Best Research I’ve seen for Glutathione – Parkinson’s connection!

Oxidative stress as a cause of nigral cell death in Parkinson’s disease and incidental lewy body disease.

  1. Dr. P. Jenner DSc1,*,
  2. D. T. Dexter PhD1,
  3. J. Sian BSc1,
  4. A. H. V. Schapira MD2,
  5. C. D. Marsden FRS3

Article first published online: 8 OCT 2004

DOI: 10.1002/ana.410320714


We examine the evidence for free radical involvement and oxidative stress in the pathological process underlying Parkinson’s disease, from postmortem brain tissue. The concept of free radical involvement is supported by enhanced basal lipid peroxidation in substantia nigra in patients with Parkinson’s disease, demonstrated by increased levels of malondialdehyde and lipid hydroperoxides. The activity of many of the protective mechanisms against oxidative stress does not seem to be significantly altered in the nigra in Parkinson’s disease. Thus, activities of catalase and glutathione peroxidase are more or less unchanged, as are concentrations of vitamin C and vitamin E. The activity of mitochondrial superoxide dismutase and the levels of the antioxidant ion zinc are, however, increased, which may reflect oxidative stress in substantia nigra. Levels of reduced glutathione are decreased in nigra in Parkinson’s disease; this decrease does not occur in other brain areas or in other neurodegenerative illnesses affecting this brain region (i.e., multiple system atrophy, progressive supranuclear palsy). Altered glutathione metabolism may prevent inactivation of hydrogen peroxide and enhance formation of toxic hydroxyl radicals. In brain material from patients with incidental Lewy body disease (presymptomatic Parkinson’s disease), there is no evidence for alterations in iron metabolism and no significant change in mitochondrial complex I function. The levels of reduced glutathione in substantia nigra, however, are reduced to the same extent as in advanced Parkinson’s disease. These data suggest that changes in glutathione function are an early component of the pathological process of Parkinson’s disease. The data presented suggest (1) there is oxidative stress in the substantia nigra at the time of death in advanced Parkinson’s disease that manifests in terms of increased lipid peroxidation, superoxide dismutase activity, and zinc levels; (2) there is a major impairment of the glutathione pathway in Parkinson’s disease; and (3) alterations in reduced glutathione levels may occur very early in the illness.


Comment: So what can you do? Well my best advise would be to sign up for the “7 Secrets to Raising Glutathione.” Consider supplementing with Glutathione but be careful as you cannot absorb through the gut or oral means. We carry the highest dose available in suppositories and nebulization.

Glutathione,Hyper-Sympathetic State, The Adrenals & The pH Challenge.

Hyper-Sympathetic State

Your nervous system is divided into the sympathetic and the parasympathetic nervous system. Stess is associated with the sympathetic nervous system which holds your fight or flight response. Your parasympathetic nervous system holds your resting and digesting signals. Many of my patients who are stressed out present to my office with a dominance of the sympathetic nervous system.  Some Common Causes of stress include; emotional, mental, chemical/nutritional, electromagnetic, structural/postural.

The Adrenals

Your pair of adrenals are located just on top of your kidneys and they are responsible for the production of cortisol, adrenaline and other catocholamines responsible for reving and charging you up in a stress response. When this system is chronically put on alert it leads to what is called a hypersypathetic state.

Prolonged Increases of Cortisol & Adrenaline can paralize your immune system by decreasing: interleukin, natural killer cell activity, T-lymphocytes,and  secretory IgA. STudies have also shown chronic stress responses linked to Increases blood sugar with a decreases insulin sensitivity (see hyperinsulinemia in chapter 11), Increases bone loss, Increases blood fats (cholesterol, triglycrides), Increases fat accumulation (especially at waist), Increases fluid retention, Increases protein breakdown (thats loss of muscle).

Symptoms of being in a hypersypathetic state include; increased allergies, osteoporotic tendencies,  loss of lean mass, increased infections, blood sugar swings, high cholesterol, obesity, edema, and poor carbohydrate utilization.

Mental and Emotional stress is very common in our society with busy schedules and deadlines to meet. Most americans are working more hours. An interesting fact is that our productivity is staying about thew same is the last couple of years, however our overall unemployment is unchanged. This says that people are working harder to keep up with production. We are the hard working “Japan” of the 1980′s!

The pH Challenge

I include a saliva pH challenge as a part of my basic lab work up,  what we do is introduce a half cup of lemon into the mouth and the pH of the saliva is checked every minute for 5 minutes. I often see a rapid rise in the saliva pH, this is a comom sign that there is a dominance of the sympathetic nervous system.

When your brain becomes stressed from adrenal stress it leads to inflamed. You have to quench this inflammation! Guess what is the main substance that does this in your brain and even to a large part your entire body?……….. Glutathione! If you’ve never heard of Glutathione then it’s likely you will hear much more about it moving forward as it’s your bodies main antioxidant.  We will look at a few dietary considerations as well as the concept of oxidative stress, the silent killer. 

Yours in Health,





John Lieurance, DC, ND

Secret: Learn how to Avoid Brain Degeneration. Glutathione and brain inflammation.

In order to avoid brain degeneration you must avoid inflammation of the brain. Since the brain doesn’t have pain sensation like other area’s of your body inflammation of the brain shows up as brain fog, balance and coordination problems, and poor memory. Digestion is key to maintaining a healthy immune system for 2 key reasons. One when your digestion is poor then your gut is inflamed and when your gut is inflamed you are likely to have a poor barrier which protects the absorption of foods that are partially broken down and metabolized. These foods are a source of immune reaction and can cause autoimmune , arthritis, hypothyroid, fatigue and generally chronic inflammation in the body and brain. The second reason is the lamina propria sub-layer and the submucosa layer of the small intestine have nodules that are part of the lymphatic system. These nodules contain white blood cells that destroy germs. Another common sense reason that poor digestion will effect your immune system is that many nutrients that are key to a healthy immune system will simply not be absorbed like zinc & B vitamins. When your brain becomes inflamed you have to quench this inflammation! Guess what is the main substance that does this in your brain and even to a large part your entire body?……….. Glutathione! If you’ve never heard of Glutathione then it’s likely you will hear much more about it moving forward as it’s your bodies main antioxidant. In the following paragraphs we will look at a few dietary considerations as well as the concept of oxidative stress, the silent killer. Read carefully to keep your brain healthy!

Neurodegeneration & Oxidata Testing. from Wellington Chen, M.D. on Vimeo.

Soy, Glutamate, and MSG

Well hidden in so many processed foods, glutamate in the form of monosodium glutamate (MSG), soy protein extract, protein isolate, hydrolyzed vegetable proteins, natual flavoring or any of the other disguised names for MSG. Its so difficult to avoid as most fast-food chains and restaurants use at least one of these forms of glutamate to enhance the taste of there food.  These substances are toxic to your brain due to an excitatory and inflammatory action they have on the neuron. They call it an excitotoxin were it literally excites the cell to the point of self destruction.

Effects of MSG on Aging and Brain Inflammation.

In 1969, Dr. Olney noticed brain destruction of test animals in the area of the hypothalamus called the arcuate nucleus. The arcuate nucleous releases a substance that is necessary for the pituitary to release growth hormone. The pituitary gland, under normal conditions, secretes growth hormone in cycles. There is usually release that occurs when we fall asleep or take a nap!  This is an excellent reason for us to take a nap during the day (see restorative pose, Chap. 14), also children are benefited greatly due to the large demand of growth hormone. I have seen recent news stories where schools have stopped providing nap time due to striving to increase education. This is a big mistake, in my opinion. In regards to the above study on MSG and its effect of growth hormone release they found animals fed MSG not only produced less growth hormone, they also lacked the normal release cycles seen in all other mammals, including humans.6

Studies using immature mice have shown decreases in LH, FSH and prolactin  which are sex and reproductive hormones, growth hormone, adrenal regulating hormone, and thyroid regulating hormone following exposure to MSG. Deficiencies  in these hormones showed up in the animals as obesity, smaller growth, inability to reproductive, and slow metabolism. 9-13

Confirmation from more studies demonstrating males with atrophy of the testes and low levels of testosterone. Females where seen with low LH, FSH and estradiol-17beta which is the main form of estrogen hormone. In There was a 68% drop after MSG was given. 10

The young girls who begin developing breasts, and beginning menses, earlier than normal may be due to glutamate consumption. Since soy contains phytoestrogens and high glutamate levels consuming soy can be a leading factor for this anomaly.13

Studies found that infant animals given  MSG have high cortisol levels than normal mice, and after stressful events it would take longer for the high levels to come down to normal levels.14

There is an area in the brain called the hippocampus and it is where your memerory centers are located. Its though that high cortisol can cause damage to these neurons through up regulating oxidation in this area. Damage and degeneration of the hippocampus results in the condition known as Alzheimer’s disease. Its though by some that having cortisol levels elevated chronically  from childhood can be quite impactful in ones ability to enjoy memory. The clearence factor is the ability to unwind and I’ve found that treating the high cortisol levels make a big impact on the ability to relax after a tuff day as well as not get so worked up over small events that would otherwise get them excited, elevating their cortisol. Studies have shown that there is a low glutathione saturation in the hippocampus which leads to this damage and inflammation.

Oxidative Stress, Rust

When metal rusts, it’s a sign of the chemical process known as oxidation. Rusting indicates the damage incurred by exposure to oxygen; we say the metal is becoming oxidized. Its when oxygen steals electron from the metal that it distroys the metal changing the physical and chemical properties. Oxidation also takes place when you bite into an apple if left out it will  turn brown as it’s exposed to oxygen in the atmosphere. The process of oxidation causes molecules with uncoupled electrons. These are called free radicals and they are linked to DNA damage which creates cancer cells, aging of organs and skin, arthritis and too many other degenerative diseases to name.

We all need oxidants in our body. However too much oxidant molecules can cause injury to our body.  Oxidative stress is the technical name for this process. This phenomenon was first noted in 1954 by Dr. Denham Harmon, an organic chemist at the University of California, Berkeley. Dr. Harmon theorized that oxidants were the cause of aging, as well as the major cause of most diseases. His theory has continued to hold up and has received substantial verification over the past half century. 

Most of the conditions that we associate with aging, such as wrinkles, heart disease, and Alzheimer’s, are related to excess oxidative stress in the body. As Dr. Harmon stated, “Very few individuals, if any, reach their potential maximum life span; they die instead prematurely of a wide variety of diseases—the vast majority being ‘free radical’ diseases.” Although Dr. Harmon’s research is a half-century old, in the last five years alone, more than five thousand articles on the subject have appeared in research journals. Until recently, tests to measure levels of oxidative stress were expensive and only available to research centers. Today there is, an extremely acurate, over-the-counter urine test available called an oxidata test. Information is available at


Sources of oxidative stress can be both internal and external. The external ones include exposure to any kind of environmental pollution, petrochemicals, or heavy metals. There are also lifestyle-related causes of oxidative stress, such as smoking, drinking alcohol, caffinated beverages like coffee and tea, excessive exercise, prescription drug-and especially overeating. Trying too hard to get a tan can also hurt too much sun (ultraviolet radiation) contributes to oxidative stress.

Internal sources of oxidative stress include infections  (both  acute and/or chronic), blood sugar imbalance lead to increased free radicals,  high levels of adrenaline and  high levels cortisol.

Reduction / Dampness

When your body is subjected to chronic oxidation over a period of time the body can become saturated with electrons. This congests a part of your cell called the mitochondria, its the part of your cell that generates all your energy. When this saturation occurs it’s called reduction. In Chinese medicine they call this dampness. Classically these people will be fatigued usually with a feeling of heaviness. Often the tongue is swollen, observed with tooth marks on the sides of the tongue.  This would not be a good time to take high amounts of anti-oxidants. This represents a good example of why nutrition programs should be closely monitored by a competent clinician with the ability to check these levels for you. Many times this shows up with a low oxidata score with abnormal adrenal states.

Vitamine C with very high bioflavinoids

Recent studies have demonstrated that flavinoids are powerful antioxidants, acting against a whole host of dangerous free radicals. In fact, some of the flavonoids can neutralize special free radicals that cannot be neutralized by antioxidant vitamins. It should be noted that there are other dangerous radicals besides oxygen radicals. Many people are unaware of  a reactive nitrogen species that can be equally, if not more, destructive than oxygen radicals (free radicals). Vitamins are poor at neutralizing these special types of radicals, while flavonoids are very efficient. I regularly test for nitate levels inpateints and bioflavinoids will greatly help normalize these levels. Many times the liver is doing a poor job and neutralizing these compounds usually due to being overburdened with toxicity Its common for these high nitrate levels to cause swelling and congestion of the sinuses. Many of the chronic sniffls, runny noses and post nasal drips are a result of excessive nitrat levels.

Flavonoids can remove (chelate) dangerous metals, such as, copper, aluminum, mercury, arsenic and lead.   Iron and aluminum accumulation is commonly associated with degenerative disorders of the nervous system such as Alzheimer’s and Parkinson’s disease.

Its the flavonoids and carotenoids that allow plants to survive in the glaring sun all day long. Without flavinoids the sun’s harsh rays would quickly destroy the leaves. Flavonoids absorb the harmful radiation from the sun by neutralizing the free radicals they generate. This is similar to how flavinoids work for us!

Recent years has yelded massive research into the medicinal properties of flavonoids. They seem to be finding they not only protect us from antioxidants, they also help in the treatment and prevention of many cancers.

Oxidata Urine testing

This tests for an end product of polyunsaturated fat chain where malondialdehydes form as a result of free radical attack. I include an oxidata urine test with my stadard lab work up on each of my pateints.3-10

Yours In Healhty,


John Lieurance, DC, ND 




1. Dhanakoti S.N., “Response of Urinary Malondialdehyde to Factors that Stimulate Lipid Peroxidation in

Vivo.” Lipids 22(9):643-6, Sept 1987.

2. Draper H.H., “Malondialdehyde Derivatives in Urine.” Basic Life Sci. 49:199-202, 1988.

3. Draper H.H., “Urinary Malondialdehyde as an Indicator of Lipid Peroxidation in the Diet and in the Tis
sues.” Lipids 19(11):836-43, Nov 1984.

4. Hubbard R., lacono R., Westengard J., and Schoonberg T., “Malondialdehyde (MDA) Studies in Palli-
dotomy Treated Parkinson Patients.” To be presented at the Experimental Biology and Medicine Meet
to be held on April 15-18, 2000 at San Diego, CA.

5. Hubbard R., lacono R., Westengard J., and Schoonberg T., “Urine Malondialdehyd (MDA) Measured in
Parkinson Disease, by a Fluorometric and a Visually Read Colormetric Assay.” To be presented at the
Experimental Biology and Medicine Meetings to be held on April 15-18 at San Diego, CA.


6. Lin JY, Pan JT. Single-unit activity of dorsomedial arcuate neurons and diurnal changes of tuberoinfundibular dopaminergic neuron activity in female rats with neonatal monosodium glutamate treatment. Brain Research Bulletin 48(1999): 103-108. Mailer D, Underwood LE, et al. Neonatal treatment with monosodium glutamate:effects of prolonged growth hormone (GH)- releasing hormone deficiency on pulsatile GH secretion and growth in female rats. Endocrinology 128(1991): 1100-1106.

7. / urinary oxidative stress test.

8.  / Nap machine.

9. Nemeroff CB, Lamartiniere CA, Mason GA, et al. Marked reduction in gonadal steroid hormone levels in rats treated neonatally with monosodium L-glutamate: further evidence for disruption of hypothalamic-pituitary-gonadal axis regulation. Neuroendocrinology 33(1981): 265-267. Miskowlak B, Limanowski A, Partyka M. Effect of perinatal administration of monosodium glutamate (MSG) on the reproductive system of the male rat. Endokrynol Pol 44(1993): 497-505.


10. Nemeroff CB, Lamartiniere CA, Mason GA, et al. Marked reduction in gonadal steroid hormone levels in rats treated neonatally with monosodium L-glutamate: further evidence for disruption of hypothalamic-pituitary-gonadal axis regulation. Neuroendocrinology 33(1981): 265-267. Miskowlak B, Limanowski A, Partyka M. Effect of perinatal administration of monosodium glutamate (MSG) on the reproductive system of the male rat.
Endokrynol Pol 44(1993): 497-505.


11. Miskowiak B, Kesa B, Limanowski A, et al. Long-term effect of neonatal monosodium glutamate (MSG) treat
ment on reproductive system of the female rat. Folia Morphol (Wan.) 58(1999): 105-113.


12. Macho L, Jezova D, et al. Postnatal monosodium glutamate treatment results in attenuation of corticosterone metabolic rate in adults rats. Endocrine Regulation 33(1999): 61-67. Miskowiak B, Partyka M. Effect of neonatal treatment with MSG (monosodium glutamate) on thyroid of the adult male rats. Histology and Histopathology 14(1999): 63-67.


13. Hsieh Y-L, Hsu C, Lue S-I, et al. The neonatal neurotoxicity of monosodium L-glutamate on the sexually dimor
phic nucleus of the preoptic area of rats. Neuroscience 19(1997): 342-347.


14. Skuletyova I, Kiss A, Jezova D. Neurotoxic lesions induced by monosodium glutamate result in increased adrenopituitary proopiomelanocortin gene expression and decreased corticosterone clearance in rats. Neuroendocrinology 67(1998): 412-420.


Kato K, Hamada N, et al. Depression of delayed-type hypersensitivity in mice with hypothalamic lesion induced
by monosodium glutamate: involvement of neuroendocrine system in immunomodulation. Immunology 58(1986):

260Vowerk CK, Gorla MS, Dreyer EB. An experimental basis for implicating excitotoxicity in glaucomatous optic
neuropathy. Survey Ophthalmology 43(1999): S142-S150.

261Kowluru RA, Engerman RL, Case GL, Kem TS. Retinal glutamate in diabetes and effect of antioxidants.
Neurochemistry International 38(2001): 385-390.

242 Olney JW. The toxic effects of glutamate and related compounds in the retina and the brain. Retina 2(1982): 341-359.

263 Blaylock RL. Food additive excitotoxins and degenerative brain disorders. Medical Sentinel 4 6(1999): 212-215.

-” Blaylock RL. Phytonutrients and metabolic stimulants as protection against neurodegeneration and excitotoxicity. Journal of the American Nutraceutical Association 2(2000): 30-39.

265Saito K, Markey SP, Heyes MP. Effects of immune activation on quinolinic acid and neuroactive kynurenines in
the mouse. Neuroscience 51(1992): 25-39.

266Beal MF, Bradley T, Koroschetz HW. Do defects in mitochondrial energy metabolism underlie the pathology of
neurodegenerative disease? Trends in Neurosciences 16(1993): 125-131.




Glutathione quenches oxidation and improves RNA metabolism. This improves Telomerase and protects Telomeres.

Below is a clip of an article that describes the enzyme telomerase. It is RNA dependent! In addition the telomeres are sensitive to oxidation. With this said Glutathione quenches oxidation and improves RNA metabolism. Both of these facts makes Glutathione an important nutrient to have in high amounts for anyone interested in anti aging or health in general.

Telomerase synthesizes chromosome ends de novo

At this point Carol Greider had started as a graduate student in Blackburn’s laboratory at Berkeley and together they embarked on an exploration of how telomere ends were synthesized, employing a biochemical approach. She developed an assay using Tetrahymena cell extracts taking advantage of the fact that on Tetrahymena rDNA molecules the required free 3’OH group is present on the G‐rich DNA strand complementary to the strand containing the CCCCAA repeats. A synthetic DNA oligonucleotide, (TTGGGG)4 , was thus used as a primer to initiate synthesis. Using this assay she could show addition of TTGGGG repeats in vitro, thus indicating the presence of enzymatic activity in her cell extracts, Fig 3. The terminal transferase‐like enzymatic activity that added single nucleotides in a stepwise fashion was proteinaceous and unique in that it added only the specific telomere sequence in an apparently untemplated manner. Functional conservation of the enzymatic process was demonstrated in a critical experiment where Tetrahymena type TTGGGG hexanucleotide repeats were added to a primer corresponding to the distinct yeast telomeric DNA ending with GTGGG. It was also observed that an extra G was first added to the yeast primer containing three G residues at the end in order to allow the subsequent correct addition of Tetrahymena TTGGGG repeats with four G residues. Greider and Blackburn published the results in Cell in 1985 20

In a following study Greider and Blackburn showed the enzyme to be a ribonucleoprotein complex critically dependent on both the protein and RNA component 21. In this second paper the name telomerase was adopted to denote the enzyme. With respect to a potential role of the RNA component Greider and Blackburn wrote; “ It is tempting to speculate that the RNA component might be involved in determining the sequence of the telomeric repeats that are synthesized and/or the specific primer recognition. If the RNA of telomerase contains the sequence CCCCAA, this sequence could act as an internal guide sequence”.

As an independent scientist at Cold Spring Harbor Laboratory Carol Greider continued to work on telomerase in collaboration with Blackburn in an effort to clone and characterize the small RNA that co‐purified with the telomerase. As reported by Greider and Blackburn in an article in Nature in 1989 the RNA component was indeed found to contain the sequence CAACCCCAA, suggested to be the template for the synthesis of TTGGGG repeats 22. Blocking availability of this sequence motif compromised telomerase enzymatic activity. Final proof of the role of the CAACCCCAA RNA sequence as a template for telomere synthesis was provided when Blackburn’s group showed that mutations in the RNA sequence resulted in corresponding alterations in the DNA sequence being synthesized 23.
At this point the salient key features of the telomerase enzyme as a unique type of reverse transcriptase with a catalytic protein component and an intrinsic RNA template had been elucidated. The basic mechanism of telomere synthesis and maintenance was thus established. (Fig 4.) It is worth noting that the discoveries of general principles of chromosomal maintenance ineukaryotes, including mammals and primates, were all made by studying relatively simple model organisms.