Brain fog: whether you’re experiencing it yourself or interacting with someone who is, it can be a frightening symptom. More formally known as cognitive dysfunction or mild cognitive impairment, brain fog is characterized by forgetfulness, trouble focusing, mental fatigue, sudden mind blanks, difficulty finding the right words when communicating, and a tendency toward “spacing out.” Cognitive dysfunction is perhaps most common in patients with neurodegenerative conditions like Alzheimer’s and Parkinson’s disease, but it has also been observed in patients with inflammatory conditions like celiac disease as well as cardiovascular conditions like postural tachycardia syndrome. Additionally, brain fog is noted as a side effect of certain medications, including carbamazepine and phenobarbital, which are used to treat patients who experience epileptic seizures.
Although cognitive dysfunction itself remains poorly understood within the research community, studies have shown that it is associated with aging, stress, reduced metabolic function, declines in neural plasticity, inflammation, and oxidative stress. Due to the latter two associations, some scientists have hypothesized that natural supplements with anti-inflammatory and antioxidant properties, like curcumin, may benefit patients who experience brain fog or cognitive dysfunction. So far, the evidence from the few clinical studies that have been conducted is inconclusive, but promising research in animal models suggests that larger, more comprehensive clinical trials are warranted in the future.
Recent Mechanistic Evidence for a Relationship between Curcumin and Cognitive Dysfunction
When justifying the use of a supplement like curcumin for cognitive dysfunction, it can be helpful to have mechanistic evidence supporting a relationship through which the supplement may modulate the symptom. In 2017, a breakthrough research study in the journal Oxidative Medicine and Cellular Longevity provided just that. A group of researchers in Romania conducted an experiment in rat models of neurodegenerative disorders and found that curcumin can reverse cognitive dysfunction by reducing oxidative stress in the brain and downregulating a specific cellular signaling pathway: the ERK 1/2 / NF-kB signaling pathway, which is involved in the inflammatory response.
For this study, the researchers simulated cognitive dysfunction by treating the rats with diazepam, a drug that is known to have comparable effects on the brain. After 28 days of curcumin administration (150 mg per kg of body weight), they measured the impact on the rat models through a combination of behavioral and biochemical tests. The rats treated with curcumin performed significantly better on a maze test that examines spontaneous alternation behavior, which is commonly used in the field as a measure of spatial learning and working memory. Additionally, biochemical studies showed that biomarkers of oxidative stress were lower in both the blood and the hippocampus (a part of the brain associated with memory) and that the ERK 1/2 / NF-kB signaling pathway was downregulated in both the hippocampus and the frontal lobe of the brain. These findings suggest that the curcumin supplements had both anti-oxidation and anti-inflammatory effects, and these processes were mediating the observed reductions in behavioral symptoms of cognitive dysfunction.
Curcumin for Drug-Induced Cognitive Dysfunction: More Evidence from Rat Models
A similar study from 2010 highlighted the potential benefits of curcumin supplements using rat models. However, this study focused on the potential benefits for patients who experience cognitive dysfunction because they use medications like phenobarbital and carbamazepine, which are commonly used to treat epilepsy. Research indicates that the brain fog experienced by these patients may be the result of oxidative damage caused by the free radicals generated by these drugs in the brain. Therefore, an antioxidant supplement like curcumin could be a viable intervention option.
For the 21-day study period, the researchers treated some of the rats with phenobarbital and/or carbamazepine alone and some of the rats with curcumin alongside the anti-epileptic drugs. Like the Romanian researchers who conducted the above-described study, they used a maze test to measure spontaneous alternation behaviors, as well as a passive avoidance paradigm to show that curcumin had a significant effect on learning and memory-related behaviors in the rats. At the same time, their biochemical tests showed that while the biomarkers in the blood of the rats increased upon treatment with the anti-epileptic drugs, the increase was significantly smaller in the rats that were simultaneously treated with curcumin. Therefore, the authors concluded that curcumin can be a safe and effective side-by-side therapy for patients who are experiencing cognitive dysfunction as the result of pharmacological drugs like carbamazepine and phenobarbital.
Future Opportunities for Clinical Studies on Curcumin and Cognitive Disorders
While these in vivo animal studies present exciting evidence supporting the use of curcumin for cognitive dysfunction, the clinical studies on the topic have been characterized as “disappointing” by researchers in the field. According to the most recent systematic review paper, which was conducted by a research group at the University of Rome in 2016, it is not yet possible to draw conclusions from the available evidence. The reviewers acknowledged that both in vitro and in vivo animal studies indicate that curcumin can be effective for treating patients with cognitive dysfunction, but with only five small-scale clinical studies to analyze—none of which produced particularly strong evidence-—their only conclusion was that more research was warranted in the future.
In 2014, a similar systematic review out of the University of Pavia had the same outcome. After examining three published studies and several ongoing clinical trials on using curcumin for cognitive dysfunction, the researchers found that the scant data was not enough to draw a conclusion. Importantly, they also suggested that the reasons the data were insufficient were that several of the studies were poorly designed and many involved the use of curcumin formulations with poor bioavailability. Not only do these insights highlight areas for improvement in future research studies, but they also indicate that patients and practitioners today should not necessarily take the disappointing results as a sign that solid clinical evidence on the benefits of curcumin for cognitive dysfunction will never emerge. Rather, their characterization of the data indicates that curcumin may indeed be an appropriate therapy for certain individuals when its effectiveness is assessed through more thorough, rigorous methods. Their comment also reminds patients who are considering curcumin supplements that they are likely to see the best results from products that are specifically designed to optimize bioavailability.
Because researchers are still hopeful about the potential for using curcumin to treat cognitive dysfunction, clinical trials are ongoing. For example, recruitment efforts are currently underway for a clinical study on the potential effects of curcumin supplements on cognitive dysfunction in older adults who have been diagnosed with dementia. The premise of this research is that curcumin may have neuroprotective benefits, so it may one day be considered as a preventive option that can help stave off age-related cognitive dysfunction. Patients, practitioners, and researchers alike are looking forward to the results from studies like this one, which may finally verify the in vitro and in vivo animal studies at the clinical level. It will be exciting to see where the findings lead in the future.
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