Anti-Aging: Brain Cells: Maintain Health During Aging

  1. Increase Brain Growth Factors

    1. Exercise

    2. Fasting

    3. Ashwagandha

    4. Bacopa

    5. Coffee Fruit Extract

    6. Creatine

    7. Curcumin (Turmeric)

    8. Social and Intellectual Stimulation

      1. Lumosity, Elevate, BrainHQ, etc.

    9. GPC, Citicholine, or Phosphotidylcholine

    10. Huperzine

    11. Inosine

    12. Lion’s Mane

    13. Nootropics: Racetams

    14. Phosphotidylserine

  2. Increase Brain Blood Flow

    1. Ginkgo

    2. Vinpocetine

  3. Increase Cell Energy

    1. Acetyl L-Carnitine

    2. Alpha Lipoic Acid, Biotin

    3. Apigenin

    4. Coenzyme Q-10

    5. Creatine

    6. L-Arginine, a-Ketoglutarate, Whey Protein

    7. Melatonin

    8. Phosphotidylserine

    9. PQQ

    10. Resveratrol, Quercertin

  4. Protect the Nerves

    1. Acetyl L-Carnitine

    2. Carnosine

    3. Creatine

  5. Increase Helpful Neurotransmitters

    1. Phosphotidylserine

    2. Psychiatric Medications

    3. Psychiatric Supplements

      1. 5-HTP or L-Tryptophan

      2. L-Tyrosine

    4. Increase Memory and/or Concentration

      1. Acetyl L-Carnitine

      2. Choline, Citicholine, CDP-Choline

      3. DMAE

      4. Phosphotidylserine

      5. Pyroglutamate

      6. Racetams

      7. Vinpocetine

Sauna Therapy

Mild Cellular Stress to Preserve or Increase Brain Function:

Brain cells are at particular risk of being damaged by free radicals because the brain has a high oxygen turnover, and brain cell membranes are rich in polyunsaturated fatty acids, which are particularly prone to free radical lipid peroxidation. (Endocrinology, 1997 Vol 138, No. 1 p101-106) In addition, the brain is relatively deficient in antioxidants. To evaluate your own protection from this, measure lipid peroxidation as well as levels of antioxidants. 

Supplements, Herbs, Vitamins, Minerals and other Brain Building Blocks:

Vitamin E
Of the various types of chemicals found within the body, fat is the most susceptible to being damaged by free radicals. This explains why the brain, having such a high content of fat, is at such an increased risk for free radical damage. Vitamin E is a “fat soluble” antioxidant meaning that its protective effect is most realized in tissues with a high fat content–like the brain. This explains why vitamin E has been so extensively studied in such brain disorders as Parkinson’s disease and Alzheimer’s disease. It is vitamin E’s profound ability to limit the damaging action of free radicals in the brain that likely explains why it outperformed a so called “Alzheimer’s drug” in a clinical trial of Alzheimer’s patients in a 1997 report in the New England Journal of Medicine.1 Indeed, diets rich in natural sources of vitamin E are associated with a reduction in the risk of Parkinson’s disease by an incredible 61%.2 In individuals already given the diagnosis, the progression of Parkinson’s disease has been dramatically slowed with vitamin E and C supplementation.

Vitamin A                                                                                                                                           Vitamin A supplementation represents a preventive strategy for maintaining brain memory capacity.   RA receptor β and retinoid X receptor , known to be involved in STWM (Wietrzych et al., 2005), are also required for LTDM. Hence, aging-related retinoid signaling hypoexpression disrupts hippocampal cellular properties critically required for STWM organization and LTDM formation.

Gingko biloba
Like vitamin E, it has potent antioxidant activity. It also directly improves brain metabolism and increases brain blood flow. Gingko biloba is clearly one of the most extensively studied nutritional supplements, especially in neurodegenerative conditions. In a placebo-controlled, double-blind randomized trial published in the Journal of the American Medical Association, not only did Gingko biloba stabilize Alzheimer’s disease, but in many of the subjects there was an actual improvement noted in various standardized psychological tests.

Coenzyme Q-10
Plays an important role in the critical process of cellular energy and is found in every living cell of every living being. In addition, it serves an important role as a brain antioxidant. When administered orally it is readily absorbed and measurably increases the efficiency of cellular energy production as demonstrated in studies performed at the Massachusetts General Hospital. This explains why Coenzyme Q-10 is being vigorously evaluated at major institutions around the world as a therapeutic aid in brain disorders. Interestingly, Parkinson’s disease patients demonstrate dramatically lowered levels Coenzyme Q-10 which may in part explain why these patients experience higher levels of brain damaging free radical activity.

Alpha Lipoic Acid
This powerful antioxidant is the subject of intensive worldwide study in neurodegenerative diseases because of its powerful antioxidant activity as well as its ability to regenerate other important brain antioxidants including vitamins E, C, and glutathione. Unlike other antioxidants, alpha lipoic acid is both fat soluble and water soluble. This greatly enhances its ability to be absorbed from the gut and permits increased penetration into the brain.

N-Acetyl-L-Cysteine (NAC)
While glutathione represents one of the most important of the brain’s antioxidant’s defenses, it is generally considered useless when given orally. NAC is readily absorbed from the gut and dramatically increases the body’s production of brain protecting glutathione. The ability of NAC to increase brain glutathione is enhanced in the presence of adequate amounts of vitamin C and E. In addition to enhancing glutathione production, NAC itself is a potent antioxidant and has been demonstrated to reduce the formation of the free radical nitric oxide which has been implicated as having a causative role in Parkinson’s disease, Alzheimer’s disease, and several other neurodegenerative disorders.8

Damaged brain neurons are characterized by a decreased ability to produce energy. Like coenzyme Q-10, acetyl-L-carnitine enhances neuronal energy production by functioning as a shuttle–transporting fuel sources into mitochondria, the energy producing machinery of the neuron. It also assists in removing toxic by products of brain metabolism and acts as a potent antioxidant. Acetyl-L-carnitine has been demonstrated to protect laboratory animals from developing full-blown Parkinsonism when exposed to specific chemicals know to induce the disease. It has been extensively studied in Alzheimer’s disease and, as reported in a recent issue of the journal Neurology, acetyl-L-carnitine can profoundly reduce the rate of progression of Alzheimer’s disease in younger patients.

Research carried out at Stanford University evaluating 149 patients suffering from dementia demonstrated that orally administered phosphatidylserine produced a marked improvement on performance tests related to memory and learning in demented patients. Like acetyl-L-carnitine and coenzyme Q-10, phosphatidylserine plays an important role in maintaining the ability of brain neurons to produce energy. Phosphatidylserine is a fundamental component of the fatty membranes surrounding the mitochondria where energy production occurs. In addition, it also serves as a critical component of the membrane surrounding neurons and thus plays a fundamental role in the process by which brain cells both receive and transmit chemical messages.


This non-essential amino acid is found in high concentrations in serum, cerebro-spinal fluid and muscle tissues. Glutamine serves several key functions in human health, most notably as a key building block for glutathione, the body’s front-line antioxidant complex. Glutamine can easily cross the blood brain barrier where it is converted into glutamic acid, a precursor of GABA, a vital neurotransmitter that supports the central nervous system. Glutamine is utilized to 1) enhance metabolic energy, 2) increase mental alertness and clarity of thought, and 3) improve mood. Glutamine also raises blood sugar levels and may aid in treatment of hypoglycemia and controlling cravings for sugar and carbohydrates. Research has shown that supplementation of glutarnine may reduce the craving for alcohol. Other noted areas of interest are depression, senility, behavioral problems and autism in children.

Curcumin (or turmeric):

In particular, curcumin, a powerful antioxidant derived from the curry spice turmeric, has emerged as a strong inducer of the heat shock responseIn light of this finding, curcumin supplementation has been recently considered as an alternative, nutritional approach to reduce oxidative damage and amyloid pathology associated with AD.Consistent with this notion, maintenance or recovery of the activity of vitagenes, such as the HO gene, conceivably may delay the aging process and decrease the occurrence of age-related neurodegenerative diseases.

Vitamin D Deficiencies have been found in Parkinson’s disease, multiple sclerosis, and Alzheimer’s disease. It is only in the past several years that vitamin D has been recognized as having far more important role in human health than simply aiding bone formation. Vitamin D is now recognized as a potent fat-soluble antioxidant. Several studies have indicated that vitamin D’s ability to quench free radicals is even more powerful than vitamin E.

Vitamin B12
Deficiency of vitamin B12 has been associated with mental slowness, confusion, depression, memory difficulties, abnormalities of nerve function, Alzheimer’s disease, and multiple sclerosis. Not only is vitamin B12 critical for the maintenance of myelin, the protective insulating coat surrounding each neuron, but it also helps reduce the level of a particular amino acid, homocysteine, which has been associated with increased risk for Alzheimer’s disease, stroke, and myocardial infarction.

This important mineral is critical in a program designed to preserve and enhance brain function for several important reasons. First, adequate amounts of magnesium are necessary for the electrical depolarization of the neuronal membrane. This is the process by which chemical messages are transmitted from one neuron to the next. Next, magnesium enhances the function of various brain antioxidants thus helping to protect the brain against free radical damage. Finally, magnesium helps to prevent the production of free radicals within in the brain which increase inflammation. In Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis, this inflammation is accepted as one of the fundamental problems.

However, there seems to be some difficulty in getting magnesium into the brain. Research has shown results with a special form of magnesium (magnesium-threonine chelate) that can get into the brain more easily.  Animal models revealed improvements of 18% for short-term memory and 100% for long-term memory using this form of magnesium. Also, Magnesium-L Threonate is available from Life Extension.

Folic Acid
A large number of studies have confirmed a direct relationship between folic acid status and various neurological problems including dementia, memory loss, and even depression. Like vitamin B12, the importance of folic acid in preserving normal brain function likely stems from its role in reducing homocysteine. Homocysteine is a toxic amino acid, elevation of which is associated with more rapid deterioration in some forms of dementia as well as a dramatic increase in stroke risk.

Pyridoxine is a B vitamin critical for maintenance of adequate cellular metabolism. Its role in preserving brain function has been demonstrated in several studies showing a direct relationship between low levels of pyridoxine and severity of dementia. Like folic acid and B12, pyridoxine helps reduce homocysteine.

Niacin (as niacinamide)
Like pyridoxine, niacin is a B vitamin and a key co-factor in the fundamental process of brain cell energy production. Deficiencies of niacin can profoundly affect brain cell metabolism resulting in dementia.

Consider supplements such as vinpocetine, galantamine and ginseng. (Cognitive and behavioral responders to galantamine therapy show clinically related improvements in prefrontal network metabolism along with thalamic activation.)

The Destruction Of Brain Cells From Free Radical Oxidative Stress:

Many brain diseases now seem to be at least partially caused by the destruction of brain cells by free radicals, or more technically, “lipid peroxidation.” Although the body produces antioxidants, over time their production declines.

There is more and more research that suggests that the major change in the CNS that is associated with aging is free radical-induced oxidative damage. (Ames BN 1993 Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad 90:7915-7922)

In addition to the supplements outlined above, there are other strategies to help prevent this decline. Vegetables are key sources of antioxidants.(The Journal of Neuroscience October 1998;18.) A diet rich in vegetables may help prevent age-related mental decline. This particular research shows that vegetables, particularly spinach, may be beneficial in retarding age-related central nervous system and cognitive behavioral deficits.

Supplement combinations may work particularly well as antioxidants.

Vitamin E, beta-carotene and N-acetylcysteine protect the brain from oxidative stress by restoring glutathione content and normalizing the mitochondrial/cytosolic hexokinase ratio in the brain in addition to lowering levels of plasma corticosterone and glucose


Those in the scientific and medical communities generally agree nutrition is an integral aspect of preserving healthy brain function. Nutrition has been linked with better cognitive abilities, and several nutrients have effects in the realm of memory and cognitive performance.

Antioxidant vitamins, for example, are believed to reduce oxidative damage to the brain, thereby protecting cognitive function. Animal research out of Perth in Western Australia showed oxidative mechanisms related to neuronal cell death might play a major role in aging, and antioxidants can protect against neurodegeneration. Human research out of Italy also showed a link between cognitive decline and antioxidant status: Elderly subjects with mild cognitive impairment or Alzheimers disease showed lower plasma antioxidant levels compared to healthy controls.

One antioxidant, vitamin E, may prevent cognitive decline. A rat study conducted in Japan showed vitamin E prevented learning deficits commonly seen as a result of age-related oxidative stress.5 In addition, animals given vitamin E exhibited significantly accelerated learning functions compared to the control group.

A human study conducted by researchers at the Rush Institute for Healthy Aging in Chicago also demonstrated protective effects with vitamin E intake.6 Researchers analyzed data from a longitudinal, population-based study of 2,889 community residents (ages 65 to 102) and reported those in the highest quintile of vitamin E intake had 36-percent less cognitive decline than subjects in the lowest quintile. A similar study conducted by the same researchers showed increasing vitamin E intake from foods reduced the risk of Alzheimers in a subgroup of subjects who tested negative for the APOE-e4 allele (a protein associated with an increased risk of late-onset Alzheimers disease). A study conducted at Brigham and Womens Hospital in Boston further showed vitamin E supplements conferred modest cognitive benefits among elderly women, particularly among those who were also taking vitamin C another antioxidant.

A large body of evidence shows that both vitamins E and C are important for the central nervous system and that a decrease in their concentrations causes structural and functional damage to the cells, according to a research review out of the Jean Mayer USDA (U.S. Department of Agriculture) Human Nutrition Research Center on Aging at Tufts University in Boston.9

Additional animal research out of the same Brazilian university was conducted with vitamins C and E to investigate the link between homocysteine-induced oxidative stress and memory decline.11 According to the researchers, high levels of homocysteinean amino acid produced in the body that may increase the risk of Alzheimers disease when it occurs in high levelsare linked to an increase in free radical production, which can impair memory. The Brazilian researchers demonstrated how pretreatment with vitamins E and C prevented homocysteine-induced memory impairment.

Heat shock protein expression in aging and neurodegenerative disorders associated with oxidative stress: a nutritional approach.

Authors: Calabrese V, Scapagnini G, Colombrita C, Ravagna A, Pennisi G

Oxidative stress has been implicated in mechanisms leading to neuronal cell injury in various pathological states of the brain. Alzheimer’s disease (AD) is a progressive disorder with cognitive and memory decline, speech loss, personality changes and synapse loss. Many approaches have been undertaken to understand AD, but the heterogeneity of the etiologic factors makes it difficult to define the clinically most important factor determining the onset and progression of the disease. However, increasing evidence indicates that factors such as oxidative stress and disturbed protein metabolism and their interaction in a vicious cycle are central to AD pathogenesis. Brains of AD patients undergo many changes, such as disruption of protein synthesis and degradation, classically associated with the heat shock response, which is one form of stress response. Heat shock proteins are proteins serving as molecular chaperones involved in the protection of cells from various forms of stress. Recently, the involvement of the heme oxygenase (HO) pathway in anti-degenerative mechanisms operating in AD has received considerable attention, as it has been demonstrated that the expression of HO is closely related to that of amyloid precursor protein (APP). HO induction occurs together with the induction of other HSPs during various physiopathological conditions. The vasoactive molecule carbon monoxide and the potent antioxidant bilirubin, products of HO-catalyzed reaction, represent a protective system potentially active against brain oxidative injury.

Given the broad cytoprotective properties of the heat shock response there is now strong interest in discovering and developing pharmacological agents capable of inducing the heat shock response. Increasing interest has been focused on identifying dietary compounds that can inhibit, retard or reverse the multi-stage pathophysiological events underlying AD pathology. Alzheimer’s disease, in fact, involves a chronic inflammatory response associated with both brain injury and beta-amyloid associated pathology. All of the above evidence suggests that stimulation of various repair pathways by mild stress has significant effects on delaying the onset of various age-associated alterations in cells, tissues and organisms. Spice and herbs contain phenolic substances with potent antioxidative and chemopreventive properties, and it is generally assumed that the phenol moiety is responsible for the antioxidant activity.

NeuroRx 1:111-116, 2004
NeuroTherapeutics Prophylactic Activation of Neuroprotective Stress Response Pathways by Dietary and Behavioral Manipulations

Mark P. Mattson, Wenzhen Duan, Ruqian Wan and Zhihong Guo

Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center, Baltimore, Maryland 21224

Summary: It is well established that when most types of cells,including neurons, are exposed to a mild stress they increase their ability to resist more severe stress.

This “preconditioning”phenomenon involves up-regulation of genes that encode cytoprotectiveproteins such as heat-shock proteins and growth factors. Wefound that a similar beneficial cellular stress response can be induced in neurons throughout the brain by a “meal-skipping”dietary restriction (DR) regimen in rats and mice.

DR is effective in protecting neurons and improving functional outcome in models of stroke, Alzheimer’s, Parkinson’s and Huntington’sdiseases. DR induces an increase in the levels of brain-derivedneurotrophic factor (BDNF) and heat-shock proteins in neurons.DR also stimulates neurogenesis in the hippocampus, and BDNFplays a role in this effect of DR.

Physical exercise and environmental enrichment are two other manipulations that have been shown to induce BDNF expression in the brain, presumably because itis a mild cellular stress. When taken together with epidemiological and clinical studies in humans, the data from animal studie ssuggest that it may be possible to reduce the risk for age-related neurodegenerative disorders through dietary and behavioral modificationsthat act by promoting neuronal plasticity and survival.



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