Isothiocyanates and Indole-3-Carbinol

Question 1

Isothiocyanates

Answer 1

Isothiocyanates (ITCs) are biologically active breakdown products of the sulphur rich compounds, glucosinolates
* Each glucosinolate forms a different ITC when hydrolysed e.g.
– Glucoraphanin forms sulforaphane.
– Sinigrin forms allyl isothiocyanate.

Question 2

Isothiocyanates - Food Sources

Answer 2

• Cruciferous vegetables (e.g. Brussel sprouts, broccoli, cabbage, kale, ).
• Horseradish.
• Mustard greens.

Question 3

Isothiocyanates: Bioavailability

Answer 3

• Myrosinase is the enzyme that catalyses the hydrolysis of glucosinolates to form ITCs.
• It is stored in another compartment of the cell and is only released when the cell wall is damaged e.g. by chopping, slicing, chewing.
• Heat / cooking inactivates myrosinase, though gut bacteria are able to hydrolyse glucosinolates to some extent.
• Cooking, particularly boiling or stir frying also
  decreases glucosinolate content. Steaming is a better cooking method.

Question 4

Isothiocyanates: Functions

Answer 4

Antioxidant / Anti-inflammatory
Liver detoxification
Anti-cancer

Question 5

Isothiocyanates: Antioxidant / Anti-inflammatory

Answer 5

• Switches on genes coding for cellular antioxidant defence mechanisms.
• Increase tissue glutathione levels.
• Inhibit pro inflammatory signaling molecules and
  cytokines.

Question 6

Isothiocyanates: Antioxidant / Anti-inflammatory

Answer 6

• Reduce the risk of chronic diseases including: diabetes, heart disease, cancer, neurodegenerative
  disease, autoimmune conditions.

Question 7

Isothiocyanates: Liver detoxification

Answer 7

• Potent inducer of phase II detoxification enzymes; down regulates phase I enzymes.

Question 8

Isothiocyanates: Anti-cancer

Answer 8

Chronic inflammation and ↑ oxidation, along with poor detoxification pathways are key factors in cancer development.
* ITCs have been shown to:
‒ Protect DNA from carcinogenic damage and
reduce cell proliferation by regulating apoptosis.
‒ Inhibit angiogenesis and tumour metastasis.
‒ Enhance glutathione S transferase phase II
enzymes involved in the detoxification of carcinogens.
‒ ‒↓ the secretion of inflammatory signalling molecules and decrease binding of the pro inflammatory NF kB.

Question 9

Isothiocyanates: Dosage

Answer 9

• Glucosinolates are present in relatively high concentrations in commonly consumed portions of cruciferous vegetables.
• For example ½ cup of raw broccoli can provide more than 25 mg of total glucosinolates
• Consumption of at least five weekly servings
  (80 g per serve) of cruciferous vegetables has been associated with significant reductions in cancer risk.
• There are no specific recommendations for
  supplement dosages.

Question 10

Isothiocyanates: Safety

Answer 10

• Dietary sources are generally regarded as safe.
• Safety of purified isothiocyanates / supplements
  during pregnancy and lactation have not been established.
• Some glucosinolates degrade to goitrin and thiocyanate, compounds referred to as goitrogens . They decrease the thyroids uptake of iodine. In those with low thyroid function ensure good intake of iodine and limit brassica vegetables to 1‒2 serves / day.

Question 11

Isothiocyanates: Interactions

Answer 11

• ITCs are not known to interact with any
  pharmaceutical drugs.

Question 12

Indole-3-Carbinol

Answer 12

Indole-3-carbinol (I3C) is derived from the breakdown of glucobrassicin ; a glucosinolate found in cruciferous vegetables:
* In the acidic environment of the stomach, I3C
forms a number of biologically active indole products, most notably, 3,3’ diindolylmethane (DIM). I3C primarily acts via its major metabolite, DIM
* I3C and DIM have the same physiological effects.

Question 13

Indole-3-Carbinol: Food sources

Answer 13

• Cruciferous vegs broccoli, kale, cauliflower.
• Broccoli sprouts are between 20 and 50 times
  more abundant in I3C than normal broccoli.

Question 14

Indole-3-Carbinol: Functions

Answer 14

Oestrogen modulation
Cervical intraepithelial neoplasia ( CIN) (Cervical
dysplasia)
Breast and prostate cancer

Question 15

Indole-3-Carbinol: Oestrogen modulation

Answer 15

• Selectively binds to oestrogen receptors acting as an oestrogen antagonist.
• Influences phase I CYP enzymes to ↑ the conversion of oestradiol to the weaker / protective form of oestrogen (2 hydroxyestrone) over 4 and 16
  hydroxyestrone (carcinogenic potential).
• Inhibits aromatase, reducing conversion of testosterone to oestrogen.
  Dosage: up to 50 g of broccoli sprouts / day (or supplement 200 to 800 mg daily

Question 16

Indole-3-Carbinol: Oestrogen modulation - Therapeutic doses

Answer 16

• Conditions associated with oestrogen dominance,
  e.g. fibroids and endometriosis.
• Oestrogen sensitive cancers (e.g. breast cancer)
• Benign prostatic hypertrophy.

Question 17

Indole-3-Carbinol: Cervical intraepithelial neoplasia (CIN) (Cervical dysplasia)

Answer 17

• I3C modulates important risk factors for CIN (and in turn, cervical cancer) including elevated oestrogen and heightened inflammation
• Reduces activity of the pro inflammatory NFkB, decreases cytokines that drive cellular changes.
• Dosage: 200 to 400 mg daily promote CIN regression.

Question 18

Indole-3-Carbinol: Breast and prostate cancer

Answer 18

• Regulates oestrogen and androgen levels / activity.
• Induces cell cycle arrest, activates tumour
  suppressor genes, reduces angiogenesis and supports DNA repair.
• Antagonises the effects of dihydrotestosterone (DHT)
• Dosage: 200 to 800 mg daily

Question 19

Indole-3-Carbinol: Dosage

Answer 19

• Dietary levels commonly range from 20‒120 mg daily.
• One head of cabbage contains approximately 1200 mg of I3C.
• General therapeutic dosage range: 200-800 mg daily.

Question 20

Indole-3-Carbinol: Safety

Answer 20

• No serious adverse events reported. The most common side effects are mild gastrointestinal symptoms and headaches.
• Safety in pregnancy and lactation has not been established.

Question 21

Indole-3-Carbinol: Interactions

Answer 21

• No drug interactions in humans reported. Theoretically may interact with drugs metabolised by CYP1A2. Significance unknown.