Subject: The Advantage of Single Daily Dosages of Herbal Medicines

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" JoAnn Guest " <angelprincessjo

Thu Sep 16, 2004 10:30 pm

The Advantage of Single Daily Dosages of Herbal Medicines

 

 

The Advantage of Single Daily Dosages of Herbal Medicines

 

Introduction

 

Since the early 1980s there has been a tremendous increase in the

use and appreciation of herbal medicine in North America. I have

termed this process the Herbal Renaissance. The key fuel for this

increased popularity of herbal medicine has been scientific

research. During the last 20 to 30 years there has been a virtual

explosion of scientific information concerning the medicinal use of

plants. Through science we now have a better understanding of how a

particular herb might work to promote health. We also now know how

to grow a plant for highest medicinal effect, when to harvest it and

how to concentrate the medicinal components in extracts.

 

One area of herbal medicine that is still in its relative infancy is

the field of pharmacokinetics - the study of the absorption of

compounds by the body and their biotransformation, distribution,

metabolism, and elimination from the body. The same scientific

methods used to determine the pharmacokinetics of drugs have been

applied to some of the more popular herbal medicines as well as

other natural products.

 

Pharmacokinetic studies can provide the answer as to what is the

best delivery vehicle for a substance. For example, some compounds

need to be protected from the harsh secretions of the stomach by

incorporating them into specially coated capsules or tablets that

can withstand gastric acids while other compounds may be required to

be administered in a soft-gelatin capsule with other lipid (fatty)

substances for maximum absorption.

 

 

The alpha-lipoic acid example

 

One of my favorite examples in pharmacokinetics is immediate-release

alpha-lipoic acid vs. timed-release alpha-lipoic acid. Alpha-lipoic

acid is a vitamin-like substance that is often described

as " nature's perfect antioxidant. " The primary clinical use of alpha-

lipoic acid has been for the treatment of diabetic neuropathy. In

fact, it has been successfully used in Germany for over thirty years

as an approved drug for this condition. Detailed absorption studies

have shown that immediate-release alpha-lipoic acid is quickly

absorbed with dosage proportionality – meaning that roughly the same

percentage is absorbed whether the dosage is 50 or 600 mg with about

30% of the actual dosage getting into the bloodstream before it is

broken down by the liver.1

 

While we know a great deal about how immediate-release alpha-lipoic

acid is handled by the body and its clinical effectiveness, there

has been only one study with a timed released preparation – it was a

pharmacokinetic study that concluded that the timed-released formula

was associated with an approximately 40% reduction in overall

bioavailability compared to the immediate-release product.2 While

the timed-release product was absorbed more slowly over time, it did

not produce as high of peak value as the immediate release nor was

the area under the curve (AUC) as high as the immediate release. The

AUC is often used to show the total absorption of compound over

time. In this case, the AUC for the immediate release alpha-lipoic

acid was 4,466 ng/ml compared to 2,621 ng/ml. Based upon the

clinical research over the last 30 years and the pharmacokinetics of

immediate-release alpha-lipoic acid, it appears to be obviously

superior to the timed-release product.

 

I like this example because it suggests that the key to the

effectiveness of immediate-release alpha-lipoic acid may be in

achieving higher peak values vs. trying to achieve a steady state in

the blood.

 

 

Steady state vs. high peaks

 

For many drugs, nutrients, and herbs the idea has been that multiple

dosing or utilizing pharmaceutical technology to produce timed-

released absorption for a more steady state in blood levels was the

best way to go. However, many drugs that were once given in multiple

doses throughout the day are now being given once a day, once a

week, or even once a month dosages. Why? Well the easy answer to

this question is that clinical results or pharmacokinetic studies

have indicated that the compound was absorbed, distributed, and

eliminated in such a manner that multiple dosing was simply not

necessary.

 

Let me offer a couple examples of popular drugs that require a

steady state or constant blood level in order to produce their

benefit: lithium, digitalis (digoxin), and anti-seizure medications

like Dilantin. Many chemotherapy drugs also require a constant blood

level.

 

In contrast to these sorts of agents, some compounds work better

therapeutically if there is a rapid rise in blood levels. The reason

has everything to do with one of two processes: diffusion and active

transport. Diffusion refers to the transfer of molecules from an

area of high concentration to an area of low concentration. There

are many factors that determine the diffusion rate of a substance

across cell membranes, but from a simplistic view it is much easier

if the concentration on one side of the cell is substantially larger

than the other.

 

Diffusion, however, is not the only way molecules enter the cells.

Cells are also equipped with transport mechanisms to actively carry

molecules across the cell membranes. Again, it is often easier for

these transport sites to do their jobs when there is an increased

concentration in the external environment of the compounding needing

to be transported. The point I am trying to make here is that by

rapidly raising the concentration in the blood with some compounds,

it makes it easier for these molecules to get into the cells where

they produce their beneficial effects.

 

It may eventually turn out that even better results will be obtained

with single daily dosage compared to multiple doses with some herbs

just like what has been observed with some drugs and natural

products. Here is something to think about; in a study in beagle

dogs repeated oral administration of the main polyphenols found in

green tea (epigallocatechin gallate or EGCG) during the day resulted

in significantly lower blood levels compared to the concentration

following a single dose.3 In a human study, single daily dosages of

EGCG were shown to produce a >60% increase in blood EGCG values over

a 4-week period compared to the same dosage given as a twice daily

dose.4 The researchers concluded that the twice daily dosage " did

not result in significant changes in the AUC (area under the curve)

of free EGCG. " The reason seems to be the fact that absorption of

EGCG is mediated by a transporter in the intestinal tract.5 Again,

an immediate higher concentration of a substance makes it easier for

some transporters to do their job. These results indicate that the

benefits of green tea extract may best be achieved if a larger

single dose is given all at once rather than being split into

multiple doses.

 

 

The problem with generalizations

 

Generalizations about what is the best form, delivery vehicle, or

dosage protocol for herbal medicines are even more inaccurate than

those made about single ingredient drugs or natural products. Let me

give you an example of what I am referring to with a common

generalization that I have heard about the timing of taking herbal

products. I have heard it said that it is best to take herbal

medicines on an empty stomach away from foods. While that is

certainly true for some herbal products, it is not true for many

others. It is simply too general of a statement that does not hold

up.

 

I want to be clear here that I am not making a generalization here

that all herbal products are best taken in single daily dosages. The

point that I am trying to make is that for some herbal products it

appears to be the best route. The answer to the question about the

best form, delivery vehicle, or dosage protocol must be based upon

the existing scientific understanding. Hopefully, part of that

includes results from clinical and/or pharmacokinetic studies.

 

 

Single, daily dosage herbal products

 

Recently, Natural Factors launched a several herbal products with

an " All You Need is One " label. These products include CranMax®, Saw

Palmetto Extract, Black Cohosh Extract, L-theanine, Rhodiola

Extract, and Green Tea Extract. These natural compounds were

selected based upon the scientific understanding of the

pharmacokinetics or clinical response indicating single daily

dosages are at least equally effective as multiple dosages during

the day, or as given above with the EGCG example perhaps even more

effective.

 

To illustrate this point further, let's take a look at saw palmetto

extract, perhaps the botanical medicine with the greatest acceptance

and clinical documentation of effectiveness. Numerous double-blind

studies have shown the fat-soluble saw palmetto berry extracts

standardized to contain 85-95% fatty acids and sterols can

significantly improve the signs and symptoms of benign prostatic

hyperplasia (BPH). The typical dosage has been 160 mg twice daily,

however a one-year study demonstrated no difference in therapeutic

efficacy or safety comparing this dosage with a single dosage of 320

mg daily.6 Both dosage schedules produced significant improvements

in signs and symptoms of BPH.

 

A similar result was found with CranMax®, an all natural proprietary

product manufactured from the whole cranberry (not just the juice).

In the case of CranMax®, although it is a single daily dosage it

does utilize an exclusive delivery technology that allows the

product to be effectively time released over a 12-16 hour period

while also protecting the key active nutrients from the acidic

environment of the gut. It also is important to point out that

CranMax® is extremely concentrated – it takes 34 pounds of whole

fresh cranberries to produce one pound of Cran-Max®.

 

As well as being more beneficial, a single daily dosage

recommendation results is much more convenient.

 

 

Final Comment

 

The study of herbal medicine spans the breadth of the scientific

field of pharmacology: the study of the history, source, physical

and chemical properties, mechanisms of action, absorption,

distribution, biotransformation, excretion, interactions, and

therapeutic uses of " drugs " . In many respects, the pharmacological

investigation of herbal medicine is just beginning. It is an

exciting time.

 

Key References:

 

1. Teichert J, Kern J, Tritschler HJ, Ulrich H, Preiss R.

Investigations on the pharmacokinetics of alpha-lipoic acid in

healthy volunteers. Int J Clin Pharmacol Ther 1998;36(12):625-8

2. Evans JL, Heymann CJ, Goldfine ID, Gavin LA. Pharmacokinetics,

tolerability, and fructosamine-lowering effect of a novel,

controlled-release formulation of alpha-lipoic acid. Endocr Pract

2002;8(1):29-35.

3. Swezey RR, Aldridge DE, LeValley SE, et al. Absorption, tissue

distribution and elimination of 4-[(3)h]-epigallocatechin gallate in

beagle dogs. Int J Toxicol 2003;22(3):187-93.

4. Chow HH, Cai Y, Hakim IA, Crowell JA, et al. Pharmacokinetics and

safety of green tea polyphenols after multiple-dose administration

of epigallocatechin gallate and polyphenon E in healthy individuals.

Clin Cancer Res. 2003;9(9):3312-9.

5. Vaidyanathan JB, Walle T. Cellular uptake and efflux of the tea

flavonoid (-)epicatechin-3-gallate in the human intestinal cell line

Caco-2. J Pharmacol Exp Ther. 2003;307(2):745-52.

6. Braeckman J, Bruhwyler J, Vandekerckhove K, et al. Efficacy and

safety of the extract of Serenoa repens in the treatment of benign

prostatic hyperplasia: therapeutic equivalence between twice and

once daily dosage forms. Phytotherapy Res 1997; 11: 558-563.

 

 

 

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