Life Extension Magazine®

Man in garden holding broccoli with the compound sulforaphane

How to Obtain Broccoli's Beneficial Compounds

Sulforaphane, a compound found in broccoli, is poorly absorbed, and depleted by cooking. A dual-layered delivery system mimics nature to deliver more sulforaphane into the bloodstream.

Scientifically reviewed by: Dr. Gary Gonzalez, MD, in October 2024. Written by: Michael Downey.

Up to 90% of all cancers are caused by environmental and lifestyle factors.1,2

Research shows that a higher intake of broccoli and other cruciferous vegetables is associated with a reduced risk of cancer.3,4

But until recently, optimizing intake of a beneficial cruciferous vegetable compound called sulforaphane has been challenging.

A novel delivery system keeps the sulforaphane precursor (glucoraphanin) apart from the myrosinase enzyme until they reach the small intestine.

Once in the small intestine, myrosinase converts glucoraphanin into sulforaphane for absorption into the bloodstream.

Cruciferous Nutrients Inhibit Cancer

Cruciferous vegetables include broccoli, kale, cabbage, cauliflower, watercress, and Brussels sprouts.

Studies going back decades have shown that large dietary intake of these foods is associated with a reduced risk of developing different forms of cancer, including many of the most common types, like lung and colorectal cancer.4-6

That’s because cruciferous vegetables are loaded with compounds that shield cells from processes that can transform them into malignant tumors.3,4

Two of the most protective compounds are:7-9

  • Sulforaphane and
  • 3,3’-diindolylmethane (DIM).

DIM is a stable compound that is readily absorbed from the digestive system.

Sulforaphane, however, is unstable. It rapidly degrades into non-active substances if it isn’t quickly absorbed or if the vegetable is cooked.

Nature has found a way around this problem.

How Plants Produce Sulforaphane

Cruciferous vegetables that produce sulforaphane

Sulforaphane is a cancer-fighting compound we get from cruciferous vegetables. And yet it isn’t present in them.

Instead, a precursor called glucoraphanin is stored inside the cells of these plants. In a separate compartment in these cells is an enzyme called myrosinase.

When mixed together, the myrosinase converts the glucoraphanin into sulforaphane.

This is what happens when the vegetable is eaten raw. During digestion, sulforaphane is formed. It can then be absorbed within the small intestine before it degrades.4,5,9

But maximizing these anti-cancer benefits would require the consumption of massive amounts of raw broccoli.

The challenge for scientists was to find a way to deliver glucoraphanin and myrosinase separately to the small intestine.

Mimicking Nature

Scientist examining isolated glucoraphanin and myrosinase

One group of scientists came up with an ingenious solution that copies nature.

They isolated glucoraphanin and myrosinase from broccoli, then developed a delivery system that keeps them separate, just the way plants do.

A dual-layered tablet was given an enteric coating to prevent its ingredients from being released until it reaches the small intestine.

With this unique delivery system, the compound glucoraphanin and the enzyme myrosinase meet and mix in the small intestine. There, they come together to create sulforaphane, just as nature planned.

The results have been striking. Research at the Johns Hopkins University School of Medicine demonstrated that sulforaphane levels from this glucoraphanin-myrosinase mix are three to four times more bioavailable (absorbable) than those created by glucoraphanin supplementation alone.10

Sulforaphane Reduces Cancer Risk

Maximizing production of sulforaphane can have a huge impact on fighting cancer.

Lab and animal studies show sulforaphane:11-13

  • Kills cancer stem cells,
  • Slows the growth of tumors, and
  • Promotes the death of cancer cells.

In one study, rats were divided into two groups. One was given sulforaphane and the other was not. Both groups were then given a strong carcinogen.

The animals that had been given sulforaphane developed fewer tumors compared to controls. The tumors that did develop were smaller and grew more slowly.14

A large body of preclinical research has revealed great promise for sulforaphane as regards reducing the risk of many cancers, including those of the:

The Anti-Cancer Effects of DIM

The benefits of the cruciferous nutrient DIM have been evaluated in a study of women with a history of breast cancer.27

In this study, women were randomized to receive either DIM (108 mg per day in one study) or a placebo.

DIM was found to significantly alter the mix of estrogen metabolites, increasing “good” estrogen metabolites, and reducing “bad” estrogen metabolites.

DIM has also been evaluated for prevention of cervical cancer.5,7,28

In one remarkable study, women with a cervical precancer lesion—cervical intraepithelial neoplasia—were randomized to receive either 100 mg of DIM, 200 mg of DIM, or a placebo. After three to six months, all patients’ cervical intraepithelial neoplasia resolved completely with the 200 mg dose of DIM. With the lower 100 mg dose of DIM, 90.5% regressed.7

What you need to know

Researcher using syringe to extract compounds from broccoli

Maximizing the AntiCancer Effects of Cruciferous Vegetables

  • Cruciferous vegetables, such as broccoli, cabbage, cauliflower, Brussels sprouts, and kale, are associated with reduced risk of cancer.
  • Two cruciferous compounds are especially well-validated for their cancer-fighting properties: sulforaphane and 3,3’-diindolylmethane (DIM).
  • While DIM is stable, sulforaphane rapidly degrades if not absorbed quickly.
  • Scientists have developed a way to separately package a sulforaphane precursor and an enzyme that converts it into sulforaphane. The sulforaphane is then created in the small intestine, where it’s rapidly absorbed into the bloodstream.
  • Early research shows that DIM and bioavailable sulforaphane can prevent changes that lead to cancer, stop tumors from developing and spreading, and even cause cancer cells to die off.

Four Ways Sulforaphane and DIM Fight Cancer

What’s striking about sulforaphane and DIM is that they have demonstrated anticancer effects in virtually every tissue studied.

Equally impressive, these compounds can both prevent cancerous changes in cells, and in preclinical studies have been shown to reverse the progression of existing tumors.

These nutrients have been shown to reduce cancer risk in four main ways:

1. Preventing Harmful Changesto Gene Expression

Older man having physical done after epigenetic changes

Cancer can be caused by epigenetic changes, which can turn protective genes “off” and flip “on” genes that enable uncontrolled cellular proliferation. Adverse changes to gene expression can be triggered by behavior (like smoking) or exposure to environmental toxins.

Sulforaphane and DIM can reverse some of these cancer-associated changes.17

For example, sulforaphane reverses alterations of histone proteins involved in the regulation of genes that could otherwise contribute to cancer.29,30

This gene regulation mechanism is a target of cancer drugs now under development.31-33

2. Attacking Pre-Cancerous Cells and Blocking Tumor Development

Even after a cell starts down the path to cancer, its progression can be halted or reversed.

Sulforaphane has the ability to suppress signals and enzymes that spur the growth of tumors. It can also reduce the formation of blood vessels that feed them.34-39

DIM also has been shown preclinically to block the formation of new blood vessels in tumors, starving them of oxygen and nutrients needed to grow.40

Both sulforaphane and DIM also turn on genes associated with cancer cell apoptosis (programmed cell death). This causes the abnormal cells to die off, while leaving healthy cells unharmed.41,42

It is believed that these effects could prevent pre-cancerous cells from developing into cancer and slow the growth of existing cancer.

3. Fighting Estrogen-Driven Cancer Growth

An estrogen metabolite called 16-alpha hydroxyestrone can stimulate proliferation of breast and prostate cancers.43-45

DIM helps shift the estrogen balance away from 16-alpha hydroxyestrone that promotes cancer and toward one (2-hydroxyestrone) that inhibits it.27

In women who have had breast cancer, daily DIM intake shifts these estrogen metabolites toward a preponderance of the healthier form.27

In men, higher estrogen levels are associated with prostate enlargement and cancers. Studies show DIM can prevent estrogen-induced stimulation of prostate cancer cells.46,47

Sulforaphane reinforces this protection by fighting the potential DNA-damaging effects of estrogen, which could help to prevent the early DNA damage that leads to cancers.48-50

4. Blocking a Key Inflammatory ‘Switch’

Our bodies have a “switch” that activates inflammation, including chronic inflammation that contributes to cancer and other age-related diseases.

This switch is called nuclear factor-kappa B (NF-kB).

Preliminary research shows that sulforaphane blocks NF-kB, reducing the inflammation that contributes to cancer growth. It also kills cancer stem cells that can trigger tumor recurrence.12,51,52

These mechanisms are likely reasons why sulforaphane and DIM are two of the most robust cancer-fighting compounds found in nature.

Summary

Older couple cooking with broccoli for beneficial compounds

Raw cruciferous vegetables like broccoli are associated with a reduced risk for many types of cancers.

Many of these anti-cancer effects are due to two compounds derived from these vegetables: sulforaphane and DIM.

DIM is stable and easily absorbed when taken orally. But sulforaphane is not.

Scientists have solved this problem by creating a delivery system that separates a sulforaphane precursor and an enzyme that converts it to sulforaphane.

This enables sulforaphane to be formed in the small intestine where it can be rapidly absorbed, delivering higher blood levels of the beneficial compound. •

If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.

Sulforaphane May Help Prevent Alzheimer’s Disease

Preclinical research suggests that sulforaphane may help prevent some of the pathogenic factors that lead to Alzheimer’s disease.

A review published in the March 2021 issue of International Journal of Molecular Sciences noted that sulforaphane, known for its anti-inflammatory effects, has recently been studied for its effects on brain health.53

Dr. Jiyoung Kim, the scientist who conducted this study, pointed out that changes occur within the brain 10-15 years before the cognitive decline that leads to a diagnosis of Alzheimer’s.

For this reason, she focused on studies that investigated the effects of sulforaphane on five different preclinical biomarkers for Alzheimer’s: beta amyloid, tau, inflammation, oxidative stress, and neurodegeneration.53

  • Most significantly, cell and animal studies demonstrated that sulforaphane can prevent the production of both beta amyloid and tau, proteins involved in Alzheimer’s disease.
  • Evidence also showed that sulforaphane inhibits the Alzheimer’s-associated preclinical biomarkers of inflammation, oxidative stress, and neurodegeneration.

These effects were seen in many different cell and animal models. This suggests that there is a future possibility of an effective, sulforaphane-based strategy for Alzheimer’s prevention.

References

  1. Anand P, Kunnumakkara AB, Sundaram C, et al. Cancer is a preventable disease that requires major lifestyle changes. Pharm Res. 2008 Sep;25(9):2097-116.
  2. Wu S, Powers S, Zhu W, et al. Substantial contribution of extrinsic risk factors to cancer development. Nature. 2016 Jan 7;529(7584):43-7.
  3. Dinkova-Kostova AT, Fahey JW, Kostov RV, et al. KEAP1 and Done? Targeting the NRF2 Pathway with Sulforaphane. Trends Food Sci Technol. 2017 Nov;69(Pt B):257-69.
  4. Verhoeven DT, Goldbohm RA, van Poppel G, et al. Epidemiological studies on brassica vegetables and cancer risk. Cancer Epidemiol Biomarkers Prev. 1996 Sep;5(9):733-48.
  5. Higdon JV, Delage B, Williams DE, et al. Cruciferous vegetables and human cancer risk: epidemiologic evidence and mechanistic basis. Pharmacol Res. 2007 Mar;55(3):224-36.
  6. Tang L, Zirpoli GR, Jayaprakash V, et al. Cruciferous vegetable intake is inversely associated with lung cancer risk among smokers: a case-control study. BMC Cancer. 2010 Apr 27;10:162.
  7. Ashrafian L, Sukhikh G, Kiselev V, et al. Double-blind randomized placebo-controlled multicenter clinical trial (phase IIa) on diindolylmethane’s efficacy and safety in the treatment of CIN: implications for cervical cancer prevention. EPMA J. 2015;6:25.
  8. Kyung SY, Kim DY, Yoon JY, et al. Sulforaphane attenuates pulmonary fibrosis by inhibiting the epithelial-mesenchymal transition. BMC Pharmacol Toxicol. 2018 Apr 2;19(1):13.
  9. Su X, Jiang X, Meng L, et al. Anticancer Activity of Sulforaphane: The Epigenetic Mechanisms and the Nrf2 Signaling Pathway. Oxid Med Cell Longev. 2018;2018:5438179.
  10. Fahey JW, Holtzclaw WD, Wehage SL, et al. Sulforaphane Bioavailability from Glucoraphanin-Rich Broccoli: Control by Active Endogenous Myrosinase. PLoS One. 2015;10(11):e0140963.
  11. Bose C, Awasthi S, Sharma R, et al. Sulforaphane potentiates anticancer effects of doxorubicin and attenuates its cardiotoxicity in a breast cancer model. PLoS One. 2018;13(3):e0193918.
  12. Burnett JP, Lim G, Li Y, et al. Sulforaphane enhances the anticancer activity of taxanes against triple negative breast cancer by killing cancer stem cells. Cancer Lett. 2017 May 28;394:52-64.
  13. Yang F, Wang F, Liu Y, et al. Sulforaphane induces autophagy by inhibition of HDAC6-mediated PTEN activation in triple negative breast cancer cells Life Sci. 2018 Nov 15;213:149-57.
  14. Zhang Y, Kensler TW, Cho CG, et al. Anticarcinogenic activities of sulforaphane and structurally related synthetic norbornyl isothiocyanates. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3147-50.
  15. Abbaoui B, Telu KH, Lucas CR, et al. The impact of cruciferous vegetable isothiocyanates on histone acetylation and histone phosphorylation in bladder cancer. J Proteomics. 2017 Mar 6;156:94-103.
  16. Wang DX, Zou YJ, Zhuang XB, et al. Sulforaphane suppresses EMT and metastasis in human lung cancer through miR-616-5p-mediated GSK3beta/beta-catenin signaling pathways. Acta Pharmacol Sin. 2017 Feb;38(2):241-51.
  17. Wong CP, Hsu A, Buchanan A, et al. Effects of sulforaphane and 3,3’-diindolylmethane on genome-wide promoter methylation in normal prostate epithelial cells and prostate cancer cells. PLoS One. 2014;9(1):e86787.
  18. Ali Khan M, Kedhari Sundaram M, Hamza A, et al. Sulforaphane Reverses the Expression of Various Tumor Suppressor Genes by Targeting DNMT3B and HDAC1 in Human Cervical Cancer Cells. Evid Based Complement Alternat Med. 2015;2015:412149.
  19. Cheng YM, Tsai CC, Hsu YC. Sulforaphane, a Dietary Isothiocyanate, Induces G(2)/M Arrest in Cervical Cancer Cells through CyclinB1 Downregulation and GADD45beta/CDC2 Association. Int J Mol Sci. 2016 Sep 12;17(9).
  20. Sharma C, Sadrieh L, Priyani A, et al. Anti-carcinogenic effects of sulforaphane in association with its apoptosis-inducing and anti-inflammatory properties in human cervical cancer cells. Cancer Epidemiol. 2011 Jun;35(3):272-8.
  21. Fimognari C, Turrini E, Sestili P, et al. Antileukemic activity of sulforaphane in primary blasts from patients affected by myelo- and lympho-proliferative disorders and in hypoxic conditions. PLoS One. 2014;9(7):e101991.
  22. Koolivand M, Ansari M, Piroozian F, et al. Alleviating the progression of acute myeloid leukemia (AML) by sulforaphane through controlling miR-155 levels. Mol Biol Rep. 2018 Dec;45(6):2491-9.
  23. Shang HS, Shih YL, Lee CH, et al. Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-28.
  24. Bauman JE, Zang Y, Sen M, et al. Prevention of Carcinogen-Induced Oral Cancer by Sulforaphane. Cancer Prev Res (Phila). 2016 Jul;9(7): 547-57.
  25. Kumar R, de Mooij T, Peterson TE, et al. Modulating glioma-mediated myeloid-derived suppressor cell development with sulforaphane. PLoS One. 2017;12(6):e0179012.
  26. Miao Z, Yu F, Ren Y, et al. d,l-Sulforaphane Induces ROS-Dependent Apoptosis in Human Gliomablastoma Cells by Inactivating STAT3 Signaling Pathway. Int J Mol Sci. 2017 Jan 4;18(1).
  27. Dalessandri KM, Firestone GL, Fitch MD, et al. Pilot study: effect of 3,3’-diindolylmethane supplements on urinary hormone metabolites in postmenopausal women with a history of early-stage breast cancer. Nutr Cancer. 2004;50(2):161-7.
  28. Sepkovic DW, Stein J, Carlisle AD, et al. Diindolylmethane inhibits cervical dysplasia, alters estrogen metabolism, and enhances immune response in the K14-HPV16 transgenic mouse model. Cancer Epidemiol Biomarkers Prev. 2009 Nov;18(11):2957-64.
  29. Tortorella SM, Royce SG, Licciardi PV, et al. Dietary Sulforaphane in Cancer Chemoprevention: The Role of Epigenetic Regulation and HDAC Inhibition. Antioxid Redox Signal. 2015 Jun 1;22(16):1382-424.
  30. Bayat Mokhtari R, Baluch N, Homayouni TS, et al. The role of Sulforaphane in cancer chemoprevention and health benefits: a mini-review. J Cell Commun Signal. 2018 Mar;12(1):91-101.
  31. Bai Y, Ahmad D, Wang T, et al. Research Advances in the Use of Histone Deacetylase Inhibitors for Epigenetic Targeting of Cancer. Curr Top Med Chem. 2019;19(12):995-1004.
  32. Damaskos C, Tomos I, Garmpis N, et al. Histone Deacetylase Inhibitors as a Novel Targeted Therapy Against Non-small Cell Lung Cancer: Where Are We Now and What Should We Expect? Anticancer Res. 2018 Jan;38(1):37-43.
  33. Srinivas NR. Clinical pharmacokinetics of panobinostat, a novel histone deacetylase (HDAC) inhibitor: review and perspectives. Xenobiotica. 2017 Apr;47(4):354-68.
  34. Annabi B, Rojas-Sutterlin S, Laroche M, et al. The diet-derived sulforaphane inhibits matrix metalloproteinase-9-activated human brain microvascular endothelial cell migration and tubulogenesis. Mol Nutr Food Res. 2008 Jun;52(6):692-700.
  35. Hunakova L, Sedlakova O, Cholujova D, et al. Modulation of markers associated with aggressive phenotype in MDA-MB-231 breast carcinoma cells by sulforaphane. Neoplasma. 2009;56(6):548-56.
  36. Pawlik A, Wiczk A, Kaczynska A, et al. Sulforaphane inhibits growth of phenotypically different breast cancer cells. Eur J Nutr. 2013 Dec;52(8):1949-58.
  37. Davis R, Singh KP, Kurzrock R, et al. Sulforaphane inhibits angiogenesis through activation of FOXO transcription factors. Oncol Rep. 2009 Dec;22(6):1473-8.
  38. Liu P, Atkinson SJ, Akbareian SE, et al. Sulforaphane exerts anti-angiogenesis effects against hepatocellular carcinoma through inhibition of STAT3/HIF-1alpha/VEGF signalling. Sci Rep. 2017 Oct 4;7(1):12651.
  39. Wang Y, Zhou Z, Wang W, et al. Differential effects of sulforaphane in regulation of angiogenesis in a co-culture model of endothelial cells and pericytes. Oncol Rep. 2017 May;37(5):2905-12.
  40. Chinnakannu K, Chen D, Li Y, et al. Cell cycle-dependent effects of 3,3’- diindolylmethane on proliferation and apoptosis of prostate cancer cells. J Cell Physiol. 2009 Apr;219(1):94-9.
  41. Pledgie-Tracy A, Sobolewski MD, Davidson NE. Sulforaphane induces cell type-specific apoptosis in human breast cancer cell lines. Mol Cancer Ther. 2007 Mar;6(3):1013-21.
  42. Kim SM. Cellular and Molecular Mechanisms of 3,3’-Diindolylmethane in Gastrointestinal Cancer. Int J Mol Sci. 2016 Jul 19;17(7).
  43. Yager JD, Davidson NE. Estrogen carcinogenesis in breast cancer. N Engl J Med. 2006 Jan 19;354(3):270-82.
  44. Santen RJ, Yue W, Wang JP. Estrogen metabolites and breast cancer. Steroids. 2015 Jul;99(Pt A):61-6.
  45. Briganti A. Oestrogens and prostate cancer: novel concepts about an old issue. Eur Urol. 2009 Mar;55(3):543-5.
  46. Smith S, Sepkovic D, Bradlow HL, et al. 3,3’-Diindolylmethane and genistein decrease the adverse effects of estrogen in LNCaP and PC-3 prostate cancer cells. J Nutr. 2008 Dec;138(12):2379-85.
  47. Chen D, Banerjee S, Cui QC, et al. Activation of AMP-activated protein kinase by 3,3’-Diindolylmethane (DIM) is associated with human prostate cancer cell death in vitro and in vivo. PLoS One. 2012;7(10):e47186.
  48. Wu Q, Odwin-Dacosta S, Cao S, et al. Estrogen down regulates COMT transcription via promoter DNA methylation in human breast cancer cells. Toxicol Appl Pharmacol. 2019 Mar 15;367:12-22.
  49. Yager JD. Mechanisms of estrogen carcinogenesis: The role of E2/E1-quinone metabolites suggests new approaches to preventive intervention--A review. Steroids. 2015 Jul;99(Pt A):56-60.
  50. Yang L, Zahid M, Liao Y, et al. Reduced formation of depurinating estrogen-DNA adducts by sulforaphane or KEAP1 disruption in human mammary epithelial MCF-10A cells. Carcinogenesis. 2013 Nov;34(11):2587-92.
  51. Ren K, Li Z, Li Y, et al. Sulforaphene enhances radiosensitivity of hepatocellular carcinoma through suppression of the NF-kappaB pathway. J Biochem Mol Toxicol. 2017 Aug;31(8).
  52. Sturm C, Wagner AE. Brassica-Derived Plant Bioactives as Modulators of Chemopreventive and Inflammatory Signaling Pathways. Int J Mol Sci. 2017 Sep 1;18(9).
  53. Kim J. Pre-Clinical Neuroprotective Evidences and Plausible Mechanisms of Sulforaphane in Alzheimer’s Disease. Int J Mol Sci. 2021 Mar 13;22(6).