Br J Nutr. 1991 Mar;65(2):285-99. Links
A fraction derived from brewer's yeast inhibits cholesterol synthesis
by rat liver preparations in vitro.Holdsworth ES, Kaufman DV, Neville
E.
Biochemistry Department, University of Tasmania, Hobart, Australia.

Brewer's yeast was grown on a defined medium containing tracer 51Cr
with or without added chromium. The two batches of yeast contained 10
microgram/g (high-Cr) or 80 ng/g (low-Cr). Extracts were prepared and
fractionated. A third batch of yeast (third batch) was grown with
added Cr, and fractionated. Rats were reared on either rat cubes
(normal diet) or on a low-Cr diet (low-Cr), or on rat cubes with added
cholestyramine (cholestyramine diet). Preparations of rat liver, both
cell-free and intact hepatocytes, incorporated acetate-carbon into
fatty acids and cholesterol. These processes were inhibited by a yeast
fraction containing small, neutral, water-soluble compounds. The
degree of inhibition was the same whether the liver came from normal
rats or rats fed on the low-Cr diet. Similarly the inhibitory effect
was found with identical amounts of extracts from low- or high-Cr
yeasts. Therefore, Cr compounds do not appear to account for the
inhibitory effects of brewer's yeast. Use of other substrates
indicated that the site of inhibition of sterol synthesis was
apparently between acetyl-CoA and mevalonate. One inhibitory substance
was isolated from yeast and was found to be nicotinamide riboside.
This may have been produced from NAD(P) during the preparation of
yeast extracts, and it may be produced from dietary yeast supplements
during digestion in vivo. Nicotinamide riboside may be partly
responsible for the reported effects of yeast supplements on plasma
lipids in humans.

PMID: 2043605 [PubMed - indexed for MEDLINE]

PHARMACEUTICAL COMPOSITION CONTAINING POLYPHENOLS FROM GRAPES, IN
PARTICULAR RESVERA- TROL, AND YEAST EXTRACTS The present invention
refers to a new pharmaceutical composition containing polyphenols, in
particular 3,5,4'-trihydroxystilbene (resveratrol), combined with
yeast, i.e. saccharomyces cerevisiae, whereby the oral absorption of
polyphenols, in particular resveratrol, and the tissual activity of
the same, are surprisingly increased.

State of the Art.

The polyphenols contained in grapes and products thereof, and in
particular resveratrol, are regarded as mostly responsible for the
beneficial effects on a cardiovascular level and on health in general,
which, according to recent epidemiological investigations, may be
attributed to wine-drinks.

Several studies report that the moderate use of wine lowers the
incidence of cardiovascular diseases and the consequent mortality in
wine-drinking populations (Seigneur M.J., Appl. Cardiol., 5, 215,
1990; Renaud S., De Longeri M., Lancet, 341,1103, 1993).

Said beneficial effect is not produced by alcohol, but by other active
components present in wine, especially belonging to the class of
polyphenols.

Wine and grapes have been found to contain several polyphenols
exerting biological activity, e.g. the group of flavonoids, among
which catechins and oligomers thereof; flavonols and anthocyanidols,
proanthocyanidins, quercitins, as well as their polymers known as
tannins. Stilbene derivatives, such as resveratrol, are among non-
flavonoid poiypenols present in wine.

The polyphenols derived from grapes (vitis vinifera, vitis
rotundifolia, vitis labrusca) are characterized by the presence of
resveratrol in its various forms (cis and trans isomers of 3,5,4'-
trihydroxystilbene) and in the form of a glycoside, as well as of
anthocyanins, proanthocyanidins, catechins.

While most polyphenols are present in several parts of grapes,
resveratrol is especially present in the skin and, like the other
polyphenols, is transferred from grapes to wine.

Among the polyphenols derived from grapes and wine, resveratrol has
received most attention, due to its varied biological activities. This
stilbene, which belongs to the group of phytoalexins, is found in
grapes and wine in the form of the cis and trans isomers of
resveratrol and in the form of glucoside (cis and trans) which
exhibits the same biological activity as non-glucosate resveratrol.

Unlike other polyphenols that are found in several vegetables,
resveratrol is especially present in grapes or wine, which represents,
therefore, one of the most important sources of resveratrol supply for
human beings (Siemann E.H., Creasy L.L., Am. J. Enol. Vitic., 43-52,
1992).

Almost all polyphenols exert antioxidant activity, block the formation
of free radicals, which cause several pathologies, reduce oxidative
enzymes, and decrease the concentration of lipoperoxides in plasma
(Frankel E.N., Kanner Y., German G.B., Parks E., Kinsolle Y.E.,
Lancet, 341, 454, 1993) (Yuting C.Z., Rongliang Y., Free Radical Biol.
Med., 19, 19, 1990).

Said effects are especially produced by resveratrol (Frankel E.N.,
Waterhouse A.L., Kinsella Y.E., Lancet, 341, 1103, 1993b).

In any case, as reported in several studies, resveratrol is
characterized by several biological activities that may have a
beneficial effect on health, especially in the prevention of some
metabolic alterations or functional disorders, not only due to
oxidative processes.

In fact, evidence has been provided that it can develop an anti-
inflammatory and antilipaemic action (Kimura Y., Okuda H:, Arichi S.,
Biochem. Biophys. Acta, 834, 275, 1985) as well as a thrombocytic
antiaggregating action (Bertelli A.A.E., Giovannini L., Int. J. Tiss.
Reac., 17, 1, 1995) (Bertelli A.A.E., Giovannini L., Fibrinolysis, 10,
Suppl., 1, 1, 1996) (Pace-Ascia K.C.R., Chimica Clinica Acta, 235,
207, 1995).

Resveratrol also reduces vascular damages (Wang Yao-Zhong, Lue Su-
Fany, Acta Pharmacologica Sinica, 16, 159, 1995) and carcinogenic
processes (Yang M., Cai L., Udeani G.O., Slewug K.V., Thomas C.F.,
Beecher C.W., Fong H.S., Farusworth N.R., Kinghorn D.A., Mehta R.,
Moon R., Pezzuto Y.M., Science, 275, 218,1997).

Polyphenols, such as catechins, and anticyanoids exert a complementary
and synergic action; for example, the vascular dilatation action is
more evident when resveratrol is combined with catechins and
anthocyanins (Fitzpatrick D.F., Hirsfield S.L., Coffey R., Am. J.
Physiol., 265; Hearth, J. Physiol., 34, H774, 1993).

The vasculo-protective action is, among other actions, a specific
activity of anthocyanosides. In fact, vasal permeability and heart
activity are protected by anthocyanosides and, in particular, by
proanthocyanidins that are the most active of all polyphenols (Ricardo
da Silva Y.M., J. of Agric. Food Chemistry, 39, 549, 1991; Hagerman
A.E., Butler L.G., J. Biol. Chem., 256, 4494, 1981; Tayeau F., Nivet
R., Masqueller Y., Dumas M., Bull. Soc. Chim. Biol., 40, 671, 1958).

Anthocyanosides too, like other polyphenols and, in particular,
resveratrol, have shown anticancer activity in vitro (Kanei H., Kojima
T., Umeda T., Terabe K., Cancer Investigation, 13, 590, 1995), also
evidenced through the tumour growth markers (Chen G., Perchellet E.M.,
Gao X.M., Anticancer Res., 15, 1183, 1995).

As concerns yeasts, it is known that they promote the fermentation
causing the transformation of grapes must to wine. The best known
yeasts are leuconostoc mesenteroides, leuconostoc oenos kloetrera
apiculata, candida stellata, pediococcus pentosaceus, etc. (Martini
A.N., Wine Res., 4-165, 1993; Groves S., The Biochemist, 18-13,1996).

Among said yeasts, the most important and best known is saccharomyces
cerevisiae also because of its biological effects. It is rich in
proteins, enzymes and vitamins, especially of the vitamin B group,
which can be used by the organism for activating glycolytic processes
and producing energy bound to ATP formation.

In addition to the vitamin B complex, the yeast proteic fraction
includes several enzymes, which may be utilized in important
intestinal and organic metabolic activities (Rowland l.R., Drug Metab.
Rev., 19, 243, 1988).

In fact, the saccharomyces cerevisiae contains enzymes such as
sucrase, lactase, maltase and glucosidase (Harms H.K., Bertele-Hams
R.M., Brues-Kleis D., N.

Engl. J. Med., 316, 1306, 1987).

The enzymatic action of saccharomyces cerevisiae may be direct as well
as indirect, in that it activates the production of enzymes of
intestinal microflora (Rowland N., Nugon-Baudon L., Robot S.,
Intestinal Flora, Immunity, Nutrition and Health, World Rev. Nutr.
Diet., Symposium A.P., Corzing T., Rérat A., Eds., Basel, Karger 174,
123, 1933).

Given the interesting biological properties of polyphenols from grapes
and wine, it is important to find pharmaceutical compositions wherein
such properties are improved.

The present invention addresses to the problem of obtaining oral
pharmaceutical composition of polyphenols with improved biological
activity.

Summary Pharmaceutical composition consisting of a combination of
grapes and wine polyphenols, in particular resveratrol, with yeast,
i.e. saccharomyces cerevisiae, exhibiting an improved absorbability
when administered by the oral way and a synergic action for the
prevention and treatment of organic conditions connected with the
production of free radicals and with tissual anoxia, such as
senescence, cardiovascular disorders or intestinal biochemism
disorders.

Detailed description of the invention The Applicant has surprisingly
found that polyphenols, when administered in combination with
saccharomyces cerevisiae, has a higher bioavailability and a greater
biological effect. This was unexpectedly proved by the tests
conducted, which are at the basis of the claimed composition.

Polyphenols combined with yeast exert a noticeable synergic effect for
absorption and the metabolic and pharmacodynamic actions. The synergic
effect cannot be estimated simply by summing up the effects of the
single components of the combination. The absorption of polyphenols,
in particular of resveratrol, is consideably and unexpectedly favoured
when said products are used in combination with the yeast
saccharomyces cerevisiae. This is an excellent result considering that
polyphenols, in particular resveratrol, when administered per os, are
scarcely absorbed by the intestine (Bertelli A.A.S., Giovannini L.,
Stradi R., Bertelli A., Tillement J.P., Int. J. Tiss. Reac., 18, 67,
1996).

Out of the several polyphenols, the new composition particularly
contains the polyphenols that are present in grapes (vitis vinifera)
and products thereof, e.g. wine, and more particularly the
biologically most active polyphenols, e.g. anthocyanins, catechins, a
phytoalexin such as resveratrol, and yeast.

The yeast is one of the yeasts involved in the various steps of the
fermentation processes for the transformation of grapes into wine; in
particular it is saccharomyces cerevisiae, preferably deprived of
bitter substances, in the living and freeze-dried form and in the
dried form.

Therefore, the new pharmaceutical compositions consist of an extract
in the powdery or granular or other forms, obtained by drying or by
other treatments of grapes or of the residue remaining after pressing
of grapes (pomace) or of other wine components, among which wine
itself or grape skins or seeds, whereto a dry powder or an extract of
yeast, in particular saccharomyces cerevisiae, is combined.

In alternative the compositions according to the invention may
comprise a combination of yeast with one or more polyphenols, e.g.
resveratrol, wich have been previously isolated from grapes or wine.

The compositions may further contain vitamins, mineral salts and
pharmaceutically acceptable excipients.

Preferably the pharmaceutical compositions have a polyphenols/yeast
estract ratio ranging from 1:1 to 1:10,000.

The compositions may be solid, semisolid or liquid, and may be used
for treating all pathologies responsive to polyphenol therapy.
Examples of these conditions are tissue anoxia, cardiovascular
disorders, intestinal biochemism disorders, senescence, free radical
damages.

It is a further feature of the present invention the use of a
combination of polyphenols of grapes and wine, in particular
resveratrol, with yeasts, for the manufacture of a medicament having
improved polyphenol absorption.

The present invention is further illustrated by the following non
limiting examples.

Experimental part 1. Product characterization The composition
according to the present invention was characterized by analysis of
the total polyphenols present therein, according to the method
developed by Folin-Ciocalteu, modified by Teissedre (Teissedre P.L.,
Bull. O.I.V., 781-251, 1996). Characterization of 3,5,4'-
trihydroxystilbene (resveratrol) was carried out by HPLC-MS according
to the method of Lamuela-Raventos (Lamuela-Raventos R.M., J. Agric.
Food Chem., 43-283, 1995).

The other polyphenols were identified by HPLC via colourimetric
electrode (Achilli G., J. Chromatography, 632-111, 1993).

2. Toxicology and pharmacology The low toxicity and good tolerability
of polyphenols, in particular resveratrol, as well as yeasts, e.g.
saccharomyces cerevisiae, are well known.

In the tests conducted to estimate the LD, of said products, the mouse
and the rat were administered a mixture of polyphenols or resveratrol
alone or dry yeast or a combination of said substances.

The mixture of polyphenols, without resveratrol, was characterized by
the presence of catechin (100 mg), epicatechin (25 mg), gallic acid
(85 mg), quercitin (12 mg), caffeic acid (25 mg), rutin (20 mg) in a
proportion analogous to that present in freeze-dried dealcoholized red
wine (Teissedre P.L. and Watherhouse A.L., Bull. O. I. V., 781,
1996).

The resveratrol used was available from Sigma Chemical Co. (St. Louis,
MO).

In these tests, no death or toxic effect were ascertained in the
treated animals even after administration of 0.5 g/kg polyphenols or
0.25 g/Kg resveratrol or 5 g/kg dry yeast.

Furthermore, no toxic effect was produced by the mixture of the three
components administered at the abovesaid doses.

Chronic toxicity tests conducted on the rat administered the
pharmaceutical composition, containing a mixture of 0.20 g/kg
polyphenols, 0.1 g/kg resveratrol, and 1 g/kg dry yeast or twice said
doses, did not show any sign of toxicity or intolerance in respect of
body growth or of various hemochromocytometric or hematochemical
parameters.

3. Absorbability of resveratrol administered per os Tests were
conducted on the absorbability of resveratrol, administered per os
either alone or in combination with a mixture of polyphenols or with
the dry yeast saccharomyces cerevisiae.

The tested animals were male Wistar rats averagely weighing 300 g
each.

Products administration was performed per os by gastric probing.

Resveratrol concentrations were determined in the plasma of rats at
different times from administration, with HPLC-UV-Vis HPLC-MS
apparatus with sensitivity limits of 1 ng/ml, according to the methods
described by Bertelli et al. (Bertelli A.A.E., Giovannini L., Stradi
R., Bertelli A., Tillement J.P., Int. J. Tissue Reac. XVII (2/3),
67-71,1996).

In the various tests, resveratrol was administered either alone at
doses of 200 and 400 ,ug/kg or in combination with 10 mg/Kg of a
mixture of polyphenols or in combination with yeast (1-2 g/kg).

Resveratrol concentrations in plasma were determined k h, 1 h, and 2 h
after products administration (Table 1).

It was found that the administration of resveratrol in combination
with yeast resulted in a considerably higher concentration in plasma
in comparison with that obtained with resveratrol alone. In fact, as
shown in Table 1, the average resveratrol concentration in plasma 1 h
after administration was 26 ng/ml, whereas its concentration was
almost doubled when it was administred in combination with yeast (40
ng/ml).

The increased concentration induced by yeast was apparent also k h
after administration and said concentration levels did not decrease
with elapsed time. In fact, the values observed half an hour after
administration of resveratrol alone equalled 25 ng/ml, of resveratrol
combined with yeast equalled 40 ng/ml. After 1 h, the values were of
35 nglml and, respectively, 59 ng/ml.

Therefore, the results obtained show that yeast increases resveratrol
absorption.

Said increase is also evident when yeast is combined with dehydrated
and dried grapes powder containing resveratrol and with a dry
dealcoholized concentrated red wine extract, containing a known
quantity of resveratrol.

As shown in Table 2 for resveratrol contained in dehydrated and dried
grapes powder the average concentration in plasma 1 h after
administration was 8 ng/ml, whereas its concentration was almost
doubled when it was administred in combination with yeast (14 ng/ml).

The same results were obtained with the dry dealcoholized concentrated
red wine estract containing resveratrol, which average concentration
in plasma 1 h after administration was respectively 18 ng/ml and 30 ng/
ml when it was administered alone or in combination with saccharomyces
cerevisiae.

Analogous tests on the effect of saccharomyces cerevisiae on
resveratrol absorption were conducted using catechin as a polyphenol
component, present in appreciable concentrations in grapes and wine.

Said tests were performed on chickens fed with a diet deprived of
catechin, according to Teissedre P.L. et al. (Bulletin de l'O.I.V.,
781, 1996); catechin was then dosed according to the method developed
by Jaworski A.W. et al. (J. Agric.

Food Chem., 35, 257, 1987) and modified by Lamuela Raventos et al.
(Am. J.

Enol. Vitic., 45, 1,1994).

Chickens were administered 400 mg/kg catechin alone or in combination
with 2 g/kg yeast, saccharomyces cerevisiae, every day for 10
consecutive days. The catechin plasma levels obtained with catechins
combined with saccharomyces cerevisiae were approx. twice those
obtained in the absence of yeast (2.58+0.34 nmol/l in animals treated
with catechin alone and 4.48+4.2 nmol/l in animals treated with
catechin plus yeast). Evidence is thus provided that saccharomyces
cerevisiae can increase the absorption of polyphenol catechin.

Table I - Resveratrol average concentrations in the blood of the rat
(10 rats per group) after oral administration of resveratrol alone
(200 µg/kg and 400 µg/kg) or in combination with a mixture of
polyphenols (10 mg/kg) or in combination with yeast, saccharomyces
cerevisiae (1 g/kg and 2 g/kg) Treatment Dose ng/ml plasma 30 60 120
minutes after administration Resveratrol 200 µg/kg 18#02 26#2.1 12#0.9
Resveratrol 400 µg/kg 25#1.8 35#2.9 15#1.1 Polyphenols + 10 mg/kg
Resveratrol 200 µg/kg 20#1.5 28#2.5 15#1.7 Polyphenols + 10 mg/kg
Resveratrol 400 µg/kg 27#2.2 37#3.2 18#1.9 Yeast + 1 g/kg Resveratrol
200 µg/kg 22#2.8 33#2.7 17#0.6 Yeast + 2 g/kg Resveratrol 200 µg/kg
30#2.1 40#3.3 24#1.9 Yeast + 1 g/kg Resveratrol 400 µg/kg 36#2.9
50#5.5 30#3.1 Yeast + 2g/kg Resveratrol 400 µg/kg 40#4.1 59#6.7 34#2.9
Table 2 - Resveratrol average concentrations in the blood of the rat
(10 rats per group) after oral administration of dehydrated and freeze-
dried grapes (pomace) powder or of dry dealcoholized concentrated wine
extract containing resveratrol, alone or in combination with
saccharomyces cerevisiae (2 glkg) Treatment Dose ng/ml plasma 30 60
120 minutes after administration Dehydrated and 2 g/kg 5+0.2 8+0.5
4+0.2 freeze-dried grapes powder (resveratrol concentration = 150 mg/
100 g) Dry dealcoholized 2 g/kg 9+1.1 18f1.9 6+0.3 concentrated wine
extract (resveratrol concentration = 500 mg/100 g) Dehydrated and 2 g/
Kg freeze-dried grapes powder (resveratrol concentration = 150 mg/100
g) + Yeast 2 g/Kg 8+0m9 14+lem6 6+0.8 Dry dealcoholized 2 g/Kg
concentrated wine extact (resveratrol concentration = 500 mg/100 g) +
Yeast 2 g/Kg 12i1.2 30+2.2 9+1.1 4. Pharmacological activity Rats were
injected intravenous I unitlkg pitressin spontaneously to induce
myocardial anoxia.

The coronaric spasm resulted in a decreased myocardial oxygenation,
while the electrocardiogram showed a typical asphyxial T curve.

In these tests, male Wistar rats averagely weighing 300 g each, before
being injected pitressin, were administered resveratrol alone, or
resveratrol in combination with the mixture of polyphenols or in
combination with yeast, or the combination of the three groups of
products. Said products were administered every day for seven
consecutive days before pitressin injection. The doses administered
were as follows: 100 pg/kg resveratrol, 100 mg/kg polyphenols, and 1 g/
kg yeast. The combination consisted of 100 pg/kg resveratrol with 100
mg/kg polyphenols or with 1 g/kg yeast or of resveratrol with
polyphenols and yeast at the doses indicated above.

The same tests were also carried out after administration, for seven
consecutive days, of dehydrated and freeze-dried grapes powder with
resveratrol concentration of 150 all9/100 g or of a dry dealcoholized
concentrated wine extract with resveratrol concentration of 500 Clg/
l00 g.

Tests were conducted by administering said products alone or combined
with 2 glkg yeast.

The pitressin injected caused the appearance of the asphyxial T wave
in the group of animals treated with polyphenols and with yeast; its
appearance was reduced by 30% in animals treated with resveratrol, by
40% in animals treated with resveratrol and polyphenols, and by 80% in
animals treated with resveratrol and yeast.

The appearance of the asphyxial T wave was completely hindered in
animals treated with resveratrol combined with polyphenols and yeast.

Therefore, said tests suggest that yeast potentiates the antianoxic
properties of resveratrol.

Analogous positive results were obtained from tests carried out with
dehydrated and freeze-dried grapes powder and dry dealcoholized
concentrated wine extract.

In these tests too, the appearance of the asphyxial T wave was reduced
by more than 50% in respect of controls.

It is a further feature of the present invention the use of a
combination of polyphenols or of grapes and wine, in particular
resveratrol, with yeasts, for the manufacture of a medicament having
improved polyphenol absorption.

Preferably the pharmaceutical compositions have a polyphenols/yeast
estract ratio ranging from 1:1 to 1:10,000.

The compositions may be solid, semisolid or liquid, and may be used
for treating all pathologies responsive to polyphenol therapy.
Examples of these conditions are tissue anoxia, cardiovascular
disorders, intestinal biochemism disorders, senescence, free radical
damages.

5. Preparation of pharmaceutical compositions The various compositions
forming the object of the present invention were prepared by different
routes depending on the formulation considered. The concentrated wine
extract was generally obtained as follows: wine was dealcoholized by
distillation and concentrated in a rotary evaporator under vacuum at a
temperature of 20 to 30"C. Final drying was carried out in an air
stream at a temperature of 30 to 41"C.

Grape-seed powder was prepared once seeds had been separated from
pomace by sieving. Grape-seeds were washed with water, dried at room
temperature, subjected to oil extraction by pressure or with solvents
(hexane), and finely ground to obtain a brownish-grey dry powder.

The grape skins or pomace powder was prepared by drying the starting
product in a hot air stream (30 to 40"C). The resulting product was
then ground and triturated to a brownish-red powder, which may be used
as is or in the freeze-dried form.

For the preparation of tablets resveratrol was mixed with
saccharomyces cerevisiae, and the powder of grapes or of seeds or the
dry dealcoholized wine extract was mixed with the same yeast
(saccharomyces cerevisiae), in appropriate proportions after addition
of microcristalline cellulose, in a suitable powder mixer.

The powder was homogenized by causing it to pass through an
appropriate stainless steel screen. An additional quantity of
micronized cellulose, and magnesium stearate were added; the resulting
powder was mixed until obtaining a homogeneous dispersion. The powder
was compressed using a tablet machine provided with flat or hollow
stainless steel punches. Convex tablets could be filmed with
gastrosoluble polymers.

For the preparation of capsules resveratrol was mixed in a suitable
powder mixer with saccharomyces cerevisiae and with the powder of
grapes or of seeds or the dry dealcoholized wine extract, in
appropriate proportions, added with powdery lactose, talc and
magnesium. Once the blend had become homogeneous, it was filled into
hard gelatine capsules.

Some examples, given to provide an illustration, without any limiting
effect, of the present pharmaceutical compositions formulated
according to the traditional pharmaceutical technique, wherein the
polyphenols derived from grapes or wine may be standardized by the
present concentrations of resveratrol, anthocyanins and
proanthocyanidins, catechins or other polyphenolic components, are as
follows: Grapes or wine polyphenols 100 mg 1 Resveratrol 0.5 mg Yeast
(saccharomyces cerevisiae) 100 mg Grapes or wine polyphenols 300 mg 2
Resveratrol 5 mg Yeast (saccharomyces cerevisiae) 300 mg Dehydrated
and freeze-dried grapes powder 400 mg 3 Polyphenols 100 mg Resveratrol
1 mg Yeast (saccharomyces cerevisiae) 100 mg Dry dealcoholized
concentrated wine extract 250 mg 4 Polyphenols 50 mg Proanthocyanidins
20 mg Anthocyanosides 10 mg Resveratrol 1 mg Yeast (saccharomyces
cerevisiae) 200 mg Polyphenolic wine extract 300 mg 5 Resveratrol 0.3
mg Anthocyanidins 10 Yeast (saccharomyces cerevisiae) 400 mg
Dehydrated and dried grapes powder 200 mg 6 Polyphenols 100 mg
Resveratrol 0.25 ll9 Catch ins 2.5 mg Epicatechins 2.5 mg Yeast
(saccharomyces cerevisiae) 200 mg Grapes seeds powder 100 mg 7
Resveratrol 0.1 mg Proanthocyanidins 20 mg Yeast (saccharomyces
cerevisiae) 300 mg Grapes seeds oil 100 mg 8 Resveratrol 0.1 mg
Proanthocyanidins 20 mg Yeast (saccharomyces cerevisiae) 300 mg Grapes
or wine polyphenols 100 mg 9 Resveratrol 1 mg Yeast (saccharomyces
cerevisiae) 200 mg Vit. B, 1 mg Vit. B2 1 mg Vit. Be 3 mg Pantothenic
acid 3 mg Vit. E 2 mg p-carotene 6 mg Selenium 1 mg Copper 1 mg Zinc 3
mg Mgnesium 5 mg

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