Phytonutrients - Indole-3-Carbinol

Question 1

Indole-3-carbinol (I3C):

Answer 1

• 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 2

Food sources:

Answer 2

• Cruciferous vegs —broccoli, kale, cauliflower.
• Broccoli sprouts are between 20 and 50 times more abundant in I3C than normal broccoli.
  Indole= aromatic heterocyclic compound
  Carbinol = methanol

Question 3

Functions:

Answer 3

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

Question 4

Oestrogen modulation:

Answer 4

Functions:
* 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).
Therapeutic uses:
* Conditions associated with oestrogen dominance, e.g. fibroids and endometriosis.
* Oestrogen sensitive cancers (e.g. breast).
* Benign prostatic hypertrophy.

Question 5

Cervical intraepithelial neoplasia (CIN)
(Cervical dysplasia):

Answer 5

Therapeutic uses:
* I3C modulates important risk factors for CIN (and in turn, cervical cancer) including elevated oestrogen and heightened inflammation (prev. slide).
* Reduces activity of the pro-inflammatory NF-kB,  cytokines that drive cellular changes.
* Dosage: 200 to 400 mg daily promote CIN regression.
cervical dysplasia = precancerous cervix cells

Question 6

Breast and prostate
cancer:

Answer 6

Therapeutic uses:
* 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 7

Dosage:

Answer 7

• 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 8

Safety:

Answer 8

• 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 9

Interactions:

Answer 9

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

Question 10

Supporting Oestrogen Clearance

Answer 10

Other ways of supporting oestrogen clearance:
* Optimise soluble and insoluble fibre intake (e.g. whole grains, legumes, nuts / seeds) to bind and excrete oestrogen via bowel.
* Optimise the gut microbiome (e.g. probiotics / prebiotics) to prevent the de-conjugation of excreted oestrogens.
* Support methylation with folate, B6, B12 rich foods.
* Avoid dairy and oestrogen-mimicking agents, e.g. BPA (in plastic, cans), dioxins (e.g. pesticides), phthalates (e.g. in cosmetics). Also avoid smoking, alcohol and caffeine to prevent over-burdening the liver —preventing it from detoxifying oestrogen.