Syndrome X

Those who are in the sub-clinical phase (age 35-45) and clinical phase of aging (age 45 and above) have a one in three chance of getting this syndrome and not knowing it. Perhaps the following signs are more recognizable: feeling sluggish, physically and mentally, especially after a meal. Gaining a pound here and a pound there-and having increasing difficulty losing them. Having blood pressure creep up year after year. And finding that the blood cholesterol, triglycerides, and blood sugar levels are doing the same. These are all accepted signs of aging. They are also all of the symptoms of Syndrome X.

Syndrome X can explain why you feel lousy today -- such as being tired and fuzzy-minded. It can explain why you have high triglycerides, high cholesterol or high blood pressure, why you are feeling lousy after meals, and why you are seeing your health spin out of control without knowing why. It can also explain why you are aging faster than your peers. More importantly, Syndrome X sets the stage for catastrophic health problems, such as heart disease, diabetes, Alzheimer's, cancer, and other age-related diseases.

It is estimated that this syndrome afflicts over 60 million Americans and one in four adults over age 35. Hypercholesterolemia, cigarette smoking, hypertension, and obesity are the main culprits for the development of artherosclerotic coronary artery disease (CAD). However, these account only for half of the cases of CAD. The other pathologic processes underlying atherosclerosis remain unknown. Syndrome X may be the cause of up to fifty percent of all heart attacks. It is an epidemic of massive proportion.

How do you develop Syndrome X?

Syndrome X develops slowly over time, often over a course of 20 years or more. It is the end result from years (often decades) of taking in a modern day diet high in refined carbohydrates such as breads, starches and sweets. These foods, once taken, trigger a rapid increase in blood sugar levels, and the body responds by raising levels of insulin secretion that in turn helps to move the sugar out of the blood stream into the cells. Insulin is a hormone secreted by the pancreas. It helps the body utilize glucose (blood sugar) by binding with receptors on cells like a key would fit into a lock. Once the key - insulin - has unlocked the door of the cell, the glucose passes from the blood into the cell. Inside the cell, glucose is either used for energy or stored for future use in the form of glycogen in liver or muscle cells.

The more carbohydrates you eat, the more your pancreas releases insulin to lower the excessive blood sugar. This is especially so with simple or refined carbohydrates that are converted into sugar quickly (the high-glycemic index foods like white bread and white flour) once inside your body. While insulin levels rise and fall with each meal and is part of the normal metabolic process, chronic carbohydrate overload causes chronic insulin overload. The cells of the body, be they the muscles or the fat tissues, recognize that excessive sugar is toxic. They try to shut down the influx of sugar into the cells and therefore go through a down-regulation process to resist the command of insulin. This state is called insulin resistance. The pancreas, in response to the insulin resistance and resulting lowered transport of glucose out of the blood stream to the cell, puts out even more insulin in order to avoid too high a blood sugar level. This compensatory increase in insulin output continues until the pancreas fails to keep up. Some people produce two, three or four times the normal amount of insulin. Yet, because the cells have lost their sensitivity to insulin, they require even more of it to maintain normal glucose levels. In advanced stages of insulin resistance, when the pancreas becomes exhausted and can no longer maintain the insulin production, insulin production drops, resulting in adult onset diabetes mellitus (also called type 2 diabetes). Insulin resistance plus compensatory hyperinsulinemia is nature's way of preventing the evolution into type 2 diabetes. It is often referred to as a pre-diabetic state.

As long as there is insulin resistance, the blood sugar and blood insulin levels are both high. Over time, high blood sugar and high insulin cause a myriad of destructive damages to almost every tissue they touch. It is important to recognize while insulin resistance or high blood sugar is each bad for health on its own, it takes both insulin resistance and compensatory hyperinsulinemia, to result in the various manifestations. These manifestations represent the resultant damage and surface as a compilation of symptoms representative of multi-system dysfunction. This includes the cardiovascular system, muscular system, kidney system, reproductive system, and lipid metabolic system, just to name a few. These symptoms, when grouped collectively in a setting of insulin resistance, is called Syndrome X. It can go undetected for up to 40 years, and a family history of type 2 diabetes, CHD, or hypertension increases the risk for Syndrome X.

SYNDROME X as explained by Dr Reaven

Syndrome X was first discovered by Stanford University Professor and researcher Gerald Reaven, MD. In 1988, he first presented the results of twenty years of study that showed that the effect of an array of changes around a little known medical condition called insulin resistance to increased heart disease.

In his book Syndrome X, Dr Reaven describes the condition as follows:

This deadly heart ailment begins in the bloodstream, shortly after we eat. That's not a startling idea, for we know that eating fatty or cholesterol-laden foods can be bad for our hearts. However, the Syndrome X culprit isn't red meat or butter, it's carbohydrates. Yet these carbohydrates are reluctant, inadvertent offenders.

Before entering the body proper, our food is broken down into various constituent parts in the intestine. One of these is glucose (blood sugar) from carbohydrates. Upon entering our cells, some of the glucose is put right to work providing the energy that cells need to perform their various tasks. The rest is stored in certain cells for later use. But the glucose doesn't simply flow into the storage cells. Instead, it must be guided in by insulin, a protein secreted by the pancreas.

Insulin acts like a shepherd, herding its precious flock into the cellular "corrals". Unfortunately, in many of us, glucose behaves like a group of errant sheep, stubbornly refusing to go where the shepherd directs. When that happens, the pancreas pumps out more and more insulin. That's the biochemical equivalent of sending out more and more "shepherds" to get the "sheep" into the "corrals". Imagine hundreds of shepherds chasing thousands of sheep across a pristine field covered with thick, beautiful green grass. Those hundreds of feet and thousands of hoofs will quickly tear up the field, ripping out or flattening down clumps of grass. Soon, the field that once looked so green and lush will be trampled and scarred, brown and dirty.

Something similar happens inside your body when glucose refuses to move into the storage cells at the insulin's command. The interior linings of your arteries, like the grassy field, are "ripped" and "trampled" as the body attempts to overcome this problem.

Eventually, the insulin "shepherds" corral the glucose, and order is restored in the body. But all is not well, for the "field" (the lining of your coronary arteries) has been damaged, and there's other damage, as well. This damage sets the stage for heart disease.

Pathology of Syndrome X

The fundamental defect in patients with Syndrome X is insulin resistance in both adipose and muscle tissue. The net result is hyperinsulinemia. The term hyperinsulinemia refers to higher-than-normal levels of insulin in the blood.

Each cell reacts to insulin differently. Some organs are highly sensitive to high insulin, while others are less so. Insulin resistance per se therefore does not cause damage, but it is the reaction of the various tissues to chronic high insulin that is the main problem. An example is the kidney. The ability of insulin to stimulate sodium re-absorption by the kidney could be very normal but at the same time the muscles in that individual could be quite resistant to insulin action. The kidney is therefore an "innocent bystander" of the increased insulin secretion in this person due to the muscle insulin resistance.

Excessive insulin causes damage to the whole body, including:

• Endothelium. The inner lining or endothelium of the arterial walls comes under attack by excess insulin. The risk of arterial blood clots, which can cause heart attacks or strokes, is increased. The pathophysiology is very complicated. It is clear, however, that the damages include reduced nitrous oxide activities (which could lead to hypertension), increased platelet and monocyte adhesion, increased pro-coagulant activity, impaired fibrinoloytic activity, and impaired degradation of glycosylated fibrin. The net result: increased blood pressure, increased formation of atherosclerotic plaques, increased thrombus formation, angina, and heart attack. The risk of cardiovascular disease is significantly increased when the endothelium is damaged.

• Pancreas. Type 2 diabetes
develops when the pancreas ultimately "burns itself out" from the excessive demand for insulin production which it cannot keep up in an insulin resistance state. Only 20% of people with excessive insulin due to insulin resistance develop diabetes. The rest continues to produce enough insulin to meet the demand.

• Ovaries. The ovary, being exposed to consistently higher levels of insulin, increases its testosterone secretion accordingly, the ovary being insulin sensitive. It is a major factor in the development of polycystic ovary syndrome.

• Cancer. Some research indicates it might also increase the risk of prostate, colon and breast cancer.

• Premature Aging. Syndrome X also generates high levels of cell-damaging free radicals and causes premature aging. Some researchers believe it can also increase the risk of Alzheimer's disease.

• Kidneys. Excessive insulin leads to sodium retention. Fluids follow sodium, resulting in excessive fluid in the body and ultimately hypertension, a condition that is present in 50% of those with Syndrome X

Manifestation of Syndrome X

The manifestations of Syndrome X can be broken down into eight major categories:

1. Glucose intolerance: Not all individuals with Syndrome X have diabetes by definition. However, their blood glucose concentration is usually higher than those individuals who do not have Syndrome X. Many people who are insulin resistant produce large enough quantities of insulin to maintain near normal blood glucose levels. In Syndrome X, VLDL, chylomicrons and their metabolic remnants (chylomicron and VLDL remnants) are removed more slowly from the plasma by virtue of their increased concentrations, resulting in increased postprandial lipemia. Unfortunately, the increased VLDL also reduces the ability to remove postprandial newly absorbed chylomicrons. More often than not, they have impaired glucose tolerance (IGT). A glucose tolerance test, where insulin and blood glucose are measured, can help determine if someone is insulin resistant.

2. Dyslipidemia: The characteristic findings are high plasma triglycerides and low HDL cholesterol. This combination is a hallmark of Syndrome X. The pathway is quite interesting. With high blood insulin level, the liver produces more triglyceride rich VLDL, a carrier of fat. The amount of triglycerides therefore increases. Cholesterol ester transfer protein (CETP) transfers cholesterol from HDL to VLDL, exchanging it for triglycerides. As a result, the HDL ("good") cholesterol falls.

In addition, there is a shift in the LDL particle diameter to smaller and denser LDL cholesterol fractions, which is the most potent and damaging kind. The dense LDL cholesterol will attack the endothelium, causing inflammatory responses that ultimately results in fatty streak and plaque formation characteristic of atherosclerosis.

3. Uric acid metabolism: There is a decrease in the ability of the kidney to excrete uric acid, so renal uric acid clearance is decreased and the blood uric acid concentration is increased.

4. Kidney manifestation: It appears that half the patients with hypertension are insulin resistant. This is due to fluid retention caused by high insulin level.

5. Hemodynamic manifestations: There is evidence that the sympathetic nervous system activity is increased in insulin resistant individuals. Systolic pressure is often greater than 140 mmHg, and diastolic pressure higher than 90 mmHg. This further contributes to hypertension.

6. Fibrynolytic changes: There is an increase in Plasminogen activator inhibitor 1 (PAI-1). When PAI-1 is high, dissolution of blood clot is reduced, and fibrinogen and thrombus formation increases. The increase in fibrinogen tends to increase coagulation. This plays a role in the development of coronary heart disease.

7. Obesity. Obesity is a common feature. The body mass index (BMI) is often greater than 25 kg/sq.m. Until recently, insulin resistance was thought to cause obesity only in adults, because it is considered an age-related condition. This is clearly wrong. A 1998 evaluation of more than 2,000 Finnish men led to the finding that insulin resistance is associated with obesity beginning in early childhood and middle age. The researchers also noted that each five percent weight increase at age 20, over the average for that age, was associated with a nearly 200 percent greater risk of full-blown Syndrome X by middle age.

High insulin itself does not cause obesity. On the contrary, obesity leads to increased insulin resistance. We are all born with a certain degree of insulin resistance or sensitivity. As one gains weight, one's body becomes more insulin resistant. Studies have shown that tissue sensitivity to insulin is decreased by about 30-40% in people who are 35% over their ideal body weight.

Why obesity makes us more insulin resistant is not totally clear. It may be related to the fact that people who are obese because of their increased levels of body fat release more fatty acids from their fat depots, which in turn can inhibit insulin action.

8. Antioxidant Depletion. Low levels of antioxidant vitamins and DHEA (dehydroepiandrosterone) and high cortisol levels are commonly found in people with Syndrome X. It is likely to due to the increased free radical activity, and concurrent reduction in the endogenous antioxidant level as the body tries to neutralize the free radical activities. It has been shown, for example, that atherosclerotic plaques not only contain cholesterol but also oxidized ascorbate (vitamin C). The body deposits the antioxidant ascorbate there in an attempt to overcome the free radical damage.

Laboratory Values

Fortunately, no complicated tests are needed to diagnose Syndrome X. Very simple measurements and good interpretive skills and careful attention in history taking are needed to have an accurate diagnosis of insulin resistance. It comes down to the clinician's knowledge of metabolism and endocrinology. Abnormal test results include elevated blood pressure, triglycerides, uric acid and glucose levels accompanied by a low HDL count. If these results are all normal, the chance of being insulin resistant is very low. Let us take a closer look.

• Fasting triglyceride level above 1.9 mmol/L (170 mg/dl) is a very good marker of the increase in postprandial lipemia, the appearance of small dense LDL, and the increase in PAI-1 levels. A high fasting triglyceride is a key marker for Syndrome X (or insulin resistance)

• HDL cholesterol level that is less than 1.0 mmol/L (38 mg/dl) is also a good indicator of insulin resistance.

• Fifty percent of individuals with hypertension have insulin resistance. Systolic pressure is often greater than 140 mmHg and diastolic pressure greater than 90 mm/Hg without medication.

• Fasting glucose above 5.5 mmol/L (100 mg/dl) indicates that a person is at risk of insulin resistance. The higher the blood glucose within the normal glucose range, the greater the insulin resistance. A two hour glucose concentration post glucose load of greater than 7.8 and less than 11.1mmol/L (140 and 198 mg/dl respectively) may not merit the diagnosis of type 2 diabetes, but will suggest insulin resistance.

• Triglyceride to HDL cholesterol ratio of more than 2 is a warning sign. If the ratio is over 4, it is a good indicator of insulin resistance.

Interesting, fasting insulin level may not be the best indicator. The measurements are hard to do, and the values are going to differ from lab to lab. One can have a high insulin level and not have syndrome X.

It should also be noted that a high LDL in itself is not a key marker for Syndrome X.

 LDL in most laboratories is derived from calculations. The formula is:

          LDL = total cholesterol - HDL cholesterol - (triglyceride / 5).

It should be noted if the triglyceride level is above 300 mg/dl, the LDL calculation will not be accurate because of correlation problems. In this case, the actual measured LDL level should be obtained. While a high LDL is a good indicator of cardiovascular risk, a low HDL cholesterol level is even more significant, as well as a low (<4.5) total cholesterol/hdl cholesterol ratio. Furthermore, advanced cardiovascular indicators such as lipoprotein (a), homocysteine, and C reactive protein (an indicator of endothelial inflammatory response) should be part of the routine workup of anyone suspected of Syndrome X.

Syndrome X in a Nutshell

The underlying cause of Syndrome X is insulin resistance - a diet-caused hormonal logjam that interferes with your body's ability to efficiently burn off the sugar you eat. The more sugar you eat, the higher the risk for syndrome X. Syndrome X occurs when the high insulin level damages our bodies' internal systems, producing a crop of symptoms. Specifically, this group of health problems includes insulin resistance (the inability to properly deal with dietary carbohydrates and sugars), abnormal blood fats (such as elevated cholesterol and triglycerides), being overweight, and high blood pressure.

Symptoms of Syndrome X include:

• Insulin resistance
• Abnormalities of blood clotting
• Low HDL and high LDL cholesterol levels
• High triglyceride levels
• Central obesity (excessive fat tissue in the abdominal region)
• Impaired glucose tolerance
• High blood pressure
• Low levels of antioxidant vitamins and DHEA, with high anti-inflammatory and anti-stress hormone cortisol

If you have 3 or more of the above, you should consider yourself either having or at high risk of Syndrome X.

Cardiac Syndrome X

The term "cardiac Syndrome X" refers to a heart condition where chest pain and electrocardiographic changes suggest that ischemic heart disease are present, but without angiographic findings of coronary disease. Some research has shown that people with cardiac Syndrome X also have lipid abnormalities. This suggests that Syndrome X and cardiac Syndrome X may be one and the same.

Causes of Syndrome X

No one knows for sure what causes syndrome X. Some scientists think that a defect in specific genes may cause insulin resistance and intensive research is now underway. What we do know so far is:

• Insulin resistance is aggravated by obesity and physical inactivity; both of which are increasing in the U.S.

• The more sugar you take in, the higher the chance of you developing Syndrome X.

The fact that many obese people have high insulin levels but do not develop diabetes or syndrome X is interesting. Many obese people have high insulin sensitivity and do not have insulin resistance at all. There is evidence of a widespread variability in insulin mediated glucose disposal by muscle in non-diabetic individuals. In a study conducted by Dr.Reaven on 500 individuals, there is an apparent ten-fold difference between the most insulin sensitive and the most insulin resistant non-diabetic individual.

Syndrome X and Type 2 Diabetes

There are over 60 million people in the United States alone who have Syndrome X. There are an additional 24 million people that have glucose intolerance, a pre-diabetic state. In addition, there are over 16 million people who have adult onset diabetes mellitus (Type 2 diabetes) and only half of these individuals knows they have diabetes. Some diabetics have had their disease for over 8 to 10 years before the physician even makes the diagnosis. This may account for the fact that over 60% of their diabetic patients already have major cardiovascular disease at the time of diagnosis of diabetes.

Science has not yet determined why some people with insulin resistance eventually develop diabetes and others do not. Type 2 diabetes develops in a relatively small number of individuals who are insulin resistant. Most individuals who are insulin resistant continue to secrete large amounts of insulin and do not get type 2 diabetes. We do know that insulin resistance is the body's natural defense against chronic high sugar load. It is the body's defense against the evolution to diabetes. In other words, type 2 diabetes is often the advanced stage of insulin resistance.

The point to remember is that while most insulin resistant patients do not get diabetes, they are still at risk for coronary heart disease.

Ideal fasting blood sugar level

The easiest way to measure the status of sugar in your body is through a simple fasting blood sugar laboratory test. A fasting serum glucose level of more than 125 mg/dL is the current threshold for identifying patients with diabetes. This was based on the incidence of diabetic retinopathy. Now physicians are increasingly focused on the diabetes-related risk of coronary heart disease. In a cross-sectional study of 2,440 people, researcher Dr. Dennis Sprecher reported that people with a fasting serum glucose level of 100-125 mg/dL had an adjusted, 2.8-fold higher risk of having a coronary heart disease event than people with a fasting glucose level of less than 79 mg/dL. This finding suggests that patients with high levels of serum glucose in the nondiabetic range (100-125 mg/dl) also face a substantial risk of having coronary heart disease. In fact, the Cleveland Clinic Foundation now uses a fasting serum glucose of 90 mg/dL or higher as a biomarker of coronary heart disease risk. Ideal fasting blood sugar should be no higher than 90mg/dl, regardless of age.

Syndrome X and Coronary Heart Disease

Individuals with Syndrome X have an increased risk of heart disease according to the American Heart Association (AHA). The relationship is not Syndrome X leading to CHD or one factor being responsible for the increased risk, but rather that, taken as a cluster, there is increased prevalence of CHD in people with insulin resistance and the various manifestations. Those afflicted with syndrome X is akin to have been injured by a shotgun blast, with multiple bullet wounds. While none of the multiple bullet wounds may by itself lead to death, the collative damage caused by the multiple bullet wounds raises the chances of death significantly. In real-life terms, we are talking about increasing risks of cardiovascular disease, cancer, stroke, and pre-mature aging.

Only one study has shown that in people followed prospectively, insulin resistance increases the risk of CVD. There are multiple studies showing that insulin level, as a predictor or surrogate measure of insulin resistance, predicts CHD. We also know that a low HDL is a powerful predictor of CHD. There is more and more evidence that small dense LDL particles and increased remnant lipoprotein concentrations due to the increased postprandial lipemia are linked to CHD.

Syndrome X and Aging

Vladimir M. Dilman, M.D., co-author of The Neuroendocrine Theory of Aging, refers to insulin resistance as an "age-related pathology." In fact, it is one of the few consistent indicators of longevity. Centenarians have a lower blood sugar and blood insulin level relative to their age.

In the mid-1970s, biologist Anthony Cerami discovered that chronically high blood glucose levels was the main trigger in a chemical process that produced advanced glycosylation end products (AGES), which were implicated in normal and advanced aging and age-enhanced diseases. AGEs form at accelerated rates whenever blood-sugar levels are high as with age.

AGEs damage to the body is extensive. Referred to as a carmelization or browning reaction, cross-linking by AGEs involve a chemical reaction between sugar and protein molecules. No one part is spared. Serious damage to cell membranes and collagen fibers is near universal. This cross-linking leads to the stiffening of connective tissue and hardening of arteries, leading to pre-mature aging and hypertension. As cross-links increasingly reduce the flexibility and permeability of tissues and cells, cellular communications and repair processes also begin to break down. A compensatory inflammatory response may be launched by the body, especially in the endothelium. This leads to a cascade of damaging events resulting in fatty streaks and atherosclerosis. Eventually, the tissues of the body become irreversibly transformed, and the inevitable result is aging, disease and finally death.

It is well known that bathing your cells in high sugar (as in diabetics) causes premature aging. This is because this sugar-driven damage acquires breakneck speed, raising their levels of AGE-infused collagen to those of elderly people. Diabetics suffer a very high incidence of nerve, artery and kidney damage because high blood sugar levels in their bodies markedly accelerate the chemical reactions that form advanced glycation products. The endothelium of diabetic patients also secretes unwanted growth factors that leads to blood vessel hypertrophy and reduced lumen size. This reduces the blood flow, exacerbating the already compromised insulin delivery and further increases the chances of insulin resistance. The reduced blood flow leads to reduced oxygen delivery to needy tissues, resulting in increased peripheral neuropathy commonly seen in diabetes.

Conventional Treatment of Syndrome X

Physicians have been concentrating on treating the symptoms of Syndrome X such as hypertension and dyslipidemia rather than concentrating on the underlying problem, which is insulin resistance. Since over 50% of the prescriptions filled in the United States are for hypertension, elevated cholesterol levels, heart disease, and diabetes, you can get a glimpse of the economic importance of this problem.

Syndrome X is usually totally reversible without drugs. The key is to slow down carbohydrate absorption while increasing insulin sensitivity. This can be done by lowering your carbohydrate intake (the low-carb diet), together with a nutritional supplementation program designed to slow carbohydrate absorption, increase insulin sensitivity, and normalize blood sugar levels.

However, human nature (and human metabolism) being what it is, the majority of patients with syndrome X cannot accomplish these goals. In these cases, each metabolic disorder associated with syndrome X needs to be treated individually, and aggressively. A short-term treatment with drugs is seldom but may be needed.

Treating the lipid abnormalities. The lipid abnormalities seen with syndrome X (low HDL, high LDL, and high triglycerides) respond nicely to weight loss and exercise. Treatment should be aimed primarily at reducing LDL and triglyceride levels, and raising HDL levels. Successful drug treatment usually requires treatment with a statin or one of the fibrate drugs, or a combination of a statin with either niacin or a fibrate. It should also be noted that the use of statin drugs is not without its problems.

Treating the clotting disorder. Patients with syndrome X have several disorders of coagulation that make it easier to form blood clots within blood vessels. These blood clots are often a precipitating factor in developing heart attacks. Patients with metabolic syndrome X should generally be placed on daily aspirin therapy to help prevent such clotting events.

Treating the hypertension. High blood pressure is present in more than half the people with metabolic syndrome X, and in the setting of insulin resistance, high blood pressure is especially important as a risk factor. Recent studies have suggested that successfully treating hypertension in patients with diabetes can reduce the risk of death and heart disease substantially. Low dose diuretics should be used according to Dr.Reaven. No more than 12.5 mg of hydrochlorathiazide should be prescribed. People with Syndrome X should not be prescribed the anti-hypertensive dosages of thiazides that have been recommended in the past. Difficult cases should be controlled with ACE inhibitors. ACE inhibitors increase levels of nitrous oxide (a potent endothelium generated vasodilator), resulting in vasodilatation and blood pressure reduction. ACE inhibitors also have been shown to improve endothelial function, and so have HMG-CoA reductase inhibitors (such as lovastatin and pravastatin), and to a lesser degree, calcium channel blockers (such as verapamil and nifedipine).

Treating High Blood Sugar. High blood sugar must be normalized. Traditionally there are four points of intervention to reduce blood sugar:

   • Pancreas. Two major classes of drugs are the sulonylureas and the meglitinides. Sulfonylureas have been used for more than 4 decades. Their primary goal is to increase the level of endogenous insulin by stimulating the pancreatic secretion. These agents have no direct effect on insulin resistance. They may decrease the resistance slightly by reducing plasma glucose level. The meglitinide class, of which repaglinide is approved in the U.S., also stimulates insulin release from the pancreas. Clearly, these should be avoided among those with Syndrome X who already have a high insulin level. Further insulin will only worsen the problem.

   • Intestines. Alpha-glucosidase inhibitors are currently represented by acabose. The primary mechanism of action of these agents is to inhibit specific enzymes that break down carbohydrates in the small intestine. Absorption of carbohydrates is delayed, resulting in a reduction of postprandial hyperglycemia. No specific action on insulin resistance has been reported.

   • Liver. The biguanides, of which metformin is the agent used in the U.S., mainly decrease hepatic glucose production, They also increase peripheral insulin sensitivity, leading to reduced plasma glucose level. They also have some effect in reducing intestinal glucose absorption. Clearly this is a better drug to use than the previous two.

  • Muscle. This class of oral agents is known as the thiazolidinediones, of which troglitazone is approved for use in the U.S. It reduces insulin resistance by increasing the uptake of glucose by peripheral tissues such as skeletal tissue.  It is therefore uniquely designed to attack insulin resistance.

Natural Treatment of Syndrome X

While there are no drug treatments that can directly reverse the insulin resistance that causes syndrome X; there is, in fact, a way to reverse the insulin resistance - and that is through diet, exercise, and nutritional supplementation.

1. Diet

Clearly, the following goals should be met in any diet for Syndrome X sufferers:

a. Reduction of carbohydrates. With less carbohydrates around, there will be less insulin needed.
b. Reduction of LDL cholesterol which can lead to heart disease
c. Reduction of blood glucose level
d. Increase in insulin sensitivity

The question is: If you reduce carbohydrate, and reduce fat, then how are you going to get enough calories? If one food group is reduced, the calories must be supplied by another food group. The strategy is clear - reduce carbohydrates, especially simple refined carbohydrates. How you make up the calories is less clear. There are only two options available: carbohydrates can be replaced with proteins or with fats. Clearly saturated fats should be restricted to reduce the risk of cardiovascular disease and to lower LDL cholesterol level. Therefore, part of the carbohydrate should be replaced with "good" fat. Replacing carbohydrates with proteins ignores the fact that protein, once in the intestinal tract, converts to amino acid. Amino acids increase insulin secretion. It is unclear, however, whether proteins are as potent as carbohydrates in stimulating insulin secretion.

Dr Reaven's Syndrome X diet derives 45 percent of calories from carbohydrates, 15 percent from proteins and a hefty 40 percent from fats. In contrast, American Heart Association recommends keeping fat intake to no more than 30 percent of your total calories and boosting the carbohydrates to at least 55 percent.

What makes Dr Reaven's diet different from the latest run of carbohydrate diets is that his eating plan is low in protein. This is very different from Dr Atkins' diet that is high in protein.

A diet high in protein is suitable for those with normal insulin sensitivity, but inappropriate for those with syndrome X. It is important to note that there are good fats and there are bad fats. The fats recommended by Dr.Reaven are mostly heart-friendly unsaturated fats from plant and vegetable sources such as olive oil and nuts, not from the artery-clogging saturated fats present in steaks.

Dr Reaven suggests replacing saturated fats with and mono- and poly -unsaturated fats will equally benefit LDL cholesterol lowering as compared to replacing saturated fats with carbohydrates. This is confirmed in multiple studies. Mono- and poly-unsaturated fats do not raise insulin levels, so you get the benefit of both LDL cholesterol and Syndrome X control. Unsaturated fats are found in foods such as vegetable oils (olive oil in particular is high in mono-unsaturated fats) nuts, and avocados, whereas saturated fats are abundant in fatty cuts of meat and whole milk dairy products.

It has been postulated that use of low glycemic-index carbohydrates will avoid worsening the manifestations of Syndrome X due to its slow glucose release and absorption rate. There is little doubt that low glycemic-index carbohydrates such as fruits and vegetables are superior when compared to high glycemic-index carbohydrates such as white flour and white bread. Dr Reaven studied this by increasing the fiber intake to the level recommended by the ADA for diabetics, and it had almost no effect. In a recent paper, substantial increases in the fiber level (exceeding the ADA recommendation) resulted in improved metabolic characteristics, as compared to a high carbohydrate/low fat diet. No comparison was made between the very high fiber diet vs. a diet low in carbohydrates and high in unsaturated fats.

The simplest and most effective approach is to replace the carbohydrates with poly- and mono-unsaturated fats and restrict saturated fat intake, to achieve both lower LDL cholesterol and improve Syndrome X.

2. Nutritional Supplementation.

A variety of natural non-toxic food based compounds can be used. The goals are to normalize blood sugar, and increase insulin sensitivity.

Treating the lipid abnormalities. For Dyslipidemia, the following can be considered: pantethine (300 -1,200 mg), panthothenic acid (300-1,300 mg), guccolipid (50-150 mg), polycosinol (5-10 mg), mineral ascobates (2-5 grams), lysine (2-5 grams), proline (1-2 grams), chromium polynicotinate (400 -1200 mcg), and fish oils (1000 to 4000 mg).

Treating the clotting disorder.
To reduce the blood clot risk, natural compounds such as vitamin E (300 to 1200 I.U.) and gingko biloba extracts (30 to 150 mg) have blood thinning properties and help promote circulation. Antioxidant therapy with optimum doses of Vitamin A, C, and E helps to stabilize plaques, improve vascular tone, and reduce thrombus.

Treating the hypertension. To lower blood pressure, antioxidant therapy helps to stabilize plaques and improve vascular tone by inhibiting oxidation of LDL cholesterol.

Treating high blood sugar. For glucose normalization and to increase insulin sensitivity, natural non-toxic compounds that have sugar modulation effects include chromium polynicotinate (400 -1200 mcg), venadyl sulfate (25 -100 mg), lipoic acid (100-300 mg) can be considered.

For rebalancing the internal terrain to enhance digestive balance and efficiency,
digestive enzymes, green foods such as chlorella, spirulina, algae, soluble fiber, and probiotics should be considered

For antioxidant deficiency: a strong multi-vitamin with at least 10,000 I.U. of beta carotene, 500 mg of vitamin C, 200mg of selenium, 100 mg of grape seed extract, 30 mg of co-enzyme Q10.

For normalization of adrenal function, pantethine 300-900 mg, pantothenic acid 400-1,200 mg should be considered.


Because of tremendous individual variation, the use of nutritionals should therefore be personalized for your body. One person's nutrient can be another person's toxin. If you have a specific health concern and wish my personalized nutritional recommendation, write to me by clicking here.

3. Exercise.

Epidemiological studies have shown that modest exercise is beneficial. However, unequivocal metabolic benefits from exercise will not be achieved from a casual walk a couple of nights a week. Significant, regular, chronic exercise is required to see improvements in insulin action, triglycerides, and HDL cholesterol. Exercise is as powerful a tool as weight loss.

4. Weight Management.

Every attempt should be made to reduce total body weight to within 20% of the "ideal" body weight calculated for age and height. If this is done Syndrome X will improve significantly. There is little question about its effectiveness.

5. Other lifestyle Factors:

a. Alcohol. In population-based studies, moderate drinkers are found to have lower insulin levels as compared to non-drinkers. Our small-scale studies have shown moderate drinkers to be more insulin sensitive. There have been no intervention studies to show that initiating alcohol consumption in individuals who are insulin resistant with low HDL is beneficial. So it is not reasonable to suggest that non-drinkers should start to drink 1-2 drinks per day. On the other hand, we do not have the evidence to recommend abstaining from alcohol.

b. Smoking. Smoking is unequivocally bad, asspciated with high triglycerides, low HDL cholesterol and insulin resistance.


Two of the key factors that affect our health is glucose (also known as blood sugar) and the hormone insulin. Because of the high carbohydrate foods we, as a whole population, now eat, our bodies' levels of glucose and insulin have gone out of control. Such high carbohydrate foods probably include cereals, muffins, breads and rolls, pastas, cookies, donuts, and soft drinks.

Quite simply, we are overdosing on glucose and insulin -- two substances which in high doses will accelerate the aging of our bodies and encourage the onset of diseases. Insulin resistance is the body's way to resist excessive sugar and carbohydrate levels, and 60 million Americans have this problem. When insulin resistance is accompanied by compensatory hyperinsulinemia- (not explained in article), the systemic damage is collectively known as Syndrome X.

Fortunately, Syndrome X can be reversed with dietary, lifestyle, and nutritional supplements. Dr Reaven, the acknowledged father of Syndrome X, advocates a diet high in unsaturated fat (45%), low in protein (15%), and moderate in carbohydrate (40%). Exercise, weight management, and optimum nutritional supplements such as chromium polynicotinate, vitamin C, proline, lysine, and other antioxidants help to normalize sugar and increase insulin sensitivity.


© 2004  Michael Lam, M.D. All Rights Reserved.

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