Introduction
The bad effects of alcohol have been known for decades, but from the late 1980 some paradoxes have been observed in Tuscany (known as the “Chianti Paradox”) and in France, where the more famous “French Paradox” shocked the scientific community in 1991. This term describe the relatively low incidence of cardiovascular diseases in the French population, despite a relatively high dietary intake of saturated fats, and potentially attributable to the consumption of red wine. (vino e salute)
Recent epidemiological studies show that coronary heart disease mortality is lower in the Mediterranean area than in other developed countries, even than in northern Europe. This is mainly due to the fact that wine is a component of the Mediterranean diet and suggest that moderate wine, especially red wine, consumption may produce additional beneficial effects on cardiovascular morbidity and mortality. The cardiovascular protective effects of wine may be attributed to polyphenols, which are abundant in wine, in particular in red wine, and possess antioxidant and superoxide ion scavenging properties.(Bonum vinum laetificat cor hominum. 2001)
Flavonoids
In red wine, up to 90% of the phenolic content falls under the classification of flavonoids. The terms flavonoid and bioflavonoid have been more loosely used to describe non-ketone polyhydroxy polyphenol compounds. The three cycle or heterocycles in the flavonoid backbone are generally called ring A, B and C. (Flavonoid) The benzene ring A is condensed with a six-member ring (C-ring), which in the 2-position carries a phenyl benzene ring (B-ring) as a substituent. Ring C may be a heterocyclic pyran, which yields anthocyanins (Figure 1c), or 4-oxo-pyrone, which yields flavones (Figure 1d), flavonols (Figure 1e), flavanones (Figure 1f) and isoflavones (Figure 1g).
These phenols, mainly derived from the stems, seeds and skins, are often leached out of the grape during the maceration period of winemaking. These compounds contribute to the astringency, color and mouthfeel of the wine. In white wines the number of flavonoids is reduced due to the lesser contact with the skins that they receive during winemaking. There are on-going studies into the health benefits of wine derived from the antioxidant and chemopreventive properties of flavonoids. (Phenolic content in wine)
Polyphenols from red wine can, indeed, prevent oxidation of low density lipoproteins (LDL). (Bonum vinum laetificat cor hominum.2001)
Ox-LDL have an essential role in atherosclerosis because they have many biological properties that start the inflammatory response. These ox-LDL are no more recognized by LDL-R but they bind scavenger receptors, which are not setted by negative feedback, and cause the store of ester cholesterol leading to the transformation of macrophage in foam cells, tipical of atherosclerotic lesion. Furthermore ox-LDL induce the expression of transcriptional factors that begin the inflammatory response.(Atherosclerosis)
The ability of flavonoids to act as antioxidants depends on their molecular structure. The position of hydroxyl groups and other features in their chemical structure. The presence of a 3′,4′-ortho-dihydroxyl on B-ring, a 3-hydroxyl on C-ring and a 2,3-double bond of C-ring appeared to be the main structural requirements for the antioxidant activity, while a 5,7-meta-dihydroxyl on A-ring was correlated to the anti-inflammatory capacity of 4-oxo-flavonoids. (Chemical Structures of 4-Oxo-Flavonoids in Relation to Inhibition of Oxidized Low-Density Lipoprotein (LDL)-Induced Vascular Endothelial Dysfunction.)
Study on apoE deficient mice
In an important trial to find out the effect of red wine consumption on atherosclerosis, researchers used the apo E deficient (E(0)) mice. In these mice, red wine consumption for two months resulted in a 40% decrement in basal LDL oxidation, a similar decrement in LDL oxidizability and aggregation, a 35% reduction in lesion size, and a marked attenuation in the number and morphology of lesion's macrophage foam cells. (Wine flavonoids protect against LDL oxidation and atherosclerosis. 2002)
This trial clearly shows a strict relation between wine consumption and the progression of atherosclerosis.
Flavonoid intake and cardiovascular disease mortality in a prospective cohort of US adults
Researchers examined the association between flavonoid intake and cardiovascular diseases mortality among participants in a large, prospective US cohort.
During 7 years of follow-up, 1589 cardiovascular diseases deaths in men and 1182 cardiovascular diseases deaths in women occurred. Men and women with total flavonoid intakes in the top (compared with the bottom) quintile had a lower risk of fatal cardiovascular disease.
In conclusion this shows that flavonoid consumption was associated with lower risk of death from cardiovascular disease, and an inverse association was also observed with intermediate intakes suggesting that even small amount of flavonoid-rich foods may be beneficial. The mechanism for a cardioprotective role of flavonoids likely involves more than one pathway, including antioxidant and antiinflammatory functions and vascular effects. (Cohort study,2012)
Since atherosclerosis is a multifactorial disease and develops through several steps, flavonoids have a wide range of action and have multiple functions:
- Inhibit oxidation of LDL
- Antioxidative effects
- Direct scavenging of free radicals
- Inhibition of xanthine oxidase
- Chelating trace elements involved in free radical production
- Decrease in the number of immobilized leukocytes
- Increase NO bioavailability
- Increase HDL-cholesterol
- Decrease platelet aggregation
- Biological effects
- Inhibit the transcription factors NFkB and AP-1
- decrease pro-inflammatory mediators (TNF-a, IL, PGE2) and activities of proinflammatory enzymes (COX 2, iNOS)
Many cardiovascular risk factors contribute to oxidative stress.
Flavonoids, such as those occurring in wine, are an example of a class of bioactive and antioxidant compounds that may confer beneficial effects on a number of important risk factors for cardiovascular disease. Nevertheless, protective antioxidant mechanisms are complex and multifactorial.
(Flavonoids: Antioxidants Against Atherosclerosis, 2010)
Conclusion
Cardiovascular diseases are now a current major problem in causing mortality in both Western and developing countries. Oxidative stress associated with atherosclerosis and endothelium-dependent vascular inflammation plays a major role in the development of cardiovascular disease. Red wine contains antioxidative components, like flavonoids, that exert protective functions like free radical scavenging effects, decreasing the oxidative stress and reducing the inflammatory atherosclerotic lesion in both animals and humans. From these findings, it has been concluded that red wine as a diet supplement might be beneficial for cardiovascular risk factors. This raises the possibility that flavonoids may act as a lead compound for the development of therapeutic agents, which can be used in atherosclerosis prevention and therapy.
Bibliografy
vino e salute
Flavonoid, wiki
Phenolic content in wine, wiki
Atherosclerosis, wiki
bonum vinum laetificat cor hominum, 2001
wine flavonoids protect against LDL oxidation and atherosclerosis, 2002
Moderate red wine consumption and cardiovascular disease risk: beyond the French paradox, 2010
Flavonoids: Antioxidants Against Atherosclerosis, 2010
Chemical Structures of 4-Oxo-Flavonoids in Relation to Inhibition of Oxidized Low-Density Lipoprotein (LDL)-Induced Vascular Endothelial Dysfunction, 2011
Cohort study, 2012
