Amyloid Benefits™
INTRODUCTION
Individuals as they get older are not necessarily concerned about their brain health until they begin to notice changes in how their brain is working. At first they may ascribe their increasing forgetfulness to a “senior moment” or as a normal part of just getting older, but then as their ability to remember names, where they left their keys and what they were doing or saying just a few moments before diminishes, they realize that their mental functions seem to be failing. At that point they begin to ask “What is happening to my brain?”
There is growing concern among health providers that due to the aging population, the number of people afflicted by age-related brain dysfunction is expected to rise significantly over the next few years. In the past 15 years, there has been an alarming 123% increase in death from poor cognitive health in this country. At present there is an estimated 5.7 million older Americans who are afflicted with major loss of memory, cognitive health, and learning ability. It is estimated that globally, over 36 million people are affected by this progressive loss of brain function. The economic cost and social burden on families is enormous. In 2018, direct cost for serious conditions affecting the brain was more than 277 billion dollars (Biogen Report, 2018). At present, the medical community provides limited support to treat or help control these alarming statistics. This situation will put a growing burden on patients, care partners and the healthcare system in the years ahead.
Background
The symptoms of progressive brain dysfunction include mental confusion, disorientation, memory loss, impaired cognitive function and in advanced stages, the inability to perform routine tasks and to recognize friends and relatives. This loss of brain function, learning ability and memory is a sign of neurological breakdown that may increase over time as a person ages. The cause is thought to be related to adverse changes in the brain that produce metabolic, functional and structural abnormalities, which interferes with the normal working of nerve cells in the brain.
Clinical signs include development and build-up of amyloid plaque, neurofibrillary tangles, oxidative stress and neuro-inflammation. Other changes may include excessive brain shrinkage, loss of brain neurons and loss of connectivity between the nerve cells.
There Is Hope: Key Areas of Focus
There is substantial evidence outlining a clear path toward supporting healthy brain function, including but not limited to working memory, neuronal health, and even long-term memory. Several hypotheses have emerged as key areas of focus including 1) adequate amounts of acetylcholine with pathway optimization 2) supporting the body’s ability to appropriately metabolize beta amyloid protein and minimizing neurofibrillary tangles called tau 3) healthy levels of inflammatory cytokines present in the brain 4) adequate antioxidant levels in the brain and 5) optimization of the innate immune response. Other factors may include ensuring sufficient nutritional intake of critical nutrients like folate, vitamin B-12, zinc and omega 3 fatty acids as well as the supporting detoxification pathways relative to heavy metals such as mercury and aluminum. All of the above factors have the potential to contribute to optimum neurological function. (Rogers J et al. (2007:Beal M et al. (20o5); Boldogh I et al. (2008); Sochocka M et al. (2019). An overview of some of these key factors follows.
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Acetylcholine
Acetylcholine is the neurotransmitter associated with learning, neuronal communication and the storage of short and long term memory. It also functions in the transmission of neural impulses across cholinergic synapses in the brain. It has been reported in the literature that individuals with low acetylcholine levels do not demonstrate the same cognitive capacity, including memory, comprehension, creativity, physical orientation and working memory, as those with adequate levels (Kharrazzian, 2013). Current medical interventions aimed at improving cognitive capacity include cholinesterase inhibitors, whose mechanism of action is to slow the degradation of acetylcholine in the body.
Basics: Amyloid Proteins
There are over 30 different amyloid protein structures which can develop from a parent molecule called the amyloid precursor protein (APP). In the brain, abnormal amyloid plaque can accumulate outside neuronal cells and appear through the microscope to be clumps of dark proteins concentrated in the cortex and hippocampus. These clumps of amyloid proteins are very sticky and clump together very readily. For this reason, they are not easily removed or dissolved.
These amyloid proteins can easily spread throughout the brain and can cause new clumps to form, resulting in further plaque development. As amyloid plaques accumulate in the brain, they become cytotoxic and interfere in the normal processing and function of neuronal cells, especially in the hippocampus. It is this area of the brain that is involved in learning and memory.
Factors that may accelerate and/or contribute to amyloid buildup may include aging, gene mutation, a lack of mental and physical exercise, poor diet or brain injury according to Dr. Ricard Hartman, Loma Linda University Professor of Psychology. (Hartman R, et al 2006)
Free radical formation and oxidative stress appear to be contributing factors to the cytotoxicity of the beta amyloids. The presence of abnormal plaques may also trigger inflammation brought about by a response from the immune system.
Research: Beta Amyloid
Many researchers believe that beta amyloid buildup is a key player in brain function. This protein is found in everyone in a soluble state within the brain, however, it is essential for the brain to be able to metabolize these proteins and avoid aggregation, at which point the amyloid proteins have the potential to clump together forming insoluble plaques that can impair the functionality of the neurons in the brain.
Two studies in the 2009 issue of Archives of Neurology reported that higher levels of abnormal beta amyloid protein deposits in older people can be linked to symptoms of progressive brain dysfunction (Morris, J et al. 2009, Storandt et. al. 2009). According to the authors, the accumulation over time of beta amyloid proteins and the development of plaquing puts aging adults at risk for developing brain dysfunction, which impacts memory and learning skills. The studies also found that higher amyloid amounts in the brain were associated with greater declines in vocabulary and verbal expression.
Neurofibrillary Tangles
Another factor involved in functionality of the brain is the presence of densely twisted bundles of neurofibrillary tangles which can form within the neuronal brain cell. They are made up of protein structures called tau. When these micro tubal protein structures become hyper-phosphorylated (which can occur for a number of reasons including abnormal glucose metabolism), these tangles have the potential to impair internal cellular communication and function of the brain cell. Impaired ability to metabolize amyloid protein (leading to plaquing) combined with the presence of hyper-phosphorylated tau proteins (leading to neurofibrillary tangles) can cause interference within the neuron cellular structure itself and, ultimately, the function of the brain. It can also shorten the life span of the brain cell.
Oxidative Stress and Inflammation
Adequate antioxidant levels have been identified as a contributing factor to optimized brain function. When inadequate levels are present, free radicals can be very destructive to the cellular environment in the brain. Research has indicated that adequate metabolism of amyloid peptides leads to less free radical generation and, subsequently, less oxidative stress on the neuronal cells in the brain. Evidence has clearly demonstrated that providing free radical scavenging support can support molecular integrity, cell activation signaling and the ability for neurons to thrive within the central nervous system (Boldogh, I and Kruzel, M, 2008).
Amyloid Benefits™
Amyloid Benefits™ is a comprehensive, science-based supplement containing unique and branded ingredients formulated to effectively support cognitive function and memory in the aging brain.* The five compounds in this synergistic product were selected based upon published studies that revealed their individual effectiveness for supporting a healthy brain. Amyloid Benefits™ provides individuals with clinically tested ingredients that have been proven to cross the blood brain barrier and support the maintenance of healthy beta amyloid metabolism and tau protein aggregation as well as cortisol, blood glucose and antioxidant levels in the aging brain.*
This product contains:
- Immulox® Colostrum Extract
- Longvita® Curcumin Extract
- Shoden® Ashwagandha Extract
- Pomegranate Extract
- Palmfruit Bioactive Complex™
Immulox Colostrum Extract
Immulox® Colostrum Extract is a trademarked ingredient which contains a number of bioactive compounds that are useful in supporting the immune system, digestive tract and brain function. These compounds include immunoglobulins, lactoferrin and protein structures that are abundant in proline rich peptide complexes (PRP). PRP are important signaling proteins which aid immune modulation and support brain function.
Research has shown that colostrum rich in PRP can have a stabilizing effect on cognitive function (Biliekiewicz A., et al. 2004; Lesez J., et al. 1999, 2002). Another important finding is that colostrum rich in PRP’s helped improve beta amyloid metabolism and alleviate beta amyloid induced toxicity in rat hippocampus cultures (Shuster D. et al. 2005).
Though the mechanism of activity is not clearly known, research indicates that that the PRP may induce signaling pathways that produce changes that regulate stress kinase pathways, support the healthy production of inflammatory cytokines and chemokines (Szaniszlo P et al. 2008). It is interesting to note that PRP may alter gene expression related to beta amyloid precursor protein synthesis and increase levels of enzymes that break down the amyloid structures themselves. PRP can also decrease the activity of enzymes that promote hyper-phosphorylation of tau proteins. Other cell culture studies show that PRP modulate intracellular levels of reactive oxygen species (ROS) via up-regulating glutathione metabolism. Supporting the activity of antioxidant enzymes and mitochondrial function supports the overall aging process in both cell cultures and experimental animals (Boldough L 2000). When given to mice, PRP rich colostrum increased the life span and improved their various motor and sensory functions (Bolough, L 2007).
Longvida® Curcumin Extract
Curcumin is a bioactive flavonoid found in the spice turmeric that has a wide range of beneficial properties that support the health and well-being of individuals. In studies on cell culture and in experimental animals, curcumin has shown bioactivity that affects the cardiovascular system, inflammatory pathways, immune responses, antioxidant reactions and neurological processes in the brain.
As an isolated ingredient, curcumin has been shown to be poorly absorbed within the GI tract. Longvida® Curcumin Extract, on the other hand, is a highly absorbable and bioavailable form of lipid bound curcumin. This delivery system is key to the reported benefits of Longvida® Curcumin Extract in a number of studies. Research has shown that Longvida® is readily absorbed into the blood stream and can be found to cross the blood brain barrier within 3 hours after the initial dose. Longvida® Curcumin was found to be better absorbed and vastly superior to other unformulated Curcumins (Begum, et al., 2008).
There is compelling evidence in the literature that Longvida® can effectively support brain structure and function in the elderly population. In a ground-breaking study published in the Journal of Psychopharmacology, it was concluded that daily Longvida® supplementation (400 mg) helps support cognitive function in older heathy individuals (ages 60-80) when compared to a placebo group. Significant changes were seen in the areas of memory, attention span, fatigue, stress, and mood in as little as one hour after the first dose (Cox, K, et al., 2015). These positive results were confirmed in a more recent study using the same Longvida® Curcumin supplement (400 mg given daily) in a 12-week evaluation. Outcomes focused on cognitive performance and memory evaluated at 4 and 12 weeks. Compared to the placebo group, those on the Curcumin had significantly better working memory at 12 weeks, measured by three different procedures. These results confirm that Longvida® Curcumin Extract supports attention span, mood and working memory in healthy older individuals (Sholey, A. etal. , 2019).
Another recently published in vitro study reported that curcumin is able to bind to tau proteins and prevent tau fibril formation. The authors showed that this binding process inhibited the aggregation of these tau proteins and further led to their disintegration. This important discovery hopefully will lead to further work in animal models and give better understanding of how curcumin can support cognitive health, memory and learning processes in aging people (Rane J et al. 2017).
Robert DiSilvestro and his research team at Ohio State University reported that a low daily dose of Longvida® Curcumin (80 mg) produced a number of positive health benefits in a group of healthy middle-aged participants. The ingredient had a statistically significant effect on helping to normalize plasma beta amyloid protein concentrations, down regulating plasma triglyceride values, and by supporting antioxidant protection by raising salivary free radical capacity (DiSilvestro, R, et al. 2012).
Longvida® Curcumin Extract has also been studied in several mouse models showing its benefits in supporting cognitive function and brain health.
- Longvida® effectively counteracted mediated glial activation and progression of inflammatory markers, tau/amyloid activity and in turn supported cognitive function in a p25 transgenic mouse model ( Suraram J et al., 2017).
- Longvida® was found to down regulate beta amyloid production of ROS species, phosphorylated tau and apoptotic cell death in a cultured mouse neuroblastoma cell line (Maiti ,P. et al. 2017).
- Longvida® was found to support the downregulation of the production of soluble tau oligomers and behavioral patterns in aged tau transgenic mice.
- Mice given Longvida® were able to recover memory and cognitive function. (Ma, T , et al 2013).
Shoden® Ashwagandha Extract
Shoden® Ashwagandha (Withania somnifera) Extract is a clinically tested and multi-patented ingredient derived from the leaves and roots of the ashwagandha plant. Shoden® Ashwagandha offers high bioavailability and provides a full spectrum of over eight bioactive Withanolide Glycosides, which have been standardized to a concentration of 35% as compared to the average withanolide content hovering around 2.5% and more concentrated forms topping out at 8%.
Ashwagandha can be considered an adaptogenic herb that is able to mimic the stress normalizing activity of the body. As a result, it can support the body’s recovery from negative stress by promoting balance and a more normal equilibrium in the body. Ashwagandha provides a wide range of benefits to human health including strong antioxidant and inflammatory balancing properties (Archana R. 1999). It also helps to support better sleep, hormone balancing (including cortisol), immune modulation and physical endurance (Singh, et al. ,2011). Ashwagandha has been used for many years to support memory, concentration and cognitive functions by slowing the degradation of brain cells and by protecting and producing new neuronal networks and synapses within the brain (Kulkarni S, Dhir A. 2008; Kuboyama T et al. 2005,2006; Ahmad M et al. 2005).
When it comes to amyloid proteins, in a human neuronal cell line study, ashwagandha root extract was found to have a neuroprotective effect against beta amyloid toxicity (Kraipati K, et al. (2013). Previous work has shown that beta amyloid cytotoxicity has been identified as one of the major features of age-related brain dysfunction (BertramL, et al. 2010).
Ashwagandha was found to normalize cognition, memory and behavioral conditions in middle-aged male APP/PS1 mice that were injected with beta amyloid proteins. A reversal of the beta amyloid burden was attributed to the up-regulation of liver low density lipoproteins (Sehgal N et al. 2012).
Das and colleagues have reported in a review article that the Glycowithanolide Withaferin A, isolated from Ashawagandha, produces an increase in cholinergic markers and modulates inflammatory mediators, such as IL-1 and TNF-α, in beta amyloid plaque formations (Das T, et al, 2015).
In another study, Ashwagandha extract was administered to a group of older adults with mild cognitive impairment. The authors reported that there was improved performance on various cognitive tasks, attention span and reaction time (Ng Q et al 2019).
Pomegranate Extract
Research studies have shown that pomegranate fruit, especially the juice, has significant positive impact on brain health. Pomegranate is rich in polyphenols, flavonoids and tannins which support a wide range of biological activity including antioxidant levels, inflammatory cytokine production and immune function. A good review of the research on pomegranate’s benefits for the brain can be found in the book Food and Brain Health, chapter 15 entitled Pomegranate and Brain Health (Daradkeh G et al. 2014). It has been found that pomegranate extract (PE) may have a strong neuroprotective effect against the accumulation of beta amyloid levels in the brains of experimental animals (Ahmed A, et al. 2014: Yuan T. et al. 2016).
In a study using a rat model, PE was shown to inhibit cholinesterase activity by 20% (causing an increase in acetylcholine concentration). The PE also affected antioxidant capacity, showing a decrease in the production of malondialdehyde (MDA) levels as well as an increase in superoxide dismutase and glutathione peroxidase activity.
One particularly interesting and carefully controlled study on pomegranate juice was conducted by Dr. Richard Hartman of Loma Linda University. His lab employed a strain of transgenic mice (APP/Tg2576) that would encourage the accumulation of beta amyloid peptides in the brain as they aged. This development led to a significant loss of learning and memory ability. The test group received fresh pomegranate juice (PJ) while the control group received sugar water to match the sugar content of the juice. To summarize the results, “The PJ treated mice learned water maze tasks more quickly and swam faster than the controls. Mice treated with PJ had significantly less (about 50%) accumulation of soluble amyloid beta 42 and amyloid deposition in the hippocampus as compared to control mice.” Dr. Hartman calculated that the amount PJ consumed by the mice was equivalent to a person drinking from one to two eight ounces of PJ daily. These results point out the potential benefit of using pomegranate juice or extract to support the structure and function of the aging brain (Hartman R et al. 2006).
A recent innovative study published in the journal Oncotarget showed that laboratory mice fed a diet of 4% pomegranate juice over a 15-month period resulted in a range of neuroprotective effects. The genetically bred mice over time would develop increased beta amyloid build up in the brain. Compared to the control group, the test mice had decreased oxidative stress, less neurologic inflammatory cytokines present, healthy amyloid peptide metabolism and they also experienced improved synaptic plasticity in the brain. The authors concluded that the polyphenols found in pomegranate may provide significant nutritional and health benefits to the aging brain (Braidy N et al. 2016).
And finally, a placebo controlled randomized study of pomegranate juice (PJ) was conducted in older men who were exhibiting age-related memory loss. Thirty-two subjects were randomly assigned to drink 8 ounces of PJ or a matched placebo drink for 28 days. After 4 weeks, the PJ group showed a significant improvement in both verbal memory and an increased antioxidant capacity. The study suggested a role for PJ in supporting the “memory function through task-related increases in functional brain activity.” (Bookheimer S et al. 2013).
Palm Fruit Bioactive Complex™
The Palm Fruit Bioactive Complex™ (PFBC) is an exclusive ingredient that is produced by Phenolaeis USA. PFBC is a 100 % natural, water soluble complex that is produced from the oil derived from the fruit of the palm tree (Elaeis guineensis). Among other components, the ingredient contains five unique polyphenolic compounds that can give rise to a wide range of biological activity that can support a healthy brain (Sambanthamurthi R et al. 2011).
Palm fruit oil can support a number of metabolic functions including immune modulation, antioxidant activity and balancing inflammatory pathways. In one animal study, PFBC was found to support cardiovascular health as well as healthy glucose levels (Sambanthamurthi R et al.2011). In a cell culture study, PFBC was found to reduce oxidative damage to cell walls and increase intracellular glutathione levels (Leow S et al. 2013). BFBC has also been shown to down regulate the NF-kB pathway, a pro-inflammatory signaling pathway that gives rise to the expression of several pro-inflammatory markers including TNF-α (Leow S et al. 2016).
The benefit of PFBC in supporting brain health centers on its antioxidant and anti-inflammatory normalizing properties as well as its ability to protect the neurons in the brain through healthy amyloid peptide metabolism. The polyphenols inherent to this compound impact a number of pathways, ultimately lending the support necessary for optimal cognitive function, memory and learning skills in the healthy brain. (Weinberg R et al. 2018) Palm Fruit Bioactive Complex™ holds a promising role in supporting brain health and cognitive function in the aging population.
Amyloid Benefits™ offers a synergistic, science based and well balanced formula that provides support for maintaining a healthy brain.* It provides the aging brain with naturally sourced ingredients that support cognitive activity, memory and learning processes.* Research has shown that these ingredients provide neuroprotection by supporting the metabolism of beta amyloid levels, healthy expression of inflammatory cytokines, and adequate levels of antioxidant activity in the brain.* Amyloid Benefits™ has been formulated to lend the highest level of support to the both the structure and function of the brain as a person ages and aims to contribute to their health, vitality and wellbeing.*