Mending the Mind With Smart Nutrients

 This article is a preliminary article that was later published in Healthy Aging magazine, Age Management Medicine for Physicians as "Energizing the Heart with CoQ10".  Click on the magazine to the right to read the final article from Healthy Aging Magazine, "Sharpen the Mind With Smart Nutrients".

     In a recent commentary appearing in the Journal of Nutrition, Health and Aging  researchers predict that by the year 2050, 30% of the American population will be 65 years of age or more.  As this trend continues, there is increased concern by healthcare professionals about preserving and restoring brain function.  In fact, in the largest and most detailed study concerning the nation’s overall mental health, data suggests that globally the United States is poised to rank number one in mental health disorders. This landmark study headed by Dr. Ronald Kessler of Harvard University and known as the National Comorbidity Survey Replication and published in the Archives of General Psychiatry, found that half of all lifetime cases of mental dysfunction began at age 14.

Undetected and Undertreated

     The National Comorbidity Survey Replication study also revealed that despite many various treatment options to improve cognitive function, decades generally past before treatment is sought, thus leading to the development of more serious mental disorders and co-occurring mental health illnesses. However, since the brain is mechanically influenced, scientist content that it’s deterioration should be slow and doesn’t co-exist with the physical degeneration of body organs generally seen with aging.  In practical terms, the brain should be one of the last organs to deteriorate. 

     Despite the fact that conventional medicine has made only small strides in treating and or preventing the development of many age-related cognitive disorders,emerging data indicates there are safe, natural and potent dietary supplements that can restore neurological structure and function. Data presented at the recent third International Conference on the Mechanisms of Action of Nutraceuticals confirms the notion that a number of natural supplements can prevent and treat Alzheimer’s, senility, improve brain function, sharpen memory and keep the mind youthful at any age. 
Rejuvenating Strategies for the Brain

     Scientists have identified several different supplemental strategies that focus on regulating many different modes of action that either prevent neurological degeneration and or preserve the integrity of various neurological systems.  One system that has been the focal point of neurological restoration is that of brain energetics. This is due to the fact that mitochondrial supported bioenergetics decline with age, while oxidative stress increases during aging. The accumulation of oxidative damage to mitochondria, protein and nucleic acids in the brain can cause neuronal and cognitive dysfunction.However, researchers at the Institute of Brain Aging and Dementia at the University of California have identified a group of nutrients that can directly or indirectly protect mitochondria from oxidative damage and improve mitochondria function.  Conversely, these guardians were named mitochondrial nutrients.

The Mitochondrial Energy System

    Mitochondria are known as the powerhouse of the cells.  There is considerable evidence that memory loss is associated with brain mitochondrial decay and RNA/DNA oxidation.  These specialized cells, composed of inner compartments are designed to manufacture energy, a small portion being electrical, and the largest portion being adenosine triphosphate (ATP).  ATP is the body’s main energy currency and it is within the mitochondria that 90 percent of cellular ATP is produced.The following synopsis summarizes some of the most compelling data concerning these nutrients that improve mitochondrial function and in some cases slows down and or reverses the negative aspects of age related cognitive decline.

Mitochondrial Nutrients

Acetyl-L-Carnitine (ALCAR)

     Acetyl-L-carnitine is a derivative of the amino acid L-carnitine and readily crosses the blood brain barrier much more efficiently.Well-formulated studies suggest that ALCAR prevents damage to nerve growth factor, which are proteins that stimulate the growth and development of central and peripheral nerve cells. Scientists have also found that acetyl-L-carnitine prohibits the destruction of brain cells in culture.  This mechanism of action demonstrates how injury to brain cells induced by the amyloid beta peptide, prevalent in the brains of Alzheimer’s patients and in other degenerative cognitive disorders is minimized or abruptly stopped.                                                    

Dietary Considerations

     Current data indicates that diet alone can’t supply the mitochondria with adequate amounts of acetyl-L-carnitine (and carnitine) that are needed to maximize mitochondria function.  Supplementation is clearly warranted and as a direct result of inadequate levels of acetyl-L-carnitine, normal brain metabolism is severely compromised.  This negative physiological process is directly linked to the development of the cognitive abnormalities associated with Alzheimer’s disease.

Down Regulation and Binding to Cells

     Researchers at the University of California Berkeley testing whether age-related cognitive decline was a direct result of the down-regulation and binding affinity of carnitine acetyltransferase (CAT), a key major mitochondrial enzyme used for fuel utilization.  Analyzing the efficacy of CAT by studying the brains of young and old rats, supplemented for 7 weeks with acetyl-L-carnitine, the above researchers found that old rats supplemented with high levels of CAT showed decreased oxidative damage, improved mitochondrial enzyme activity, increased substrate-binding affinity, and a reversal  of mitochondria dysfunction and decay. Additionally, acetyl-L-carnitine in doses of 1.5 to 3 grams daily for a three month period showed a marked improvement in mental clarity and memory in individuals experiencing mild neuro-degeneration. Some studies suggest that this may be due in part to the fact that acetyl-L-carnitine serves as a neurotransmitter itself.  In its acetylated  form , carnitine enhances the production of acetylcholine, one of the brain’s most important neurotransmitters and a neuro-protective system referred to as the cholinergic system.

The Cholinergic System

     There is evidence that now confirms that the cholinergic signaling pathway of nucleotides in neural and non-neural tissues, while some differences exist, there are striking similarities.  Both acetylcholine (ACH) and ATP is taken up and stored in synaptic vessels released in a Ca (2+) dependent manner, and acts on nearby ligand-gated or excitatory metabolic receptors.  Conversely, both ATP and acetylcholine are co-stored and co-released, having a profound affect as neurotransmitters that appear to correct a variety of pathological neural disorders originating from dysfunctions or malfunctions within the cholinergic system.

Mounting Confirmation

     Recently, scientists at the Department of Neurology at Hadassah University Hospital reported that in light of new studies, the maintenance of a balanced cholinergic system is  crucial to the proper functioning of the central nervous system, the peripheral nervous system and the neuromuscular junction.  New data indicates that the cholinergic system is not only involved with neuron and synapse excitability, it may also be linked to proper immune function and has anti-inflammatory properties.  In practical terms, the cholinergic system, while regulating or enhancing many cognitive functions, its multiple and opposing regulatory actions expand beyond that of just a mitochondrial neuronal nutrient.

The Acetyl-L-Carnitine Arginate Phenomenon

     Acetyl-L-carnitine arginate is a patented version of carnitine.  Combined with the amino acid arginine this form of carnitine was able to stimulate neurite out growth in animal models similar to that of nerve growth factor. Neurites are the branch like pathways that brain cells use to communicate with one another.  Neurites by promoting new connections known as synapse, they can significantly improve communnication between cells within the central nervous system, the home of the brain and the spinal cord.

     Current data indicates that acetyl-L-carnitine stimulates neurite growth by 5.6% in five days.  However, in a landmark study appearing in Neurochemical Research, acetyl-L-carnitine arginine in the same time period stimulated neurite growth by 19.5%.  Acetyl-L-carnitine arginate also inhibits the toxicity that occurs when B-amyloid cells proliferate, as seen in aging brain cells and Alzheimer’s patients.  This dynamic combination also increases the sum and substance of neurtotransmitters.

Alpha Lipioc Acid (ALA)

      Alpha Lipoic-acid is referred to as the universal antioxidant and heightens the overall activity of the entire inborn antioxidant defense system. Proliferation of pro-oxidants accelerates the production of free radicals , speeds up the aging process and destroys genetic material within the cells.  In the mitochondria  alpha lipoic acid compensates for the reduction of a key nutrient during oxidation, namely, glutathione. 

     Glutathione scavenges the mitochondria and neutralizes heavy metal ions that have the potential to stimulate free radical production and heighten oxidative stress.  However, with the administration of R-lipoic acid, the biologically active half of ALA this increases glutathione levels within the cells and enhances the mitochondrial membrane potential. ALA also stimulates increased oxygen consumption at the cellular level, dramatically restoring them to youthful ranges as seen in animal models. Other animal studies have demonstrated that ALA can reduce damage to neurons caused by toxic substances that are by-products of inflammatory processes.  Alpha-lipoic acid is also involved with a variety of metabolic functions that regulate energy production in muscles, glucose metabolism, liver and nervous system function, and all physiological processes that are intimately linked to proper brain function.

Combining Forces

      According to professor  Bruce Ames of the University of California Berkeley, acetyl-L-carnitine and lipoic acid used together can inhibit the age-associated increase of oxidative damage to lipid membranes, proteins and nucleic acids in old rats.  By combining these two mitochondrial nutrients he was able to restore the activity and substance binding affinity of carnitine acetyltransferase, a key mitochondrial enzyme.30  Professor Ames and fellow researchers also found that not only did alpha lipoic acid (ALA) and acetyl-L-carnitine reverse brain aging, but also improved memory and physical activity of subjects within one month after the administration of this dynamic combo.  These researchers found  that 250 mgs of alpha lipoic acid and 1500 mgs of ALC daily to be very beneficial.  In new studies emerging data indicates that alpha-lipoic acid scavenges free radicals and inhibits oxidant reactivity, while activating cofactors of defective mitochondrial enzymes to stimulate enzyme activity.  ALA also improves mitochondrial structure and function, age-related cognitive decline as well as oxidative damage.  Researchers at the University of California also recently reported that ALA and coenzyme 10 used in combination improves cognitive dysfunction and reduces oxidative damage much more effectively that either of these mitochondrial nutrients alone.

CoQ10 and Brain Mitochondria
     Co-enzyme Q10 (CoQ10), also known as ubiquinone is a naturally occurring compound found in all cells of the human body.  As a fat soluble substance it serves as a coenzyme in the energy producing metabolic pathways of the cells.  Highly concentrated in the heart, liver and kidneys  ,this mitochondrial nutrient protects proteins and mitochondrial DNA from oxidation and has powerful antioxidant capabilities.  Over 90% of the body’s metabolic energy needs are regulated by CoQ10.In fact CoQ10 is responsible for the reactions of at least three mitochondrial enzymes, making it the essential component of the electron transport chain where metabolic energy is released.

     In trials conducted at the University of Hong Kong, Chinese researchers exposed SHSY5Y neuroblastoma cells to neurrotoxic beta amyloid peptides, while starving cells of oxygen and glucose to asses the neuro-protective effects of CoQ10 in doses of 10 microM.  According to these researchers CoQ10 had a dramatic effect against abeta neurotoxicity by preventing the opening of mitochondrial transition pores and by reducing concentrations of superoxide anions, which are known to disrupt normal metabolic processes.  
     This study also demonstrated that CoQ10 plays a profound role in increasing mitochondrial cell survival rates. In a related study appearing in Experiment Neurology, researchers in Portugal using brain mitochondria isolated from 20-month-old diabetic goto-kakizaki rats, found that CoQ10 was very efficient in preventing mitochondrial dysfunction.  These researchers reported that CoQ10 inhibited significant decreases in ATP production and in hydrogen peroxide production induced by the neuro-toxic peptide abetal-40.  This study strongly suggests that CoQ10 therapy can help maintain adequate mitochondrial energy levels, which when are low ,often accelerates the manifestation of diabetes and Alzheimer’s disease.

     Additional clinical trials have demonstrated  that CoQ10 plays a role in combating a number of neuro-degenerative disorders (Alzheimer’s, Parkinson’s and Huntington’s) via its ability to scavenge free radicals produced during oxidative phosphorylation in the inner mitochondrial membranes.  For example, in a 16 month randomized placebo-controlled study of 80 subjects with mild Parkinson’s disease, there was a marked improvement in halting the functional deterioration of this disorder at 1,200 ms/day of CoQ10.  Furthermore, studies indicate that CoQ10 prevents the development of many other neurodegenerative disorders like amyotrophic lateral sclerosis (ALS) via its co-ability to act as an antioxidant and as a electron acceptor at the mitochondrial level.

     In conclusion here, the late eminent CoQ10 researcher and former President of the New England Institute, Dr. Emile G. Bliznakov, M.D., stated that without CoQ10 there is no spark, no ignition, no creation of energy.  Take CoQ10 out of the mitochondria and you have a cell that has as much potential as a V-8 engine without spark plugs.  You have, in essence, a dead engine.

Mitochondria and Oxidative Damage

     While disruption within mitochondria energy systems and the cholinergic system can lead to a number of brain related malfunctions, oxidative damage to mitochondria also increases susceptibility to the development of a number of neuro-degenerative maladies. Scientists now know that brain cells are like electrical power-plants operating at extremely high metabolic rates.  In the process `a lot of high energy fuel (like ATP and creatine) are utilized, giving rise to the natural release of free radicals .  Free radicals as stated are highly charged oxidative molecules that damage cellular structures and have been linked to the cause and development of several age related diseases, including   neuro- degenerative disorders.  Current data indicates that brain cells are very susceptible to free radical damage and without some viable way to quickly repair the damage caused by these rouge agents and to naturally rekindle refueling processes, brain cells quickly die.  This phenomenon is a key factor that  causes the brain to age at an accelerated rate, thus causing memory loss, cognitive decline, and serious mental conditions such as Alzheimer’s and Parkinson’s disease.

Stress: A Key Culprit

     While stress is a key adaptive factor that can be very beneficial, uncontrolled stress can lead to heart disease and brain disorders.  This happens as a direct result of the continual release of high levels of excitatory neurotransmitters and the stress hormone cortisol.
     A large body of research has conclusively shows that supplemental nutrients like Vitamin C, E and selenium can neutralize free radical aggression and restore metabolic balance.  There is also emerging research on a number of new natural substances that have shown remarkable results in also preventing mitochondrial oxidation, as exampled by the herb Rhodiola.

Restoration of Brain Function and Rhodiola

     Rhodiola, also known as Golden Root, was approved for medical use in 1969 in Russia by the pharmacological committee of the USSR Ministry of Health.  First discovered by Drs. Zakir  Ramazonov and Maria de Bernal Suarez, Ph.D.’s, this herb has over thirty years of clinical research.  Studies indicate that Rhodiola helps regulate the function of neurotransmitters, the agents the brain uses to send messages to other cells.43  Dr. Richard P. Brown, M.D., an associate clinical professor of psychiatry at Columbia University and author of The Rhodiola Revolution maintains that Rhodiola supports brain health in a variety of ways.  First, it reduces damage to the mitochondria, cell membranes and neutralizes oxidation by free radicals acting as a cellular antioxidant.  Secondly, it keeps energy transport systems working at optimal levels by increasing the production of the high-powered energy molecules creatine phosphate (CP) and adenosine tri-phosphate (ATP).  This action helps counteract fatigue and sustain brain and intellectual function, especially in times of intense stress and work over-load.  Thirdly, as stated above, at the neurochemical level,  Rhodiola enhances the production of neurotransmitters like serotonin, norepinephrine and dopamine. These eurotransmitters are key to the optimal function of the brain and its long-term health.  Dr. Brown also makes note of the fact that Rhodiola  switches on what is referred to as nerve networks in the brainstem called the reticular activating system , that literally wakes up the brain and also increases the manufacture of the above neurotransmitters.  As a adpatogen, this herb relieves stress and reduces cortisol production while helping the body supply oxygen and other vital nutrients that assist in keeping the brain healthy, thus insuring its smooth and efficient operation.

Rhodiola and Depression

     To assess how well Rhodiola combats depression, researchers at the Department of Neurology at the Armenian State Medical University in a phase III clinical randomized double-blind placebo-controlled study, administered Rhodiola in doses of 340 and 680 mg/day for 6 weeks  to subjects.  At the end of this trial group A (340 mg/day) and group B (680 mg/day), all of the subjects showed improvements in overall depression, as well as with decreased insomnia, emotional instability and somatization.  The placebo group(C) that was administered 2 tablets daily, didn’t show any improvements.  The researchers concluded that in patients with mild to moderate depression, Rhodiola in dosages of 340 and or 680 mg/day has powerful anti-depressive properties with no side effects.
     In addition to the above, Chinese researchers found that Rhodiola reduced the oxidative damage to cells, specially protecting PC12 cells against glutamate excitotoxic damage by inhibiting the production and entry of Ca2+ and the release of calcium stores.

Some Other Smart Nutrients

B Vitamins

     While B vitamins are well-known for their ability to help convert food into fuel, and combat stress, they are essential to preserving mental health.  In fact, deficiencies of various B-vitamins can cause neuro-degeneration resulting in mental and cognitive decline, as well as the development of brain atrophy.

     Several well-controlled studies have confirmed the efficacy of B-vitamin therapy in preserving and restoring mental health.  For example, researchers at the Department of Psychiatry at the University of Birmingham recently reported that more clinical studies are needed to guide clinicians in the dose, frequency, route or duration of thiamine (B1) in treating the personality disorder known as Korsakoff’s syndrome.  Used as the treatment of choice in treating the above disorder, there is some uncertainty about appropriate dose and duration.

     In a fascinating study recently conducted at the University of Oxford in the United Kingdon involving 1,648 men and women, 65 and over, researchers found that low levels of vitamin B12 accelerates mental decline. Low levels of this nutrient have been associated with the development of Alzheimer’s disease, dementia, and cognitive impairment.Italian researchers in a dementia-free cohort-study of 816 subjects composed of 434 women and 382 men, with an average age of 74, found that low serum concentrations of the B vitamin folate is an independent prediction of the development of dementia and Alzheimer’s disease.  In a related study conducted at the King’s College Hospital psychiatry department in London, investigators administered either folic acid (folate) or a placebo for six weeks to patients with low levels of this nutrient. There was a dramatic improvement in the group taking folic acid, which consisted of both depressed and schizophrenic patients.

     Vitamin B6 also has neuro-protective properties and has been used as an anti-depressive agent to treat schizophrenic patients. Studies indicate that it helps transform amino acids into substance known as monoamines which are key groups of neurotransmitters.  Conversely niacin (vitamin B5) has a long history of use in the treatment of schizophrenia.

Phosphatidylserine (PS)

     Phosphatidylserine is a naturally occurring phospholipid found abundantly in brain tissue and is a component of all cellular membranes.  A large body of evidence suggests that  phospholipids are critical to proper cognitive function.  Well controlled human studies show that PS enhances membrane transport which improves communication between cells, neurotransmitter function and membrane receptor conductivity.  One of the largest initial studies conducted in Italy with PS tracked 494 elderly individuals  suffering from mild to severe mental decline, over the course of a six-month treatment period of either 300 mgs daily of PS or a placebo revealed  that  PS showed substantial improvement in both behavior and mental function versus the placebo group. 

     Nicotinamide in its reduced form known as NADH (adenine dinucleotide) with the H standing for hydrogen, this highly energized compound is well-known for its ability to produce the neurotransmitter dopamine.  Dr. George Birkmayer, a pioneer of NADA research and Director of the Birkmayer Institute for Parkinson Disease, discovered that NADH inhibits dopamine destruction ,the neurotransmitter which is found in extremely low levels in individuals suffering from Parkinson’s disease as a result of auto-oxidation. According to Dr. Birkmayer during normal physiological processes, the neurotransmitter dopamine is subjected to auto-oxidation, which forms cytotoxic chemicals that appear to damage very sensitive areas in the basal brain.  Studies indicate that NADH inhibits this damage by minimizing cell death and regeneration of brain tissue.

Omega 3 Fatty Acids

     Omega 3 from fish oils contain essential fatty acids that are necessary for optimum brain health.  Researchers at Stirling University ( Scotland) found that in autistic children a enzyme defect removes fatty acids from brain cell membranes at an accelerated rate.  By supplementing the diet with omega-3 fatty acids, these nutrients help to slow down the activity of this enzyme.  These researchers reported a marked increase in improving behavior, mood, imagination, spontaneous speech, sleep patterns and focus of autistic children as a direct of the inclusion of omega 3 fatty acids.

Glycerophosphocholine (GPC)

     GPC, once referred to as L-alphaglycerylphosphorylcholine or choline alfoscerate is found in virtually all body cells.  Because it is found abundantly within human breast milk researchers speculated that its role in sustaining human health was significant.  It is now well documented that GPC is vital to newborns and the developing brain as a result of the demands the brain has for the B-vitamin choline.  Additionally, GPC is a phospholipid metabolite found concentrated in neuronal membranes, made from lecithin.  Absorbed extremely well , GPC crosses the blood brain barrier with ease supporting brain function and learning processes by directly increasing the synthesis and secretion of new acetylcholine.  This action is similar to that of the cholinesterase inhibitor drugs donepezil (Aricept) and rivastigmine (Exelon) which are prescribed to treat Alzheimer’s by activity interfering with the enzyme that sabotages acetylcholine production. As just cited, GPC activity stimulates the production of new acetylcholine, which to a greater degree has a more direct impact on preserving and improving brain health. Studies indicate that GPC also protects neurons and improves signal transmissions by acting as a precursor to the development of membrane phospholipids.                                

New Ways, New Approaches, New Thoughts

     Based on new and emerging data, age-related cognitive decline may begin much earlier than once thought or perceived. Although many negative factors can contribute to altering normal brain function, the good news today is that modern scientific inquiry has unlocked the secrets behind nature’s intelligence. Current data indicates that certain natural nutrients can interact and communicate with various neuroreceptors , and other physiological and neurological systems  that can prevent, improve, and in many cases restore the brain to normal functional levels, thus supporting the brain’s natural restoration and repair efforts throughout life. With this new found knowledge science now tells us that age- related cognitive decline is not inevitable, it is now a unexpected neurological event. 

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 In a recent commentary appearing in the Journal of Nutrition, Health and Aging  researchers predict that by the year 2050, 30% of the American population will be 65 years of age or more.  As this trend continues, there is increased concern by healthcare professionals about preserving and restoring brain function.

Healthy Aging

Dr. George Redmon