Liquid Vitamin Research: Chromium, Diabetes, Hypoglycemia
What's The Connection?

Dietary Chromium: An Overview
By Barry Mennen, M.D.
Executive Director, Chromium InformationBureau, Inc.

Definition and Function

Chromium is an element; that is, it is one of the basic building blocks of all things, both living and non-living. And, like certain of the elements such as carbon, nitrogen, iron and calcium (among others), chromium plays an essential role in our life and health.

Chromium's function in our bodies is critical: without it, the hormone insulin would not work. Most people are familiar with insulin as the shot diabetics give themselves in order to control their high blood sugar. But, what most people don't realize is that insulin is the "master hormone" of our metabolism; it not only controls blood sugar levels and many other aspects of carbohydrate breakdown and storage, but also directs much of the metabolism involving fat, protein and energy (calories).

Because insulin requires chromium to function properly, this trace element has significant biological effects in the body. (See below for more on insulin)

Discovery of Chromium's Role in Human Health

It was known by the 1950s that chromium was required by animals to control blood sugar, but it wasn't until the 1970s that chromium's essential role in humans was clearly proven. This proof came accidentally, as a result of a new procedure that had been introduced to nourish hospitalized patients who could not take in any food by mouth. This procedure, giving specially-made feeding solutions directly through the patient's vein, is referred to as Total Parenteral Nutrition or TPN.

TPN was designed to give patients all the carbohydrates, proteins, fats, vitamins and minerals they needed to maintain health until they could once again eat normally and obtain these nutrients from food. Some of these patients who had been fed intravenously for months developed high blood sugars just as if they were diabetic (which they weren't). The doctors then had to start insulin therapy in order to treat this diabetes-like condition and even then the insulin they were given didn't appear to work as well as it should have.

Since it was already known that chromium was necessary for insulin action, it was thought that this trace element may have been lacking in these patients' TPN solutions. Thus it was deduced that these patients were showing signs of very severe chromium deficiency. The physicians caring for them then added chromium in very small amounts less than 50 micrograms (abbreviated as mcg; equal to 1/1000 of a milligram) to their IV feeding solution and quickly noted an improvement.

The patients no longer required insulin injections, and their blood sugars and other abnormalities returned to normal. After these cases of chromium deficiency and its serious consequences were reported, medical and nutrition experts agreed that chromium was an essential nutrient for humans and advised health professionals administering TPN about the danger of omitting chromium from the solutions.

Both the Food and Drug Administration (FDA) and the Food and Nutrition Board of the National Research Council (the quasi-governmental body that determines the Recommended Dietary Allowances or RDAs ) have therefore designated chromium an essential nutritional trace element.

Although insulin mainly works in muscle, fat and the liver,this hormone also exerts profound effects on many other body tissues. Insulin is the primary hormone that controls how the body's cells absorb, use and store nutrients and energy. Besides regulating the cellular absorption and utilization of glucose, amino acids (the building blocks of protein) and fatty acids, insulin also activates and inactivates enzymes (the protein catalysts for the body's biochemical reactions) and directly affects certain genetic processes including protein synthesis.

While trivalent chromium works with insulin to move glucose into cells, we currently do not know how many other critical actions of insulin require chromium to function. However, regarding the insulin-induced movement of glucose into cells, it is likely that chromium is either involved with the binding of insulin toits receptor (the site on the cell membrane which responds to signals from biochemical messengers such as hormones, drugs and nutrients and then stimulates or inhibits specific cellular functions) or with certain of the reactions which take place after the initial receptor site activation, reactions that are referred to as post-receptor events.

Chromium and Diabetes

Because of chromium's connection to insulin function, it should come as no surprise that most of the research with this trace mineral relates to diabetes or to non-diabetic persons who develop high blood glucose levels after ingesting simple sugar.There are at least 16 clinical studies which have tested specific chromium compounds in such patients using proper scientific methods (other studies on chromium supplementation in diabetics which used questionable methods in their study design are not included in the following summary).

While three of the 17 properly designed studies showed no benefit of chromium supplementation in diabetics, 14 did showblood glucose improvements in the patients tested. For example,a recent study that has been reported (which was presented in1995 at the annual meeting of the American College of Nutrition)showed dramatic improvements in blood sugar using less than one milligram of supplemental chromium picolinate in a group of women who developed gestational diabetes (that is, they showed symptoms and signs of diabetes only during their pregnancies).

The latest study to examine the issue of chromium supplementation and adult-onset diabetes was presented in June,1996 at the annual Scientific Sessions of the American Diabetes Association held in San Francisco, CA. Researchers from the Human Nutrition Research Center of the United States Departmentof Agriculture collaborated with Chinese researchers from the Beijing Medical University.

They randomized 180 adult-onset diabetics into 3 groups of 60 each: one group received placebo twice per day, the second received 100 mcg twice daily of chromium as chromium picolinate and the third received 500 mcg of chromium as chromium picolinate twice daily. Their blood work was examined at baseline, at 2 months and at 4 months.

The patients were told to remain on their anti-diabetic medications and continue with their diets and activity levels as before.

The results were impressive: blood glucose, insulin levels, cholesterol and glycated hemoglobin (a measure of blood sugar control over the previous few months) all decreased, with the higher dose generally (but not always) more effective than the200 mcg.

How could such tiny amounts of chromium have such profound effects on insulin's action? Again, the answer is not known with certainty, but the evidence so far suggests that chromium strengthens certain effects of insulin on the body's cells; in other words, it doesn't work by stimulating the body to make more insulin, but rather chromium makes the insulin which is present function more effectively in the cells of the body.

When the body does not respond to insulin in the normal manner, doctors refer to this as insulin resistance. Insulin resistance signifies that the insulin which is circulating in the blood is not able to have its usual effects on various tissues in thebody. This is not the problem with the type of diabetes (referred to as type I or juvenile-onset) that strikes young children: these individuals cannot make insulin anymore and thusmust take it by injection. However, most diabetics suffer from maturity-onset diabetes (or type II; increasingly referred to as NIDDM or non-insulin dependent diabetes mellitus; this type of diabetes affects 90% of people with the disease).

It is these patients with NIDDM who demonstrate insulin resistance and are the ones most at risk for chromium deficiency and its consequences. Further, there is some evidence that marginal chromium deficiency may be important in other areas of health and disease. These other diseases where chromium may be important are some of the most common and significant illnesses of industrialized nations (see below).

The following is the ending to the chapter on chromium nutrition in the latest edition of the standard reference textbook on medical nutrition:

"Based on current knowledge of chromium function and nutrition.the possibility cannot be ignored that inadequate chromium status may be responsible in part for some cases of impaired glucose tolerance, 'hyperglycemia, hypoglycemia, glycosuria [sugar in urine], and refractoriness to insulin."

Modern Nutrition in Health and Disease, Eighth Ed.., 1994.Shils, Olson and Shike, eds.

HEALTH NOTE

It is important to note that persons with diabetes who are on insulin or other anti-diabetic medications should check with their doctors before supplementing their diets. Because chromium may decrease the amount of insulin resistance present, it may change the type or amount of medication needed to treat the diabetes and/or the frequency with which blood sugar monitoringneeds to be done.

This is especially important for those persons with diabetes who are under tight blood glucose control. Adding supplemental chromium in this situation has the potential to cause low blood sugar (hypoglycemia).

The Insulin Resistance Syndrome (Syndrome X; Reaven's Syndrome; Insulin-Metabolic Syndrome)

The combination of obesity, diabetes, hypertension (high bloodpressure) along with abnormalities in blood cholesterol and fat (lipid) has long been noted in the medical literature. By the late 1980s, a noted diabetes expert from Stanford University(Dr. Gerald Reaven) proposed that the basic combination of highblood sugar, high blood pressure and abnormal blood lipids all constituted disease that was based on increased insulin resistance; he noted that while increased insulin resistance isthe first step in the development of maturity-onset or type II diabetes, it is the body's response to the insulin resistance which determines whether or not the individual becomes a diabetic or not.

"Even if high blood sugar does not develop, insulin resistance does not appear to be a good thing to have: The fact that an insulin-resistant subject may not become diabetic does not meanthat they suffer no untoward consequences. Indeed, an argumentcan be made that the more insulin sensitive an individual, the better off he or she is, and that the attempt to compensate for insulin resistance sets in motion a series of events that playan important role in the development of both hypertension and coronary artery disease."

Reaven GM. Role of Insulin Resistance in Human Disease.Diabetes, 37:1595, Dec., 1988.

Since chromium reduces insulin resistance, this essential trace element could therefore have wide-ranging effects on high blood pressure and abnormal blood lipids in addition to lowering blood sugar.

However, Dr. Reaven did not connect any insulin resistance to possible marginal chromium status, and we cite him here only to point out his contribution to describing this syndrome. It is also important to note that while studies in peer-reviewed medical journals have shown that chromium supplementation lowers blood lipids such as triglycerides, for now there are no human data on chromium and blood pressure.

Chromium and Body Composition

Another area that is gaining more interest lately is the possible effect of chromium on body composition; that is, how chromium affects the relative amounts of lean body mass (mainly muscle) compared to the amount of body fat. At present, there are positive results from studies with four separate animal species supplemented with chromium picolinate: pigs, lambs, rats and chickens. In all of these species, there were increases in muscle mass and decreases in fat body mass. And, in the case of pigs, these findings have been confirmed by several additional studies.

For humans, however, the evidence was not as clear until quiterecently. In October, 1996 a study published in a peer-reviewed medical journal looked at 154 slightly overweight individuals split into three groups who were supplemented with either 200 mcg of chromium as the picolinate compound, 400 mcg of chromiumas the picolinate compound or a placebo.

Previously, some human studies had shown either no effect, an effect similar to that seen in animals (that is, reduction in fat and increase in muscle) or an effect in women but not inmen. The main problem with these older studies was that they had looked at very few individuals sometimes as few as 12; so, while it appeared that chromium was having an effect on body composition, since there were so few persons involved in thestudies we could not be absolutely certain.

Further, some of the prior studies looked at young athletes (such as college football players) who, because of their high degree of fitness upon entering the study would not, in all likelihood, make the best subjects in which to observe these changes.

This latest study examined average Americans in Texas who were given no special instructions in diet or exercise just the chromium at either dosage level or the placebo. The study was double-blind and randomized. What these researchers found after the 72 days of the study was a statistically significant difference in the chromium groups vs. the placebo group in change of body composition index (BCI, a sum of the loss in body fat plus the gain in muscle mass) loss of body fat and total weight loss.

The authors conclude:

These data suggest that supplementation with chromium picolinate can lead to significant improvements in body composition when aBCI [body composition index] is used as the outcome criterionthat represents a sum of the net gains in nonfat mass added to the sum of the net losses of body fat.

Kaats GR, Blum K, Fisher JA and Adelman JA. Effects of chromium picolinate supplementation on body composition: A randomized, double-masked, placebo-controlled study. Current Therapeutic Research, 57(10):747-765, Oct. 1996

While the mechanism of action whereby chromium has this apparent effect is not known, it is interesting to note that therapies for diabetes that increase insulin levels in the blood are associated with weight gain (insulin injections and sulfonylureas such as Diabinese and Micronase) while therapiesthat decrease insulin levels (such as Glucophage and the not-yet-released oral agent troglitazone) are associated with no weight gain or even weight loss. Since chromium supplementation has been associated with decreased insulin levels, it is tempting to speculate that it is through this effect (that is, decreasing insulin resistance withthe attendant drop in circulating insulin) that chromium worksin altering body composition.
Dietary Intake of Chromium

Data from U. S. Government sources show that the great majority of Americans get less chromium in their daily diets than the amount recommended by nutrition experts (the RDA Committee recommends 50-200 mcg of chromium/day; the vast majority of Americans get less than 50 mcg/day).

"In the majority of all chromium supplementation studies in the United States, at least half the subjects with impaired glucose tolerance improved upon chromium supplementation, suggesting that the lower ranges of chromiumintake from typical U.S. diet are not optimal with regard to chromium nutriture."

RDA 10th Edition 1989

Few foods are rich sources of chromium in the Western diet, the best being organ meats, mushrooms, wheat germ, broccoli and processed meats. It is theorized that Stone Age people ingested more chromium than modern people because they regularly ate organ meats from the animals they hunted (which contained higher levels chromium as well as other trace elements).

Not only did these early people likely have a higher chromium intake than modern ones, but perhaps more important than their higher intakes, it is most likely that they lost less chromiumin their urine than we do. This is because Stone Agers did not ingest nearly as much simple sugars as modern people and simple sugar intake causes chromium to be lost in the urine. These ingested sugars (such as table sugar and products made with it) bring insulin and chromium into the blood and cause chromium tobe excreted in the urine after it's through working with the insulin on the increase in blood sugar.

We Americans consume an average of 120 pounds of sugar per year from all sources. Thus, we can conclude that for hundreds of thousands of years of human evolution, our ancestors most likelytook in more and lost less of this essential trace element than modern Americans.

Another interesting fact demonstrated in large numbers of people both in the U.S. and the U.K.--is that chromium tissue levels inhumans decrease over our lifetimes. In fact, the highest tissue levels of chromium are found in newborns: they get chromium inthe womb across the placenta from their mothers. There is also evidence that pregnancy depletes a woman's chromium stores, which may be one reason that as a total population our bodies show loss of chromium as we age.

From this evidence inadequate chromium intake, increased chromium losses, decreasing chromium tissue levels as we age, improvement in blood sugar insignificant numbers of diabetics and pre-diabetics with modest chromium supplementation and widespread insulin resistance (25%of Americans have some degree of insulin resistance, though only a portion of this insulin malfunction appears to be due to chromium deficiency) experts in chromium nutrition urge supplementation with small amounts of this trace element on adaily basis.

These experts feel that chromium supplementation for diabetics should take its place alongside the two other proven ways of decreasing insulin resistance: low-fat, high complex-carbohydrate diets for weight loss/weight maintenanceand regular exercise.

Safety

It is extremely difficult to poison laboratory animals with oral chromium. For example,cats fed 1,000 mg of trivalent chromium per day showed no signs of toxicity (the equivalent daily dose for a 150 lb person would be approximately 35,000 mg per day or3.5 million mcg per day. In terms of the number of 200 mcg tablets, this would be 175,000 tablets per day for a human.

On March 14, 1996, a safety study conducted by the U. S. Department of Agriculture was presented at the Society of Toxicology's annual meeting. This study looked at various supplemental doses (including none) of chromium chloride and chromium picolinate fed to rats for 6 months, The highest doses were equal to a human consuming 5,000 tablets of 200 micrograms chromium picolinate. At regular intervals during the study the rats were weighed and blood was taken for laboratory tests.

At the end of the study the livers and kidneys (organs that would have the highest tissue levels of chromium) were examined under the microscope. There were no differences in any of the measurements or examinations between the various groups. The investigators were unaware ("blinded") as to which group the animals were in when the measurements and evaluations were performed.

The safety issue had been raised by a study published inDecember, 1995 which attempted to link chromosomal damage in the test tube to oral supplementation of chromium picolinate. These researchers used cultured Chinese hamster ovarian cancer cells to which they directly added unnaturally high amounts of chromium compounds, including chromium picolinate. Some of these cells showed chromosomal damage (clastogenic effects).

This was not particularly surprising, since this concentration directly applied to these cells in a test tube was 3,000 times the blood level of people who are ingesting chromium picolinate as supplements!

Very few essential minerals tested in this way would be found to be without toxicity; for example, merely doubling the blood concentration of the mineral calcium is fatal to humans. When tested by the Ames test (a specific test for mutagenicity) for cancer-causing potential, chromium picolinate was proven negative.

Again, the standard medical reference on nutrition:

"Trivalent chromium has such a low order of toxicity that deleterious effects from excessive intake of this form of chromium do not occur readily. Trivalent chromium becomes toxic only at extremely high amounts.- chromium then acts as a gastric irritant rather than as a toxic element interfering with essential metabolism or biochemistry."

Modern Nutrition In Health and Disease, Eighth Ed., 1994.Shils, Olson and Shike, eds.

Assessment of Chromium Status

One of the main problems that has hindered a more widespread interest and possible usage of chromium by the medical profession is the fact that gauging whether or not someone is chromium deficient or not cannot easily be done. The only generally accepted method for assessment ofchromium status is to supplement an individual (who has abnormalities of either blood sugar, cholesterol, triglycerides or all three) with the trace clement and see if the laboratory values improve. If they do, then chromium insufficiency is presumed. This is an expensive and cumbersome process (especially when doing a glucose tolerance test).
Summary

Indications are that marginal deficiency of chromium, an essential trace mineral, may be widespread in industrialized nations. Further, the consequences of this deficiency may contribute to some of the manifestations of obesity, diabetes, abnormal blood lipids, hypertension and coronary artery disease in 20th century western society.

Although some of the above is speculative, it would seem prudent for Americans to supplement their diets with small amounts of trivalent chromium (for example, 200 mcg of chromium picolinate) since the benefits of supplementation may be significant for certain individuals and the safety of this regimen is well-supported by a large amount of data.

Postscript: What do Doctors Think About This?

You may now be asking: Why haven't I heard about this? Do my friends who are diabetics known about this? Does my doctor know anything about this? These are reasonable questions, and there are several issues involved in dealing with issues relating to the apparent lack of interest in chromium for diabetics.

• Doctors have traditionally shied away from techniques involving nutritional management of their patients
• There is still no reliable way to test individuals for chromium status
• The first few decades of chromium research was complicated by contamination of the food or tissues being examined by significant amounts of chromium from the environment (the use of stainless steel laboratory equipment, for example). This resulted in confusing and contradictory results from different research facilities. By the early 1980s, this problem was resolved, however.
• The marketing of nutritional therapies to physicians and other health professionals is not nearly as extensive as pharmaceutical marketing; since profits from nutritional therapies are significantly smaller than those from pharmaceuticals, supplement manufacturers cannot justify the large capital outlays needed for the promotional and educational materials for physicians. In addition, representatives of drug manufacturers frequently call on physicians to present them with new research data and samples of their products. Direct mail and advertising are other means by which pharmaceutica lmanufacturers get important information about their products to doctors. The same promotional and educational budgets are not available in the nutritional area.

Copyright: The Chromium Information Bureau, Inc. March, 1966; revised,June, 1996 and November, 1996