Neuronutraceuticals

Neologisms are Necessary Evils
Neurodegenerative and “functional” disease is now the focus of nutritional approaches for prevention and treatment. With “new” approaches to disease come neologisms. The age of the therapeutic use of nutritionals and natural agents for psychiatric, neurological and behavioral disorders is encompassed in the neologism “neuronutraceutical” – or perhaps “psychoneuronutraceutical?” Beyond the quest for new terminology is an increasing recognition that nutritional factors can make significant contributions to psychoneurological wellness.

The recognition of the ubiquitous nature of “Molecules of Emotion” (Candace Pert, PhD) such as hormones and peptides and the role of disordered immune function in chronic neurodegenerative disease have led to the concept of neuroimmunomodulation. This discipline has bred its own group of experts with their chosen label as “neuroimmunologists” – or perhaps “psychoneuroimmunologists?” The term neuroimmunology was coined by the scientist and popular health care writer Dr. Candace Pert PhD, further presented by Dr. Max Gerson, MD and recently reinforced by Dr. Jay Lombard MD (see resource section). Curiously, these authors write as though they have not read each others work – or if they have, they provide incomplete, interindividual acknowledgments.

The science of psychoneuroimmunomodulation focuses on the recent identification of messenger molecules that seem to cross over from the regulation of immune or gastrointestinal function to neuronal function, or vice versa. The importance of the inextricable linkage of digestive and neurological function has stimulated much contemporary interest and it is featured in my new book entitled “The Natural Way to Digestive Health”. What is known, however, about the “new science” of neuroimmunology was inferred by the zealous vivisectionist, Claude Bernard and his colleagues, in the mid 19th Century; implying that neologisms are not necessarily descriptive of new or even novel discoveries.

A Role for Psychoneuronutrition
At law, dietary supplements are not to be used to prevent or treat disease; but “at medicine” this legal dictum (Dietary Supplement and Health Education Act of 1994) has been superseded by necessity in the management of neurological disease. Drug therapy for neurodegenerative disorders still has relatively few triumphs. The promise that a defined chemical derangement in the nervous system is amenable to a focused, chemical correction with a drug is subject to frequent reappraisal and the role of psycho-neuronutrition is appealing increasingly to neuroscientists.

There is no single diet that is optimal for the treatment of central nervous system (CNS) disease, but balanced nutrition with an adequate supply of macronutrients, vitamins, minerals and essential fats is required as nutritional support for healthy brain function. There is a role for “functional foods” or foods for “special nutritional purposes” to manage certain neurological diseases (e.g. branched – chain amino acids for hepatic encephalopathy), but recent attention has focused on selective botanical and nutritional agents for neurological wellness.

The Omega-3 Story
The role of essential fatty acids has become increasingly clear with reports of their benefit in demyelinating diseases, attention deficit disorder (ADD), chronic organic brain syndromes and affective disorders, including bipolar and unipolar depression. Essential fatty acids, especially of the omega-3 type, are a principal, structural component of nerve cell membranes, which play a pivotal role in neurotransmission. It has been suggested that Western populations have a widespread deficiency of omega-3 fatty acids in their diet and this is a particular concern for children and infants where brain development is crucial for subsequent health. Scientific studies imply that intellectual quotients and psychoneurological function are highly associated with optimal intake of active types of omega-3 fatty acids, principally docosahexanoic (DHA) and eicosapentanoic acid (EPA).

The best source of active omega-3 fatty acids (DHA and EPA) is cold water fish, such as mackerel, cod and salmon. Unfortunately, the Western diet is loaded with fried fish, coated with refined flour in a “reconstituted” format. These food items are relative strangers to omega-3 fatty acids, but fresh, well prepared fish is expensive and often out of the reach of many people. Busy lifestyles have directed more informed types of consumers to take fish oil as a dietary supplement.

Recent scientific studies have shown the enhanced bioavailability and clinical efficacy of enteric coated fish oil. Compliance with fish oil supplements is a major problem that can be overcome by this novel delivery system, where enteric coating of fish oil capsules provides targeted release of active, stabilized DHA and EPA in the gut, resulting in enhanced absorption. Enteric coating of fish oil capsules enhances compliance with fish oil supplements and it helps to facilitate the administration of higher doses of fish oil that are desirable in selected clinical circumstances, such as the treatment of inflammatory disease or depression.

One major “deception” in current nutritional practice, reflected in misguided advice to consumers, has been the widespread notion that plant sources of omega-3 fatty acids are optimal. Flax seed oil and other plant oils e.g. soy, and walnut oil are not a reliable source of active omega-3 fatty acids. These oils contain the omega 3 precursor (alpha linolenic acid, ALA) of the longer chain length, active, omega-3 fatty acids DHA and EPA. There is great inter-individual variability in the ability of the body to convert ALA to EPA and DHA, thereby mandating that fish oil, in a stabilized format is required for reliable correction of omega-3 fatty acid deficiency or for the reliable use of these fatty acids in therapy. Before the advent of enteric coated fish oil, taking fish oil has been difficult and fraught with compliance problems.

If there was one message that is important to contribute to the brain (and cardiovascular) health of our nation, it is the recognition of the importance of the potential preventive and therapeutic benefits of DHA and EPA. Considerable debate has occurred about the relative importance of DHA or EPA for brain health. Protagonists of omega-3 fatty acid therapy for CNS disorders, especially depression, have focused on the importance of EPA, but it is recognized that one of the main building blocks of the nervous system is DHA. I believe that DHA supplementation is more relevant for the correction of structural disorders of the CNS, whereas EPA may have a greater role in more “functional disorders”, of the CNS, such as depression. Having proposed this “naïve” differentiation of the effects of omega-3 fatty acids, it appears that DHA works for ADD!

Depression tends to occur at certain times in life e.g. middle age and following childbirth in women. I support the notion that there is a simple and readily understandable reason why postnatal depression occurs. In the latter part of pregnancy, the fetus goes through a stage of accelerated brain development which requires abundant supplies of omega-3 fatty acids. These fatty acids are derived from maternal sources. I believe that depletion of essential fatty acids of the omega-3 series may be one important reason why depression occurs often following pregnancy. Also, omega-3 supplementation in pregnancy may be very important for primary growth of the fetal brain, with its important implications for normal central nervous system functioning in later life. Clearly, grandmother was correct when she made us “choke” on the end of a teaspoon full of cod liver oil!

Free Radical Damage
The generation of free radicals and their negative effects on cellular function has formed a foundation of theories to explain many chronic diseases. Essential fatty acids are surprisingly efficient free radical scavengers, but in this process lipid peroxidation and cell membrane damage occurs. Recent attention has focused on the use of powerful antioxidants for CNS health including: vitamins C and E, glutathione, lipoic acid, n-acetyl-cysteine, polyphenolic compounds (bioflavonoids), flavone glycosides, coenzyme Q10 and s-adenosyl methionine (SAMe). There has been “much a do” about SAMe and its beneficial effects on brain function, including its natural antidepressant potential. SAMe is involved in the production of cellular antioxidants (e.g. glutathione) and it operates with beneficial effects on the regional density and function of acetylcholine receptors in the CNS. In addition, it promotes selective neurotransmitter production. It remains to be seen if SAMe will measure up to some of the early, “hyperbolic” claims of its value.

Hormonal Issues
One major area of interest has been the role of estrogen in the prevention or correction of cognitive deficits in chronic brain disease, such as Alzheimer’s disease. In Alzheimer’s disease the deposition of beta amyloid (and aluminum fibrils) may be dependent upon certain cytokines (e.g. interleukin-6). Estrogen appears to inhibit amyloid synthesis by interfering with certain cytokines. The observation that estrogen replacement therapy (ERT) may protect against postmenopausal Alzheimer’s disease has been an important prompt to further explore remedies of natural origin for this untreatable disorder.

Our knowledge about estrogen receptors has been expanded in the past two years by the identification of different types of estrogen receptor that seem to preferentially operate in different cellular and anatomic locations in the body. Whilst the application of ERT is not questioned in the prevention of osteoporosis and perhaps cardiovascular disease in the mature female, the use of estrogenic agents to prevent chronic neurodegeneration is more debatable.

One emerging area of interest is the use of soy isoflavones for CNS health. Soy isoflavones have both estrogenic and powerful antioxidant effects. This is a new and intriguing possible application of these phytoestrogens, genistein and daidzein, in the promotion of brain wellness. Some nutritionists have focused on the potential value of dehydroepiandrosterone (DHEA) for the maintenance of cognitive function in mature individuals. DHEA seems to have beneficial effects on the structure and function of neuronal dendrites. Although DHEA may have similar effects to estrogen in the area of neuroimmunomodulation, the “jury remains out” on its real benefits in states of accelerated declines in cognitive function.

Neurotoxins
Environmental toxins, such as alcohol, cigarette smoke, heavy metal poisoning, food additives, industrial chemicals, and insecticides or pesticides have been implicated in neurological damage and behavioral disorders. Conventional medicine has tended to manage behavioral or psychiatric disorders, such as ADD or depression, with drug therapy, without consideration of neurotoxicology. There has been a public reaction against the overuse of stimulating drugs such as Ritalin for ADD or Prozac for depression. With increasing evidence that chemical neurotoxins may cause psychological, psychiatric and neurological disorders, nutritional attempts to “clean up” the body stores of these toxins have been popularized.

The efficacy of nutritional “clean ups” is questionable. Standard and popular forms of “body cleansing” or “detoxification” with herbs and purges are unlikely to benefit individuals with toxic, chemical damage to the CNS. Many environmental chemicals with demonstrated or suspected toxicity are stored in body fat or fatty tissue, such as the brain. A role for novel lipid compounds, such as squalene (extracted from deep sea, shark liver oil), in removing certain lipophilic toxins is an interesting prospect.

Specific Neuronutriceuticals
Certain nutrients or compounds of natural origin have been popularized for the management of dementia, memory loss and abnormal cognition. These popular remedies include Gingko biloba extract, phosphatidylserine (PS), acetyl-l-carnitine (ALC), vinpocetine and Bacopa monniera (Bacopa).Whilst Gingko biloba has been shown in clincial trials to improve brain function in mature individuals, PS is highly regarded as beneficial in the partial reversal of declines in cognitive function in patients with dementia.

Evidence to support the use of ALC and vinpocetine in cognitive dysfunction is emerging, but it is not as strong as the scientific data that supports the use of PS and Gingko biloba. Bacopa is an Ayurvedic herb, with much precendent for its use in CNS disorders. It is worthy of much more scientific study for cognitive and behavioral disorders. St. John’s Wort and Kava are used in a widespread manner for natural approaches to depression and anxiety disorders, with the revelation of their respective ability to cause photosensitization (St. John’s Wort) and “odd” skin rashes (Kava). Perhaps, a reminder is necessary that natural therapies are not always “innocuous”.

The recent recognition that the brain possesses regenerative powers due to the defined presence of stem cells (adjacent to the corpus callosum) has opened the door for the use of natural growth factors and it has rekindled interests in protomorphogenesis (the supply of natural nutrient, building blocks to tissues). A number of natural compounds and drugs may serve the basis of treatments that could result in the variable reversal of traumatic, inflammatory, toxic, immune and vascular damage to nervous tissue.

Non-drug, non-nutraceutical options
Any discussion about psycho-neurological function must include “behavioral” medicine (psychology, psychiatry, mind-body medicine, mental gymnastics). Brain exercises, such as cognitive therapy can be shown to exert a major positive effect on psychiatric disorders such as depression and obsessive compulsive disorders.
Social isolation and lack of environmental stimulation are important causes of failure to thrive in infancy and diminished cerebral function in the elderly. Earlier assumptions by scientists that learning on the visceral level was not possible have been overturned. Whilst we have recognized the importance of touch, love, nurturing, relationships religion and prayer in healing and psychological well-being, we are only just starting to let these treatment modalities percolate approaches to disease management.

Conclusion
It is misleading to propose that chronic neurological disease is explainable totally in nutritional terms. There are many causes and risk factors for CNS disorders including genetic predispositions, adverse lifestyle, toxic, infective and coexisting disorders such as cardiovascular disorders. Some of the commonest causes of declines in neurological or cognitive function are often overlooked. For example, more than 10% of all apparent declines in cognition in the elderly may be iatrogenic due to the overuse of prescription and OTC sedatives and tranquilizers. The implications of toxic chemicals in our environment for CNS health in children and adults has been grossly underestimated and much CNS disease is caused by cardiovascular disorders.

Psychoneuronutrition presents exciting options for the practice of neurology, but conventional medicine remains somewhat slow on the uptake. These circumstances are surprising in the face of great difficulties that exist in the effective treatment of many of the diseases of the CNS that present themselves. New horizons are being created by neuronutriceuticals (psychoneuronutraceuticals) and optimal nutritional approaches (psychoneuronutrition) to promote the health of the central nervous system.

Resources

1) Fredericks C., Psycho-Nutrition, Grosset and Dunlap, NY, NY, 1976.
2) Gerson M., The Second Brain —– ?
3) Holt S., The Natural Way to a Healthy Heart, M. Evans Inc., NY, NY, 1999.
4) Holt S., The Natural Way to Digestive Health, M. Evans Inc., NY, NY, 2000 (due July 2000).
5) Jonas G., Visceral Learning: Toward a science of self-control, Viking Press, NY, 1972.
6) Lombard J., Germano C., The Brain Wellness Plan, Kensington Books, NY, NY, 1997.
7) Pert C., Molecules of Emotion, —– ?
8) Sharpe R., The Cruel Deception, Thorsons Publishing Group, Wellingborough, UK, 1988.
9) Weiner MA, Reducing the Risk of Alzheimer’s, Stein and Day Publishers, NY, NY, 1987.

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