Sustain the Brain This section is compiled by Frank M. Painter, D.C.
Send all comments or additions to: Frankp@chiro.org
From The February 2001 Issue of Nutrition Science News
by Jill Stansbury, N.D.
High on the aging populations' list of fears is losing one's mental faculties. With Alzheimer's disease and other forms of senile dementia affecting some 25 percent of all people older than 80, it certainly isn't an irrational fear. Hope lies in research that is revealing nutrition's role in both treating and preventing cognitive impairment.
Certain types of mental decline result from exposure to toxins and to both endogenous and exogenous oxidizing agents—all of which appear to contribute to brain inflammation, scarring and cognitive impairment. Brain inflammation may result from the presence of toxins and from allergies, stress or low nutrient levels in the tissues. The inflammatory process creates chemicals such as free radicals that cause oxidative damage. This oxidative damage may contribute to senile dementia. Exposure to free radicals can be especially damaging when brain tissues lack adequate levels of antioxidants and other nutrients to mitigate the consequences of chronic inflammation. The aging brain can have low levels of such nutrients for several reasons including a poor diet or inadequate nutrient absorption. Thus, antioxidants and B vitamins should top anyone's list of brain food.Antioxidant nutrients such as beta-carotene, bioflavonoids, essential fatty acids, selenium, vitamins C and E, and zinc all reduce inflammation. Animal studies have shown antioxidant levels in the brain decline with age. The lowest levels are associated with the greatest neuronal impairment. [1] Polyphenols in green tea, namely the catechins, have antioxidant properties that may help protect the central nervous system from oxidative damage. [2]
B Vitamins are also essential nutrients for mental health, with deficiencies potentially manifesting as psychosis and cognitive impairment. [3]The psychotic personality disorder known as Korsakoff's syndrome, for example, is a consequence of thiamin (vitamin B1) deficiency. Niacin (vitamin B3) deficiency is associated with delirium, dementia, and memory deficits. Vitamin B6 helps transform amino acids into monoamines, an important group of neurotransmitters. Hormone replacement therapy and birth control pills deplete vitamin B6, and many hormone-induced mental or emotional disturbances may be improved with B6 supplementation. Abnormally low levels of vitamin B12 are associated with Alzheimer's disease. Folic acid deficiency is associated with forgetfulness, psychosis, dementia, nd Alzheimer's disease. [4]
Clearly, B vitamins are essential for optimal mental function. Supplementation with these and antioxidant vitamins is useful for preventing, and possibly treating, cognitive impairment.
Brain-Function Boosters
In addition to antioxidants and B vitamins, various nutrients and plant derivatives may help reduce inflammatory damage to the central nervous system as well as prevent and treat impaired brain function.Acetyl-L-Carnitine (ALC), a transport molecule important to cellular energy production, has become a central focus in neurodegenerative disease research. Carnitine is a vitaminlike compound that plays a role in mitochondrial energy production. ALC is one form of carnitine and is structurally similar to the neurotransmitter acetylcholine. Acetylcholine plays a central role in basic nerve transmission, concentration, memory and learning. The leading pharmaceutical drugs used for senility are, in fact, aimed at elevating acetylcholine levels in the brain. Congenital conditions such as muscle and heart weakness and mental retardation are associated with maternal ALC deficiency. [5] Supplementing with ALC is said to improve general metabolism in many organ systems, including the nervous system. ALC is noted to protect and stabilize muscarinic receptors (mediators of the parasympathetic nervous system) and intracellular membranes, as well as support mitochondrial metabolism and general cholinergic (processes involving acetylcholine) neurotransmission. [6] By enhancing membrane stability, energy production, and neurotransmission, ALC may improve mental function. [7] In addition, it may also have anti-inflammatory effects that reduce free radical generation.
Several studies have explored ALC's usefulness for Alzheimer's disease patients. ALC may increase B-endorphin levels, which are frequently low in Alzheimer's patients. [8] B-endorphin is a naturally produced opiatelike compound associated with general mood and mental demeanor. ALC's ability to bind cortisol and increase nerve growth factor production within the hippocampal region may explain its positive effects on neurons.
In a double-blind Italian study, 236 elderly patients with mild senility were treated with either 1,500 mg ALC or placebo. The ALC group showed significant improvements in memory and cognition compared with controls. [9] Several smaller studies have also noted positive effects on cognitive function in Alzheimer's disease patients. The designers of one 40-patient study evaluated the efficacy and tolerability of ALC therapy. In the double-blind trial, senile patients were divided into two groups of 20 and treated for 40 days with either two 500 mg ALC tablets or placebo three times daily. Mental parameters were assessed at zero, 20, and 40 days of treatment. Researchers concluded that short-term, intensive 3,000 mg/day ALC treatment could improve the main mental parameters of senility without significant side effects. [10]
Alpha-Lipoic Acid (ALA) has been researched since the 1950s as a treatment for Alzheimer's and Parkinson's diseases. ALA (synonymous with thioctic acid) is an antioxidant produced endogenously; because it is both fat- and water-soluble, it travels throughout the body. ALA may protect the body from oxidative damage by enhancing detoxifying agents such as glutathione, which occurs in the brain and serves as an antioxidant in these tissues. [11]
Results of animal studies demonstrate that ALA can reduce damage to neurons caused by toxic substances that are by-products of inflammatory processes. [12] Another animal study showed memory improvement in aged rats given ALA. [13]
ALA is also involved with numerous metabolic functions including energy production in muscles, glucose metabolism, liver function, and nervous system function, all of which ultimately have effects on the brain. [14] Clinical trials conducted in Germany have shown ALA to be valuable for treating diabetic polyneuropathy, a disease involving the peripheral nerves. Supplementation was shown to improve motor and sensory nerve conduction. [15] Doses ranging from 600 to 1,800 mg per day were used both orally and intravenously. Higher dosages administered intravenously reduced symptoms most quickly, but lower dosages taken orally for several months also provided relief.
Docosahexaenoic Acid (DHA), an omega-3 long-chain fatty acid, is one of the primary structural components of the brain. Adequate DHA levels are necessary for proper neurotransmissions, and deficiencies of this essential fat have been linked to memory loss and depression. In a 1995 multicenter European study, 494 elderly persons treated for six months with 90 mg per day DHA (contained in 300 mg bovine phosphatidylserine) showed marked improvement in apathy and social withdrawal symptoms. [16]
Huperzine A (HUPA), a purified alkaloid compound isolated from Chinese club moss (Huperzia serrata), may benefit memory and cognition in several ways, one of which is influencing cholinergic activity. Hyperzine's actions are very similar to that of cognitive drugs, because it is a highly purified single chemical.
Several studies indicate that HupA has a highly selective affinity for acetylcholinesterase (an enzyme that breaks down unused acetylcholine) and inhibits it primarily. [17]By doing so, HupA inhibits the degeneration of the neurotransmitter acetylcholine, which is rapidly broken down in the brains of Alzheimer's patients. A shortage of the neurotransmitter also appears to contribute to memory loss. HupA has also been observed to bind to nicotinic receptors in the central nervous system, [18] an activity believed to improve mental function. Finally, HupA acts as a neuronal cell protector, [19] which may be both therapeutic and preventive for Alzheimer's disease.
For these actions on the brain, HupA may be useful in cases of dementia and memory impairment. In animal tests, HupA is orally bioavailable and well absorbed. [19] HupA appears to act quickly and remain active for many hours. [20] Repeated doses do not appear to promote tolerance or unresponsiveness. [21]Animal studies show it easily crosses the blood-brain barrier and enters all areas of the brain. [18] HupA trials have not shown significant toxicity or side effects.
Phosphatidylserine (PS), a phospholipid present in large amounts in brain tissue and a component of all cell membranes, is thought to be necessary for optimal cognitive function. Supplementing with PS is believed to improve membrane transport, which enhances communication between cells, as well as neurotransmitter release and membrane receptor activity. [22] PS supplements are produced from soy or animal brain phospholipids, but most research has been conducted on products derived from animal sources.
PS may reduce stress-induced cortisol response, which, when excessive, promotes brain inflammation. One placebo-controlled study of nine healthy men was conducted at the University of Naples in Italy. Patients received 800 mg/day PS derived from bovine brain cortex. The dose counteracted stress-induced cortisol release. [23]
Several other small research trials have been conducted in Italy, including a placebo-controlled test involving a 300 mg/ day PS dose administered to a group of depressed, elderly women. Researchers noted that PS improved depression, memory, and behavior. [24]
Results from other trials conducted at Italian medical universities have shown PS to produce in both healthy and senile patients predictable EEG changes suggestive of improved concentration and awareness. [25, 26]Both Alzheimer's and Parkinson's diseases produce characteristic EEG changes. EEG mapping is being used to help diagnose and monitor brain diseases, as well as to investigate the effects of therapies such as PS. One such study conducted at a psychiatric hospital in Munich, Germany, used EEG mapping to monitor the effects of PS in 33 patients with mild dementia. The eight-week, double-blind, placebo-controlled, crossover trial showed significant EEG changes and symptom improvement for patients taking 300 mg/day PS compared with patients receiving placebo. [27]As positive as these findings may be, many people have concerns about using animal brain tissue until more studies can determine its safety. Some animal brain tissue may harbor contaminants such as prions, which are protein particles believed to cause various infectious nervous system diseases such as bovine spongiform encephalopathy, also known as Creutzfeldt-Jakob disease or mad cow disease (For more information on this, please see related news story). Because most studies involve brain-derived PS, many clinicians and physicians are waiting until more vegetable-based PS research is conducted before they seriously consider PS. Additionally, the therapeutic dose, which ranges from 50 to 100 mg several times a day, can be cost prohibitive.
Plant-Based Brain Boosters
"Why should anyone die who has sage in their garden", and "rosemary is for remembrance," as the old sayings go. Both of these herbs have been found to promote acetylcholine, the most versatile and common neurotransmitter. Rosemary (Rosmarinus officinalis) and sage (Salvia officinalis) have both been shown to enhance the actions of acetylcholine through cholinergic activity [28] and are listed as memory enhancers in old herbal compendiums. Lemon balm (Melissa officinalis), often called the gladdening herb, also has been found to improve cholinergic activity, [28] and is recommended in old herbals for improving mood and cognition. Two other herbs more commonly associated with memory enhancement are ginkgo and ginseng.Ginkgo (Ginkgo biloba) has been well documented to improve cerebral blood flow and to have antioxidant activity on the nerves and vasculature. Ginkgo may also reduce the age-related decline of neurotransmitters and receptors. Through these actions ginkgo may improve cognitive function and reduce central nervous system degeneration. [29]
Ginkgo also may slow the progression of Alzheimer's by promoting cholinergic activity, which is known to be deficit in patients with Alzheimer's disease [30].
Ginkgolide-B, a terpene-based active constituent of ginkgo, has been shown to act as a platelet activity factor antagonist, which improves blood viscosity and reduces blood vessel inflammation. The herb's flavonoids, which are potent free radical scavengers, combined with the ginkgolides, provide neuroprotection. [31]
Ginseng (Panax ginseng) contains glucosides known as saponins, which have, in laboratory studies, improved learning and memory in rats. [32] These saponins raise the levels of biogenic monoamines and promote hippocampal neuron function. Animal studies have shown ginseng to help prevent age-related cognitive decline. [33] One theory explaining how ginseng works suggests the herb may improve nitric oxide synthesis in the brain, heart, lung, and kidneys. Nitric oxide plays a role in vasodilation, and ginseng may improve the delivery of blood and oxygen to tissues.
Ginseng and ginkgo may also work synergistically, according to a small, double-blind study of 64 healthy patients previously diagnosed with neurasthenia, a condition of nervous debility derived from impaired spinal cord function. Subjects were divided into four groups and given either 80, 160, or 320 mg of the ginseng/ginkgo combination or placebo twice a day and evaluated at one, 30, and 90 days for cognitive and cardiac function. The different doses provided statistically significant improvements in several measures at various intervals compared with the control group. [34]
Results are far from conclusive about how certain supplements affect brain function and mental acuity. But the nutrients and botanicals mentioned here hold promise. With what's at stake, they deserve the attention of researchers and formulators.Sidebars:
Vinpocetine — a Stroke of Good Luck
Jill Stansbury, N.D., maintains a private practice in Battleground,Wash., where she specializes in botanical and natural therapies.
References1. Fariello RG. Peroxidative stress and cerebral aging. Int J Clin Pharmacol Res 1990;10(1-2):49-51.
2. Matsuoka Y, et al. Ameliorative effects of tea catechins on active oxygen-related nerve cells injuries. J Pharmacol Exp Ther 1995 Aug;274(2):602-8.
3. Riggs KM, et al. Relations of vitamin B-12, vitamin B-6, folate, and homocysteine to cognitive performance in the Normative Aging Study. Am J Clin Nutr 1996 Mar;63(3):306-14.
4. Ebly EM, et al. Folate status, vascular disease and cognition in elderly Canadians. Age Ageing 1998 Jul;27(4):485-91.
5. Winter SC, et al. Plasma carnitine deficiency: clinical observation in 51 pediatric patients. Am J Dis Child 1987 Jun;141(6):660-5.
6. Calvani M, et al. Action of acetyl-L-carnitine in neurodegeneration and Alzheimer's disease. Ann NY Acad Sci 1992:663:483-6.
7. Kanfer JN, et al. Clinical and neurochemical effects of acetyl-L-carnitine in Alzheimer's disease. Neurobiol Aging 1995;16(1):1-4.
8. Sano M, et al. Double-blind parallel design pilot study of acetyl levocarnitine in patients with Alzheimer's disease. Arch Neurol 1992;49:1137-41.
9. Cipolli C, Chiaria G. Effects of L-acetylcarnitine on mental deterioration in the aged: initial results. Clin Ter 1990;132:479-510.
10. Bonavita E. Study of the efficacy and tolerability of l-acetyl carnitine therapy in the senile brain. Int J Clin Pharmacol Ther Tox 1986;24:511-6.
11. Rauhala P, Chiureh CC. Effects of atypical antioxidative agents, S-nitrosoglutathione and mangancese, on brain lipid peroxidation induced by iron leaking from tissue disruption. Ann NY Acad Sci 2000;899:238-54.
12. Anuradha B, Varalakshmi P. Protective role of DL-alpha lipoic acid against mercury-induced neural lipid peroxidation. Parmacol Res 1999 Jan;39(1):67-80.
13. Stoll S, et al. The potent free radical scavenger alpha-lipoic acid improves memory in aged mice: putative relationship to nmda receptor deficits. Pharmacol Biochem Behav 1993 Dec;46(4):799-805.
14. Salazar MR. Alpha lipoic acid: a novel treatment for depression. Med Hypotheses 2000 Dec;55(6):510-2.
15. Ziegler D, et al. Alpha-lipoic acid in the treatment of diabetic polyneuropathy in Germany: current evidence from clinical trials. Exp Clin Endocrinol Diabetes 1999;107(7):421-30.
16. Cenacchi T, et al. Cognitive decline in the elderly. A double-blind placebo-controlled multicenter study on efficacy of phosphatidyl serine administration. Aging Clin Exp Res 1993;5:123-33.
17. Tang X, et al. Cognition improvement by oral Huperzine A: a novel acetylcholinesterase inhibitor. In: Alzheimer strategies. Giacobini E, Becker R, Editors. Boston(MA): Birkhauser; 1994. p 113-9.
18. Tang X, et al. Effect of Huperzine A, a new cholinesterase inhibitor, on the central cholinergic system of the rat. J Neuroscience Res 1989;24:276-85.
19. Raves M, et al. Structure of acetylcholinesterase complexed with the nootropic alkaloid, (-)Huperzine A. Nat Struc Biol 1997;4:57-63.
20. Wang Y, et al. Pharmacokinetics of Huperzine A in rats and mice. Acta Pharmacol Sin 1988;9:193-6.
21. Laganiere S, et al. Acute and chronic studies with the acetylcholinesterase Huperzine A: effect on central nervous system cholinergic parameters. Neuropharmacology 1991;30:763-8.
22. Cenacchi T, et al. Cognitive decline in the elderly: a double-bind, placebo-controlled, multi-center study on efficacy of phosphatidylserine administration. Aging (Milano) 1993 Apr;5(2):123-33.
23. Monteleone P, et al. Blunting by chronic phosphatidylserine administration of the stress-induced activation of the hypothalamo-pituitary-adrenal axis in healthy men. Eur J Clin Pharmacol 1992;42(4):385-8.
24. Maggioni M, et al. Effects of phosphatidlyserine therapy in geriatric patients with depressive disorders. Acta Psychiatr Scand 1990 Mar;81(3):265-70.
25. Rosadini G, et al. Phosphatidylserine: quantitative EEG effects in healthy volunteers. Neuropsychobiology 1990-91;24(1):42-8.
26. Fungeld EW, et al. Double-blind study used 100 mg of phosphatidylserine (PS) in Parkinsonian patients with senile dementia of Alzheimer's type (SDAT). Prog Clin Biol Res 1989;317:1235-46.
27. Engel RR, et al. Double-blind cross-over study of phosphatidylserine vs. placebo in patients with early dementia of the Alzheimer type. Eur Neuropsychopharmacol 1992 Jun;2(2):149-55.
28. Perry EK, et al. Medicinal plants and Alzheimer's disease: integrating ethnobotanical and contemporary scientific evidence. J Altern Complement Med 1998 Winter;4(4):419-21.
29. DeFeudis FV. Ginkgo biloba extract (Egb761): pharmacological activities and clinical applications. Elsevier 1991;13(3):163-7.
30. Kieszek S. Trials and perspectives in pharmacotherapy of Alzheimer's disease. Psychiatr Pol 1999 May-Jun;33(3):331-40.
31. Smith PF, et al. The neuroprotective properties of the Ginkgo biloba leaf: a review of the possible relationship to platelet-activating factor (PAF). J Ethnopharmacol 1996 Mar;50(3):131-9.
32. Wang A, et al. Effects of Chinese ginseng root and stem-leaf saponins on learning, memory and biogenic monoamines of brain in rats. Chung Kuo Chung Yao Tsa Chih 1995 Aug;20(8):493-5.
33. Liu M. Studies on the anti-aging and nootropic effects of ginsenoside Rg1 and its mechanisms of actions. Sheng Li Ko Hsueh Chin Chan 1996 Apr;27(2):139-42.
34. Wesnes KA, et al. The cognitive, subjective, and physical effects of a ginkgo biloba/panax ginseng combination in healthy volunteers with neurasthenic complaints. Psychopharmacol Bull 1997;33(4):677-83
Return to VINPOCETINE
Return to NUTRITION ARCHIVES
| Home Page | Visit Our Sponsors | Become a Sponsor |
Please read our DISCLAIMER |