Resveratrol--influences cancer at initiation, promotion, and progression
Resveratrol is one of a group of compounds (called phytoalexins) that are produced
in plants during times of environmental stress, such as adverse weather or insect,
animal, or pathogenic attack. Resveratrol has been identified in more than 70
species of plants, including mulberries and peanuts, and the skins of red grapes,
which are a particularly rich source (Jang et al. 1999). According to Pezzuto, "Of
all the plants we’ve tested for cancer chemopreventive activity, this one
[resveratrol] has the greatest promise" (Pezzuto 1997).
Resveratrol was effective against cancer during all three phases of
the cancer process: initiation, promotion, and progression. For example,
resveratrol displayed antimutagenic and antioxidant activity, providing
greater protection against DNA damage than vitamins C, E, or beta-carotene.
Resveratrol restored glutathione levels, considered by some as the most
essential of antioxidants (Jang et al. 1999). It increased levels of
a Phase II detoxifying enzyme (quinone reductase), an enzyme responsible
for metabolically disassembling carcinogens.
Resveratrol inhibited the activity of cyclooxygenase-2 (COX-2), reducing
the inflammatory response in human epithelial cells (Subbaramaiah et
al. 1999). Upregulation of COX-2 is associated with the physical manifestations
of various human cancers, as well as other inflammatory disorders. Since
inflammation is closely linked to tumor promotion, substances with potent
anti-inflammatory activities are thought to exert chemopreventive effects,
particularly in the promotion stage of the disease.
Resveratrol prompted differentiation of human promyelocytic leukemia
cells. The development of preneoplastic lesions in mouse mammary glands
was inhibited by resveratrol (Kang et al. 2003; Asou et al 2002; Tsan
et al. 2002).
The following studies illustrate the many pathways resveratrol employs
to inhibit cancer:
Italian researchers recently determined that resveratrol exhibited a
protective role against colon carcinogenesis, with the defense attributed
to changes occurring in Bax protein, which encourages cell death (apoptosis),
and p21 expression (Tessitore et al. 2000). Reduced Bax activity is associated
with resistance to cytotoxic therapy (Bosanquet et al. 2002). p21 is
able to arrest the cell cycle at the G1 phase by inhibiting DNA replication
(Aaltomaa et al. 1999). Suppressing the growth cycle allows for a critical
phase in cellular development referred to as differentiation, that is,
an abnormal cell becomes more normal.
Resveratrol appears a promising anticancer agent for both hormone-dependent
and hormone-independent breast cancers. At high concentrations, resveratrol
caused suppression of cell growth in three breast cancer cell lines: estrogen-receptor
(ER)-positive KPL-1 and MCF-7 and ER-negative MKL-F. Growth inhibition was
credited in part to up-regulation of Bax protein and activation of caspase-3
(a key mediator of apoptosis in mammalian cells). Resveratrol was also able
to lessen the growth stimulatory effects of linoleic acid, a fatty acid frequently
over-consumed in Western diets (Nakagawa et al. 2001).
Resveratrol significantly reduced tumor volume (42%), tumor weight (44%), and
metastasis (56%) in mice with highly metastatic Lewis lung carcinoma. Resveratrol
was able to inhibit angiogenesis and reduce oxidative stress (Kimura et al.
2001; Kozuki et al. 2001).
Different wine polyphenols (catechin, epicatechin, quercetin) including resveratrol
may be effective against prostate cancer. Prostate cancer cell lines (LNCaP
and DU145) produce high concentrations of nitric oxide; PC3 produces low concentrations.
Researchers propose that the anti-proliferative effects of polyphenols are
due to their ability to adjust nitric oxide production (Kampa et al. 2000).
Grape extract, a rich source of resveratrol, inhibited prostate cancer growth
up to 98% in a dose- and time-dependent manner (Agarwal et al. 2000b).
Resveratrol appears to be promising in the control of acute monocytic leukemia
(Tsan et al. 2000). Resveratrol induced apoptotic cell death in human leukemia
cells (HL60) (Clement et al. 1998) and stopped the growth of lymphocytic leukemia
cells during the S-phase of the growth cycle (the time of DNA replication)
(Bernhard et al. 2000).
Resveratrol inhibits NF-kB, thus inhibiting cell proliferation and cytokine
production (Gao et al. 2001). The inhibition of cytokine production by resveratrol
was found to be irreversible.
If using pure resveratrol, the suggested dosage is 7-50 mg a day. Beware of
diluted supplements that provide very little active resveratrol. At the time
of this writing, there were only a few sources of pure high-potency resveratrol
available as dietary supplements.
Resveratrol & Quercetin - Anti Heart & Anti
by James South MA
Heart disease and cancer are the two main causes of death in America and Europe,
eventually killing about 2/3 of all adults. For the past 40 years, it has been
virtually a dogma of Western medicine that a diet high in saturated fat/cholesterol,
and/or a high blood cholesterol level, is the primary cause of heart disease.
The high blood cholesterol so typical of Western peoples is alleged to cause
atherosclerotic plagues to develop over a lifetime, eventually "plugging
up" heart arteries and leading to death by "heart attack" (i.e.
myocardial infarction (MI) or coronary thrombosis).
The so-called "fatty/cholesterol plague" that can occlude arteries
is called "atheroma"; the gradual development of atheroma in heart
arteries is referred to as "coronary atherogenesis"; and the chief
culprit in the process of atherogenesis is alleged to be cholesterol/saturated
fat. More recent refinements of the atherogenesis dogma posit high LDL cholesterol
and/or low HDL cholesterol as the chief culprit in atherogenesis.
THROMBI VS. ATHEROMA
Yet there has been a mass of evidence dating back 40 years that clearly points
to atheroma/atherogenesis as being secondary phenomena in the 20th century
epidemic of heart attacks. In a 1984 review article summing up the case against
atheroma as the primary cause of MI, Wayne Martin noted that 'Keely and Higginson
in 1957 reported [widespread] atheroma among the Bantus, even though they
seemed to be free from MI. They suggested that thrombi [abnormal blood clots]
rather than atheroma may be the major cause of MI. In 1959 Gore et al found
the same degree of atheroma in Japan and in the United States.... In 1968
Strong et al reported on a world-wide study showing that atheroma is as prevalent
among women as it is among men, and further, that all populations of the
world suffer from atheroma to about the same degree, even among populations
such as the Bantus, who are known to suffer little from MI. In 1960 Thomas
et al reported on a study in pathology, showing the black population of Uganda
to be free from MI; however they did note that these blacks had atheroma.
They, like Keeley and Higginson, said that it was high time more concern should
be shown over the danger of thrombi and less concern about atheroma. Strong
et al are continuing a study comparing atheroma in New Orleans, USA and Tokyo,
Japan, finding that in New Orleans, USA, where the death rate from MI was very
high as of 1978, there was very little difference in atheroma as compared with
Tokyo men, among whom MI is much less common.
In 1980 Sinclair noted that in Jamaica, where there is severe atheroma caused
presumably by coconut oil in diet, atheroma does not seem to cause coronary
thrombosis. Sinclair stated that thrombosis and not atheroma is the major causal
factor in MI.
There is now abundant evidence that man, world-wide, is afflicted with atheroma,
but that many populations in Africa and Asia co-exist with atheroma without
being afflicted with MI.' (1).
Kinsella et al also highlight the importance of platelet aggregation/thrombogenesis
in MI deaths: '... the antioxidative agents in plant foods and wine may also
be very effective in reducing thrombosis and blockage of narrowed arteries,
which is a fatal event in more than 90% of deaths from CHD [coronary heart
disease].... Thus, the partially occluded [by atheroma] artery is easily
blocked by thrombi formed mostly from aggregated blood cells that rapidly
aggregate and clump in response to specific stimuli.'(15).
In a classic 1992 article about the 'French paradox for heart disease, Õ Renaud
and de Lorgeril present evidence that dietary fat and blood cholesterol are
not primary MI villains, at least among the French. They note that the annual
mortality rate per 100,000 population from coronary heart disease (CHD) is
78 in Toulouse, France, and 105 in Lille, France (for men), compared to 182
in Stanford, USA, 348 in Belfast, UK, and 380 in Glasgow, UK. Yet the saturated
fat intake is about the same for these groups - 15% of total calories. The
mean serum cholesterol is notably lower for men in Stanford (209 mg%) than
in France (230 in Toulouse, 252 in Lille), while Belfast (232) and Glasgow
(244) levels are similar to France, yet all three have higher MI mortality
rates than France. Renaud and de Lorgeril report that 'Stepwise multivariate
analysis ... shows that in the 17 countries that report wine consumption, wine
is the only foodstuff in addition to dairy fat that correlates significantly
with mortality.... wine has a negative sign indicating a protective effect
that accords with previous reports.'(2). Renaud and de Lorgeril then present
evidence that it is not through inhibitory effects on atherosclerotic lesions
(atheroma) that wine provides MI protection, but rather through a decrease
in the tendency of platelets to pathologically aggregate and 'plug up' heart
arteries. They note "... we have compared farmers from Var, Southern France
(low in CHD mortality), with farmers from south-west Scotland for [platelet
aggregation tendencies]. Platelet aggregation was strikingly lower in Var.
Secondary aggregation to ADP, the test that undergoes the greatest decrease
with alcohol, was 55% lower in Var than in Scotland, whereas mean HDL [allegedly
MI-protective] cholesterol was 69 mg/dl in Girvan, Scotland, 66 mg/dl in Stranraer,
Scotland, and 63 mg/dl in Var. Consumption of alcohol was greatest in Var (45g
per day vs 20g per day in Scotland), mostly in the form of wine." (2).
Lest anyone derive from this the moral that alcohol per se is beneficial for
heart health, several points should be noted. As Goldberg et al state, "...ethanol
or a metabolite impairs the platelet function as a consequence of... platelet
injury." (3). It is not sound nutritional or medical practice (although
it is the essence of allopathic medicine) to try to oppose pathology by creating
a new 'opposing' pathology.
THE RED WINE CONNECTION
Goldberg et al also note that "...Klatsky and Armstrong recorded the lowest
risk of CHD mortality among those who drank wine compared with those preferring
[other alcoholic] beverages, especially at higher rates of consumption." (3).
And, when "...16 healthy subjects were given [pure] alcohol, white wine
and red wine [for 15 days for each beverage], alcohol enhanced [i.e. increased]
... platelet aggregation.... Red wine led to a fall in ADP-induced [platelet]
aggregation and increased HDL-cholesterol, clearly the most favourable response
to the three beverages tested." (3).
Klurfield and Kritchevsky reported that "Rabbits were fed on atherogenic
diet together with water (controls), or one of five different beverages containing
equal amounts of ethanol. After 3 months, all the control rabbits had developed
atherosclerotic lesions in the coronary arteries. The alcoholic beverages,
except beer, reduced the incidence of such lesions, but the most dramatic reduction
(to 40% of controls) occured in the rabbits receiving red wine." (3).
This is just a sampling of the evidence that it is primarily red wine, not
spirits or beer, that is 'heart-friendly.' Yet even red wine contains alcohol,
and alcohol, especially through its chief metabolite, acetaldehyde, is a powerful
and broad-acting metabolic toxin, with liver damage being just the 'tip of
the iceberg' of alcohol's destructive side. (for more detail on the dark side
of alcohol/acetaldehyde, see my article 'Acetaldehyde: A common and potent
As it became clear by the early 1990Õs that something relatively unique
to red wine provided significant heart protection, nutritional scientists began
searching to find the 'active ingredient(s).'
In a 1995 article, researcher David Goldberg rhetorically asked "What
on earth has the color of the wine got to do with it all? A great deal it seems.
The only consistent difference between the red and white wines is that the
red contains more phenolic compounds; among these phenols, the major difference
is in the flavonoids... [including] compounds such as quercetin, rutin, catechin
and epicatechin...." (5). Goldberg points out that 'flavonoids' have been
demonstrated to have powerful biological effects, including the ability to
inhibit eicosanoid synthesis and pathological platelet aggregation, as well
as the ability to inhibit cancer growth and development. Goldberg also notes
these red wine-phenolics are individually and collectively 10 to 20 times more
potent than vitamin E in protecting low-density lipoproteins (LDL) against
oxidation, (oxidized LDL is now considered to be a powerful initiating mechanism
of atherogenesis). Yet Goldberg also points out that people who eat a decent
amount of fruits and vegetables will already ingest a fairly healthy dose of
flavonoids, so 'why the fuss about red wine?' (Indeed, the Zutphen Elderly
study showed that even the modest amount of flavonoids, primarily quercetin,
found in tea, onions and apples, seemed to provide significant protection against
death from MI among elderly men consuming these 3 foods, compared to those
not consuming them. (6).
Goldberg then asked the rhetorical question "Does [red] wine contain a
biological component that is present only in limited amounts in a typical diet?" Indeed,
it does: resveratrol. This trihydroxystilbene is synthesized by [grapes], being
present in the canes, leaves and the skins of the berries. Because these are
present during the fermentation of red wines, but not white wines, only the
former contain significant amounts of resveratrol in the finished product....
Apart from peanuts, no other human-consumed foodstuff contains significant
The resveratrol story does not begin with its (recent) discovery in wine. It
actually started in the early 1980's among Japanese scientific researchers.
Reporting in 1982, Arichi et al noted that the dried roots of Polygonum cuspidatum
have been used in traditional Japanese and Chinese medicine in a product called
'Kojo-kon,' used to treat a wide range of afflictions, including fungal diseases,
various skin inflammations and diseases of the heart, liver and blood vessels.
Resveratrol and its glycoside 'polydatin' have been shown to be the primary
active ingredients of Kojo-kon. (7).
In 1985 Kimura et al discovered the key to resveratrol's metabolic activity.
Working with rat leukocytes (white blood cells), they showed that resveratrol
possesses a powerful ability to inhibit eicosanoid production.
EICOSANOSIS THE QUASI-HORMONES
Eicosanoids are powerful 'quasi-hormones,' extremely short-lived, generated
from three 20-carbon fatty acids: dihomogamma-linolenic acid (DGLA), arachidonic
acid (AA) and eicosapentaenoic acid (EPA, common in fish oils). AA predominates
in mammalian cells, being stored in cell membranes. Through the cyclooxygenase
(COX) enzymes AA is transformed into the powerful pro-inflammatory and platelet-aggregating
thromboxanes, as well as inflammatory prostaglindins. Through the lipoxygenase
(LOX) enzymes AA becomes the powerful inflammatory and white cell stimulating
agents known as leukotrienes, hepoxillins and lipoxins. (8).
Kimura et al found that the resveratrol concentration needed to reduce by 50%
(IC50) the AA-LOX product 5-HETE was only 2.72 micromoles resveratrol (=62mcg
resveratrol /100cc!), while the IC50 to reduce thromboxane B2 production from
AA by COX required only 0.81 micromoles resveratrol (=18.5 mcg resveratrol
/100cc!). Kimura et al also reported resveratrol to inhibit platelet aggregation
induced by AA, thrombin and ADP. (9).
As Soleas et al noted, "Platelets were the next biological system to be
tested, and a series of papers from Chinese laboratories... described the ability
of resveratrol... to inhibit the aggregation of rabbit platelets as well as
their formation of thromboxane B2 from arachidonate. Finally, resveratrol was
shown to inhibit the antigen induced contraction of isolated trachea from guinea
pigs rendered sensitive to albumin... inhibition of arachidonate metabolism
was the like; y mechanism." (10).
In 1995 Pace-Asciak et al reported a dose-dependent inhibition by both trans-resveratrol
and quercetin of the aggregation of platelets prepared from healthy human
subjects. The IC50 concentrations for both resveratrol and quercetin were
approximately 100 micromoles, while ethanol required 1000 times higher concentrations
to achieve the same effect. The standard antioxidants BHT and vitamin E were
ineffective at inhibiting platelet aggregation, as were the major wine phenolics
catechin and epicatechin. (11).
Pace-Asciak et al also found that trans-resveratrol strongly inhibited the
COX-catalyzed thromboxane synthesis by platelets, with approximately 60% inhibition
at 10 micromoles resveratrol. Neither Quercetin or any of the other wine phenolics
or antioxidants tested had any major effect at that concentration. At a concentration
of 10 micromoles, Quercetin inhibited the platelet LOX pathway by 70%, while
only resveratrol of the other phenolics and antioxidants tested exerted modest
LOX inhibition at higher levels. Platelet LOX activity generates hepoxillins
from AA, which induce vascular permeability and neutrophil activity, two partial
causes of atherogenesis. (8,11). As Soleas et al note, "...resveratrol
at micromolar concentrations is able to inhibit thromboxane A2 production,
and quercetin can likewise inhibit the formation of hepoxillins. Between them,
these two red wine phenolics can virtually shut down eicosanoid synthesis of
human platelets in vitro [and excessive platelet eicosanoid synthesis is the
basis of thrombogenesis]. (10). And in 1997 Soleas et al reported that "...by
applying information obtained from dose-response curves, the [platelet] antiaggregatory
effect of dealcoholized red wines could be computed as approximately that expected
from its concentrations of resveratrol and quercetin." (12).
BLOOD VESSEL BIOLOGY
To more fully grasp the importance of eicosanoids in platelet aggregation,
it is necessary to understand a simple fact about blood vessel biology. Healthy,
smooth, intact blood vessel linings (the endothelium, a layer only one cell
thick) "...synthesize and secrete prostacyclin [PGI2] is a strong vasodilator
and the most potent inhibitor of platelet aggregation known." (13). "...the
platelet thromboxane pathway is activated markedly in acute coronary syndromes....
PGI2...contributes to the non-thrombogenic properties of the endothelium....
PGI2 and TXA2 [thromboxane A2] represent biologically opposite poles of a
mechanism for regulating platelet-vessel wall interaction and the formation
of hemostatic plugs and intraarterial thrombi." (8). In other words,
PGI2 prevents clots from plugging up heart arteries, keeps the arteries dilated
(wide open), and promotes healthy endothelial lining. TXA2, however, promotes
pathological clotting, constricts arteries, and can damage the blood vessel
endothelial lining-i.e. promote atheroma. (8).
PGI2 is routinely made by healthy endothelial cells from AA, and then secreted
into the bloodstream. Prostacyclin synthase (PS) is the enzyme that transforms
AA into PGI2.
FREE RADICALS AND ANTI-OXIDANTS
And what impairs the activity of PS? Various free radicals and oxidants, especially
lipid peroxides and hydroperoxides- these are, essentially, 'rancid' fats.
(14,18). Kinsella et al state that the prevailing hydroperoxide 'tone' or
concentration is a result of the balance of pro-oxidants (e.g. free copper
or iron ions, cigarette smoke), antioxidants and oxidative substrates (i.e.
the fatty acids in the blood), and that this balance influences the propensity
toward oxidation/free radical production. (15). Thus, in order to maximise
production of heart-friendly PGI2, it is necessary to minimize the 'prevailing
hydroperoxide tone' in the blood, since high hydroperoxide tone = low PGI2
synthase activity = low PGI2. (It also helps PGI2 to minimize or eliminate
fried fats from the diet, too-these provide rich sources of hydroperoxides/peroxides.) "Antioxidants
inhibit lipid peroxidation by reducing general [hydroperoxide] tone.... The
polyphenolics [including resveratrol and Quercetin], commonly found in wine,
are potent antioxidants.... DeWhalley et al (1990) reported that flavonoids
act by protecting (and perhaps regenerating) the primary antioxidant, tocopherol
[vitamin E], by direct antioxidant effects, and by scavenging free radicals
and peroxy radicals." (15). Frankel et al reported both resveratrol
and Quercetin to be more powerful antioxidants than vitamin E in protecting
human LDL against copper-catalyzed oxidation. (16).
In 1994, B. Stavric wrote that "It appears that a number of the biological
effects of quercetin and other flavonoids may be explained by their antioxidative
activity and ability to scavenge free radicals. The antioxidative function
of quercetin was enhanced by ascorbate [vitamin C]. This enhancement is attributed
to the ability of ascorbate to reduce oxidized quercetin and of quercetin to
inhibit ascorbate photoxidation. Even more potent beneficial effects of quercetin,
as a radical scavenger and/or as inhibiting lipid peroxidation [key to enhancing
PGI2 production] were found in its combination with alpha-tocopherol [vitamin
E] and ascorbic acid." (17).
It also turns out to be very important to minimize free radical/lipid
peroxide production in order to minimize pathological platelet aggregation
due to TXA2 excess. thus, "the synthesis of these compounds [TXA2
and PGH2] by cyclo-oxygenase is enhanced by lipid hydroperoxides." (15). "Free
radical production is intrinsically linked with the enzymatic generation
of prostaglandins, thromboxanes and leukotrienes from [AA]... Lipid-derived
hydroperoxides (HPETE's) are obligatory intermediates in the generation
of prostaglandin/ thromboxanes ... from AA .... Bryant et al reported
that GP [glutathione peroxidase] reduces the hydroperoxide compound 12-HPETE
derived from AA, to its [relatively harmless] derivative 12-HETE....
Any impairment of GP (by lack of availability of [selenium]...) may lead
to abnormal accumulation of the HPETE peroxides, which are potent inhibitors
of the prostacyclin synthetase." (18).
CONCLUSION FOR BLOOD
Thus, a combination of resveratrol, Quercetin, vitamin E, vitamin C, and the
trace mineral selenium may be expected to have a highly synergistic effect
in reducing pathological platelet aggregation (thrombogenesis), maximizing
PGI2/minimizing TXA2 (thus dilating arteries for healthy blood flow as well
as opposing platelet aggregation) and minimizing free radical damage/disruption
to blood vessel linings (i.e. preventing/minimizing atherogenesis).
These same 5 compounds may also have a similarly beneficial effect in preventing
cancer, or even aiding in its cure. In 1997 Jang et al reported the results
of a series biochemical, cell culture, and animal studies with resveratrol
in the prestigious journal Science. They reported that "Resveratrol
inhibits cellular events associated with tumor initiation, promotion and
progression." (19). They also wrote that "... we studied tumorigenesis
in the two-stage mouse skin cancer model in which DMBA was used as initiator
and TPA as promoter. During an 18-week study mice treated with DMBA-plus
TPA developed an average of two tumors per mouse with 40% tumor incidence.
Application of 1, 5, 10 or 25 [micromoles] of resveratrol together with TPA
twice a week for 18 weeks reduced the number of skin tumors per mouse by
68, 81, 76 or 98% respectively, and the percentage of mice with tumors was
lowered by 50, 63, 63 or 88%, respectively. No overt signs of resveratrol
induced toxicity were observed...." (19). Jang et al also noted in their
paper the importance and potency of resveratrol's anti-cox activity and antioxidant/antimutagenic
activity in preventing tumor promotion and initiation.
Quercetin has also shown potent anti-cancer activity. Quercetin has "been
shown to inhibit the growth of cells derived from human and animal cancers,
such as leukemia and Ehrlich ascites tumors, the estrogen receptor-positive
breast carcinoma (MCF-7), squamous cell carcinoma of head and neck origin,
gastric cancer and colon cancer, as well as human leukemia HL-60 cells in culture
[Vang et al reported resveratrol to be active in normalizing HL-60 cells in
culture back into normal cells].... Quercetin has antiproliferative activity
against breast and stomach cancer cell lines and human ovarian cancer primary
cultures and can potentiate the action of [the anti-cancer drug] cisplatin
Furthermore, in vivo synergy with cisplatin against Walker lung cancer xenografts
in nude mice has been described." (12).
Hoffman et al in 1988 related both Quercetin's direct anti-cancer activity,
as well as its synergistic effect with several standard anti-cancer drugs to
its ability to inhibit the enzyme protein kinase C. They also noted that Quercetin "...is
a licensed [anti-cancer] drug in many countries, and is non-toxic at the required
dose range." (20). It is interesting to note that resveratrol was also
reported by Jayatilake et al to be a protein kinase inhibitor, also. (21).
In his textbook Cancer & Natural Medicine, J. Boik reports the importance
of platelet aggregation and eicosanoid issues in cancer. Thus he writes: "The
importance of platelet aggregation in cancer metastasis is more widely accepted....
Activated platelets are sticky and may enhance the adhesion of tumor cells
to the endothelial lining. Platelet-secreted factors... may stimulate the growth
of tumor cells and contribute to their survival within the blood circulation.
Experimental studies have shown that migrating cells from some cancers induce
platelet aggregation by modifying the eicosanoid balance.... Tumors promote
platelet aggregation by stimulating the production of PGI2.... Tumors synthesize
eicosanoids through both the [COX and LOX] pathways. The [LOX] pathway of [AA]
is important, if not essential, to tumor promotion." (23). Given the prior
discussion in this article of resveratrol as premier COX-inhibitor and Quercetin
as premier LOX-inhibitor, and both as excellent anti-platelet aggregators,
their combined potential anti-cancer benefit should be evident.
Garrison and Somer state that "Several studies report that vitamin E reduces
tumor growth and exerts an anti-cancer effect in both the initiation and promotion
stages because of its antioxidant and immuno-enhancing actions.... vitamin
E appears more effective in conjunction with other nutrients, such as selenium
and ascorbic acid, than by itself in the prevention of tumor growth." (22).
Some question has been raised over the oral absorbability of both resveratrol
and Quercetin, but recent results clearly demonstrate their absorption. Thus
Soleas et al comment that "...the difference in thrombin-induced platelet
aggregation between the commercial and resveratrol-enriched grape juices argues
in favor of the absorption of this compound in biologically active concentrations
by human subjects...." (10).
Hollman et al recently completed a study of Quercetin absorption in healthy
ileostomy patients with complete small intestines. They found a 100mg dose
of pure Quercetin to be absorbed approximately 24%. (24).
USES AND DOSES
A simple yet elegant and potent anti-heart attack/anti-cancer program may thus
be constructed from the 5 synergistic nutrients: resveratrol, Quercetin,
vitamin E, vitamin C and selenium. Recommended dosages: 1-10mg trans-RSV,
3 times daily. 100-500mg Quercetin, 4 times daily. 100-400 IU d-alpha tocopherol
or d-alpha tocopheryl succinate (vitamin E), once daily with a fat-containing
meal. 250-1000mg ascorbate (vitamin C), 4 times daily. 100mcg once daily,
or 50-100mcg twice daily, selenium as l-selenomethionine and/or sodium selenate.
Although pioneer resveratrol researcher D. Goldberg remarks that both cis and
trans-isomers of resveratrol appear to be biologically active, 5 most of
the studies mentioned in this article used either plant-extracted or synthetic
IAS offers the trans-Resveratrol as used in clinical studies.
Caution: Anyone who suffers from platelet deficiency or blood-clotting difficulties
should use this program only under medical supervision, if at all. Similarly,
anyone taking medical blood-thinning drugs (e.g. aspirin, coumadin) should
use this program only under medical supervision, if at all.
1. W. Martin (1984) "The combined role of atheroma, cholesterol,
platelets, the endothelium and fibrin in heart attacks and strokes" Med
Hypoth 15, 305-22.
2. S. Renaud, M. de Lorgeril (1992) "Wine, alcohol, platelets,
and the French paradox for coronary heart disease" Lancet 339, 1523-26.
3. D.M. Goldberg et al (1995) "Beyond alcohol: Beverage consumption
and cardiovascular mortality" Clin Chim Acta 237, 155-87.
4. J. South (1997) "Acetaldehyde: A common and potent neurotoxin" VRP
Nutr News 11, 1-2, 9-11.
5. D.M. Goldberg (1995) "Does wine work?" Clin Chem 41, 14-16.
6. M.G. Hertog et al (1993) "Dietary antioxidant flavonoids and
risk of coronary heart disease: the Zutphen Elderly study" Lancet
7. H. Arichi et al (1982) "Effects of stilbene components of the
roots of Polygonum cuspidatum... on lipid metabolism" Chem Pharm
Bull 30, 1766-70.
8. J.G. Hardman et al, eds. (1996) Goodman & Gilman's The Pharmalogical
Basis of Therapeutics NY: McGraw-Hill, 601-10.
9. Y. Kimura et al (1985) "Effects of stilbenes on arachidonate
metabolism in leukocytes" Biochim Biophys Acta 834, 275-78.
10. G.J. Soleas et al (1997) "Resveratrol: A molecule whose time
has come? and gone?" Clin Biochem 30, 91-113.
11. C.R. Pace-Asciak et al (1995) "The red wine phenolics trans-resveratrol
and quercetin block human platelet aggregation and eicosanoid synthesis:
Implications for protection against coronary heart disease" Clin
Chim Acta 235, 207-19.
12. G.J. Soleas et al (1997) "Wine as a biological fluid: History,
production and role in disease prevention" J Clin Lab Anal 11, 287-313.
13. J.H. Reinders et al (1986) "Cigarette smoke impairs endothelial
cell prostacyclin production" Arterioscler 6, 15-23.
14. D. Lonsdale (1986) "Free oxygen radicals and disease" in
1986: A Year in Nutritional Medicine, J. Bland, ed. New Canaan:Keats,
15. J. Kinsella et al (1993) "Possible mechanisms for the protective
role of antioxidants in wine and plant foods" Food Tech, April 85-89.
16. E.N. Frankel et al (1993) "Inhibition of human LDL oxidation
by resveratrol" Lancet 341, 1103-4.
17. B. Stavric (1994) "Quercetin in our diet: From potent mutagen
to probable anticarcinogen" Clin Biochem 27, 245-48.
18. S.A. Levine, P.M. Kidd (1986) Antioxidant Adaptation: Its Role in
Free Radical Pathology S.F.: Biocurrents Pub., 36-37, 164-167.
19. M. Jang et al (1997) "Cancer chemopreventive activity of resveratrol,
a natural product derived from grapes" Science 275, 218-220.
20. J. Hoffman et al (1988) "Enhancement of the antiproliferative
effect... by inhibitors of protein kinase C" Int J Cancer 42, 382-88.
21. G.S. Jayatilake et al (1993) "Kinase inhibitors from Polygonum
cuspidatum" J Nat Prod 56, 1805-10.
22. R.H. Garrison, E. Somer (1995) The Nutrition Desk Reference New
Canaan: Keats, 88-89.
23. J. Boik (1996). Cancer & Natural Medicine Princeton, MN: Oregon
Medical Press, 40-41, 48-49. 24. P.C. Hollman et al (1995) "Absorption
of dietary quercetin glycosides and quercetin in healthy ileostomy volunteers" Am
J Clin Nutr 62, 1276-82.
Resveratrol 60t 500mg SN1011 $NZ32.36
Resveratrol 30t 500mg SN1010 $NZ21.08
DISCLAIMER; ALL INFORMATION IS EDUCATIONAL AND SHOULD NOT REPLACE THE ADVICE
OF YOUR PHYSICIAN.