Grapes are rich in polyphenols with 60 to 70% of the polyphenols of grapes being in the seed. The active phenolic compounds in grape seeds are the flavonoids and polyphenols.
Grape seeds contain flavonoids (4.5%) including kaemferol-3-O- glucosides, quercitin-3-0-glucosides, quercitin and myriceitin (Nassiri-Asl and Hosseinzadeh, 2009).
Grapes are rich in polyphenols with 60 to 70% being found in the seed. The polyphenols are mainly flavan-3-ol derivatives which occur as their monomeric and polymeric forms (1 to > mers). The monomeric of flavan-3-ol derivatives are (+)-catechin, (-)-epicatechin, (-)-epicatechin-3-O-gallate, epigallocatechin and epigallocatechin-3-O-gallate (Figure 1). The monomers of flavanol-3-ol condense to form dimers, trimers, tetramers, pentamers and longer chain polymers. Collectively the polyphenols of grape seed extract are referred to oligomeric proanthocyanidins (OPCs) or alternatively as procyanidins proanthocyanidins, or condensed tannin. As indicated above, proanthocyanidins are essentially polymeric chains of flavanoids such as catechins and epicatechins. (Figure 2).
Figure 1. Structures of the major flavan-3-ols identified in grape seed extract. The large number of hydroxyl groups are responsible for their powerful antioxidant and free-radical savaging ability (from Shoji et al., 2006).
Figure 2. Structures of proanthocyanidin oligomers. The oligomeric proanthocyanidins are composed of flavan-3-ols units linked together from the C4 of one unit to either the C6 or C8 of the adjacent unit (from Shoji et al., 2006).
Total monomeric and polymeric amounts of OPCs
The total flavanol content of GSE has been reported to be 592 mg/g dry weight, including gallic acid (49 mg/g), catechin (41 mg/g), epicatechin (66 mg/g) and proanthocyanidins (437 mg catechin equivalents/g), (Wang et al., 2009). Wang et al. (2012) separated flavanols in GSE into catechin and epicatechins as monomers plus dimers, and into oligomers and polymers using HPLC analysis. The monomers plus dimers in their study was equal to 40% of the total proanthocyanidins.
Waterhouse (2002) reported that the proportion of flavanols, mostly as (+) – catechin and (-) – epicatechin, in the seed ranges from a low of less than 40% to a high of over 90%. Most GSE sold commercially contain 80% OPC’s. In typical red wines, the amount of polymer plus oligomer flavanols range from 25 to 50% for new wines and higher in older wines due to conversion of monomers into polymers.
The level of polymers in red wine are between 0.5 g/L and 1.5 g/L or even higher in red wines from Sardinia while in white wines, they range from 10 to 50 mg/L and are highly dependent on pressing techniques. The amount of total monomeric flavanols in typical red wine ranges from 40 to 120 mg/liter with the majority usually being catechin. The amount of the monomer flavanols vary from a low of 41 mg/kg seed for the variety Carigon to a high of 1,100 mg/kg seed for Pinot Noir.
Absorption and bioavailability of flavan-3-ol
In general most polyphenols are poorly absorbed compared with other nutrients. After absorption in the digestive tract, they are transported to the liver where they form glucuronide and/or sulfate or methyl conjugates, followed by transport to body tissues (Shoji et al., 2006 for citations).
Shoji et al. (2006) purified different proanthocyanidin (referred to us procyanidins) fractions from apples including monomers of catechin and epicatechin, 2-5 mers (dimers, trimers, tetramers and pentomers) and those larger than the hexamers (> 7 mer). They reported that procyanidins (1 to 5 mers) were absorbed from the upper portion of the digestive tract such as the small intestine but unlike some reports were not degraded into compounds with lower molecular weights by the colonic microorganisms.
The dimers, trimers, tetramers and pentomers isolated from the procyanidin were all absorbed with that of the dimers being about one-third of that of the other compounds. Also, the procyanidin in each dimer to pentomer group were not reduced to compounds with molecular weight lower than those of the native procyanidins including the free monomers. Although procyanidins with molecular sizes, equal to or greater than 8-mers were not absorbed themselves, they were able to considerably enhance the absorption of the 1-5 mer procyanidins.
They proposed that the procyanidins with a high molecular weight (≥8-mers) were bound to mucosal protein of the digestive tract, thereby allowing the larger procyanidin oligomer (>5 mers) to be absorbed rather than being bound themselves to the numerous intestinal proteins. In another study, Wang et al. (2012) separated the propanthocyanidins (procyanidins) from GSE into two fractions, monomers plus dimers (Mo), and oligomers and polymers (Po).
The primary circulating forms of the polyphenols from Mo were the glucuronide conjugates of catachin (C) and epicatechin (EC). They reported that only the Mo fraction accumulated in the brain and that only this fraction from GSE was effective in treatment of Alzheimers disease in a mouse model of the disease.
In summary, the results of several studies have demonstrated that the flavanol monomers plus the 2-5 mer oliomers are absorbed from the digestive tract and are found in the plasma. In contrast, the larger oligomers (≥ 8 mers) are not absorbed but greatly increase the absorption of the smaller polymers (< 5 mers). Only the monomers and possibly the dimers are able to cross the blood brain barrier and produce a beneficial effect.
What is the estimated daily intake of proanthocyanidins (PA or OPCs) in the USA diet (mainly wines, tea and daily legumes)?
The estimated intake of proanthocyanidins (PA) in the USA for adults over 19 years was estimated to be 95 mg/day, in order of polymers (30% or 29 mg/day), monomers (22% or 21 mg/day), dimers (16% or 15 mg/day), trimers (5% or 15 mg/day) and 4-6 mers (15% or 14 mg/day). The major food sources, (tea, legume and wines,) contributed 45 mg (48%) to the daily intake (Wang et al., 2011).
The Health Canada recommended intake of GSE (80% OPCs) is 400 mg/day which would be equal to a total daily supplemental intake of OPCs (PAs) of 320 mg/day (400 × 0.8). Supplemental GSE would, therefore, greatly increase the average daily intake of OPCs from 95 mg/day/person to 415 mg/day/person (95 + 320).
An alternative means of increasing the intake of PA would be to consume additional red wine. This can be achieved by consuming 0.6 liters of red wine per day containing 0.5 g/liter of PA or smaller amounts if the PA content of the wine was higher. This may not be practical as most people do not consume wine on a daily bases and information is not generally available on the PA content of most red wines. White wines would not greatly increase the total intake of PA as they have low concentrations of these compounds. The best solution to ensure an adequate intake of PA (OPCs) is to take All Natural Nutritional Products GSE supplement.