Exerciseinduced Cognitive Plasticity Implications for Mild Cognitive
A new approach to the prevention of Mild Cognitive ...invittanutrition.com/pdf/Melanin...
Transcript of A new approach to the prevention of Mild Cognitive ...invittanutrition.com/pdf/Melanin...
Neuromelan®
A new approach to the prevention of Mild Cognitive Impairment (MCI) and
memory enhancement
Because remembering this face shouldn’t be a problem
“Long ago, in the childhood tale that we all know, Ali Baba’s secret words “open sesame” held the key to a gold mine. 300 years later, with the very same key, we have found a path to a golden mind.”
The Story of Sesame
An oldie but a goodie
Sesame (Sesamum indicum) is considered one of the oldest oilseed crops known to
human kinds. 3000 years ago, people have already domesticated sesame, and
harvested. Today, you probably see many of them in your favorite Asian or fusion dishes,
long since our ancestors’ time we have been enjoying this delicacy, but the real value of
this family “jewel” passed down from generations to generations have been overlooked
until now. It is not until recent decades that humans have begun applying modern
science on food products. These little gems are packed with nutritious values such as
minerals, proteins and other valuable goods.
Black is the new Black
In the fashion world “you can never go wrong with a little black dress”, well now the
same saying applies for the health food world. Recent advance in science has discovered
that the color of the skin of the food actually matters. There’s a new obsession over dark
skinned food which are packed with potent anti-oxidants with health benefits such as
anti-aging, reducing risk factor for heart disease and stroke and brain protection as
opposed to their lighter counterparts, this makes black sesame a superior candidate
than white sesame.
Black sesames are “armed” meaning they retain their shells. White sesames are hulled,
which means their shells are removed. Nutrition wise, of course the more the merrier.
With this new health trend that’s heating up, more and more food are put under the
microscope.
The shells of the sesame not only contain nutrition value such as higher calcium fiber
and etc… but most importantly it is packed with a secret ingredient melanin.
Melanin - the secret ingredient
Melanin is a group of natural pigments occurring in many organisms. The pigments are
derivatives of the amino acid tyrosine, however the pigment itself is neither an amino
acid nor a protein, and it is produced in melanocytes.
There are many types of melanin, Eumelanin, Pheomelanin, Allomelanin and
Neuromelanin. The predominant functions of melanin-like pigments in humans are
coloring of the hair, eye and gray matter of the brain. Studies have shown a deficiency
in these compounds may cause Parkinson’s or Alzheimer’s.
Neuromelan®
Neuromelan®, naturally derived from the shell of black
sesames harvested in the land bathed under the sun, with our
innovative advanced technique to extract melanin that are rich
in the reduced form.
Why Neuromelan®?
Sesame is very abundant. It can be adaptable to varieties of
soil and water conditions and can be easily harvested
In comparison to other “dark skin” counterparts sesame
hold the highest surface area to volume ratio Structure of Neuromelan®
We’ve selected double hulled black sesame, double the shell double the goods
Study indicates in comparison to other oxidative states, reduced pigment possess
the most antioxidant (Figure 1.)
Neuromelan® not only maintains its antioxidant properties post gastrointestinal
digestion, but also releases components that exert positive protective effect on basal
and induced oxidative stress
Other than its anti-oxidant activities, Neuromelan® showed marked binding
properties to heavy metals, may pose as a neurotransmitter and semi-conductor in
brain
Clinically proven to prevent the progression of MCI, and enhance memory function
Figure 1, Native or reduced sesame pigment inhibit LDL-oxidation; oxidized sesame pigment showed
almost no effect
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Mild Cognitive Impairment
“Mild cognitive impairment (MCI) is an intermediate stage between the expected
cognitive decline of normal aging and the more serious decline of dementia. It can
involve problems with memory, language, thinking and judgment that are greater than
normal age-related changes. ”- MAYO CLINIC
Most predominate symptoms of MCI are memory impairment and language.
Studies carried out in memory clinics suggests that 10-15 per cent of people with MCI
went on to developing a form of dementia per year. MCI represents a significant increase
for risk of developing dementia, roughly 3 to 5 times higher the risk than someone
without dementia.
There are 7 types of Dementia, but the most common type is Alzheimer’s which
accounts for 60-80% of the cases.
Every 68 seconds,
Someone in the United States develops Alzheimer’s!
YOU COULD BE NEXT
President Ronald Ragan, 6th year after his presidency he announced that he had Alzheimer’s and
promoted awareness for Alzheimer’s
Prevalence
1 in 3 seniors dies with Alzheimer’s or another dementia
In 2013, 15.5 million family and friends provided 17.7 billion hours of unpaid care to
those with Alzheimer’s and other dementias- care valued at $220.2 billion, 8 times
the total revenue of McDonald’s in 2012
It is estimated that 5.2 million Americans have Alzheimer’s disease, including
200,000 individuals younger than 65 of age with early onset of Alzheimer’s
By 2050, the estimated number of individual with 65 or older may triple, from 5
million to as many as 16 million
Alzheimer’s disease is the most expensive condition in the U.S.(est. $214 billion)
Mechanism of action
Alzheimer’s and other neurodegenerative diseases are defined by the progressive loss of
specific neuronal cell populations. Studies indicate that a common feature of these
diseases is the oxidative stresses that are responsible for dysfunction and death of
neuronal cells that contribute to this disease pathogenesis. Neurons are highly
vulnerable to free radical attack due to the following factors:
Low in Glutathione, a natural antioxidant that occurs in the body
High in polyunsaturated fatty acids in their membranes
Brain metabolism requires large amount of oxygen
Neuromelan® was treated under conditions mimicking the gastric and intestinal
digestion with alternating pH conditions, enzyme component as well as bile salts. A
cellulose dialysis tube was used to assess the serum availability of the components post
digestion, with the IN sample indicating material that enters the serum; the OUT sample
represents the component that remains in gastrointestinal tract. The experiment
indicates that even post digestion; not only does the pigment and soluble fraction
maintain its antioxidant activity, but also releases components that exert positive
protective effect on basal and induced oxidative stress. Among these metabolites, NMR
and LC/ESI(+)/MS analysis identified the key component as vanilic acid.
Figure 2, Reduction of DPPH by the mixtures obtained after digestion of the pigment.
Lipid Oxidation
Studies indicated an increased in Lipid Oxidation of Alzheimer’s patients. Neuron
membranes are packed with polyunsaturated acids. Unsaturated lipids are highly
susceptible to oxidative modification and lipid peroxidation. Lipid peroxidation is the
result of attacks by radicals on double bound of the unsaturated fatty acids thus
generating highly reactive lipid peroxy radical that initiate a chain of reactions that leads
to break down of products including 4-hydroxy-2,3-nonenal(HNE), acrolein,
malondialdehyde and F2-isoprostanes, each component which have been identified in
Alzheimer’s brain, cerebrospinal fluid or plasma.
In a study performed on vanlic acid, lipid peroxidation was monitored via TBARS through
male rat’s liver and brain. Results indicate the inhabitation activity not only exceed that
of vanillin but also significantly exceeded trolox (water-soluble analog of vitamin E,
which is a common anti-oxidant therapy used for Alzheimer’s) in brain tissue. To further
investigate the scavenge free radicals in cellular environment, intracellular ROS
evaluation was conducted via DCFH-DA fluorescent. Results indicating vanilic acid
inhibited ROS activity in BNLCL2 cells more strongly than Ascorbic Acid (another
well-known anti-oxidant a.k.a Vit. C) and Trolox.
Figure 3, Inhibition of lipid peroxidation, TBARS activities and intracellular ROS level by vanillin and
vanillic acid. (a) Inhibition of lipid peroxidation in Fe2+ ⁄ ascorbate system using liposomes as an
oxidizable substrate by the investigated vanillin, vanillic acid and the standard of AA. (b) After
treatment with vanillin, vanillic acid and trolox (20 lg ⁄ ml) with mice liver and brain homogenate, the
formation of malonaldehyde was determined by TBARS assay. (c) Changes in the intracellular ROS
level indicated by the DCFH-DA fluorescence intensity in BNLCL2 cells treated with the 20 lg ⁄ ml of
vanillic acid, AA and trolox. The intracellular ROS generation level of BNLCL2 cells was measured by
the DCFH-DA which is vanillic acid to detect produced H2O2 (0.1 mM). Each value is presented as
mean ± S.D. from triplicate independent experiments.
Heavy metals
Metals may serve as a catalyst in the generation of free radical, and themselves alone
may also act as an contributing factor to neurodegeneration.
Mercury is a common metal that occurs in fish, dental amalgam, vaccines and other
sources. Several studies measuring plasma and CSF concentration of metals in
Alzheimer’s that mercury was significantly higher in subjects with AD than healthy
controls.
Mercury is capable of increasing the prevalence of Alzheimer’s via different aspects of
the disease shown in Table 1. For example, rats exposed to mercury vapor four times a
day shown similar molecular changes as those in human brain cultures after 14 days.
Mercury is capable of inhibiting the binding of GTP which is necessary for neurotubulin
synthesis and several other cellular functions. Mercury has also shown to have synergic
effect with other metals such as Cadmium and Lead is capable of potentize mercury
effects.
Table 1. Overview of the effects of mercury found by in vitro studies and animal experiments
Neuromelan® has shown strong metal chelating activities both prior and post digestion,
it is capable of attenuating the synergic effect of Hg and Cd or Hg and Pb by binding to
Cd or Pb, as well as to binding to Hg directly, to further preventing the damage that
mercury causes for neurodegenerative disease.
Figure 4, Comparison of heavy metal chelating properties at pH 7.0 of black sesame pigment before
(black bars) and after (grey bars) the digestion treatment. Metal concentration= 15 µM, pigment
concentration= 0.05 mg/mL
Neuromelan® has not only demonstrated important radical scavenging activities
directly or via one of its metabolites vanilic acid in prevention of lipid oxidation, as well
as the binding activity to heavy metals, which act as an modulator/catalyst in the
pathology of Alzhemir’s disease.
Dopamine & Alzheimer’s
Current drugs on alzheimer’s mainly targets acetycholine however study indicates
dopamine the “feel good” nuerotransmitter is a feasible candidate.
Study indicated that Vanilic acid effect on DOPA oxidase activity in the B16F0 cells,
showed significant reduced celular DOPA oxidase activity by 87.5% and 96.7% more
sigfinacantly than common antioxidant Absoribic acid and arbutin.(Figure 5.)
According to figure 6, L-dopa oxidase depletes cell of L-dopa source which is a precursor
to Dopamine. Vanilic acid is capable of inhibiting L-Dopa oxidase activites, restore the
cell of its L-dopa resevior.
Study done in Germany recruited
elderly subjects and were given
dopamine precursor Levodopa and
tested them on meomry test. Post two
and six hours following participants
have memorized the given photos,
reaserchers have requested them to
recognize new images from old. After 2
hours, there was no difference in
memorization between L-dopa and
placeb group, however surprise finding
indciated that post 6 hours, the L-dopa
group was capable of memorzing 20%
more photo than controls. when
memories are encoded, certain images
take places at the synapses(nerve
ending) , this is only temporary (at 2
hour mark) only when dopmaine is
newly formed at the synapses, this can stablize the memories and retained over time as
opposed to short term synpase activation. This explain why no difference was noticed at
2 hour mark, but after 6 hour there was a long term, and subjects are capable of
learning and actully retain what they learned, and capable of keeping long term memory,
which is often a difficulty in Alzhemir’s patients.
Figure 6, L-dopa oxidation pathway.
Levodopa, though often a common L-DOPA supplement, however, side effects tends to
be servere. Common side effects include abnormal thinking, agitation, anxiety, clusiness
or unsteadiness, confusion, false sens of well being, hallucination and other unpleasent
cognitive and physical sensation.
Neuromelan® on the other hand, has none of those reported unpleasant side effects
and unlike direct ingestion of L-DOPA, it serves as a precursor to avoid these unpleasant
effects, and possess other cognitive protective activities.
Clinical Trial
A randomized double blind study with 134 patients of both sex between the ages of 51
to 81 years participated in a two year study.
Selected participants must pass the MoCA (Montreal Cognitive Assement Test) and
performed below the average result on a 6 subtest subjective complaint-test (LGT-3)
indicative for figural and verbal memory. The participants were divided into two groups,
and given placebo, and Neuromelan® (sesame) in the form of identical capsules.
Neuromelan® indicated no change in figural memory whereas placebo indicated a
progression in cognitive decline. (Figure 7.)
Neuromelan® indicated only a slight change in cognitive decline, placebo indicated a
substantial decline in cognitive function. (Figure 8.)
LGT-results between 40-60 are considered “normal range”. The overall percentage of
Lgt-results between 40-60 decreased by 15% in the placebo group. However, in the
Neuromelan® group, the population LGT score increased by 7%.
The result of the study indicated the effects of Neuromelan® are big enough to show an
apparent improvement in the overall study population.
FIGURE 7. CHANGE OF MEDIAN FOR THE SUBJECTIVE FIGURE 8. CHANGE OF MEDIAN FOR THE SUBJECTIV
COMPLAINT-TEST (Figural Memory) COMPLAINT-TEST (Verbal Memory)
FIGURE 9, Change in % of LGT score in the course of 24 months
of oral administration of Neuromelan®
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Sesame Natural Course (Placebo)
Safety
Neuromelan® is extracted from sesame at low temperature with water as solvent, the
processing is fully complies with the relevant requirements of Old Dietary Ingredients
defined in Dietary Supplement Health and Education Act of 1994(DSHEA), therefore can
be used in dietary supplement as dietary ingredient without restriction in US.
Recommended Dosage
It is recommended to uptake 250 mg of Neuromelan® for adults per day.
Other beneficial effects
Semi-conductor
Aside from its amazing oxidation prevention functions, Neuromelan® proves to be
similar in structure with substantia nigra melanin. Studies indicate that they might be
involved in with transmitting and modulating nerve impulses, due to the fact that their
occurrence are scarce in new born babies (when movement isn’t fully developed) and
Parkinson’s (when movement isn’t controlled anymore), the correlation with motor
neurons are highly linked.
Eye protective effect
It has frequently been reported that ocular melanin protects the eye tissues, binding
heavy metals and trapping oxygenated free radicals. The lack of melanin in the eye
causes various problems (reduced visual acuity; nystagmus; strabismus; sensitivity to
bright light and glare). The most severe problem is found in the fovea, the small area of
the retina which permits acute vision, which does not develop completely because of the
lack of the melanin pigment which is needed for prenatal growth of the intraocular fine
structures and a normal pattern of nerves routes from the back of the eye to the brain.
Neuromelan®, as natural melanin pigment, could be a good dietary supplement for eye
health.
Hearing protective effect
It’s also reported people with albinism are at an increased risk for hearing impairment.
Melanin appears to play a role in the ability to hear properly and is important for the
overall function of inner ear canal. According to a 1994 study published in the journal of
"Pigment Cell Research," individuals who suffer hearing loss or are deaf lack adequate
melanocytes, which are cells found throughout body that are responsible for producing
melanin. According to the researchers, a lack of melanocytes in the inner ear results in
cochlear impairment, or hearing loss.
Prevention of cardiovascular disease (CVD)
A recent study suggested a beneficial effect of dietary black sesame meal on a reduction
in blood pressure in prehypertensive humans. It is likely that the antihypertensive effect
is due to decreased oxidative stress. Taken together with the absence of side effects, the
regular ingestion of dietary black sesame meal may be beneficial for CVD prevention in
individuals with prehypertension, or even those with hypertension. Therefore,
Neuromelan® is beneficial on prevention of cardiovascular disease (CVD).
Reference
1.Thomas Eidenberger,et al(2012).Black Sesame Pigment: DPPH Assay-Guided Purification, Antioxidant /Antinitrosating Properties
and Identification of a Degradative Structural Marker.J. Agric. Food Chem.,DOI: 10.1021/jf2053096 • Publication Date (Web): 16
Mar 2012
2.Tzung-Han chou, et al(2010). Antioxidative characteristics and inhibition of a-melanocyte-stimulating hormone-stimulated
melanogenesis of vanillin and vanillic acid from Origanum vulgare. Experimental Dermatology, 4 feb 2010.
3.Kevin J.Barnham, et al(2004).Neurodegenerative Diseases and oxidative stress. Nature Reviews, March 2004.
4.Yves Christen. Oxidative stress and Alzheimer disease. Am J clin Nutr,1 April 2014.
5.Farhana Zahir, et al(2005). Low dose mercury toxicity and human health. Enviornmental Toxicology and Pharmocology,17 May
2005.
6.Joachim Mutter, Alzheimer Disease: Mercury as pathogenetic factor and apolipoprotein E as a moderator.Neuroendocrinology
Letters, 4 Aug 2004.
7.Rumana Chowdhury. Dopamine Modulates Episodic Memory Persistence in Old Age.J.Neurosci,10 Oct, 2012
8.Jatuporn Wichitsranoi,et al(2011).Antihypertensive and antioxidant effects of dietary black sesame meal in pre-hypertensive
humans. Nutrition Journal, 10:82.
9.Bruno J. R. Nicolaus, A CRITICAL REVIEW OF THE FUNCTION OF NEUROMELANIN AND AN ATTEMPT TO PROVIDE A UNIFIED
THEORY
“In 2013, 15.5 million family and friends provided 17.7 billion hours of unpaid care to those with
Alzheimer's and other dementias – care valued at $220.2 billion, which is nearly eight times the total
revenue of McDonald's in 2012.” – Alzheimer’s association
Don’t let you or your loved ones be a burden to each other’s, start
PREVENTING TODAY!
The “Iron Lady”, Margaret Thatcher, one of the most influential politicians of all times, Thatcher died
on the morning of 8th April 2013 at a suite in The Ritz Hotel in London, because she was having
difficulty with stars at her Chester Square home due to brain decline of Alzheimer’s disease.