Broccoli sprouts

Broccoli sprouts - five days old

Broccoli sprouts are three- to four-day-old broccoli plants that look like alfalfa sprouts, but taste like radishes. The radish flavor comes from a phytochemical that may act as protection against vectors (see also radical or free-radical theory) while the broccoli plant is still young.[1] This phytochemical not only benefits the young plant, but also when eaten by humans, may act as an antioxidant to stimulate the ability of cells to protect against disease.

History

While health-conscious people in the 1970s embraced raw sprouts as a dietary staple, it was not until the 1990s that broccoli sprouts became the mainstream. This is because in 1992[2] a team of Johns Hopkins University scientists isolated a cancer-fighting phytochemical in broccoli called glucoraphanin, which is the glucosinolate precursor of sulforaphane (SGS).[3] When chewed, broccoli releases glucoraphanin and myrosinase, an enzyme found in another part of the plant cell, which work together to produce sulforaphane, which, in turn, activates a transcription factor, Nrf2 in the cell. Once activated, Nrf2 then translocates to the nucleus of the cell, where it aligns itself with the antioxidant response element (ARE) in the promoter region of target genes. The target genes are associated with process which assists in regulating cellular defences. Such cytoprotective genes include that for glutathione. Around 200 genes have been well-characterised, as many as 1700 are thought to be related to this aspect of cellular defense.

The 1992 study was followed by the discovery in 1997[4] that glucoraphanin is in higher concentrations in the three- to four-day-old broccoli sprouts, at least 20 times the concentration of full grown broccoli. This discovery was written about in the New York Times,[5] and created a global shortage of broccoli seed that could not meet the sudden high demand.

Nutrition

Broccoli sprouts actually have lower nutritional values than full sized broccoli according to the USDA.[6] Many studies compare the nutritional value of dry, dormant seeds to sprouts to obtain an exaggerated positive result for sprouts. However, the sprouts are not typically consumed for their nutrient content; they are consumed for their content of bioactive molecules with potent nutrigenomic potential. Broccoli sprouts contain a particular glucosinolate compound, glucoraphanin, which is found in vacuoles within the cytoplasm of the plant cell. The membrane of the plant cells also contain an enzyme, myrosinase, which is walled off from the vacuoles of glucoraphanin. Only when the plant cell is ruptured by cutting, chewing, etc. do the two substances come into contact with each other. In the moist environment of the cell, this leads to a chemical reaction wherein the myrosinase converts the glucoraphanin to an isothiocyanate, sulforaphane. It is predominantly the sulforaphane for which broccoli sprouts have been so widely researched. The glucoraphanin of itself is inert.

Research

Hundreds of research studies occur every year on the cancer preventive potential of plant nutrients. The cancer preventive property of cruciferous vegetables and sulforaphane is the subject of over 700 research studies to date. The following table is a representation of the epidemiological evidence of cancer prevention by cruciferous vegetables.

Epidemiological Evidence of Cancer Prevention by Cruciferous Vegetables

Site of cancer Amount of crucifers eaten RR - relative risk
OR-odds ratio
(P value)		 Reference
Bladder >5 servings/week RR 0.49 (0.008) Michaud et al. (1999)
Lymphoma >5 servings/week RR 0.67 (0.03) Zhang et al. (2000)
Prostate 5 servings/week OR 0.61 (0.006) Kolonel et al. (2000)
Prostate >3 servings/week OR 0.50 (0.02) Cohen et al. (2000)
Colon (men) Top 20% RR 0.76 (0.011) Voorips et al. (2000)
Colon (women) Top 20% RR 0.51 (0.004) Voorips et al. (2000)
Breast Top 25% OR 0.05 (0.01) Fowke et al. (2003)
Kidney Top 25% OR 0.53 (0.001) Yuan et al. (1998)

Source: E.H. Jeffery, Phytochemical Review, 2008.

Sulforaphane works as a potent catalyst to boost Phase 2 enzymes in the body. These detoxification enzymes trigger ongoing antioxidant action for at least 72 hours. As a result, the indirect antioxidant activity of sulforaphane lasts significantly longer than that of direct antioxidants, such as vitamins C, E and beta carotene, although it also boosts the regeneration of the active forms of these vitamins. Furthermore, three-day-old sprouts have a much higher concentration of glucoraphanin than the average mature broccoli (73 mg v. 11 mg per serving, respectively), which means one ounce of broccoli sprouts contains as much glucoraphanin as over 1.25 pounds (20 ounces) of average market-stage broccoli. However, the range of glucoraphanin varies considerably with the variety of broccoli grown, so that in market broccoli, there is at least a 15-fold range of glucoraphanin (Brown et al., J.Am. Hort. Soc. 2002). The highest concentration of glucoraphanin is found in the seed. Eating the raw, unsprouted seed could provide high amounts of sulforaphane, but seeds also contain the antimetabolite erucic acid, which is metabolized during sprouting, so eating seeds is not recommended.

Prepared extracts of either broccoli seeds or broccoli sprouts typically lose their myrosinase activity. As a result, the content of glucoraphanin may remain, but without the presence of the myrosinase, the ability to convert the bioactive sulforaphane has been lost. Based on some limited evidence from animal studies, the colonic microflora may have some myrosinase-like activity. One study suggests this may provide no more than 8% conversion.[7] A human study[8] showed there is such large interindividual variability in the population of colonic microflora in humans, such that any conversion to sulforaphane is not only limited, but also unpredictable. Other researchers have similarly found there is limited sulforaphane bioavailability in broccoli sprouts preparations in which the myrosinase has been destroyed.

The body of scientific knowledge concerning sulforaphane and broccoli sprouts continues to grow at a rapid rate; key studies with respect to broccoli sprouts are summarized below. Although research suggests a promising role for broccoli sprouts in promoting health, the research results do not permit definitive scientific conclusions on specific health benefits. At this time, the US FDA has not reached any such conclusions or authorized any claims specifically for glucoraphanin, sulforaphane or broccoli sprouts.

Summaries of some key studies:

Cancer

Carcinogen detoxification

An elevated level of hepatitis virus and environmental toxins results in a very high prevalence of liver cancer in a rural area of China. Scientists performed a clinical test to assess whether broccoli sprouts influenced the body’s abilities to detoxify carcinogens. In a single-blind, placebo-controlled trial, 100 test and 100 control subjects drank a water extract of three-day-old broccoli sprouts or a placebo daily over a period of two weeks. The broccoli sprouts group showed a significant decrease in aflatoxin-DNA adduct (a biomarker of DNA damage) levels with increasing levels of broccoli sprout consumption. The change in these biomarkers signals an enhanced detoxification (neutralization) of carcinogens from the human body, leading to a reduction in cancer risk.[9]

Tumor progression and activity

For the inhibition of breast cancer tumors, scientists reported sulforaphane and phenethyl isothiocyanate (PEITC) could prevent initial benign tumors in the lungs of mice produced by a cigarette carcinogen from developing into malignant cancer tumors. Using a model in which the animals were exposed to the carcinogens, scientists demonstrated sulforaphane inhibits the progression of the disease by causing the programmed death of the damaged cells. These findings suggest chemoprotective agents might be useful among people exposed to tobacco carcinogens, including current smokers, exsmokers or those exposed to second-hand smoke.[10]

Stomach cancer

Infection with the bacterium H. pylori can cause stomach ulcers and markedly increases the risk of developing stomach cancer. In vitro and animal experiments showed potent and selective antibacterial properties of sulforaphane and sulforaphane’s ability to selectively target the H. pylori bacteria, which are often difficult to eradicate. Also, sulforaphane was effective against H. pylori strains that had developed resistance to the typical antibiotic treatment. In a Japanese study involving patients infected with H. pylori bacteria, patients eating 100 grams (approximately 3.5 ounces) of broccoli sprouts daily for two months experienced substantially reduced measures of H. pylori infection when compared with control subjects fed a vegetable with no glucoraphanin. These results suggest sulforaphane from myrosinase-active broccoli sprouts may be responsible for the reduction of the bacteria, and a diet rich in myrosinase-active broccoli sprouts may be useful in reduction of H. pylori infection and chemoprevention against gastric cancer.[11][12]

Skin tumors

Some skin tumors form after exposure to UV radiation. Mice were exposed to damaging levels of UV light for 20 weeks in a study conducted at Johns Hopkins Medical School. Following the exposure, application of sulforaphane resulted in a 50% reduction in the number of mice with tumors. The number of tumors per mouse and the mass of tumors were also reduced. A significant aspect of the study is that administration of the chemoprotective agent was after carcinogen exposure, suggesting an ability to prevent the progression of cancer after cells are already damaged.[13][14][15][16]

Breast cancer

Work from Johns Hopkins, published in 1994, demonstrated chemoprotective effects of sulforaphane, showing its ability to reduce mammary tumor formation in rats. Scientists at Shanghai Cancer Center in China conducted a retrospective (epidemiological) study of 350 pairs of women. One of each pair had breast cancer. The other was cancer-free. The study results revealed the women who had eaten higher levels of Brassica vegetables—broccoli, cabbage, cauliflower and kale—all of which contain glucoraphanin and related compounds—were 50% less likely to be diagnosed with breast cancer. Cornblatt and colleagues (2007) have now shown that sulforaphane actually reaches breast tissue in humans within an hour or so of consumption.[17][18][19]

Prostate cancer

Human prostate cancer cells responded to treatment with sulforaphane in the form of broccoli sprout extracts, showing dramatic increases in their Phase 2 protective enzymes. Dr. James D. Brooks, Urology Department, Stanford University, suggests broccoli sprouts, a rich natural source of sulforaphane, might be appropriate for use in intervention trials in humans.[20][21][22]

Colon cancer

American Health Foundation researchers showed sulforaphane significantly inhibited the formation of colon cancer in rats. Much work has demonstrated the ability of sulforaphane and broccoli sprouts extracts to inhibit cancer in vitro in human colon cancer cells.[23][24][25]

Bladder cancer

Epidemiological evidence strongly suggested a role for cruciferous vegetables in prevention of bladder cancer. Indeed, although an analysis of 47,909 men in the Health Professionals Follow-Up Study showed virtually no correlation between cancer reduction and high consumption of fruits and vegetables overall, or yellow or green leafy vegetables specifically, it did show a statistically significant reduction among those men who consumed large amounts of cruciferous vegetables.

Several studies have suggested the bladder is one of the most responsive organs to induction of detoxification enzymes by extract, and demonstrated this was evident in human bladder cancer cells in vitro and using broccoli sprouts rich in sulforaphane potential in animal models in vivo. In addition, studies have also shown sulforaphane and broccoli sprout extract can induce apoptosis and cell cycle arrest in human bladder cancer cells in vitro, while showing the activity levels from pure sulforaphane and broccoli sprout extracts were virtually equivalent, and confirming this effect is due exclusively to the sulforaphane potential in the sprouts, not other components.[26][27][28][29]

Impact on developing or developed cancers

French researchers showed sulforaphane might do more than just activate antioxidants. Their research describes the ability of sulforaphane to cause cancer cells to self-destruct, known as apoptosis or programmed cell death. The multidimensional ability of sulforaphane both to eliminate or detoxify carcinogens and to kill cells with potential cancer-causing mutations suggests sulforaphane may have broader effects on developed cancer at various stages, as well as prevention.[30][31]

Scientists at the Amala Cancer Research Centre in India reported sulforaphane may inhibit the spread of B16F-10 melanoma cells in vitro. Mice were treated with sulforaphane either prior to, simultaneously, or following exposure to the carcinogens. Results indicated the simultaneous treatment of sulforaphane was most effective with a 95% reduction of lung tumor formation and a 94% increase in the life span of the animals. The findings suggest sulforaphane may have the ability to prevent metastasis of established cancers, rather than simply preventing development of cancers.[32]

Other health conditions

Cholesterol levels

In a pilot study, researchers at Tokyo University of Agriculture and Technology and the Japan Institute for the Control of Aging found that individuals who ate 100 grams of broccoli sprouts a day for just one week showed decreased overall levels of cholesterol, while increasing HDL or good cholesterol. The glucoraphanin in broccoli sprouts also appears to reduce the amount of oxidative stress or cell destruction caused by free radicals.[33]

High blood pressure

In laboratory studies with animals bred to have high blood pressure and are therefore at high risk for stroke, Dr. Bernhard Juurlink at the University of Saskatchewan in Saskatoon, Canada, found sulforaphane-induced Phase 2 enzymes from broccoli sprouts improved cardiovascular health by decreasing inflammation and improving heart, artery and kidney function.[34]

Macular degeneration

Johns Hopkins University scientists studied the ability of sulforaphane to protect retinal pigment epithelial cells from damage by chemical carcinogens and by ultraviolet light. These processes are the similar to the kind of damage that can lead to macular degeneration in the eye. Macular degeneration is the leading cause of blindness among the elderly.[35][36][37]

COPD

Researchers in the Department of Environmental Health Sciences and the Division of Pulmonary and Critical Care Medicine at Johns Hopkins School of Medicine reported sulforaphane increases the activity of the phase II enzyme gene Nrf2 in human lung cells, which protects cells from damage caused by toxins. Thus, presenting the possibility of therapy directed toward enhancing Nrf2-regulated antioxidants, reducing the effects of oxidative stress in COPD.[38]

Diabetes

Sulforaphane activates the Nrf2 protein, which protects cells and tissues from damage by stimulating the phase 2 enzymes, which detoxify ROS molecules. Sulforaphane reduced reactive oxygen species (ROS) molecules by 74%, thus reducing damage to blood vessel cells by hyperglycemia. High glucose levels can cause a threefold increase in ROS levels, which can damage human cells. These results suggest sulforaphane from broccoli may help reverse the damaging effects of diabetes-linked vascular disease.[39]

A collaborative group in Iran showed a myrosinase-active broccoli sprout powder had favorable effects on oxidative stress status in type 2 diabetes patients over a four-week period. The study used doses of 5 or 10 grams daily, delivering 112 and 225 micromoles sulforaphane, respectively. Positive effects were seen at both doses, although effects on lipid peroxidation were only seen at the higher dose.[40]

Availability

Broccoli sprouts are available in grocery and natural foods stores across the US and in other countries. Broccoli seeds are available for home growing. One can sprout broccoli seeds using a jar or a commercial sprouting kit. Broccoli sprout powders and capsules are also available. However, many of these products are produced from myrosinase-inactive sprout or seed extracts. It is difficult, if not impossible, for the consumer to identify which products contain both the essential precursor glucoraphanin as well as the active myrosinase enzyme. With a myrosinase-inactive product, an individual may not convert any of the glucoraphanin to sulforaphane. Because so little is known about the role of human gut microflora at this stage, reliance on the gut microflora with its wide variability could pose a significant limitation on the achievement of a biochemical response.

Sprout safety

The US Food and Drug Administration (FDA) issued suggested protocols [41] recommending commercially grown sprout seeds be soaked and sterilized with 20,000 PPM calcium hypochlorite prior to sprouting.

A study published in Nutrition Journal[42][43] quantifies the effectiveness of sprout safety programs.

References

  1. ↑ "Broccoli May Help Protect Against Repiratory Conditions Like Asthma". Nursing Today. Mar 1 2009; ISSN 1940-6975.
  2. ↑ Y Zhang, et al. (1992) A major inducer of anticarcinogenic protective enzymes from broccoli: isolation and elucidation of structure, Proc. Natl Acad. Sci., 89:2399–2403 .
  3. ↑ Angier, Natalie (1992-03-15). "Potent Chemical To Fight Cancer Seen in Broccoli - The". New York Times. Retrieved 2009-11-16.
  4. ↑ P. Talalay, et al. (1997) Broccoli sprouts: An exceptionally rich source of inducers of enzymes that protect against chemical carcinogens, Proc. Natl. Acad. Sci., 94:1036710372.
  5. ↑ Angier, Natalie (1997-09-16). "Researchers Find a Concentrated Anticancer Substance in Broccoli Sprouts - The". New York Times. Retrieved 2009-11-16.
  6. ↑ Nutrient Data Laboratory
  7. ↑ Rungapamestry et al. British Journal of Nutrition (2007), 97;644–652
  8. ↑ Kensler et al. Cancer Epidemiol Biomarkers Prev 2005;14(11)
  9. ↑ Cancer Epidemiology, Biomarkers Prevention, 2005; 14(11).
  10. ↑ Yang, YM; Jhanwar-Uniyal, M; Schwartz, J; Conaway, CC; Halicka, HD; Traganos, F; Chung, FL (2006). "N-acetylcysteine conjugate of phenethyl isothiocyanate enhances apoptosis in growth-stimulated human lung cells". Cancer Research 65 (18): 8538–8547. doi:10.1158/0008-5472.CAN-05-0236. PMID 16166335.
  11. ↑ Proc. Natl. Acad. Sci. USA, 2002, 99(11):7610–7615.
  12. ↑ Cancer Epidemiology, Biomarkers & Prevention, 2005, 14(11.2): 2754s.
  13. ↑ Cancer Epidemiology, Biomarkers & Prevention, 2005, 14(11).
  14. ↑ Cancer Letters, 2006, 240:243–252.
  15. ↑ Cancer Research, 2006, 66:8293–8296
  16. ↑ Proc. Natl. Acad. Sci., USA, 2007, 104(44):17500-5.
  17. ↑ Cancer Research, 2003, 63:3980–3986.
  18. ↑ Carcinogenesis, 2004, 25:219–227.
  19. ↑ Carcinogenesis, 2007, 28(7):1485–1490.
  20. ↑ Cancer Epidemiology, Biomarkers & Prevention, 2001, Vol. 10, pp. 949–954.
  21. ↑ Carcinogenesis, 2004, 25:83–90.
  22. ↑ BMC Cancer, 2006, 6:62.
  23. ↑ Proceedings of the American Association for Cancer Research, 2000; 41:660.
  24. ↑ J. Nutrition, 2005, 135: 1865–1872.
  25. ↑ Cancer Chemother. Pharm., 2006, 57:317–327.
  26. ↑ Journal of the National Cancer Institute, 1999, 91(7):605–613.
  27. ↑ J. Nutrition, 2004, 134:2004–2010.
  28. ↑ Mol. Cancer Ther., 2006, 5(4):935–944
  29. ↑ Cancer Research, 2008, 68(5):1593–1600.
  30. ↑ Cancer Research, 2001, 61(16): 6120–6130.
  31. ↑ Current Cancer Drug Targets, 2006, 6:135–145.
  32. ↑ Life Science, 2006; 78(26):3043–3050.
  33. ↑ Biofactors, 2004, 22:271–275.
  34. ↑ Proc. Natl. Acad. Sci. USA, 2004, 101(18):7094–7099.
  35. ↑ Proc. Natl. Acad. Sci. USA, 2001, 98(26):15221–15226.
  36. ↑ Proc. Natl. Acad. Sci. USA, 2004, 101( 28): 10446-10451.
  37. ↑ Invest. Ophthalmol. Vis. Sci., 2005, 46: 979–987.
  38. ↑ Am J Resp Crit Care Med, 2008, 178(6):592–604.
  39. ↑ Diabetes, 2008, 57:2809–2817.
  40. ↑ European Journal of Clinical Nutrition, 2011, http://www.nature.com/ejcn/journal/vaop/ncurrent/full/ejcn201159a.html.
  41. ↑ Guidance For Industry: Reducing Microbial Food Safety Hazards For Sprouted Seeds
  42. ↑ J.W. Fahey, et al. (2006) Pathogen detection, testing, and control in fresh broccoli sprouts, Nutritional Journal, retrieved Dec. 2008.
  43. ↑ "Nutrition Journal | Full text | Pathogen detection, testing, and control in fresh broccoli sprouts". Nutritionj.com. Retrieved 2009-11-16.