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Glutathione: It’s Your Gut

glutathione levelsSome things are so grossly unconventional that we think they’ll never get off the ground. To the contrary is the ultimate use of waste water, but not the kind you’re thinking of. This is olive water, the leftovers from the olive grinding mill. It seems that this material is able to influence some measures of oxidative stress in humans by affecting levels of glutathione, the body’s premier endogenous (self-made) antioxidant, able to be synthesized by all cells of the body.

It has already been accepted that plant phenols are beneficial compounds. Because of increasingly sophisticated testing techniques, those in olives are receiving more and more attention as amplifiers of the body’s antioxidant capacity. A French study performed in 2009 discovered that olive mill waste water has a positive effect on plasma antioxidant potency. Ingesting a mere 2 milliliters of this benevolent elixir contributed to,”…a significant increase in total plasma glutathione concentration…,” involving, “…both the reduced and oxidized forms…”  (Visioli. 2009)  It is widely recognized that specific groups of individuals benefit substantially from increased glutathione levels, most notably the geriatric population. Research has robustly demonstrated that the natural compounds in olives and now, apparently, their waste, play important roles within the living organism.

Glutathione is made from three amino acids—cysteine, glycine, and glutamine—none of which is absolutely essential.  In times of great physical stress, such as major surgery, however, glutamine may be conditionally essential, meaning it has to come from a food or a supplement. Glutathione is your personal antioxidant powerhouse, and it pays super dividends to keep stores as healthy as possible. It’s the presence of a sulfur group on the cysteine portion of the molecule that’s at the foundation of its powerful antioxidant capacity.

Widely found in all forms of life, glutathione plays an essential role in the health of an organism. Cysteine, the businessman of the molecule, but itself a relatively insoluble entity at normal pH, needs to be part of the glutathione tripeptide to do its work. Glutathione synthesizes and repairs DNA, transports amino acids, metabolizes toxins and carcinogens, strengthens the immune system, prevents oxidative damage, and activates enzymes.  It’s pretty busy, don’t you think? Levels of glutathione increase during exercise, but fall with old age, and are found to be deficient in age-related macular degeneration, diabetes, lung and gastrointestinal disease, pre-eclampsia, Parkinson’s disease, and other neurological maladies.

Glutathione exists within cells in its reduced form (GSH), meaning it has an extra electron. In the process of neutralizing reactive oxygen species it becomes oxidized (GSSG), but reacts with another oxidized glutathione to become glutathione disulfide.  Because of enzymatic activity, glutathione is self-healing, particularly in the presence of available cysteine.  (Miller. 2002)  In healthy cells, more than ninety percent is the reduced form…and it should stay that way.  (Owen. 2010) This has strong implications for dietary habits.

Raising GSH through direct supplementation is difficult.  Research suggests that oral glutathione is not well-absorbed across the gastrointestinal tract, since it may be inactivated by peptidase enzymes in the gut.  (Witschi. 1992)  At least in the brain, GSH may be elevated by vitamin D. (Garcion. 2001)   However, the supplements, N-acetyl cysteine (NAC) and lipoic acid can increase GSH levels.  (Gross.1993)   (Busse. 1992)   (Shay. 2009) Ongoing research will determine the true bioavailability of oral supplementation.  In cases of Acetaminophen (Tylenol) poisoning, the number one cause of emergency room poisoning visits, the hospital will likely use NAC as an antidote.  Among health care providers, at least a little speculation has focused on the inclusion of NAC in acetaminophen tablets and capsules.

Although no specific foods contain glutathione, there are some that can elevate levels, most by virtue of their sulfur content, including animal products, red peppers, cabbage, broccoli, Brussels sprouts, onions, oats, lentils, beets, eggs, and parsley.  Because it is fundamental to a raft of physiological process, especially as an antioxidant, it’s wise to eat the foods that will ramp it up, including olives.

References

Visioli F, Wolfram R, Richard D, Abdullah MI, Crea R.
Olive phenolics increase glutathione levels in healthy volunteers.

J Agric Food Chem. 2009 Mar 11; 57(5):1793-6.

Lauren T. Miller, Walter H. Watso, Ward G. Kirlin, Thomas R. Ziegler and Dean P. Jones
Oxidation of the Glutathione/Glutathione Disulfide Redox State Is Induced by Cysteine Deficiency in Human Colon Carcinoma HT29 Cells
J. Nutr. 132:2303-2306, 2002

Owen JB, Butterfield DA.
Measurement of oxidized/reduced glutathione ratio.
Methods Mol Biol. 2010;648:269-77.

Witschi A, Reddy S, Stofer B, Lauterburg BH.
The systemic availability of oral glutathione.
Eur J Clin Pharmacol. 1992;43(6):667-9.

Garcion E, Wion-Barbot N, Montero-Menei CN, Berger F, Wion D.
New clues about vitamin D functions in the nervous system.
Trends Endocrinol Metab. 2002 Apr;13(3):100-5.

Gross CL, Innace JK, Hovatter RC, Meier HL, Smith WJ.
Biochemical manipulation of intracellular glutathione levels influences cytotoxicity to isolated human lymphocytes by sulfur mustard.
Cell Biol Toxicol. 1993 Jul-Sep;9(3):259-67.

Busse E, Zimmer G, Schopohl B, Kornhuber B.
Influence of alpha-lipoic acid on intracellular glutathione in vitro and in vivo.
Arzneimittelforschung. 1992 Jun;42(6):829-31.

Kate Petersen Shay, Régis F. Moreau, Eric J. Smith, Anthony R. Smith, and Tory M. Hagen
Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential
Biochim Biophys Acta. 2009 October; 1790(10): 1149–1160.

Wu G, Fang YZ, Yang S, Lupton JR, Turner ND.
Glutathione metabolism and its implications for health.
J Nutr. 2004 Mar;134(3):489-92.

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

Pantothenic Acid—Vitamin B5

legumes-and-cerealsPantothenic acid (vitamin B5) is essential to the metabolism of carbohydrates, proteins, and fats, as well as for the synthesis of hormones and cholesterol. Deficiency is rare and likely to occur in cases of malnutrition. Its anti-inflammatory, anti-oxidant, wound healing, and antiviral actions are now being studied.

BENEFITS

  • Synthesizes cholesterol to produce vitamin D and  (stress) hormones
  • Controls serum cholesterol levels
  • Protects against lipid peroxidation
  • Elevates reduced glutathione (the body’s premier anti-oxidant)
  • Radioprotective
  • Turns fat into energy
  • Metabolizes carbohydrates

DEFICIENCY

  • Acne
  • Parasthesia (tingling in extremities)
  • Sleepiness and headache
  • GI complaints
  • Susceptibility to infections

SOURCES

  • Liver
  • Egg yolks
  • Fresh vegetables
  • Legumes
  • Yeast

At neutral pH, pantothenic acid is stable, but 20% of the B5 in raw meat is destroyed by cooking.  Vegetables lose between 40% and 75% during processing.   Vegetarians with rheumatoid arthritis experienced relief with injected pantothenic acid, as reported in a 1963 issue of Lancet.

 

Electromagnetic Fields (EMF)

young-businesswomanHave you ever had the feeling that your body, mind and spirit were in three separate places, and that you needed the better part of the day to call them to a serious get-together? How about the nondescript notion that something is amiss, but you can’t quite put your finger on it, and it’s not sufficiently debilitating to see the doctor? You might be living with—or through—electromagnetic sensitivity (ES). What makes this hard to understand is that some scientists and physicians recognize this state as a legitimate concern, while others treat it disdainfully. (Genuis. 2011) Often it is connected to multiple chemical sensitivity (MCS), which is also a controversial diagnosis, despite being recognized by the Social Security Administration and the U.S. Department of Housing and Urban Development as a disabling condition. Too many medical professionals have tried to convince patients that their incapacitation is “in their heads,” or is the manifestation of a “poor attitude.” The sufferers of ES / MCS can conclude that their physicians’ training and education stopped at the medical school portals…narrow door, narrow mind. What worked for medicos a decade ago may not be part of today’s tool kit.

ES is an environmentally-triggered illness that produces symptoms in those exposed to common levels of electromagnetic fields (EMF) from electrical sources in the environment: power lines, motors, computers, trains, stereos, kitchen appliances, electric blankets, cell phones, and more, including the microwave oven. The nervous system is the primary site affected by electromagnetic fields, and those with nervous system damage from prior insult seem predisposed to ES. (Rea. 1991) Persons with chronic fatigue and mercury toxicity (from dental amalgams) are among the more susceptible. Although possibly begotten from other causes, symptoms include fatigue, nausea, headaches, loss of memory and concentration, buzzing ears (tinnitus), skin problems, insomnia, seizures, dizziness, and vague feelings of illness. Because the etiology is evasive, patients may be dismissed as psychosomatic.

One’s exposure to electromagnetic fields (EMF) varies according to occupation, venue, and routine. The general population is likely to see EMF as more invasive than those in occupations that employ electromagnetism regularly, such as radiographers or certain security personnel who work around metal detectors. (van Dongen. 2011) This attitude may be a matter of education, or what some may term selective indoctrination (brainwashing). Perceived health risks, therefore, are subjective. For people suffering ES, a trip to the doctor is akin to jumping from the pan into the fire, since the office is loaded with EMF’s from computers and their monitors, fluorescent lights, and testing equipment. It’s even worse in a hospital. MRI machines and ultrasound sources are especially bothersome. Regular cell phone use, and even wearing one, can contribute to misery. No medicine is available to bring relief…only avoidance, which is practically impossible.

Studies on the effects of EMF on pregnant women have returned mixed results. Group sizes have been too small to be significant; the combined expertise in EMF physics, engineering and reproductive biology has been absent; and the properties of the electromagnetic waves themselves are listed as confounding factors. To some scientists, this sounds more like excuses than truth. But it’s been determined that exposure to “normal” levels of EMF are not harmful to the developing fetus. (Brent. 1993) (Brent. 1999) In this context, “normal” levels of exposure relate to video display terminals. All common EMF sources were reviewed in Italian research, where video display terminals again were exculpated. However, electric blankets, power lines, heated waterbeds, and other sources that directly contact the body or that emit high intensity pulses have been weakly associated with congenital defects and growth retardation. (Luchini. 1992)

Microwave exposure, regardless of source, has been seen to reduce levels of glutathione in the human (and lab animal) body. Glutathione occurs widely in plant and animal tissue, where it plays a role in cellular respiration and serves as a cofactor for several enzymes. It’s best known as the prime protector against oxidative stress where, for example, it protects red blood cells against the toxic hydrogen peroxide that results from certain metabolic activities. Furthermore, such exposure leads to the overproduction of reactive oxygen species and the inhibition of protective enzymes and hormones (Kesari. December, 2011), such as melatonin, the hormone that regulates sleep, mood, and even ovarian cycles, and may be protective against cancer. (Kesari. November, 2011) These studies focused on 2.45 GHz microwave radiation, that which comes from microwave ovens, radio-controlled toys, and some phone systems. The EMF’s found in parts of the house where FM radios, blue tooth and television sets are common are often very low, sometimes not measurable. (Breckenkamp. 2011)

There are no objective tests to diagnose ES, but there have been enough subjective reports to warrant a closer look. Some people are bothered only when devices are put through on-off cycles; others all the time, reporting constant headaches, muscle twitches and even skipped heartbeats. (McCarthy. 2011) As luck would have it, it’s hard to duplicate most symptoms in a blinded laboratory setting, leading investigators to question biophysical hypersensitivy without completely denying its existence. (Rubin. 2005) One symptom that appears often is tinnitus—ringing in the ears. More than half the subjects with self-reported EMS experience this, adding that it disrupts sleep and work. Individual use of a cell phone has been excused from tinnitus causation in at least one report. (Landgrebe. 2009)

But that does not excuse cell phones from all purported debilitations. Memory function was impaired in laboratory animals exposed to cell phone radiation for as little as two hours a week for almost a year. But these creatures are considerably smaller than an adult human, so interpretation of the results calls for a light touch. (Nittby. 2008) Pulsed EMF, which results from storage and sudden release of energy, may have adverse effects on neuronal function, as determined by German studies on subjects whose auditory discrimination tasks suffered following exposure. The ensuing recommendation of these investigators is to remove cell phones from children, the elderly, and the sick. (Maier. 2004)

As research gains momentum and relates EMF’s to a multitude of ills, including Alzheimer’s disease, impaired red blood cell flow and conditions of lesser chronicity, we may come to realize that progress has more take than give. People react to some frequencies more than to others, but not all people respond the same way. Altering an environment to accommodate all comers is neither feasible nor likely. That means taking matters into one’s own hands. There is little room to get into the physics of EMF, but suffice it to say that 2.5 mG (milligauss) is close to the tolerable limit of exposure, though no RDA has been set. Most states in the U.S. have adopted a 3.0 mG cutoff, though some researchers prefer 1.0. The EPA says 1.0 mG, which agrees with Sweden. The Russians view .001 mG as enough. Protecting yourself is as simple as turning off the electric blanket before getting into bed, shutting off the TV and computer monitor when not using them, stepping away from the microwave while it’s on, eschewing fluorescent lamps where possible, testing appliances with a handheld meter before purchasing, and fighting the power company that wants to put high tension wires in your neighborhood. If you own a gauss meter, look for a level of 0.5 mG in your home. That’s where you put your pillow. Of course, you may not be a victim of electromagnetic sensitivity. You might be interested in http://cetf.us/2010/02/16/david-carpenter-high-voltage-power-lines-pose-health-risks/, where Dr. David Carpenter, noted EMF researcher, looks at high-voltage power lines.

References

Aalto S, Haarala C, Brück A, Sipilä H, Hämäläinen H, Rinne JO.
Mobile phone affects cerebral blood flow in humans.
J Cereb Blood Flow Metab. 2006 Jul;26(7):885-90.

Breckenkamp J, Blettner M, Schüz J, Bornkessel C, Schmiedel S, Schlehofer B, Berg-Beckhoff G.
Residential characteristics and radiofrequency electromagnetic field exposures from bedroom measurements in Germany.
Radiat Environ Biophys. 2011 Oct 1.

Brent RL, Gordon WE, Bennett WR, Beckman DA.
Reproductive and teratologic effects of electromagnetic fields.
Reprod Toxicol. 1993 Nov-Dec;7(6):535-80.

Brent RL
Reproductive and teratologic effects of low-frequency electromagnetic fields: a review of in vivo and in vitro studies using animal models.
Teratology. 1999 Apr;59(4):261-86.

Cao Z, Liu J, Li S, Zhao X.
Effects of electromagnetic radiation from handsets of cellular telephone on neurobehavioral function.
Wei Sheng Yan Jiu. 2000 Mar 30;29(2):102-3.

Eulitz C, Ullsperger P, Freude G, Elbert T.
Mobile phones modulate response patterns of human brain activity.
Neuroreport. 1998 Oct 5;9(14):3229-32.

Feychting M, Jonsson F, Pedersen NL, Ahlbom A.
Occupational magnetic field exposure and neurodegenerative disease.
Epidemiology. 2003 Jul;14(4):413-9; discussion 427-8.

Genuis SJ, Lipp CT.
Electromagnetic hypersensitivity: Fact or fiction?
Sci Total Environ. 2011 Dec 5.

International Commission on Non-Ionizing Radiation Protection
ICNIRP STATEMENT ON THE “GUIDELINES FOR LIMITING EXPOSURE TO TIME-VARYING ELECTRIC, MAGNETIC, AND ELECTROMAGNETIC FIELDS (UP TO 300 GHz)”
Health Physics. 97(3):257-258, September 2009.
doi: 10.1097/HP.0b013e3181aff9db
http://www.icnirp.net/documents/StatementEMF.pdf

Kesari KK, Behari J, Kumar S.
Mutagenic response of 2.45 GHz radiation exposure on rat brain.
Int J Radiat Biol. 2010 Apr;86(4):334-43.

Kesari KK, Kumar S, Behari J.
Pathophysiology of Microwave Radiation: Effect on Rat Brain.
Appl Biochem Biotechnol. 2011 Nov 29.

Kesari KK, Kumar S, Behari J.
900-MHz microwave radiation promotes oxidation in rat brain.
Electromagn Biol Med. 2011 Dec;30(4):219-34.

Michael Landgrebe, Ulrich Frick, Simone Hauser, Goeran Hajak, Berthold Langguth
Association of Tinnitus and Electromagnetic Hypersensitivity: Hints for a Shared Pathophysiology?
PLoS ONE 4(3): e5026. March 27, 2009

Levallois P, Neutra R, Lee G, Hristova L.
Study of self-reported hypersensitivity to electromagnetic fields in California.
Environ Health Perspect. 2002 Aug;110 Suppl 4:619-23.

Luchini L, Parazzini F.
Exposure to low-frequency electromagnetic fields and pregnancy outcome: a review of the literature with particular attention to exposure to video terminals.
Ann Ostet Ginecol Med Perinat. 1992 Mar-Apr;113(2):102-13.

Maier R, Greter SE, Maier N.
Effects of pulsed electromagnetic fields on cognitive processes – a pilot study on pulsed field interference with cognitive regeneration.
Acta Neurol Scand. 2004 Jul;110(1):46-52.

McCarty DE, Carrubba S, Chesson AL, Frilot C, Gonzalez-Toledo E, Marino AA.
Electromagnetic hypersensitivity: evidence for a novel neurological syndrome.
Int J Neurosci. 2011 Dec;121(12):670-6.

Nittby H, Grafström G, Tian DP, Malmgren L, Brun A, Persson BR, Salford LG, Eberhardt J.
Cognitive impairment in rats after long-term exposure to GSM-900 mobile phone radiation.
Bioelectromagnetics. 2008 Apr;29(3):219-32.

William J. Rea, MD, FACS, Yaqin Pan, MD, et al
Electromagnetic Field Sensitivity
Journal of Bioelectricity, 1991; 10(1&2), 241-256.

Röösli M, Moser M, Baldinini Y, Meier M, Braun-Fahrländer C.
Symptoms of ill health ascribed to electromagnetic field exposure–a questionnaire survey.
Int J Hyg Environ Health. 2004 Feb;207(2):141-50.

Rubin GJ, Das Munshi J, Wessely S.
Electromagnetic hypersensitivity: a systematic review of provocation studies.
Psychosom Med. 2005 Mar-Apr;67(2):224-32.

Tynes T, Klaeboe L, Haldorsen T.
Residential and occupational exposure to 50 Hz magnetic fields and malignant melanoma: a population based study.
Occup Environ Med. 2003 May;60(5):343-7.

van Dongen D, Smid T, Timmermans DR.
Perception of health risks of electromagnetic fields by MRI radiographers and airport security officers compared to the general Dutch working population: a cross sectional analysis.
Environ Health. 2011 Nov 9;10(1):95.

*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.
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Mishra S, Palanivelu K.
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Packer L, Tritschler HJ, Wessel K.
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William M. Pardridge, MD
Targeting Neurotherapeutic Agents Through the Blood-Brain Barrier
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Shah GN, Mooradian AD.
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Spittle B.
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STINS, MONIQUE F.
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Research Portfolio Online Reporting Tool, 2009
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Q Xiang , Y Liang , L Chen , C Wang , B Chen), X Chen , M Zhou
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Zhai JX, Guo ZY, Hu CL, Wang QN, Zhu QX.
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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.

Solvents In The Home And Workplace

kitchen-cleanersThere are too many things we take for granted.  When it comes to health, if it doesn’t hurt, we don’t pay attention to it.  This is the case with the solvents we use around the house, including the apparently harmless cleaners and the more aggressive degreasers and thinners.  The solvents used at the workplace are considerably more powerful.  In general, quite a few of the products we use at home fit the definition of toxic.

The term solvent refers to liquid (usually organic) chemicals used to dissolve solids.  Some, like turpentine and the citrus solvents, are naturally derived.  Others are made from petroleum or other synthetic sources.  None is “safe,” although there are degrees of “un-safeness.”   (CDC. 2010)  Skin contact and inhalation are both means of entry into the body, and may be categorized by duration as long or short, and by intensity as low or high.  Acute effects occur after short-term exposure; chronic effects after a longer period of time.  Health consequences may be subclinical, meaning that symptoms are not yet manifest.

Some solvents—this includes pesticides—are fat-soluble and allow metabolites access to the central and peripheral nervous systems (CNS and PNS).  While narcosis (stupor) may be reversible, demyelination and cell death often are not.  Researchers in France looked at the relation between Parkinson’s disease and exposure to pesticides in a population whose exposure to these chemicals is prevalent (exterminators), and found that relation to be positive, especially for organochlorine insecticides.  (Elbaz. 2009)  Prior studies on the epidemiology of Parkinson’s by the same team came to a similar conclusion.  (Elbaz. 2008)

All solvents can dissolve the skin’s protective barrier of oils, causing the skin to dry and chap and leading to some form of dermatitis.  Some of the natural ones, like turpentine, may cause allergic reactions.  Some cause no overt damage but penetrate the skin, enter the bloodstream, and damage other organs, particularly the liver.  (Nachman. 2002)  Most of us connect toxicity to physical contact, never thinking that the vapors alone can cause damage, but scientists in Messina, Italy found depletion of reduced glutathione, decreased antioxidant activity, and oxidative damage in subjects exposed to the vapors of organic solvents.  (Costa. 2006)  All studies agree that early detection of toxicity is important to resolution.

The effects of solvent exposure upon the eyes and respiratory tract are realized quickly if concentrations are high enough, but workers are commonly unaware of a solvent’s effects at low concentrations.  Often the only indication of exposure is an increased frequency of colds and respiratory infections.  Over time, chronic bronchitis may develop.   However, the instigating factor(s) may be out of mind and the relationship is never made.  The ubiquity of certain solvents, especially formaldehyde, takes a toll on unsuspecting consumers.  (Schenker. 1996)   Wall finishes, carpeting, cabinetry, plywood, insulation, timber paneling, and even some shampoos, lotions, baby wipes, and body washes may contain formaldehyde.  Some manufacturers will use unfamiliar synonyms to mask the presence of this proven carcinogen.  Formalin, methanol, urea, methylaldehyde, and formic aldehyde are but a few.  Tightness in the chest, breathing difficulty, unexplained rash, and swelling of the mouth and tongue are the more-common signs of exposure to formaldehyde.  Changes in heart rate are not uncommon with over-exposure to any organic solvent, with “over-exposure” being the key modifier, however subjective that may be.  (Morrowa.  1995)

An area lacking in study is reproductive health, but the little research already done points to solvents’ culpability.   Small studies indicate that subjection to solvents that are particular to specific industries may induce decline in sperm motility.  The painting and sheet metal trades and others that use naphtha, methyl ethyl ketone, xylene, toluene and the like are most likely to experience detrimental reproductive consequences.  (Lemasters.  1999)   Although tests in females are not nearly so definitive, infertility, spontaneous abortion, and reproductive cancers have been reported in some studies after chemical exposures.  The ambiguity of testing in females may be due to multiple confounders that include poor methodology and small sample size.  (Sharara. 1998)

Alternatives to harmful solvents are available, but, because they might demand more physical labor, are not the most popular items on the shelf.  Baking soda can kill foul odors.  Vinegar in water or cream of tartar in water can clean aluminum.  Borax cleans the bathroom, and bleach + water will remove mildew from grout.  TSP and water can clean almost anything.  Dismissing solvents is not only a matter of “going green,” but also a matter of personal and family health.  Thinking that your hobby is great fun, you might be surprised to hear that exposure to the solvents used in building models and in artwork during the year preceding childbirth has been associated with elevated risk of childhood leukemia.  (Freedman.  2001)

References

CDC, 2010
Workplace Safety & Health Topics
ORGANIC SOLVENTS
Page last updated:July 20,2010
http://www.cdc.gov/niosh/topics/organsolv/

Elbaz A, Clavel J, Rathouz PJ, Moisan F, Galanaud JP, Delemotte B, Alpérovitch A, Tzourio C.
Professional exposure to pesticides and Parkinson disease.
Ann Neurol. 2009 Oct;66(4):494-504.

Elbaz A, Moisan F.
Update in the epidemiology of Parkinson’s disease.
Curr Opin Neurol. 2008 Aug;21(4):454-60.

Nachman Brautbar, John Williams II
Industrial solvents and liver toxicity: Risk assessment, risk factors and mechanisms
International Journal of Hygiene and Environmental Health. Vol 205, Iss 6, 2002, Pp 479-491

Chiara Costa, Rita De Pasquale, Virginia Silvari, Mario Barbaro, Stefania Catania
In vitro evaluation of oxidative damage from organic solvent vapours on human skin
Toxicology in Vitro  Volume 20, Issue 3, April 2006, Pages 324-331

M.B. Schenker , J.A. Jacobs
Respiratory effects of organic solvent exposure
Tubercle and Lung Disease. Volume 77, Issue 1, February 1996, Pages 4-18

Lisa A. Morrowa, , Stuart R. Steinhauerb
Alterations in heart rate and pupillary response in persons with organic solvent exposure
Biological Psychiatry.  Volume 37, Issue 10, 15 May 1995, Pages 721-730

Grace Kawas Lemasters, Donna M Olsen, James H Yiin, James E Lockey, Rakesh Shukla, et al
Male reproductive effects of solvent and fuel exposure during aircraft maintenance
Reproductive Toxicology.  Volume 13, Issue 3, May-June 1999, Pages 155-166

Fady I Sharara M.D., David B Seifer M.D., Jodi A Flaws Ph.D.
Environmental toxicants and female reproduction
Fertility and Sterility.  Volume 70, Issue 4, October 1998, Pages 613-622

D M Freedman, P Stewart, R A Kleinerman, S Wacholder, E E Hatch, R E Tarone, L L Robison, and M S Linet
Household solvent exposures and childhood acute lymphoblastic leukemia
Am J Public Health. 2001 April; 91(4): 564–567.

Seaton A, Jellinek EH, Kennedy P.
Major neurological disease and occupational exposure to organic solvents.
Q J Med. 1992 Sep;84(305):707-12.

Ng TP, Lim LC, Win KK.
An investigation of solvent-induced neuro-psychiatric disorders in spray painters.
Ann Acad Med Singapore. 1992 Nov;21(6):797-803.

Y. Lolin
Chronic Neurological Toxicity Associated with Exposure to Volatile Substances
Hum Exp Toxicol July 1989 vol. 8 no. 4 293-300

*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.
Diabetes Res Clin Pract. 2005 Jan;67(1):3-21.


Bengmark S, Mesa MD, Gil A.
Plant-derived health: the effects of turmeric and curcuminoids.
Nutr Hosp. 2009 May-Jun;24(3):273-81.


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.
In Vivo. 2009 Mar-Apr;23(2):245-58.


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.
Advanced glycoxidation end products in commonly consumed foods.
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
Circulation. 2006; 114: 597-605


Jakus V, Rietbrock N.
Advanced glycation end-products and the progress of diabetic vascular complications.
Physiol Res. 2004;53(2):131-42.


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
Planta Med. 2012; 12: 1311-1398 DOI: 10.1055/s-0032-1315257


Okamoto T, Yamagishi S, Inagaki Y, Amano S, Koga K, Abe R, Takeuchi M, Ohno S, Yoshimura A, Makita Z.
Angiogenesis induced by advanced glycation end products and its prevention by cerivastatin.
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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.
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P. P. Sarvalkar, M. V. Walvekar and L. P. Bhopale
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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.

Hey Cowboy, Is It Roundup Time?

glyphosateWe hope not.

Good old Fred Nietzsche said, “That which does not kill us makes us stronger.”

Since we’re quoting people, check out Will Rogers’ aphorism, “It isn’t what we don’t know that gives us trouble; it’s what we know that ain’t so.”  Truth is really not that elusive…if you know where to look.

At your age, you’ve probably heard of an herbicide called Roundup®. Entities and agencies with greater clout than we have would like you to believe that this glyphosate herbicide is as safe as can be. Yeah, that’s what Snow White thought about the apple. Eve, too. You know, Adam’s girl.

Glyphosate is a broad-spectrum, non-selective systemic herbicide that is oneof the most widely used in the world. California alone uses almost five millionpounds of it a year. Monsanto brought it to market in the 1970’s, announcingits low toxicity compared to other herbicides. That’s tantamount to saying thatdiesel fumes are less noxious than carbon monoxide from your car. Well, now,there have been experiments with animals that demonstrate comparative low toxicitywith the chemical itself, but the additive ingredients, the surfactants (wettingagents that reduce the surface tension of a liquid, making it “wetter”) are anotherstory. Even the New York AG’s office disapproved of Monsanto’s advertisementthat Roundup® is environmentally friendly and biodegradable (Agrow, 1996).

It is essential to know that animals, namely murine mammals, can be bred to have body systems that mimic humans’. In this way reactions to exogenous substances, both good and bad, can be investigated.

Glyphosate is stable in the environment, binding to many soil types, which makes it immobile in the ground. It moves into groundwater when the soil particles are washed into streams and rivers. Glyphosate also inhibits soil micro-organisms by decreasing soil oxygen consumption (Abdel-Mallek, 1994). Its rate of degradation is hastened when it fails to bind to soil particles. That’s good, but most soils are highly absorbent, so that slows down degradation. Because it adheres to the soil, glyphosate is not usually taken up by a plant’s roots. The LD50 (the dose that is lethal to half the tested subjects) is greater than 4,600 milligrams per kilogram of body weight. That’s 4.6 grams per kilogram, or more than eleven ounces for a 150-pound person. That’s unlikely to happen. But glyphosate does not come to the party alone. Since it isn’t very good at staying in place on a plant’s leaves, it has a chaperone…the surfactant.

Roundup® is not a pre-emergent weed killer. It’s used largely on genetically modified plants, those that are designed to be immune to its biocidal properties, to prevent weeds from competing with the plants’ livelihood and eventual promise. Tests in rats found that the Leydig cells peculiar to the potentiation of testosterone were damaged after two days’ exposure to the chemical. Even at low doses—one part per million—Roundup® disrupted the endocrine system (Clair, 2012). What this substance does to the placenta was observed in agricultural workers using it. Within eighteen hours of exposure to Roundup®, the enzyme activity responsible for estrogen synthesis and placenta integrity was severely disrupted (Richard, 2005). But it wasn’t the glyphosate alone that did the dastardly deed. It was the formulation that included the surfactant. Scientists call it an adjuvant, one which was later seen to induce necrosis in umbilical, placental, testicular and embryonic cells (Benachour, 2009) (Clair, 2012).

Controversy abounds in the world of scientific research. Where some say glyphosate is safe, others gainsay it. MIT scientists found that CYP enzyme disruption severely compromises its ability to metabolize drugs, chemical residues and environmental toxins by interfering with the salubrious activity of the gut microflora (Samsel, 2013).

Aquatic vertebrates are not bred to mimic human physiology, but their responses to environmental insults are a barometer for the health of the biome. Neural defects and cranio-facial malformations were observed in amphibians exposed to the runoff of glyphosate-based herbicides. In this case, the chemical itself, without the surfactant accompaniment, was to blame (Paganelli, 2010). Here, a genetic change was noted.

Sooo, what is this nefarious surfactant?  Its name is polyethyloxylated tallowamine, also known as polyoxyethyleneamine—POEA. The toxicity of the “adjuvant” is greater than the toxicity of glyphosate alone. Not that anybody would drink this stuff, but ingestion will grant you a whale of a stomach ache, corrosion of the GI system, mouth and throat pain, and dysphagia, which you might know better as odynophagia or aglutition—difficulty in swallowing (Bradberry, 2004). Gotcha!  Other responses include kidney and liver impairment, respiratory distress, pulmonary edema and metabolic acidosis, but these usually appear just before death (Stella, 2004). Comforting, eh?

While the study of toxins keeps scientists occupied, the investigation of antidotes does likewise. Using mice, Turkish toxicologists found substantial abnormalities in liver function among subjects exposed to the active ingredient in Roundup®. Markers for oxidative stress were increased, and chromosomal aberrations were profound. Treatment with Ginkgo biloba was discovered to ameliorate the indices of liver and kidney toxicity, and to sequester lipid peroxidation (Cavusoglu, 2011). Of all the alternative treatments out there, what made these people pick ginkgo?  Prior knowledge and attention to the possibilities and realities of complementary medicine make us analytical thinkers. Mitochondrial failure attributed to Roundup® ingredients (but not proven) caused Swiss researchers to sit up and take notice of ginkgo’s unheralded talents, which were able to restore the electron transport system and to rescue defects in energy metabolism (Eckert, 2012). This may provide a happy ending to the story. But it also opens another story about GMO foods, whose corn might just compromise more than a few body parts (de Vendomois, 2009), with or without adjuvants.

References

Abdel-Mallek AY, Abdel-Kader MI, Shonkeir AM
Effect of glyphosate on fungal population, respiration and the decay of some organic matters in Egyptian soil.
Microbiol Res. 1994 Apr;149(1):69-73.
Agrow: World Crop Protection News. Monsanto settles over New York advertising claims:
13 December 1996

Amerio P, Motta A, Toto P, Pour SM, Pajand R, Feliciani C, Tulli A.
Skin toxicity from glyphosate-surfactant formulation.
J Toxicol Clin Toxicol. 2004;42(3):317-9.

Benachour N, Sipahutar H, Moslemi S, Gasnier C, Travert C, Séralini GE.
Time- and dose-dependent effects of roundup on human embryonic and placental cells.
Arch Environ Contam Toxicol. 2007 Jul;53(1):126-33.

Benachour N, Séralini GE.
Glyphosate formulations induce apoptosis and necrosis in human umbilical, embryonic, and placental cells.
Chem Res Toxicol. 2009 Jan;22(1):97-105. doi: 10.1021/tx800218n.

Bradberry SM, Proudfoot AT, Vale JA.
Glyphosate poisoning.
Toxicol Rev. 2004;23(3):159-67.

Brausch JM, Smith PN.
Toxicity of three polyethoxylated tallowamine surfactant formulations to laboratory and field collected fairy shrimp, Thamnocephalus platyurus.
Arch Environ Contam Toxicol. 2007 Feb;52(2):217-21.

Cavuşoğlu K, Yapar K, Oruç E, Yalçın E.
Protective effect of Ginkgo biloba L. leaf extract against glyphosate toxicity in Swiss albino mice.
J Med Food. 2011 Oct;14(10):1263-72.

Clair E, Mesnage R, Travert C, Séralini GÉ.
A glyphosate-based herbicide induces necrosis and apoptosis in mature rat testicular cells in vitro, and testosterone decrease at lower levels.
Toxicol In Vitro. 2012 Mar;26(2):269-79.

de Vendômois JS, Roullier F, Cellier D, Séralini GE.
A comparison of the effects of three GM corn varieties on mammalian health.
Int J Biol Sci. 2009 Dec 10;5(7):706-26.

Eckert A.
Mitochondrial effects of Ginkgo biloba extract
Int Psychogeriatr. 2012 Aug;24 Suppl 1:S18-20.

Eino Hietanen, Kaija Linnainmaa, Harri Vainio
Effects of Phenoxyherbicides and Glyphosate on the Hepatic and Intestinal Biotransformation Activities in the Rat
Acta Pharmacologica et Toxicologica. Volume 53, Issue 2, pages 103–112, August 1983

Larsen K, Najle R, Lifschitz A, Virkel G.
Effects of sub-lethal exposure of rats to the herbicide glyphosate in drinking water: glutathione transferase enzyme activities, levels of reduced glutathione and lipid peroxidation in liver, kidneys and small intestine.
Environ Toxicol Pharmacol. 2012 Nov;34(3):811-8.

Malhotra RC, Ghia DK, Cordato DJ, Beran RG.
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J Clin Neurosci. 2010 Nov;17(11):1472-3.

Mesnage R, Bernay B, Séralini GE.
Ethoxylated adjuvants of glyphosate-based herbicides are active principles of human cell toxicity.
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Francisco Peixoto
Comparative effects of the Roundup and glyphosate on mitochondrial oxidative phosphorylation
Chemosphere. Volume 61, Issue 8, December 2005, Pages 1115–1122

Richard S, Moslemi S, Sipahutar H, Benachour N, Seralini GE.
Differential effects of glyphosate and roundup on human placental cells and aromatase.
Environ Health Perspect. 2005 Jun;113(6):716-20.

Alejandra Paganelli, Victoria Gnazzo, Helena Acosta, Silvia L. López, and Andrés E. Carrasco
Glyphosate-Based Herbicides Produce Teratogenic Effects on Vertebrates by Impairing Retinoic Acid Signaling
Chem. Res. Toxicol., 2010, 23 (10), pp 1586–1595

Sawada Y, Nagai Y, Ueyama M, Yamamoto I.
Probable toxicity of surface-active agent in commercial herbicide containing glyphosate.
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Anthony Samsel  and Stephanie Seneff
Glyphosate’s Suppression of Cytochrome P450 Enzymes and Amino Acid Biosynthesis by the Gut Microbiome: Pathways to Modern Diseases
Entropy 2013, 15, 1416-1463

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

Gut Bacteria And The Brain

brain-gears

They’re called flora. Their name comes from the Roman goddess of plants, flowers and fertility, and refers to the plant life occurring in a particular region. The region in this case is the intestine, and the florae that occupy it are micro-organisms that total almost a hundred trillion, a number considerably larger than the number of cells in the human body. So phenomenal are the metabolic activities of these bacteria that they are considered an organ (O’Hara, 2006). Gut bacteria are so influential that they affect more than just a few bodily functions, from immunity to weight control to behavior and concentration (Bravo, 2011). And without them we couldn’t make biotin, vitamin K, or the short-chain fatty acids that energize intestinal cells. An absence of intestinal bacteria is associated with reduction in mucus cell turnover, muscle wall thickness, cytokine production (regulatory proteins), and of course, digestion. The micro-organism population begins in the mouth, where about two hundred different kinds live. They bypass the almost-sterile stomach and then increase on their way to the colon, where several hundred species thrive (Canny, 2008). For all that we know about the body, this area is not completely understood.

Gut diversity is more pronounced in adults than in children and, once developed, tends to remain stable unless dietary changes are dramatic. Generally, those who consume lots of vegetables and fiber have a different composition from those whose diets typify the Western regimens that are high in unwholesome fats and carbohydrates. Studies have demonstrated that what happens in the gut affects what happens in other areas of the body as well, including those that manage mood, anxiety, and possibly the onset of chronic and degenerative diseases (Tillisch, 2013). Suppose we could manipulate intestinal conditions to address health issues, either one at a time or as a group, by using probiotics.

Lactic acid bacteria and Bifidus bacteria are the most common ones used as probiotics, but others may also be employed. The WHO recognizes probiotics as living micro-organisms that confer a health benefit when taken in adequate amounts. The “health benefit,” however, is undefined. What is defined is that specific strains of a beneficent bacteria offer specific effects that cannot be ascribed to other strains, even in the same variety. Therefore, the probiotic used to treat irritable bowel syndrome will be different from the one used for pediatric diarrhea (Verna, 2010). What’s more, the optimal remedial number of colony forming units (CFU’s) for each bacterial strain is still uncertain; and the doses used in animal studies do not necessarily translate to humans. Then there’s the delivery system. Do we use yogurt, milk or a capsule? The gut environs make a difference, too. If too acidic or alkaline, some bacteria cannot survive.

One micro-organism has shown significant promise as a therapeutic agent in the matter of hypertension. It’s called Lactobacillus helveticus, a bacterium used to add a nutty flavor to American Swiss cheese and to prevent bitterness, although it lends character to other cheeses, including cheddar and various Italian varieties. The name helveticus derives from a Gallic tribe that occupied Switzerland in the first century B.C.

L. helvicus produces a compound called a tripeptide. A peptide consists of two or more amino acids linked end to end, sort of like joining batteries in series (That would be positive to negative in order to increase voltage.)  They always hook up between the oxygen-bearing carbon end of one amino and the nitrogen-bearing end of the other. When you get ten or more amino acids in this parade, it’s called a polypeptide; fifty or more give you a protein. That’s the stuff we’re made from. Some peptides, though, are hormones. The biological synthesis of protein depends on messenger RNA that lives on ribosomes; that of peptides doesn’t. A tripeptide has three amino acids. A familiar one is glutathione, an antioxidant made by the body to shield itself from reactive oxygen species. When L. helveticus is used to make a fermented milk product, it forms a tripeptide called IPP, or isoleucine-proline-proline, which acts like an ACE inhibitor.

Without getting too complicated, an ACE inhibitor deals with angiotensin-converting enzyme, a substance that makes angiotensin, which narrows blood vessels after the lub-dub and consequently raises blood pressure. Most of these drugs end in “-pril,” but have different brand names, such as Univasc, Altace or Vasotec. As with all pharmaceuticals, there are side effects, the most common being a bothersome cough. With L. helveticus there are none.  The Finns realized this after conducting a gold-standard clinical trial—randomized, double-blind, placebo-controlled—in which one hypertensive group received no intervention and the other received 150 milliliters (5 oz.) of L. helveticus fermented milk twice a day for ten weeks. There was a four-point difference in systolic pressure and a two-point difference in diastolic pressure between groups, indicating efficacy of the IPP tripeptide (Jauhiainen, 2005). Though these numbers don’t seem like much, they are, indeed, significant. If you prefer higher numbers, another, earlier, Finnish study reported six point and four point differences (Seppo, 2003). Contributing to this positive outcome is a reduction in the arterial stiffness that contributes to hypertension, particularly as we age. Additional study along these lines found that L. helveticus dairy wrought moderate changes in gene expression in the aorta, which you know to be the main artery leading away from the heart (Ehlers, 2011).

Finland is not the only venue enjoying the anti-hypertensive nature of fermented dairy. The Sant’Orsola-Malpighi University Hospital, in Bologna, Italy, noticed that subjects with high-normal blood pressure experienced a drop in numbers, while those with normal readings were unaffected, which is not a surprise (Cicero, 2010). To make this enterprise even more affable, the Japanese used powdered fermented milk to draw similar results, adding a kind of portability to the protocol (Aihara, 2005).

It’s almost hard to bridle one’s encouragement at the prospect of a hypertension management system based on functional food. A few probiotics already contain the strain: Dr. Stephen Langer’s, Garden of Life, and New Chapter are three. Spectra Probiotic by Integrative Therapeutics is another. Kefir, a probiotic drink available in the supermarket, contains L. helveticus, as well as other beneficent micro-organisms. Be advised not to stop any medications. Just know that any decrease in BP is welcome.

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