Chromium and Cholesterol: Part II: The Niacin Connection

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In recent years, niacin has become popular as a potent cholesterol fighter. Numerous studies have shown that high doses of niacin lower harmful LDL cholesterol, decrease triglycerides and increase beneficial HDL cholesterol.[ 67-70]

However, niacin's use as a cholesterol-lowering agent is also causing concern among medical and scientific professionals. Recent reports show that the amount of niacin normally required to lower cholesterol (500-4500mg/day) can produce serious side effects. According to The American Journal of Medicine (1988), high doses of niacin can cause skin flushing, itching and rashes, as well as nausea, diarrhea, aggravation of peptic ulcers, gout, liver disorders and heart arrhythmia.[ 71]

Niacin's side effects caught national attention in 1990 when the Journal of the American Medical Association reported four cases of liver damage in people who took sustained- or time-release niacin purchased without a prescription.[ 72] One patient, who spent 10 days recovering in a hospital, was taking only 500 milligrams of timed-release niacin a day for two months.

New hope may be emerging from this dilemma Recently, researchers have found that a combination of chromium and niacin can dramatically reduce the levels of niacin required to lower cholesterol, thereby reducing or eliminating niacin's side effects altogether. Dr. Martin Urberg of Michigan's Wayne State University found that when niacin and chromium are taken together, the amount of niacin needed to reduce cholesterol is significantly less.

His study, published in The Journal of Family Practice (1988), found that a combination of 200 micrograms of chromium and only 100 milligrams of niacin daily resulted in decreases of LDL cholesterol of 23 and 30 percent in two patients.[ 6] Previously, the lowest daily dose of niacin reported to be effective in lowering cholesterol was 750 milligrams.

Although Dr. Urberg's patient population was limited, the study has led some experts to question niacin's primary role in lowering cholesterol. In fact, some scientists believe that niacin may actually be enhancing chromium's cholesterol-lowering effects in the body.

Niacin-Bound Chromium

A new study recently reported at the 1991 Federation of American Societies for Experimental Biology (FASEB) in Atlanta may actually confirm speculation surrounding chromium and niacin's synergistic effect.

Dr. Robert Lefavi, director of Research for the Health and Human Performance Laboratory at Georgia Southern University, found that cholesterol levels in a group of young male adults taking a niacin-bound chromium complex for eight weeks were significantly reduced when compared with a placebo group.

The double-blind study consisted of thirty-four college-age male athletes with normal cholesterol levels. Subjects were assigned to one of three groups receiving either a placebo, 200 micrograms (mcg) of chromium as niacin-bound chromium, or 800 mcg of chromium as niacin-bound chromium. After eight weeks, average serum cholesterol in the 200 mcg group dropped 14%, while the 800 mcg group dropped 18%. The placebo group showed no improvement.

According to Dr. Lefavi, the data support a growing body of evidence showing that chromium supplements can have a positive effect on serum lipids. "We were able to lower serum lipids from the normal range," Lefavi said. "This may have profound implications for people with high cholesterol levels."

Since the 200 and 800 mcg chromium supplements used in the study contained only 2 and 8 milligrams niacin, respectively, the Lefavi study suggests that even less niacin is required to lower cholesterol if it is bound to chromium. At these levels, the risk of niacin's side effects is virtually eliminated.

The reductions in cholesterol reported by Dr. Lefavi were substantial compared to reductions reported in other chromium supplementation studies, especially since the subjects generally had moderate cholesterol levels to begin with. It is possible that niacin-bound chromium may have even a greater effect on hyperlipidemics.

Apparently, a strong synergistic relationship exists between chromium and niacin. Other studies have shown that a combination of chromium and niacin improves glucose tolerance of the elderly and increases insulin binding to white blood cells, while no consistent effect was seen when either chromium or niacin were given alone.[ 73, 74]

Dr. Urberg has stated that chromium and niacin may both act by the same mechanism in the body - serving as substrate for endogenous GTF synthesis. This comes as no surprise. Dr. Walter Mertz, director of the USDA's Human Nutrition Research Center and discoverer of GTF chromium, identified a chromium-niacin complex as the active component of Glucose Tolerance Factor some 20 years ago.[ 75]

Biologically Active Chromium

According to the RDA's, experiments have demonstrated substantial differences in the biological activity of different chromium compounds. Although the chemical form of chromium in foods is not known with certainty, a chromium-niacin-amino acid complex with high bioavailability has been identified in brewer's yeast, the richest known source of biologically active chromium in nature.[ 2]

Early research indicated that biologically active chromium consisted of a vitamin-like substance called Glucose Tolerance Factor. According to Dr. Mertz, GTF differs from simple chromium compounds in its ability to potentiate insulin, cross the placental barrier and concentrate in physiological tissue stores. GTF is also absorbed better ( 10-15% compared to 0.5-2% for inorganic chromium) and is about three to four times less toxic than inorganic chromium.[ 75]

The importance of niacin to biologically active chromium was confirmed in experiments showing that synthetic complexes of chromium and niacin were equal to or better at potentiating insulin activity than pure GTF extracted from brewer's yeast. Further, when niacin isomers - nearly identical chemical compounds including picolinic acid - were substituted as ligands, the latter had no effect on insulin activity.[ 75]

Dr. Mertz states, "That the strong potentiation of insulin in vitro depends on the coordination of nicotinic acid [niacin] to chromium is shown by the ineffectiveness of other pyridine carboxylic acid derivatives [picolinic acid] as ligands."[ 75]

Assessing the biological equivalence of chromium may further be complicated by the manner in which chromium and niacin are bound together. Complexes of chromium and niacin are known to exist as one or more atoms of chromium bound to either the oxygen or nitrogen atom of one or more molecules of niacin. These products vary in color (yellow, orange, red, green, blue, purple) as well as biological activity.[ 76-79]

Following Dr. Mertz's original research, scientists at Massey University in New Zealand discovered that an oxygen-coordinated complex of niacin-bound chromium was 18 times more biologically active than other chromium-niacin complexes tested.[ 76]

According to the researchers, "it is the shape of the complex which is likely to be the important factor in determining the presence or absence of biological activity....This arrangement must resemble the part of the GTF structure which is recognized by the [insulin] receptors or enzymes involved in the expression of the biological effect."

It is not known whether niacin-bound chromium is used directly by the body or is readily converted to the GTF form, but it appears to be the most concentrated source of biologically active chromium available as a nutritional supplement.

Animal studies show that a commercially available niacin-bound chromium supplement exhibits greater biological activity and lower toxicity than other chromium supplements tested, including chromium fortified yeast-based products.[ 80]

The body's ability to convert simple chromium compounds into the GTF form declines with age,[ 81] and is impaired in diabetics[ 48] and probably hyperlipidemic and atherosclerotic patients.[ 82] In contrast, malnourished children are known to respond quickly to simple chromium compounds, indicating a rapid conversion of the chromium to GTF.[ 83, 84]

Dr. Mertz has emphasized that the response of adults to simple chromium salts is noticed only after several weeks or months, a lag that cannot be shortened by increasing the dose.[ 81, 85] This lag phase probably reflects poor absorption and/or slow conversion of absorbed chromium to GTF. Time is probably also required to replenish tissue chromium stores to normal levels following a lifetime of inadequate dietary intake and normal chromium losses.

Although many people would probably benefit from taking a simple inorganic chromium supplement, the evidence suggests that adults, diabetics and hyperlipidemics are likely to benefit the most from a biologically active supplement such as niacin-bound chromium.

Excessive Intakes and Toxicity

According to the RDAs, the toxicity of trivalent chromium (CRY), the chemical form that occurs in diets and nutritional supplements, is so low that there is a substantial margin of safety between the amounts normally consumed and those considered to have harmful effects.[ 2]

No adverse effects were seen in rats and mice consuming 5 mg Cr/liter in drinking water throughout their lifetimes, and no toxicity was observed in rats exposed to 100 mg Cr/kg in the diet. Cats have been shown to tolerate up to one million micrograms of trivalent chromium daily -roughly 5000 times the maximum recommended amount for humans.[ 86] No adverse effects of trivalent chromium in humans have been reported in the medical literature.

Accidental ingestion of hexavalent chromium (Cr+6) used in industry has been correlated with liver and kidney damage as well as lung cancer.[ 57] But since humans cannot oxidize the nontoxic trivalent form to the hexavalent form, the potential toxicity of hexavalent chromium bears no relevance to the nutritional role of trivalent chromium.[ 2]

Conclusion

A strong association exists between chromium deficiency, high blood insulin and elevated blood cholesterol levels - a problem that can manifest itself as a result of inadequate chromium intake. Since it appears that most Americans may not be getting enough chromium in their diet and that some may have difficulty absorbing or converting simple chromium compounds into the biologically active GTF form, supplementing with niacin-bound chromium might not only benefit most people, it appears advisable for adults, diabetics and people with high blood cholesterol levels.

While regular exercise and a low-fat, low-cholesterol diet are important parts of a complete cholesterol-lowering program, for many people, supplementing with niacin-bound chromium may offer a safe and effective augment in combatting high blood cholesterol.

Robert M. Hackman, Ph.D., is a recognized leader in the field of nutrition and human performance. An Associate Professor at the University of Oregon, Eugene, Dr. Hackman has conducted extensive research and trained hundreds of individuals in the area of applied nutrition and health promotion. Professor Hack man is a n expert consultant to numerous progressive companies, including HealthComm, Inc., Athletics West (Nike's track and field tea m), InterHealth Company, the Heinz Foundation, and the National Awareness Health Institute. This article was prepared with assistance from InterHealth Company.

Editor's Note:

The niacin-bound chromium compound referred to in this article is ChromeMate brand of chromium polynicotinate - U.S. Patents 4,923,855, 4,954,492 and patents pending. For more information on ChromeMate, call 1-800-783-INFO.

Correspondence: Robert M. Hackman, Ph.D. c/o InterHealth Company 2490 Arnold Industrial Way #N Concord, CA 94520
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By Robert M. Hackman

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