Kliniken & Institute … Kliniken Chirurgische Klinik… General, Visceral and… Research Pankreasforschung Sektion… Molecular OncoSurgery … For Patients

What effect does sulforaphane have against tumor stem cells?

Tumor stem cell marker in fluorescent staining of a tissue of a ductal pancreatic cancer

We were the first worldwide which have shown in laboratory experiment on mice, that sulforaphane attack the particularly aggressive tumor stem cells and thereby makes them sensitive to chemotherapy. We suspect that tumor stem cells – which survive conventional chemo- and radiotherapy, are responsible for the emergence and spread of cancer. Since the normal tumor cells are more sensitive, they die off during treatment and the tumor often shrinks, especially during the early courses of therapy.

However, since the resistant tumor stem cells remain, they can form the tumor again. We can even see that the tumor stem cells are enriched, during repeating chemotherapy treatment and therefore the tumor becomes resistant after several cycles. Based on our laboratory data a sulforphan rich diet counteracts the enrichment of tumor stem cells and could therefore slow down the tumor growth and make chemotherapy more effective.

Broccoli seeds, which begin to germinate after 24 h in water

How can sulforaphane been taken?

To our knowledge, Sulforaphane can’t be bought as a pure substance in a drug, but may be absorbed through the diet in therapeutically effective doses. Cruciferous plants contain Sulforaphane and similar effective mustard oils. They include broccoli and cauliflower as well as all other types of cabbage, e.g. sauerkraut, as well as watercress, nasturtium, arugula, radish, horseradish, rutabaga with turnip greens, rape, mustard and capers (see above).

Meanwhile many manufacturers make the broccoli seeds or freeze-dried broccoli sprouts available packed as a powder or in capsules. Please note that we do not test these products and therefore cannot give any information. In addition, as a university we are not allowed to advertise for a specific product. Please decide and compare yourself the prices and the ingredients.

 

 

 

 

Broccolit seeds, according to an analysis, 2 tps contain 80 - 100 mg sulforaphane

In which dose should sulforaphane be taken?

 

Based on our experience in the laboratory tests we recommend a human dose of 0.36 mg of sulforaphane per kg body weight. This is equivalent to 25.2 mg sulforaphane daily for a person weighing 70 kg. Ongoing pilot studies on patients use 90 mg sulforaphane daily.

 

Unfortunately, there are no clinical trials that show which dose is best suited to inhibit the growth of an aggressive growing pancreatic cancer in humans. Epidemiological studies indicate that a salutary dose of sulforaphane and related mustard oils can be supplied through the regular diet that includes plenty of vegetables from the cruciferous family.

 

 

 

 

 

Freshly pressed juice made of oranges, broccoli and apples

What must be considered by the intake of suforaphan through cabbage and broccoli sprouts?

 

 

Heat destroys sulforaphane substantially, so you should just slightly braise / steam / or fry the broccoli and consume it while still crisp. Sulforaphane is released from the plant cell into the cooking water, i.e. if broccoli is boiled, rather then discarding the cooking water, it should be used to prepare a sauce or soup. The effect of microwaves on the ingredients of broccoli is controversial. A very good source of sulforaphane may be broccoli seeds or broccoli sprouts, as these may contain, depending on variety and growing conditions, 10 to 100 times the sulforaphane progenitor glucoraphan.

Sprout containers

Self-Breeding of sprouts for herb curd, lettuce and bread topping

For the self-cultivation of sprouts, a simple clay saucer or sprout glass is suitable. More decorative is a sprout hedgehog, which for example the Company Römertopf offers. You don’t have to limit yourself to broccoli when cultivating sprouts, but rather use all members of crucifers. Warning: should sprouts spoil during growth in the clay container, wash the clay pot with a soft nylon brush and clean water and disinfect the container through heating in the oven for 45 minutes at 200°C.

Side effects of broccoli sprouts

Crucifers plants produce sharp or bitter-tasting mustard oils to ward off pests. Therefore, it can be assumed that toxic effects occur at very high dosages. With normal consumption of cruciferous vegetables, no side effects have been observed so far. From livestock breeding, we know that rapeseed cake, which contains too many mustard oils, makes the cattle sick. Broccoli seeds or sprouts shouldn’t be overdosed when consumed. So far we only know that a daily intake of 90mg of sulforaphane over several weeks, had no side effects in patients. A relatively harmless side effect of cabbage and of broccoli sprout are flatulence, which can smell like sulfur, as this is part of the mustard oils.

Cruciferous vegetables contain a lot of fiber and therefore have a positive effect on digestion. In addition, sulforaphane act indirectly antioxidant. Known antioxidants are vitamins and currently it is discussed critically whether such substances weaken the effect of chemotherapy and radiotherapy. There is no clear data on this. In our in vivo studies we find no weakening, but rather a reinforcement of chemotherapy: different cytostatic eliminate tumor xenografts better is sulforaphane is given simultaneously.

These laboratory tests are promising, but cannot be transferred seamlessly to the situation of the patient – again lengthy and costly patient studies are required.

 

Broccoli cream soup with sour cream made ​​from fermented soya Soyananda - after cooking broccoli or broccoli sprout seeds can be scattered as an additional Sulforaphanquelle .
Cabbage cake with carraway seeds - eat to heated cabbage radish, arugula or cress so myrosinase is supplied. hrough this enzyme, the precursors of the mustard oils are converted into the active form. It is present in fresh cruciferous vegetables , but breaks down when heated . Most mustard oils are inactive precursor in vegetables
Pumpernickel bread topped with avocado cream, humus and horseradish cream cheese, garnished with broccoli sprouts, radishes, cress and radish sprouts.

Have you been advised to give up cabbage? Nevertheless you still can benefit from the valuable ingredients

You have been advised to refrain from legumes and cabbage, to avoid flatulence in a restricted digestion after a Whipple- or other operation of the digestive tract. Unfortunately, you don’t come to benefit the valuable ingredients. The flatulent fiber is important for the bowels health. I recommend you to strike a tolerable balance. Here are some tips:


Broccoli and cauliflower are easily digested, if just eat the florets, but not the stem.

-   Pointed cabbage doesn’t cause flatulence.

-   Cook all types of cabbage long to make them more digestible – simultaneously eat to boiled cabbage fresh cruciferous (radish, watercress, arugula, mustard, rapeseed oil), so that the inactive precursors are activated.

-    Prepare cabbage with caraway or fennel, which relaxes the intestinal muscle and makes flatulence more tolerable.

-    Smaller portions throughout the day are easier to digest.

These foods contain proven substances against tumor stem cells.

Other bioactive substances against tumor stem cells

Meanwhile we were able to prove that yet another substance from broccoli, the polyphenol quercetin, attacks pancreatic cancer stem cells and thus complements the effect of sulforaphane. Quercetin is found in many other fruits and vegetables, including citrus fruits, apples, onions, berries, parsley, sage, grapes, olive oil and in green and black tea. Likewise triptolide, a substance that is used in traditional Chinese medicine, could attack tumor stem cells. A joint mechanism across the sulforaphane, quercetin and triptolide to attack tumor stem cells is their anti-inflammatory action via the factor NF-kB. Aspirin works similarly, which was developed from the salicylic acid of the willow bark. Our recent research data show that aspirin actually attack very effective the tumor stem cells of pancreatic cancer. Research teams worldwide have now discovered that many more plants contain ingredients against tumor stem cells. So far, it is proved in legumes (genistein from soybeans), turmeric (curcumin, for example in curry), tomatoes (lycopene), grapes, berries, plums and peanuts (resveratrol, for example in red wine), black pepper (Piperine), green tea (EGCG), fish, egg yolk and cod-liver oil (vitamin D). For vitamin D it is important to note, that only 10 percent are absorbed through food and the remaining 90 percent are formed through the sunlight on the skin. Certainly there will be more nutritional contents with an effect against tumor stem cells be found in the near future, however, intensive research is still necessary.

In general: To receive a wide range of an active ingredient mixture against tumor stem cells, a balanced, most vegetarian diet with a high proportion of raw food, is important. Daily outdoor exercise for at least 30 minutes is important to store vitamin D, a healthy way to alleviate stress and ensure a good mood.

Kitchen appliances for healthy eating: mixer for fresh smoothies, grater for crudite´s, steamer for the gentle preparation of vegetables and a juicer for fresh fruit and vegetable juices.

How can the immune system be strengthened even further?

You’ve done a lot for your immune system, if you take in a freshly in a juicer or mixer prepared vegetable juice or a green smoothie, and in return waive the widespread breakfast with coffee, bread, cake, butter, sausage, egg and jam.

For the vegetable juice use for example, apples, pears, red beets, carrots, parsnips, broccoli, turnip and other cruciferous vegetables.

For the smoothie even collected wild herbs (e.g. stinging nettle, young dandelion, clover, buckhorn, buttercup, young sorrel, ground ivy, daisies, garlic mustard, yarrow, balsam flowers, leaves and fruit from strawberries, blackberries, raspberries…), broccoli sprout, salad, linseed oil, walnut oil and avocado.

Many variations and mixtures between vegetable juices and smoothies are possible. When preparing smoothies with self-collected wild herbs you kill two birds with one stone: you exercise in fresh air (vitamin D, stress compensation, anti-depressive) and your body gets concentrated bioactive plant compounds, vitamins and minerals to strengthen the body’s defense.

It is indicated that a high carbohydrate diet and red meat promote tumorgenesis and their progress.

What you should avoid

Based on our own research data and recommendations from leading institutions for cancer, lifestyle and diet (e.g. AICR) we recommend the following for prevention and to avoid progression of cancer:

 

Avoid:

-   Overweight, eating too much.

-   Sugar and white flour products, red meat and sausage.

-   Pollutants (e.g. alcohol, nicotine, to much coffee, salt, grilled, roasted, fried, corned beef, or highly heated food)

-   Environmental toxins (e.g. cosmetics, cleaning products, radiation, contaminated building materials in the home).

-   Negative stress, grief, concerns, discontent, and depression.

 

Eat daily:

-    Fruit that is not sweet, salad, raw vegetables, legumes (peas, beans, lentils, chickpeas, soya), cruciferous vegetables (broccoli, cauliflower, cabbage, arugula salad, cress, radishes, horseradish, rutabaga, turnip greens, canola e.g. as rapeseed oil, mustard…), onions, leeks, whole grains, pepper, paprika, tomato, turmeric. The vegetables should be cooked – best steamed or short crispy roasted, so the plant substances remain active.

 

Eat rarely or not at all:

Meat, sausage, cheese, milk products, sweet fruit, noodles, potatoes, white rice, white bread, cake and sweets.

 

If you loose much weight due to cancer, pay attention to an adequate calorie intake:

Very nutritious are nuts, avocado and healthy vegetables oils with a lot of omega 3 fatty acids (in particular fresh linseed-, walnut-, false flex- and rapeseed oil), cashew or almond butter are very tasty. You’ll get high quality and fresh oil from oil mills. Avoid calorie intake from sugar – also the fats should be mainly from herbal substances and unsaturated.

 

Answers to common questions:

Potato and rice starch split quickly into sugar by the body and let the blood sugar rise rapidly. The less potatoes are processed, the lower the glycemic index. In French Fries, chips and instant mashed potatoes the blood sugar rises faster then in boiled potatoes.

Sweet fruit is easily recognized on the sweet taste. Sweet fruits include, for example, bananas and ripe fruit – also sweet grapes.

More information can be found in the literature on low carb diets or by a nutritionist.

 

More tips can be found in our Flyer

Patient studies with Broccoli sprouts

Capsules containing broccoli sprout grain. In the Heidelberger Powder study patients receive 15 capsules (90mg sulforaphane) daily concomitant to chemotherapy

 

Other researchers in malignant tumors of the breast and prostate confirmed now our laboratory data. Our laboratory tests are supported by epidemiological studies in which dietary habits of large populations respective to the risk of cancer or the progression of a cancer were evaluated.

In a nutritional study for patients with prostate cancer, the researchers found that the frequent consumption of broccoli or cauliflower (3 to 5 servings a week), reduced the scattering of the tumor in some patients by 50%. A cancer preventive effect of cruciferous vegetables has been widely demonstrated in other studies. Numerous studies show that sulforaphane and his relatives help against inflammation, bacterial infections and viruses and inhibit tumor growth. Likewise recent data point to a positive effect on the intestinal flora by broccoli and cauliflower. This is of great importance, as a healthy intestinal flora is the basis for a healthy immune system and strong body’s defense against tumor cells.

 

 

Recurrent Prostate Cancer: At OHSU Knight Cancer Institute in Portland (Oregon, USA), a pilot study was conducted to investigate the effect of sulforaphane from broccoli sprouts extract in 20 patients with a recurrent prostate cancer (ClinicalTrials.gov Identifier: NCT01228084). For 20 weeks daily, sulforaphane was administered in doses of 200 μmol (88 mg), in four capsules of 50 μmol. This study has been completed and the preliminary studies show:

 

  • in 25% of patients the PSA level dropped more then 50% without the patient showing any serious side effects.
  • in 90% of patients the PSA level did not double.
  • there have been no serious side effects (grade 3 toxicity).
  • Half-life of sulforaphane in the blood: 2 to 5,5 hours

Although it is only a pilot study, this data raise hope and must be confirmed now with a larger number of patients. Detailed study results are not yet published, preliminary data can be found here:

 

Skin cancer prevention:  A now ongoing pilot study, which is conducted at the University of Pittsburgh (USA), examines the effectiveness of broccoli sprouts in atypical nevi, which are precursor lesions of malignant melanoma (ClinicalTrials.gov Identifier NCT01568996). Eighteen individuals receive a capsule with sulforaphane from broccoli sprout extract in the concentrations of 50 μmol (22 mg), 100 μmol (44 mg) or 200 μmol (88 mg) for 28 days orally. Study results are not available yet, the current status can be found here.

 

Bladder cancer: In another at the moment conducted pilot study at the Rosswell Park Cancer Institute in New York (USA), the effect of sulforaphane from broccoli sprouts extract is examined on the growth of urothelia carcinoma of the bladder. (NLM Identifier: NCT01108003). After the resection of the carcinoma the patients receive 200 μmol (88 mg) sulforaphane for 14 days daily. Study results are not available  yet, the current status can be found here. 

 

 

Pancreatic cancer: A study with broccoli sprouts packed in capsules as an adjuvant therapy of advanced pancreatic cancer started in December 2013 at the Surgical University Clinic Heidelberg (ClinicalTrials.gov identifier: NCT01879878). Forty patients with advanced pancreatic cancer who are undergoing surgery in Heidelberg are included. Half of the patients receive a chemotherapy AND broccoli sprouts with 90 mg sulforaphane daily, the other half gets only chemotherapy. The effect of the quality of life, tumor marker, tumor growth and survival is evaluated. The performance of this pilot study was supported by the Foundation of Surgery and a donation by Mr. Deiters (Deiters & Florin).

Interim report 9.4.2018:

Unfortunately, results of the broccoli patient study are not available yet - there was just an interim result, which has shown that too much data is missing to make credible statements. The problem was that there were too many external patients who we couldn't follow up from Heidelberg and who did not report back as agreed. Another big problem was that the supervising study doctor changed the clinic and therfore the leader was missing. The few existing data from tumor markers speak so far for the broccoli sprouts, albeit beyond a statistical significance. It is encouraging that there were no serious side effects, except partially disgust from the cabbage flavor, which is of course particularly bad in existing digestive disorder. Many patients were also bothered that they did not know if they were in the placebo or drug group. because broccoli sprouts are freely available, some patients have discontinued the study and taken broccoli sprouts on their own. In order to complete the study, funds for a study nurse and the procurement of broccoli sprouts must first be raised again. So far there is no sponsor.

 

 

 

 

 


Additional Information can be found here.

 

Do you need medical consultation, treatment or a second opinion?

We are researchers and will gladly inform you about new scientific findings. Since we are no medical doctors, we are not allowed to give any medical recommendations. If you wish a medical consultation or a second opinion, following locations are available:

European Pancreas Center at the University Clinic Heidelberg

(Pancreas, Bile Duct Cancer)

Appointments: 06221 56-7807 / Fax 06221-56 5075

Information: 0700 726 27 327


pankreas@med.uni-heidelberg.de

 

 

Oncology consultation (liver-, stomach, colon cancer) at the University Clinic Heidelberg

For patients with cancer (liver, stomach, intestines) an indisciplinary consultation takes place five days a week, with colleagues from the medical oncology. Patients get cared for together, in whom a multimodal treatment concept is planned. Partly the oncological consultation takes place at the National Center for Tumor Diseases (NCT) Heidelberg.

Appointments: 06221/56-6252

 

National Center for Tumor Diseases (NCT) Heidelberg

At the National Center for Tumor Diseases NCT, supported by the University Clinic Heidelberg, the German Cancer Research Center, the German Cancer Aid, tumors are treated at the current state of scientific research. An essential element of the treatment is the interdisciplinary tumor board, where specialists decide what therapy is best for the patient. The NCT also established itself as a center for a second opinion.

Appointments can be made through:

http://www.nct-heidelberg.de/fuer-patienten/terminvereinbarung.html

NCT-Homepage:

http://www.nct-heidelberg.de/de/patienten/index.php

Pointed cabbage, plus bell pepper stuffed with whole grain cooked in tomato sauce with soya mince

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