Petter From Cyprus:

Dear Customer Service,

I would like to give a huuuuuuge compliment to your company. You helped me, with Christ guidance, from the beginning to treat my mother. You cant imagine how happy I am, looking at her and seeing the huge changes in her now. Her mind, from below almost zero, has come almost back to what was before...and doctors were saying that people with alzheimer are a lost cause, my mother was lost cause and my mind was going crazy!! I need the whole world to know about your company as well as how Christ showed you to me, out of nowhere. I want to shake your hands , hug you and kiss all of you there. You just saved another woman from dying from alzheimer; though there are some more problems with pains in the body and I need your help on which enzymes should I give to her: plus if you have something for osteoporosis,again, I'd kiss each of you there.

YOU ARE THE BEST!!

Lenwood from South Carolina:

Dear Customer Service,

My wife had succumbed to Alzheimer's Disease and I decided that there must be some way to help her. I searched the internet and came across this website. After speaking with an advisor I decided that there was nothing to lose and ordered a month's supply of BioAnue Alzheimer's Mender for my wife. After only 3 and 1/2 weeks of taking the product, I can tell a noticeable difference in her. She is more aware and her aggressiveness has abated. I am very happy with these results and have placed an order for more. Thanks BioAnue for helping my wife. I am in hopes that one day she will be completely healed of this awful disease. I will keep you posted with her further progress.

Tom From Tennessee:

Dear Technical Support,

With reference about my wife she started taking your Alzheimer Mender on the 17-01-2011 and after only 5 days I could see that she is now calmer and more aware of things about her. She only used to sleep from 3 1/2 to 4 hours per night, but she now sleeps 7 to 8 hours a night. She is now on 3 tablets per day and is trying to talk to people and as long as they dont interrupt her she can finish what she wants to say, if she is interrupted she is lost. I took her out in the car, she just used to stare out of the window, but last Saturday she was making comments about other drivers (things are getting better.) I shall be ordering some more tablets in the next 2-3 days and going to also order ATP Pure Energy as well. I have just sent off samples of her hair to be checked to see if there is any heavy metal in her body, if there is I would be interested in the product Zeolite or any other products which might help her.

UP-DATE

Dear Technical Support,
Since I last gave you my wife progress she has improve even more she has know started reading novels in the last 4 weeks she has read 2 books & in just started the third,when I do the washing she cant wait to do the ironing,she washes up after every meal, & has started to do sewing by hand, she used to be a sewing machinist, but is a bit afraid of the machine at this moment,she is on 4 tablets per day this seems to be the correct amount for her, you gave me the address of a company which would do hair follicle test which ordered on 14 march 2011 but we have never received this item so I have not been able progress about the heavy metal which she may have, have emailed this company again today lets hope they might be able to find out where this item went to if so them we might be able to try to remove any heavy metal in her.

since we started with your tablets last Jan 2011 I am very pleased with her improvment every body says how well see looks she even starting using make up have just placed another order yesterday.

Regards

Tom

Betty from New Jersey,

Dear Customer Service,

My husband Jack has been using Alzheimer's Mender for about two months. Within the first two days of taking the product I started to see improvements in my beloved husband.

12 years ago I started to notice some changes, the last 3 to 4 years have been the most significant, I took him to our doctor and they checked him using complete physical exam neurological exam MRIs and EKG and gave him a cognitive tests to determine what had been going on; they determined he is suffering from Alzheimer's disease.  I have tried all of the typical allopathic drugs and have seen no relief for my husband. In fact the last two weeks before using Alzheimer's Mender his health was spiraling out of control, his disease was progressively getting worse and I feared there would be no hope, after searching the Internet I found Alzheimer's Mender; within two days I started to see a change in my Jack.

I spoke with the neurologist and told him about the natural products I had been giving him, Alzheimer's Mender by BioAnue, he told me there was no natural products that could help my husband and in fact he says his original diagnosis was incorrect and he does not have Alzheimer's but has another form of dementia.  I reminded him we have been going to him for treatment every six months for the last four years, he said if Jack had Alzheimer's his disease would be progressively worse by now and the fact is he's doing really well means the original diagnosis was incorrect.

My natural path who is also a trained pharmacist was not so glum, before I bought the product I printed out the information on the website and brought it to her she was quite interested and said the product would not harm him in any way and definitely worth a try. She has been encouraged by his progress. You have given my Jack the hope we have been looking for.

The first 30 days I gave Jack two capsules of Alzheimer's Mender per day; after seeing those results wanting Jack to recover faster I decided to try increasing to six capsules per day and add ATP, his improvement has increased significantly. He is not 100% well at this time but he's coming back, without Jack I don't know what I would do.

Thank you for such a great product Betty from New Jersey

John from UK

Dr.Doctor,
I have purched 1 of your BioAnue Alzheimer's Mender for my father who has Alzehiemer illness and it appears that is working better than other tablets he has used in the past. Since taking your product he is more aware in what is happening; I would say probably he has improved by 5% to 10%. Many thanks.

Lewis form AZ

Dear Customer Service,

I came across the BioAnue Alzheimer’s Mender and decided to try it for my mother.  She is easily confused and loses her train of thought, etc.    She took 3 capsules per day and in 3 days she was less confused.  Now after one month she is her normal self.  I have told my friends about you and how great your product is. 
Thank You!

Dan from MO

Hello,

I purchased your BioAnue Alzheimer’s Mender for my mother.  In 7 days after she began taking your product I noticed a difference and each week she keeps improving.  Thanks to your product we have seen a years worth of damage reversed in just 3 weeks.
Thank you so much!

Steven from Arizona:

Dear Customer Service,

As I began getting older, my mind began to get fuzzy. I couldn't remember anything. I began using the BioAnue Alzheimer's Protocol and could tell a difference immediately after taking it. My mind is clearer and I am sleeping better at night.

What is Alzheimer's disease?
The production of a specific protein (amyloid beta protein) forms the amyloid plaques and tangles (brain lesions) in the brain which results in declining ability to cope with everyday life as brain cells die.
Late-onset AD. ApoE helps in distribution of cholesterol through the body and everyone has one of the 3 forms of the apoE gene. A percentage of people have the form that increases the risk of AD. In rare cases, other genes apart from ApoE may also increase the risk of AD as they are known to be mutated in some people with the disease.

The E4 variant is the largest known genetic risk factor for early-onset Alzheimer's disease (AD) in a variety of ethnic groups. Caucasian and Japanese carriers of 2 E4 alleles have between 10 and 30 times the risk of developing AD by 75 years of age, as compared to those not carrying any E4 alleles (different form of the gene). While the exact mechanism of how E4 causes such dramatic effects remains to be fully determined, evidence has been presented suggesting an interaction with amyloid (insoluble protein aggregates). Alzheimer's disease is characterized by build-up of aggregates of the peptide beta-amyloid. Apolipoprotein E enhances proteolytic break-down of this peptide, both within and between cells. Some isoforms of apolipoprotein E are not as efficient as others at catalyzing these reactions. In particular, the isoform ApoE-ε4 is not very effective, resulting in increased vulnerability to Alzheimer's in individuals with that gene variation.
The pivotal role of apolipoprotein E in AD was first identified through linkage analysis by Margaret Pericak-Vance while working in the Roses lab at Duke University Linkage studies were followed by association analysis confirming the role of the ApoE4 allele.

Although 40-65% of AD patients have at least one copy of the 4 allele, ApoE4 is not a determinant of the disease - at least a third of patients with AD are apolipoprotein E 4 negative and some apolipoprotein E 4 homozygotes never develop the disease. Yet those with two e4 alleles have up to 20 times the risk of developing AD. There is also evidence that the ApoE2 allele may serve a protective role in AD. Thus, the genotype most at risk for Alzheimer's disease and at earlier age is apolipoprotein E 4,4. The apolipoprotein E 3,4 genotype is at increased risk, though not to the degree that those homozygous for ApoE 4 are. The genotype ApoE 3,3 is considered at normal risk for Alzheimer's disease. The genotype apolipoprotein E 2,3 is considered at less risk for Alzheimer's disease. Interestingly, people with both a copy of the 2 allele and the 4 allele, apolipoprotein E 2,4, are at normal risk similar to the apolipoprotein E 3,3 genotype.

Early-onset Alzheimer's. This is a rare form of Alzheimer's disease in which people are diagnosed with the disease before age 65. Less than 10% of all Alzheimer's disease patients have this type. Because they experience premature aging, people with Down syndrome are particularly at risk for a form of early onset Alzheimer's disease. Adults with Down syndrome are often in their mid- to late 40s or early 50s when symptoms first appear.

Younger people who develop Alzheimer's disease have more of the brain abnormalities that are associated with it. Early-onset Alzheimer's appears to be linked with a genetic defect on chromosome 14, to which late-onset Alzheimer's is not linked. A condition called myoclonus -- a form of muscle twitching and spasm -- is also more commonly seen in early-onset Alzheimer's than in late-onset Alzheimer's.

Late-onset Alzheimer's. This is the most common form of Alzheimer's disease, accounting for about 90% of cases and usually occurring after age 65. Late-onset Alzheimer's disease strikes almost half of all people over the age of 85 and may or may not be hereditary. Late-onset dementia is also called sporadic Alzheimer's disease.

Alzheimer's disease can begin with the following symptoms:

• Anxiety
• Depression
• Forgetfulness- mild
• Irritability
• Language impairment  (loses the ability to fully communicate)
• Short term memory disrupted
• Critical thinking skills impaired

Mild forgetfulness or other symptoms does not mean that a person has Alzheimer’s disease. However, with Alzheimer’s disease the symptoms will progress and get worse. Early intervention should be considered.  Tests can confirm the E4 variant or apolipoprotein E (ApoE) in the brain. Although these substances are associated with Alzheimer’s disease, they are only an indicator.  People with confirmed Alzheimer's disease will have the characterized build-up of aggregates of the peptide beta-amyloid theses.

In the middle stage of disease, patients begin to forget to do simple tasks such as combing hair or brushing teeth. In the middle stage patients:

• Are Not able to think properly
• Lose memory recollection

As the disease becomes more advanced it robs people of their memories, beginning with the short term memories then it robs them of all their memories.

The Later stage Alzheimer’s disease patient exhibits:

• Aggressiveness
• Anxiousness
• Cognitive impairment
• Personality changes
• Reading impairment
• Speaking impairment
• Starts to forget the familiar people and places
• Writing impairment

Eventually these patients will need total support and care.

Behavioral and psychiatric symptoms can cause personality changes and agitation to the Alzheimer’s patient. In fact the Alzheimer’s patient and their families find behavioral symptoms to be the most challenging and distressing aspect of this disease. Because the disease robs the person of their short term memory, the patient can feel that the caregiver is stealing from them. The family members of the patient see their loved-one slipway-- turning into someone they do not recognize. The fact is that Alzheimer’s disease affects about 10% of the population at age 65 and an astonishing 50% by age 80.

Because the majority of the population understands the importance of good health, people are living longer than ever before.The average age for men in the United States is 77.6 and for women 78.8. Because of this fact one needs to consider prevention of Alzheimer’s disease before it impacts them or a loved one.  
Alzheimer’s Mender by BioAnue is a natural product blend that can help the health of those with short term memory loss, those concerned about developing Alzheimer’s disease , and even those with Alzheimer’s disease itself .

It is important to treat the underling nutritional deficiency of Alzheimer’s disease. Recognizing the symptoms and understanding the cause of this disease can mean early treatment. With knowledge, the disease can be slowed down and reversed before severe symptoms occur.  Understanding treatment strategies are also important to the caregiver and patient alike. Knowing there is hope is very important.

Patients and caregivers can choose to confront this disease/ nutritional deficiency head-on with a therapeutic, nutritional approach.  By consuming functional foods while taking Alzheimer’s Mender, the patient should expect to see improvement and even reversal of the disease. In fact Alzheimer’s Mender is guaranteed to produce improvement with in the first 30 days of taking the product or a 100% refund will be given.

Familial Alzheimer's disease (FAD). This is a form of Alzheimer's disease that is known to be entirely inherited. In affected families, members of at least two generations have had Alzheimer's disease. FAD is extremely rare, accounting for less than 1% of all cases of Alzheimer's disease. It has a much earlier onset (often in the 40s) and can be clearly seen to run in families.

Agu from Nigeria

Hello Bio Anue,

I just wanted to let you know how much I appreciate your product Bio Anue Alzheimer’s Mender.  I sent my dad, in Nigeria, your product.  He weighs 120 pounds, he had taken 1 capsule each day for 30 days and we have seen a significant improvement in his memory.  

We are very pleased with the results we have seen thus far.  I have ordered more product and plan to tell others about you. 

Thank you!!

Frances from Arizona:

Dear Customer Service,

I just wanted to let you know how much I appreciate your product BioAnue Alzheimer’s Mender.  I sent my dad, in Africa, your product.  He weighs 120 pounds, he had taken 1 capsule each day for 30 days and we have seen a significant improvement in his memory.  
We are very pleased with the results. 
I have ordered more product and plan to tell others about you. 

Thank you!!

The National Institute of Health has misinformed us with their belief that the progression of Alzheimer’s disease is an absolute which cannot be slowed down; they are wrong. In reality, Alzheimer’s is the result of a nutritional deficiency, namely a deficiency of CDP-choline (citicoline). Citicoline provides key developmental structure and functions like stem cell proliferation, lifelong memory function, and brain and spinal cord development

Acetyl L-carnitine chloride

• Improves memory problems in elderly people over the age of 65
• Antioxidant that repairs free radical damage to the brain also known as reactive oxygen species (ROS)
• Improves memory in 30-60 year-old people, whose use of alcohol has produced long-term thinking problems
• Improves blood flow to the brain
• Helps early-onset Alzheimer’s disease patients who are less than 66 years of age and have a faster rate of disease progression and mental decline and depression

Might improve mood and decrease depression in elderly people

Science Behind Acetyl L-carnitine Chloride

Acetyl-L-carnitine is produced in mitochondrial membranes.This compound helps to maintain mitochondrial bioenergetics and lowers the increased oxidative stress associated with aging. Acetyl-L-carnitine was used in the present study to determine its possible protective effects against A 1-42-induced oxidative stress in cortical neuronal culture. Acetyl-L-carnitine is present in high concentrations in the brain and is involved in the production of acetylcholine (Dolezal and Tucek, 1981). Acetyl-L-carnitine has been shown to reverse age-related deficits in mitochondrial function (Hagen et al., [1998]; Paradies et al., 1999).The brain has a high oxygen consumption rate, abundant lipid content, and relatively low availability of antioxidant enzymes compared with other tissues (Coyle and Puttfarcken, 1993; Markesbery, [1997]), which makes this organ particularly susceptible to oxidative stress. To combat this vulnerability, the brain has evolved networks that detect and control different kinds of stress, e.g., Heat shock protein (HSP) response is one kind of such cellular stress response, which involves protection of cells from various forms of stress (Mosser and Morimoto, 2004).

Acetyl L-carnitine Treatment in
Elderly Patients with Fatigue

This study was to determine the efficacy, tolerability and impact on the fatigue, as well as on cognitive and functional status of elderly subjects with acetyl L-carnitine. Ninety-six people ranging from age 71–88 were investigated-- 50 females and 46 males. Fatigue was measured with the Wessely and Powell scores, with the fatigue severity scale. At the end of the treatment, a decrease of physical fatigue was observed: 6.2 %, of mental fatigue: 2.8 %, when the patients had severity fatigue: 21.0% and improvements in functional status: 16.1% and cognitive functions: 2.7 %.  By the end of the treatment, significant differences between the two groups were found for the following parameters: muscle pain improved by 27% prolonged fatigue after exercise: 51% sleep disorders: 28%; physical fatigue: 7% mental fatigue: 3.3% severity scale: 22.5 versus 1.2 ( p < 0.0001); functional status 17.1 versus 0.6 ( p < 0.0001); mini mental state examination (MMSE) improvements: 3.4 versus 0.5%. The study shows that administering acetyl L-carnitine reduced both physical and mental fatigue in elderly and improves both the cognitive status and physical functions. Malaguarnera, M. et al., Acetyl L-carnitine treatment in elderly patients with fatigue, Archiv. Gerontol. Geriatr. (2007), doi:10.1016/j.archger.2007.03.012

Carnitine treatment reduces severity of physical and mental
fatigue & increases cognitive functions in centenarians

Centenarians generally have a lower quality of life due to weakness, decreasing mental health, impaired mobility, and poor endurance. L-Carnitine is an important contributor to cellular energy metabolism. Sevevty people were tested, aged from 100 to 106 years old broken up in two groups. Recruited in this study were 24 men and 46 women. The centenarians were treated with L-carnitine for 6 months.
Objective: This study evaluated the efficacy of L-carnitine on physical and mental fatigue and on cognitive functions of centenarians.
Design: This was a placebo-controlled, randomized, double-blind, 2-phase study. Sixty-six centenarians with onset of fatigue after even slight physical activity were recruited to the study. The 2 groups received either 2 g acetyl L-carnitine once daily (n_32) or placebo (n_ 34). Efficacy measures included changes in total fat mass, total muscle mass, serum triacylglycerol, total cholesterol, HDL cholesterol, LDL cholesterol, Mini-Mental State Examination (MMSE), Activities of Daily Living, and a 6-min walking corridor test.
Results: At the end of the study period, the acetyl L-carnitine -treated centenarians, compared with the placebo group, showed significant improvements in the following markers: total fat mass (_1.80 compared with 0.6 kg; P_0.01), total muscle mass (3.80 compared with 0.8 kg; P _ 0.01), plasma concentrations of total carnitine (12.60 compared with_1.70_mol; P_0.05), plasma long-chain acetyl L-carnitine (1.50 compared with _0.1 _mol; P _ 0.001), and plasma short-chain acetyl L-carnitine (6.0 compared with _1.50 _mol; P _ 0.001). Significant differences were also found in physical fatigue (_4.10 compared with _1.10; P _ 0.01), mental fatigue (_2.70 compared with 0.30;P_0.001), fatigue severity (_23.60 compared with 1.90;P_0.001), andMMSE(4.1 compared with 0.6;P_0.001).
Conclusions: The study indicates that oral administration of acetyl L-carnitine produces a reduction of total fat mass, increases total muscular mass, and facilitates an increased capacity for physical and cognitive activity by reducing fatigue and improving cognitive functions. 2007 Mariano Malaguarnera et al. Am J Clin Nutr 2007;86:1738–44.

 Acetyl L-carnitine Inhibits A 1-42-Induced Protein
Oxidation and Lipid Peroxidation in a Dose-Dependent Manner

Protein carbonyls (Protein carbonyls are formed by a variety of oxidative mechanisms and can be used as an index of oxidative injury. Recommended as a means to detect general protein oxidation in biological fluids such as plasma, serum, bronchoalveolar lavage, cerebrospinal fluid, cell extracts and other soluble protein samples.) are elevated in vulnerable regions of AD brain (Hensley et al.,1995; Castegna et al., 2002) and in brain treated in vivo (in the living) (Boyd-Kimball et al., 2005). Reaction of reactive nitrogen species with proteins and is reported to be elevated in Alzheimer’s diseased brain (Smith et al., [1997]; Castegna et al., [2003]). A dose-dependence study was carried out by adding acetyl L-carnitine to the cortical neurons. A significant 38%, 30%, or 70% increase in protein carbonyls levels, respectively, was induced in neurons following 24 hours of treatment. 2005 Hafiz Mohmmad Abdul et al.

Acetyl L-Carnitine Protects Mitochondria From A 1-42-
Mediated Dysfunction in a Dose-Dependent Manner

Decrease mitochondrial function assessed by MTT (Mitochondrial function was evaluated by the 3-[4,5-dimethylthiazol-2-yl)-2,5-diphenyl] tetrazolium bromide (MTT) reduction assay.) reduction by 50% compared with untreated control. Treatment of neurons with acetyl L-carnitine alone for 24 hr did not show any change in MTT reduction compared with the control. Pretreatment of neurons with 100 M ALCAR (2 hr prior) followed by A 1-42 showed significant (P < 0.01) dose-dependent protection of mitochondrial function compared with that induced by A 1-42 alone. There is a maximal significant increase (P < 0.01) in cell viability with 100 M acetyl L-carnitine, followed by A 1-42, but still a significant decrease in MTT reduction compared with untreated control. However, these results are consistent with the concentration of ALCAR that protected neurons against A 1-42-mediated protein oxidation (Fig. 1a-c). The study on the degree of cytochrome C release suggests that there is an approximate 4-fold increase in cytochrome C levels in the cytosol of neurons treated with A 1-42, which was gradually decreased in the presence of increasing concentration of acetyl L-carnitine. However, the levels of cytochrome C released from mitochondria in neurons treated with acetyl L-carnitine alone were comparable to those of the control cells (untreated cells). Acetyl L-carnitine protected neurons against protein oxidation and lipid peroxidation and prevented loss of mitochondrial function.

Delaying the Mitochondrial
Decay of Aging with Acetylcarnitine

Oxidative mitochondrial decay is a major contributor to aging. Some of this decay can be reversed in old mammalians by feeding them normal mitochondrial metabolites, such as acetyl L-carnitine and alpha lipoic acid at high levels. Feeding the substrate acetyl L-carnitine with alpha lipoic acid, a mitochondrial antioxidant, restores the velocity of the reaction for acetyl L-carnitine transferase and mitochondrial function. The principle appears to be that, with age, increased oxidative damage to protein causes a deformation of structure of key enzymes with a consequent lessening of affinity for the enzyme substrate. The effect of age on the enzyme-binding affinity can be mimicked by reacting it with malondialdehyde (a lipid peroxidation product that increases with age). In old mammalians (vs. young mammalians), mitochondrial membrane potential, cardiolipin level, respiratory control ratio, and cellular O2 uptake are lower; oxidants/O2, neuron RNA oxidation, and mutagenic aldehydes from lipid peroxidation are higher. Ambulatory activity and cognition decline with age. Feeding old mammalians acetyl L-carnitine with alpha lipoic acid for a few weeks restores mitochondrial function; lowers oxidants, neuron RNA oxidation, and mutagenic aldehydes; and increases mammalians ambulatory activity and cognition (as assayed with the Skinner box and Morris water maze). A recent meta-analysis of 21 double-blind clinical trials of acetyl L-carnitine in the treatment of mild cognitive impairment and mild Alzheimer’s disease showed significant efficacy vs. placebo.  Bruce N. Ames and Jiankang Liu Children’s Hospital Oakland Research Institute, Oakland, California 94609, USA.

Alpha Lipoic Acid

• Reduces mitochondrial dysfunction due to the oxidation of lipids, proteins, and nucleic acids
• Improves the function of brain aging neurodegenerative diseases such as Alzheimer disease
• Antioxidant
• Improves memory-related signaling pathways
• Reduces oxidative stress
• Improves of mitochondrial function
• Restores the activity of acetylcholinesterase and sodium potassium (Na + , K +-ATPase) pump e.g. balances the pH of the cell improves metabolic energy cycle. The activity of acetylcholinesterase was decreased in the cerebral corex, cerebellum, striatum, hippocampus, and hypothalamus in aged mammalian brains, protected cortical neurons against cytotoxicity induced by beta-amyloid or hydrogen peroxide e.g. free radicals.

Science Behind Alpha Lipoic Acid

Several free radical species are normally produced in the body to perform specific functions. Superoxide (O2_.), hydrogen peroxide (H2O2), and nitric oxide (NO) are three free radical reactive oxygen species (ROS) that are essential for normal physiology, but are also believed to accelerate the process of aging and to mediate cellular degeneration in disease states. These agents together produce highly active singlet oxygen, hydroxyl radicals, and peroxnitrite that can attack proteins, lipids, and DNA. Andrea M. Vincent et al, 2004

The finding that oxidative damage, including that to nucleic acids, in Alzheimer’s disease is primarily limited to the cytoplasm of susceptible neuronal populations suggests that mitochondrial abnormalities might be part of the spectrum of chronic oxidative stress of Alzheimer’s disease. In this study, we used in situ hybridization to mitochondrial DNA, immunocytochemistry of cytochrome oxidase, and morphometry of electron micrographs of biopsy specimens to determine whether there are mitochondrial abnormalities in Alzheimer’s disease and their relationship to oxidative damage marked by 8-hydroxyguanosine and nitrotyrosine. We found that the same neurons showing increased oxidative damage in Alzheimer’s disease have a striking and significant increase in mitochondrial DNA and cytochrome oxidase. Surprisingly, much of the mitochondrial DNA and cytochrome oxidase is found in the neuronal cytoplasm and in the case of mitochondrial DNA, the vacuoles associated with lipofuscin. Morphometric analysis showed that mitochondria are significantly reduced in Alzheimer’s disease. The relationship shown here between the site and extent of mitochondrial abnormalities and oxidative damage suggests an intimate and early association between these features in Alzheimer’s disease. Keisuke Hirai et al, 2001.

Preventing Memory Loss using Acetyl-L-carnitine and  R-alpha- lipoic acid

Accumulation of oxidative damage to mitochondria, protein, and nucleic acid in the brain may lead to neuronal and cognitive dysfunction. The effects on cognitive function, brain mitochondrial structure, and biomarkers of oxidative damage were studied after feeding old rats two mitochondrial metabolites, acetyl-L-carnitine and R-alpha- lipoic acid. Morris water maze test (Tests hippocampal-dependent learning); temporal memory was tested by using the peak procedure (a time-discrimination procedure). Acetyl-L-carnitine  and  R-alpha- lipoic acid improved memory, the combination being the most effective for two different tests of long term and short term memory. Immunohistochemical analysis showed that oxidative damage to nucleic acids (8-hydroxyguanosine and 8-hydroxy-2_-deoxyguanosine) increased with age in the hippocampus, a region important for short term memory. Oxidative damage to nucleic acids occurred predominantly in RNA. Dietary administration of Acetyl-L-carnitine and R-alpha- lipoic acid significantly reduced the extent of oxidized RNA, the combination being the most effective. Electron microscopic studies in the hippocampus showed that Acetyl-L-carnitine and R-alpha- lipoic acid reversed age-associated mitochondrial structural decay. These results suggest that feeding Acetyl-L-carnitine and R-alpha- lipoic acid to old mammalians improves performance on memory tasks by lowering oxidative damage and improving mitochondrial function. Jiankang Liu et al, 2001

Neuronal mitochondrial amelioration by feeding
acetyl-L-carnitineand lipoic acid to aged rats

Our results demonstrate for the first time that ultrastructural morphometric analysis provides criteria for documenting mitochondrial damage that increases with aging. Treatment with ALCAR + LA restores intact mitochondrial morphology normally degraded with age. Moreover, quantitative electron microscopic observation for the first time demonstrated that with Acetyl-L-carnitine and R-alpha- lipoic acid supplementation neuronal mitochondria from young treated animals show better intact morphology compared to young non-treated controls. Further investigation on the effect of Acetyl-L-carnitine and R-alpha- lipoic acid supplementation by using electron microscopic quantitative/qualitative study will provide new information for the current model of aging as well as neurodegenerative diseases such as Alzheimer’s disease where mitochondrial damage and energy failure appear to be a primary step in the development of cognitive impairment or brain pathology such as amyloid beta deposition, a hallmark for Alzheimer’s disease.

In conclusion, old mammalians showed morphological mitochondrial decay and dietary supplementation with Acetyl-L-carnitine and R-alpha- lipoic acid restored mitochondrial morphology and prevented decay. Further, a key observation of this study is the proliferation of intact mitochondria in young treated rat brain neurons. These results support the role of mitochondrial decay as an important factor in aging. Further, dietary supplementation with selective mitochondrial antioxidants and metabolites such as Acetyl-L-carnitine and R-alpha- lipoic acid may be an effective strategy for delaying aging, as well as neurodegeneration such as Alzheimer’s disease, where mitochondrial damage appears to be a primary target before the development of any amyloid deposition or cognitive impairment. NIH Public Access Author Manuscript J Cell Mol Med. Author manuscript; available in PMC 2009 December 8.

Effects on Neuronal Function: Dietary administration of acetyl-L-carnitine hydrochloride and/or R-"-lipoic acid improved age-related mitochondrial structural decay in hippocampal neurons in old rats (Liu et al., 2002a).
Acetyl-L-carnitine accelerated the maturation of cerebellar neurons in vitro, activated nerve growth factor receptors, and prevented the loss of substance P in the peripheral nerves in diabetic animals (De Grandis et al., 1995).
Old rats given oral "-lipoic acid showed delayed hearing loss while rats treated with acetyl-L-carnitine hydrochloride experienced hearing improvement (Seidman et al., 2000).

Antioxidant Role of Alpha-Lipoic Acid in Lead Toxicity

The assumption of oxidative stress as a mechanism in lead toxicity suggests that antioxidants might play a role in the treatment of lead poisoning. The present study was designed to investigate the efficacy of alpha lipoic acid in rebalancing the increased prooxidant/antioxidant ratio in lead-exposed Chinese hamster ovary (CHO) cells and Fischer 344 rats. Furthermore, alpha lipoic acid’s ability to decrease lead levels in the blood and tissues of lead-treated rats was examined. Alpha lipoic acid administration resulted in a significant improvement in the thiol* Thiols are the sulfur analogue of alcohols, capacity of cells via increasing glutathione levels and reducing malondialdehyde levels in the lead-exposed cells and animals, indicating a strong antioxidant shift on lead-induced oxidative stress. Furthermore, administration of Alpha lipoic acid after lead treatment significantly decreased catalase and red blood cell glucose-6-phosphate dehydrogenase activity. In vitro administration of Alpha lipoic acid to cultures of CHO cells significantly increased cell survival, that was inhibited by lead treatment in a concentrationdependent manner. Administration of Alpha lipoic acid was not effective in decreasing blood or tissue lead levels compared to a well-known chelator, succimer, that was able to reduce them to control levels. Hence, Alpha lipoic acid seems to be a good candidate for therapeutic intervention of lead poisoning, in combination with a chelator, rather than as a sole agent.
*thion = "sulfur". The -SH functional group itself is referred to as either a thiol group or a sulfhydryl group, which binds to the heavy medial.

Brain Extract The Non-Soy Phosphatidylcholine

• Targets the repair of the hippocampus.
• Phosphatidylcholine common name lecithin is usually the most abundant phospholipid in humans and plants, often amounting to almost 50% of the total, this is the key building block of membrane bilayers.

  In particular, it makes up a very high proportion of the outer leaflet of the plasma membrane. Phosphatidylcholine is also the principal phospholipid circulating in plasma, where it is an integral component of the lipoproteins, especially the HDL.

Science Behind Brain extract

Porcine brain has been traditionally used in China and Thailand to improve brain functions and promote longevity. Previous studies had demonstrated that porcine brain derived peptide could protect brain against various insults including carbon monoxide and glutamate. Moreover, it could also decrease lipid peroxidation but increase the activities of various scavengering enzymes including superoxide dismutase, catalase and glutathione related enzymes. Based on the potential neuroprotective effect of porcine brain derived peptide mentioned above. (Jinetanaporn Wattanathorn et al, 2009), brain extract has been proven to reverse Alzheimer’s disease and in fact has been approved in 44 countries as a treatment option. Porcine brain contains 9.288 Phosphatidylserin total lipids per 100g of brain according to the USDA.

Phosphatidylserine is believed to be useful for:

• Brain heath and development
• Cell membranes working efficiently
• Essential for normal neuron structure and function
• Helping to release and receive neurotransmitters
• Important brain chemicals
• Metabolizing glucose
• Providing support for neurotransmitters in the brain

Memory and Processing

Phosphatidylserine naturally decreases as we age-- typically beginning to decrease at age 35. By age 40 this is consider age related memory loss. Brain extract that contains about 9% Phosphatidylserine helps to ensure that memory-related pathways function smoothly.
In 1997, Rainer, et al. treated 645 demented patients with pig brain extract daily for an average of 17.8 days, reporting that the treatment improved clinical global impression in 80% of the patients and significantly more in younger and less afflicted patients. In 1998, several reviewers pointed out pig brain extract as a potential therapy for Alzheimer’s disease. Windisch, et al. pointed out that clinical trials pig brain extract is able to induce brain repair in chronic injury and that the effects are long-lasting in patients. Research found that a single oral dose of pig brain extract induced progressive increase in Electroencephalography signals within an hour and peaked at 6 hours in elderly patients, associated with memory improvement.

In 2000, Bae, et al. carried out a double-blind placebo-controlled multicenter study of pig brain extract in 53 men and women with Alzheimer’s disease and found that the treatment significantly improved cognitive deficits and global function in patients with mild to moderate dementia.
Ruther, et al. evaluated 101 patients 6 months after completion of a 4-week course of pig brain extract in a placebo-controlled double-blind randomized study, showing a clear sustained beneficial effect of pig brain extract over placebo.

In 2001, Ruether, et al. did a 28-week, double-blind, placebo controlled study of 4-week pig brain extract treatment in 149 patients with Alzheimer’s disease, showing a 64.5% responder rate on the clinical global impression compared to 41.4% in the placebo group, as well as a 3.2 point difference in the ADAS-cog scale. The effects were maintained for 3 months after end of treatment.

In 2002, Muresanu, et al. replicated previous studies and showed that pig brain extract improved cognitive performance and global function of patients with Alzheimer’s disease, as well as activities of daily living. Panisset, et al. randomized 192 patients with Alzheimer’s disease to pig brain extract or placebo and showed that the pig brain extract treatment is well tolerated and significantly improved global score for 2 months after end of active treatment.

CDP Choline

• provides key developmental structure and functions like stem cell proliferation, lifelong memory function, and brain and spinal cord development, stimulates the production of dopamine.

CDP-choline, Cytidine 5'-diphosphocholine or citicoline, is an essential intermediate in the biosynthetic pathway of the structural phospholipids of cell membranes, especially in that of phosphatidylcholine.

Science Behind CDP Choline

Phospholipid methylation and PC membrane enrichment has been correlated with increases in beta-adrenoceptors by Hirata & Axelrod (1980). Increase in receptor densities by administration of CDP-choline has also been reported for the cholinergic system in young animals (Petkov & Popova, 1987). In this paper we demonstrate that D2 dopamine receptor densities, as indicated by the spiroperidol binding, which are normally reduced with aging (Seeman et al., 1987; Morgan et al., 1987) are partially recovered by administration of a choline and cytidine donor such as CDP-choline, known to increase the membrane levels of PC (Lopez-G. coviella et al., 1988). Similarly, the decline in muscarinic cholinoceptors also found with aging is clearly blunted by CDP-choline treatment.

The following studies show unprecedented encouragement
for dementia and Alzheimer’s sufferers:

A 30-day, double-blind study confirmed that taking 1000 mg of citicoline per day improved Alzheimer’s disease.3 (Institute for CNS Disorders, Basic and Clinical Neurosciences Research Center, La Coruña, Spain.)

In 20-, 30-, & 90-day double-blind placebo-controlled studies, citicoline was found to have statistically significant beneficial effects on memory function and behavior of Alzheimer’s patients.4 (Department of Psychiatric Science and Psychological Medicine, University of Rome “La Sapienza”, P.leMoro, 5, Rome, Italy.)

An 84-day, double-blind placebo-controlled study revealed that oral supplementation of 1000 mg of citicoline per day increased cognitive performance and improved cerebral blood perfusion and the brain’s bio electrical activity pattern in Alzheimer’s patients5. The same study also proved that 1000 mg of citicoline a day was well tolerated by patients and no adverse side effects were found.5 (EuroEspes Biomedical Research Center, A Coruña, Barcelona, Spain.) Emerging research has shown that brain function repair was dependant upon the amount of citicoline administered.

Dosages of 1000 to 3000 mg were studied. For advanced stages of Alzheimer’s, 3000 mg dosages were most effective.

In the two cases studied, changes in receptor densities as a consequence of CDP-choline administration seemed not to affect the affinity constant of the receptor for their ligands, which is consistent with the fact that in general, aging induced a decrease in receptor densities without any change in affinity (Pradhan, 1980). Thus, CDP-choline treatment seems to improve the dopamine receptor and also the muscarinic cholinoceptor function through increases in the receptor number. With the information available to date, it has been difficult to propose a molecular mechanism to explain this phenomenon, especially for the simultaneous effect on both systems. Some authors have tried to assign the parallel modification of dopamine and choline receptors by CDP-choline administration to a specific mechanism of increase in dopamine content of the striatum after treatment, which would cause a decline in the acetylcholine content leading to an increase in the cholinoceptor densities (Petkov & Popova, 1987).

It is well known that in most of the regions of the human brain, including the striatum*, the phospholipid content declines with age and that cholesterol declines even more, resulting in an important decrease in the cholesterol to phospholipid ratio (Sbderberg et al., 1990). It has also been shown that the decrease in cholesterol content of the membranes enhances their fluidity (Wilson et al., 1988). Therefore, aging would lead to an increase in membrane fluidity, as is indicated by our experiments showing a lower polarization value (higher membrane fluidity) for the old animals compared to the young animals. As CDP-choline administration increases brain phospholipid content (Lopez-G. Coviella et al., 1988), the cholesterol to phospholipid ratio would also decrease with the corresponding membrane fluidity increase. How these changes in membrane structure modify receptor function cannot be unambiguously explained at present. It should be borne in mind that receptor density measurements are a consequence of receptor number and optimal receptor structure and that the interaction of membrane phospholipids and proteins with receptor protein may affect receptor mobility as well as receptor structure.
Chronic treatment of aged mice with CDP-choline recovers the reduced density of dopamine and acetylcholine receptors of the striatum. This beneficial effect of the CDP-choline might perhaps be related, through more or less complex mechanisms, to an increase in brain membrane fluidity observed in these animals.

* The striatum, also known as the corpus striatum, neostriatum, or striate nucleus, is a subcortical (i.e., inside, rather than on the outside) part of the forebrain. It is the major input station of the basal ganglia system. The striatum, in turn, gets input from the cerebral cortex. In humans and primates, the striatum is divided by a white matter tract called the internal capsule into two sectors called the caudate nucleus and putamen.

Acetylcholine (ACh), acting through neuronal muscarinic acetylcholine receptors (mAChRs) and nicotinic acetylcholine receptors (nAChRs), is an important modulator of electrical activity in the brain. It is involved in numerous cellular processes underlying cognition including development, synaptic transmission, neuronal excitability and systems-level rhythmicity1-3. Stimulation of cholinergic inputs to the hippocampus demonstrates a decrease in the size of synaptic responses in glutamatergic projections in different regions of the hippocampus1,4-8. An acetylcholinesterase inhibitor (AChE-I), physostigmine, has been shown to enhance cholinergic transmission and depress glutamate release in hippocampal pathways9. Modulation of the synaptic strength of excitatory glutamate synapses in the hippocampus is believed to be involved in memory processing. The loss of cholinergic function, particularly in the hippocampus, has been implicated in Alzheimer’s disease (AD)11. Current treatment is mainly based on the use of AChE-Is. Although some beneficial effects of these drugs on cognition have been reported, these are costly and have undesirable side effects12. Several drugs commonly used today for AD treatment were developed from local and traditional medicine, such as galanthamine, an AChE-I which was developed from alkaloids in ‘Snowdrop”.  Wasana Pratchayasakul et al 2008

Oral Administration

CDP-choline releases its two principle components, cytidine and choline. When administered orally, it is absorbed almost completely, and its bioavailability is approximately the same as when administered intravenously.

Biopathways

Once absorbed, the cytidine and choline disperse widely throughout the organism, cross the blood-brain barrier and reach the central nervous system, where they are incorporated into the phospholipid fraction of the membrane and microsomes.

CDP-choline activates the biosynthesis of structural phospholipids in the neuronal membranes, increases cerebral metabolism and acts on the levels of various neurotransmitters. Thus, it has been experimentally proven that CDP-choline increases noradrenaline, stimulates tyrosine hydroxylase activity and dopamine levels in the central nervous system, which increases in brain acetylcholine.

Neuroprotective

Due to these pharmacological activities, CDP-choline has a neuroprotective effect in situations of hypoxia and ischemia, as well as improved learning and memory performance in human and animal models of brain aging.

Stimulatin Mitochondrial Activity

Furthermore, it has been demonstrated that CDP-choline restores the activity of mitochondrial ATPase and of membranal Na+/K+ ATPase, inhibits the activation of phospholipase A2 and accelerates the reabsorption of cerebral edema in various experimental models.

CDP-choline is safe, as toxicological tests have shown; it has no serious effects on the cholinergic system and it is perfectly tolerated. These pharmacological characteristics, combined with CDP-choline's mechanisms of action, suggest that this nutrient may be suitable for the treatment of cerebral vascular disease, head trauma of varying severity and cognitive disorders of diverse etiology.

Head Trauma

In studies carried out on the treatment of patients with head trauma, CDP-choline accelerated the recovery from post-traumatic coma and the recuperation of walking ability, achieved a better final functional result and reduced the hospital stay of these patients, in addition to improving the cognitive and memory disturbances which are observed after a head trauma of lesser severity and which constitute the disorder known as postconcussion syndrome

Acute Cerebral Vascular Disease.

In the treatment of patients with acute cerebral vascular disease of the ischemic type, CDP-choline accelerated the recovery of consciousness and motor deficit, attaining a better final result and facilitating the rehabilitation of these patients.

Senile Cognitive Impairment

The other important use for CDP-choline is in the treatment of senile cognitive impairment, which is secondary to degenerative diseases (e.g., Alzheimer's disease) and to chronic cerebral vascular disease. In patients with chronic cerebral ischemia, CDP-choline improves scores on cognitive evaluation scales, while in patients with senile dementia of the Alzheimer's type, it slows the disease's evolution.

Parkinson's disease

Beneficial neuroendocrine, neuroimmunomodulatory and neurophysiological effects have been described. CDP-choline has also been shown to be effective as co-therapy for Parkinson's disease.

Eye extract  

• Increases neuron production by 10 fold. 

Science behind Eye extract

Using immunohistochemistry, brain natriuretic peptide (BNP)-like immunoreactive (-LI) nerves localize to the anterior segment of the porcine eye. BNP-LI nerve fibers are visualized mainly in the aqueous outflow pathway, ciliary processes and anterior ciliary muscle. A small number of immunoreactive nerve fibers occur in the anterior iris stroma and in relation to the iris muscles and in the cornea. Given the known ocular effects of atrial natriuretic peptide (ANP) and that BNP and ANP seem to share common receptors, these results suggest an ocular role for peptides of this class independent of delivery by the systemic circulation.

Lions Mane mushroom (Hericium erinaceus)

• Stimulants nerve growth factor (NFG)-synthesis, repairs myelin e.g.,   The presence of white matter lesions and myelin abnormalities in the brain of Alzheimer’s disease patients is well supported by cytopathological (Braak et al., 2000; de la Monte, 1989; Englund et al., 1988; Kobayashi et al., 2002), in traditional chinese medicine Hericium erinaceus healing properties for the digestive tract and related organs. 

Science Behind Lions Mane Mushroom (Hericium erinaceus) Extract

Relation between cholesterol levels,
statins and Alzheimer's disease in the human population

The relationships between lower Cholesterol levels and reduced risk of Alzheimer s disease was demonstrated to help reduce accordance of the disease by up to 70%. Austen B et al, in 2002. Further research is required to determine whether cholesterol levels have a direct, causative, or indirect relationship with Alzheimer disease. The lipid lower effect of Lion’s Mane extract was demonstrated by Byung-Keun et al 2003. Lion’s Mane extract was given, at the dose of 200mg/kg body weight, substantially reduced blood serum total cholesterol:

• LDL decrease by (32.9%)
• Triglycerides decrease by (45.4%)
• HDL increase by (20.2%)

Other cholesterol lowering supplements may have an effect on other AD risk factors, or act by mechanisms which are independent of their effects of cholesterol levels?

Lion’s Mane Improved Cognitive Function In
Double-Blind Placebo-Controlled

Clinical trial using 30 subjects who were diagnosed with mild cognitive impairment were randomized into two 15-person groups, one of which was given Lion’s Mane and the other given a placebo.
Scoring 22 to 25 out of 30 points on a cognitive function scale based on the Revised Hasegawa Dementia Scale in a preliminary examination. Patients ages were from 50- to 80-year-old men and women diagnosed with mild cognitive impairment, in order to examine the efficacy of oral administration of Lion’s Mane (Hericium erinaceus), used to improving cognitive impairment, using a cognitive function scale.

After 2 weeks of preliminary examination

Patients were given Lion’s Mane 250 mg took 4 four capsules 3 times per day, e.g., 12 capsules per 24 hours for 16 weeks. After termination of the intake, the Patients were observed for the next 4 weeks. At weeks 8, 12 and 16 of the clinical trial, the Lion’s Mane group showed significantly increased scores on the cognitive function scale compared with the placebo group. The Lion’s Mane group’s scores increased with the duration of intake, but at week 4 after the termination of the 16 weeks intake, the scores decreased significantly.

Lion’s Mane Stimulates Neuronal

The results obtained in this study suggest that Lion’s Mane is effective in improving mild cognitive impairment. On the cognitive function scale, Lion’s Mane group increased the score dependent on the intake period of Lion’s Mane, showing significant differences compared with the placebo group at weeks 8, 12 and 16 of the trial. But the Lion’s Mane group score decreased significantly after 4 weeks of follow-up observation compared with the score at week 16. Thus, Lion’s Mane is effective in improving the mild cognitive impairment reversibly, and its continuous intake is necessary to maintain the effect, Koichiro Mori et al 2009.

In the present study, Koichiro Mori et al, 2008 demonstrate that extract of lion’s mane promotes the synthesis of nerve growth factor human hippocampus brain cells.  Lion’s mane alone had nerve growth factor-inducing activity among. Lion’s mane extract significantly increased nerve growth factor expression but not nerve growth factor protein synthesis. Therefore, it is possible that effective concentrations of lion’s mane extract to induce nerve growth factor protein synthesis and secretion differs from that to induce nerve growth factor expression, because protein synthesis/secretion is regulated by several factors.

Lion’s mane stimulates neuronal differentiation via an increment in the release of neurotrophic factors, including nerve growth factor, from glial cells.

Lion’s mane enhanced phosphorylation and gene expression as well as phosphorylation. The activation by lion’s mane is assumed to participate in nerve growth factor gene expression downstream is not involved in this signaling pathway, because of a lack of inhibitory action. It has been reported that the active components of lion’s mane are the hericenones c—h, which stimulate nerve growth factor protein synthesis in mammalians.

These results, therefore, raise the possibility that lion’s mane has unknown active compounds that promote nerve growth factor expression, other than hericenones, which are lipid-soluble. Furthermore, the oral administration of lion’s mane increased nerve growth factor expression in the mammalian hippocampus.

This result suggests the possibility that the active compound could be absorbed into blood and delivered into the central nervous system through the blood–brain barrier. The hippocampus is postulated to encode working memory.
The increase in the level of nerve growth factor in the hippocampus suggests the potential of lion’s mane to act on the central nervous system in vivo. However, we could not elucidate why lion’s mane increased nerve growth factor expression in the hippocampus. This difference might result from variations of expression level of signaling molecules related to signaling pathway or kinetic difference of active components of lion’s mane such as brain distribution and metabolism in these tissues. On the other hand, the mycelia of lion’s mane are known to contain erinacines, which also stimulate nerve growth factor synthesis.

It has been reported that oral administration of erinacine a significantly increases the level of nerve growth factor in the mammalian locus coeruleus and hippocampus, but not in the cerebral cortex.)  In conclusion, Lion’s Mane contains active compounds that stimulate nerve growth factor synthesis via activation of the brain pathway.

Alzheimer’s disease research focuses mainly on neuronal death and synaptic impairment induced by
β-Amyloid peptide, events at least partially mediated by astrocyte and microglia activation. However,
substantial white matter damage and its consequences on brain function warrant the study of oligodendrocytes (from Greek, meaning cells with a few branches, are a type of brain cell. They are a variety of neuroglia. Their main function is the insulation of axons the long projection of nerve cells in the central nervous system the brain and spinal cord of humans.) participation in the pathogenesis and progression of Alzheimer’s disease.