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Maple Syrup – M’m! M’m! GOOD!

anti-diabetes maple-syrupAstounding as it may seem, maple syrup—real maple syrup—has been found to have anti-cancer and anti-diabetes properties. Plant researchers at the University of Rhode Island have isolated compounds from maple tree sap that are strikingly beneficial to human health. What’s more, some of these compounds are brand new, and surface only after the sap is processed into syrup.

A Science Daily report from March, 2011, announces that the University of Rhode Island medicinal plant researcher, Navindra Seeram, has discovered thirty-four new beneficial compounds in pure maple syrup to be added to the twenty he found the year before, “…five of which have never been seen in nature.” The researcher is quoted, “It’s important to note that in our laboratory research we found that several of these compounds possess anti-oxidant and anti-inflammatory properties, which have been shown to fight cancer, diabetes and bacterial illnesses.” Seeram applauds Mother Nature as the best chemist, commenting that, “…maple syrup is becoming a champion food when it comes to the number and variety of beneficial compounds found in it.” (Science Daily; Mar. 30, 2011) Seeram’s team acknowledges that inflammation is at the center of several nefarious disease, including heart disease, diabetes, certain cancers, and neurodegenerative diseases such as Alzheimer’s. The maple syrup compounds may show medicinal promise, but the scientists suggest that consumers not consume large quantities of the syrup, but to use it instead of artificial products found in the marketplace.

The scientific names of the compounds derived from maple syrup are enough to scare you away.  With thirty or more letters and numbers, these unpronounceable words sound serious.  And they are.  Among them are phenolic compounds and plant lignans, the former having anti-oxidant properties and the latter having hormonal properties.  Of these two major constituents, the phenolics are more active (Li and Seeram. 2010), and were found to be comparable to vitamin C (Li and Seeram. 2011).

Plants make certain chemicals for themselves, often to remain protected from predation or environmental damage, as may occur from heavy metal exposure via exhaust from the electric company’s smokestack, which often contains mercury.  These beneficial chemicals transfer to us when we eat those plants, where they may act as chelators besides anti-oxidants.  The more a plant is stressed, the more it produces phenolic anti-oxidants, the bioflavonoids being the best-known among them.

Real maple syrup demonstrates quite a nutritional profile compared to the fake stuff, which is primarily high-fructose corn syrup (HFCS) flavored with a synthetic ingredient.  Ounce for ounce, maple syrup has slightly fewer calories and carbohydrates than HFCS, eleven times the calcium, and more magnesium and zinc.  Plus, it tastes a whole lot better.

Two phenols in maple syrup, ethyl acetate and butanol, are able to inhibit enzymes that are relevant to Type 2 diabetes (Apostolidis. 2011), with butanol being more active.  Additionally, butanol converts to butyric acid, which plays a role in DNA transcription.  Real maple syrup is allowed to be labeled as such.  In Quebec, the largest producer of real maple syrup, the locals refer to imitation syrup as “pole syrup,” implying that it has been tapped from telephone poles.  That’s not too outlandish a comment.   In fact, a brand new compound that forms only during the processing of the sap has been named quebecol, in honor of the Province.  (Li and Seeram. J Func Food. 2011)  It is not uncommon for heat (in this case, sap boiling) to separate chemical components and then rearrange them to form something else, all mass being retained.

It had already been established that anti-oxidants reside in the leaves, bark and twigs of the maple tree, so examining the sap is a logical step.  Exposure to direct sunlight appears to enhance anti-oxidant production.  Besides Seeram, other research teams, especially from Canada, have hopped onto the maple syrup train.  Because all these scientists are headed in the same direction, why not?

References

http://www.sciencedaily.com/releases/2011/03/110330131316.htm
54 Beneficial Compounds Discovered in Pure Maple Syrup
Science Daily (Mar. 30, 2011)

J. Agric. Food Chem., 2010, 58 (22), pp 11673–11679
Maple Syrup Phytochemicals Include Lignans, Coumarins, a Stilbene, and Other Previously Unreported Antioxidant Phenolic Compounds
Liya Li and Navindra P. Seeram

J. Agric. Food Chem., 2011, 59 (14), pp 7708–7716
Further Investigation into Maple Syrup Yields 3 New Lignans, a New Phenylpropanoid, and 26 Other Phytochemicals
Liya Li and Navindra P. Seeram

Journal of Functional Foods. Volume 3, Issue 2, April 2011, Pages 100-106
In vitro evaluation of phenolic-enriched maple syrup extracts for inhibition of carbohydrate hydrolyzing enzymes relevant to type 2 diabetes management
Emmanouil Apostolidis, Liya Li, Chong Lee and Navindra P. Seeram

Journal of Functional Foods. Volume 3, Issue 2, April 2011, Pages 125-128
Quebecol, a novel phenolic compound isolated from Canadian maple syrup
Liya Lia and Navindra P. Seeram

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Blood-Brain Barrier – What Is It?

brain-barrier“Homeostasis” is not a topic commonly discussed at parties or at the dinner table. Nobody pays attention to it unless it’s severely out of order. That’s because few of us know what it is. Your body is able to control everything that goes on inside—the composition of body fluids, the physiological responses to stimuli, the maintenance of body temperature, and whatever else we need to keep equilibrium. That’s homeostasis. Nowhere in the body is it more important than in the brain. The mechanism for supporting this lies in the blood-brain barrier, the BBB. This comprises a network of capillaries that supply blood to the brain. The permeability of these particular capillaries is such that some substances are prevented from entering the brain tissue while others are allowed. Sometimes it’s only a matter of big molecules versus small molecules. The BBB was discovered by a bacteriologist named Paul Ehrlich, who found that a dye injected into the bloodstream colored the tissues of most organs except the brain.

Further study realized that the barrier is located in the endothelial (skin-like) cells of the capillaries, which are joined by tight junctions of substantial electrical resistance, providing a barrier against some molecules. The BBB is both a physical barrier and a system of cellular transport mechanisms. It restricts the passage of potentially harmful materials from the blood, yet allows the traverse of nutrients. Fat-soluble substances, such as ethanol and caffeine, are able to get through by way of the lipid membranes of the cells. Oddly, water-soluble materials, such as sodium and potassium, may not cross the barrier without an escort molecule of some type.

The BBB becomes more permeable during inflammatory attacks, allowing some medications (mostly antibiotics) and phagocytes to pass through. That’s good. A not-so-good thing is that opportunistic bacteria and viruses can get through, too. Most of them are too big, though. Therefore, brain infections are rare. One exception is the spirochete, Borrelia, associated with Lyme’s disease, which seems to be able to infiltrate blood vessel walls after causing inflammation of the central nervous system. (Rupprecht. 2008)  There are very few fat-soluble small molecules that can get through, and that can cause problems when life-saving chemicals are barred entrance. (Pardridge. 2002)  Other than some infectious diseases, no chronic diseases are cured by small-molecule drugs. Large-molecule drugs have the potential to heal patients with neurological conditions, but none can cross the BBB.

INSULTS TO THE BBB

What can harm the blood-brain barrier?  Alcohol, fluoride, oxidized LDL and brain concussions, to name a few.  Alcohol crosses the BBB (Stins. 2009) and forms metabolites that act as signaling molecules to activate enzymes leading to BBB dysfunction and to neuro-inflammatory disorders. (Haorah. 2007)  Furthermore, alcohol causes oxidative neuron damage and results in cognitive deficits that characterize stupor and memory lapses, all because it inhibits the glucose transport upon which the brain depends as a source of energy. (Abdul Muneer. 2011)

As beneficial as topical fluoride might be in the prevention of tooth decay, its ingestion is another story, where elevated levels have been associated with increased rates of mental deficiency and borderline intelligence. Chinese researchers found that high fluoride levels in drinking water have a profound effect on the intelligence of developing children. (Xiang. 2003)  Simultaneous study concluded that fluoride accumulates in the hippocampus—the part of the brain involved in memory—and inhibits activity of cholinesterase, the enzyme that regulates the function of the neurotransmitter, acetylcholine, which mediates synaptic activity. (Zhai. 2003)  In earlier investigations, scientists found that the chemical had impact on those persons chronically exposed to industrial fluoride pollution, wherein there occurred symptoms of impaired central nervous system functioning and faulty cognitions and memories. (Spittle. 1994)  From the outside, fluoride is acceptable treatment for the prevention of caries; from the inside, no.

Oxidized LDL (oxLDL), which appears when LDL spends too much time in the blood before getting repackaged as fat by the liver or being taken up by peripheral tissue, is capable of inducing cell injury. When cerebral endothelial cells are exposed to OxLDL, their viability decreases in a concentration- and time-dependent manner, and their programmed cell death is hastened. Intracellular reactive oxygen species are increased, and mitochondria become dysfunctional. (Chen. 2007)  A blow to the head can cause a concussion, but so can violent jarring or shaking. This sudden change of momentum (the resistance to changes in motion or stability) may evoke unconsciousness or disruption of vital functions of the brainstem. The increased pressure that may result will render the BBB increasingly permeable, particularly at the site of insult. (Beaumont. 2001)

BBB PROTECTION

Is there a way to protect the BBB?  Yes, but there is space here to address only a few. Caffeine—we all know how to get that—has been shown to block disruption of the blood brain barrier in a rabbit model of Alzheimer’s disease (AD). So, what do rabbits have to do with people?  Lab animals are selected based on their organ systems’ similarity of function to corresponding systems in humans. In a cholesterol-induced model of AD, scientists found that caffeine was able to block substances that compromise the integrity of the molecules (called occludins) that hold the tight junctions of the BBB together. (Chen. 20081)  Perhaps caffeine and related drugs may be useful to treat AD. But there’s more. In Parkinson’s disease (PD), similar BBB disruptions are characteristic, and caffeine again was the rescue agent. (Chen. 20082)  (Chen. 2010)

Indian neurologists have studied the effects of curcumin (from turmeric) on patients with AD, and have found the herb’s anti-oxidant and anti-inflammatory properties to be beneficial in treating dementia and traumatic brain injury. The pharmacological effects of curcumin have decreased beta-amyloid plaques, delayed degradation of neurons, and decreased microglia formation while improving overall memory in AD patients. (Mishra. 2008)

Valproic acid (VPA), a histone deacetylase inhibitor, is a drug used to prevent seizures and to stabilize mood, used mostly in epilepsy treatment. Histone acetylation plays an important role in the regulation of gene expression. Keeping it intact is vital. Valproic acid and others of its kind do just that. It protects against cerebral ischemia (decrease of blood supply) and prevents disruption of the BBB. The effects of VPA are mimicked by a companion molecule, sodium butyrate, a compound available as an OTC supplement. (Wang, et al. 2011)  Inflammation and macrophage infiltration follow a cerebral ischemic attack. Injected sodium butyrate or VPA was found to be effective at reducing the area of infarction and inhibiting inflammatory markers, as long as administration occurred within a three-hour window. The potential for use in stroke patients is being studied. (Kim. 2007)

One of the hottest supplements on the market is resveratrol, the magical ingredient in grapes, peanuts and red wine that purports to protect against aging.  Whether it can do that or not is insignificant in light of its use as an anti-mutagenic, anti-inflammatory, and anti-oxidant agent, which render it useful in addressing cardiovascular disease and some cancers. Scientists in Taiwan have found resveratrol to protect the BBB from the damaging effects of oxLDL attack on its tight junctions and the substances responsible for its integrity. (Lin. 2010)  (Chang. 2011)  In normal aging the BBB seems to remain intact, but its permeability becomes an issue. Certain drugs and physical conditions, such as hypertension, may have deleterious effects on its stability. The reactive oxygen species (ROS) spawned by these vehicles can be attenuated by a low molecular weight substance known as alpha-lipoic acid, a sulfurated fatty acid (a thiol) regarded as a member of the B vitamin family and used to metabolize carbohydrates. One of lipoic acid’s claims to fame is the capability to regenerate and to recirculate both the fat-soluble vitamin E and the water-soluble vitamin C, while simultaneously raising intracellular glutathione levels. In this regard it was cited as a meaningful tool in the treatment of oxidative brain damage and neural disorders involving free radicals, such as would arise from ischemia, excitotoxic amino acid brain insult, mitochondrial dysfunction, diabetes and diabetic neuropathy, inborn errors of metabolism and other causes of neural damage. What is deemed the most important thiol anti-oxidant, glutathione, is not usually directly administered, whereas alpha-lipoic acid may be. (Packer. 1997)   Analysis of studies on alpha-lipoic acid finds it to be a participant in processes of cell growth and differentiation, thus adding to its moniker, anti-oxidant of anti-oxidants. (Bilska. 2005)

No mention of anti-oxidants would be complete without vitamin C, the oxidized version of which—dehydroascorbic acid—can cross the BBB via glucose transporters. Though best known for its anti-oxidant powers, vitamin C is also involved in enzyme reactions and the manufacture of collagen in conjunction with amino acids. Because it can traverse the BBB, vitamin C (ascorbic acid) has welcome anti-oxidant potential in the central nervous system. (Agus. 1997). Its use in the treatment of cerebral compression insult, as from a concussion, has preserved BBB integrity and rescued somatosensory function from debilitation. (Lin. 2010)

For years, the failures of clinical trials in the treatment of neurological diseases have been blamed on the tested substances’ ineffectiveness, when the whole time none could get past the blood-brain barrier.

References

Abdul Muneer PM, Alikunju S, Szlachetka AM, Haorah J.
Inhibitory effects of alcohol on glucose transport across the blood-brain barrier leads to neurodegeneration: preventive role of acetyl-L: -carnitine.
Psychopharmacology (Berl). 2011 Apr;214(3):707-18. Epub 2010 Nov 16.

Abraham Al Ahmad, Carole Bürgi Taboada, Max Gassmann and Omolara O Ogunshola
Astrocytes and pericytes differentially modulate blood–brain barrier characteristics during development and hypoxic insult
Journal of Cerebral Blood Flow & Metabolism 31, 693-705 (February 2011) |

D B Agus, S S Gambhir, W M Pardridge, C Spielholz, J Baselga, J C Vera and D W Golde
Vitamin C crosses the blood-brain barrier in the oxidized form through the glucose transporters.
J Clin Invest.(December 1, 1997);100(11):2842–2848.

Beaumont A, Marmarou A, Fatouros P, Corwin F.
Secondary insults worsen blood brain barrier dysfunction assessed by MRI in cerebral contusion.
Acta Neurochir Suppl. 2002;81:217-9.

Bilska A, Włodek L.
Lipoic acid – the drug of the future?
Pharmacol Rep. 2005 Sep-Oct;57(5):570-7.

Carman Aaron J, Jeffrey H. Mills, Antje Krenz, Do-Geun Kim, and Margaret S. Bynoe
Adenosine Receptor Signaling Modulates Permeability of the Blood–Brain Barrier
The Journal of Neuroscience, 14 September 2011, 31(37): 13272-13280

Chang HC, Chen TG, Tai YT, Chen TL, Chiu WT, Chen RM.
Resveratrol attenuates oxidized LDL-evoked Lox-1 signaling and consequently protects against apoptotic insults to cerebrovascular endothelial cells.
J Cereb Blood Flow Metab. 2011 Mar;31(3):842-54.

Chen TG, Chen TL, Chang HC, Tai YT, Cherng YG, Chang YT, Chen RM.
Oxidized low-density lipoprotein induces apoptotic insults to mouse cerebral endothelial cells via a Bax-mitochondria-caspase protease pathway.
Toxicol Appl Pharmacol. 2007 Feb 15;219(1):42-53.

Chen X, Gawryluk JW, Wagener JF, Ghribi O, Geiger JD
Caffeine blocks disruption of blood brain barrier in a rabbit model of Alzheimer’s disease.
J Neuroinflammation. (1) 2008 Apr 3;5:12.

Chen X, Lan X, Roche I, Liu R, Geiger JD.
Caffeine protects against MPTP-induced blood-brain barrier dysfunction in mouse striatum.
J Neurochem. (2) 2008 Nov;107(4):1147-57.

Chen X, Ghribi O, Geiger JD
Caffeine protects against disruptions of the blood-brain barrier in animal models of Alzheimer’s and Parkinson’s diseases.
J Alzheimers Dis. 2010;20 Suppl 1:S127-41.

Garbuzova-Davis S, Louis MK, Haller EM, Derasari HM, Rawls AE, Sanberg PR.
Blood-brain barrier impairment in an animal model of MPS III B.
PLoS One. 2011 Mar 7;6(3):e16601.

Haorah J, Knipe B, Gorantla S, Zheng J, Persidsky Y.
Alcohol-induced blood-brain barrier dysfunction is mediated via inositol 1,4,5-triphosphate receptor (IP3R)-gated intracellular calcium release.
J Neurochem. 2007 Jan;100(2):324-36.

Kim HJ, Rowe M, Ren M, Hong JS, Chen PS, Chuang DM.
Histone deacetylase inhibitors exhibit anti-inflammatory and neuroprotective effects in a rat permanent ischemic model of stroke: multiple mechanisms of action.
J Pharmacol Exp Ther. 2007 Jun;321(3):892-901.

Lin JL, Huang YH, Shen YC, Huang HC, Liu PH.
Ascorbic acid prevents blood-brain barrier disruption and sensory deficit caused by sustained compression of primary somatosensory cortex.
J Cereb Blood Flow Metab. 2010 Jun;30(6):1121-36.

Lin YL, Chang HC, Chen TL, Chang JH, Chiu WT, Lin JW, Chen RM.
Resveratrol protects against oxidized LDL-induced breakage of the blood-brain barrier by lessening disruption of tight junctions and apoptotic insults to mouse cerebrovascular endothelial cells.
J Nutr. 2010 Dec;140(12):2187-92.

Mishra S, Palanivelu K.
The effect of curcumin (turmeric) on Alzheimer’s disease: An overview.
Ann Indian Acad Neurol 2008;11(1):13-19

Packer L, Tritschler HJ, Wessel K.
Neuroprotection by the metabolic antioxidant alpha-lipoic acid.
Free Radic Biol Med. 1997;22(1-2):359-78.

William M. Pardridge, MD
Targeting Neurotherapeutic Agents Through the Blood-Brain Barrier
Arch Neurol. 2002;59:35-40.

Rupprecht TA, Koedel U, Fingerle V, Pfister HW.
The pathogenesis of lyme neuroborreliosis: from infection to inflammation.
Mol Med. 2008 Mar-Apr;14(3-4):205-12.

Shah GN, Mooradian AD.
Age-related changes in the blood-brain barrier.
Exp Gerontol. 1997 Jul-Oct;32(4-5):501-19.

Spittle B.
Psychopharmacology of fluoride: a review.
Int Clin Psychopharmacol. 1994 Summer;9(2):79-82.

STINS, MONIQUE F.
ALCOHOL MEDIATED BLOOD BRAIN BARRIER DYSFUNCTION
U.S. Dept. of Health and Human Services
Research Portfolio Online Reporting Tool, 2009
http://projectreporter.nih.gov/project_info_description.cfm?icde=0&aid=7588182

Q Xiang , Y Liang , L Chen , C Wang , B Chen), X Chen , M Zhou
Effect of fluoride in drinking water on children’s intelligence.
Fluoride 2003; 36(2): 84-94

Zhai JX, Guo ZY, Hu CL, Wang QN, Zhu QX.
Studies on fluoride concentration and cholinesterase activity in rat hippocampus.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2003 Apr;21(2):102-4.

Zhifei Wang, Yan Leng, Li-Kai Tsai, Peter Leeds and De-Maw Chuang
Valproic acid attenuates blood–brain barrier disruption in a rat model of transient focal cerebral ischemia: the roles of HDAC and MMP-9 inhibition
Journal of Cerebral Blood Flow & Metabolism (2011) 31, 52–57

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

B-Vitamins And Memory

confused-young-womanFrancis Bacon, who was a philosopher in the 16th century, said that, “Some books are to be tasted, others swallowed, and some few to be chewed and digested.” The same principle can apply to the written word of the present. If we took everything we read in magazines or over the internet as gospel, conflicting words and ideas would create such confusion that the truth would be more elusive than it has been for decades. While we are able to identify and to reject half-truths in the spoken word, we tend to give them credence if they appear in print. Such is the case with news and reports about the human body and its health and maintenance, and the things we can do and take to guarantee them.

Reports from Fox, Reuters and Medline, among other news services, have said that
B-vitamins can boost memory. Seeing that headline is all some folks need to draw a hasty conclusion, hoping that their loved ones with Alzheimer’s or some other neurological irregularity will be cured. At best, such a conclusion might be drawn following a syllogistic approach, a form of reasoning that relies on major and minor premises:  if this causes this, and if that causes that, then this causes that. Whether or not this is true depends on acceptance of the phrases, “some of the time” and “all of the time.”  Let’s see if we can make sense of the original proposition, that B-vitamins can boost memory.

The study cited by the news services was conducted by Dr. Janine Walker, a mental health researcher from the Australian National University, who reported in the American Journal of Clinical Nutrition that long-term supplementation with folic acid and vitamin B12 promotes improvement in cognitive functioning. (Walker, 2012)  What the headline doesn’t tell us is that the study lasted two years, and that physical exercise was part of the protocol. You have to read the small print, which means the details of the study need to be chewed and digested. The confounding factors and specific provisions must be considered.

Homocysteine (Hcy) is such a factor–and a provision if it’s measureable. Homocysteine is a homologue of the amino acid, cysteine, differing by an additional methylene group (CH2). It’s best known as a marker for inflammation associated with increased risk of cardiovascular disease. Whether or not lowering homocysteine will also lower CVD risk is still under examination, but it has been accepted that raised Hcy is associated with poor cognitive performance in the general population, not only in the elderly. Increases in serum folic acid levels are accompanied by decreases in Hcy levels. (Durga, 2007)  But this doesn’t mean that cognitive function will automatically improve. It takes time, another factor to be weighed. After three years of folic acid supplementation, Durga and his Dutch colleagues learned that the molecule, did, in fact, improve specific domains of cognitive function, particularly those that decline with age. What we are not told is that folic acid (vitamin B9) works best in the company of vitamins B12 and B6, where its role as a promoter of brain function can be fully realized.

If there is a pin to be put into this balloon, it comes courtesy of the Cochrane Database and its systematic reviews of primary research in health care and health policy. One of its 2008 reviews examined the effects of folic acid on demented people and their cognitive shortcomings, only to announce that no consistent evidence supports the use of folic acid—with or without vitamin B12—to effect improvement. They are carefully deliberate to add, however, that long-term use of folic acid (also known as folate in foods) does appear to improve the cognitive function of those individuals with elevated homocysteine levels. (Malouf, 2008)  Do you see the factor?  Long-term use.

Many elderly present with movement disorders to some degree. Swedish investigators looked at a population of community-dwelling septuagenarians who suffered both movement and cognitive disadvantages, treating them with vitamins B9, B6, and B12. More than 60% of the men and almost 50% of the women had high Hcy levels and high methylmalonic acid (MMA) concentrations, the latter indicating B12 deficiency. Vitamin therapy lowered both markers, but failed to mitigate both the movement and cognitive deficits. This does not mean the therapy is useless, though. The report allows that dosage could have been too low to prove effective, or that the physical and mental declines could have become irreversible. (Lewerin, 2005)  If such decline is recognized at all, could it / should it have been identified years—or even decades—sooner?   With all illness and debility, isn’t that ounce of prevention worth lots more than the pounds of cure?   To be considered also is that stores of nutrients decline sharply with age. For how long were they deficient?  How about the form of the nutrient?  Methylcobalamin is the much preferred form of vitamin B12, but the Swedish study used cyanocobalamin, a form that is unnatural to plants and animals. And, it contains an “insignificant” amount of cyanide that still must be eliminated from the body. Isn’t the mere four months duration of this study too little time to come to a righteous conclusion?  The factor?  Time.

“Over the short or medium term,” announces a Glasgow paper, cognitions did not improve with the vitamin cocktail. This study population, older than sixty-five and comparatively small at 185 participants, suffered ischemic vascular disease, that which decreases blood supply to an organ by constricting a blood vessel. Since all ischemia is not the same for all people, that condition might just confound the matter. This study lasted three months to one year. Here is a senior population with constrictive vascular disease, probably taking one or more medications, whose compliance is not monitored, with unknown dietary habits and unmentioned polypharmacy, and possibly experiencing other health issues. (MacDonald, 2005). Are we expected to accept the conclusion without question?

In ameliorative protocols where the patient is ambulatory, exercise is warranted, either as an isolated or as a supportive element. (Wen, 2010)  (Harkcom, 1085)  (Kirkcaldy, 1990)  Nonetheless, the administration of selected B-vitamins has an effect on the factors that interfere with brain function and memory, if only because they can mitigate the adverse effects of inflammation. Homocysteine is a documented CVD factor that is related to both vascular dementia and Alzheimer’s disease. (Stabler, 2003)  It appears that the attenuation of Hcy with folic acid, vitamin B6 and vitamin B12, accompanied by a modicum of exercise, and conducted over a reasonable period of time, can yield the desired result in cognitive change. IF homocysteine is related to cognitive decline, and IF a B-vitamin cocktail reduces homocysteine, THEN the cocktail may be able to reverse faulty cognition (in certain circumstances). Because these supplements are water-soluble, toxicity is of little concern regardless of the elevated dosage required.

References

Durga J, van Boxtel MP, Schouten EG, Kok FJ, Jolles J, Katan MB, Verhoef P.
Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial.
Lancet. 2007 Jan 20;369(9557):208-16.

Feng L, Ng TP, Chuah L, Niti M, Kua EH.
Homocysteine, folate, and vitamin B-12 and cognitive performance in older Chinese adults: findings from the Singapore Longitudinal Ageing Study.
Am J Clin Nutr. 2006 Dec;84(6):1506-12.

Ford AH, Flicker L, Alfonso H, Thomas J, Clarnette R, Martins R, Almeida OP.
Vitamins B(12), B(6), and folic acid for cognition in older men.
Neurology. 2010 Oct 26;75(17):1540-7.

Garcia A, Zanibbi K.
Homocysteine and cognitive function in elderly people.
CMAJ. 2004 Oct 12;171(8):897-904.

Thomas M. Harkcom MD, Richard M. Lampman PhD, Barbara Figley Banwell PT, C. William Castor MD
Therapeutic value of graded aerobic exercise training in rheumatoid arthritis
Arthritis & Rheumatism. Volume 28, Issue 1, pages 32–39, January 1985

Kirkcaldy, Bruce D.;Shephard, Roy J.
Therapeutic implications of exercise.
International Journal of Sport Psychology, Vol 21(3), Jul-Sep 1990, 165-184.

Lewerin C, Matousek M, Steen G, Johansson B, Steen B, Nilsson-Ehle H.
Significant correlations of plasma homocysteine and serum methylmalonic acid with movement and cognitive performance in elderly subjects but no improvement from short-term vitamin therapy: a placebo-controlled randomized study.
Am J Clin Nutr. 2005 May;81(5):1155-62.

Lonn E, Yusuf S, Arnold MJ, Sheridan P, Pogue J, Micks M, McQueen MJ, Probstfield J, Fodor G, Held C, Genest J Jr; Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators.
Homocysteine lowering with folic acid and B vitamins in vascular disease.
N Engl J Med. 2006 Apr 13;354(15):1567-77.

Malouf R, Grimley Evans J.
Folic acid with or without vitamin B12 for the prevention and treatment of healthy elderly and demented people.
Cochrane Database Syst Rev. 2008 Oct 8;(4):CD004514.

McCaddon A, Hudson P, Davies G, Hughes A, Williams JH, Wilkinson C
Homocysteine and cognitive decline in healthy elderly.
Dement Geriatr Cogn Disord. 2001 Sep-Oct;12(5):309-13.

McCaddon, Andrew
Homocysteine and cognitive impairment; a case series in a General Practice setting
Nutrition Journal. 15 February 2006, 5:6

Oulhaj A, Refsum H, Beaumont H, Williams J, King E, Jacoby R, Smith AD.
Homocysteine as a predictor of cognitive decline in Alzheimer’s disease.
Int J Geriatr Psychiatry. 2010 Jan;25(1):82-90.

Sally P Stabler
Vitamins, homocysteine, and cognition
American Journal of Clinical Nutrition, Vol. 78, No. 3, 359-360, September 2003

A. David Smith, Stephen M. Smith, Celeste A. de Jager, Philippa Whitbread, Carole Johnston, Grzegorz Agacinski, Abderrahim Oulhaj, Kevin M. Bradley, Robin Jacoby, Helga Refsum
Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial
PLoS ONE. September 8, 2010; 5(9): e12244.

Stott DJ, MacIntosh G, Lowe GD, Rumley A, McMahon AD, Langhorne P, Tait RC, O’Reilly DS, Spilg EG, MacDonald JB, MacFarlane PW, Westendorp RG.
Randomized controlled trial of homocysteine-lowering vitamin treatment in elderly patients with vascular disease.
Am J Clin Nutr. 2005 Dec;82(6):1320-6.

van Uffelen JG, Chin A Paw MJ, Hopman-Rock M, van Mechelen W.
The effect of walking and vitamin B supplementation on quality of life in community-dwelling adults with mild cognitive impairment: a randomized, controlled trial.
Qual Life Res. 2007 Sep;16(7):1137-46.

van Uffelen JG, Chinapaw MJ, van Mechelen W, Hopman-Rock M.
Walking or vitamin B for cognition in older adults with mild cognitive impairment? A randomised controlled trial.
Br J Sports Med. 2008 May;42(5):344-51.

Walker JG, Batterham PJ, Mackinnon AJ, Jorm AF, Hickie I, Fenech M, Kljakovic M, Crisp D, Christensen H.
Oral folic acid and vitamin B-12 supplementation to prevent cognitive decline in community-dwelling older adults with depressive symptoms–the Beyond Ageing Project: a randomized controlled trial.
Am J Clin Nutr. 2012 Jan;95(1):194-203.

Wen D, Xu J, Xie X, Zhang J, Zhong Y, Sun Y, Duan Y.
Effect of physical exercise on the efficacy of mitoxantrone-loaded nanoparticles in treating early breast cancer.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2010 Feb;27(1):109-12.

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

AGE’s and Curcumin

high-blood-sugarThe title of this may be misleading because, although it’s about AGE, it isn’t actually about age.  The two—the acronym and the word—are related, however.  AGE is the acronym for Advanced Glycation End-products, substances that have something to do with aging, but that are part of a bigger picture. An AGE forms after a chain of chemical reactions that yield glycation, which is the result of a sugar molecule bonding to a protein or lipid molecule without the controlling action of an enzyme. AGE’s may form outside the body by cooking sugars with proteins or inside the body via normal metabolism and aging. In certain circumstances, such as the oxidative stress that occasionally accompanies the hyperglycemia of diabetes, AGE formation can exceed normal levels.

What Do AGE’s Mean For Me?
In diabetes-related AGE formation, high glucose levels ultimately cause reactive oxygen species (ROS) that have the potential to attack DNA and to become prime factors in aging and in age-related chronic diseases. From this come the vascular complications of diabetes, where a cascade of events leads to inhibition of vascular dilation (contributing to elevated blood pressure), to the oxidation of low-density lipoprotein (LDL), and to the secretion of pro-inflammatory chemicals that increase oxidative stress.  In the long run, atherosclerosis, arthritis, myocardial infarction (heart attack), retinopathy, or any of several other conditions may develop.

AGE’s may be more reactive than the sugars from which they are made, two of which are fructose and glucose. Glycation is a haphazard process, and is not the same thing as glycosylation, which is controlled by enzymes. Glycation occurs in the Maillard reaction, the phenomenon that makes food taste exceptional when it gets browned.  Remember that this entails an amino acid and a sugar in an event that is enhanced in an alkaline environment. Toasted bread, fried onions, roasted coffee, maple syrup, biscuits, dark-colored sodas, donuts, barbecued meats and tater tots are examples.  Although the results are similar to the naked eye, caramelization is quite a different process. Yes, both involve heat, but caramelization excuses amino acids from the party and relies solely on some kinds of sugars. Once in a while Maillard and caramelization occur at the same time. High temperature, low moisture and alkaline conditions promote the Maillard reaction. Browning doesn’t happen until water is vaporized at a temperature exceeding the boiling point.

What Happens Inside The Body?
Maillard-type reactions occur inside the body, albeit at much lower temperatures. There are slow, complex reactions that cause the formation of AGE’s, some of which are believed to be responsible for the amyloid proteins that lead to Alzheimer’s disease.  Degenerative eye disease and diabetes have received the most attention, however, followed by recent interest in an association of glucose to neurodegeneration. Recent study has associated type 2 diabetes with cerebral atrophy, cognitive impairment and dementia at glucose levels deemed to be within normal range (Herbuin, 2012).

Some animals, notably rats and mice, either already have, or can be bred to have, physiological traits that parallel those of human body systems and mechanisms. Animal models can develop diabetes, for example, either spontaneously via breeding or by chemical or surgical means. Of course, for each advantage there may be a limitation, but it is recognized that without such laboratory partners there would be little progress in medical research (Chatzigeorgiou, 2009). Oxidative stress has been studied as a factor in degenerative diseases for years. Its inhibition has been the goal, and appears to have been realized in experiments with diabetic rats performed in India in the late 1990’s, where AGE’s and the cross-linking of collagen were addressed by the use of curcumin, the active ingredient of the turmeric spice. Doses as high as 200 mg/kg of body weight, for a period of two months, attenuated not only degradative processes, but also the accumulation of lipid peroxidation by-products (Sajithlal, 1998).

Malondialdehyde is an organic compound used as a marker for the specific oxidative stress resulting from the corruption of polyunsaturated fats (PUFA’s). As a reactive aldehyde, malondialdehyde is analogous to AGE’s. One of the wear-and-tear pigments remaining after this assault on PUFA’s is called lipofuscin, whose presence is viewed as a symptom of membrane damage or of damage to the mitochondria. Accumulation of lipofuscin is implicated in Alzheimer’s disease, Parkinson’s disease, ALS, COPD, and macular degeneration, among other disorders. Calorie restriction and increased glutathione are but two approaches to control this symbol of aging and its sequelae.   The anti-oxidant and anti-aging characteristics of curcumin were found to wield considerable influence in the prevention of malondialdehyde and lipofuscin formation, even at comparatively low doses of 30 mg/kg (Sarvalkar, 2011).

Those suffering the diabetes complications that corrupt vision, renal function, nerves, blood vessels, and the skin have found hope in the interruption of protein glycation by curcumin, where it was seen to be one of several natural substances to interfere with the reaction of glycated materials and their respective receptors. The therapeutic potential in delaying or preventing diabetic complications using curcumin is viewed as a safe and simple complement to conventional therapies (Elosta, 2012) (Ahmed, 2005).

Besides the diminution of AGE potency, curcumin inhibits the unfavorable activities tied to enzymes such as the pro-inflammatory COX2, the peroxide-forming lipoxygenase and the unfriendly nuclear factor kappa beta. Remarkably, curcumin also was discovered to have probiotic characteristics and to enhance treatment routes for such refractory conditions as Crohn’s, certain cancers, cirrhosis of the liver, and COPD (Chronic Obstructive Pulmonay Disease) (Bengmark, 2009).

It has become clear that some natural substances can replace drugs, without side effects. Anti-AGE strategies, addressing more than one body system and using curcumin in the arsenal, are here right now.

References

Ahmed N.
Advanced glycation end products–role in pathology of diabetic complications.
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Bengmark S, Mesa MD, Gil A.
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Ishita Chattopadhyay, Kaushik Biswas, Uday Bandyopadhyay, and Ranajit K. Banerjee
Turmeric and curcumin : Biological actions and medicinal applications
Current Science. 2004, 10 July; 87 (1): 44-53


Chatzigeorgiou A, Halapas A, Kalafatakis K, Kamper E.
The use of animal models in the study of diabetes mellitus.
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Cherbuin, Nicolas, Sachdev, Perminder, MD, PhD, Anstey, Kaarin.
Higher normal fasting plasma glucose is associated with hippocampal atrophy: the path study.
Neurology Journal. September 2012 Volume 79 Issue 10: Pages: 1019-1026


Elosta A, Ghous T, Ahmed N.
Natural products as anti-glycation agents: possible therapeutic potential for diabetic complications.
Curr Diabetes Rev. 2012 Mar;8(2):92-108.


Goldberg T, Cai W, Peppa M, Dardaine V, Baliga BS, Uribarri J, Vlassara H.
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J Am Diet Assoc. 2004 Aug;104(8):1287-91.


Alison Goldin, BA; Joshua A. Beckman, MD; Ann Marie Schmidt, MD; Mark A. Creager, MD
Basic Science for Clinicians: Advanced Glycation End Products—Sparking the Development of Diabetic Vascular Injury
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Jakus V, Rietbrock N.
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Krajcovicová-Kudlácková M, Sebeková K, Schinzel R, Klvanová J.
Advanced glycation end products and nutrition.
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Manmei Li, Zhong Liu, Zhulin Zhang and Lin Ma
Inhibitory effects of curcumin derivatives on nonenzymatic glucosylation in vitro
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Lin J, Tang Y, Kang Q, Chen A.
Curcumin eliminates the inhibitory effect of advanced glycation end-products (AGEs) on gene expression of AGE receptor-1 in hepatic stellate cells in vitro.
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Lin J, Tang Y, Kang Q, Feng Y, Chen A.
Curcumin inhibits gene expression of receptor for advanced glycation end-products (RAGE) in hepatic stellate cells in vitro by elevating PPARγ activity and attenuating oxidative stress.
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Ji-ping Liu, Liang Feng, Mao-mao Zhu, Ru-Shang Wang, Ming-hua Zhang, Shao-ying Hu, Xiao-bin Jia, Jin-Jie Wu
The In Vitro Protective Effects of Curcumin and Demethoxycurcumin in Curcuma longa Extract on Advanced Glycation End Products-Induced Mesangial Cell Apoptosis and Oxidative Stress
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Okamoto T, Yamagishi S, Inagaki Y, Amano S, Koga K, Abe R, Takeuchi M, Ohno S, Yoshimura A, Makita Z.
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Rees DA, Alcolado JC.
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Sajithlal GB, Chithra P, Chandrakasan G.
Effect of curcumin on the advanced glycation and cross-linking of collagen in diabetic rats.
Biochem Pharmacol. 1998 Dec 15;56(12):1607-14.


P. P. Sarvalkar, M. V. Walvekar and L. P. Bhopale
Antioxidative effect of curcumin (Curcuma longa) on lipid peroxidation and lipofuscinogenesis in submandibular gland of D-galactose- induced aging male mice
Journal of Medicinal Plants Research. 30 September, 2011 Vol. 5(20): 5191-5193

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Alzheimer’s Disease And Visual Clutter

senior-coupleSuppose you were at a football game where the home team spectators were wearing red hats, but your sister was wearing a yellow one because nobody told her that today was red hat day. Could you pick her out of the crowd? Kind of easy, right? Now, suppose one of her friends gave your sister the extra red hat she carried in her tote bag.  Finding her in the crowd would be more of a challenge, eh? What is it that causes the confusion? Is it the hat or that your sister tends to look like everyone else? How sorry do you feel for the guy who comes to work wearing one maroon and one brown sock because he is retinal rod-deficient and has a hard time distinguishing shades (despite that he has another pair just like this one)? Under some circumstances, recognition can be a challenge, particularly when crowding of images occurs, as in both the stadium and the sock drawer. Such is the trial of the Alzheimer’s or the mildly demented patient, only it happens more often.

Those with Alzheimer’s disease may be unable to recognize once-familiar faces and objects because of infirm perceptions or the incapacity to recall from memory. The face is important to social interaction. Its perceptions are complexed by the myriad facial expressions and shapes that need to be analyzed and interpreted. Additionally, context affects recognition. Although you’ve seen a colleague in the office day after day for years, you may suddenly forget his name when seeing him, after your or his retirement, in a venue that is unfamiliar to both of you, such as a shopping mall in a distant city.  Face perception involves more than one area of the brain, with some areas being more important than others. One of these is called the medial temporal lobe, a kind of garage that houses the memory “toolbox,” most notably the hippocampus, the part that is critical to memory formation. In here sits the perihinal cortex, which receives data from the sense organs. It favors visual perception and memory while the rest of the hippocampus processes spatial and temporal relationships (Murray, 2007) (Buckley, 2005).

Damage to, or interference with, the perihinal cortex or its immediate surroundings can hamper the availability of semantic (long-term factual) memory and the formation of new memories from recent perceptions. The capacity to attach meaning to new percepts is compromised, and memories are not completely formed. Because faces share common features, ambiguity of interpretation can occur and recognition becomes an uncertain proposition. Recognition of faces may also be tied to events. Reliving the past, using episodic memory, may be able to jar recall, but not always and not always with the same reliability. Impairment of episodic memory is the hallmark of Alzheimer’s disease, but in some circles is viewed more as the inability to encode and store information than an inability to retrieve it (Traykov, 2007).

Because perception and memory are linked, it is possible that one affects the other.  Your mentally challenged aunt may fail to recognize you not only because she forgot who you are, but also because she can’t clearly perceive the distinct combination of facial features that make you, you. But this is more apt to happen in a crowd of other, competing, faces than if you walk into her room by yourself. It’s been determined that minimizing the degree of perceptual interference can improve facial/object perception by eliminating features that are visually similar. Low interference conditions, where perceptually dissimilar objects occupy proximal space, present less visual clutter, often resulting in improved cognitive performance (Newsome, 2012). The less feature ambiguity, the more meaningful the perceptual representation (Barense, 2010). This means that a person with a square facial feature would be more easily recognizable than if he had a rounded feature, like everybody else. Thus, if the whole family comes to visit your demented aunt, it can be supposed that entering the room one at a time, allowing her to react and to respond to one face at a time, may be more positive an encounter  that entering en masse. Object or facial recognition in clutter may also depend on whether or not the original perception occurred in visual clutter, which purportedly has an effect on later discrimination. Meeting a person for the first time while in a large group, compared to meeting him in a twosome or threesome, will have an effect on the recognition of that person at a later time, whether alone or not. Unless special attention is paid to new perceptions, memory lapses should not be a surprise.  Visual clutter demands competitive selection, and reducing clutter could help not only the cognitively impaired with everyday tasks, but also the inattentive, distracted or disinterested people around us.

Everyone sometimes has trouble recognizing faces, and it’s even more common for people to forget names. There is a name for face “blindness.” It’s prosopagnosia. One of the complaints of sufferers is that they can’t follow the plot of a TV serial because they don’t recognize the characters they saw on the previous show. Most cases involve brain damage, including that from trauma, stroke or the degeneration of AD. In these instances, face recognition was normal at one time. Of course, this can cause serious social problems, but it is downright frightening when people cannot recognize themselves in a mirror.

References

Barense MD, Rogers TT, Bussey TJ, Saksida LM, Graham KS.
Influence of conceptual knowledge on visual object discrimination: insights from semantic dementia and MTL amnesia.
Cereb Cortex. 2010 Nov;20(11):2568-82.

Barense MD, Ngo JK, Hung LH, Peterson MA.
Interactions of memory and perception in amnesia: the figure-ground perspective.
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Buckley MJ.
The role of the perirhinal cortex and hippocampus in learning, memory, and perception.
Q J Exp Psychol B. 2005 Jul-Oct;58(3-4):246-68.

Duarte LR, Syssau A, Jiménez M, Launay M, Terrier P.
Deficit of access or storage: semantic memory processing in Alzheimer disease.
Can J Aging. 2007 Fall;26(3):227-39.

Jay Hegdé, Serena K. Thompson, Mark Brady and Daniel Kersten
Object recognition in clutter: cortical responses depend on the type of learning
Front. Hum. Neurosci. 6:170. Publ online: 19 June 2012.

Laisney M, Giffard B, Eustache F.
Semantic memory in Alzheimer’s disease: contributions of semantic priming.
Psychol Neuropsychiatr Vieil. 2004 Jun;2(2):107-15.

McCarley, Jason S.; Yamani, Yusuke; Kramer, Arthur F.; Mounts, Jeffrey R. W.
Age, clutter, and competitive selection.
Psychology and Aging, Vol 27(3), Sep 2012, 616-626.

Murray EA, Bussey TJ, Saksida LM.
Visual perception and memory: a new view of medial temporal lobe function in primates and rodents.
Annu Rev Neurosci. 2007;30:99-122.

Elisabeth A. Murray, Steven P. Wise
Why is there a special issue on perirhinal cortex in a journal called hippocampus? The perirhinal cortex in historical perspective
Hippocampus–Special Issue: Perirhinal Cortex: At the Crossroads of Memory and Perception
Volume 22, Issue 10, pages 1941–1951, October 2012

Rachel N. Newsome, Audrey Duarte, Morgan D. Barense
Reducing perceptual interference improves visual discrimination in mild cognitive impairment: Implications for a model of perirhinal cortex function
Hippocampus–Special Issue: Perirhinal Cortex: At the Crossroads of Memory and Perception
Volume 22, Issue 10, pages 1990–1999, October 2012

Traykov L, Rigaud AS, Cesaro P, Boller F.
Neuropsychological impairment in the early Alzheimer’s disease.
Encephale. 2007 May-Jun;33(3 Pt 1):310-6.

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Good News About Coffee

cup-of-coffee-on-saucerThe inveterate coffee drinkers among us will appreciate the good news about one of our favorite beverages. After all the flak we took about the vices of coffee, now’s the chance to respond. After water and tea, coffee is the next most popular drink on the planet, having a starring role in the history of several cultures. It came from the Muslim world, travelled to Italy and then to the rest of Europe, finally landing in the New World. At one time, it was limited only to religious observances.

The coffee bean is contained inside a “cherry” that grows on a small evergreen bush.  The Arabica strain is the more highly regarded of the two chief varieties, but the robusta strain is more resistant to the diseases peculiar to this plant, though less flavorful and more bitter. Arabica prefers the coolness of the mountainside; robusta will grow at lower elevations and in warmer climates. Since the best tasting coffee really is mountain grown, the sales talk of a particular brand is true. But Mrs. Olsen never told us that other brands also use mountain grown beans. She merely capitalized on a little-known fact.

One effect of coffee consumption is moderately elevated blood pressure, which is not surprising because caffeine is a stimulant. Italian studies done in the early 1990’s found that 200 milligrams of caffeine, about two cups’ worth, could raise systolic blood pressure by 10% and diastolic by 5% for up to two hours after consumption. The mechanism points to vasoconstriction (which has its own benefits), but researchers found no variation in heart rate or cardiac contractility (Casiglia, 1991), leading to an assumption that this temporary state is not a major concern, especially in light of later studies that reported no association between long-term coffee consumption and increase of cardiovascular complications (Mesas, 2011) or risk of hypertension (Geleijnse, 2008) (Klag, 2002).

Vitamin B6, known as pyridoxine, is a nutrient occasionally used to tame morning sickness in pregnancy and the throes of PMS. It’s also been used to address homocysteine imbalance, carpal tunnel syndrome, immunity deficiencies, and various behavioral/psychiatric issues. However, careless dosing of vitamin B6 can cause medical concerns that outweigh the benefits of producing the monoamine neurotransmitters, serotonin and dopamine. Large doses of B6 over a period of time can cause nerve fiber damage, particularly auditory neuropathy. You’d never think that coffee can prevent and treat this malady, but it does (Hong, 2008). One active coffee component is called trigonelline (Hong, 2009), an alkaloid also found in pumpkin that is able to modulate blood glucose (van Dijk, 2009) (Yoshinari, 2009). Because auditory neuropathy may be attenuated by trigonelline, why can’t the peripheral neuropathy of diabetes or physical trauma likewise be eased? It’s worth a look (Zhou, 2012).

Late-life dementia and Alzheimer’s disease (AD) are concerns shared by an aging population across the globe. Finnish studies followed a number of middle-agers for more than twenty years, documenting their coffee (and tea) consumption along the way.  Focusing more on caffeine than on coffee’s lesser-known constituents, researchers found that, over the long haul, those who drank three to five cups of coffee a day at midlife had a lower risk of dementia and AD in old age (Eskelinen, 2009, 2010).  American studies later found that long-term coffee consumption protects against cognitive impairment by reducing the formation of amyloid beta, the protein that forms the plaques associated with AD. Here it was inferred that caffeine is part of a synergy that affords the desired effect, with many coffee constituents not yet identified (Cao, 2011).

Because early research had indicated that coffee may be protective against conditions other than neurological, scientists took the trigonelline link a little further. It’s accepted that people with diabetes are at risk for cognitive dysfunction. Initially, it was proposed that coffee was merely to be explored as a tool in the management of diabetes and related sequelae (Biessels, 2010). It was realized, however, that caffeine can decrease the risk of type 2 diabetes and consequent cognitive decline (Salazar-Martinez, 2004) (Tuomilehto, 2004).

In general, coffee increases plasma antioxidant capacity, possibly because of the contribution, bioavailability and activity of its particular group of polyphenols, including chlorogenic acid, one component linked to a reduction of type 2 diabetes risk by virtue of delaying intestinal glucose absorption and the inhibition of gluconeogenesis (Ong, 2010) (Tunnicliffe, 2011). Other medical conditions are purported to be influenced by coffee’s mechanisms, including gastrointestinal diseases (Inoue, 1998), gallstones (Leitzmann, 1999), and Parkinson’s disease (Checkoway, 2002) (Blanchette, 2000).

If coffee has a down side, it’s that it can interact with some drugs, most notably quinolone antibiotics, such as ciprofloxacin and its kin, which increase caffeine concentrations by inhibiting its clearance (Harder, 1989). Coffee’s popularity cannot be ignored. Just look at all the coffee options that run the gamut from hot to cold, from sweet to sweeter, and from low-cal to mega-cal. Since the 1989 expiration of a global agreement to stabilize supply, availability has fluctuated—and so has the price. You can’t even get the cup for a dime any more.

References

Biessels GJ.
Caffeine, diabetes, cognition, and dementia.
J Alzheimers Dis. 2010;20 Suppl 1:S143-50.

Campdelacreu J.
Parkinson disease and Alzheimer disease: environmental risk factors.
[Article in English, Spanish]

Neurologia. 2012 Jun 13. [Epub ahead of print]

Cao C, Wang L, Lin X, Mamcarz M, Zhang C, Bai G, Nong J, Sussman S, Arendash G.
Caffeine synergizes with another coffee component to increase plasma GCSF: linkage to cognitive benefits in Alzheimer’s mice.
J Alzheimers Dis. 2011;25(2):323-35.

Casiglia E, Bongiovì S, Paleari CD, Petucco S, Boni M, Colangeli G, Penzo M, Pessina AC.
Haemodynamic effects of coffee and caffeine in normal volunteers: a placebo-controlled clinical study.
J Intern Med. 1991 Jun;229(6):501-4.

Checkoway H, Powers K, Smith-Weller T, Franklin GM, Longstreth WT Jr, Swanson PD.
Parkinson’s disease risks associated with cigarette smoking, alcohol consumption, and caffeine intake.
Am J Epidemiol. 2002 Apr 15;155(8):732-8.

Eskelinen MH, Ngandu T, Tuomilehto J, Soininen H, Kivipelto M.
Midlife coffee and tea drinking and the risk of late-life dementia: a population-based CAIDE study.
J Alzheimers Dis. 2009;16(1):85-91.

Eskelinen MH, Kivipelto M.
Caffeine as a protective factor in dementia and Alzheimer’s disease.
J Alzheimers Dis. 2010;20 Suppl 1:S167-74.

Floegel A, Pischon T, Bergmann MM, Teucher B, Kaaks R, Boeing H
Coffee consumption and risk of chronic disease in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Germany study.
Am J Clin Nutr. 2012 Apr;95(4):901-8.

Yoichi Fukushima, Takashi Ohie, Yasuhiko Yonekawa, Kohei Yonemoto, Hiroki Aizawa, Yoko Mori, Makoto Watanabe, Masato Takeuchi, Maiko Hasegawa, Chie Taguchi and Kazuo Kondo
Coffee and Green Tea As a Large Source of Antioxidant Polyphenols in the Japanese Population
Journal of Agricultural and Food Chemistry 2009 57 (4), 1253-1259

Gelber RP, Petrovitch H, Masaki KH, Ross GW, White LR.
Coffee intake in midlife and risk of dementia and its neuropathologic correlates.
J Alzheimers Dis. 2011;23(4):607-15.

Geleijnse JM.
Habitual coffee consumption and blood pressure: an epidemiological perspective.
Vasc Health Risk Manag. 2008;4(5):963-70.

Harder S, Fuhr U, Staib AH, Wolff T.
Ciprofloxacin-caffeine: a drug interaction established using in vivo and in vitro investigations.
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Head KA.
Peripheral neuropathy: pathogenic mechanisms and alternative therapies.
Altern Med Rev. 2006 Dec;11(4):294-329.

Hermansen K, Krogholm KS, Bech BH, Dragsted LO, Hyldstrup L, Jørgensen K, Larsen ML, Tjønneland AM.
Coffee can protect against disease
Ugeskr Laeger. 2012 Sep 24;174(39):2293-2297.

Hong BN, Yi TH, Park R, Kim SY, Kang TH.
Coffee improves auditory neuropathy in diabetic mice.
Neurosci Lett. 2008 Aug 29;441(3):302-6. Epub 2008 Jun 22.

Hong BN, Yi TH, Kim SY, Kang TH.
High-dosage pyridoxine-induced auditory neuropathy and protection with coffee in mice.
Biol Pharm Bull. 2009 Apr;32(4):597-603.

Huxley R, Lee CM, Barzi F, Timmermeister L, Czernichow S, Perkovic V, Grobbee DE, Batty D, Woodward M.
Coffee, decaffeinated coffee, and tea consumption in relation to incident type 2 diabetes mellitus: a systematic review with meta-analysis.
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Inoue M, Tajima K, Hirose K, Hamajima N, Takezaki T, Kuroishi T, Tominaga S.
Tea and coffee consumption and the risk of digestive tract cancers: data from a comparative case-referent study in Japan.
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Kaiser permanante Division of Research
Coffee Drinking and Caffeine Associated with Reduced Risk of Hospitalization for Heart Rhythm Disturbances
3/2/2010

Klag MJ, Wang NY, Meoni LA, Brancati FL, Cooper LA, Liang KY, Young JH, Ford DE.
Coffee intake and risk of hypertension: the Johns Hopkins precursors study.
Arch Intern Med. 2002 Mar 25;162(6):657-62.

Leitzmann MF, Willett WC, Rimm EB, Stampfer MJ, Spiegelman D, Colditz GA, Giovannucci E.
A prospective study of coffee consumption and the risk of symptomatic gallstone disease in men.
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Mesas AE, Leon-Muñoz LM, Rodriguez-Artalejo F, Lopez-Garcia E.
The effect of coffee on blood pressure and cardiovascular disease in hypertensive individuals: a systematic review and meta-analysis.
Am J Clin Nutr. 2011 Oct;94(4):1113-26. Epub 2011 Aug 31.

Oba S, Nagata C, Nakamura K, Fujii K, Kawachi T, Takatsuka N, Shimizu H.
Consumption of coffee, green tea, oolong tea, black tea, chocolate snacks and the caffeine content in relation to risk of diabetes in Japanese men and women.
Br J Nutr. 2010 Feb;103(3):453-9. Epub 2009 Oct 12.

Ong KW, Hsu A, Tan BK.
Chlorogenic acid stimulates glucose transport in skeletal muscle via AMPK activation: a contributor to the beneficial effects of coffee on diabetes.
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Richelle M, Tavazzi I, Offord E.
Comparison of the antioxidant activity of commonly consumed polyphenolic beverages (coffee, cocoa, and tea) prepared per cup serving.
J Agric Food Chem. 2001 Jul;49(7):3438-42.

Ross GW, Abbott RD, Petrovitch H, Morens DM, Grandinetti A, Tung KH, Tanner CM, Masaki KH, Blanchette PL, Curb JD, Popper JS, White LR.
Association of coffee and caffeine intake with the risk of Parkinson disease.
JAMA. 2000 May 24-31;283(20):2674-9.

Salazar-Martinez E, Willett WC, Ascherio A, Manson JE, Leitzmann MF, Stampfer MJ, Hu FB.
Coffee consumption and risk for type 2 diabetes mellitus.
Ann Intern Med. 2004 Jan 6;140(1):1-8.

Tunnicliffe JM, Eller LK, Reimer RA, Hittel DS, Shearer J.
Chlorogenic acid differentially affects postprandial glucose and glucose-dependent insulinotropic polypeptide response in rats.
Appl Physiol Nutr Metab. 2011 Oct;36(5):650-9. Epub 2011 Oct 6.

Tuomilehto J, Hu G, Bidel S, Lindström J, Jousilahti P.
Coffee consumption and risk of type 2 diabetes mellitus among middle-aged Finnish men and women.
JAMA. 2004 Mar 10;291(10):1213-9.

van Dijk AE, Olthof MR, Meeuse JC, Seebus E, Heine RJ, van Dam RM.
Acute effects of decaffeinated coffee and the major coffee components chlorogenic acid and trigonelline on glucose tolerance.
Diabetes Care. 2009 Jun;32(6):1023-5. Epub 2009 Mar 26.

Yoshinari O, Sato H, Igarashi K.
Anti-diabetic effects of pumpkin and its components, trigonelline and nicotinic acid, on Goto-Kakizaki rats.
Biosci Biotechnol Biochem. 2009 May;73(5):1033-41. Epub 2009 May 7.

Zhou J, Chan L, Zhou S.
Trigonelline: a plant alkaloid with therapeutic potential for diabetes and central nervous system disease.
Curr Med Chem. 2012 Jul 1;19(21):3523-31.

*These statements have not been evaluated by the FDA.
These products are not intended to treat, diagnose, cure, or prevent any disease.

Phosphatidylcholine And Memory: Aw, Forget It. Oh, You Already Did.

Forgetful-manIn his 1932 inaugural address, FDR told the world that we have nothing to fear but fear itself. If you ask people today what they fear, the list will likely include more specific things, like public speaking, ostracism, blindness, death, poverty, failure, memory loss, disease and a host of other states, conditions or activities. Some fears can be overcome with counseling, such as acrophobia; some can be prevented by being active instead of passive, such as poverty and failure; and some might require nutritional or medical intervention, such as certain diseases. Getting and using education, which doesn’t necessarily entail sitting in a classroom, might possibly attend to these needs. A modern-day fear is that of Alzheimer’s disease (AD), one that people associate with memory dysfunction, disorientation, and eventual loss of function. It’s a matter of not knowing that you don’t know. And it’s frightening.

The loss of cognitive ability takes a while to manifest, maybe ten to fifteen years, and is associated with the development of abnormal tissues and protein deposits in the brain’s cerebral cortex, which is the outermost layer of gray matter responsible for higher brain functions, such as sensation, voluntary muscle movement, thought, reasoning and memory. The primary neurotransmitter involved with the latter three of these cerebral obligations is acetylcholine, which is released at the ends of nerve fibers to send nerve impulses from one cell to another. Other jobs of this neurotransmitter involve decreasing heart rate and contraction strength, dilating blood vessels, increasing peristalsis, and raising elimination pressure during urination.

The dementia we fear results in deterioration of mental faculties, causing apathy, confusion and occasional stupor. A couple centuries ago it was synonymous with insanity, and was termed dementia praecox, now known as schizophrenia. Of its several forms, senile dementia is the one most commonly recognized, usually occurring after age 65, though it can happen earlier.

Natural deficits of acetylcholine accompany the aging process, causing those sporadic lapses in short-term memory that many individuals experience from time to time. Called benign forgetfulness, this non-debilitating memory decline is not to be confused with Alzheimer’s disease. It’s the degeneration of neurons in the cerebral cortex that leads to difficulties with language and judgment in AD. From the cortex, degeneration proceeds to the hippocampus, which is the part of the limbic system that deals with memory and spatial navigation. The hippocampus helps us to retain facts that pertain to specific events so they can be regurgitated if needed, but it also helps to order the chronology of one’s lifetime events. All this is what we typically call recollection. Memory tasks usually excite considerable hippocampus engagement, but that response is substantially weakened by advancing age, particularly in the absence of nutrients that feed the process. In transient global amnesia, a state induced by statin drugs’ cholesterol reduction and subsequent interference with the body’s manufacture and use of co-enzyme Q10, hippocampus activity is seriously constrained, though reversible by judicious supplementation of the enzyme.

Late in the last century, scientists demonstrated interest in the enhancement of memory in lab animals by introducing the phospholipid called phosphatidylcholine (PC) to their diets. “Demented” mice showed very low levels of choline and acetylcholine. After adding PC to the rations of the experimental group, the examiners saw an expected reversal in choline and acetylcholine levels, and an improvement in memory (Chung, 1995). Yes, mice are not the same as people, but they share a commonality in cerebral function, providing a good model for this scrutiny of memory acquisition and retention (Moriyama, 1996).

PC not only increases neurotransmitter efficiency, but also improves the supportive nature of polyunsaturated fatty acids (PUFA’s) in the revival of cell membrane fluidity. Since PC is the major structural and functional component of the cell membrane, this is not small news. Its reinstatement to a place of high stature in membrane architecture helps to sequester renegade substances that inhibit the membrane’s full capabilities in directing the machinery of life (Hiratsuke, 2009) (Gong, 2004).

After it was found that Alzheimer’s disease is related to abnormal metabolism of membrane phospholipids, researchers began to examine faulty homeostasis for discovery of diagnostic biomarkers. Alterations in phosphatidylcholine and phosphatidylethanolamine values were seen as indicative of membrane breakdown that could lead to fatty acid and phospholipid-related disorders that include dementias (Gonzalez-Dominguez, 2014). This is of particular interest because the pathophysiological changes associated with AD begin decades before clinical symptoms appear (Trushina,2013) (Whiley, 2014).

Since the brain is about sixty percent fat, it seems logical to ensure its repletion. Fatty acids and phospholipids (PL’s) are the most crucial molecules to occupy the space. It’s not very likely that seniors can get sufficient phospholipids from their diets because of diminished sense of taste for food, living and eating alone, being food insecure, and being broke. We realize this doesn’t describe all people in the group, but it probably covers someone you know. Egg yolks, liver, wheat germ and peanuts have some of the precursors to PL’s, but frequency of ingestion and concentration are often insufficient. Neither are many older folks amply hydrated to allow the PL’s to become organized into carriers of helpful molecules. The administration of PL’s, notably PC, can do much to restore function—and structure—of the membranes that make life more enjoyably livable.

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