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The Biochemistry of Treatment (pg 6)



Cobalamin (B12) is a nitric oxide scavenger19,20 that reduces excess, harmful levels of inducible nitric oxide. B12 (cobalamin) is inadequate in the majority of chemically ill patients.73 The bioactive form is methylcobalamin.  The cyano form (too often sold) is not recommended (patients don’t need cyanide). Cyanocobalamin is not effective in essential enzyme function.95 Methylcobalamin can also help brain and nerve repair.

Since the nitric oxide excess is a major starting step in the vicious cycles, methylcobalamin use is essential.

Sublingual forms of methylcobalamin at 5 mg per tablet are convenient and portable. They can be used 1-2 per dose, repeating until exacerbating symptoms clear. Rapid entry into the blood stream with symptom reduction, using 2 tablets at a time under the tongue until exacerbations clear has been demonstrated in many patients.

Nebulizer use also builds body levels, but is less convenient and less portable. If a patient cannot tolerate sublingual tablets, pure methylcobalamin can be compounded at 1-5 mg/drop and placed on the tongue. This liquid will then absorb through the upper tongue surface into the blood stream. Very inflamed patients may need to dilute it further, e.g. in a 4-5 ml pharmacy bottle to start, moving up the concentration as able. It can be added to 1-2 ml of water in the nebulizer if preferred.

Past research shows effectiveness of cobalamin. For example, nasal cobalamin is rapidly absorbed, well tolerated 96,97 and increases body levels.97 Nasal cobalamin reduces frequency and severity of migraines, by reducing excess nitric oxide.98 Because of lack of a barrier between the nose and brain, nasal use can improve brain levels.99

Bioactive folate (MTHF) can also help reduce abnormal levels of nitric oxide.100



Natural Vitamin E with high gamma tocopherol protects lipid membranes.

Gamma tocopherol reduces peroxynitrite damage on lipid membranes.33,34 It complements alpha tocopherol, which activates glutathione76 and protects cells from injury.101 Roughly equal amounts of each form are needed.102 Thus “mixed tocopherols” with mostly alpha do not function as well for inflammation control because of low gamma levels. Avoid all synthetic tocopherol e.g. dl-tocopherol: it is useless and competes for tocopherol receptors. Beware of being mislead by “vitamin E” studies using synthetic or unspecified tocopherols.

Tocopherols are lipid soluble: Dr. Ziem has not seen much benefit from dry forms, using retesting.

Respiratory lipid membranes directly encounter airborne irritants, so high gamma tocopherol protection is vital. Occasionally, patients may want or need to puncture the capsule immediately before use, emptying contents on food or tongue, or even start with a drop or two and slowly increase concentration.



Glutathione is the most important antioxidant in the body.46,103 Glutathione helps protect brain cells from nitric oxide-peroxynitrite damage.13 It reduces upper and lower respiratory inflammation.35,37 It reduces NMDA activity36 and scavenges peroxynitrite.  Glutathione together with cobalamin can reduce body damage from chemicals.104

Glutathione can now be taken orally as S-acetyl glutathione capsules, (e.g. Xymogen), a fat soluble form not broken down by digestion but able to enter the blood stream through the small intestinal wall. Preliminary research, patient response and testing are very promising. It must be taken with fat for absorption (e.g. a bit of olive oil, fish oil, coconut oil, ghee, etc). Other oral forms are disappointing. Other glutathione routes are discussed below.

Improving glutathione levels in the upper and lower respiratory tract (nose, throat, bronchial tubes, lungs, etc.) can help reduce respiratory responses to irritants35,37 and help to reduce the severity and duration of the patient's reactions. This means less congestion, burning and mucous in the nose, eustachian tubes, throat, sinuses, bronchial tubes, and lungs.

Glutathione can also be absorbed through the lungs by nebulizer,105 as an aerosol and is able to cross the blood-brain barrier.106 This reduces the need of IM/injection use. The nebulizer used should generate particles of 5 microns (the size of the smallest airways) to enter the lungs and blood stream. AeronebGo brand nebulizer makes smaller particles of mist that enter the body easier from the lungs. Use of buffered nebulized glutathione improves symptoms and lung function in people with chronic lung inflammation35 compared to double blind placebo of persons not on the treatment.

Nebulized or injectable glutathione is easily oxidized (damaged) and must be compounded by an experienced pharmacy with expertise in proper glutathione compounding, packaging and shipment. It must be refrigerated and usually oxidizes after 2 months even with proper care.

Patients with more inflammation who have irritation with oral S-acetyl-glutathione or nebulizing initially can begin with injectable, e.g. 200mg/ml, 1 cc 1-2 times a day. If desired or needed, they can later try the oral or nebulized form.

A nasal spray form of compounded glutathione may be used for reactions that would otherwise harm brain function. Glutathione nasal spray also reduces symptoms of chronic rhinitis.37 There is no blood-brain barrier between the nose and the brain.15

Oral S-acetyl-glutathione is easier to use for many patients. All glutathione works best in patients who have adequate selenium for glutathione to function.

Glutathione also reduces excess brain cell “excitotoxicity” (also called neural sensitization), helping prevent impaired function and death of brain and nerve cells.36

If any irritation is experienced with glutathione, the concentration is too high for the level of inflammation at that time (nasal or nebulized). Stop immediately and promptly dilute with safe (clean, nontoxic) water to below irritation level or try injectable. As healing improves, the concentration can gradually be increased. NEVER ignore irritation symptoms: the body will let you know the amount it can handle well. For severe inflammation VERY dilute amounts are needed, or use S-acetyl-glutathione capsules.

N-acetyl cysteine often does not help much and is seldom a “rate limiting step”, based on Dr. Ziem’s review of thousands of SpectraCell tests where glutathione is low and cysteine ample. When cysteine tests low, N-acetyl cysteine in capsule form is often useful. Cysteine needs adequate B6 to not be neuroexcitatory.



Vitamin C (ascorbate) reactivates glutathione in water-based body fluids.14 It also helps protect from effects of chemical injury.75 Vitamin C reduces free radicals in water-based body fluids like the blood stream and inside cells, but not brain, nerve myelin or lipid cell membranes.14

Selenium is essential for function of the enzyme glutathione peroxidase, which reduces tissue damaging “free radicals” 14,107 and helps glutathione to function. 24,41,42

Alpha lipoic acid is a potent and lipophilic antioxidant that keeps glutathione in active form in all body areas.39,40,108 It protects lipid membranes109 of cells and membranes of cell structures (including the energy-generating mitochondria), protein/enzyme-making structures (ribosomes), genetic DNA and all other cell structures.109 It also protects brain/nerve cell myelin.110 It has been used in Germany for decades to treat neuropathy.111 Alpha lipoic acid (the effective form is also called dihydrolipoic acid) keeps many other antioxidants active in all body areas, including glutathione, vitamin C, flavonoids and tocopherols (natural vitamin E).39,112-114

Riboflavin (B2) is essential in reactivating glutathione. It does this by acting (in its bioactive form of FAD) as an essential cofactor of the enzyme, glutathione reductase.24 This enzyme keeps glutathione in its active form. With even minor reduction of riboflavin there is reduced function of this enzyme.43,44 Riboflavin has also been shown to be effective in preventing migraines.115 Migraines are a blood vessel form of neural sensitization. Riboflavin is typically low in people with chemical illness.77 The Ziem neural protocol contains riboflavin in the form the body can promptly use: riboflavin-5-phosphate.

Medical References (footnotes)--Neural Sensitization: The Key to Medical Treatment

Next page: Pg 7 - The Biochemistry of Treatment (continued)

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