Found in cruciferous vegetables like broccoli, cauliflower, kale and cabbage, this sulfur-rich plant compound that has antineoplastic (tumor forming) properties has already shown huge promise in human health. It’s called sulforaphane (SNF), and it has already been well studied in its role in cancer prevention – the link between SNF and cancer was already suggested in the early 1980s – but there’s far more to it than that! 

Let’s dive a little deeper into its properties and explore its role as a health-boosting compound. 

Sulforaphane in prevention and treatment of disease

In its raw, inactive form, SFN is called glucoraphanin. It’s only converted into its active SFN form when it comes into contact with a specific enzyme called myrosinase, which is released when the plant cell walls are damaged (1).

Interestingly to note on this is that raw, chopped (torn or chewed) cruciferous vegetables contain 10 times the amount of SNF than they do in their cooked forms, however, steaming them for 1-3 minutes helps to optimize their SNF levels (2)

It’s role as a health-boosting compound has been proposed as being through antioxidant and anti-inflammatory pathways, specifically targeting the Nrf2 and NF-kB pathways. Compounds that induce Nrf2 are typically found to exert their predominant effects under higher redox states. This means that when levels of free radicals are balanced, Nrf2 is rapidly degraded via the proteasome, which is a process whereby proteins are broken down (3)

When free radicals are in higher levels, Nrf2 pathway kicks in as a means to create balance via a pathway that involves the synthesis of the master antioxidant glutathione. SFN has been shown to promote proteasome homeostasis and induce Nrf2 activity, which increases cellular lifespan. There is evidence to suggest that SFN also acts on genetic pathways involved in DNA modification and mitochondrial function (4)

The NF-kB pathway is one that plays an important role in almost all mammalian cells. It is largely considered to be an inflammatory signalling pathway where it is involved in the expression of proinflammatory genes and subsequent release of inflammatory compounds (5). The effects of NF-kB are downregulated by SFN, which is evident of its anti-inflammatory properties and its subsequent inhibition of inflammatory molecules such as nitric oxide synthase, COX-2, TNF-a and IL-6 (6).

The World Health Organization has suggested that as many as 70% of all global deaths can be attributed in some way to inflammation in that higher levels of inflammation induce chronic diseases, most commonly, heart disease, cancer, diabetes, inflammatory bowel diseases and respiratory diseases, all of which are life threatening. What’s more is that the development of one inflammatory disease increases the risk of developing another form of chronic inflammatory disease, which not only has a significant and compounding effect on the body, it creates further risk to health and lifespan. 

Due to the high risk of adverse effects patients with multiple comorbidities experience while taking pharmaceutical medication for their conditions, they often look to natural alternatives for prevention or treatment. 

Diet in one of those interventions, and when we begin to look deeper into what makes the diet so important, we can extrapolate some of the specific compounds that have targeted health benefits, one of them being SFN. 

Preclinical studies have produced a significant amount of evidence with regards to the health benefits of SFN. More recently, clinical trials have begun to reproduce these results. 

Respiratory illnesses

Explored using a rat model, researchers determined the use of SFN to treat asthma and they found that it worked through suppression of the Th2 response via modulation of the IL-4 and IL-5 inflammatory pathways. Additionally, SFN was found to have a regulatory effect on the allergic response of IgE that is often associated with asthma (7)

In humans, inflammatory and oxidative stress in the airways is involved in the progression of respiratory illnesses such as asthma. In otherwise healthy participants, researchers set out to determine the use of SFN on a specific pathway, called the Phase II enzyme pathway, which has been shown to promote the scavenging of reactive oxygen species and free radicals as well as their metabolism. In a placebo-controlled trial, SFN was shown to induce the Phase II enzymes in the upper airways of the participants, which increased expression of specific free radical scavenging pathways such as glutathione-s-transferase M1 (GSTM1), glutathione-s-transferase P1 (GSTP1), NADPH quinone oxidoreductase (NQO1), and hemoxygenase-1 (HO-1). What’s more is that along with reducing inflammatory effects of the oxidative stress in the respiratory pathways, oral SFN was well tolerated by all subjects (8)

Various studies have found no correlation with the above. For example, when patients with allergic airway disease consumed 100g of broccoli sprout extract for three days, researchers were unable to conclude any impact on Phase II enzymes. Another study, also using the intervention of a 3-day BSE in those with airway inflammation, found no effect on these enzymes. It is important to note, however, that both of these studies could not identify the dose of SFN in their extract, and the intervention was only provided for three days. 

Another study, using very low doses of SFN for 4 weeks could not correlate any anti-inflammatory or anti oxidant activity in COPD patients, while a study using much higher doses of SFN found improved inflammatory responses and lower oxidative stress. 

In one large study, 45 participants with moderate forms of asthma, were exposed to respiratory passage narrowing metacholine. Using a 100 μmol daily dose of SFN for 1 days, researchers set out to determine the therapeutic effects on a metacholine challenge in asthmatics. 60% of participants showed improvements in their symptoms, 20% showed worsening symptoms and the remaining 20% reported no change. NQO1 was improved in those who showed reduced bronchoconstriction and their gene activity of NrF-2 were decreased, however, expression of NQO1 was decreased and NrF-2 gene activity was increased in those who had poor results. In addition, lung CT scans showed that lung resistance to the effects of the bronchoconstrictor was improved in those who had a positive response from SNF intake (9). The conclusion of the study was that SFN may block the hyperresponsiveness to factors that induce bronchoconstriction in some asthmatics. 

Finally, a study in 291 healthy individuals, using 40 mM SFN daily for 12 weeks showed positive effects on their detoxification abilities, particularly for environments carcinogens such as benzes and acrolein, both of which have been linked to a higher risk of lung disease and other pulmonary disorders (10)

Heart disease

SFN reduces inflammation in a porcine-model of cardiac bypass. When SFN was introduced into the post-surgery treatment routine, there was a significantly lower effect of p38 and NFkB inflammatory expression (11)

In a murine model, it was found that SFN at a dose of 0.5mg/kg for 5 days a week, for four consecutive weeks, prevented right ventricular dysfunction and remodeling, it reduced right ventricular inflammation and fibrosis, it upregulated the antioxidant and anti-inflammatory pathways involved in Nrf2 expression and reduced inflammatory mediator NLRP3. The effects were also seen to mitigate pulmonary dysfunction, inflammation and fibrosis, where the pulmonary system is commonly affected as a result of right ventricular dysfunction (12)

Cancer

Multiple chronic diseases have been associated with imbalances in proteasome activity. In cancer, for example, it has been shown that cancer cells have increased proteasome activity, likely as a defense mechanism arising from the increased exposure of cancer cells to oxidative stress and cytokines (13)

Pre-clinically, SFN has been well-studied in its role as a chemoprotective agent. It has the ability to inhibit phase 1 cytochrome P450 enzymes, it has been shown to induce apoptosis, or programmed cell suiced, it enhances phase II detoxification pathways, and is also a compound that inhibits angiogenesis (14)

In clinical trials, conflicting data for these mechanisms exists. In a clinical trial on prostate cancer, SFN at a high dose of 200 mM every day for 20 weeks, showed only a 50% reduction in PSA. In another trial, this time in women with abnormal breast mammograms, SFN proved to inhibit cellular proliferation. What’s more, the effects were seen in women who ate higher doses of broccoli for eight weeks; this wasn’t even a trial using the SFN extract (15).

Currently, a number of clinical trials are in effect to determine the benefits of SFN on different types of cancer, which may provide a better insight into the mechanisms of the compound, and how it may be useful as a therapeutic agent for both protection and treatment of various types of cancers. 

Diabetes

There are two studies that provide strong evidence for the use of SFN in the treatment of type 2 diabetes in humans. These two recent studies show that SFN is both able to reduce fasting blood sugar levels and improve the defective insulin response. 

In both of these studies, the dose of SFN was between 100 and 230 with the time of consumption for the first study at 12 weeks and the second at 4 weeks. The higher the level of SFN in the patient’s plasma, the better the outcome of their HbA1c and fasting glucose response. Patients were observed to have increased insulin sensitivity and a reduced HOMA index, even after only 4 weeks of taking the compound. 

This therapeutic effect of SNF is promising, particularly for those patients who are unable to take currently prescribed pharmaceutical medication such as metformin due to its potential adverse effects in some patients. SFN was shown to be well-tolerated in these higher doses, with only minimal side effects such as mild gastrointestinal discomfort being recorded in a small number of participants (16,17)

Neurological health

Disorders of the brain present a great challenge to the medical community. There is as yet no cure for many of the leading causes of cognitive decline that contribute to many cases of death and disability across the globe. Mechanisms involved in cognitive decline are numerous and complex, and involve many cellular processes including changes in mitochondrial function, increased oxidation, inflammation, protein dysfunction, toxicity and tissue injury. In the brain, one of the most important factors that aims at regulating these processes is the Nrf2 signalling cascade (18)

We have already explored the role of SFN and it’s link to increased proteasome activity via the Nrf-2 signaling pathway. As mentioned in the introduction, proteasome induction is involved in the breakdown and clearance of proteins. When we think about one of the most common age-related diseases associated with protein misfolding and aggregation, Alzheimer’s disease, we begin to notice how important this process is for health, longevity and continued effective cognitive performance. 

Vascular cognitive impairment (VCI) is another form of dementia, with its major pathological process being related to chronic ischaemia – lack of blood flow and thus low oxygen delivery to the tissues – which causes dysfunction of the blood brain barrier, white matter injury and tissue death. 

In rats, researchers provided VCI induced animals with SFN, which showed significant protective action on the brain. Compared to control animals, the rats who were fed with SFN had remarkably lower cognitive impairment, reduced death of brain cells, their blood brain barrier integrity was better maintained, and there was central activation of the Nfr2 processes. The conclusion of the study was that SFN may be a promising therapeutic compound that may protect from the serious implications of ischaemic brain disorders (19).  

These effects on the blood brain barrier are an important consideration for the use of SFN. As it penetrates the BBB, the compound offers numerous neuroprotective effects. 

In a mouse model of Huntington’s disease, a fatal neurodegenerative disease associated with compromised oxidative stress defense mechanisms as well as functionally insufficient protein degradation machinery, SFN shows increased proteasome activity, suggesting a role of SNF in the treatment of the disease via enhances proteasome mechanisms in both the brain and peripheral tissues (20).  

The role of SFN in neurological disorders has been investigated thoroughly in preclinical models, however, only very few human trials have thus far been conducted. 

Most recently, a double-blind placebo controlled trial – the gold standard of research – shows positive effects of the use of SFN in children with autism spectrum disorder (ASD). Compared to the placebo group, those children, aged between 4 and 12 years old, receiving SFN alongside the pharmaceutical drug risperidone showed significant improvements in their irritability and hyperactivity/non-compliance scores. Not only was SFN well tolerated by the children, in addition to pharmaceutical therapy, SFN may improve symptoms of hyperactivity and irritability in children with ASD (21).

Based on the significant amount of information coming from animal studies and few human studies, it is suggestive that SFN has a critical role in the protection of factors that control homeostasis of the central nervous system, which may have profound effects on both the treatment and prevention of some of the most common neurological disorders such as Alzheimer’s disease, Parkinson’s disease, epilepsy and stroke, for example (22)

Overall promotion of health and longevity

The lifespan increasing effects of SFN have been shown in the red flour beetle (Tribolium castaneum). This beetle offers a model organism of study, particularly in the event of mechanisms involved in genetics and the impact of food. In a 2013 study, SFN was supplemented into the beetle’s diet under both physiological conditions and under heat stress, as a means to determine the food-gene interaction associated with longevity via mechanisms involved in resistance to stress-induced oxidation. In this model it was evident that the intervention of SFN in the diet showed the induction of the Nrf-2 (as well as Jnk-1 and Foxo-1) pathways; all key stress-resistant signalling pathways involved in the promotion of longevity in this organism (23)

The association of increased proteasome activity via SFN signalling has already been referred to as playing a central role in Alzheimer’s disease. Proteasome activity has also been explored in relation to the process of ageing, as proteasome homeostasis has been theorized to be a main factor in protecting from the factors of ageing. We know that the proteasome pathway is responsible for both the removal of normal proteins and misfolded or damaged ones, which you may now understand to be critical to not only reducing the risk of multiple chronic diseases, but to protecting from the overall effects of ageing. 

The longest-living rat species, naked mole rats, are shown to have high proteasome activity, which has been shown to significantly contribute to their extended lifespan (24)

A 2015 study also shows the direct link between SFN and NF-kB, and the modulation of inflammation through T-cells. While the research of the NF-kB pathways involved in SFN modulatory effects is not yet well documented, we will be checking in on these mechanisms in the future, but for now, we are satisfied with the anti-aging mechanism involving the Nfr-2 pathway (25)

Nrf2 has been shown to play a critical role in the balance of the redox ratio during periods of cellular stress and increased oxidation. In animal studies, we have already seen that Nrf2-pathways are upregulated by SNF. We now need to know if the same mechanisms of action can be translated into humans. 

First, it’s important to know that induction of the Nfr-2 pathway declines with ageing due to an increase in the expression of Nrf-2 suppressing genes (26)

A 2018 in vitro study on human bronchial epithelial cells from two distinct groups of the population, namely from those in the 21-29 age range and 60-69 age range, were used to determine the effects of SFN on Nrf-2 signalling. While induction of the Nrf-2 pathways was slightly lower in the older group than in the younger group, there was a significant increase in Nrf-2 signalling in both groups (27). These findings are consistent with the findings that there is an age-related decline in the ability to induce Nrf-2, also found to be true in the mouse model (28)

Cellular senescence is the accumulation of damaged cells and has a direct correlation to the process of ageing. It is associated with mitochondrial dysfunction, which disrupts critical physiological functions, including that of the immune system and its defense against harmful metabolites and subsequent proteolytic processes and oxidative damage. In human cells, SFN has been shown to induce the Nrf-2 pathway, which delays the mechanism of cellular senescence. The pathways through which this delay occurs is believed to be via calorie-mimetic-like activity, leading to decreased oxidative damage and thus offering protection to tissues and DNA. In addition, SFN has been shown to enhance the clearance of senescent cells, further increasing the proposed health benefits of this compound (29)

Healthy individuals

SFN is not only beneficial to those who have a higher risk of inflammatory diseases, it has been suggested that the compound may be useful in healthy individuals, too. In fact, many of the clinical studies that have been conducted have been performed in healthy individuals. These studies have been used to provide information on the dose that provides therapeutic benefit, and to determine the exact nature of the pathways SFN acts upon. 

Of importance to note, is that these studies show that bioactive SFN has a far greater biological effect on health than glucoraphanin-rich supplements, which require the body to convert them to their active form (30). For this reason, it is critical to know the quality of the supplement that you’re taking, and whether it will have the desired effects you are looking for.  

Additionally, there is much to say about the dose of SFN in that in order to provide suitable and stable levels within the body, multiple doses need to be taken over time instead of one or two larger doses. 

As you can see, much evidence from a variety of studies that include tissue, animal and clinical trials, points to the potent mechanisms of SFN and its ability to regulate the essential Nrf-2 signalling pathways, which has been referred to as one of the most important pathways involved in health and disease. Along with its overall impact on oxidative molecules, SFN shows the most promise in its effects on human health and lifespan.

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Selection of studies used for this article:

  1. Vanduchova, A., et al. Isothiocyanate from Broccoli, Sulforaphane, and Its Properties. J Med Food. 2019 Feb;22(2):121-126. 
  2. Wang, G., et al. Impact of thermal processing on sulforaphane yield from broccoli ( Brassica oleracea L. ssp. italica). J Agric Food Chem. 2012 Jul 11;60(27):6743-8. 
  3. Silva-Palacios A, Ostolga-Chavarria M, Zazueta C, Königsberg M. (2018) Nrf2: molecular and epigenetic regulation during aging. Ageing Res Rev 47:31–40. 
  4. Santín-Márquez, R., Alarcón-Aguilar, A., López-Diazguerrero, N.E. et al. Sulfoaphane – role in aging and neurodegeneration. GeroScience (2019)
  5. Lawrence, T. The Nuclear Factor NF-κB Pathway in Inflammation. Cold Spring Harb Perspect Biol. 2009 Dec; 1(6): a001651. 
  6. Negi, G., et al. Nrf2 and NF-κB modulation by sulforaphane counteracts multiple manifestations of diabetic neuropathy in rats and high glucose-induced changes. Curr Neurovasc Res. 2011 Nov;8(4):294-304.
  7. Grunwald, S., et al. Longevity in the red flour beetle Tribolium castaneum is enhanced by broccoli and depends on nrf-2, jnk-1 and foxo-1 homologous genes. Genes Nutr. 2013 Sep; 8(5): 439–448.
  8. Chondrogianni, N., Sakellari, M., Lefaki, M., Papaevgeniou, N., & Gonos, E. S. (2014). Proteasome activation delays aging in vitro and in vivo. Free Radical Biology and Medicine, 71, 303–320.
  9. Rodriguez, K.A.;Edrey, Y.H.;Osmulski, P.;Gaczynska, M.;Buffenstein, R. Altered composition of liver proteasome assemblies contributes to enhanced proteasome activity in the exceptionally long-lived naked mole-rat. PLoS One 7(5):e35890; 2012.
  10. Liu, Y., et al. Sulforaphane enhances proteasomal and autophagic activities in mice and is a potential therapeutic reagent for Huntington’s disease. J Neurochem. 2014 May; 129(3): 539–547.
  11. Checker, R., Gambhir, L., Thoh, M., Sharma, D., & Sandur, S. K. (2015). Sulforaphane, a naturally occurring isothiocyanate, exhibits anti-inflammatory effects by targeting GSK3β/Nrf-2 and NF-κB pathways in T cells. Journal of Functional Foods, 19, 426–438.
  12. Sachdeva M.M., Cano M., Handa J.T. Nrf2 signaling is impaired in the aging RPE given an oxidative insult. Exp. Eye Res. 2014;119:111–114.
  13. Zhou, L., et al. Aging-related decline in the induction of Nrf2-regulated antioxidant genes in human bronchial epithelial cells. Redox Biol. 2018 Apr; 14: 35–40.
  14. Zhang, et al. Nrf2-regulated phase II enzymes are induced by chronic ambient nanoparticle exposure in young mice with age-related impairments. Free Radic Biol Med. 2012 May 1; 52(9): 2038–2046.
  15. Hariston, F., et al. Sulforaphane Delays Fibroblast Senescence by Curbing Cellular Glucose Uptake, Increased Glycolysis, and Oxidative Damage. Oxid Med Cell Longev. 2018; 2018: 5642148.
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