Archive for the ‘- Alzheimer’s’ Category
In 1980s, 65% of all East Boston residents over the age of 65 were recruited in the study of neuroprotective effects of vitamins C and E. None of the people taking vitamin C or vitamin E developed Alzheimer’s disease when followed up in 4.5 years while among vitamin C non-users, 85% developed the disease. Among vitamin E non-users, 14% developed Alzheimer’s (1)
I was shown that supplementation with vitamin E and/or vitamin C might be useful in maintaining brain acetylcholinesterase (footnote a) activity at the normal level and serotonin (footnote b) concentration for some extent under the condition to induce experimental dementia in experimental animals (2)
High intake of vitamin E from food (tocopherol), but not from supplements (which usually contain alpha-tocopherol), is shown to reduce incidence of Alzheimer’s disease. The most common alpha-tocopherol alone may not be sufficient in the protective effects (3)
Sources
MC Morris et al, Vitamin E and Vitamin C Supplement Use and Risk of Incident Alzheimer Disease. Alzheimer Disease & Associated Disorders, 1998 – V12 – 3
LEE Lilha et al., Effect of supplementation of vitamin E and vitamin C on brain acetylcholinesterase activity and neurotransmitter levels in rats treated with scopolamine, an inducer of dementia, Journal of nutritional science and vitaminology, 2001, vol. 47, no5, pp. 323-328
MC Morris et. al., Relation of the tocopherol forms to incident Alzheimer disease and to cognitive change. Am J Clin Nutrition, Vol. 81, No. 2, 508-514, February 2005
Footnotes
a) Acetylcholinesterase (AChE) is an enzyme that degrades the neurotransmitter acetylcholine at neuromuscular junctions and cholinergic synaptic transmission in the brain.
b) Serotonin is a neurotransmitter found in the central nervous system. It is best known as a “happiness hormone” though it’s no hormone but monoamine.
In 1980s, 65% of all East Boston residents over the age of 65 were recruited in the study of neuroprotective effects of vitamins C and E. None of the people taking vitamin C or vitamin E developed Alzheimer’s disease when followed up in 4.5 years while among vitamin C non-users, 85% developed the disease. Among vitamin E non-users, 14% developed Alzheimer’s (1)
I was shown that supplementation with vitamin E and/or vitamin C might be useful in maintaining brain acetylcholinesterase (footnote a) activity at the normal level and serotonin (footnote b) concentration for some extent under the condition to induce experimental dementia in experimental animals (2)
High intake of vitamin E from food (tocopherol), but not from supplements (which usually contain alpha-tocopherol), is shown to reduce incidence of Alzheimer’s disease. The most common alpha-tocopherol alone may not be sufficient in the protective effects (3)
Sources
- MC Morris et al, Vitamin E and Vitamin C Supplement Use and Risk of Incident Alzheimer Disease. Alzheimer Disease & Associated Disorders, 1998 – V12 – 3
- LEE Lilha et al., Effect of supplementation of vitamin E and vitamin C on brain acetylcholinesterase activity and neurotransmitter levels in rats treated with scopolamine, an inducer of dementia, Journal of nutritional science and vitaminology, 2001, vol. 47, no5, pp. 323-328
- MC Morris et. al., Relation of the tocopherol forms to incident Alzheimer disease and to cognitive change. Am J Clin Nutrition, Vol. 81, No. 2, 508-514, February 2005
Footnotes
a) Acetylcholinesterase (AChE) is an enzyme that degrades the neurotransmitter acetylcholine at neuromuscular junctions and cholinergic synaptic transmission in the brain.
b) Serotonin is a neurotransmitter found in the central nervous system. It is best known as a “happiness hormone” though it’s no hormone but monoamine.
Exercise during midlife comparing with exercise during late life
Most of the studies into the protective effects of exercise against cognitive decline, dementia, and Alzheimer’s disease, followed the elderly people starting their 65s and watched the results, which were relevant to the beneficial effects in late life. However, there are some results where a large cohort of 65-79-year olds has been followed-up for around 21 years so information about physical activity during midlife was available. Those who who participated in at least “leisure-time physical activity” during midlife had significantly lower risks of dementia or Alzheimer’s disease comparing with those who did not exercise at all [1].
Another study has suggested that physical activity at even earlier ages (physical activity between ages 15 and 25 years was asked retrospectively) can improve or preserve cognitive ability in late life [2]. This cognitive decline risk reduction is at least comparable to the eisks reduction reported in studies of physical activity in older persons. Thus, midlife physical activity might be as important for preventing later cognitive decline as is physical activity at older ages.
Sources
- Rovio S, et al. Leisure-time physical activity at midlife and the risk of dementia and Alzheimer’s disease. Lancet Neurol 2005;4:705–11
- Dik M, Deeg DJ, Visser M, Jonker C. Early life physical activity and cognition at old age. J Clin Exp Neuropsychol 2003;25:643–53
Caffeine, the most widely consumed behaviourally active substance in the western world (Pharmacol Rev 51 1999: 83–133), has neuroprotective effects in cases of hypoxia and ischaemia (Brain Res Rev 33 2000: 258–274). Does caffeine protect against neurodegeneration in Alzheimer’s disease as it does in Parkinson’s? Researchers from Faculty of Medicine of Lisbon, Portugal, tested the hypothesis that average daily caffeine intake in the period of 20 years before the diagnosis could be lower than caffeine intake in age- and sex-matched healthy people and showed that indeed, people who was diagnosed with Alzheimer’s consumed an average 74 mg (less than one cup) while the controls had about 200 mg.
“These results, if confirmed with future prospective studies, may have a major impact on the prevention of AD,” concluded the researchers (Eur J Neurology, Volume 9, Issue 4, 2002: 377–382).
In a Canadian study, daily coffee intake decreased the risk of Alzheimer’s by 31% during a 5-year followup in 65-year old people [Am J Epidemiol 2002, 156, 445-453.]. The Finland, Italy and the
Netherlands Elderly (FINE) Study showed that elderly men drinking three cups of coffee daily had the least cognitive decline [Eur J Clin Nutr 2007, 61, 226-232]. Tea drinking (Am J Epidemiol, 2004, 159, 959-967.], or flavonoid intake from tea has not been associated with a reduced risk of dementia.
The low coffee consumers in mid-life had the highest occurrence of dementia and Alzheimer’s at late-life, and the highest scores on the depression scale (J Alzheimer’s Disease 16: 2009, 85–91).
Caffeine, the most widely consumed behaviourally active substance in the western world (Pharmacol Rev 51 1999: 83–133), has neuroprotective effects in cases of hypoxia and ischaemia (Brain Res Rev 33 2000: 258–274). Does caffeine protect against neurodegeneration in Alzheimer’s disease as it does in Parkinson’s? Researchers from Faculty of Medicine of Lisbon, Portugal, tested the hypothesis that average daily caffeine intake in the period of 20 years before the diagnosis could be lower than caffeine intake in age- and sex-matched healthy people and showed that indeed, people who was diagnosed with Alzheimer’s consumed an average 74 mg (less than one cup) while the controls had about 200 mg. ”These results, if confirmed with future prospective studies, may have a major impact on the prevention of Alzheimer’s,” concluded the researchers (Eur J Neurology, V 9, Issue 4, 2002: 377–382).
In a Canadian study, daily coffee intake decreased the risk of Alzheimer’s by 31% during a 5-year followup in 65-year old people (Am J Epidemiol 2002, 156, 445-453.). The Finland, Italy and the Netherlands Elderly (FINE) Study showed that elderly men drinking three cups of coffee daily had the least cognitive decline (Eur J Clin Nutr 2007, 61, 226-232). Tea drinking (Am J Epidemiol, 2004, 159, 959-967.), or flavonoid intake from tea has not been associated with a reduced risk of dementia. The low coffee consumers in mid-life had the highest occurrence of dementia and Alzheimer’s at late-life, and the highest scores on the depression scale (J Alzheimer’s Disease 16: 2009, 85–91).
One possible mechanism could involve insulin and degrading enzyme that degrades both insulin and amyloid-beta, the most suspected cause of Alzheimer’s (CNS Drugs 17, 2009, 27-45). Another mechanism is via adenosine receptors (caffein mimics effects of adenosine). It has been shown in mice that both caffeine and adenosine prevent amyloid-beta induced cognitive decline (Exp Neurol 203, 2007, 241-245).
Phytochemical-rich foods have been shown to be effective at reversing age-related deficits in memory in both animals and humans. Specifically, blueberry were effective in reversing age-related deficits in neuronal signaling and behavioral parameters following 8 weeks of feeding, possibly due to their high flavonoid content. It has been reported that blueberry-supplemented diet may not only retard but also revert declining brain functions due to aging. Young and old rats were trained to memorize objects shown them an hour ago. Old rats receiving 2% of their meals as blueberries performed as young rats while old rats on regular diet failed to memorize the objects at al. In several regions of the brain, old control diet rats had significantly higher levels of so called nuclear factor-kappa B (NF-κB) than young animals on the control diet and old rats eating blueberries (Nutritional Neuroscience, V 7, No 2, 2004, 5-83-9). NF-κB is known for its involvement in vulnerability of neurons to “excitotoxicity” – a toxic biochemical condition occurring during neuronal hyperactivity (Synapse. 2000 Feb;35(2):151-9). Errors in regulation of NF-κB may lead to cancer, inflammation and improper immune development. To resist excitotoxicity, there’s so called Brain-derived neurotrophic factor or BDNF, which function is to help supporting the survival of neurons. Recent data (Free Radical Biology and Medicine, 45, 3, 008, 295-305) on blueberry supplementation may indicate that changes in working memory in aged animals are linked to the effects of flavonoids on BDNF.
It was unclear if phytonutrients from blueberries were able to cross the blood-brain barrier and directly access the brain. Researchers in Barcelona, Spain, investigated this issue. They took old rats and fed them a diet containing 2% blueberries for 2 to 2.5 months, than tested the rats for learning and memory. in the brain areas participating in learning and memory processing and storing – cerebellum, cortex, hippocampus or striatum, 14 antioxidant substances found. The antioxidant content correlated with improvements in learning and memory normally declined in old age rats (and humans). In control rats of same age fed on regular diet, there were no changes in bioche
Phytochemical-rich foods have been shown to be effective at reversing age-related deficits in memory in both animals and humans. Specifically, blueberry were effective in reversing age-related deficits in neuronal signaling and behavioral parameters following 8 weeks of feeding, possibly due to their high flavonoid content. It has been reported that blueberry-supplemented diet may not only retard but also revert declining brain functions due to aging. Young and old rats were trained to memorize objects shown them an hour ago. Old rats receiving 2% of their meals as blueberries performed as young rats while old rats on regular diet failed to memorize the objects at al. In several regions of the brain, old control diet rats had significantly higher levels of so called nuclear factor-kappa B (NF-κB) than young animals on the control diet and old rats eating blueberries (Nutritional Neuroscience, V 7, No 2, 2004, 5-83-9). NF-κB is known for its involvement in vulnerability of neurons to “excitotoxicity” – a toxic biochemical condition occurring during neuronal hyperactivity (Synapse. 2000 Feb;35(2):151-9). Errors in regulation of NF-κB may lead to cancer, inflammation and improper immune development. To resist excitotoxicity, there’s so called Brain-derived neurotrophic factor or BDNF, which function is to help supporting the survival of neurons. Recent data (Free Radical Biology and Medicine, 45, 3, 008, 295-305) on blueberry supplementation may indicate that changes in working memory in aged animals are linked to the effects of flavonoids on BDNF.
It was unclear if phytonutrients from blueberries were able to cross the blood-brain barrier and directly access the brain. Researchers in Barcelona, Spain, investigated this issue. They took old rats and fed them a diet containing 2% blueberries for 2 to 2.5 months, than tested the rats for learning and memory. in the brain areas participating in learning and memory processing and storing – cerebellum, cortex, hippocampus or striatum, 14 antioxidant substances found. The antioxidant content correlated with improvements in learning and memory normally declined in old age rats (and humans). In control rats of same age fed on regular diet, there were no changes in bioche
According to Michael Wong, MD, PhD (1), although there’s a noticeable progress in anti-epileptic drug development, two obstacles remain unchanged for many decades:
1. The number of cases resistant to the best and newest drugs does not decrease
2. The best drugs address symptoms and not the cause of the disease, namely, they might suppress the seizures but they cannot make them disappear. As a result of such a failure, we still have no anti-epileptic therapies.
Recent studies, however, addresses potential neuroprotective and anti-epileptogenic actions of substances naturally occurring in plants. For example, Resveratrol (a phytoalexin) is found in plants such as peanuts and grapes, but it’s especially abundant in red wine. In plants, Resveratrol defends the cells against the consequences of injury, parasitics, and infectious diseases — hence its antiinflammatory, antioxidant, anti-tumor, and, if given to animals, its neuroprotective effects.
In the article “Protective Effect of Resveratrol Against Kainate-Induced Temporal Lobe Epilepsy in Rats” Resveratrol is described as a potent anti-epilepsy agent, which protects against epileptogenesis (not just against seizures) in animal model of temporal lobe epilepsy (2).
Another success story was told about curcumin, which is the major ingredient in the popular Indian spice, tumeric. Tumeric has been used for centuries in parts of India as an herbal therapy; including treatment of Alzheimer’s disease and epilepsy. As resveratrol, curcumin has been shown to inhibit acute seizures. The recent study (3) studied the effect of curcumin on epileptogenesis in a rat model of post-traumatic epilepsy. Curcumin decreased the development of and seizures and improved memory and learning.
1. M Wong. HERBS AND SPICES: UNEXPECTED SOURCES OF ANTIEPILEPTOGENIC DRUG TREATMENTS? Epilepsy Currents, Vol. 10, No. 1 2010 pp. 21–23
2. Protective Effect of Resveratrol Against Kainate-Induced Temporal Lobe Epilepsy in Rats. Wu Z, Xu Q, Zhang
L, Kong D, Ma R, Wang L. Neurochem Res 2009;34(8):1393–1400.
3. Curcumin Protects Against Electrobehavioral Progression of Seizures in the Iron-Induced Experimental Model
of Epileptogenesis. Jyoti A, Sethi P, Sharma D. Epilepsy Behav 2009;14(2):300–308.
Related: The eight mechanisms of anti-Alzheimer’s effects of curcumin
HERBS AND SPICES: UNEXPECTED SOURCES OF ANTIEPILEPTOGENIC DRUG TREATMENTS?
According to Michael Wong, MD, PhD (1), although there’s a noticeable progress in anti-epileptic drug development, two obstacles remain unchanged for many decades.
- The number of cases resistant to the best and newest drugs does not decrease
- The best drugs address symptoms and not the cause of the disease, namely, they might suppress the seizures but they cannot make them disappear. As a result of such a failure, we still have no anti-epileptic therapies.
Recent studies, however, address potential neuroprotective and anti-epileptogenic actions of substances naturally occurring in plants. For example, Resveratrol (a phytoalexin) is found in plants such as peanuts and grapes, but it’s especially abundant in red wine. In plants, Resveratrol defends the cells against the consequences of injury, parasitics, and infectious diseases — hence its antiinflammatory, antioxidant, anti-tumor, and, if given to animals, its neuroprotective effects.
In the article “Protective Effect of Resveratrol Against Kainate-Induced Temporal Lobe Epilepsy in Rats” Resveratrol is described as a potent anti-epilepsy agent, which protects against epileptogenesis (not just against seizures) in animal model of temporal lobe epilepsy (2).
Another success story was told about curcumin, which is the major ingredient in the popular Indian spice, tumeric. Tumeric has been used for centuries in parts of India as an herbal therapy; including treatment of Alzheimer’s disease and epilepsy. As resveratrol, curcumin has been shown to inhibit acute seizures. The recent study (3) studied the effect of curcumin on epileptogenesis in a rat model of post-traumatic epilepsy. Curcumin decreased the development of and seizures and improved memory and learning.
Sources
- M Wong. CURRENT LITERATURE IN BASIC SCIENCE. Epilepsy Currents, Vol. 10, No. 1 2010 pp. 21–23
- Protective Effect of Resveratrol Against Kainate-Induced Temporal Lobe Epilepsy in Rats. Wu Z, Xu Q, Zhang
- L, Kong D, Ma R, Wang L. Neurochem Res 2009;34(8):1393–1400.
- Curcumin Protects Against Electrobehavioral Progression of Seizures in the Iron-Induced Experimental Model of Epileptogenesis. Jyoti A, Sethi P, Sharma D. Epilepsy Behav 2009;14(2):300–308.
The female hormones estrogens influence not only reproductive function, but also learning and memory. In postmenopausal women, a lack of estrogen increases the incidence of Alzheimer’s disease (Mayo Clin. Proc. 75 (2000), pp. 1174–1184.). Soy has a high estrogenic potency, and if soy intake is high, this kind of diet may trigger many of the biological responses. In the brain, soy-enriched diet increased the size of sexually dimorphic nucleus of the hypothalamus of males while decreasing it in females while other hypothalamic nuclei (e.g., anteroventral periventricular) displayed opposite reaction to the soy diet (Neurotoxicology and Teratology Volume 24, Issue 1, January-February 2002, Pages 5-16).
The results published in October 2010 issue of the Phytotherapy Research journal (pages 1451–1456) showed that soy isoflavones can improve memory in the intoxicated (chronically aluminum exposed) mice, possibly by modulating the metabolism of brain neurotransmitters. However, a recent study suggested that soy phytoestrogens may improve working memory through estrogen-independent mechanisms (Nutritional Neuroscience, Volume 11, Number 6, December 2008 , pp. 251-262(12).
“Possible beneficial effects (e.g., reduction of serum lipids, increased bone mineral density, relief of hot flashes and other menopausal symptoms, mammary and prostate cancer chemoprevention) in humans have been attributed to consumption of isoflavones but evidence for potential adverse effects (e.g., stimulation of estrogen-dependent mammary tumors and aberrant perinatal development) has also been reported in experimental animal models.” — Daniel R. Doerge (Toxicology and Applied Pharmacology, Article in Press)
According to this review, a simple dietary change towards lower carbohydrate intake and higher fats intake, may be efficiently protective against AD. >> read the article
The growth hormone (GH) secretion declines as we age (by 14% per decade), the process called somatopause. Drugs like pyridostigmine (an acetylcholinesterase inhibitor) are able to enhance GH secretion, but its clinical use is limited due to the strong side effects. Rivastigmine, a drug for Alzheimer’s disease (AD), was found to enhance GH release (Gerontology. 2003;49:191–195).
Oral administration of certain amino acids (arginine, glutamine, glycine, and lysine) increased the release of endogenous GH (Nutrition. 2002;18:657–661); the doses of arginine were 0.5 or 1 g/kg body weight increased GH level (J Clin Endocrinol Metab, 2011 ; Vol. 43 (3): 582-586) or roughly 35 to 70 g a day.
Arginine dissolved in distilled water was infused over a thirty-minute period in doses 1/12, 1/6 and 1/4 g. per pound of body weight. Only the highest dose (average 37.5 g total) was found to be effective in this administration mode. Interestingly, the responses of GH among females remain significantly higher than those among males (N Engl J Med 1967; 276:434-439).
The mixture of L-arginine, L-glutamine, L-lysine, and glycine at a ratio of 37:30:18.5:14.5) added as 5% of the daily meals total has been found to increase the release of endogenous GH. When mice were fed a diet containing GH-releasing supplements they had significantly fewer memory impairments and changes in acetylcholine level in hippocampus induced by Alzheimer’s amyloid beta 1–42 (J Pharmacol Sci; 2005, 99, 117 – 120).
Recently, a clinical target for improving the conditions of AD may be the activation not of GH alone but the entire GH/insulin-like growth factor-I (IGF-I) brain axis. IGF-I alone is also considered a physiological regulator of brain amyloid levels with therapeutic potential (Nature Medicine, 2002; 8, 1390 – 1397)
The growth hormone (GH) secretion declines as we age (by 14% per decade), the process called somatopause. Drugs like pyridostigmine (an acetylcholinesterase inhibitor) are able to enhance GH secretion, but its clinical use is limited due to the strong side effects. Rivastigmine, a drug for Alzheimer’s disease (AD), was found to enhance GH release (Gerontology. 2003;49:191–195).
Oral administration of certain amino acids (arginine, glutamine, glycine, and lysine) increased the release of endogenous GH (Nutrition. 2002;18:657–661); the doses of arginine were 0.5 or 1 g/kg body weight increased GH level (J Clin Endocrinol Metab, 2011 ; Vol. 43 (3): 582-586) or roughly 35 to 70 g a day.
Arginine dissolved in distilled water was infused over a thirty-minute period in doses 1/12, 1/6 and 1/4 g. per pound of body weight. Only the highest dose (average 37.5 g total) was found to be effective in this administration mode. Interestingly, the responses of GH among females remain significantly higher than those among males (N Engl J Med 1967; 276:434-439).
The mixture of L-arginine, L-glutamine, L-lysine, and glycine at a ratio of 37:30:18.5:14.5) added as 5% of the daily meals total has been found to increase the release of endogenous GH. When mice were fed a diet containing GH-releasing supplements they had significantly fewer memory impairments and changes in acetylcholine level in hippocampus induced by Alzheimer’s amyloid beta 1–42 (J Pharmacol Sci; 2005, 99, 117 – 120).
Recently, a clinical target for improving the conditions of AD may be the activation not of GH alone but the entire GH/insulin-like growth factor-I (IGF-I) brain axis. IGF-I alone is also considered a physiological regulator of brain amyloid levels with therapeutic potential (Nature Medicine, 2002; 8, 1390 – 1397)
The study conducted by researchers at McGill University in Montreal and published in January issue of Nature Neuroscience showed that the music increased dopamine levels in certain areas of the brain. Various types of music were shown to be effective depending on individual preferences. >> More at Brainfuels.com
Combined deficiency in vitamins C and E is a risk factor for neuronal death and brain necrosis
Vitamin C easily crosses the blood brain barrier and its transport into the brain is mediated by glucose transporters. Vitamin C concentrations in the brain exceed those in blood by 10-fold. In humans, hypovitaminosis C correlated with brain damage in patients with head trauma (Stroke. 2001;32:898-902). The vitamin C has important functions in the brain, for example, protecting neuronal membranes from oxidative damage acting as a scavenger of free radicals.
Another free radical scavenger Vitamin E (-tocopherol) inhibits the amyloid peptide characteristic for Alzheimer’s disease known to induced cell death (Biochemical and Biophysical Research Communications Volume 186, Issue 2, 31 July 1992, Pages 944-950).
The results of a study of Guinea Pigs’s fed either on normal or vitamin-deficient diets showed that while moderate deficiencies of vitamins E or C didn’t result in serious brain changes, their combined moderate deficienciescaused degenerative changes in the guinea pig brains in only 5 days after vitamins were removed from the feed.
Interestingly, the deficiencies in either E or C vitamins had only moderate consequences, but their combination caused severe brain lesions – inflammation, cell death with necrosis and apoptosis and animals’ death (Nutr. 136:1576-1581, June 2006).
Combined deficiency in vitamins C and E is a risk factor for neuronal death and brain necrosis.
Vitamin C easily crosses the blood brain barrier and its transport into the brain is mediated by glucose transporters. Vitamin C concentrations in the brain exceed those in blood by 10-fold. In humans, hypovitaminosis C correlated with brain damage in patients with head trauma (Stroke. 2001;32:898-902). The vitamin C has important functions in the brain, for example, protecting neuronal membranes from oxidative damage acting as a scavenger of free radicals.
Another free radical scavenger Vitamin E (-tocopherol) inhibits the amyloid peptide characteristic for Alzheimer’s disease known to induced cell death (Biochemical and Biophysical Research Communications Volume 186, Issue 2, 31 July 1992, Pages 944-950).
The results of a study of Guinea Pigs’s fed either on normal or vitamin-deficient diets showed that while moderate deficiencies of vitamins E or C didn’t result in serious brain changes, their combined moderate deficienciescaused degenerative changes in the guinea pig brains in only 5 days after vitamins were removed from the feed.
Interestingly, the deficiencies in either E or C vitamins had only moderate consequences, but their combination caused severe brain lesions – inflammation, cell death with necrosis and apoptosis and animals’ death (Nutr. 136:1576-1581, June 2006).
