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Using B Vitamins in Clinical Practice: Optimizing Patient Outcomes

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Urolithin A & Neurodegeneration

iStock-1472634406The journal Alzheimer’s & Dementia recently published results suggesting that urolithin A may have potential benefit for reducing degeneration as a consequence of Alzheimer’s disease (AD) through multiple mechanisms, at least in an animal model. This adds to a growing body of evidence that urolithin A has a critically important role in supporting mitochondrial function, especially the decline in function associated with neurodegeneration and aging, primarily by stimulating mitophagy, the removal of damaged mitochondria. This includes randomized and controlled trial data in humans indicating a boost in mitochondrial function, one that is associated with a number of benefits including increases in aerobic endurance and reductions in inflammation.

Urolithin A is a metabolite of ellagitannins (found in pomegranates, berries, walnuts, etc.) that is produced by the gut microbiota. This most recent study found that long-term use of urolithin A improved learning, memory, and olfaction in transgenic mice (an AD mouse model), and reduced biomarkers of disease pathology, including amyloid beta and tau pathologies. Multiple mechanisms of action were suggested by this study, but perhaps the most prominent was the stimulation of lysosomal function by regulating cathepsin Z (Ctsz) protein. Lysosomes are recyclers of dysfunctional cells (& mitochondria), with multiple functions related to cellular homeostasis. Cathepsins appear to be generally upregulated in brains affected by neurodegenerative diseases such as AD and Huntington’s disease but were normalized by urolithin A in this study. Urolithin A also had other effects associated with mitochondrial function, including an upregulation of sirtuins (SIRT1 and SIRT3) and a reduction in neuroinflammation. No human data related to neurodegenerative disease yet exists, though doses of 500-1000 mg per day of urolithin A were associated with exercise improvements in the controlled trial mentioned above.

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