To our knowledge, this is the first study conducted to investigate the potential association between guaraná effect on LDL and serum oxidation. The results showed that guaraná ingestion (GI) resulted in lower maximum conjugated diene production than that found in an elderly NG group (Figure 1). Furthermore, in vitro assays showed that guaraná increased the lag phase in the oxidation of LDL and serum in vitro (Figures 2 and5), and also prevented TBARS production (Figure 3) and Trp destruction (Figure 4) in LDL oxidation. Moreover, we observed that guaraná extract demonstrates a peroxyl radical scavenger activity (Figure 6).
The effects of guaraná on LDL and serum oxidation are probably associated with some bioactive compounds (catechins and xantines) that are similar to those found in other foods, such as green tea. Tea polyphenols are well studied and there are numerous studies consistently describing these compounds as having antioxidative, antithrombogenic, antiinflammatory, hypotensive, hypocholesterolemic, antihypertensive, and antiobesogenic effects. The potential beneficial effects of daily guaraná consumption described by Krewer et al include a lower prevalence of hypertension, obesity, and metabolic syndrome, and lower cholesterol (total and LDL) and AOPP levels in GI subjects. These effects are similar to those described in epidemiological studies involving green tea. We believe that the results depicted here concerning the LDL oxidation could contribute in the elucidation of potential causal factors related to these associations.
First, it is important to consider the bioactive effects of guaraná related to the main chemical compounds. The antioxidant effects of guaraná extract might be due to methylxanthines, such as caffeine, theobromine, and theophylline, and also to tannins, saponins, catechins, epicatechins, proanthocyanidols, as well as trace concentrations of many other compounds. Effect of caffeine on LDL resistance to oxidative modification has been excluded by several in vitro and ex vivo studies. Indeed, we tested the TRAP activity of caffeine and theobromine and we observed no effect for these two compounds (data not shown). On the other hand, caffeine has been linked to increased thermogenesis and decreased body weight in some clinical studies. These effects of caffeine may contribute to prevent the other risk factors related to atherosclerotic vascular disease such as waist circumference and blood pressure.
It has been shown that guaraná inhibits the lipid peroxidation process, an effect apparently associated with the high tannin content of the seeds, which reach concentrations between 16% and 31%[22, 23]. Fresh tea leaf is unusually rich in the flavanol group of polyphenols known as catechins which may constitute up to 30% of the dry leaf weight and there is no tannic acid in tea. Tannins are polyphenolic compounds having molecular masses between 500 and 3000 Da and a sufficiently large number of phenolic groups. Yamaguti-Sasaki et al. identified some procyanidins (condensed tannins) as epicatechin-(4β → 8)-epicatechin (procyanidin B2), catechin-(4α → 8)-catechin (procyanidin B3), and catechin-(4α → 8)-epicatechin (procyanidin B4). It has been demonstrated that green tea catechins demonstrate antioxidant activity by scavenging free radicals and chelating redox active transition-metal ions. Catechins have many phenolic hydroxyl groups in their structures and have been shown to inhibit oxidative modification of LDL when added before initiation of oxidation. However, the mechanisms by which these flavonoids inhibit LDL oxidation have not been clarified. Because of their amphipathic nature, flavonoids may act within the LDL particle in a manner similar to that of vitamin E, or may act in a manner comparable with that of ascorbic acid in the extraparticle environment of LDL. Considering our in vivo results (Figure 1) and the significant correlation between the total polyphenols and the LDL levels in the GI group, we may suppose that polyphenols from guaraná could incorporate into LDL, turning the serum from GI subjects less susceptible to oxidation in vitro.
Guaraná’s effect on lipid peroxidation in vitro is in agreement with Mattei et al, who showed that guaraná extract inhibited lipoperoxidation even at low concentrations (1.2 μg/mL). Besides their in vitro effects, catechins demonstrate additional effects in vivo by inhibiting redox active transcriptional factors, inhibiting pro-oxidant enzymes, and inducing antioxidant enzymes, which could explain their beneficial effects in vivo. These effects make the potential use of guaraná extract even most promising to promote protection against atherogenesis.
In our in vivo study, the diene levels were significantly lower in GI than in NG subjects. It may indicate that guaraná intake is able to provide an additional antioxidant protection to serum and, mainly, to LDL. It was in agree with our in vitro data, which could increase the lag phase of serum and LDL oxidation, prevent TBARS production and tryptophan destruction (Figures 2,3,4 and5). However, the time required to achieve 50% CD production was not significant different. We believe that it was not significant because of the low number of subjects. In the actual in vivo condition, the polyphenols and methylxanthines in plasma may work together to prevent LDL oxidation. These polyphenols may be more easily incorporated into LDL in vivo than in vitro. Although guaraná polyphenols may be metabolized quickly after entering the circulation, it is possible that these metabolites also exert preventive effects on LDL oxidation. Repeated exposure of LDL particles to guaraná polyphenols over a long period of time may enrich the LDL particles sufficiently to make them less susceptible to oxidative stress.
It is important to ponder some considerations associated with the methodological design of our in vivo protocol. Since the in vivo study was performed using a group of elderly subjects, and without controlling for the amounts of guaraná ingested or the ingestion of other foods rich in antioxidants or bioactive compounds, it is important to conduct additional controlled studies on the possible effect of guaraná ingestion on LDL oxidation levels to confirm the results described here.