Oxidative Stress in Alzheimer’s Disease: Why Did Antioxidant Therapy Fail?

Table 1

Summary of clinical trials with antioxidants to prevent or treat MCI and AD.

Compounds	Subject population	Intervention	References
Vitamin C and Vitamin E	23 patients with probable AD stably taking cholinesterase inhibitors.	Daily supplementation; Vitamin C (1000 mg) and Vitamin E (400 IU) for one year.	[84]
Vitamin C, Vitamin E, 𝛼-lipoic acid, CoQ10	78 subjects with mild to moderate AD	Vitamin C (500 mg/day), Vitamin E (800 IU/day), 𝛼-lipoic acid (900 mg/day) or CoQ10 (400 mg, 3 times/day) or placebo for 16 weeks.	[85]
Selenium and Vitamin E	30 geriatric patients	Administration of sodium selenate (8 mg) daily in two doses, organic selenium (45 𝜇g/day) and Vitamin E (400 mg) in two daily doses, or placebo for 1 year	[86]
Selenium or Vitamin E	10.000 male subjects between 60 and 90 years old with no neurological or psychiatric illness	(Ongoing study, NCT00040378); Daily doses of 400 IU Vitamin E or 200 𝜇g selenomethionine or placebo.	[87]
Curcumin	34 patients with probable or possible AD	Patients received 1 or 4 g of curcumin or placebo, orally once daily for 6 months.	[92]
Curcumin	36 subjects with mild to moderate AD.	Administration of curcumin C3 complex, 2 or 4 g/day for 48 weeks. A control group were receiving placebo for 24 weeks followed by either 2 or 4 g curcumin per day for another 24 weeks.	[93]
Curcumin	38 healthy middle-aged people of 40–60 years old.	Lipidated curcumin (80 mg/day) or placebo were given for 4 weeks.	[94]
Ginko biloba	3069 elderly people above 72 years without dementia symptoms.	Two daily doses of G.biloba extract EGb 761 (120 mg) or placebo with a median follow-up time of 6.1 years.	[96]
Ginko biloba	2854 subjects, 70 years or older, with spontaneously reported memory complaints to primary care physician.	Two daily doses of G.biloba extract EGb 761 (120 mg) or placebo with a follow-up time of 5 years.	[97]
Memory XL (folic acid, Vitamin B12, Vitamin E, acetyl-L-carnitine, SAM, NAC)	115 participants of both genders, 18–86 years with no signs of dementia or clinical memory difficulties	One daily dose of two Memory XL tablets containing folic acid (400 𝜇g), Vitamin B12 (6 𝜇g), Vitamin E (30 IU), SAM (400 mg), NAC (600 mg), and acetyl-L-carnitine (500 mg) for 2 weeks or 3 months followed by an open-label phase for 2 weeks or 3 months.	[98]
Ebenone	536 subjects above 50 years with diagnosed probable AD.	One-year treatment with daily doses of 120, 240, or 360 mg Idebenone or placebo.	[101]
Estrogen	120 women diagnosed with probable AD. All women had hysterectomies performed.	A single daily dose of 0.625 or 1.25 mg of Premarin (conjugated equine estrogens) or placebo were given for 1 year followed by a 3-month single blind placebo washout phase.	[103]
Colostrinin	33 patients with mild to moderately severe AD.	Colostrinin treatment containing 100 𝜇g PRP complex every other day for 3 weeks followed by a 2-week break. This was repeated for 16–24 months.	[107]
Colostrinin	105 patients with mild to moderate AD.	Treatment with 100 𝜇g Colostrinin or placebo for three weeks followed by a 2-week break. This was repeated for 15 weeks followed by a 15-week open-label phase.	[108]