There's something really fantastic about plant-derived nootropics. I'm a big fan of bacopa, lion's mane and the like.
Sure, they're less exciting than some obscure injectable Russian peptide. But they also have much less downside risk.
Sulforaphane is found in broccoli, brussels sprouts and other cruciferous vegetables and has robust neuroprotective and anti-oxidative effects.
The best results are probably obtained from ingesting sulphoraphane-rich foods rather than the isolated compound.
Many nootropic foods contain a blend of hundreds of compounds which enhances bioavailability and packs more of a punch than an isolated compound.
Case in point: PEITC is a compound also found in cruciferous vegetables and is thought to also have synergistic anti-inflammatory effects with sulforaphane[^25].
|Food (raw)||Serving||Total Glucosinolates (mg)|
|Brussels sprouts||½ cup (44 g)||
|Garden cress||½ cup (25 g)||
|Mustard greens||½ cup, chopped (28 g)||
|Turnip||½ cup, cubes (65 g)||
|Cabbage, savoy||½ cup, chopped (45 g)||
|Kale||1 cup, chopped (67 g)||
|Watercress||1 cup, chopped (34 g)||
|Kohlrabi||½ cup, chopped (67 g)||
|Cabbage, red||½ cup, chopped (45 g)||
|Broccoli||½ cup, chopped (44 g)||
|Horseradish||1 tablespoon (15 g)||
|Cauliflower||½ cup, chopped (50 g)||
|Bok choy (pak choi)||½ cup, chopped (35 g)||
Sulforaphane is a naturally-occurring compound belonging to the isothiocyanate group of organosulfur compounds.
It is present in relatively large quantities within cruciferous vegetables, such as broccoli. Brussels sprouts deliver 2x as much Glucosinolate (the precursor to sulphoraphane) than any other source.
Sulforaphane positively modulates cellular events and has a net-beneficial effect on bodily function. This article explores the effects of sulforaphane from food and supplementation has on the body.
In cruciferous vegetables, sulforaphane is found in the form of a prodrug known as glucoraphanin, where it is bound to a sugar moiety[^1].
When you chew a cruciferous vegetable, glucoraphanin is converted by Myrosinase into sulforaphane by cleaving the sugar group. Myrosinase is an enzyme present in the broccoli family of plants[^1].
In broccoli, sulforaphane is found in the following quantities:
What's the ideal dosage of sulforaphane? Unfortunately, it's not well established, though we can hazard an educated guess.
Studies in animal models have shown supplementation of 0.1-0.5mg/kg sulforaphane to be biologically active[^3]. Based on these findings estimated human doses are as follows[^3]:
You can obtain these doses of sulforaphane directly from cruciferous vegetables.
The effects of higher doses, while expected to be of further benefit, are not known[^3].
Another factor to take into account when considering taking sulforaphane supplements is the formulation.
Consumers are advised to use either an a-cyclodextrin inclusion or an SF-rich commercial supplement. That's because sulforaphane is more stable and bioavailable in these formulations[^3].
Once consumed, sulforaphane is well absorbed into the bloodstream via the small intestines. About 3/4 of the ingested dose is delivered into the bloodstream [^4].
Sulforaphane appears in the bloodstream 1 hour post-ingestion. Peak plasma levels are reached after 4 hours[^4]. The elimination half-life of sulforaphane is 2.2 hours and it becomes undetectable in blood 12 after consumption [^4].
Once in the bloodstream sulforaphane rapidly enters cells.
In the intracellular space, Sulforaphane interacts with glutathione, a cellular antioxidant, to form a glutathione-sulforaphane conjugate.
This process is catalyzed by the enzyme glutathione-s-transferase[^5]. Finally, once the glutathione-sulforaphane conjugate is formed, it exits the cell via the efflux protein MRP (Multidrug Resistance Protein), and to a lesser extent, P-glycoprotein[^5].
While the mechanism of action of Sulforaphane is not completely understood, Hydrogen Sulfide (H2S) likely plays a role.
Like nitric oxide, H2S is actually a gasotransmitter[^28].
H2S' main purpose in the body is to transmit chemical signals which bring about specific physiological or biochemical changes in a tissue or a cell.
The ability of sulforaphane to generate H2S lies in its isothiocyanate group (-N=C=S) which behaves as a sulfur donating molecule for its production[^6]. Interestingly, in prostatic cancer cell lines and in mouse liver cells, sulforaphane acts a potent generator of H2S[^7].
Sulforaphane exhibits cardio-protective effects.
By producing H2S, it acts on smooth muscle present in blood vessels positively impacting blood pressure[^8] and helping to prevent cardiovascular disease.
Sulforaphane is without a doubt a neuroprotective agent.
In neurons, sulforaphane is a potent inducer of Nrf-2 and an inhibitor of Nf-kB. Inducement of Nrf-2 and inhibition of Nf-kB protects against neurotoxicity and oxidative stress.
Due to its neuroprotective properties sulforaphane supplements could be of use in neurodegenerative disorders and for the management of neuropathic pain[^9]. In addition to its neuroprotective effects, sulpforaphane possesses anti-addictive properties whereby associated with reduced cocaine cravings in mice by inhibiting neuronal HDCA (Histone Deacetylase)[^10].
Aging is associated with reduced Proteosomal activity and the build up to modified proteins in cells[^11].
Sulforaphane enhances Proteosome activity, preventing cellular build-up of modified proteins and thus combats cellular aging[^12]. This effect lies in its ability to increase HSP27 and activate the heat shock response[^12].
Sulforaphane induces lipolysis. This is the processes where fat cells are broken down. This effect of sulofraphane is mediated by its ability to inhibit a protein known as AMPK which in turn enhances activity of the hormone sensitive lipase (HSL)[^13].
Sulforaphane acts on skeletal muscle by repressing a protein known as Myostatin.
Abolishment of Myostatin in the body results in muscle growth and reduction in fat mass. This effect of sulforaphane is the result of HDCA[^14] and Nrf2[^15] inhibition in myocytes.
Sulforaphane normalizes blood glucose and insulin sensitivity[^16]. However, the exact mechanism of this effect is unknown.
Sulforaphane posses potent anti-inflammatory properties by disrupting the generation of pro-inflammatory signals, an effect mediated by its ability to inhibit the action of NF-kB[^17].
Interestingly, it has shown promise for rheumatoid arthritis an autoimmune inflammatory disease. In synovial cell cultures, sulforaphane suppresses inflammation by inhibiting TNF-a generation[^18].
Sulforaphane acts as a potent anti-cancer agent.
Via HDCA inhibition, sulforaphane stimulates expression of p21 helps cells correct mutations prior to cell division[^19].
This effect is most obvious in prostate[^7] and colorectal[^20] as it is able to reach these sites at sufficient amounts to produce anti-cancerous effects[^21].
Sulforaphane slows the progression of kidney disease by suppressing inflammation and oxidative stress. Once again, this effect is mediated by Nrf2[^22].
Sulforaphane could theoretically harm the liver indirectly by increasing liver enzymes and cholesterol[^23].
Synergistic effects are observed when sulforaphane is co-administered with curcumin in regard to its anti-inflammatory actions[^24].
PEITC is a compound also found in cruciferous vegetables. It has synergistic anti-inflammatory effects with sulforaphane[^25].
Neoglucobrassicin, an agent also found in cruciferous vegetables, may reduce the anti-oxidative properties of Sulforaphane by preventing its interaction with Nrf2[^26].
When directly consuming cruciferous vegetables, mustard increases the amount of sulforaphane entering the bloodstream by stabilizing the enzyme Myrosinase leading the production of more sulforaphane[^27].
[^1]: Perocco P, et al. Glucoraphanin, the bioprecursor of the widely extolled chemopreventive agent sulforaphane found in broccoli, induces phase-I xenobiotic metabolizing enzymes and increases free radical generation in rat liver . Mutat Res. (2006)
[^2]: Nakagawa K, et al Evaporative light-scattering analysis of sulforaphane in broccoli samples: Quality of broccoli products regarding sulforaphane contents . J Agric Food Chem. (2006)
[^3]: Fahey JW, Wade KL, Wehage SL, et al. Stabilized sulforaphane for clinical use: Phytochemical delivery efficiency. Mol Nutr Food Res. (2016)
[4^]: Petri N, et al. Absorption/metabolism of sulforaphane and quercetin, and regulation of phase II enzymes, in human jejunum in vivo . Drug Metab Dispos. (2003)
[5^]: Zhang Y, Callaway EC High cellular accumulation of sulphoraphane, a dietary anticarcinogen, is followed by rapid transporter-mediated export as a glutathione conjugate . Biochem J. (2002)
[^6]: Benavides GA, et al Hydrogen sulfide mediates the vasoactivity of garlic . Proc Natl Acad Sci U S A. (2007)
[^7]: Pei Y, et al Hydrogen sulfide mediates the anti-survival effect of sulforaphane on human prostate cancer cells . Toxicol Appl Pharmacol. (2011)
[^8]: Benavides GA, et al Hydrogen sulfide mediates the vasoactivity of garlic . Proc Natl Acad Sci U S A. (2007)
[^9]: Negi G, Kumar A, Sharma SS Nrf2 and NF-κB modulation by sulforaphane counteracts multiple manifestations of diabetic neuropathy in rats and high glucose-induced changes . Curr Neurovasc Res. (201
[^10]: Host L, et al Cocaine self-administration alters the expression of chromatin-remodelling proteins; modulation by histone deacetylase inhibition . J Psychopharmacol. (2011)
[^11]: Stadtman ER. Protein oxidation and aging . Science. (1992)
[^12]: Gan N, et al. Sulforaphane activates heat shock response and enhances proteasome activity through up-regulation of Hsp27 . J Biol Chem. (2010)
[^13]: Lee JH, et al Sulforaphane induced adipolysis via hormone sensitive lipase activation, regulated by AMPK signaling pathway . Biochem Biophys Res Commun. (2012)
[^14]: Fan H, et al Sulforaphane causes a major epigenetic repression of myostatin in porcine satellite cells . Epigenetics. (2012)
[^15]: Oh CJ, et al Sulforaphane attenuates hepatic fibrosis via NF-E2-related factor 2-mediated inhibition of transforming growth factor-β/Smad signaling . Free Radic Biol Med. (2012)
[^16]: de Souza CG, et al Metabolic effects of sulforaphane oral treatment in streptozotocin-diabetic rats . J Med Food. (2012)
[^17]: Heiss E, et al Nuclear factor kappa B is a molecular target for sulforaphane-mediated anti-inflammatory mechanisms . J Biol Chem. (2001)
[^18]: Fragoulis A, et al Sulforaphane has opposing effects on TNF-alpha stimulated and unstimulated synoviocytes . Arthritis Res Ther. (2012)
[^19]: Myzak MC, et al A novel mechanism of chemoprotection by sulforaphane: inhibition of histone deacetylase . Cancer Res. (2004)
[^20]: Kaminski BM, et al Isothiocyanate sulforaphane inhibits protooncogenic ornithine decarboxylase activity in colorectal cancer cells via induction of the TGF-β/Smad signaling pathway . Mol Nutr Food Res. (2010)
[^21]: Clarke JD, et al Metabolism and tissue distribution of sulforaphane in Nrf2 knockout and wild-type mice . Pharm Res. (2011)
[^22]: Cui W, et al Prevention of diabetic nephropathy by sulforaphane: possible role of nrf2 upregulation and activation . Oxid Med Cell Longev. (2012)
[^23]: de Souza CG, et al Metabolic effects of sulforaphane oral treatment in streptozotocin-diabetic rats . J Med Food. (2012)
[^24]: Cheung KL, Khor TO, Kong AN Synergistic effect of combination of phenethyl isothiocyanate and sulforaphane or curcumin and sulforaphane in the inhibition of inflammation . Pharm Res. (2009)
[^25]: Cheung KL, Khor TO, Kong AN Synergistic effect of combination of phenethyl isothiocyanate and sulforaphane or curcumin and sulforaphane in the inhibition of inflammation . Pharm Res. (2009)
[^26]: Haack M, et al Breakdown products of neoglucobrassicin inhibit activation of Nrf2 target genes mediated by myrosinase-derived glucoraphanin hydrolysis products . Biol Chem. (2010)
[^27]: Ghawi SK, Methven L, Niranjan K The potential to intensify sulforaphane formation in cooked broccoli (Brassica oleracea var. italica) using mustard seeds (Sinapis alba) . Food Chem. (2013)
[^28]: Li YJ, Shi ZQ et al.. Hydrogen sulfide is a novel gasotransmitter with pivotal role in regulating lateral root formation in plants. Plant Signal Behav. 2014 May 15;9():
[^30]: Bi M, Li Q et al.. Sulphoraphane Improves Neuronal Mitochondrial Function in Brain Tissue in Acute Carbon Monoxide Poisoning Rats. Basic Clin Pharmacol Toxicol. 2016 Dec 16;():
[^31]: Yamagishi S, Matsui T. Protective role of sulphoraphane against vascular complications in diabetes. Pharm Biol. 2016 Oct;54(10):2329-39
[^32]: Zhang Y, Callaway EC. High cellular accumulation of sulphoraphane, a dietary anticarcinogen, is followed by rapid transporter-mediated export as a glutathione conjugate. Biochem J. 2002 May 15;364(Pt 1):301-7
[^33]: Yamagishi S, Matsui T. Protective role of sulphoraphane against vascular complications in diabetes. Pharm Biol. 2016 Oct;54(10):2329-39