A new scientific paper of ours was recently published in the Journal of Alzheimer’s Disease. It proposes that therapies to block a hormone called tumor necrosis factor, or TNF, might greatly reduce the risk of developing Alzheimer’s disease (AD). My fellow researchers and I - including two of the world’s premier Alzheimer’s prevention physicians - Dr. Gary Small from UCLA, and Dr. Richard Isaacson from Cornell - hypothesized that taking inhibitors to reduce chronically elevated levels of TNF could prevent Alzheimer’s disease and improve mental health.
My team and I conducted a comprehensive analysis of all published scientific studies and concluded that TNF-blocking agents are consistently associated with a decreased risk of Alzheimer’s disease. The most potent TNF blocking agents are injectable biological drugs including etanercept (Enbrel) and adalimumab (Humira) used to treat autoimmune diseases like rheumatoid arthritis and psoriasis.
Curcumin, the active ingredient in the spice turmeric, is a natural compound sold as a supplement that also strongly reduces TNF levels in the body. Theracurmin, a highly absorbable form of curcumin, was effective in improving memory in a small randomized trial in older adults without dementia. It was also effective for reducing beta-amyloid plaques and tau tangles - the pathologic findings seen in the brains of Alzheimer’s patients.
This is so exciting because inhibiting TNF looks like the most promising approach for preventing this devastating disease. The data are remarkably consistent from observational studies, small randomized trials, and animal data. TNF inhibition is a scientifically plausible strategy that could reduce the risk of developing Alzheimer’s disease by 50 to 70 percent. I’ve been working on research and education my whole career and published 423 scientific articles; I don’t think I’ve ever been more excited about the potential importance of a new treatment strategy.
This is still a hypothesis and I hope this new scientific analysis will convince researchers and pharmaceutical companies to do large clinical trials to further investigate potential brain benefits of TNF inhibitors like Enbrel, Humira, and Theracurmin in populations at risk of Alzheimer’s.
Curcumin Background
Turmeric has been used for centuries as a flavoring for food and a traditional remedy for various ailments. Curcumin, the primary active ingredient in turmeric, was first isolated in 1815. But turmeric only contains about 5% curcumin, which in its natural form is only absorbed in extremely small amounts. It wasn’t until modern science used nanotechnology to make curcumin water-soluble and highly absorbable by the body that its real power was unlocked.
Challenges Presented by Curcumin
The biggest challenge to unleashing the full potential of curcumin has been bioavailability. While curcumin extract has been available for decades, in its generic form most of what is ingested is passed quickly out of the body and very little is absorbed into the bloodstream. It is no wonder that some research studies using this generic form showed minimal or insignificant results. However, with the development of formulations that increase absorption and bioavailability, research results are now revealing curcumin as a game-changer in the fight against inflammation. Cardiotabs Curcumin contains Theracurmin®, a nanoparticulate formulation that forms a stabilized dispersion in water which enables the sub-micron particles to be absorbed into the bloodstream through the membranes lining the small intestine.
Mental Health Studies with Curcumin:
A randomized, double-blind, placebo-controlled study that included 40 non-demented adults (age range 51 to 84 years) assigned study participants to either Theracurmin (90 mg twice daily - same formulation and concentration as in Cardiotabs Curcumin) or matching placebo. In this 18-month trial, participants receiving Theracurmin showed significantly better memory and attention (Fig. 3) Measures of mood demonstrated an effect of curcumin on symptoms of depression, but no significant between-group differences were seen.
In this trial, positron emission tomography (PET) scans of the brain were performed on 30 of the research participants (15 in the Theracurmin group and 15 in the placebo group) before and after treatment. These PET scans suggested that the behavioral and cognitive benefits conferred by the curcumin were associated with lower levels of Aβ plaque and tau accumulation in the hypothalamus and possibly the amygdala (between-group differences showing a trend) - brain regions associated with mood and memory. Moreover, changes in amygdala binding were significantly correlated with changes in Beck Depression Inventory scores in the curcumin group. Theracurmin has also been demonstrated to improve cognitive function in a mouse model of dementia. In that study, the higher doses of curcumin augmented brain function in mice. The authors correlated the cognitive improvement with enhanced anti-oxidative activity and increased synaptic function.
A recent meta-analysis focused on randomized controlled trials evaluating curcumin’s effect on cognition. This study comprising a total of 289 subjects showed that curcumin improved scores of cognitive function and mood among non-demented older adults, but showed no benefit among patients who already had Alzheimer’s disease. To date, the cumulative RCT evidence of curcumin for improving cognition involves a modest number of participants, thus larger outcome studies will be needed to clarify its safety and efficacy.
In Good Health,
James O'Keefe, MD
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