjust the statin dose, and his adverse symptoms resolved—without raising his cardiovascular risk excessively. He and his physician together had worked out the right balance—neither too much LDL nor too much statin drug.
So while statin drugs may indeed be highly beneficial for people with serious or advanced heart disease, they may also incite some adverse effects and may block some beneficial effects. Isn’t it therefore worth asking whether or not there may be other paths to preventing LDL oxidation and arterial injury?
The answer is yes, there are. Let’s start by going back to the future again—this time all the way back to the Tang dynasty in ninth-century China. Prevailing medical lore at that time held that red yeast rice, as it was known—actually, rice on which a specific red-colored mold had grown—could “purify” the blood. In our time, controlled studies in humans on the impact of red yeast rice on blood cholesterol levels have confirmed this effect. Trials at the Center for Human Nutrition at the UCLA Medical School* found that eating red yeast rice indeed lowers LDL cholesterol; these findings complement other studies that have found that red yeast rice also reduces oxidized LDL. The reason is simple: The red mold that grows on the rice contains the very same type of substances that statins are composed of.
As it turns out, red yeast rice is only the beginning of the dietary pathways to lowering LDL cholesterol levels in the blood. A class of phytonutrients called phytosterols in particular is now known to lower LDL levels. Phytosterols are found in many plant foods—soy being a prime example, but also nuts, berries, and vegetable oils. Well-known cholesterol researcher Daniel Steinberg, who tracked how lifestyle behaviors can increase oxidized LDL, also shows us how the increased intake of particular phytonutrients can prevent the formation of oxidized LDL. In particular, foods rich in flavonoids and polyphenols—nuts and berries again but also garlic and onions, grapes, cocoa, black rice, and citrus—seem able to match statins in their power to prevent inflammation. And other classes of phytonutrients found in such vegetables and herbs as virgin olive oil, flaxseed, garlic, psyllium fiber, green tea, and curcumin from turmeric also both lower LDL cholesterol levels and reduce oxidized LDL. So once again, we see the potential of fruits and vegetables to prevent or fight the process that leads to atherosclerosis—that is, hardened arteries and cardiovascular failure.
It is also recognized that vitamin B3, niacin, when administered in doses of 2 to 3 grams a day, lowers LDL and raises HDL. Be aware that there is controversy over the clinical benefit of niacin in high doses; it can produce flushing of the skin that may be extreme in some people. At those levels of dosage, however, the individual is using the vitamin as a drug to achieve druglike effects, not as a nutritional substance. At appropriate doses, niacin is an effective nutritional therapy that can alter the pattern of cholesterol transporters from LDL to HDL.
One of the most widely studied effects of a nutritional substance on transport of fats and cholesterol in the blood is that of fish oil. Elevated levels of very-low-density lipoprotein—VLDL—found in people with high blood levels of a form of fat called triglycerides, are reduced through frequent consumption of such cold-water fish as salmon, herring, and sardines, or through a nutritional supplement of 3 grams of omega-3 fish oil daily. Omega-3 fatty acids, as I’m sure you know, are the essential fatty acids that are vital to human metabolism.
There is an interesting addendum to this, as we have now learned that vitamins D and A can also reduce the levels of oxidized LDL and improve control of cholesterol transport. What emerges from this added knowledge is that the use of a combination of omega-3 fatty acids from fish with balanced levels of vitamins D and A is proving to be a highly effective and significant way to support the healthy transport of cholesterol.
Is there a single natural source of all three of these nutrients—omega-3 fatty acids, vitamin D, and vitamin A? There is: cod liver oil. Decades ago I met Dale Alexander, the health activist affectionately known during the 1960s and 1970s as the “cod father” for his advocacy of cod liver oil as the solution to a range of health problems, including arthritis and joint pain. Alexander was resoundingly criticized by the medical community at the time because there was no scientific explanation for the connection between fish oil and inflammation. Forty years later, there is such an explanation. We now know that the omega-3 oils eicosapentaenoic acid (EPA) and docasahexaenoic acid (DHA), which exist in high levels in cod liver oil, do in fact reduce the inflammatory signaling process and therefore have an anti-inflammatory effect. It is also now known that the vitamins A and D in cod liver oil are beneficial to the gene expression controlling the health of the heart and of blood vessels; the vitamins also help prevent the oxidation of LDL. So Dale Alexander was not really wrong, just possibly a little overzealous. For with cod liver oil as with many things, a little is good, but a whole lot is not so good; vitamins A and D in particular can produce adverse effects if consumed at too high a dose.
What we have found at the Functional Medicine Clinical Research Center is that 2 to 3 grams of a clean source of cod liver oil is a safe and effective daily dose. By “clean” I mean that you want to be sure the oil you use is not from cod caught in the Atlantic Ocean; livers of Atlantic cod have been found to be contaminated with pesticides and dioxins. The source of the cod liver oil should be identified on the label, so look for oil from the livers of cod caught in the Alaskan waters of the Pacific Ocean. They’re not only cleaner; they also have a uniquely beneficial balance of EPA and DHA with vitamins A and D—no doubt a result of the particular food sources available to these fish.
But it isn’t only particular foods that can help us keep the right cholesterol balance. As we are forever hearing from our parents, our children, First Lady Michelle Obama, various celebrity fitness gurus, and of course our doctors, exercise is all-important.
And in fact, the science is crystal clear that all those preaching the benefits of exercise are right. Regular aerobic activity causes a change in the transport of fats in the blood; specifically, it increases the level of HDL cholesterol in the blood and decreases LDL and VLDL. It also reduces stress. At one time, people who had survived heart attacks were advised by their doctors not to exercise. Times have changed. Today, a cardiologist who failed to start his or her patient on a cardiac rehabilitation program would be considered negligent at best and might be sued for malpractice at worst. Meanwhile, the field of aerobics, started by the U.S. Air Force’s Dr. Ken Cooper as a test of fitness, has become a recognized form of therapy, and sports medicine has become a valid medical discipline, as we have learned how exercise turns on the genes that regulate rehabilitation of the cardiovascular system.
But there’s another important reason why exercise is so important. The bloodstream is not the only highway along which fat carriers can travel. There’s another transport system for fats—namely, the lymphatic system, the network that connects the glands of the body and across which lymphatic fluid transports hormones and other substances.
FATS, HEART DISEASE, AND LYMPHATIC TRANSPORT
I learned a lot about the lymphatic system from prominent cardiovascular surgeon Gerald Lemole, who, among other accomplishments, performed the first coronary bypass operation in Turkey in 1982. Lemole has some very clear ideas about the role of defective lymphatic transport in cardiovascular disease, ideas based on thirty years of observations as a cardiovascular specialist. Here’s what Lemole says about heart disease.
First, it is poorly correlated with blood cholesterol levels. Yes, there is a connection, but it is not as tight or as mutual as is generally believed. By itself, in other words, cholesterol is not the cause of heart disease. Second, cardiovascular disease occurs primarily in the arteries of the unmuscled regions of the body, places where the lymphatic system plays an important physiological role in the transport of lipoproteins and cholesterol, including oxidized LDL. Third, people who get cardiovascular disease often have damaged lymphatic systems as well. And finally, a sedentary lifestyle absolutely increases an individual’s risk of cardiovascular disease.
The key point that connects these factors, according to Lemole, is that the lymphatic system does not have a pump; the heart is the pump for the circulatory system, but the lymphatic system has none. The only way that things get moved through the lymphatic system is by the body’s own mechanical motion. A body at rest is a body with lymphostasis; that is, the lymphatic fluid necessary to transport lipoproteins is moving slowly, if at all, through the system. Defective lymphatic flow or lymphatic flow slowed to inactivity can be a causative factor in cardiovascular disease.
That means that it is only your own physical activity and, secondarily, manipulations like massage, yoga, acupressure, Reiki, or shiatsu that keep things flowing through the lymphatic system. There is no substitute for these physical or manipulative activities. No pill, powder, or potion can accomplish what physical activity does to keep fats and cholesterol moving through the lymphatic system, getting them to where they need to get to, and ensuring that they get cleared out of the body as well.
I have seen the results of exercise and manipulative therapy in a great many people with high LDL and low HDL cholesterol levels and who have the biomarkers of early cardiovascular disease. Many start off with just a daily walk and a massage focused on lymphatic transport, then work up to more activity and more sustained activity, combined with a personalized dietary program. There is simply no better way to lower cardiovascular disease risk while improving functional health and a sense of well-being.
TRANSPORTING CARBOHYDRATE
The body is made up primarily of water, protein, fat, minerals in bone, and a small amount of carbohydrate, mostly in the form of the sugar known as glucose. This small amount of carbohydrate in our bodies is nevertheless critical, for glucose is the principal source of energy for the body’s cells.
Since it is a sugar, glucose dissolves in water, so unlike fat, it can be transported directly across the gastrointestinal barrier and into the bloodstream after it has been ingested. No transport chaperone is needed. This means that when we eat a candy bar, all the sugar it contains is in our blood within about fifteen minutes. Since the total amount of glucose in our blood in general is approximately 5 grams, and since the amount of glucose in a single half-ounce candy bar can be 15 grams—even as much as 20 grams—the math is pretty clear: Eating the candy bar will take about a quarter of an hour to multiply the level of sugar in the blood by at least three. This would produce a condition of elevated blood sugar on a par with diabetes.
It doesn’t happen, thank heavens, because the normally functioning body transports the glucose out of the bloodstream into the tissues very, very fast. The transport operates through a tightly regulated process controlled to a great extent by the hormone insulin. Insulin—as well as its opposite number, glucagon, which raises blood sugar—is secreted by specialized cells in the pancreas, the gland adjacent to the liver on the right side of your abdomen. After you eat a meal or snack containing carbohydrate, these specialized cells, called the islets of Langerhans, secrete insulin into the bloodstream, where it is transported to all the cells of the body. Its job is to instruct the cells to let the glucose in through specialized doors called glucose transporters. That’s how the glucose gets out of the blood—and how you avoid getting diabetes from eating just a single candy bar. It all works wonderfully well as long as this complicated system of transport and cellular communication is operating as it should.
All too often, however, there is a glitch in the transport system, and this obviously causes a communication problem between insulin and the cell. If the cell’s communication apparatus doesn’t understand the transport message from insulin—if it resists the insulin message—then the pancreas puts out more insulin in an ongoing attempt to get the glucose out of the blood and into the cell. (Remember how cellular communication will “talk louder”—that is, send more of the messenger chemical to get the message across?) This insulin resistance represents the early stage of the chronic illness that is on the rise worldwide in epidemic proportions—type 2 diabetes.
Originally known as adult-onset diabetes to differentiate it from the juvenile form of the disease, it has been renamed “type 2” because so many adolescents and children are now being diagnosed with the adult form. Type 1 diabetes is due to an autoimmune response that destroys the islets of Langerhans cells so that the pancreas simply cannot secrete insulin, while type 2 diabetes stems from an imbalance in glucose transport due to a mismatch of the individual’s genes with his or her diet, lifestyle, and environment. There is no cure as yet for type 1 diabetes; for type 2, which constitutes nearly 80 percent of the global incidence of this disease, the cure is clearly in diet and lifestyle behavior to correct the transport imbalance.
We have learned so much in recent years about this physiological imbalance that it even has a name—metabolic syndrome.
INSULIN RESISTANCE AND METABOLIC SYNDROME
In 1976, I was a speaker at a medical conference on diabetes in Seattle, Washington. My talk was about the years-long transition that takes people from a state of balanced glucose transport through insulin resistance to the defect in glucose transport that today we diagnose as type 2 diabetes. After my presentation, a prominent diabetes specialist raised his hand and commented that there was “no such thing” as the transition I had described. “Either you have diabetes or you don’t,” he said emphatically.
His contention was a common one among medical practitioners, yet much work refuting the contention had already been done by the time he delivered it. In 1949, Dr. Harold Himsworth, dean of the University College Hospital and Medical School in London, published a seminal paper in The Lancet about a form of diabetes that, he said, was caused by lack of proper glucose transport; the transport defect, according to Himsworth, was due to a defective action of insulin, not to the inability of the pancreas to secrete insulin.
In 1968, Drs. John Farquhar and Gerald Reaven at Stanford University Medicine School published work on insulin resistance that defined it as part of a syndrome between proper glucose transport and type 2 diabetes. Twenty years later, in a famous lecture, Reaven, one of the nation’s most prominent endocrinologists, elaborated on this syndrome. He articulated the cluster of conditions that constitutes the functional imbalance in physiology and that derives from a dysfunctional intersection between a person’s genes and lifestyle—what we today call metabolic syndrome. Emphasizing that metabolic syndrome is not a disease, Reaven ticked off the biomarkers that characterize it: a high level of triglycerides in the blood, low HDL levels, elevated blood pressure, high levels of blood glucose, and what is called central obesity—meaning an apple-shaped body that is significantly overweight or obese. All of these characteristics, Reaven contended, derive from the common cause of insulin resistance and an imbalance in glucose transport that impairs glucose tolerance.*
Today, physicians use this cluster of conditions as diagnostic criteria to test whether a patient may be on the way to type 2 diabetes and, potentially, heart disease, dementia, gout, fatty liver disease, and other ailments. The more of these diagnostic criteria an individual has and the more the individual’s values deviate from normal, the closer she or he is to type 2 diabetes.
If you know you have some or all of these conditions, or if your doctor has spoken to you about metabolic syndrome, don’t think that you are alone. By 2011, a study reported in the journal Diabetes Care concluded that more than a quarter of the adult population in the United States has metabolic syndrome; in some specific genetic groups marked by racial or ethnic distinctions, the prevalence is above 50 percent, as was the case among the Pima Indians.
And as we saw with the Pima, the condition took root at the intersection between genes and environmental factors. For the Pima, it was the radical change in diet and activity patterns that over time interrupted their transport and cellular communications processes and led to insulin resistance. Yet, as we know, there are numerous genetic variations in the regulatory network that controls insulin signaling and glucose transport, and these can be highly individualistic. So the idea that everyone with metabolic syndrome has the same disorder and should get the same therapy makes no sense whatsoever. The constellation of conditions that we conveniently describe as metabolic syndrome can be as individual as fingerprints.
A DIFFERENT WAY TO MANAGE METABOLIC SYNDROME
Metabolic syndrome and type 2 diabetes have been a twin focus at the Functional Medicine Clinical Research Center for some time—with important results from clinical trials involving patients with one or the other.
One trial consisted of a diet plan we might describe as “modified Mediterranean” along with a program of daily walking. It is termed “modified” because the amount of refined carbohydrate is limited. The Mediterranean-style diet, as you probably know, has been shown in a number of studies to improve insulin sensitivity and to ameliorate the adverse symptoms of metabolic syndrome and type 2 diabetes. It is a low-glycemic-load diet, which means that its foods don’t spike the level of sugar in the blood after eating. This lessens the demand on the pancreas to secrete insulin, and it lowers the need to immediately transport glucose into the tissues.
Participants in our clinical trial were given no calorie limits; rather, they were encouraged to eat as much as they wanted of foods on the approved low–glycemic-load list while avoiding everything on a list of such high-glycemic-load contributors as sugary foods, white flour foods, convenience and snack foods, and sweetened beverages. In our view, the taste of sweetness, whether through sugar or through artificial sweeteners, sets up an entirely different response to foods and alters the glycemic response.
The control group followed this modified Mediterranean eating plan exclusively. But a second study group added to it a medical food containing specific phytonutrients. This food had been developed by our research team to improve glucose transport by stabilizing insulin signaling; the clinical trial was its first test.
Both groups also followed the daily walking program, which was simplicity itself: a minimum of twenty minutes daily at a walking pace, not a stroll. Regular walking, as the research makes clear, can improve insulin sensitivity in sedentary people.
The most visible result after the twelve-week trial was weight loss; participants on average lost about a pound of body fat per week. Test results were equally positive: in all participants, 70 percent of the markers for insulin resistance and metabolic syndrome simply disappeared.
The most remarkable outcome, however, was the effect of the medical food, loaded with the specific phytonutrients, taken by the special study group. Their results trumped even the positive results of the control group. In fact, the difference between the two groups was so significant that it was evident the moment we put the data onto a spreadsheet and looked at the comparison participant by participant. The phytonutrient-supplemented study group experienced better than a 30 percent improvement in reduced LDL, increased HDL, and reduced triglycerides. In other words, our study demonstrated that the excellent results the Mediterranean diet can achieve in terms of managing insulin resistance can be even further improved if the diet is supplemented with specific phytonutrients that support the glucose transport process.* We believe this was the first clinical trial showing that patients with insulin resistance and metabolic syndrome get an even better health outcome if their Mediterranean-style diet is supplemented with specific phytonutrients than from the diet alone.
PHYTONUTRIENTS AND GLUCOSE TRANSPORT
What were the phytonutrients in the medical food that supplemented the Mediterranean diet? They came from all over the world and were selected after extensive screening of more than 200 plant and spice extracts that medical anthropology tells us are used by indigenous cultures to manage the disease we call diabetes. The screening was carried out by Dr. John Babish, a onetime Cornell University research pharmacologist and the lead scientist for the trials, in a series of experiments to evaluate how each extract might influence glucose transport. Babish’s tests confirmed that the highest beneficial activity came from those substances that worked as selective kinase response modulators—SKRMs—in influencing the insulin signaling network. They were highly active when tested in diabetic animals, and they proved equally active in humans in our clinical trials.
The most active SKRM phytonutrients in supporting insulin sensitivity and balanced glucose transport? Here are the top five: soy-derived phytosterols, lignans, and isoflavones; hops-derived reduced isohumulones; and anthocyanins derived from the bark of the Acacia nilotica tree. This tree, found in equatorial Africa, has been used medicinally for centuries—mostly in a tea made from the bark and given to people with the symptoms of diabetes. Both on its home ground and in our lab, this extract proved powerful, and the combination of these top five phytonutrients, formulated into a medical food, clearly improved insulin signaling and glucose transport in the trial participants.
LESSONS LEARNED: ON A PERSONAL NOTE
For me, these results had particular resonance. As a scientist engaged for nearly fifty years in basic and clinical research, I was struck by the extraordinary consistency of the data in the trials—from cell biology screening experiments to animal testing in different diabetic models to human clinical trials. The lesson it brought home to me was the extent to which and the power with which the bioactive compounds manufactured in the plant kingdom’s own laboratory can influence human physiology and health in very specific ways, simply through their influence on cellular communications and transport.
The results of the trials also, in my view, open the door wider to an expanded role for medical foods in the safe and effective management of chronic illness. Defined as foods specially formulated and intended for the dietary management of a disease the nutritional needs of which cannot be met by normal diet alone, medical foods are regulated under the FDA’s 1988 Orphan Drug Act amendments and are subject to the general food and safety labeling requirements of the Federal Food, Drug, and Cosmetic Act. They are also one of the key tools that functional medicine practitioners use in implementing medical nutrition therapy.
Finally, the trials confirm yet again the significance of the need to individualize any therapeutic program in order to optimize the unique genetic potential of each patient or participant. There is no such thing as one perfect diet for everyone any more than there is one perfect drug for everyone. General considerations may guide us in constructing an overall plan, but the overall approach must always be fine-tuned for the individual. It means that health practitioners need to be very careful not to set rules for everyone to follow, but rather should offer guidelines and objectives that can then be personalized for the individual. More on this in Chapter 11.
CHAPTER 8 TAKEAWAY
1. Defects in cellular transport of nutrients, hormones, or other cellular messenger substances can contribute to many chronic diseases—among them, heart disease and type 2 diabetes. The latter may result from poor glucose transport caused by resistance to insulin signaling.
2. Statins reduce cholesterol in cells but may also diminish such other important cellular substances as CoQ10 and neurosteroids.
3. Omega-3 fatty acids are important cellular building materials for ensuring proper brain, eye, heart, and kidney function. Cod liver oil is an excellent source of omega-3 fatty acids and has the added value of containing vitamins A and D.
4. Lymphatic system function, essential for the efficient transport of fats and fat-soluble vitamins, is improved through physical activity and manipulative therapies.
5. A personalized therapeutic lifestyle program containing supplemental phytonutrients has been shown to improve insulin sensitivity.