Probiotic and selenium co-supplementation, and the effects on clinical, metabolic and genetic status in Alzheimer's disease: A randomized, double-blind, controlled trial

Combined probiotic and selenium supplementation may improve Alzheimer's disease (AD) by correcting metabolic abnormalities, and attenuating inflammation and oxidative stress. This study aimed to determine the effects of probiotic and selenium co-supplementation on cognitive function and metabolic status among patients with AD.This randomized, double-blind, controlled clinical trial was conducted among 79 patients with AD. Patients were randomly assigned to receive either selenium (200 μg/day) plus probiotic containing Lactobacillus acidophilus, Bifidobacterium bifidum, and Bifidobacterium longum (2 × 109 CFU/day each) (n = 27), selenium (200 μg/day) (n = 26) or placebo (n = 26) for 12 weeks.Selenium supplementation, compared with the placebo, significantly reduced serum high sensitivity C-reactive protein (hs-CRP) (P < 0.001), insulin (P = 0.001), homeostasis model of assessment-insulin resistance (HOMA-IR) (P = 0.002), LDL-cholesterol (P = 0.04) and total-/HDL-cholesterol ratio (P = 0.004), and significantly increased total glutathione (GSH) (P = 0.001) and the quantitative insulin sensitivity check index (QUICKI) (P = 0.01). Compared with only selenium and placebo, probiotic and selenium co-supplementation resulted in a significant increase in mini-mental state examination score (+1.5 ± 1.3 vs. +0.5 ± 1.2 and -0.2 ± 1.1, respectively, P < 0.001). Probiotic plus selenium intake resulted in a significant reduction in hs-CRP (-1.6 ± 1.4 vs. -0.8 ± 1.0 and +0.1 ± 0.5 mg/L, respectively, P < 0.001), and a significant increase in total antioxidant capacity (+89.4 ± 129.6 vs. +20.0 ± 62.5 and -0.7 ± 27.2 mmol/L, respectively, P = 0.001) and GSH (+122.8 ± 136.5 vs. +102.2 ± 135.2 and +1.5 ± 53.2 μmol/L, respectively, P = 0.001) compared with only selenium and placebo. In addition, subjects who received probiotic plus selenium supplements had significantly lower insulin levels (-2.1 ± 2.5 vs. -1.0 ± 1.3 and +0.7 ± 2.0 μIU/mL, respectively, P < 0.001), HOMA-IR (-0.5 ± 0.6 vs. -0.2 ± 0.3 and +0.1 ± 0.4, respectively, P < 0.001), and higher QUICKI (+0.01 ± 0.01 vs. +0.005 ± 0.007 and -0.002 ± 0.01, respectively, P < 0.006) compared with only selenium and placebo. Additionally, probiotic and selenium co-supplementation resulted in a significant reduction in serum triglycerides (-17.9 ± 26.1 vs. -3.5 ± 33.9 and +0.3 ± 9.3 mg/dL, respectively, P = 0.02), VLDL- (-3.6 ± 5.2 vs. -0.7 ± 6.8 and +0.05 ± 1.8 mg/dL, respectively, P = 0.02), LDL- (-8.8 ± 17.8 vs. -8.1 ± 19.2 and +2.7 ± 19.0 mg/dL, respectively, P = 0.04) and total-/HDL-cholesterol (-0.3 ± 0.7 vs. -0.4 ± 0.9 and +0.3 ± 0.6, respectively, P = 0.005) compared with only selenium and placebo.Overall, we found that probiotic and selenium co-supplementation for 12 weeks to patients with AD improved cognitive function and some metabolic profiles. This study was registered in the Iranian website (www.irct.ir) for registration of clinical trials (http://www.irct.ir: IRCT20170612034497N5).