Optimized Curcumin: Brain Health Breakthrough

by Chris D. Meletis, ND

The three-pound human brain is comprised of 100 billion neurons with branches that connect to more than 100 trillion connections in the brain. This mind-boggling “neuron forest” is the very foundation of connectivity to our inside and outside world. When things begin to go wrong with this network, the system starts to run slower, access to memory files become sluggish and eventually begin to fail. Just like with the office or home computer, routine maintenance prevents fragmentation of one’s hard drive, decreased CPU speed and protection against corruption of vital files.

Let’s begin our discussion of the pursuit of brain preservation with a simple foundational definition. Age-related memory loss includes a decrease in cognitive function that impacts intellectual abilities, which can interfere with daily life. Age-related memory loss has many different causes and manifestations. The focus of this article will be to understand cognitive decline from a broad perspective as well as discuss current research findings and ultimately present a new form of a well-known botanical that can significantly support cognitive health with age.

Age-Related Cognitive Decline

Millions of Americans are living with some variation of cognitive decline. Several variants of cognitive decline can affect brain cell health, leading to age-related memory loss and problems with thinking eroding away the very foundation of one’s social, work and personal life pursuits. Genetics are thought to play a role; however, as it has been stated, “genetics may predispose, yet diet and lifestyle help pull the trigger” for many health concerns affecting humans. The bottom line is that everything you did the hour before you read this article either supported your brain or hindered it.

Disruptors of optimal brain function: Tau tangles and beta amyloid plaques

The Web of Protein Deposits and Tangles

The two primary physical changes in structure that impact cognitive function with age in many individuals are protein deposits and tangles. Protein deposits may build up between nerve cells and are comprised of fragments sometimes called beta-amyloid. In turn the tangles are twisted fibers called “tau” proteins that arise from oxidative stress to neurons. Tangles (neurofibrillary tangles) are aggregates of the microtubule-associated protein tau, which has become hyperphosphorylated and accumulates inside the cells themselves. Put simply, with age-associated memory impairment and cognitive decline, it is believed that physiological changes to the brain may precipitate the cognitive effects experienced, altering conductivity and communication between neurons.¹ The brain is less able to partake in rapid and efficient nerve transmission that allows for “our brain’s connectivity” through the forest of neurons that forms the very genesis of all brain functions and is the repository of memories, thoughts and feelings.¹ In addition, this affects recall of names and words, even faces, making certain activities more challenging as we age.

Natural Solutions for Normal Brain Function

There are many approaches employed to help maintain normal brain performance; these must always start with getting enough sleep, eating a health-promoting diet, staying properly hydrated and avoiding toxins that can affect neurological health, including medications that lead to either the increased risk of nutrient depletion or an increased metabolic need for one or more nutrients in order to sustain healthy brain cell functions.

When it comes to the use of dietary supplements to support healthy brain function, there are numerous natural substances worthy of discussion. Allow me to share some of the latest research from the peer-reviewed scientific literature that I incorporate in my clinical practice. The current state of scientific understanding of the progression of most brain changes points to the need to maintain a balanced inflammatory response, decrease oxidative damage, minimize the unwanted accumulation of proteins and tangles, which ultimately can interfere with neural communication, plus decrease exposures to environmental toxins and to accommodate unique genetic susceptibilities.

In my clinical practice, I often harness the benefits of highly bioavailable curcumin with EGCG from green tea, vitamin D, niacinamide and inflammation balancers, such as the enzyme serrapeptase, to support brain wellness. Furthermore, vitamin D and curcumin have documented synergy when it comes to sustaining a healthy brain.

Curcumin

Turmeric (Curcuma longa) has been used for centuries in India and Southeast Asia, where by chance the prevalence of age-related cognitive concerns is a small fraction of what is found in the westernized world. To assert that this is the only contributing factor would overstate the case; however, without question, the scientific literature has documented clearly that this widely used spice possesses potent inflammatory-balancing and antioxidant properties. Yet, the same published literature has pointed out that this amazing botanical holds great promise to maintain the health of the brain; however, curcumin lacks the ability to be readily absorbed in significant amounts from dietary sources and does not produce adequate, sustained blood levels for optimal impact. The great news for clinicians and health savvy patients is that the diligent efforts of UCLA researchers have resolved this issue with a patented approach that is now available for those who demand the latest advances in the optimal absorption of the curcumin provided by this powerful botanical. This research “breakthrough” produces a many fold increase in the bioavailability of curcumin. This special form of bioavailable turmeric is called Longvida®, a unique form of curcumin shown to not only enter the blood stream in quantities that have the potential to produce clinically positive results and also crosses the blood-brain barrier unlike any other known form of curcumin on the market today. As I share with my patients, something may look good on paper but if it does not get to the cellular level the health-promoting mission is not accomplished. (see Table 1)^2-3

In a study conducted on mice, it was discovered that curcumin’s natural inflammatory-response balancing and antioxidant properties may reduce both oxidative effects and changes in the brain that frequently affect cognition.⁴ More specifically, curcumin has been shown to reduce the incidence of unwanted protein deposits in brain tissue by slowing the deposition of certain precursor proteins within the brain, which is hypothesized to play a role in the progression of some forms of age-related cognitive decline.⁵

Furthermore studies have suggested that Longvida does indeed enhance the normal removal of certain proteins while also boosting the body’s antioxidant defenses, addressing the development of neurofibrillary tangles. Additionally, Longvida exerts a powerful inflammatory-balancing effect even in the brain.^6-9

These mechanisms described above along with the antioxidant and inflammation-balancing properties of the special Curcuma longa extract that has been optimized for bioavailability holds great promise. As you read further the potential impact of curcumin extends to its synergy with vitamin D, which I will explore later in this article.

Green Tea

The extract of green tea, EGCG, has been shown to possess neuroprotective properties, according to research on mice bred to have age-related cognitive decline. This protection reaches far beyond antioxidant properties and has been hypothesized to arise also from the modulation of certain enzymatic processes in the brain. In fact, varying levels of activity of the enzymes alpha-, beta and gamma-secretase affect cognitive function. Compounds that enhance alpha- while down regulating beta- and gamma- were shown to have positive effects in the study. The researchers’ findings are promising as their quote reflects: “Compared with untreated mutant… mice, treatment with EGCG enhanced memory function and brain alpha-secretase activity but reduced brain beta- and gamma-secretase activities. These studies suggest that EGCG may be a beneficial agent,” in supporting sustained brain health in the face of age-related cognitive deficiencies.¹⁰

It also appears that “EGCG treatment fortified the cellular GSH (reduced glutathione) pool through elevated mRNA expression of gamma-glutamylcysteine ligase (GCL), the rate limiting enzyme in glutathione biosynthesis. It was hypothesized that EGCG may have another potential role in [supporting brain health] by augmenting cellular antioxidant defense capacity and attenuating… oxidative and/or nitrosative cell death.”¹¹

Vitamin D

There remains a need for much more research when it comes to age-related memory loss and vitamin D, yet a 2010 review of the literature reported: “Vitamin D deficiency has recently been linked to [age-related memory loss] through several mechanisms. Current clinical trials are investigating a possible link between low vitamin D levels and low cognitive test scores.”¹² It is not surprising to those of us who follow the emerging research on vitamin D that the “sunshine” vitamin may impact cognition-related genetic factors. In another 2010 research report, great detail was offered as to the role of vitamin D and immune modulation as it relates to the brain.

Aging and cognitive decline, “have been related to defective functions of both T cells and macrophages leading to an imbalanced inflammatory response. In some people, ‘inflammaging’ may be associated with an increase of incompetent memory T cells and inflammatory cytokines produced by macrophages.¹³

The same investigators go on to explain that there are two types of macrophages associated with cognitive decline: I and II. A summary of their statement once again shows the importance in most cases of the power of synergy of combined natural approaches: Natural immune supporting approaches using vitamin D3 and curcuminoids have been developed in macrophages of a subset of individuals with cognitive decline. People with age-related cognitive decline possess two types of macrophages: a majority has “Type I”, which are improved by curcuminoids and vitamin D3; whereas a minority has “Type II” responding positively to vitamin D3 but not to curcuminoids.¹³

Also reported in the 2010 literature is a powerful study, which presents the finding that vitamin D insufficiency and deficiency were associated with all-cause age-related cognitive declines and suboptimal brain and vascular health. The results of this research suggest a potential vascular supportive role of vitamin D.¹⁴

Vitamin B3

UC Irvine scientists studied the impact of nicotinamide (a form of vitamin B3) that has been shown to lower levels of the phosphorylated proteins that leads to the development of tangles, affecting brain health.¹⁴ The researchers reported that nicotinamide can help with loss of cognition in mice. An additional benefit was that nicotinamide increased the strength of microtubules, the structural scaffolding within brain cells along which information travels. These are the very structures that support neuronal (brain cell) integrity and function, which are important for optimal cognition.¹⁵

As the authors reported in their abstract, the results presented suggest that nicotinamide has potential as a novel, safe, and inexpensive natural option for brain health, either alone or in combination with other therapies.¹⁵

Serrapeptase

To sustain brain health, the overall inflammatory response must be kept in balance in the body to mitigate oxidative stress to neurons and support continuous cerebral blood flow. Thus, the use of systemic proteolytic enzymes, such as serrapeptase, may confer a degree of additional proteolytic and inflammatory-response balancing support. Serrapeptase has been shown, in research trials, to possess the desired positive effects on inflammatory balance needed to support normal inflammation control mechanisms.¹⁶ In my clinical practice I use serrapeptase to help support healthy blood flow that is essential for the proper delivery of oxygen and nutrients throughout the body, especially to the brain, which has a high oxygen requirement in order to sustain health and peak performance.

Conclusion

There are definitive nutritional, diet and lifestyle requirements for helping maintain optimal brain performance. We know that among the risk factors, oxidative damage ranks high, which is self evident since with each heartbeat some of the 60,000 miles of arteries within the body carry about 20 to 25 percent of your blood to your brain. “Inflammaging” is another very real factor that must be addressed to keep the brain functioning at peak capacity. A new supplement called Dejavida™, which contains Longvida, green tea, vitamin D, nicotinamide and proteolytic enzymes such as serrapeptase, can address all of these factors, creating a broad, secure foundation for optimal brain health. Longvida is also available as a single-ingredient supplement.

References

1. Grady CL, Furey ML, Pietrini P, Horwitz B, Rapoport SI. Altered brain functional connectivity and impaired short-term memory in Alzheimer’s disease. Brain. 2001;124(4):739-56.

2. Frautschy SA, et al. Efficacy of curcumin formulations in relation to systemic availability in the brain and different blood compartments in neuroinflammatory and AD models, at the 39th Annual Meeting of the Society of Neuroscience, Chicago, October 2009.

3. Gota VS, Maru GB, Soni TG, Gandhi TR, Kochar N, Agarwal MG. Safety and pharmacokinetics of a solid lipid curcumin particle formulation in osteosarcoma patients and healthy volunteers. J. Agric Food Chem 2010. 58(4):2095

4. Lim GP, Chu T, Yang F, Beech W, Frautschy SA, Cole GM. The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J Neurosci. 2001 Nov 1;21(21):8370-7.

5. Zhang C, Browne A, Child d, Tanzi RE. Curcumin decreases amyloid-beta peptide levels by attenuating the maturation of amyloid-beta precursor protein. J Biol Chem. 2010 Sep 10:285(37):28472-80.

6. Begum AN, Jones MR, Lim GP, et al. Curcumin Structure-Function, Bioavailability, and Efficacy in Models of Neuroinflammation and Alzheimer’s Disease. J Pharmacol Exper Thera. 2008;326(1):196-208.

7. Frautschy, SA. 38th Annual Meeting of the Society of Neuroscience , Washington DC, November 15, 2008.

8. Goel A, Kunnumakkara AB, Aggarwal BB. Biochem Pharmacol. 2008 Feb 15;75(4):787-809.

9. Gota VS, Maru GB, Soni TG, Gandhi TR, Kochar N, Agarwal MG. J Ag Food Chem Submitted 2009.

10. Lee JW, Lee YK, Ban JO, Ha TY, Yun YP, Han SB, Oh KW, Hong JT.Green tea (-)-epigallocatechin-3-gallate inhibits beta-amyloid-induced cognitive dysfunction through modification of secretase activity via inhibition of ERK and NF-kappaB pathways in mice. J Nutr. 2009 Oct;139(10):1987-93.

11. Kim CY, Lee C, Park GH, Jang JH. Neuroprotective effect of epigallocatechin-3-gallate against beta-amyloid-induced oxidative and nitrosative cell death via augmentation of antioxidant defense capacity. as an enhanced supplement for huperzine A to treat Alzheimer’s disease. Arch Pharm Res. 2009 Jun;32(6):869-81.

12. Pogge E.Vitamin D and Alzheimer’s disease: is there a link? Consult Pharm. 2010 Jul;25(7):440-50.

13. Fiala M. Re-balancing of inflammation and abeta immunity as a therapeutic for Alzheimer’s disease-view from the bedside. CNS Neurol Disord Drug Targets. 2010 Apr;9(2):192-6.

14. Buell JS, Dawson-Hughes B, Scott TM, Weiner DE, Dallal GE, Qui WQ, Bergethon P, Rosenberg IH, Folstein MF, Patz S, Bhadelia RA, Tucker KL. 25-Hydroxyvitamin D, dementia, and cerebrovascular pathology in elders receiving home services. Neurology 2010 Jan 5;74(1):18-26.

15. Green KN, Steffan JS, Martinez-Coria H, Sun X, Schreiber SS, Thompson LM, LaFerla FM Nicotinamide Restores Cognition in Alzheimer’s Disease Transgenic Mice via a Mechanism Involving Sirtuin Inhibition and Selective Reduction of Thr231-Phosphotau. Journal of Neuroscience. 2008;28(45):11500-11510.

16. Viswanatha Swamy AH, Patil PA. Effect of some clinically used proteolytic enzymes on inflammation in rats. Indian J Pharm Sci. 2008 Jan;70(1):114-7.