News Release

Researchers study metabolic, cardiovascular effects of caffeine consumed with naringin

Peer-Reviewed Publication

American Physiological Society

April 9, 2003 (San Diego, CA) -- If you are one of the millions of overweight Americans then your breakfast may be comprised of black coffee (five calories), dry toast (70 calories), and a grapefruit (60 calories for one-half). Many believe that grapefruit influences caffeine's effect on the body.

A flavonoid (plant pigment) compound found in grapefruit, naringin gives grapefruit its characteristic bitter flavor. Grapefruit processors attempt to select fruits with low naringin content, and often blend juices obtained from different grapefruit varieties to obtain the desired degree of bitterness. Naringin is believed to enhance our perception of taste by stimulating the taste buds; that's why some people consume a small amount of grapefruit juice before a meal.

But there are downsides to the healthy fruit.

Previous research has found that naringin interferes with enzymatic activity in the intestines thus slowing the breakdown of certain drugs and resulting in higher blood levels of the drug. A number of drugs that are known to be affected by the naringin in grapefruit include calcium channel blockers, estrogen, sedatives, medications for high blood pressure, allergies, AIDS, and cholesterol-lowering drugs. Consuming grapefruit or grapefruit juice may also extend caffeine levels and effects of caffeine.

While the effect of naringin on the metabolism of a drug can increase the drug's effectiveness, it can also result in dosages that are inadvertently too high. Therefore, many physicians do not recommend that patients take any drugs with grapefruit juice unless the interaction with the drug is known. In addition, the effects of drinking grapefruit juice is cumulative, which means that if you drank a glass of grapefruit juice daily with your medication for a week, the drug interaction would be stronger at the end of the week than at the beginning.

Flavonoids from grapefruit juice have been reported to affect hepatic metabolism by influencing Cytochrome P450 enzyme system, or CYP3A4. Many medications are metabolized in the liver by the cytochrome P450 enzyme complex or CYP3A4, including calcium channel blockers, HMG-CoA reductase inhibitors, anxiolytics, and some neuropsychiatrics. Adverse reactions have been reported by this drug-food interaction. The majority of caffeine (approximately 86 percent) is metabolized by a similar enzyme group, CYP1A2. Other enzymes (CYP2E1 and CYP3A4) play a minor role in caffeine metabolism. However, naringin, the bitter constituent of grapefruit juice, has been documented to inhibit CYP34A activity in human liver as well as CYP1A2.

A New Study New research has examined the metabolic and cardiovascular effects of caffeine consumed in conjunction with naringin. The authors of "Caffeine and Naringin (Grapefruit) Does Not Affect Resting Energy Expenditure" are Tasha L.P. Ballard and Matthew Vukovich, Ph.D., FACSM, of South Dakota State University, Brookings, SD. They will present their findings at the American Physiology Society (APS) conference, Experimental Biology 2003, being held April 11-15, at the San Diego Convention Center, San Diego, CA.

Dr. Vukovich hypothesized that a caffeine/naringin combined dosage would increase the half-life of caffeine and further alter metabolic markers and hemodynamic variables. The parameters of interest included oxygen consumption, respiratory exchange ratio, resting energy expenditure, heart rate and blood pressure.

Methodology Caffeine-naïve subjects were studied before and after the ingestion of caffeine (C, 200mg) with and without naringin (100mg or 200mg). Data was collected for 8 hours every half-hour. Parameters measured included resting metabolic rate, heart rate, blood pressure, blood levels of caffeine.

Results The consumption of caffeine significantly increased resting metabolic rate or calories burned at rest. However, the addition of naringin did not further enhance energy expenditure. Furthermore, blood levels of caffeine were not influenced by the co-consumption of naringin.

Conclusions Their findings suggest that naringin, when taken in conjunction with caffeine, does not significantly alter caffeine metabolism. This is evidenced by the lack of significance among the trials with all of the predetermined variables. These results differ with reported results, which found significant increases in caffeine half-life in vivo. The reasons for the differences between the two studies may be due to a number of different factors, including methodology and subject population.


The American Physiological Society (APS) is one of the world's most prestigious organizations for physiological scientists. These researchers specialize in understanding the processes and functions underlying human health and disease. Founded in 1887 the Bethesda, MD-based Society has more than 10,000 members and publishes 3,800 articles in its 14 peer-reviewed journals each year.

Contact: Donna Krupa at 703-527-7357 (vm)
Or 703-967-2751 (cell) or Through April 10th, 2003


APS Newsroom: April 11-15, 2003
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Telephone: 619-525-6340 or 6341

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