Sulforaphane

Photo: Svetlana Lukienko/Shutterstock.com

Broccoli and other members of the cruciferous vegetable category have earned a high status for their positive effects on health. Recently, one component of these vegetables has grown its own health-promoting reputation and thus become more commonly available as a supplement: sulforaphane. Is there any evidence behind these health claims? Below are some of the latest human-based studies.

What is Sulforaphane?

Before we dive into the literature, a quick overview of sulforaphane is helpful. Cruciferous vegetables, such as broccoli and cabbage, contain molecules known as glucosinolate, one of which is glucoraphanin. When glucosinolate molecules are metabolized by the myrosinase enzyme, they create isothiocyanates. In the case of glucoraphanin, the end product is sulforaphane. Myrosinase is found in the plant cells and in the microbiome but not in human cells. Activation of the enzyme, which is a beta-thioglucosidase, occurs after injury to the plant tissue, including during chewing.

Some of the proposed effects of sulforaphane include:

While many of the initial reports on the benefits of sulforaphane came from mechanistic and animal studies, the last few decades have led to more human and clinical trials confirming at least some of these proposed effects.

Sulforaphane and Eliminating Toxins

Because of its purported ability to activate Nrf2 signaling pathways and activate phase II detoxification, there have been many studies on whether consuming sulforaphane-rich foods and/or supplements may mitigate some of the negative effects of pollution.

Researchers, using a randomized trial, found that doses of a broccoli sprout beverage helped to detox benzene. In this study, participants were randomized into four groups: a placebo control, a full dose with 600 umol glucoraphanin (GR) and 30 umol sulforaphane (SF), a half dose with 300 umol GR and 20 SF, and a 1/5 dose with 125 umol GR and 8 umol of SF. The group who consumed the full dose experienced a significant increase in urinary benzene mercapturic acids at +63.2%, correlating with an increase in benzene excretion.

In another randomized controlled study, almost 300 participants living in the He-He Township of Quidong in China, which has substantial levels of airborne pollution, consumed a beverage derived from broccoli sprout containing 600 umol of glucoraphanin and 40 umol of sulforaphane for 12 weeks. The metabolites of benzene, acrolein, and crotonaldehyde, known pollutants, were tested. The researchers found a statistically significant increase in excretion of benzene and acrolein (61% and 23%, respectively), although there was no difference in crotonaldehyde.

A separate study in Quidong, China, used two different kinds of beverages derived from broccoli sprouts, one with a high level of sulforaphane and the other with a high level of glucoraphanin, to see the impact on detoxing toxins including acrolein, crotonaldehyde, ethylene oxide, and benzene. The 50 participants consumed one of the beverages for 7 days, had a washout period of 5 days, and then consumed the other beverage for 7 days. The researchers found a statistically significant increase of excretion (20 – 50%) with both beverages, and there was no significant difference between the two. One more study found that a 4-day challenge with broccoli sprout extract mitigated the response to diesel exhaust particles by reducing the total white blood cell counts.

These studies point to the potential benefit of including sulforaphane-rich foods in the diet to reduce toxic burden.

Metabolic Health

Another area of health in which there are several studies on the efficacy of sulforaphane is metabolic and heart health, often related to its antioxidant and/or anti-inflammatory properties.

Forty healthy, overweight individuals consumed 30 g/day of broccoli sprouts for 10 weeks followed by a 10-week typical diet phase. During the broccoli consumption, there was a significant decrease in IL-6 levels (38%) which was maintained during the control phase. There was also a reduction in C-reactive protein levels, but they were not maintained during the control phase.

In one randomized, placebo-controlled, double-blind study on 52 patients with non-alcoholic fatty liver disease (NAFLD), consuming broccoli sprout extract with 30 mg of the sulforaphane precursor glucoraphanin daily for two months led to improved liver markers, including ALT and gamma-GTP but not AST (-10.7% and -8.9%, respectively). There was also a significant positive impact on oxidative stress markers, which the researchers posited likely impacted the liver markers.

Sulforaphane, or at least broccoli sprouts, may help with insulin resistance in type 2 diabetes. In one study, consuming 10 grams of broccoli sprouts powder that had a high concentration of sulforaphane daily for four weeks led to a significant decrease in serum insulin and HOMA-IR.

Furthermore, another research study looked at two independent double-blind, randomly allocated parallel studies. Researchers found that, compared to 400 g of standard broccoli, the same amount of high-glucoraphanin broccoli led to a significantly higher reduction in LDL cholesterol, with 1.8% compared to 7.1%, respectively, in one study and 2.5% and 5.1%, respectively, in the second study.

There has been some concern with individuals who have thyroid problems consuming broccoli and other cruciferous vegetables, often due to goitrogens. However, it appears that sulforaphane does not negatively impact thyroid function. A randomized trial looked at the safety of long-term consumption (84 days) of sulforaphane products on thyroid function. In this study, participants consumed either a drink made from a powder with 360 g glucoraphanin and 24 g sulforaphane in water added to pineapple juice and lime juice with a total of 600 umol of glucoraphanin and 40 umol of sulforaphane or a placebo. The participants’ thyroid function was screened using TSH, fT4, thyroglobulin, and anti-TG and anti-TPO antibodies. There was a small but statistically significant difference in TSH levels in the groups, but the mean remained in the reference range, and there was no difference in those with subclinical hypothyroidism. There was no difference in the TG or antibodies either.

Other Health Benefits

In the literature, there are many other areas of health in which sulforaphane demonstrates the potential to impart positive effects.

For example, in one placebo-controlled, randomized trial, daily sulforaphane treatment improved behavior symptoms in young men with autism. In this study, 29 adolescent and young adult males with autism consumed sulforaphane for 18 weeks, and the 15 control subjects took a placebo and then had no treatment for four weeks. After 18 weeks, the participants with the sulforaphane experienced improved results in the scores for three behavioral measure tests: The Aberrant Behavior Checklist, Social Responsiveness Scale, and Clinical Global Impression Improvement Scale. After ceasing the use of the sulforaphane, their scores returned to pretreatment numbers.

In a study on patients with H. pylori, consuming a broccoli sprout extract with sulforaphane twice daily (for a total of 2,000 ug of sulforaphane) for four weeks did not directly impact the H. pylori infection, but it did mitigate and prevent the lipid peroxidation in the gastric mucosa, thereby potential protecting against gastritis. Another study also found that sulforaphane protected against oxidative damage in the mucosa from NSAIDs.

In a phase 1, open-label, dose-escalation clinical trial on patients with sickle cell disease, the participants consumed broccoli sprout homogenate at 50 g, 100 g, or 150 g for 21 days. The results pointed to a statistically significant increase in platelets and trends for increased erythrocyte MCV and decreased creatinine, although the latter two did not reach statistical significance. At higher doses, there was a significant upregulation of a few of the Nrf2 genes.

Taking 100 umol of sulforaphane daily for 14 days led to improvements in asthma symptoms. There was a significant improvement in bronchoconstriction due to methacholine (MCh) in 60% of the participants, although in 20% the sulforaphane aggravated it. This effect was linked to the impact on the Nrf2-regulated genes. Another study found that consuming 200 g of broccoli sprouts homogenate did induce phase II enzyme expression in the airway, likely by Nrf2-activation, demonstrating a potential for reducing inflammation associated with an allergic response.

To maintain a proper balance, it’s important to note that not all studies on sulforaphane demonstrate efficacy. In a parallel, placebo-controlled, phase 2, randomized trial, 89 patients with COPD took a placebo, 25 umol of sulforaphane, or 150 umol of sulforaphane daily for four weeks. The researchers tested to see whether the sulforaphane impacted the Nrf2 gene expression, one of the purported mechanisms of sulforaphane, in the alveolar macrophages and bronchial epithelial cells, as well as any impact on oxidative stress and inflammation and overall pulmonary function. They found that there was no significant impact on Nrf2, oxidative stress, or inflammation. Short-term intake of 100 g of broccoli sprouts (3 days) also did not positively impact pulmonary inflammation, oxidative stress, or clinical symptoms in adults with atopic asthma compared to alfalfa sprouts in another double-blind, placebo-controlled trial.

While not all studies demonstrate the proposed effects of sulforaphane, many do point to the potential health-promoting benefits.

How to Get Sulforaphane from Your Diet

As you can see from the above research, most of the studies have used broccoli sprouts, broccoli sprouts extract, or broccoli (including high-glucoraphanin varieties). Therefore, consuming broccoli sprouts and broccoli, especially raw or lightly cooked, is the most evidence-based ways to get your sulforaphane. Other cruciferous vegetables also contain glucoraphanin, including:

  • Broccoli sprouts
  • Brussels’ sprout
  • Cabbage
  • Cauliflower
  • Kale
  • Radishes

There are some important factors to consider when choosing ways to consume sulforaphane, one of which is the inclusion of myrosinase. Consuming cooked broccoli may reduce the amount of sulforaphane, as the heat denatures the myrosinase enzyme. One randomized crossover study found that consuming 1 gram of powdered brown mustard along with 200 g cooked broccoli to provide the enzyme led to four times enhanced bioavailability of sulforaphane in the cooked broccoli compared to without the mustard, based on urinary levels of the sulforaphane metabolite. However, this was a small study of 12 participants.

For supplements using broccoli sprouts extract or similar substances containing glucoraphanin, having active myrosinase activity leads to a significantly higher bioavailability of sulforaphane. Another study found that up to 80% reduction of myrosinase did not impact the total amount of sulforaphane metabolites in urine, while complete inactivation did lead to the lowest amount. Cooking may also mitigate the amount of bioavailable sulforaphane and glucoraphanin, with raw or lightly-cooked broccoli having higher levels of the urinary metabolites of sulforaphane than fully-cooked broccoli. One study found about three times higher bioavailability of isothiocyanates such as sulforaphane from raw broccoli compared to steamed broccoli. Another study found higher sulforaphane absorption from fresh broccoli sprouts compared to broccoli sprout extract.

The amount of glucoraphanin, which is variable based on the growing of a plant, in a product may also impact the end results, based on one study that compared consuming three different types of broccoli in soup with different amounts of glucoraphanin. The researchers found a correlation between the increased amount of glucoraphanin in the broccoli and increased levels of sulforaphane in the tissues of the participants.

The action of sulforaphane, at least from whole food sources such as broccoli, may be lessened by the GSTM1 genotypes, with the amount of sulforaphane retained in the body depending on the genotype. Those with GSTM1-null genotypes may need to consume more than their GSTM1-positive counterparts.

Absorption and metabolism of isothiocyanates and metabolites may depend upon BMI. In one study, consuming broccoli daily altered the plasma AUC (plasma time curve) of total metabolites differently depending on BMI. In the group with a BMI of less than 26, the plasma AUC was 17% higher when consuming broccoli daily compared to no broccoli. Conversely, the group whose BMI was higher than 26 had plasma AUC 28% lower on the daily broccoli diet. In this study, the participants acted as their own controls. Similarly, the maximum plasma mass of total metabolites was increased by the “daily broccoli” diet in the low-BMI group but decreased by 33% in the high-BMI subjects. The study did not determine the mechanisms why this may be the case, but the microbiome, gut transit time, or metabolism may be involved.

Sulforaphane may be one reason for cruciferous vegetables’ beneficial reputation. Adding broccoli and other members of this vegetable family to your colorful, varied, plant-based diet may further support your health goals. Keep in mind that a personalized approach is best. Some individuals may be sensitive to the goitrogen content or intolerant of sulfur-containing vegetables. If you want to further enhance your sulforaphane consumption, talk to your doctor, dietitian, nutritionist, or another member of your healthcare team about the best ways to do so.

 

 

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