Neurosupportive effects of Longvida® Optimized Curcumin

Neurosupportive effects of Longvida®Optimized Curcumin. . . shown in new research

By Blake Ebersole,
Technical Director at Verdure Sciences.

Alzheimer’s disease (AD)
involves a complex pathological
cascade which is triggered by the
accumulation of amyloid-beta and
tau peptide aggregates. Multiple
age-related causes contribute to
peptide aggregation. These causes
include aberrant cell signaling, lipid
dysregulation, inflammatory and
oxidative stress, and the normal
ageing process. Together, these
result in large-scale neuron death

A New Paradigm for Healthy Brain Ageing
Based on the current understanding of neurodegenerative
diseases, a new paradigm for healthy brain ageing and
neuroprotection is now emerging which encompasses
three primary aims: 1) reduction of oxidative damage;
2) reduction of inflammation caused by genetic
predisposition and environmental and age-related stresses
and 3) regulation of lipid and protein aggregates which
accumulate as a result of ageing, inflammation and
oxidation.
Curcumin and Amyloid-beta
At low concentrations, curcumin inhibits accumulation
of amyloid beta peptide and formation of beta-amyloid
fibrils, and disaggregates preformed fibrils in the central
nervous system (Lim). The effective concentration of
curcumin required to inhibit the formation, extension,
and stabilization of amyloid fibrils is between 0.1 to 1
micromolar — making curcumin an attractive therapeutic
target for the treatment of Alzheimer’s disease (AD).
Curcumin possesses many of the characteristics of an
‘ideal’ broad-spectrum neuroprotective agent including
anti-inflammatory, antioxidant, and anti-protein/anti-lipid
aggregation activities, along with a strong safety profile.
Blood levels of amyloid-beta are strongly associated with
brain amyloid plaque deposits, which, as a primary risk
factor for Alzheimer’s disease, kill brain cells en masse and
prevent healthy brain ageing. New research is revealing
that amyloid and other deposits (such as tau) can begin to
accumulate in the brain more than 20 years before signs
of cognitive loss (Figure 1). Thus, a decrease of amyloidbeta
in healthy, middle-aged individuals could represent a
clearance of amyloid from the brain and excretion from the
body.
Figure 1. Amyloid-beta and tau begins to accumulate
many years before cognitive function declines.
Progression of Brain Ageing, Criteria for Preclinical
Alzheimer’s Disease, International Conference on
Alzheimer’s Disease, September 25, 2010.
The Key Limitation of Curcumin: Bioavailability
In the current clinical use of curcumin, a critical factor
is overlooked: curcumin has limited bioavailability.
Hundreds of published studies in animal and cell culture
show curcumin’s potential efficacy in a variety of disease
models, but at high doses often impractical for human use.
Further, several failures of curcumin to fulfill its promise
in clinical studies fuel the common belief that curcumin’s
poor bioavailability prevents its practical ability for use as a
neurotherapeutic compound (Baum 2007, Baum 2008).
Even with ‘enhanced-bioavailability’ formulations,
curcumin has only been detected after oral dosage in its
inactive glucuronide conjugate form (Baum 2007 and 2008,
Cuomo, Kanai, Lao, Marczylo). As curcumin glucuronide,
curcumin is not able to cross the blood-brain barrier at
significant levels.
New Technologies for Curcumin
Longvida®, based on patent-pending SLCP™ Technology
developed by the University of California – Los Angeles
(UCLA), has shown the capability to reach therapeutic
levels of free (unconjugated) curcumin at manageable
doses in more than a dozen pharmacokinetic trials (Figure
2). In recently published research, a single dose of
just 40mg curcumin led to blood concentrations of free
curcumin reaching the target anti-amyloid level of 0.1micromolar (Shah).and loss of cognitive function.

 

The therapeutic blood levels from Longvida have resulted
in significant results in placebo-controlled clinical trials.
Recently, a significant 8% decrease in plasma amyloidbeta
was observed after just 80mg curcumin daily (from
400mg Longvida) for 30 days (Figure 3) (Disilvestro)
Figure 3. Longvida 30-day dosing led to significant
reduction in plasma beta-amyloid (DiSilvestro)
Diverse Effects on Lipid Regulation: A Critical
Key for Healthy Brain Ageing
Triglyceride levels are also related to healthy brain ageing
and Alzheimer’s disease (Razay 2007). The genetic
predisposition for a sub-type of apolipoprotein whose
function is to transport triglycerides, ApoE4, is the largest
known genetic risk factor for Alzheimer’s disease.
Likewise, plasma triglycerides are strongly correlated
with plasma amyloid-beta levels in human populations
(Fujiwara). Elevated plasma triglycerides precede
amyloid-beta deposits in Alzheimer’s disease models, and
a reduction of triglycerides correlates to a decrease in
amyloid-beta (Burgess).
Cholesterol also induces the production of amyloidbeta.
As a primary cardiovascular risk factor, cholesterol
is associated with healthy levels of brain deposits
(Fujiwara). Circulating levels of total cholesterol are
strongly correlated with ApoE genotype and plasma
triglyceride levels. Statin therapy, which reliably reduces
total cholesterol and targets inflammation, is considered a
potential treatment for Alzheimer’s disease (Sparks).
After 30 days of SLCP™ based Longvida, a significant
14% reduction in plasma triglycerides was observed
(p<0.05). This coincided with a trend for decrease of total
cholesterol (Disilvestro)
Curcumin, inflammation and stress
Curcumin blocks many steps in the inflammatory cascade,
including C-reactive protein and nitric oxide synthase.
Likewise, curcumin may represent one of the few
compounds which safely addresses neuroinflammation.
C-reactive Protein (CRP) is a pro-inflammatory marker
highly correlated with healthy levels of amyloid-beta
deposits and cognitive function in meta-analyses (Kuo). In
the DiSilvestro study, an 11% reduction in CRP (significant
from baseline) was observed.
Soluble intercellular cell adhesion molecule 1 (sICAM-1),
Nitric oxide (NO), salivary amylase, and catalase are all
markers of inflammatory and physiological stress, and their
proper function is key for healthy ageing. In the study by
DiSilvestro and colleagues, all four of these markers were
improved in just 30 days with Longvida over placebo.
Safety of Curcumin
Curcumin has a long history of use. It is an approved
food additive and coloring by the U.S. FDA and equivalent
global health agencies, and has undergone hundreds of
studies supporting its safety during continuous dosing.
However, long-term safety studies should be performed
and published in peer review on ‘enhanced’ forms of
curcumin to understand whether increased absorption is
safe.
Longvida was recently determined to be Generally
Recognized as Safe (GRAS) by an independent,
internationally recognized panel of scientists (Thomas).
The safety determination, conducted by an independent,
internationally recognized expert panel of scientists, is
based on more than a dozen clinical, preclinical and safety
studies on Longvida®, including a published 90-day
subchronic toxicity study consluding no dose-related
toxicity at 100 times the dosage range recommended for
human use.
Conclusion
A new model for neuroprotection is now emerging which
defines the requirements for a safe, efficacious dosage
form of curcumin – and one which results in threshold
blood levels of free curcumin. Three primary aims for
this model include addressing age-related dysregulation
of proteins (e.g. amyloid-beta) and lipids, along with
inflammation and oxidative/physiological stress.
As a result, a diverse range of effects has been
observed in recent clinical research on a low-dose
curcumin formulation of curcumin (Longvida® Optimized
Curcumin) that is a prime candidate for neuroprotective
and neurotherapeutic development. The effects of this
formulation are wide-ranging, and include relatively fast
onset of anti-amyloid, anti-inflammatory, and antioxidant
effects. Future research will determine how cognitive
function relates to changes in these critical biomarkers
associated with healthy brain ageing.
For any further technical information Longvida, please contact
the Eu Distributor Gee Lawson Ltd. www.geelawson.co.uk