Sulforaphane slows down phase I detoxification and speeds up phase II detoxification.
"And so sulforaphane slows down phase one and then speeds up phase two so you don't get that detox flu" (said at 0:22:36)
Preclinical cell and animal studies support the premise that sulforaphane can inhibit certain Phase I cytochrome P450 enzymes (such as CYP3A4 and CYP2E1) and induce Phase II detoxification enzymes (such as glutathione S-transferases and NQO1 via the Nrf2 pathway). However, this effect is isozyme-specific rather than a universal suppression of all Phase I enzymes, and some models demonstrate induction of specific CYPs such as CYP1A1. Furthermore, there is no clinical evidence linking this enzymatic modulation to the prevention of 'detox flu', a colloquial naturopathic concept with no established medical definition.
- supports: Cruciferous vegetables: cancer protective mechanisms of glucosinolate hydrolysis products … (Integrative cancer therapies 2004) · cited 314x in the literature
"These mechanisms include altered estrogen metabolism, protection against reactive oxygen species, altered detoxification by induction of phase II enzymes, decreased carcinogen activation by inhibition of phase I enzymes, and slowed tumor growth and induction of apoptosis." (abstract, passage verified)
pubmedfull study (doi) - context: Sulforaphane induces CYP1A1 mRNA, protein, and catalytic activity levels via an AhR-depend… (Cancer letters 2009) · cited 63x in the literature
"This is the first demonstration that the broccoli-derived SUL can directly induce Cyp1a1 gene expression in an AhR-dependent manner and represents a novel mechanism by which SUL induces this enzyme." (abstract, results, passage verified)
pubmedfull study (doi) - supports: Inhibition of cytochromes P-450 and induction of glutathione S-transferases by sulforaphan… (Cancer research 1997) · cited 231x in the literature
"In SF-treated human hepatocytes, hGSTA1/2 but not hGSTM1 mRNAs were induced, and the expression of CYP1A2 was unaffected, whereas the expression of CYP3A4, the major CYP in human liver, was markedly decreased at both mRNA and activity levels. These observations demonstrate that in intact human and rat hepatocytes, SF may both induce a number of GSTs and cause enzyme inhibition of some but not all CYPs and, in the case of CYP3A4, inhibit both its enzyme activity and its expression." (abstract, results, passage verified)
pubmed
Glucuronidated curcumin is completely biologically inactive.
"everybody's competing for the amount of um glucuronidated curcumin because it's completely inactive." (said at 1:14:05)
In direct cellular and molecular assays, glucuronidated curcumin is widely documented to lack the primary antiproliferative, anti-inflammatory, and signaling-inhibition activities seen with free (aglycone) curcumin. However, stating that it is 'completely inactive' requires context: while intrinsically inactive or markedly attenuated at target cellular receptors, curcumin glucuronide serves in vivo as a transport form or prodrug that can undergo deglucuronidation by tissue beta-glucuronidases (e.g., in bone marrow, inflamed sites, or tumor microenvironments) to regenerate active free curcumin.
- supports: Curcumin glucuronides: assessing the proliferative activity against human cell lines. (Bioorganic & medicinal chemistry 2014) · cited 75x in the literature
"Biological data revealed that as much as 1 μM curcumin 1 exhibited anticancer activity and almost 100% cell kill was noted at 10 μM on two out of four cell lines; while curcumin mono-glucuronide 2 as well as di-glucuronide 3 displayed no suppression of cell proliferation." (abstract, results, passage verified)
pubmedfull study (doi) - context: Curcumin β-D-Glucuronide Plays an Important Role to Keep High Levels of Free-Form Curcumin… (Biological & pharmaceutical bulletin 2017) · cited 51x in the literature
"The in vivo antitumor effects of CMG following intravenous injection were then evaluated in tumor-bearing mice with the HCT116 human colon cancer cell line. The tumor volume within the CMG group was significantly less than that of the control group." (abstract, results, passage verified)
pubmedfull study (doi) - supports: Curcumin, but not curcumin-glucuronide, inhibits Smad signaling in TGFβ-dependent bone met… (The Journal of nutritional biochemistry 2019) · cited 54x in the literature
"While curcumin inhibited TGFβ-receptor-mediated Smad2/3 phosphorylation in all BCa cells studied (human MDA-SA, MDA-1833, MDA-2287 and murine 4T1 cells), curcumin-glucuronide did not. Similarly, curcumin, but not curcumin-glucuronide, blocked TGFβ-stimulated secretion of PTHrP from MDA-SA and 4T1 cells. Because the predominant serum metabolite, curcumin-glucuronide, lacked bioactivity, we examined tissue-specific metabolism of curcumin in mice." (abstract, results, passage verified)
pubmedfull study (doi) - supports: Beta-Glucuronidase Catalyzes Deconjugation and Activation of Curcumin-Glucuronide in Bone. (Journal of natural products 2019) · cited 46x in the literature
"Consistent with this postulate, aglycone, but not glucuronidated, curcumin inhibited RANKL-stimulated osteoclastogenesis, a key curcumin target in bone." (abstract, results, passage verified)
pubmedfull study (doi)