Applications & Opportunities for Free Curcumin in Cognitive Health

According to the CDC, or Centers for Disease Control and Prevention, “More than 16 million adults 18 years and older in the United States are living with cognitive impairment”.1 This statement highlights a simple fact: cognitive health isn’t solely the concern of seniors and the elderly; people of all ages can experience cognitive impairment.

The Alzheimer’s Association (www.alz.org) emphasizes this point in its 2019 Alzheimer’s Disease Facts and Figures report: “Alzheimer’s disease [AD] is thought to begin 20 years or more before symptoms arise, with small changes in the brain that are unnoticeable to the person affected.”2 An article published in Alzheimer’s & Dementia further notes: “An estimated 40% to 60% of individuals aged 58 years and older with MCI [mild cognitive impairment] have underlying AD pathology.”3 While age is a contributing factor, cognitive impairment is not an inevitable factor of aging1; however, people of all demographics may find the aim for maintaining a dynamic mind daunting.

Putting Cognitive Decline in Perspective

The World Health Organization (WHO) recognizes some individuals may have an increased genetic or medical risk of cognitive decline; however, lifestyle factors play a bigger role in the overall population, specifically stating: “Dementia is not a natural or inevitable consequence of ageing.”4

Physical activity, a nutritious diet, and social/intellectual stimulation are all essential to cognitive well-being.5 In recent years, research suggests natural botanicals (as dietary supplements) may help. Many have shown support for neural health, oxidative stress, amyloid beta fibrillation, carbonyl stress, and protein glycation.6 Of these, curcumin, has demonstrated positive impacts across four major biomarkers associated with cognitive health.

Curcumin and the Brain

Curcumin, an active compound in turmeric, has long been recognized for its potent antioxidant and anti-inflammatory properties. In studies, curcumin has reduced levels of inflammatory molecules such as tumor necrosis factor alpha (TNF-a), interleukin-9 (IL-8)c-reactive protein (CRP), and
cyclooxygenase-2 (COX-2)7-9 Much of its ability to mediate neuroinflammation results from the way it impacts a number of major neural health biomarkers, such as oxidative stress, advanced glycation end products (AGEs), neuroplasticity, and amyloid plaques.

Oxidative Stress

In the brain, oxidative stress (an imbalance between free radicals and antioxidants) has been linked to many cognitive ailments, accelerated aging, and other neurological disorders. Free radicals (ROS – reactive oxygen species) can damage DNA, cause inflammation, and kill brain cells.10 Consuming antioxidant-rich foods and supplements bolsters the body’s antioxidant levels, making curcumin and its high antioxidant profile a potential way to mediate the effects of oxidative stress.11

Further, antioxidants are known to stimulate nitric oxide production.13 Researchers at The Ohio State University observed that optimized curcumin increased plasma nitric oxide levels providing “a variety of health promoting effects in healthy middle-aged people.”12 More recently, Santos-Parker et al reported that “in healthy middle-aged and older adults, 12 weeks of optimized curcumin supplementation improve[d] resistance artery endothelial function by increasing nitric oxide bioavailability and reducing oxidative stress.”14

Research also shows that curcumin decreases lipid peroxidation, a factor linked to accelerated aging and cognitive decline. Additionally, it stimulates production of superoxide dismutase (SOD) glutathione peroxidase (GPx), and other antioxidants produced by the body15 used for toxin removal, neutralizing free radicals, and protecting against cellular damage.

Advanced Glycation End-products (AGEs)

When proteins and sugars combine in the blood stream (called glycation), Advanced glycation end products (AGEs) are formed. AGEs are linked to many degenerative diseases and pose a clear threat to cognitive health.16 Human exposure to AGEs primarily comes from two sources:

  1. Foods that have been exposed to high temperatures such as grilling, frying, or toasting and have undergone some degree of caramelization during cooking via the Maillard reaction.17
  2. Glycation18

University of Rhode Island researchers explain the impact of AGEs to cognitive health: “AGEs bind to the transmembrane receptor for AGEs (RAGE), upregulate RAGE expression, and activate RAGE-mediated neuronal dysfunction and neuron damages. RAGE then inhibits the transportation of beta amyloid (Aß) across the blood brain barrier (BBB). Therefore, the activation of RAGE by AGEs can cause Aß accumulation in the brain. During glycation and AGE formation, ROS and reactive carbonyl species (RCS) are generated as byproducts which, in turn, promote AGE formation and cause neurotoxicity.”6

In addition to neuron damage, AGEs also increase beta amyloid levels in the brain, intensifying oxidative stress. A review of numerous studies on curcumin and AGEs published in Critical Reviews in Food Science and Nutrition concluded that “curcumin can inhibit AGEs formation and AGEs-induced disturbances.”19

Neuroplasticity

The human brain has an incredible ability to reorganize itself in response to injury, disease, and other neuronal changes; this is called neuroplasticity.20 This ability requires proper neuron function, synapse firing, and neurogenesis.

Kim SJ et al has found curcumin appears to “stimulate developmental and adult hippocampal neurogenesis, and a biological activity that may enhance neural plasticity and repair.”21 Goozee et al suggests that this is evidence that curcumin has “potentially
beneficial effects on neuroplasticity,” specifically in “modulating synaptic plasticity.”33

Additionally, the findings of a ground-breaking study examining the cognitive impact of curcumin showed that curcumin restored brain-derived neurotrophic factor (BDNF), enhanced postsynaptic reactivity, and reduced cell death25 while another study reported curcumin helps regulate serotonin.23 Each of these factors is essential to the brain’s response to injury.

Amyloid Plaques

It is well established that build-up of amyloid beta protein fragments in the brain form hard, insoluble plaques that cause neurofibrillary tangles, increased oxidative stress, and induce neuroinflammation.6 Researchers observed that curcumin bound to amyloid plaques, protecting brain cells by blocking aggregation and fibril formation related to neuroinflammation and
cell death.24 In clinical studies, patients given curcumin have shown lower amyloid beta protein levels than control groups, suggesting significant protection against this hallmark associated with cognitive impairment and decline.12

More recently, research confirmed curcumin’s plaque-binding capabilities, suggesting use not only as a neuroprotective agent but also as an imaging tool for the identification of deposits in both the brain and retina. This would allow for early detection of cognitive decline up to 20 years prior to the onset of symptoms; a dilemma that has plagued for a millennium.25,26

Overcoming Curcumin’s Bioavailability Problem

A recent review of preclinical and clinical studies of curcumin noted: “Curcumin’s molecular structure and its ability to cross the blood-brain barrier [BBB] provide a promising avenue for neuroprotection.”27 Yet, curcumin’s bioavailability has been a problem. The human body quickly metabolizes orally administered curcumin, limiting its potential health benefits.28 Mary S. Easton of the UCLA Alzheimer Translation Center explains the problem:

“There is a lot of confusion about curcumin bioavailability versus absorption. Curcumin is absorbed, but not necessarily bioavailable. Further GI and liver glucuronidation, or sulfation, “tag[s] curcumin” which interferes with bioavailability in some tissues and leads to its rapid removal by the kidneys. Unlike tagged curcumin, free curcumin readily crossed the blood brain barrier and is relatively stable.”29

Free curcumin, then, is the bioactive form that delivers the benefits observed.

Optimized Curcumin for Cognitive Health

Scientists at the University of California – Los Angeles (UCLA) investigating solutions for cognitive health sought to find a curcumin product that effectively overcame these bioavailability issues. Not finding one that successfully delivered free curcumin across the blood brain barrier, they developed Longvida® Optimized Curcumin® featuring Solid Lipid Curcumin Particle Technology™ (SLCP™).

The absorption-promoting technology of Longvida overcomes curcumin’s bioavailability problem by: protecting the curcumin against harsh stomach acids, dissolving in the gastrointestinal tract at the point of absorption, and delivering the free form of curcumin into the bloodstream where it can then circulate systemically and eventually cross the blood brain barrier.

When tested for absorption alongside three other commercially available curcumin extracts, Longvida resulted in the highest brain concentrations of free curcumin.25 Since inception, Longvida has been the focus of nearly 30 clinical trials with others underway. In one such study, Swinburne University researchers reported both acute (1-hr post dose) and chronic (after 1 month) improvements on cognition, mood, and blood biomarkers in healthy older adults.31

Mounting evidence in support of cognitive applications for curcumin, along with promising results in their initial study has led Swinburne researchers to take a second look at chronic cognitive benefits. Recently published results “confirm that Longvida® Optimized Curcumin® improves aspects of mood and working memory in a healthy older cohort. The pattern of results is consistent with improvements in hippocampal function and may hold promise for alleviating cognitive decline in some populations.”32

Curcumin’s Potential for Better Cognitive Outcomes

Today, scientists, medical experts, and healthcare professionals, as well as many consumers, understand keeping cognitive health strong into old age relies on taking active steps earlier in life, long before any symptoms manifest. As Goozee K., et al noted: “The fresh approach of targeting early AD pathology (by treating healthy, pre-clinical and mild cognitive impairment-stage cohorts) combined with new curcumin formulations that increase bioavailability is renewing optimism concerning curcumin-based therapy.”33 The wealth of clinical substantiation supporting supplementation with optimized curcumin for overall well-being and the promotion of cognitive health continues to support all demographics alike in mediating the effects of aging and cognitive decline.

Curcumin, specifically a highly bioavailable one like that of Longvida® Optimized Curcumin® offers a lot of promise for anyone looking to support, promote, and maintain memory, mood, focus, and overall cognitive health.

By: Leisha Jenkins

References

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