A clinical study published in 2007 involving 40 human subjects suggests one possible explanation for the curious contradiction of lab and animal study success with some antioxidants and poor bioavailability. While the data confirmed that resveratrol levels which demonstrated inhibitory effects on cancer cells in the lab were never attained in the participants of the 2007 human trial, the study uncovered evidence that three resveratrol metabolites reached close to or greater than that level. The researchers in this trial speculated that resveratrol metabolites could be the actual source of resveratrol’s chemopreventive activity, similar to other metabolite compounds derived from beneficial flavonoids. In other words, while the parent molecule of resveratrol is necessary to produce its metabolites, it is the metabolites that are actually bioavailable in concentrations that may help prevent cancer.151

In support of this theory, a lab study combining two derivatives of resveratrol (TMS and MR-4) yielded a hybrid molecule (PMS) that not only demonstrated greater inhibition of colon cancer cell reproduction, but also induced significant tumor cell death.159 More recently, animal studies showed that a form of resveratrol called hexahydroxystilbene (M8), by itself and in combination with a conventional chemotherapy drug for melanoma, significantly inhibited this particularly aggressive skin cancer.57

Two later clinical trials were conducted after the one published in 2007—one involving 40 healthy volunteers and a second 20 people with colorectal cancer. The healthy participants received doses of 0.5-5.0 g/day of resveratrol for 29 days while the cancer patients took 0.5-1.0 g/day for 8 days prior to surgical removal of tumors. While blood tests indicated that resveratrol systemic levels was still lower than necessary levels demonstrated in the lab for predicted anti-tumor activity, the levels of resveratrol’s primary metabolite were significantly higher. Moreover, blood tests indicated that inflammatory pro-tumor markers were significantly reduced in both the healthy volunteers (8%) and the cancer patients (33%). The cancer patients also showed 5.5% reductions in tumor cell proliferation. Only the volunteers who received the 2.5 g/day dosage had any significant adverse increases in markers indicative of oxidative damage.32

Other researchers have focused on improving bioavailability of phytochemical antioxidants by replicating a mechanism typically used for conventional chemotherapy agents. Encapsulating it in tiny, fat-like particles called liposomes could increase absorption of resveratrol as they do for other fat-soluble substances.160

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Greater than 5 mol/L.
Specifically, two resveratrol monoglucuronides and resveratrol 3-sulfate.
Specifically, 2,3',4,5'-tetramethoxy-trans-stilbene (TMS) and 3,4,4',5,-tetramethoxy-trans-stilbene (MR-4).
Specifically, dacarbacine.
Chemical compounds that occur naturally in plants and offer a variety
of health benefits to humans and animals.

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