Althealth

Antioxidants - General Anti-Oxidant Information

General Anti-Oxidant Information

Looking After Your Body


people in countries where a lot of fruit and vegetables are consumed seem to enjoy a longer and healthier life. Scientists suggest that one of the reasons fruit and vegetables exert a beneficial effect is through the variety of antioxidants they contain - like beta carotene, Vitamin C, and flavonoids.


Antioxidants are believed to be a means of providing protection to the body, as they limit the potentially damaging actions of free radicals.


Free Radicals


Occurring naturally in the body, as by-products of metabolism, some free radicals are essential for the body to function effectively. However certain environmental factors such as sunlight, smoking and pollutants may lead to the increased formation of free radicals in the body. Free radicals are unstable and highly reactive, but their reactivity may be quenched by antioxidants. Scientists now believe that the delicate balance between antioxidants and free radicals within our bodies, may be a fundamental mechanism in the maintenance of our bodies' health.


Dietary Antioxidants


Dietary antioxidants like those found in teamay help to inactivate the highly reactive, unstable free radical by converting it into a stable molecule. Foods contain different mixtures of free radicals in varying amounts. The antioxidants in black and green tea are called flavonoids (also known as tea polyphenols), and are thought to be particularly powerful. About a quarter of the weight of tea leaves used by the consumer is flavonoid. Flavonoids are released as soon as the tea starts to brew.


Author's Note


As my research progresses I find that whatever medications or supplements you may be prescribed or choose to take, the ability of your body to metabolise these medications and supplements is as important as the dose or product taken. It is my belief that this metabolisation process can be improved to some extent by using combinations of supplements rather than mega doses of one or two. The organ most heavily involved in the metabolisation of most medications and supplements, plus the elimination of harmful toxins from the body, is the liver. Liver function can be improved and optimised by following a few simple dietary principles, increasing hydration and (if you choose) taking certain herbal supplementation. please read the Liver Function page on this website for complete details.


Many "supplements" are an extracted "active ingredient" from a food source or herb that, in its natural state, may contain numerous other beneficial elements, enzymes, etc. that may assist in the metabolisation of the supplement(s) being taken. It is a good idea therefore to "assist" supplemental medications - antioxidants for example - by also eating or juicing the fresh fruit and vegetables these are sourced from. An example would be to drink carrot juice as well as taking a beta carotene supplement. please note that excessive beta carotene consumption can be toxic. "More" of a good thing is not always best.


Taking anti oxidants combats excvessive free radical damage. Here is a brief description of how free radicals work:


Free radicals play an important role, in both health and disease and have been implicated in countless human disease processes. Free radicals are vital to human health. These molecules (Reactive Oxidant Species) are extremely important to human metabolic processes.


Any molecule can become a free radical by either losing or gaining an electron and molecules containing these uncoupled electrons are very reactive. Once free radicals are initiated, they can propagate by becoming involved in chain reactions with other less reactive types. The resulting chain reaction compounds generally survive longer in the body and therefore increase the potential for cellular damage.


A free radical has three stages: the initiation stage, propagation and finally, termination. They are terminated or neutralized, by nutrient antioxidants, enzymatic mechanisms, or by recombining with each other. The aim is to attain a delicate balance between free radical activity and optimum antioxidant activity, thereby achieving a state of balance (homeostasis).


Vitamins A, C and E are all anti oxidants and tests imply that 5000mg of vitamin E is an effective daily dose for a person with ALS/MND (see Vitamin E below). An anti gout drug called allopurinol (available from your doctor) may also boost the effect of the vitamin E therapy (see possible ALS/MND Medications). Vitamin C is a more effective anti oxidant than vitamin E but passes through your system quickly and must be taken frequently throughout the day to assist in the treatment of ALS/MND. As it is excreted via the same process that rids the body of excess sugars, vitamin C is best taken at least two hours before or after meals and sugared drinks and/or first thing in the morning and last thing at night. Vitamin A is stored in the liver and an effective therapeutic dose for ALS/MND has yet to be established.


It may be possible that, instead of taking 5000mg of vitamin E daily (ten large 500mg tablets), ALS/MND patients may obtain the same anti oxidant effect by taking just 100mg (two small tasteless tablets or capsules, easily blended with food if necessary) of high quality grape seed extract. This contains an ingredient called OpC and is fifty times more efficient than vitamin E.


OpC has not been widely used, or recommended, to specifically treat ALS/MND but, as virtually all research information I have read refers to motor neurone oxidation, it seems possible that an efficient anti oxidant in combination with other supplements may well slow the progress of motor neurone destruction. The pilot study I am conducted is designed to assess whether this hypothesis is worthy of further, large scale, clinical investigation. I have communicated with many people who have used OpC and have been told it was beneficial or, at worst, caused no negative side effects unless excessive doses were taken. please note that EVERYBODY IS DIFFERENT. What benefits one person may not suit you, that is why I have included information on a variety of anti oxidants. I leave it to your judgement as to which anti oxidant treatment, if any, you feel would be appropriate for you.


The use of OpC/grape seed extract has yet to be "proved" to be of benefit to ALS/MND patients but information I have collected from around the world would tend to indicate that OpC/grape seed extract, in combination with other supplements, may be beneficial. The choice of OpC/grape seed extract was made after considering cost, global availability, anti oxidant efficiency compared to alternatives, availability of product data and apparent lack of unwanted side effects. The choice was prompted more by logistical than clinical factors.


A month's supply of grape seed extract should cost around $20-$30 which should be considerably cheaper than 5000mg of vitamin E complex per day. There are many reputable brands of grape seed extract to choose from but be sure that each tablet or capsule contains at least 50mg of OpC. Many contain varying quantities of "grape seed extract" but this does not necessarily translate into OpC content. Check the product label or with your supplier as to how much actual OpC is contained in each tablet.


I believe the grape seed extract (an Oligameric proanthocyanidin Complex or OpC) to be one of the most effective anti oxidants cheaply, widely and readily available. Extensive clinical trials, and it's application to other disorders and diseases in the last ten years, have shown it to be "completely harmless". I have ALS/MND and have sampled two brands of this grape seed extract in addition to my prescribed medication and have experienced no negative side effects.


The following list of anti oxidants - none of which have been "proven" to be effective in the treatment of ALS/MND - is included for your information. Some are not readily available world wide. Some are relatively expensive, and many are untried in the treatment of ALS/MND. Some have been claimed by people with ALS/MND to be beneficial in slowing the progress of the disease or merely improving general wellbeing (see Feedback & General Topics). At this stage I can not personally recommend any of the following products but include them in this list to enable you to research them further.


Vitamins


Vitamin A


Is a term loosely used to describe members of a family of anti-oxidant substances called carotenoids. These carotenoids have anti oxidant and other qualities and are converted by the body into vitamin A, which is not strictly speaking an anti oxidant. "Vitamin A" supplements are usually sold in the form of Beta Carotene and does not include the other carotenoids. Another carotenoid is called lycopene. A paper by Christen et. al. suggests "a much greater reactivity of the carotenoid lycopene toward peroxynitrite (research suggest that nitric oxide, and especially peroxynitrite, could be involved in oxidation leading to motor neurone death) than beta carotene."


A carotenoid supplement called "CAROTeam" is sold by Vitamin Research products http://www.vrp.com. According to the label it contains alpha, beta and gamma carotenes, xanthophylls and lycopene.


Vitamin C (ascorbic acid)


Must be obtained from food or vitamin supplements. It may be important in the treatment of ALS because ascorbate and glutathione can "spare" one another and ascorbate slows down glutathione loss and vice versa. The reasons for this relationship is unclear. While cellular concentrations of ascorbate react poorly with peroxynitrite molecules, this anti oxidant might slow down loss of glutathione, which can effectively neutralise some destructive cell oxidants.


The superoxide dismutase enzyme can be defective in some cases of ALS/MND and ascorbate may be able to remove superoxide radicals. While neurones (nervous cells) have lots of Cu/Zn-superoxide enzyme, they may be unique among cells (except perhaps white blood and adrenal gland cells) in having extremely high ascorbate levels. Some evidence suggests that ascorbate levels may be close to 10,000 times than for SOD, a level that would allow them to compete with that enzyme for superoxide radical removal in the neuronal cell's cytoplasm (fluid). A Japanese research showed that SOD could only account for a portion of superoxide removal in brain preparations, offering indirect evidence for this relationship.


Body tissue and the brain are both resistant to taking up ascorbate and most of a large vitamin C dose will be quickly eliminated from the body. To keep ascorbate available to the brain (and spinal cord) spread vitamin C supplement intake throughout the day or use a "slow release' form of vitamin C. As vitamin C uses the same transporter that removes glucose (blood sugar) from the blood, take it only between meals (or at night) and especially never in association with sugary foods or drinks.


Vitamin E


Occurs in food in several forms - alpha, beta, delta, and gamma-tocopherols and alpha, beta, delta and gamma tocotrienols. Most E supplements contain only the alpha tocopherol form because it is believed to have the greatest biological activity. Research at the University of California, Berkeley reported in the proceedings of the National Academy of Sciences that gamma-tocopherol is able to quench certain free radicals that alpha-tocopherol does not. Of the E vitamins it has been stated that only gamma-tocopherol gets rid of peroxynitrite, a highly destructive nitric oxide radical. ALS researchers suggest that nitric oxide, and especially peroxynitrite, could be involved in the oxidative-stress chain of events leading to motor neuron death. See the web page http://www.pnas.org for more information about peroxynitrite.


It is not suggested that gamma-tocopherol is a cure for ALS, but ALS patients who want to take vitamin E should take supplements that contain the mixed forms of the vitamin rather than simple alpha-tocopherol. It has been suggested that high levels of alpha-tocopherol in the blood can *reduce* the level of the gamma form. Different tocopherol forms appear to have complementary but not identical functions.


Both alpha and gamma-tocopherol occur in natural vitamin E, but the vitamin supplements generally sold as vitamin E contain only alpha-tocopherol, which may then displace gamma-tocopherol in the body. Gamma-tocopherol may be a more effective anti-oxidant than alpha-tocopherol. (Christen S., et al., Gamma-tocopherol traps mutagenic electrophiles such as NOx and complements alpha-tocopherol: physiological implications. proc. Natl. Acad. Sci. USA, vol 94, pp. 3217-3222, Apr 1997.) An article can be accessed at: http://www.pnas.org.


WASHINGTON, Feb. 23 /pRNewswire/ via Individual Inc. SOURCE Food for the Future (Foods for the Future provides factual information to the media concerning food products, health and nutrition. It is a project of the T. Dean Reed Company and is supported by U.S. agribusiness.)


A major new survey of 47 health studies concludes that vitamin E plays not only an important role in preventing or alleviating neurological disorders, but that natural vitamin E, as opposed to synthetic products, supplies far more concentration to the brain and other body tissues. Natural Vitamin E puts five times the concentration in the brain than does the synthetic version, the survey said. "The importance of Vitamin E in maintaining neurological structure and function has been well documented in clinical research," said the Veris Research and Information Service.Veris, based in LaGrange, Ill., is a not-for-profit group providing information to health professionals, researchers and educators on the role of nutrition in health, emphasizing antioxidants. The company's summary of scientific studies from 1980 to 1997 concluded: "Long-term Vitamin E deficiency is associated with a progressive neurological syndrome that can be alleviated by Vitamin E therapy."


Comparing natural vitamin E to synthetic, the survey said: "It appears that the nervous system has a marked preference for natural-source Vitamin E, which may be significant in treatment of neurological disorders Studies have demonstrated a preference for natural-source Vitamin E by various body tissues, including the brain and spinal cord, compared to synthetic Vitamin E" the survey said. "There was preferential uptake of natural-source Vitamin E by the lung, red blood cells, blood plasma and brain The brain showed the highest discrimination for natural-source vitamin E. The concentration of natural source Vitamin E in the brain increased gradually to a five-fold higher concentration than the synthetic isomer after five months, suggesting that natural-source Vitamin E will be significantly more available to the brain than the equivalent intake of synthetic Vitamin E."


The study continued: "Oxidative damage has been implicated in a number of neurological disorders and diseases, and the majority of available research has demonstrated a protective role for Vitamin E ... Research shows that antioxidant therapy has "significantly beneficial effects in reducing associated disability," the survey said.


It has been suggested that vitamin E is best taken in the morning or during the day (never at night) and that it be taken at a different time to other supplements for best results. Avoid taking it with magnesium supplements.


Some brands of Vitamin E that include alpha, beta, gamma, and delta tocopherols can be obtained via L & H Vitamins (see Links to Useful Sites). (See also Tocotrienols below).


Vitamin D


Is not normally classified as an anti oxidant but as R.Ackley points out "vitamin D is one of the 2 vitamins our body produces under certain conditions (vitamin D is produced when our skin is in the sunlight - approximately 15 minutes exposure of arms to sunlight supplies daily vitamin D requirements).


Drug research to help ALS sufferers is often based on the theory of a toxic buildup of glutamic acid in the brain. Glutamic acid needs vitamin B6 in order for it to be metabolized. B6 needs phosphorus to be absorbed by the body. phosphorus needs vitamin D or it can't be absorbed. All starts with vitamin D."


The suggested daily dose, in the form of emulsified cod-liver oil, is 400iu or more*. Cod-liver oil, as a source of vitamin D, is inexpensive and can be purchased in peppermint and other flavours and also tasteless capsules. (see R. Ackley's e-mail on Feedback & Articles page).


*please note that vitamin D, like Vitamin A can be toxic if taken in excessive doses but this does not mean that these vitamin supplements should be totally avoided. Toxic dose levels are unclear in the case of ALS/MND.


Vitamin B group


Use of B vitamins is a complex issue and not entirely clear at this stage. Frequently pALS are found to be low in B1 and B6 but supplemental B1 and B6 only provide temporary improvement. Good but temporary results were observed using injectable B12 and B6 several decades ago but recent evidence suggests that B3/niacin may play an important role in the treatment of ALS/MND. ("Motor Neurone Disease and the life of Motor Neurones..." Reading C M: Journal of The Australian College of Nutritional and Environmental Medicine: December 1997). Simple supplementation with B3 is ineffective in reestablishing levels of B3 in the body and central nervous system. Zinc, vitamin C, magnesium, maganese, B1, B2 and B6 must exist in adequate quantities for B3 to be metabolised and made bioavailable. This example is true of many supplements. Taking huge doses of any medication/supplement is often pointless or even harmful if the medications/supplements are not supported with the other substances required to metabolise them. I believe that combined supplementation is essential.


More detailed information on the B group vitamins will be include here when I can separate useful data from conjecture.


OpC, proanthocynidin & pycnogenol


I can find no evidence that one brand of OpC, whether extracted from grape seed or pine bark is significantly better than another and can not recommend one brand as being better than another. prices of OpC vary widely depending on the manufacturer/distributor and the ingredients (sometimes unnecessarily) combined with the OpC. An effective dose of OpC in the treatment of ALS/MND would seem to be approximately 100mg daily, especially when combined with other anti oxidant medications. OpC with added compounds may or may not assist in the absorption of the OpC (and frequently cost considerably more than plain OpC). Some examples of available product are given below. My personal inclination would be to "keep it simple" and use a dose rate of approximately 1mg of OpC per 1kg (2.2lb) bodyweight and no more than 100mg in total daily. Claims have been made that higher doses are necessary for optimum efficacy. You must decide on a dose rate to suit you. This will depend on the extent of symptoms and form of your ALS/MND and the other medication you are taking. OpC does not appear to conflict with other medications if excessive doses are avoided.


There are various brands and combinations of anti oxidants based primarily around OpC or proanthocynidins. The first to be granted a US patent was the OpC professor Masquelier called "pycnogenol" protected by U.S. patent 4,698,360. A random sample of just a few of the many compounds based primarily on OpC are listed below this first entry, in alphabetical order. I would suggest doing a word search on the Internet in order to compare products and prices. Search proanthocynidin, OpC, pycnogenol, grape seed extract and, for a general overview, anti oxidants.


It makes sense to add dietary antioxidants such as vitamins C, E, and beta carotene but the "blood-brain barrier" tends to exclude these antioxidants from the central nervous system. The blood-brain barrier is permeable only to a small number of molecules and chemicals allowing them passage to the brain and spinal cord.


Al Kok commented that: "If procyanidine compounds are oily, as suggested by one study, they may show an ability to penetrate the blood brain barrier, which would at least get the drug into the Central Nervous System where you want it to go. However, even in the face of desperate patients, I would expect safety tests in animals will need to be performed first. Blood levels and levels of brain penetration are unclear".


It has been widely claimed that proanthocynidins/pycnogenol/OpC is able to penetrate the blood-brain barrier and may be one of the most powerful naturally occurring antioxidant known. pycnogenol/OpC is widely available in health food stores, from naturopaths/herbalists and by mail order. It does not require a doctor's prescription.



Some Examples of OpC preparationsENZOGENol This appears to be one of the better forms of OpC if only because it is extracted from pine bark (pinus radiata) using de-ionized water. No potentiallly harmful solvents are used to extract and isolate the OpC, flavonoids, etc. The combination of anti oxidants and supplements in this product has been well researched. For more information see http://www.kaireint.com or e-mail cjanssen@kw.igs.net. or Chris.Janssen@wilcris.on.ca Enzogenol is made by Enzo-Nutraceuticals in New Zealand and is marketed by Kaire International. Kaire head office in Australia at 6/7 Salisbury Rd, Castle Hill, NSW, Australia, 2154.


pycnogenol/OpC


Grape seed/pinebark extract provides a weapon against premature aging of living structures. Oxygen free radicals are believed to be responsible for the deterioration of these structures. The lengthening of life expectancy, observed for 50 years in the western world seems to have reached its limits: little by little we have found remedies for the accessible causes of aging. What remains is oxygen, of which nobody had thought 20 years ago and of which we now know constitutes life's principal wear and tear factor. Oxygen free radicals do have a physiological mission to accomplish: the burning of refuse matter, but we should prevent them destroying the sensitive structures of the living cell. OpC offers protection against oxygen free radicals supposes a long term, even permanent use of the scavenging antidote. Used in therapeutics for 40 years, it has never provoked direct or secondary effects of a toxic nature. This is hardly surprising because we find it in the various foods consumed since the beginning of history.


In the USA INC's distributor primary Services International (pSI) is the only supplier of Masquelier's OpC-85 extract from grape seeds that may be sold and used as an anti oxidant.


There is extensive information on the Internet about pycnogenol and professor Masqueler's anti oxidant research.


Muscadine Extract


Muscadines have a unique characteristic- they are naturally resistant to plant diseases due to their extremely high antioxidant content. In 1996 the fruit was dried and put it into capsule form. For more information see http://www.newu.net


Revenol


60 + OpCs claimed to be up to 150 times more powerful than vitamin E and 60 times more powerful than vitamin C. OpCs from pycnogenols had been considered the most powerful anti oxidant sold commercially before Revenol. It combines and uses both the water - soluble maritime pine bark and the oil-soluble grape seed OpC extracts - and results are better than if either were used separately. Revenol is also supported with additional anti oxidants to increase its broad spectrum potentialities and synergy. Curcuminoids - a natural extract - has been added. The makers claim that it is almost three times higher than pycnogenols from maritime bark or grape seed OpC extracts.


Up to 400% more Revenol is absorbed in the digestive system. It bonds to the intestinal wall potentially allowing greater absorption. The product contains Ginkgo biloba to aid absorption. Esterified vitamin C configures vitamin C molecules to increase retention in the body. Normally 80% of vitamin C is eliminated in 24 hours. Only about 5% of esterified vitamin C is eliminated and some is retained for three days. Since OpCs and vitamin C have a synergistic effect, an increase in retention time is important. The vitamin E used is claimed to be more effective than vitamin E used in other products. Over 60 mg per tablet of pine bark (and) grape seed OpC increase bio availability and boost anti oxidant content. Ingredients include esterified vitamin C, natural vitamin E, Ginkgo biloba, alpha and beta carotene and a phytosome digestive absorption system.


Revenol has not been clinically tested as a formula for ALS/MND and no claims are made for its effectiveness. Any claims have not been evaluated by the Food and Drug Administration and the product is not intended to diagnose, treat, cure or prevent any disease. For more information e-mail dbierman@best.com


Other Medications and Anti Oxidants


Allopurinol


Is a prescription drug, primarily used for the treatment of gout. Although it is not, strictly speaking, an anti oxidant it does suppress the body's production of an oxidation catalyst (an enzyme called xanthine oxidase). If an ALS/MND patient wants to try this therapy, a doctor must prescribe allopurinol. It is manufactured by several companies and therefore may have a different name on the packaging when prescribed.


Dr. Stanley Appel of the Baylor ALS/MDA Clinic in Houston has been prescribing allopurinol for his ALS patients for several years. The dosage is 200mg/day to start, working up to 600mg/day. I have included allopurinol in my Self Assessment study.


In the article "Anti oxidant drugs block in vitro the neurotoxicity of CSF from patients with amyotrophic lateral sclerosis" (Terro, F. at al *Neuro Report*, v7, n12, pp1970-72, Aug 12, 1996) the authors measured neuronal death in rat cortical cell cultures exposed to cerebro-spinal fluid (CSF) from ALS patients. CSF was quite neurotoxic, but Vitamin E and allopurinol separately protected cells and in combination "completely prevented the neurotoxicity of ALS CSF." The authors conclude, "A combination of allopurinol and vitamin E may be useful in ALS therapy." Note that Vitamin E has already been shown to delay onset of ALS-like symptoms in ALS mice. It is becoming accepted that a vitamin E complex (including gamma tocopherol) is better than ordinary vitamin E (containing only d-alpha tocopherol) in treating neurodegenerative disorders.


Alpha Lipoic Acid (ALA)


Is both a water and lipid soluble, sulfur containing antioxidant. Alpha lipoic acid plays an important function as an enzyme in the pyruvate dehydrogenase complex. Although it was discovered several decades ago, it wasn't until recently that it's activity as a potent free radical scavenger was demonstrated. As a "chain-breaking" antioxidant, it has been shown to play a pivotal role in the regeneration of the redox reaction between vitamin C, E, and glutathione. Alpha lipoic acid has been receiving generous funding from the NIH for investigations into ameliorating the known degenerative processes of oxidative damage.


ALA has benefits beyond those of other antioxidants. It appears to reduce the risk of conditions aggravated by free radicals. Any one antioxidant is not "ideal" in it's self. "From a therapeutic viewpoint, few natural antioxidants are ideal," says Lester packer, ph.D., a molecular and cellular biologist at the University of Californian. "An Ideal therapeutic antioxidant would fulfil several criteria. These include absorption from the diet, conversion is cells and tissues into unusable forms' a variety of antioxidants actions (including interactions with other antioxidants) in both membrane and aqueous phases,and low toxicity.


passwater says. "Alpha lipoic acid not only protects the nervous system, but also may be involved In regenerating nerves." He adds that lipoic acid's antioxidant function is of major importance and helps protect the body against about 80 diseases.


"Lipoic acid has also been used for decades to protect the liver and to detoxify the body of heavy metal pollutants, such as excessive iron and copper and toxic metals such as cadmium, lead and mercury," passwater continues. Neither animal nor human studies have shown serious side effects with the use of alpha-lipoic acid. However, it is not recommended for pregnant women without proper supervision.


Alpha lipoic acid both interacts with its antioxidant partners vitamin E and vitamin C and also helps to conserve them. When the body is deficient in lipoic acid, the other antioxidants do not network together properly.


Although we make some lipoic acid in our bodies, it is usually not enough, so we rely on potatoes, red meat, etc. to supply what we need for optimal health. ALA supplements are now available in health food stores to insure a sufficient intake of the nutrient. An expert panel has recommended 50 mg/day as a preventive measure against diseases caused by free-radicals.


For more information contact http://www.vitaminconnection.com/framefree/alphalip.html


References


packer, Lester, ph.D., et al. "Alpha-Llpoic Acid As A Biological Antioxidant," Free Radical Boilogy and Medicine 19:227-25O, 1995. Also - passwater Richard A., ph.D. Lipoic Acid: The Metabolic Antioxidant. New Canaan, Conn. Keats publishing, Inc., 1995 pp. 7-8.


Astaxanthin


Is a kind of carotenoid (a preliminary stage of vitamin A). Astaxanthin is made from a microalg called Haematocococcus pluvialis. It is indissoluble (many anti oxidants are fat or water soluble). As Beta carotene is sometimes recommended as an anti oxidant for ALS and Astaxanthin is a kind of carotenoid, it may be safe to take - although a precise dosage has yet to be established.


Astaxanthin has been claimed to be ten times more effective then Q10 and 100 times more effective than vitamin E. However, as vitamin E and Astaxanthin work in different ways it may be necessary to take both as they may complement each other.


Azulenic Retinoid Compounds


Retinoids are compounds related to Vitamin A and retinoic acid. A new type of azulene-containing retinoid has been synthesised and is similar in size and shape to Vitamin A, but its electronic properties are different. This is due to the stabilising effect of azulene on the chemical bonds in the molecule. New azulenic retinoids might also be effective anti-oxidants and free radical scavengers.


E-mail Dave Murai at murai@hawaii.edu University of Hawaii, Office of Technology Transfer and Economic Development, 2800 Woodlawn Drive, Suite 280 Honolulu, HI 96822.


Chocolate


Carries high levels of chemicals known as phenolics according to researchers at the University of California, Davis. The study showed that chocolate can contribute a significant portion of dietary anti oxidants but it remains to be seen whether phenolics consumed in food products actually provide a protective anti oxidant effect in the body. A 1.5 ounce piece of milk chocolate contains nearly the same amount of phenolics as a 5 ounce glass of red wine. The phenolic compounds in chocolate exhibit an anti oxidant effect equal to or greater than that of red wine. It is not known if the different chemical structures of chocolate phenolics versus wine phenolics alter their effects on the body. If dietary phenolics do act as anti oxidants in the body, then chocolate would likely be a good source of those anti oxidants.


Findings are published in the September 21, 1996, issue of The Lancet, UK.


(please note that milk added to tea negates the anti oxidant effect of the tea. It would seem logical to assume that dark - milk free - chocolate would have a greater anti oxidant effect than milk chocolate. Unfortunately, the fats and excessive sugar in chocolate may tend to stress the liver so I would not personally eat chocolate as an anti oxidant source. SS)


Coenzyme Q-10


Because of its strong antioxidant properties, coenzyme Q-10 is being tested in patients with degenerative neurological diseases, parkinsons disease, Huntingtons disease, ALS/MND and multiple sclerosis at major medical centers, including the University of Rochester Medical School and the University of California at San Diego. The hope is that coenzyme Q-10 can slow down progression of the diseases. Andrew Weil, MD personally takes 100 milligrams of coenzyme Q-10 once a day with food as a general health-booster and feels it is harmless. Dr. Weil is a nationally-known physician and director of the program in Integrative Medicine at the University of Arizona and also a graduate of Harvard College and Harvard Medical School. He has published many books on health and healing. Dr. Weil's website is at : http://www.dr.weil.com/


The following information was copied from the Neuropathology Digest -ALS for August 1998 and is provided for information purposes only: (proc Natl Acad Sci U S A 1998 Jul 21;95(15):8892-8897 Coenzyme Q10 administration increases brain mitochondrial concentrations and exerts neuroprotective effects. Matthews RT, Yang L, Browne S, Baik M, Beal MF Neurochemistry Laboratory, Neurology Service, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA).


Coenzyme Q10 (CoQ10) or ubiquinone is an essential cofactor of the electron transport chain as well as a potent free radical scavenger in lipid and mitochondrial membranes. Feeding with coenzyme Q10 increased cerebral cortex concentrations in 12- and 24-month-old rats. In 12-month-old rats administration of coenzyme Q-10 resulted in significant increases in cerebral cortex mitochondrial concentrations of coenzyme Q10. Oral administration of coenzyme Q10 markedly attenuated striatal lesions produced by systemic administration of 3-nitropropionic acid and significantly increased life span in a transgenic mouse model of familial amyotrophic lateral sclerosis. It has been previously demonstrated that administration in these same mice with vitamin E resulted in a delay in disease onset but no increase in survival time. The data suggest that the antioxidant action and preservation of mitochondrial function apparently provided by CoQ10 may contribute to neuron cell protection from free radical effect upon membranes, thus resulting in longer survival seen in these transgenic animals. This suggests that Coenzyme Q10 may be better strategy than vitamin E in treatment of neurodegenerative diseases in increasing survival time. Oral administration of coenzyme Q-10 increases both brain and brain mitochondrial concentrations. The results provide further evidence that coenzyme Q10 can exert neuroprotective effects that might be useful in the treatment of neurodegenerative diseases.


Glutathione


Yeast is a good (and cheap) natural source of Glutathione. (see also pROCYSTEINE & NAC )


Glutathione + (NAC) is designed for double protection by glutathione both inside and outside of body cells. Each capsule supplies both prformed L-Glutathione, for direct antioxidant action, and N-Acetyl-L-Cysteine (NAC see below), a valuable starting material used by the body for glutathione synthesis inside our cells. This valuable glutathione precursor boosts cellular antioxidant protection. This sulfur-containing compound derived from the amino acid cysteine, can serve as a nutritional substrate for synthesis of intracellular glutathione, an important antioxidant. NAC is virtually non-toxic and is the preferred nutrient for enhancing glutathione levels inside cells. NAC also has antioxidant properties of its own, and can donate its sulfur content for other body needs. Glutathione plus provides Glutathione, a biologically active, naturally-occurring tripeptide composed of L-Cysteine, L-Glutamic Acid, Glycine, and N-Acetylcysteine.


L-Cysteine


Is believed by some researchers to achieve essentially the same results as N-Acetylcysteine (NAC) in increasing available glutathione. For full details see NAC below. L-cysteine should be used with caution by diabetics as it may reduce certain disulphide bonds that determin the structure of insulin. Have a blood test to rule out diabetes if you are uncertain.


Maharishi Amrit Kalash (MAK)


Is claimed by some to be the strongest, most widely effective anti oxidant ever researched. This supplement is said to be up to 1000 times more effective than vitamins A, C and E. The cost per month is around $75US. Contact Franklin Healy Milton, FL. e-mail lasingo@pen.net for more details or telephone 1-800-255-8332 in the USA and please mention that he provided the contact number.


Melatonin


Dr Stanley Appel of the Baylor Clinic, Texas has been prescribing 3mg melatonin at bedtime for ALS/MND patients for its anti oxidant effects. The following describes how it works:


"Dopamine (DA) neurons are uniquely vulnerable to damage and disease. Their loss in humans is associated with diseases of the aged, most notably, parkinson's Disease (pD). There is now a great deal of evidence to suggest that the destruction of DA neurons in pD involves the accumulation of harmful oxygen free radicals. Since the antioxidant hormone, melatonin, is one of the most potent endogenous scavengers of these toxic radicals, we tested its ability to rescue DA neurons from damage/death in several laboratory models associated with oxidative stress...(The) results indicate that melatonin possesses the remarkable ability to rescue DA neurons from cell death in several experimental paradigms associated with oxidative stress". (Feb 98, Neuropathy Digest "Melatonin rescues dopamine neurons from cell death in tissue culture models of oxidative stress". Iacovitti L, Stull ND, Johnston K. Department of Neurobiology and Anatomy, Allegheny University of the Health Sciences, philadelphia, pA 19102, USA. IacovittiL@AUHS.edu)


"Studies on rat cortical cultures... (The) data favour the view that the damage caused to the cells by glutamate and hypoxia/reperfusion is mediated via NMDA receptors. The damage to the cells could also be prevented by melatonin (100 microM). The melatonin effect is not mediated by specific receptors because it was not blunted by the melatonin antagonist, luzindole... The combined findings suggest that melatonin counteracts the in vitro destructive effects of NMDA or hypoxia/reperfusion by preventing accumulation of excessive free radicals". (Brain Res 1997 Sep 12;768(1-2):120-124 "Melatonin protects primary cultures of rat cortical neurones from NMDA excitotoxicity and hypoxia/reoxygenation". Cazevieille C, Safa R, Osborne NN Nuffield Laboratory of Ophthalmology, Oxford University, UK.)


(NAC) N-Acetylcysteine


Is the only anti-oxidant that's been in a well-controlled clinical trial specifically for the treatment of ALS/MND. See the following article: TI: "Randomized, double-blind, controlled trial of acetylcysteine in amyotrophic lateral sclerosis" AU: Louwerse, E.S., et al. JO: *Archives of Neurology* v52, p559-564, June 1995.


NAC is produced in living organisms from the amino acid cysteine. Thus, N-Acetyl-L-Cysteine is a natural sulfur-containing amino acid derivative found naturally in foods and is a powerful antioxidant. These dual properties help repair oxidative damage in the body. Both NAC and glutathione are well absorbed. NAC is rapidly metabolized, and only about ten percent of the amount consumed stays in the blood for an appreciable time. Much of the NAC is very rapidly consumed in producing intracellular glutathione. However, even the thiol metabolites of N-Acetyl-L-Cysteine are good antioxidants.


NAC readily crosses cell membranes and does not seem to raise tissue or blood levels of glutathione above the desired ranges. Thus, the nutrient role of NAC is to help maintain healthy levels of intracellular glutathione , especially whenever a condition has limited glutathione production. This nutrient role of maintaining optimal levels of essential body compounds is different from "drug roles" in which body compounds are just elevated without homeostasis or normal body regulation.


NAC, cysteine and glutathione contain sulfur in the form of sulfhydryl groups. Sulfhydryl groups directly react with many poisons, especially heavy metals such as lead, mercury and cadmium. These sulfur-containing nutrients are the body's first line of defense against many poisons as they tie-up the poisons right in the gut. They also offer second-line and third-line defenses in the liver and various individual cells. Sulfhydryl groups also help remove toxins indirectly via an enzyme system called the p-450 System.


N-Acetyl-L-Cysteine also has a secondary role in detoxification since it helps produce optimal amounts of glutathione which also conjugates with most "foreign" compounds and excess oxidizers that enter cells. The harmful compounds that have been conjugated with glutathione then pass harmlessly out of the body through the biliary system.


Although NAC is a food component and a nutrient accessory factor, it is also marketed as a drug with approved medical claims. It has been typically been utilized at dosages from 200 mg to 1200mg per day. Higher doses have been utilized in more severe disease states, but for general use as an antioxidant, most would want to consume from 200 mg to 600 mg daily. people exposed to large sources of oxidants and glutathione depleters, such as smokers or drinkers would probably want to use NAC at the upper level of this range. No NAC-associated toxicity has been reported.


Recent studies indicate that other antioxidants, such as vitamin C, vitamin E, and seleniumin also play a role in the metabolism and regeneration of glutathione and may work synergistically to enhance N-Acetyl-L-Cysteine properties.


Metabolism of NAC


NAC is easily absorbed through oral administration, with blood levels peaking within an hour. N-Acetyl-L-Cysteine is metabolized in the gut wall and liver and is converted to L-cysteine, and ultimately, from cysteine into glutathione. Oral NAC has been shown to increase glutathione levels in numerous different tissues of the body in both animals and humans.


The discovery that NAC (and the glutathione formation it promotes) is an effective antidote for acetaminophen (TylenolTM) poisoning first indicated NAC's importance as an antioxidant. It has the capacity to scavenge hydrogen peroxide hypochlorous acid, and the hydroxyl radical, but most of its antioxidant value is due to its promotion of glutathione formation. This activity of NAC protects membranes from damage by superoxide radical systems. NAC is receiving growing interest from both scientists and physicians, due to the enormous role that oxidation and free-radical mediated damage play in many diseases.


NAC directly detoxifies reactive oxygen mutagens such as superoxide, hydrogen peroxide, and singlet oxygen, and inhibits environmental carcinogens such as cigarette smoke condensate and aflatoxin. Within cells, N-Acetyl-L-Cysteine is rapidly converted to cysteine and then to glutathione which detoxifies carcinogens inside cells and helps decrease carcinogen-induced DNA damage. In its role as an inhibitor of DNA mutations in various organs and tissues, NAC and glutathione may prove potent protectors of a wide variety of diseases.


(NAC should be used with caution by diabetics as it may reduce certain disulphide bonds that determin the structure of insulin. Have a blood test to rule out diabetes if you are uncertain).


Olive Oil


Olive Oil contains several anti oxidants. Cold pressed, extra virgin olive oil is best because no chemicals are used in the extraction process. When added to salads it helps in the digestion of vitamins in the food. For cooking it can be reused, unlike many other oils that produce toxins after being heated and should therefore be discarded. It is high in fat but is classed as a "good" fat. Although slightly more expensive than other cooking oils its benefits repay the extra expense. Cooking oils generally do not improve with age and should be stored in a refigerator after opening.


phenolics


phenolics are naturally occurring anti oxidant substances found in the skins of many fruits, vegetables and herbs. Fruits and vegetables with brightly coloured skins are generally considered to be relatively high in phenolics as are the skins and seeds of the grapes (vitus vinifera) used to make red wine.


pyrimidines


pyrimidines are a novel group of antioxidant compounds, the pyrrolopyrimidines, discovered recently. Many of these possess significantly improved oral bioavailability (56-70% in rats), increased efficacy and potency in protecting cultured neurons against iron-induced lipid peroxidative injury and as much as a 5-fold increase in brain uptake compared with the 21-aminosteroid antioxidant compound, tirilazad mesylate (U-74006F). They appear to quench lipid peroxidation reactions by electron-donating and/or radical-trapping mechanisms. U-101033E has been found to be protective in the context of focal cerebral ischemia, reducing infarct size in the mouse permanent middle cerebral artery occlusion model, in contrast to tirilazad which is minimally effective. These results suggest that antioxidant compounds with improved brain parenchymal penetration are better able to limit certain types of ischemic brain damage than those which are localized in the cerebral microvasculature. However, the activity of U-101033E in improving early post-traumatic recovery in mice subjected to severe concussive head injury is similar to that of tirilazad. The oral bioavailability of many pyrrolopyrimidines suggests that they may be useful for certain chronic neurodegenerative disorders in which lipid peroxidation plays a role.


(Excerpt from AU: Hall ED; Andrus pK; Smith SL; Fleck TJ; Scherch HM; Lutzke BS; Sawada GA; Althaus JS; Vonvoigtlander pF; padbury GE; Larson pG; palmer JR; Bundy GL TI: pyrrolopyrimidines: novel brain-penetrating antioxidants with neuroprotective activity in brain injury and ischemia models. SO: JOURNAL OF pHARMAColOGY AND EXpERIMENTAL THERApEUTICS, 281 (2) 895-904/1997 May)


Red Wine


Red Wine please note that alcohol stresses liver function. As liver function is important in metabolising supplements and medications that may aid in slowing ALS/MND is is advisable to minimise alcohol consumption or discontinue it entirely.


A super anti oxidant has been discovered inside the seeds of the increasingly astounding red grape whose wine, juice, skin, and now seeds may offer significant protection against certain types of cancer, heart disease, rheumatoid arthritis, cataracts and many other chronic and degenerative diseases. In a new study, researchers at Creighton University in Omaha say that a compound extracted from the seeds of red grapes called Activin(TM) is a powerful new super anti oxidant. The research tested the ability of Activin to neutralise and inhibit the damage caused by free radicals in the brains and livers of mice, then compared the effects of the new compound to those of vitamins E, C and beta-carotene. "Our studies show that Activin is a more potent anti oxidant than vitamins C, E and beta-carotene - up to seven times more potent," said Dr. Debasis Bagchi, lead researcher of the Creighton team, who announced the findings at the Experimental Biology conference in New Orleans. "Activin is a powerful inhibitor of free radical-induced lipid peroxidation and DNA fragmentation," stated Bagchi. "This is significant because free radicals can destroy cell membranes and damage DNA, and may be a root cause of certain types of cancer, heart disease and even the aging process itself. "Our findings may also explain why red wine is more beneficial than white in preventing heart disease," Bagchi added, "since red wine is fermented with the seeds while white wine is not."


This most recent discovery of significant anti oxidant benefits of Activin adds to the growing reputation of the red grape as a healthful food. It follows recent findings about the role of red grape juice in reducing blood clots and preventing heart disease and the study of the cancer-fighting properties of Resveratrol, a compound extracted from red grape skins. All these studies, in turn, were inspired by the French paradox the seemingly contradictory finding that the French have a lower rate of heart disease than other Western nations, despite the fact that the French diet is high in fat and cholesterol. Scientists believe that the generous consumption of red wine among the French at least partially accounts for the lower rate of heart disease, since the biologically active flavonoids in the wine reduce blood platelet aggregation. "The beneficial effects of Activin appear to be due to its high flavonoid content," explained Bagchi. "The highest concentration of flavonoids in red grapes is in the seeds." According to InterHealth Nutritionals, a company that produces the grape seed extract, Activin is a nutritional ingredient, not a drug, and is currently available in a variety of dietary supplements at drug and health food stores.


SAM (s-adenosyl methionine)


SAM occurs naturally in all body cells. SAM serves to detoxify cell membranes and synthesize neurotransmitters. Besides clearing toxins from your body, SAM enhances the body's own defense mechanisms by removing 'used up' steroid hormones, thyroid hormones, and stale neurotransmitters. SAM has proven effective in increasing the brain's production of catecholamines, the neurotransmitters we rely on to effectively transmit nerve impulses.


SOD (Superoxide Dimutase)


SOD can now be taken orally in a bioavailable. Defects in the gene influencing SOD have been implicated as a factor provoking the incidence of some cases of familial ALS/MND. A SOD supplement may possibly prove to be extremely useful in the treatment of both familial and sporadic (common) ALS/MND.


Researchers initially reported that even though SOD and other antioxidant enzymes are far more powerful than vitamins and other nutrients at scavenging free radicals, they couldn't be taken orally because they would be destroyed in the digestive tract and thus couldn't be assimilated by the body. Recent studies published in leading medical journals report that the world's first SOD antioxidant enzyme can be assimilated by the human body. It is now available only through a whole food, flower pollen extract product called prozyme. Superoxide dismutase enzymes have been extracted from pollen and pistills of Zea mays (maize) and in two commercial products, Baxtin and polbax, derived from the same material.


per Christer Odn, Department of Forest Genetics and plant physiology, Swedish University of Agricultural Sciences, S-901 83 Ume, Sweden and Roland Einarsson, pharmacia Diagnostics, S-751 82 Uppsala, S

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