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Natural Support for Neurologic Health: A Multiple Pathway Approach

Article summary   Renata Trister DO

Advances in medicine, science and hygiene have allowed modern man to become the longest living humans in history. As life expectancy lengthened, disorders of the nervous system in the aging population are seen more frequently. Dementia, cerebrovascular disease as well as progressive disorders such as peripheral neuropathy and Alzheimer’s are a growing concern for the aging patient.  Diseases of the nervous system are being diagnosed in record numbers in the United States: up to 6.8 million suffer from dementia; approximately 4 million have Alzheimer’s disease (AD), and roughly 1.5 million may suffer from Parkinson’s disease (PD), with 50,000 newly diagnosed patients every year. These numbers are projected to continue to increase.  Dysfunction in older patients should not be assumed to be the result of the aging process.  Although progressive decline in neurologic functioning is a normal aging process, progression to a neurologic disease is not inevitable.  Early intervention may prevent and delay the deterioration in these disorders.

Research suggests that a cumulative effect of imbalanced biochemical pathways can greatly impact neurologic cellular decline. Four major biochemical pathways are thought to mediate both aging and premature neurologic decline. By maintaining adequate function in these pathways, it may be possible to achieve optimal neurologic health and brain function.

Environmental factors such as poor diet, toxins and oxidative damage can stress biochemical pathways in the body and accelerate the biological aging of tissue.

Four Biochemical Pathways Implicated in Nervous System Decline

I.  Chronic Inflammation—Research suggests that chronic inflammation is a possible mechanism in aging associated neuro-degeneration. Multiple aspects of the inflammatory pathway are capable of propagating premature aging and neuron cell death. Chronic inflammation beyond its protective role, can cause harm to tissue.  Epidemiological evidence indicates that populations taking anti-inflammatory drugs for other conditions have a reduced risk of neurodegenerative conditions.  Inflammation and oxidation are closely linked.  Oxidants serve as signaling agents for the pro-inflammatory factors.  Several natural substances offer safe and effective alternatives to anti-inflammatory drugs, which are known to cause various adverse side effects.

II. Mitochondrial Dysfunction—Tissues with a high-energy requirement, such as the brain and heart, have a greater density of mitochondria—the cell’s energy-producers. Since the brain depends so highly on mitochondrial energy supply, dysfunction of mitochondria can affect the central nervous system (CNS) more severely than other tissues.  Research suggests two methods of supporting mitochondrial health and function: 1) promoting healthy mitochondrial energy production, and 2) combating free radical production and damage by increasing mitochondrial antioxidants.


III. Endocrine Imbalance—Aging is associated with a reduced ability to adapt to stress and chronic elevations of stress hormones called glucocorticoids (e.g., cortisol).Animal and human data suggest that high levels of glucocorticoids can be particularly detrimental to the hippocampus (the brain structure involved in learning and memory). In addition, changes in glucose and insulin handling during the aging process can lead to neuronal degeneration due to negative effects on nerve cell structure and function. Proper diet, exercise, and nutritional interventions may help reduce glucocorticoid levels, enhance the body’s ability to cope with stress, and improve glucose and insulin metabolism.

IV. Hypomethylation—Methylation, the transfer of a methyl group (CH3) from one molecule to another, is required for numerous biochemical reactions vital to good health. However, insufficient levels of folate and vitamins B6 and B12 can cause reduced methylation, or hypomethylation, which in turn can produce elevated levels of the amino acid homocysteine (Hcy). Elevated Hcy levels are strongly linked to cognitive decline and irreversible dementia.  See tables below.

Nutritional Modulation of the Four Pathways

Fortunately, interventions begun in the initial stages of the disease process may prevent or delay the course of neurologic deterioration, resulting in an overall improvement.  The following nutrients may help prevent and interrupt the damaging cascade that contributes to neurologic decline.

Niacinamide—Niacinamide, a form of the B vitamin niacin, is a potent inhibitor of inflammatory cascade.  In animal models, administration of niacinamide resulted in reduced brain damage and reduced neurologic functional losses.

Essential Fatty Acids—Fish oils, which contain eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are well known for their anti-inflammatory activity. Furthermore, DHA is required for normal brain function in adults. Decreases in brain DHA content are associated with age-related cognitive decline, dementia, and AD.

Resveratrol—Resveratrol is a polyphenol found in the skins of red grapes and various other plants. In vitro, animal, and epidemiologic research suggests that resveratrol may protect against inflammation and CNS disorders.  It is also a potent antioxidant.

N-Acetylcysteine (NAC)—The protective effect of NAC is likely related its restoration of brain glutathione (GSH) levels.GSH is central to antioxidant defenses in the brain and cellular detoxification of free radicals. In addition, NAC has been shown to support proper mitochondrial function.

Alpha-Lipoic Acid (ALA)—ALA is a cofactor in the synthesis of ATP (energy required for tissue function) and improves overall mitochondrial function. ALA is also an excellent antioxidant agent in neurodegenerative diseases due to the fact that it can interrupt free radical damage at several points. Animal research has shown that ALA supplementation elevates antioxidants in various brain regions and improves memory in aged mice.In addition, ALA supports healthy blood glucose levels and insulin activity.

Acetyl-L-Carnitine (ALC)—ALC is a vitamin-like substance that may improve energy production within brain cells via its effect on mitochondria.An analysis of studies reports that persons with dementia given 1.5 to 3 grams of ALC daily have shown improvement in numerous clinical measures of cognitive function such as memory, depression, and mental deterioration.

Magnesium & Thiamin—Magnesium plays an important role in maintaining the integrity and permeability of the mitochondrial membrane as well as assisting in energy-producing machinery of the mitochondria. Thiamin is a cofactor needed for mitochondrial energy production.

Coenzyme Q10 (CoQ10)—CoQ10 is a mitochondrial antioxidant cofactor that has been shown to be neuro-protective. In addition to being a potent free radical scavenger, CoQ10 is also critical for energy production by the mitochondria. CoQ10 supplementation has proven effective in a wide variety of age-related conditions.

Vitamin E—Vitamin E is the primary antioxidant found in all tissues. Low vitamin E levels are consistently associated with an increased risk and occurrence of neurologic disease, including AD and Parkinson’s. In a study of patients with AD, treatment with 2000 IU of vitamin E per day for 2 years was beneficial in delaying the primary outcome (time to the occurrence of death, institutionalization, loss of ability to perform activities of daily living, and severe dementia) of disease progression.

Ginkgo (Ginkgo biloba)—Ginkgo biloba extract (GBE) is an approved treatment for dementia in Germany, and it is the only nonprescription substance considered a treatment for dementia in Canada. Many clinical studies have demonstrated the effectiveness of GBE in the treatment of patients with dementia, AD, and age-associated memory and cognitive impairment. In addition, GBE may also prevent changes in mitochondrial structure and function associated with aging of the brain.

Adaptogenic herbsAdaptogens are plants that help to decrease cellular sensitivity to stress. Herbs with adaptogenic properties may be beneficial in ameliorating the decreased ability to handle stress and the increased levels of glucocorticoids associated with aging and neurodegeneration. Ayurvedic herbs such as ashwagandha (Withania somnifera), holy basil (Ocimum sanctum), and brahmi (Bacopa monniera) have a positive influence on stress response, mental function, and cognition.

Mixed Carotenoids—Carotenoids are a class of naturally occurring plant pigments that provide the bright red, orange, and yellow colors of fruits and vegetables. A balanced intake of mixed carotenoids, as found in a healthy diet, provides the best protection against oxidative damage. In addition, the carotenoids lutein and zeaxanthin are found concentrated in the retina of the eye where they offer protection from conditions such as age-related macular degeneration.

Folate, Vitamin B6, and Vitamin B12—Folate and vitamins B6 and B12 are needed for proper methylation and to keep Hcy within a normal range.Insufficiencies of these nutrients may result in forgetfulness, memory loss, confusion, depression, dementia, and mood and sensory changes.


Healthcare professionals and their patients must take a preventative stance against neurologic decline. Due to the great deal of interest and research in this area, information about appropriate nutritional supplementation is constantly evolving. By looking for early warning signs and providing nutritional guidance that simultaneously addresses chronic inflammation, mitochondrial dysfunction, endocrine imbalance, and hypomethylation, perhaps more people can live out their most rewarding years with mind and body intact.