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Table 2 Clinical studies with curcumin and other natural compounds

From: Epigenetic changes induced by curcumin and other natural compounds

Disease

Dose/frequency

Patients

End point modulation

References

Curcumin

 Safety trials

  Phase 1

2,000 mg/day

10

Piperine enhanced bioavailability by 2,000%

Shoba et al. (1998)

  Phase 1

500–12,000 mg/day × 90 days

25

Histologic improvement of precancerous lesions

Cheng et al. (2001)

  Phase 1

500–12,000 mg/day

24

Safe, well-tolerated even at 12 g/day

Lao et al. (2006)

 Efficacy trials

  Alzheimer’s disease

1 g once daily, 4 g once daily

36

–

Baum et al. (2008)

  Atherosclerosis

10 mg; 2×/day × 28 days

12

Lowered LDL and ApoB, increased HDL and ApoA

Ramirez Bosca et al. (2000)

  Cadaveric renal transplantation

480 mg; 1–2/day × 30 days

43

Improved renal function, reduced neurotoxicity

Shoskes et al. (2005)

  Cardiovascular disease

500 mg/day × 7 days

10

Decreased serum lipid peroxidase (33%), increased HDL cholesterol (29%), decreased total serum cholesterol (12%)

Soni and Kuttan (1992)

  Chronic anterior uveitis

375 mg; 3×/day × 84 days

32

86% decrease in chronic anterior uveitis

Lal et al. (1999)

  Crohn’s disease

360 mg; 3/day × 30 days; 4 for 60 days

5

Improved symptoms

Holt et al. (2005)

  CRC

36–180 mg/day × 120 days

15

Lowered GST

Sharma et al. (2001)

  CRC

450–3,600 mg/day × 120 days

15

Lowered inducible serum PGE2 levels

Sharma et al. (2004)

  CRC

450–3,600 mg/day × 7 days

12

Decreased M1G DNA adducts

Garcea et al. (2005)

  Colon cancer

10 g (n = 6) and 12 g (n = 6)

12

Pharmacokinetics

Vareed et al. (2008)

  CRC, ACF

2 g or 4 g/day for 30 days

44

A significant 40% reduction in ACF number occurred with the 4 g dose (P < 0.005), whereas ACF were not reduced in the 2 g group

Carroll et al. (2011)

  External cancerous

1% ointment for several months

62

Reduction in smell in 90% patients, reduction of itching in all cases, dry lesions in 70% patients, reduction in lesion size and pain in 10% patients

Kuttan et al. (1987)

  FAP

480 mg; 3/day × 180 days

5

Decrease in the number of polyps (60.4%), decrease in the size of polyps (50.9%)

Cruz-Correa et al. (2006)

  H. pylori infection

300 mg/day × 7 days

25

Significant improvement of dyspeptic symptoms

Di Mario et al. (2007)

  HIV

625 mg; 4×/day × 56 days

40

Well tolerated

James (1996)

  IIOP

375 mg; 3×/day × 180–660 days

8

Four patients recovered completely; one patient showed decrease in swelling, no recurrence

Lal et al. (2000)

  Gall bladder function

20 mg, single dose

12

Decreased gall bladder volume (29%)

Rasyid and Lelo (1999)

  Gall bladder function

20–80 mg, single dose

12

Decreased gall bladder volume (72%)

Rasyid et al. (2002)

  ICF

–

1,010

Better MMSE score

Ng et al. (2006)

  IBS

72–144 mg/day × 56 days

207

Reduced symptoms

Bundy et al. (2004)

  Liver metastasis

450–3,600 mg/day × 7 day

12

Low bioavailability

Garcea et al. (2004)

  Pancreatic cancer

8 g by mouth daily every 2 months

25

Oral curcumin is well tolerated and, despite its limited absorption, has biological activity in some patients with pancreatic cancer

Dhillon et al. (2008)

  Pancreatic cancer

8 g

21

Safe and feasible in patients with pancreatic cancer

Kanai et al. (2010)

  Postoperative inflammation

400 mg; 3×/day × 5 days

46

Decrease in inflammation

Satoskar et al. (1986)

  PIN

–

24

–

Rafailov et al. (2007)

  Psoriasis

1% curcumin gel

40

Decreased PhK2, TRR3, parakeratosis, and density of epidermal CD8+ T cells

Heng et al. (2000)

  Psoriasis

4.5 g/d

18

The response rate was low

Kurd et al. (2008)

  Rheumatoid arthritis

1,200 mg/day × 14 days

18

Improved symptoms

Deodhar et al. (1980)

  Tropical pancreatitis

500 mg/day × 42 days

20

Reduction in the erythrocyte MDA levels, increased erythrocyte GSH levels

Durgaprasad and Pai (2005)

  Ulcerative proctitis

550 mg; 2–3/day × 60 days

5

Improved symptoms

Holt et al. (2005)

  Ulcerative colitis

2,000 mg/day × 180 days

89

Low recurrence; improved symptoms

Hanai et al. (2006)

EGCG

 Safety trials

 Phase 1

200, 400, 600, and 800 mg

20

Systemic availability

Chow et al. (2001)

 Efficacy trials

  OHT and OAG

200 mg/day for 3 months

36

Influenced inner retinal function in eyes with early to moderately advanced glaucomatous

Falsini et al. (2009)

  EE and fat oxidation

Catechins: 493.8–684 mg

15

Small acute effects on EE and fat oxidation

Gregersen et al. (2009)

  Influenza infection

Catechins: 200 μg/mL 3/day for 3 months

124

Influenza infection was significantly lowered

Yamada et al. (2006)

  Inhalation of MRSA

3.7 mg/mL 3/day for 7 days

72

Reduced the MRSA count in sputum

Yamada et al. (2006)

Resveratrol

 Safety trial

  Pharmaco-kinetics

0.5, 1, 2.5, or 5 g daily for 29 days

40

2.5 and 5 g doses caused mild to moderate gastrointestinal symptoms

Brown et al. (2010)

  Phase 1

0.5, 1, 2.5, or 5 g

10

High systemic levels of resveratrol conjugate metabolites

Boocock et al. (2007)

 Efficacy trials

  Cerebral blood flow

250 and 500 mg

22

Modulated cerebral blood flow variables

Kennedy et al. (2010)

  Drug- and carcinogen-metabolizing enzymes

1 g of resveratrol once daily for 4 weeks

42

Modulated enzyme systems involved in carcinogen activation and detoxification

Chow et al. (2010)

  CRC

8 daily doses of 0.5 or 1 g

20

Reduced tumor cell proliferation by 5%

Patel et al. (2010)

Genistein

 Safety trial

  Phase 1

600 mg/day for 84 days

18

Safe and well tolerated

Pop et al. (2008)

  Pharmaco-kinetics

2, 4, 8, or 16 mg/kg

24

Minimal clinical toxicity

Bloedon et al. (2002)

 Efficacy trials

  Endometrial hyperplasia

54 mg/day for 6 months

56

Useful for the management of endometrial hyperplasia

Bitto et al. (2010)

  Prostate cancer

450 mg daily for 6 months

53

Did not lower PSA levels

deVere White et al. (2010)

  CV risk

54 mg/day for 24 months

198

Favorable effects on both glycemic control and some cardiovascular risk markers

Atteritano et al. (2007)

  Coronary heart disease

71 mg

33

Neither harmful nor beneficial

Webb et al. (2008)

  Bone metabolism

–

208

Protective against bone loss

Kritz-Silverstein and Goodman-Gruen (2002)

  Asthma

–

1,033

Better lung function

Smith et al. (2004)

  1. ACF Aberrant crypt foci, CRC colorectal cancer, CV cardiovascular, EE energy expenditure, EGCG epigallocatechin, FAP familial adenomatous polyposis, GSH glutathione, GST glutathione S-transferase, HDL high-density lipoprotein, HIV human immunodeficiency virus, IBS irritable bowel syndrome, ICF improved cognitive function, IIOP idiopathic inflammatory orbital pseudotumors, LDL low-density lipoprotein, MDA malondialdehyde, MMSE mini-mental state examination, MRSA methicillin-resistant Staphylococcus aureus, OAG open-angle glaucoma, OHT ocular hyper-damage tension, PGE2 prostaglandin E2, PhK2 phosphorylase kinase 2, PIN prostatic intraepithelial neoplasia, PSA prostate-specific antigen, TRR3 transferrin receptor 3