Hypertension and Quercetin

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Hypertension and Quercetin

Thunder Jalili, Ph.D.

Director, Nutrition Sciences Program

Division of Nutrition

250 S. 1850 E., Room 214

University of Utah

Salt Lake City, UT 84112 USA

/ (FAX)

http://www.vitasearch.com/CP/experts/TJaliliAT11-15-07.pdf

" Quercetin Reduces Blood Pressure in Hypertensive Subjects, "

J Nutr, 2007; 137(11): 2405-11. 45787 (1/2008)

Kirk Hamilton: Can you please share with us your educational background

and current position?

Thunder Jalili: I received my BS and PhD from The Ohio State University

in Nutrition. I completed a

postdoctoral fellowship at Harvard School of Public Health in the

Department of Cancer Biology, and another

postdoctoral fellowship in the Division of Cardiology at the University

of Cincinnati Medical Center. My

current position is Associate Professor of Nutrition at the University

of Utah.

KH: What got you interested in studying the role of quercetin and

hypertension? What exactly is quercetin,

its biochemistry and how might it lower blood pressure?

TJ: Quercetin is a polyphenolic compound produced in plants and is

classified as a flavonol. It is found in

foods such as apples, onions, and berries. I became interested in

quercetin a few years ago because it was

reported to be able to inhibit protein kinase C in vitro, a signal

transduction pathway that is thought to regulate

cardiac hypertrophy. We tested quercetin supplemented diets in a rat

model of cardiac hypertrophy and found

that it actually had a potent antihypertensive effect, which is why it

prevented cardiac hypertrophy in vivo. After

some more animal studies on our part and a review of studies that were

done by others using rat models, I

decided to test quercetin in hypertensive patients. Though we had

positive results with reducing blood pressure

in patients with stage 1 hypertension, quercetin did not appear to act

through the mechanism that we

hypothesized. Studies using pressure overloaded rats and spontaneously

hypertensive rats indicated that

quercetin reduced blood pressure by lowering oxidative stress. However,

in humans, we saw no evidence of a

reduction in oxidative stress, so the mechanism in humans is still a

mystery. At this point we have a pretty

reasonable idea of what the mechanism could be, and are preparing

another study to test the idea.

KH: Where did you come up with a dose of 730 mg of quercetin daily? What

is quercetin made from? Was it

given in a single dose or divided dose? With meals or away from meals?

TJ: The dosage used came from studies that gave rats 10 mg/kg of

quercetin via a stomach tube. We

produced tablets containing 365 mg of quercetin and had the patients

take 2 per day along with meals. The

quercetin itself was sourced from a commercial chemical manufacturer,

which extracts polyphenolic

compounds such as quercetin from plants.

KH: Is there quercetin levels in the body or does quercetin get

converted to some other metabolite once it is

digested?

TJ: Quercetin is rapidly metabolized, so there is little free quercetin

in the blood. One can assay the plasma

for a number of known metabolites to get a sense of “plasma load.”

KH: Can you tell us about your study and the basic result?

TJ: We conducted a placebo controlled double blind study in which

subjects with stage 1 hypertension (140-

159 mmHg / 90-99 mmHg) who took quercetin supplements for 4 weeks

experienced a 7, 5, 5 mmHg reduction

in systolic, diastolic, and mean arterial blood pressure respectively.

These changes were not correlated to any

change in parameters of oxidative stress or plasma antioxidant power. We

concluded that the antihypertensive

action of quercetin is not related to an antioxidant effect.

KH: Why would quercetin have some benefit in stage I hypertension but

not pre-hypertension?

TJ: We don’t really know, but we have seen this same response in

normotensive rats as well, in that they do

not experience any reduction in blood pressure compared to hypertensive

rats. All of our rodent based data, and

this current human trial indicates that a certain degree of hypertension

is required for quercetin to work. Having

normal or “high normal” blood pressure is not enough.

KH: How was the patient compliance? Were there any side effects with the

quercetin?

TJ: Based on tablet counts at the end of each treatment period we

believe that patient compliance was good.

There were some who forgot to take a pill here and there, but it was not

too bad. We tried to call patients on a

regular basis to remind them to take pills and check on their status.

Since each phase (quercetin and placebo)

was only 4 weeks long it was a little easier to keep compliance up. We

saw no side effects during the quercetin

or placebo phases.

KH: Who is a candidate for quercetin therapy? All hypertensive patients?

Could the dose be increased?

TJ: The potential of quercetin therapy is just being realized right now.

There are still questions about dose

response and the isoform of quercetin being used in our studies. Right

now it’s hard to say who is a candidate

for quercetin therapy because we may be able to increase the

anti-hypertensive effect of quercetin by using

different isoforms, dosages, and/or delivery methods. Our goal is to be

able to recommend quercetin as an

alternative for blood pressure medication in those who are on the lower

end of stage 1 hypertension and do not

want to take medication. We are also interested in exploring the

potential of quercetin being used as adjunct

therapy to conventional antihypertensive approaches in patients who have

difficulty controlling their blood

pressure. However, we would not recommend anyone drop their current

anti-hypertensive medication in favor

of quercetin supplements at this time until further studies are done to

understand mechanism of action and dose

response.

KH: Do you have any further comments you would like to share on this

very interesting subject?

TJ: There are some quercetin supplements available commercially that can

be ordered online. Some are as

pure quercetin, others are in combination with vitamin C. However, there

are a few problems with these. 1) the

typical dosage depending on the brand is 100-1000 mg, so you may be

buying a supplement that does not have

enough quercetin in it. 2) Combining quercetin with other ingredients

(such as vitamin C) may or may not affect

its biological action, no one knows because it has not been clinically

tested. 3) Supplements are not required by

law to do any quality control testing to verify amount and purity of

active ingredients. This is a very critical

point because as a consumer you can’t be sure you are actually getting

the ingredient that is advertised on the

bottle, or if its in the advertised dosage.

--

ne Holden, MS, RD < fivestar@... >

" Ask the Parkinson Dietitian " http://www.parkinson.org/

" Eat well, stay well with Parkinson's disease "

" Parkinson's disease: Guidelines for Medical Nutrition Therapy "

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