Albert Szent-Gyorgyi: Ascorbic Acid- devoid of flavonoids proven ineffective

[Guest guest]

Dr. Szent-Gyorgyi: His Initial discovery of Vitamin C/Ascorbic Acid--

 

Laboratory tests determine that when vitamin C/ascorbic acid is

Devoid of additional Biological Constituents of Flavonoids,

Ascorbic Acid is found to be ineffective

 

Interview With Dr. Miklos Gabor

Interviewed By Richard A. Passwater Ph.D.

 

http://www.healthy.net/asp/templates/interview.asp?

PageType=Interview & ID=172

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In October, I was privileged to meet Professor Miklos Gabor of the

Albert Szent-Gyorgyi Medical University of Szeged, Hungary. Dr.

Gabor has published more than 200 research reports and five books on

flavonoids. He has also served as the scientific editor of other

books on bioflavonoids.

 

In 1990, Dr. Gabor received the Jancso Medal and Award for his

outstanding results and scientific work of high quality, and in

1993, he received the Novicardin Prize awarded by the Hungarian

Academy of Sciences.

 

Professor Gabor and I had a common interest besides Pycnogenol®

research.

 

We had a common friend, the late Nobel Laureate, Dr. Albert Szent-

Gyorgyi (1893-1986).

 

Professor Gabor was now carrying on bioflavonoid research at the

University named in honor of Dr. Szent-Gyorgyi (Americanized

pronunciation is Saint Jor'-jee).

 

Before I share what I learned about bioflavonoids from Dr. Gabor

with you, let me tell you a little about Dr. Szent-Gyorgyi, who

discovered the biological importance of bioflavonoids.

 

Dr. Szent-Gyorgyi was born in Budapest, but was claimed by the U.

S. and Hungary alike, and he conducted his research while spending

time in Cambridge, England; the Mayo Clinic, Minnesota; Woods Hole,

Massachusetts and Hungary.

 

Dr. Szent-Gyorgyi was more than a pioneer of biochemistry -- he was

a " father " of biochemistry. He was awarded the Nobel Prize in

Medicine in 1937 for his discovery of the biological oxidation

process with special regard to vitamin C and fumaric acid catalysis.

 

 

In 1928 he isolated what he at first called " hexuronic acid, " but is

now called " ascorbic acid " or vitamin C.

 

He also " discovered " the muscle protein actin, actomyosin and their

relationship to ATP.

 

He discovered the C4 dicarboxylic acid catalysis that forms the

basis of the Krebs cycle which was pioneering research on how food

is converted into energy.

 

His keen mind and bright ideas opened the doors to many areas of

biochemical research. He taught us so much, yet he was often labeled

a " maverick " because of his new ideas.

 

Dr. Szent-Gyorgyi always professed that his discovery of the

biological function of bioflavonoids was serendipitous.

 

He found something he did not seek.

 

While he was trying to isolate vitamin C, his colleague Professor

I. (St.) Rusznyak had a patient with subcutaneous capillary

bleedings.

 

They thought that vitamin C might help, so they gave the patient an

impure preparation that contained vitamin C plus other compounds.

 

They achieved a rapid success.

 

Later, a similar patient was treated with a pure solution of

vitamin C expecting quicker success,

 

but instead, the pure solution had no effect.

 

 

 

So they went back to the impure solution.

 

Dr Szent-Gyorgyi suspected that a flavone might be the key factor.

 

 

 

In 1935, Dr. Szent-Gyorgyi and his associate Dr. I. (St.) Rusznyak,

isolated a " factor " from lemon juice that decreased the permeability

and increased the resistance of the capillary wall.

 

At first, chemical analysis indicated that this factor was a single

flavonoid compound and it was named " citrin. "

 

Because of the effect on capillary health, Dr. Szent-Gyorgyi also

called this factor " vitamin P. " [Nature 138:798;1936, Nature

137:27;1936]

 

 

 

He chose " a letter on the far unoccupied side of the ABC " letters

already being used to designate vitamins in case that bioflavonoids

were not found to be true vitamins " correction could be made without

confusion. "

The letter " P " was convenient because it could stand

for " permeability, " " purpura " or " petechiae. " The " vitamin P "

normalized the low capillary resistance of vascular purpura patients.

 

 

In 1936, Dr. Szent-Gyorgyi and his associate, Dr. V. Bruckner found

that citrin was actually a mixture of the flavone hesperidin and

eriodictiol glycoside, a flavonol glucoside. [Nature 138:1057;1936]

 

By 1936, studies by Dr. Szent-Gyorgyi and associates with guinea

pigs indicated bioflavonoids and vitamin C were synergistic and

interdependent.

 

In 1936, Dr. Janey reported the favorable effects of flavonoids on

intact and poisoned frog hearts. In 1937, Dr. Huszak reported on the

biochemistry of parenterally administered " citrin. "

 

Other researchers such as Zemplen, Bognar, and Farkas actively

researched the biochemistry of flavonoids. However, in 1938, Dr.

Szent-Gyorgyi reported that he could not substantiate that

bioflavonoids were truly essential nutrients.

 

 

 

It was the discovery in Szeged that called attention to the

biological actions of flavonoids, and from 1940 onwards, researchers

from many countries began studying the biochemical effects of

flavonoids such as catechins, proanthocyanidins, rutin, etc.

Hungarian researchers had started the research on the biochemistry

of flavonoids, and today remain leaders in the field.

 

 

 

I had the pleasure of discussing vitamin C and the role of electron

transport and the electronic desaturation of protein molecules in

the cancer process with Dr. Szent-Gyorgyi many times during 1972

through 1979, as well as lecturing together. Dr. Szent-Gyorgyi would

discuss my joint research with Dr. Keith Brewer on energy transfer

in cell membranes via double bond excitation. This research was

published in American Laboratory in a five-part series from 1974

through 1976.

 

In a March 19, 1973 letter to me, Dr. Szent-Gyorgyi remarked, " I

have not published anything on cancer in a long time, though I have

been working very hard. I arrived at a new concept, but my ideas are

not in disagreement with yours, they are complementary. "

 

We were both working on our " electronic theory for cancer, " or as

Dr. Szent-Gyorgyi liked to call it, the " electronic dimension of

life and cancer. "

Dr. Szent-Gyorgyi called our approaches complementary because we

were both examining the participation of cellular structures -- not

just the liquid-state compounds. Also, I was publishing on the free-

radical initiation of cancer and he was investigating the electron

transfer system within structural proteins that allowed them to

become semiconductors by oscillating between two states -- one of

which was a free radical state.

 

He had observed that structural proteins in cells are the color

of " a good Swiss chocolate. " The color is due to the presence of an

electron transfer system in structural proteins which transforms

them into free radicals. However, the structural proteins in cancer

cells are colorless, indicating that their electron acceptors are

missing or have been damaged.

 

Dr. Szent-Gyorgyi also found that dicarbonyls produced by the

electron transfer process were capable of stopping cell division. He

reasoned that the defective electron transfer system in cellular

proteins allowed the cells to engage in uncontrolled cell division,

thus become cancer cells.

 

Cancer cells have lost their ability to be semiconductors. Their

structural proteins can no longer accept the single electrons of

free radicals, and thus in turn temporarily become free radicals

themselves, and then cause the formation of cell-regulating by-

products such as dicarbonyls.

 

Dr. Szent-Gyorgyi was a fascinating man with many brilliant

concepts, and provided much encouragement for my research. He often

shared his views on true discovery and how it must by nature seem

radical and wrong to everyone -- or it wouldn't be a true discovery.

 

Occasionally, Dr. Szent-Gyorgyi and I would discuss the role of

bioflavonoids as nutrients, and that Dr. Szent-Gyorgyi still thought

that some good modern research would clarify the " essential or

nearly essential " importance of bioflavonoids. You can see that my

meeting Dr. Gabor has brought back many fond memories of Dr. Szent-

Gyorgyi and that Dr. Gabor and I had some long chats about our

mutual friend.

 

In the foreword to one of Professor Miklos Gabor's books, Dr. Szent-

Gyorgyi remarked in 1972, " American science did not take in a

friendly spirit to vitamin P and the name " vitamin " was dropped.

 

More than that, discussions have been going on to strike the

flavones altogether from the lists of (nutrients and) drugs, since

no therapeutic action has been found.

I think the contradiction is due to the fact that in the USA,

citrus fruits belong to people's regular daily diet. They are rich

in flavones, so a (total) lack in flavones is very rare, and if

there is no deficiency, a vitamin has no action. In contrast to

this, in countries where citrus fruits are expensive, the lack of

flavones may cause trouble and their medication may show favorable

effects. While these discussions were going on, important

experimental material was collected in Hungary which, in my mind,

leaves no doubt about the vitamin nature and the biological activity

of flavones. "

 

However, others do not share this conclusion. In Dr. Gabor's 1986

book, Dr. Middleton writes in the foreword, " There seems to be a

resurgence of interest in flavonoid research in recent years after

the vitamin P era had come to its proper conclusion. "

 

Dr. Middleton also remarks, " For many years one worker and his

colleagues in the " flavonoid fields " persistently has kept our

attention focused on the relevance of flavonoid research. This

individual, Professor Miklos Gabor, deserves great credit for his

insight and perseverance. "

 

In October 1993, I had the chance to chat with Dr Gabor who is the

world's leading expert on the role of bioflavonoids and capillary

health and also to compare stories about Dr. Szent-Gyorgyi. I will

try to share some of his knowledge of bioflavonoids and capillary

health with you.

 

Passwater: Dr. Gabor, did you have the opportunity to do research

with Dr. Szent-Gyorgyi?

 

Gabor: No, during the stay of Dr. Szent-Gyorgyi at Szeged, I was a

student. However, I did attend his lectures and have the opportunity

to know him then, and of course, we had a continuing scientific

dialog through the years.

 

Passwater: You are the world's leading authority on bioflavonoids

and capillary health. You have published many research reports and

have written several books on bioflavonoids, capillary permeability

edema and inflammation. What originally aroused your interest in

this field, and what continues to hold your interest?

 

Gabor: During the period from 1950 to 1954 in the Department of

Pharmacology of the Szeged University Medical School, I began my

research with some naturally occurring compounds -- haematoxylin,

haematein, brasilin and brasilein -- which can be broadly considered

as members of the bioflavonoid family. Our research group

demonstrated that these natural dyestuffs can decrease the increased

vascular permeability in guinea pig eyes and skin capillaries of

rats.

 

After we demonstrated the permeability-decreasing action of

haematoxylin compounds, we examined their ability to normalize

lowered capillary resistance. The permeability of capillaries is

quite important to health, and the effect of various nutrients on

capillary permeability fascinates me. My first book deals with the

pharmacology of capillary resistance, including the effects of

bioflavonoids. This book " Die Pharmakologische Beeinflussung der

Kapillarresistenz und Ihrer Regulationsmechahanismen " was published

by the Hungarian Academy of Sciences (Akademiai Kiado, Budapest) in

1960.

 

In 1965, the Hungarian Academy of Sciences founded a Committee for

Flavonoid research. In 1965 and 1967, I was privileged to organize

the first and second international symposia on bioflavonoids. Since

then, these symposia have been held every four-to-five years. The

next international bioflavonoid symposium entitled the " Ninth

Hungarian Bioflavonoid Symposium " will be held in Wien (Austria) in

1995. However, I have to emphasize that a conference more limited in

scope was the conference on " Bioflavonoids and the Capillary, " which

was organized by the New York Academy of Sciences and held on

February 11, 1955.

 

In 1972, Dr. Szent-Gyorgyi wrote the foreword for my English-

language book, " The Anti-inflammatory Action of Flavonoids. "

 

 

The foreword to my 1986 English-language book, " The Pharmacology of

Benzopyrone Derivatives (Flavonoids) and Related Compounds " was

written by Professor Elliott Middleton, Jr. of the State University

of New York at Buffalo.

 

So you can see that my interest in bioflavonoids is very strong.

 

Passwater: Yes, and so is the interest of Professor Middleton. I

have co-authored a book on Pycnogenol® [Keats Publ., 1993] with a

colleague of Professor Middleton at Buffalo, Dr. Chithan Kandaswami.

We discuss Drs. Middleton's and Kandaswami's research on cancer and

bioflavonoids in this new book and in upcoming Health Connection

columns continuing the interview series with Dr. Kandaswami.

 

I also note that Dr. Hans Selye wrote a foreword to your 1974

book, " Pathophysiology and Pharmacology of Capillary Resistance. "

 

Evidence is lacking that bioflavonoids are essential nutrients. Is

that because they are not essential or is it merely because that no

diets have been developed that are totally free of bioflavonoids?

 

I note that in the scientific literature you have studied the blood

brain barrier and aorta structural abnormalities produced by what

you call " P avitaminosis " (a deficiency of " vitamin P " ) produced by

flavonoid-free diets.

 

Would you please elaborate a little for us on " P avitaminosis? Do

humans and other animals get enough bioflavonoids in their

experimental or normal diets to prevent a recognized bioflavonoid

deficiency from being observed?

 

Gabor: Many experimental " fragilizing " diets have now been developed

that are totally free of bioflavonoids. Humans and other animals get

enough bioflavonoids in their normal or experimental diets to

prevent a frank bioflavonoid deficiency.

 

I should like to mention here that the estimated daily dietary

intake of flavonoids in the United States is about one gram. This

originates from cereals, potatoes, bulbs, roots, peanuts, nuts,

vegetables, herbs, fruits, fruit juices, cocoa, cola, coffee, beer

and wine.

 

Flavonoids may be present in amounts up to a hundred milligrams per

kilogram of fresh weight in soft fruits and their juices.

Anthocyanin may be present in rich amounts in some foods such as

raspberry, which can contain hundreds of milligrams per hundred

grams of fresh weight.

Notable sources of anthocyanins are red cabbage, onion, beans,

radishes, and rhubarb sticks.

 

The concentration of catechins in ripe fruits is about five -to-

twenty milligrams per hundred grams of fresh weight. Dimeric

proanthocyanidins occur in unripe berries and the leaves of soft

fruit plants in amounts ranging between fifty and five hundred

milligrams per hundred grams of fresh weight. Some proanthocyanidins

are present in apples and grapes. Flavonoids are in tea, cocoa, wine

and beer.

 

Perhaps, Dr. Szent-Gyorgyi was technically correct in saying that

certain bioflavonoids, as a group, should have vitamin status.

 

However, frank bioflavonoid deficiency is not a major problem. Today

we don't seem to eat enough bioflavonoids for optimal health, but we

do seem to get enough to prevent " P avitaminosis. "

 

Keep in mind that bioflavonoids are important to blood vessel

health and even protection from heart disease, and there is a

definite benefit to be obtained by optimizing dietary bioflavonoid

intake. We should do more research on the benefits of bioflavonoids

and not be distracted by the question of whether or not

bioflavonoids should have vitamin status.

 

Keep in mind that Dr. Szent-Gyorgyi's experiments indicated that at

least a trace of vitamin C must be present to observe the vitamin-

like effect of the bioflavonoids.

In his experiments, guinea pigs were kept on the scorbutic Sherman -

La Mer - Campbell deficiency diet. One group, the untreated

controls, died in an average of 28.5 days. The group given one

milligram of citrin daily for six weeks lived an average of 44 days.

All of the animals in both groups showed the typical symptoms of

scurvy. Dr. Szent-Gyorgyi and his colleagues concluded, " these

results suggest that experimental scurvy, as commonly known, is a

deficiency disease caused by the combined lack of vitamins C and P. "

 

Dr. Szent-Gyorgyi asked other scientists to repeat his studies. The

results were partly corroborative and partly negative. In 1937, Drs.

Szent-Gyorgyi and Bentsath stated, " vitamin P requires for its

activity the presence of ascorbic acid.

 

A scurvy diet frequently contains traces which in themselves have

no influence on the development of scurvy, but enable vitamin P to

act. In the total absence of ascorbic acid, vitamin P is inactive. "

[Nature 140:426;1937]

 

Passwater: There certainly is a synergism between vitamin C and the

bioflavonoids. They protect each other against oxidation and have

other interactions. Let's move on to the importance of bioflavonoids

to health. Capillaries are important because they carry nutrients to

cells and carry away waste. Capillaries must be permeable enough to

allow fluids to seep out of the capillaries, mix with the fluid that

surrounds all of the cells, and then reenter the capillaries. If the

capillaries are too permeable, too much fluid and protein seep out

resulting in edema, and even red blood cells may also seep out

causing bruising and red spots. You have even designed a simple

portable petechiometer to measure the degree of petechiae (small

hemorrhages appearing as red spots) formation permitted by weak

capillaries. If capillaries are too permeable, they are no longer a

barrier to infection. Dr. Gabor, what has your research shown

regarding Pycnogenol® and capillary permeability.?

 

Gabor: I have studied the effect of water-soluble flavone

derivatives including proanthocyanidins and hesperidin-

methylchalcone on the vascular wall resistance in rats with

spontaneous hypertension (high blood pressure). My investigation

revealed that the pathologically low capillary resistance in rats

with spontaneous hypertension was normalized by treatment with

oligomeric proanthocyanidin. This research will be published this

year in Scripta Phlebologica.

 

Thus, Pycnogenol® increases pathologically low capillary

resistance, decreases undesirably high capillary permeability and

improves circulation. As I explain in my upcoming Scripta

Phlebologica report, the anti-inflammatory action of

proanthocyanidins may be based on increasing the capillary

resistance, but additional factors should be considered. The

antioxidant action of Pycnogenol® has been reported; it can

scavenge superoxide radicals, it reduces UV-B radiation-induced

cytotoxicity of fibroblasts and inhibits lipid peroxidation.

 

Free radicals and other reactive oxygen species are formed at the

sites of inflammation and contribute to tissue damage.

 

The scavenging effect of Pycnogenol® for radicals correlates with

its anti-inflammatory activity. Pycnogenol® may also act by

inhibiting lipoxygenase and cyclooxygenase.

 

Passwater: Aha! Most people assume that it's the high blood pressure

alone that bursts the blood vessels, but it is the decreased

capillary resistance and increased permeability that cause the blood

vessel to bleed and weaken enough to burst.

 

So, if low capillary resistance is common in people with high blood

pressure, and this is a major factor that leads to stroke and

retinal hemorrhage, your study is of major importance to the

millions of people with high blood pressure. Your findings could

drastically reduce the incidence of strokes. Please elaborate on

your study.

 

Gabor: It has long been known that the capillary resistance is

pathologically decreased in a considerable proportion of

hypertensive persons [Griffith and Lindauer, 1944; Kuchmeister and

Scharfe, 1950; Gough, 1962; Davis and Landau, 1970; etc.]

 

Special mention should be made of the observation that, if

hypertension is associated with a low capillary resistance, the

incidence of cerebral insults (apoplexy, stroke) and retinal

hemorrhage is essentially higher [Griffith and Lindauer, 1944]. It

was established by Paterson in 1940 that capillary rupture

accompanied by intimal bleeding plays a role in the mechanism of

cerebral arterial thrombosis. He assumed that, at the intracapillary

pressure resulting from the high blood pressure, the capillary

fragility (which is enhanced for various reasons) is responsible for

the intimal rupture of the cerebral arterial capillaries.

 

These data stimulated us to carry out capillary resistance

determinations in spontaneous hypertension rats. As the results

reveal, pathologically low values were observed in the large

majority of the experimental animals.

 

In connection with the flavonoids used, it may be mentioned that

oligomeric proanthocyanidin, isolated from Pinus maritima, was

selected because its indications are to increase pathologically low

capillary resistance, to decrease an enhanced capillary

permeability, and to improve the circulation.

 

My study revealed that the pathologically low vascular wall

resistance of spontaneous hypertension rats can be elevated by

treatment with oligomeric proanthocyanidin.

 

Passwater: Does your research indicate that Pycnogenol® would be

of help to people having fragile capillaries that might result in

problems such as bleeding gums, floaters caused by bleeding into the

retina, glaucoma, bleeding kidneys, and stroke? Also, I have seen

European studies that show that Pycnogenol® is a nutritional

adjunct that helps against varicose veins, heavy menstrual bleeding,

hemorrhoids and the complications of diabetes.

 

Gabor: I have not personally conducted clinical trials on these

conditions per se, however, capillary health is compromised in all

of these conditions, and Pycnogenol® acts to improve capillary

health by improving their bioflavonoid nourishment.

 

Passwater: For many years you have been studying the effects of

flavonoids on the capillary resistance of psoriatic patients. A

friend of mine in Manchester, England, Dennis Gore, has reported

anecdotal data to me that proanthocyanidins seem to be effective

against psoriasis itself. Have you noticed this in your studies?

 

Gabor: Proanthocyanidins are used successfully against diseases

characterized by capillary bleeding associated with increased

capillary fragility. The capillary resistance of psoriatic patients

is significantly lower than that of healthy persons. Pycnogenol®

tends to restore normal capillary resistance in these psoriatic

patients. However, I have not conducted a clinical trial of the

effect of Pycnogenol® on psoriasis as a disease state. I have

studied what may be the causative component of the disease and I

have shown that bioflavonoids can correct this factor.

 

Passwater: How do the bioflavonoids help capillaries maintain their

proper resistance and permeability?

 

Gabor: As you know, I have been studying the actions of the

flavonoids in elevating capillary resistance since the early 1950's

and in 1974 I published a detailed survey of the results of all of

the relevant research up to that date. However, just as with

inflammation, we still have a lot to learn about the " how " part.

Even though we need to learn more about the mechanism involved, we

do know that the effects are real. I have observed that Pycnogenol

® improves the capillary resistance within two hours and maintains

it longer than eight hours.

 

Passwater: What has your research shown about bioflavonoids and

inflammation?

 

Gabor: I earlier reported that proanthocyanidin significantly

decreased the inflammation and edema induced by serotonin,

prostaglandin or carrageenin. The decrease is dose-dependent and

statistically significant. [Gabor & Razga, Acta Physiol. Hung.

77:197-207 (1991)] Pycnogenol®, sophoricoside and fisetin are the

most effective flavonoids against inflammation that I have tested,

and Pycnogenol® has the advantage of being very water soluble and

bioavailable.

 

The mechanisms at play involve the inhibition of several chemical

mediators including histamine, prostaglandins, 5-hydroxytryptamine

and kinins. Also, these flavonoids can block undesirable actions of

lipoxygenase and cyclooxygenase.

 

The actions of Pycnogenol® against inflammation are different than

those of rutin, hesperidin and the citroflavonoids.

 

Passwater: What are your interests for future research?

 

Gabor: Sixty years after the pioneering research by Rusznyak and

Szent-Gyorgyi, the question naturally arises as to the explanation

of the renaissance in flavonoid research. The answer is clear:

chemists have synthesized new flavonoid derivatives with previously

unknown biological effects; phytochemists have isolated numerous new

flavonoids from many plants; biochemists have demonstrated the most

varied effects on different enzymes; and an ever increasing number

of pharmacologic effects have become known through variations of the

chemical structures of the flavonoids and related compounds. This

research has led to the discovery of many new drugs that can be

applied for therapeutic purposes. In these words you can find the

future of the research of bioflavonoids. Personally, I am working

now with experimentally induced edema and with the effects of

various drugs on this phenomenon.

 

Thank you, Dr. Gabor.

 

All rights, including electronic and print media, to this article

are copyrighted to © Richard A. Passwater, Ph.D. and Whole Foods

magazine (WFC Inc.).