220 replies to this topic

[Lufega]

I've been using Source natural's pancreatin 8x for a few months now to aid in digestion. In the last month or so, I began to use it on an empty stomach along with other nattokinase, serrapeptase and bromelain to act as systemic enzymes. Could this be the cause of my sudden and acute alpha-1-antitrypsin (AAT) deficiency which I suspect is causing respiratory problems?

Pancreatin contains the pancreatic enzymes trypsin, amylase, and lipase...

Parenteral administration of trypsin triggers lung emphysema.
Eight weeks after a single intravenous injection of trypsin, more than half of 26 treated rats showed pulmonary emphysema, as demonstrated by a significant increase of the mean linear intercept (MLI = 107 microns) in comparison with 11 controls (69 +/- 15 microns) (mean +/- SD). As observed 56 days after the injection, the intraperitoneal administration of trypsin (24 rats) also leads to lung emphysema (MLI = 101-106 microns), as does endotracheal instillation of elastase (13 rats), (MLI = 108 microns). The intraperitoneal administration of trypsin in animals constitutes a model close to human pathology with which lung alterations in acute pancreatitis may be studied. Having no elastolytic properties, trypsin cannot directly induce emphysema. The observation of a pulmonary leucostasis in eight rats sacrificed early after the trypsin injection suggested that leucocyte trapping and activation are important for the genesis of this trypsin-triggered emphysema.

I don't have emphysema perse, just difficulty breathing. It feels like my lungs can' explain, probably due to a decreased elasticity as a result of the deficient AAT. This doesn't directly explain the AAT deficiency or what exactly the mechanism is, but it's a clue.

Or...

http://www.ncbi.nlm....8?dopt=Abstract

Mechanisms of lung injury in the copper-deficient hamster model of emphysema.

The full article is free to read.

[nameless]

I don't have emphysema perse, just difficulty breathing. It feels like my lungs can' explain, probably due to a decreased elasticity as a result of the deficient AAT. This doesn't directly explain the AAT deficiency or what exactly the mechanism is, but it's a clue.

What were the results of your heart tests? You mentioned heart failure + heart enlargement in a different post. Did the MRI or other tests back this up?

If your ejection fraction is low, or you have other heart issues, it can cause difficulty with breathing. How was your pulmonary pressure?

[Lufega]

I don't have emphysema perse, just difficulty breathing. It feels like my lungs can' explain, probably due to a decreased elasticity as a result of the deficient AAT. This doesn't directly explain the AAT deficiency or what exactly the mechanism is, but it's a clue.

What were the results of your heart tests? You mentioned heart failure + heart enlargement in a different post. Did the MRI or other tests back this up?

If your ejection fraction is low, or you have other heart issues, it can cause difficulty with breathing. How was your pulmonary pressure?

I receive the results of the CT scan tomorrow so I'll know if the heart is really enlarged or what. The ejection fraction was 65% per the Eco which is great but there is tricuspid and mitral regurgitation....which is very bad. I also do have pulmonary hypertension but I don't know the measurement.

A Hypothesis: The Role of Magnesium and Possibly Copper Deficiency in the Pathogenesis of the Adult or Acute Respiratory Distress Syndrome (ARDS) as it Occurs in Infants, Children, and Adults

JOAN L. CADDELL, M.D. ABSTRACT

This is a hypothesis that magnesium (Mg) deficiency, often with associated copper (Cu) deficiency, contributes to the pathogenesis of the adult or acute respiratory distress syndrome (ARDS). ARDS occurs at all ages and is particularly lethal to infants and children. ARDS is an acute, life-threatening respiratory failure after widely diverse insults in patients with no prior history of cardiopulmonary dysfunction. The multiple predisposing factors include shock, sepsis, alcoholism, burns, gastroenteritis, and trauma. These are often treated with Mg-poor sodium-rich infusions, which increase renal excretion of Mg, or with multiple emergency transfusions of citrated blood, which temporarily binds Mg. Glucose or amino acid-rich infusates may result in translocation of Mg into intracellular space. Gastrointestinal loss of both Mg and Cu may be high. Unless specifically repleted, there may be major Mg and Cu losses. Within four d, about 1% of such patients in intensive care units, or 200,000 Americans a year, develop acute respiratory distress, with a survival rate of only 35%. The common denominator of injury is damage to the alveolar endothelium and epithelium, leading to increased permeability to protein, protein-rich alveolar edema, microatelectasis, and hyaline membranes. The pathogenesis is unknown. This hypothesis focuses on one aspect of this complex syndrome: The possible role of Mg deficiency and possibly Cu deficiency in the pathogenesis of ARDS. Deficiency of Mg leads to increased intracellular calcium (Ca), enhanced platelet aggregation, and increased secretion of thromboxane A₂ (TXA₂) from aggregated platelets. TXA₂ is pro-aggregratory, and is a potent vasoconstrictor and bronchoconstrictor. As more platelets aggregate and are activated, there may be waves of exaggerated release of major vasoconstrictors that include TXA₂, serotonin, and epinephrine, leading to pulmonary hypertension. Platelets release histamine which contributes to increased vascular permeability. Microvascular thrombosis of platelets, leukocytes, and thrombin lead to microatelectasis. Intrapulmonary shunting causes hypoxemia that is refractive to oxygen therapy. Cu is required for enzymes such as CuZn-superoxide dismutase (CuZnSOD) that provide major defense against damaging oxygen radicals. Mg and Cu are each required for normal immune response against infection and for oxidative phosphorylation (energy metabolism). Mg is required for protein synthesis, Cu for collagen and elastin synthesis. It appears to be of critical importance to investigate the roles of Mg and Cu in ARDS.

[Lufega]

I am copper deficient, yes. However I think my last hernia was brought upon by copper supplementation. What I think I have is a copper storage problem.

Alpha-I-antitrypsin and copper in the liver.

The incidental finding of orcein positive granules, indicating copper associated protein, in alpha-1-antitrypsin (AAT) positive liver biopsies stimulated a histochemical search for evidence of copper and copper-binding protein in a series of 46 liver biopsies with histological evidence of AAT accumulation. Hepatic accumulation copper and copper-binding protein occurred in all 19 cirrhotics (100%) and in 14 out of 27 non-cirrhotic livers (51.85%). The overall percentage was 71.73%. AAT and copper deposits coexisted in the same periportal hepatocytes. AAT globules showed positive reactivity both to rhodanine and orcein stains. The severity of chronic liver damage correlated with increasing amounts of copper deposition. It is suggested that in AAT storage, not only is the metabolism of this substance disturbed, but also that of proteins involved in copper metabolism and excretion, resulting in copper accumulation within hepatocytes.

[nameless]

I receive the results of the CT scan tomorrow so I'll know if the heart is really enlarged or what. The ejection fraction was 65% per the Eco which is great but there is tricuspid and mitral regurgitation....which is very bad. I also do have pulmonary hypertension but I don't know the measurement.

That's actually good news. No heart failure & heart is pumping properly. The regurgitation may not be ideal, but what matters is to what extent it's occurring. Minor or trace regurgitation isn't a biggie really.

As for heart size, they can determine that by the echo. And I believe pulmonary pressure can be determined by the echo too. You should ask for the report, if it's available.

And what type of CT scan did you get there? I think the only reason for a CT scan on the heart is for checking the arteries and look for blockages. But that's a pretty big radiation dose as a preventative test.

Or did you mean an MRI? An MRI of the heart could make some sense and is more accurate than an echo is. It's a very noisy test though...

[Lufega]

http://www.ncbi.nlm....8?dopt=Abstract

Mechanisms of lung injury in the copper-deficient hamster model of emphysema.

The full article is free to read.

Lysyl oxidase activity was found to be no different in control and experimental animals on either a per lung or per unit protein basis....
Total SOD activitywas diminished to 14.5% and 41% of control values in erythrocytes and liver homogenates, respectively, from copper-deficient animals compared to controls...

DISCUSSION
Elastin and collagen contents are not altered in adult human lungs with emphysema’s nor in the latter phases of elastase-induced emphysema, although collagen content may be somewhat increased in the latter.4 Therefore, similar findings were not surprising in the copper-deficient model. The mechanism involved in maintaining collagen, elastin, and cross-link contents at control values in the copper deficient model may result from collagen and elastin being laid down in an architectually deranged fashion and producing the structural and functional impairments that we call emphysema. However, since cross-link formation and lysyl oxidase activity were not significantly inhibited in this system, the possibility exists that other mechanisms (most likely copper-dependent) are operative in the development of this dramatic lesion. Diminished Cu-Zn SOD activity in copper-deficient hamster tissues, especially lung, supports an alternate hypothesis for the mechanisms involved in producing the emphysematous form of lung injury in this model. One possibility is that excess free radicals may cleave peptide bonds in elastin directly. Fragments of elastin may in turn attract inflammatory cells to the lung which, in addition to their proteolytic enzymes, may, in their activated state, produce more free radicals and create a positive feedback loop. Secondly, the oxygen species produced may oxidize the methionines near the active site of a,-protease inhibitor, rendering the molecule inactive and allowing endogenous elastase-induced injury to occur. (this is what causes the alpha-1-antitrypsin deficiency directly) Thirdly, lowered ceruloplasmin production or activity may contribute to the lack of oxidant protection in addition to lowered SOD activity. These hypotheses are currently being tested in our model. With respect to the latter mechanisms, extremely preliminary data indicate that plasma ceruloplasmin oxidase activity (normalized to protein) is diminished in copper-deficient hamsters compared to controls. The reproducibility and significance of this reduction is currently being tested.

To think, this study dates back to 1984. This is the kind of forward thinking I like.... Now, how do I convince my Doc. that my problems are due to decreased SOD acvitivity? lol

SUMMARY
1) Dietary copper-deficiency induces emphysema in hamsters.
2) Copper-deficiency-induced emphysema develops chronically and, therefore, the time course of its development mimics that of the human disease.
3) Mechanisms other than inhibition of lysyl oxidasemediated cross-link formation may be involved in the pathogenesis of emphysema that develops in copperdeficient hamsters. These mechanisms may be similar
to those involved in the pathogenesis of human emphysema.

In this article, researchers induced copper deficiency in mice and found and both control group and test subjects had equal amounts of collagen, elastin and desmosine but did develop copper-def. induced emphysema. So the damage caused by copper-D was not caused by decreased cross-linking activity, perse rather it's postulated that it was caused by a decrease in copper dependent superoxide dismutase activity, a very important anti-oxidant, and this lead to some form of oxidative damage which caused the structural problems in the body.. It's a new direction but it does make perfect sense. I do show signs of being a slow oxidizer with low levels of ceruloplasmin. I am also deficient in zinc, copper and manganese, all minerals used as cofactors for SOD molecules. So, the current manifestation of alpha-1-antytrypsin and the emphysema like symptoms I'm manifesting COULD be due to low SOD levels. This,

from wiki-
"In humans (as in all other mammals and most chordates), three forms of superoxide dismutase are present. SOD1 is located in the cytoplasm, SOD2 in the mitochondria and SOD3 is extracellular. The first is a dimer (consists of two units), while the others are tetramers (four subunits). SOD1 and SOD3 contain copper and zinc, while SOD2 has manganese in its reactive centre. "

"Superoxide is one of the main reactive oxygen species in the cell and as such, SOD serves a key antioxidant role. The physiological importance of SODs is illustrated by the severe pathologies evident in mice genetically engineered to lack these enzymes. Mice lacking SOD2 die several days after birth, amidst massive oxidative stress"

I did mention in another post that I have aged significantly in the last year, probably due to increased oxidative stress and this coincided with my use of copper supplements. Whether or not I have a copper storage problem, which lead to toxic levels, is still to be determined. To combat this, I started using ala, egcg, berry extract, blueberry pills, etc. But what if all I need is SOD/glisodin? A few years ago, the only supplements I used were curcumin (LEF), drank lots of green tea and ate lots of fruits everyday. During this period, I was looking my best, young, thin, fit. This is even though i've been carrying magnesium, copper, manganese deficiencies all along but I was unknowinly combatin excess oxidative stress due to lack of SOD but using good anti-oxidants. I think this is the direction my regime should take.

This should be easy to test. If my theory is correct, using Glisodin should halt the attack on alpha-1-antitrypsin and these should increase again overtime. Lucky for me, LEF is having an overstock sale and their glisodin is marked down 60%.

I decided to take a break from using MOST of my supplements and I'm going to adopt a chelation therapy I've been putting off until those supplements run out. I'll repeat the hair mineral test and we'll see where this goes....

Note: This is not addressing the general cause of my maladies. I still have to investigate why I'm mineral deficient, rule out storage disease problems, etc. I'm simply doing this to help me manage.

[Lufega]

Low copper as a cause of low dopamine and norepinephrine:

I have hypotension. This seems to be caused by low NE. I also have social anxiety, low motivation, apathy, anhedonia, basically, the negative symptoms of schizophrenia. These all seem to be caused by low dopamine.

Now I can tie this all to low copper levels.

Copper and neurological function.

Hunt DM.
The role of copper in maintaining normal neurological function has been examined in animals copper-deficient by dietary means, and in the genetic disorders of copper homeostasis -- Menkes' kinky-hair disease in humans and the mottled (Mo) mutants in the mouse. With the exception of the disorder in Mo mice, reduced myelination is a constant feature of these copper diseases but there is otherwise a lack of conformity in the structural defects produced in different species. Dietary copper-deficient animals show a reduction in noradrenaline and dopamine concentrations, together with a depressed tyrosine 3-monooxygenase activity (EC 1.14.16.2). Noradrenaline concentrations are also reduced in brain tissue of Mo mice and this reduction is associated with a decrease in the vivo activity of the copper metalloenzyme, dopamine beta-monooxygenase (EC 1.14.17.1). Many tissues contain potent inhibitors of dopamine beta-monooxygenase activity, and assays of this enzyme have utilized cupric ions to inactivate these inhibitors. The elevated in vitro activities of dopamine beta-monooxygenase obtained for both Mo brain and adrenal tissue may therefore reflect either a reduced inactivation of these endogenous inhibitors in the intact animal or the activation in vitro of apoenzyme. Concentrations of dopamine and tyrosine 3-monooxygenase are unchanged in Mo mice. The reduction in dopamine and tyrosine 3-monooxygenase activity in dietary copper-deficient animals may therefore reflect neuronal loss rather than reduced catalytic activity of the catecholamine biosynthetic pathway. The possible effects of depressed activities of cytochrome c oxidase (EC 1.9.3.1) and superoxide dismutase (EC 1.15.1.1) in the development of neurological dysfunction are also discussed, and attention is drawn to the possible significance of the elevated uptake of neutral amino acids, especially tyrosine and tryptophan, by Mo brain tissue.

Effect of dietary or genetic copper deficiency on brain catecholamines, trace metals and enzymes in mice and rats.

Prohaska JR, Smith TL.
Previous studies by others indicated that alterations in brain catecholamines were different for perinatal copper deficiency produced by diet in rats and that resulting from a genetic mutation of the X-chromosome, Menkes' syndrome in humans and brindled mice. Thus, copper deficiency was studied in a model in which dietary and genetic deficiency (brindled mice) were compared in two strains of the same species. C57BL and C3H/HeJ mice. Dietary copper deficiency was also produced in rats for comparison. In brain, both dietary and genetic copper deficiency resulted in impaired growth, low brain copper levels, greatly decreased norepinephrine concentrations but normal dopamine levels. The activity of brain cytochrome oxidase was greatly depressed following both dietary and genetic copper deficiency, suggesting a functional deficit of copper. However, the activity of another cuproenzyme, dopamine-beta-hydroxylase, was significantly elevated in deficient animals. The elevation was observed when either copper or N-ethylmaleimide was added to inactivate an endogenous inhibitor. The cause of low brain norepinephrine remains unknown; however, depressed brain norepinephrine may be partly responsible for functional changes in the deficient animals, such as hypomyelination, since the activity of the myelin protein, 2',3'-cyclic nucleotide 3'-phosphodiesterase, was lower in the most deficient animals.

Cardiac and splenic levels of norepinephrine and dopamine in copper deficient pigs and rats.

Vitamin and Mineral Nutrition Laboratory, Beltsville Human Nutrition Research Center, U.S. Department of Agriculture, Agricultural Research Service, MD 20705.
1. Copper deficiency decreased the concentration and content of norepinephrine in the hearts of pigs and rats. 2. Concentration, but not content, of norepinephrine was decreased in spleen of copper-deficient pigs, while splenic norepinephrine levels in rats were not altered by copper deficiency. 3. Cardiac and splenic concentrations and contents of dopamine were elevated in copper-deficient pigs and rats. 4. Tissue concentrations of catecholamines and the magnitude of change due to copper deficiency were greater in pigs than rats.

Cardiac catecholamine metabolism in copper-deficient rats.


Vitamin and Mineral Nutrition Laboratory, Beltsville Human Nutrition Research Center, MD 20705.
After parturition, Sprague-Dawley dams were fed diets containing either 0.6 (-Cu) or 6 (+Cu) mg of copper/kg of diet. Pups were weaned either to the diet of their dam or to the diet fed to dams in the other treatment group in a crossover design. At 7 wk of age, Cu-deficient rats were characterized by low tissue Cu and an enlarged heart with increased levels of dopamine (DA) and decreased levels of norepinephrine (NE). These changes resulting from Cu deficiency were independent of gender. In vivo synthesis of cardiac NE from DA in Cu-adequate rats was significantly greater than in Cu-deficient rats. Turnover of cardiac NE was estimated from the temporal change in the specific activity of [3H]NE. Fractional turnover rates (percentage per hour) of cardiac NE were similar in both dietary groups, although the cardiac turnover of NE (nanograms per hour) was 1.4-fold higher in Cu-adequate rats than in Cu-deficient rats. Repletion of Cu-deficient rats with dietary Cu increased the total amount of cardiac NE to 78 and 93% of control values after 1 and 2 d, respectively. Significant changes in the quantities of NE and DA in the heart of rats whose intake of Cu was restricted from birth were first detected at 4 wk of age, but cardiac hypertrophy was not observed until 5 wk of age. The data support the proposal that the altered levels of DA and NE in the heart of Cu-deficient rats are primarily the result of decreased activity of DA-B-monooxygenase and demonstrate that Cu supplementation rapidly repletes cardiac NE in Cu-deficient rats. Moreover, changes in the concentrations of NE and DA in the heart precede and may contribute to the development of cardiac hypertrophy.

Roles of zinc and copper in the nervous system.

O'Dell BL.
Department of Biochemistry, University of Missouri, Columbia 65211.
Zinc deficiency in chicks and guinea pigs results in unique neurological signs, including abnormal stance and locomotion. Guinea pigs develop hypersensitivity to touch and show evidence of pain in movement. Both species exhibit decreased sciatic nerve conduction velocity. Clinical signs correlate with the peripheral neuropathy and are readily reversed by zinc therapy. Copper deficiency in second generation rats produces low dopamine levels in the corpus striatum and results in clinical signs analogous to those of Parkinson's disease. The dopamine concentration is not readily reversed by copper therapy; it correlates with striatal copper concentration, but not with liver concentration, an index of copper status. The neuropathology occurs in only part of the copper deficient population and is dam and litter related, suggesting a genetic component in addition to copper deficiency.

EFFECT OF COPPER DEFICIENCY ON THE CONCENTRATIONS OF CATECHOLAMINES AND RELATED ENZYME ACTIVITIES IN THE RAT BRAIN

Immature rats were made copper deficient by feeding them a low (< 1 p. p. m.) copper diet. During the gestation and lactation periods their dams consumed the same diet. Controls received a dietary supplement of 10 p. p. m. copper. At approx 7 weeks of age, the deficient animals exhibited signs of neurological dysfunction and gross lesions of the brain. Cytochrome oxidase activity and copper content of the liver and brain were used as criteria of copper status and confirmed the existence of severe deficiency. The whole brains minus cerebella of the deficient animals contained approx 30% less dopamine and norepinephrine than those of the controls. The tyrosine hydroxylase activity was depressed more than 25% in the copper deficient brains while the superoxide dismutase activity was lowered more than 35%. There was a high correlation between the chief criterion of copper status, liver cytochrome oxidase activity, and the brain concentrations of dopamine, norepinephrine and tyrosine hydroxylase activity. The decrease in activity of tyrosine hydroxylase was sufficient to account for the lowered concentrations of the catecholamines.

This keeps getting more and more interesting...

Edited by Lufega, 10 April 2009 - 08:28 PM.

[FunkOdyssey]

So why do you think your copper levels are low despite adequate intake?

For testing copper levels, are there any other options or recommended tests besides ceruloplasmin, serum copper, and hair mineral analysis?

[nameless]

I noticed this comment you originally made:

-I often forget to eat or simply have 1 meal per day.

Could this be the reason why you have some mineral deficiencies? Perhaps there is no medical reason, but it's simply that you aren't eating properly?

And high dose manganese, which you have been taking, is a copper antagonist. Your mineral imbalances could perhaps be due to poor diet and high dose manganese.

Edited by nameless, 11 April 2009 - 12:37 AM.

[Lufega]

Funk,

I am not really sure. Now I'm exploring the idea of a copper storage problem like menke's disease, wilson's disease or some other but I don't manifest the typical symptomatology. The other tests for copper aside from the ones you mentioned are liver copper taken by biopsy. It's done in an outpatient setting but it still involves a degree of risk, such as bleeding, so I'm a bit hesitant. I will get it done soon to confirm, however.

I have been showing signs of copper deficiency since I was a kid. For example, had my first hernia at 11 years old. I'm really not sure of the cause. Maybe there is some "genetics" involved here as much I hate to take that route. I'm starting to notice that these same problems seem to run in my family as well. My cousing, who is 20 years old is starting to manifest the same symptomatology almost in the same order I did when I was that age. Lack of motivation, hernias, other connective tissue problems, valvular problems, anxiety, etc. He's lucky in way to have me around...I already have him on magnesium, zinc, life-style modification, better eating habits and a few other things.

After the age of 11, I didn't have the best eating habits, not my fault, food wasn't always around. We lived on food stamps for many years after migrating to the US. Maybe this caused some kind of permanent damage? After over 1 years of copper supplementation, my levels are still low. The same goes for magnesium, etc. So even though I eat very little per day, a sort of involuntary CR diet, I still eat very wholesome and diverse foods so I should be getting all the nutrients I need.

I really do have a strange case, I seem to manifest disease half-assed. I "almost" have marfan syndrome. I have a marfanoid habitus, tall, lanky, long arms. I am thin, have thoracic cage malformation, valvular problems, aortic dilatation..I don't have a blue sclera, but I have a prominent scleritis and there's more. This site was of great help to me ctds.info but the why of everything I am not sure of. My symptoms present "like" marfan syndrome, but it's not. I think whatever I have disrupts specific biochemical pathways, like that of copper that lead to the manifestations of marfan-like symptoms. The only thing I've learned about that can do this is Lyme disease but there are other such as mucopolyssacharidosis, immune deficiencies, etc.

I have only taken 5 or 6 doses of the maganese and I don't think its enough to really have a negative impact.

[nameless]

I have only taken 5 or 6 doses of the maganese and I don't think its enough to really have a negative impact.

You are right, then manganese dosing isn't the reason. I was just trying to think if anything you could have been taking could have caused some mineral oddness. What I find most peculiar is your mag deficiency. That's pretty low, if the hair analysis is correct. Have you had a magnesium loading test done? It's probably annoying to do, but it'd be more accurate than most other tests.

[Lufega]

Started LDN tonight at 4.5 mg. I'm very sensitive to most supplements and drugs and I tend to feel their effects almost instantly. It's only been a couple of minutes and already I feel something funny in my head. I'm really curious about the effects of this one....

[4eva]

Didn't you post something about some anemia problems at different times? Biounavailable copper would explain that too.

You might research an eye exam for copper storage issues. I think that's how they diagnose Wilson's (Keyser Fliescher rings). I'm not sure how well it works for copper toxicity though.

I also think that high copper stored in the body might show in red hightlights. Some think men with red highlights in their beard may be copper toxic. I know women show dark patches on their face (melasma) from pregnancy (high estrogen causes high copper). The point being high levels of copper stored in the body should show some signs either on the skin or in the hair, and maybe in your iris, especially if you have had this problem for years.

I only suggest this because its a lot easier to look for signs of copper toxicity than it is to get a liver biopsy.

[k10]

Keep us posted on the LDN, I'm very interested to see the benefits (if any) you get from it, and if there are any obvious effects in the first few weeks of adjusting to the medication. If there are any problems with the medication, I would reduce it to 1mg and slowly raise the dose as tolerated.

[FunkOdyssey]

I would have started at at 1 or 1.5mg and titrated up slowly after my experience with it. You set in motion some things that cannot be undone (beta-endorphin levels continue to rise for a month after stopping therapy) and this can, depending on the individual, result in unavoidable unpleasantness. Or things might go really well. I don't mean to scare you, I'm just saying there is reason to be cautious.

[Lufega]

I don't know if it was the awful taste of it but it made my stomach turn in every which direction. I stayed up for a few hours after dosing and I felt like a zombie most for most of it. It slowed me down, dumbed me down very noticeably. Today I feel a bit run down but that could be due to the week I'm having. My tremors are a lot worse today, more than normal. I think I will start at a lower dose. How fast should I titrate to 4.5 mg?

[FunkOdyssey]

I don't know if it was the awful taste of it but it made my stomach turn in every which direction. I stayed up for a few hours after dosing and I felt like a zombie most for most of it. It slowed me down, dumbed me down very noticeably. Today I feel a bit run down but that could be due to the week I'm having. My tremors are a lot worse today, more than normal. I think I will start at a lower dose. How fast should I titrate to 4.5 mg?

Its commonly recommended to start at 1.5mg and go up 1.5mg a week but I would not use arbitrary timeframes myself. I'd start at 1.5mg and stay there until things stabilized and I was sure I was tolerating it well and nothing bad was happening before increasing the dose. When it is used for MS there is typically a flare of symptoms initially followed by later improvement. If we believe MS is actually a chronic infection then the initial flare might represent a vigorous, LDN-boosted immune response that clears some of the infection, with improvement following as things calm down. One competing theory suggests LDN raises T-reg cells that prevent autoimmunity and that is what results in improvement, but I do not think that is the case, because in my research on the effects of beta-endorphin on immune cells it seems to uniformly piss them off (production of inflammatory cytokines).

[stephen_b]

4eva,

I suspected pyroluria before and it's on my list of differentials. How can I test for this?

I've used pyroluriatesting.com -- as it turns out their center is near where I live. The disorder itself is somewhat controversial, just so you are aware.

StephenB

[Lufega]

I saw the Doctor today. To date I've involved a rheumatologist/internist (my own Dr. House), a pneumologist, an infectious disease doctor, Radiologist and as of tomorrow, 2 G.I.'s and one cardiologist. Together, they look like headless chickens running around scared in den. They are clueless.

To date, I've been diagnosed as a hypochrondriac about a dozen times and recently, as a chronic cocaine user. LOL

My new differential diagnosis is Hemochromatosis or some other type of storage disease. Funny, I came to this same conclusion myself but instead, with copper. They want to do a liver biopsy anyways so lucky me, I didn't have to beg for it. I'm also going to see the G.I. for a colonoscopy and endoscopy to get to the bottom of this malabsorption problem. Lastly, they want to biopsy one of the many micro-nodules I have in my lungs and mediastinum. That should be a fun experience

On the other hand, I suspect that my years of supplementation have done me good. The Doc's are surprised as my blood work doesn't show to be as bad as it should. For example, in my condition, I should have severe anemia and my liver enzymes should be through the roof. None are. But I understand this is also throwing them offcourse and making my diagnosis that much more difficult. I'm considering stopping everything for a while, even my dear magnesium. The logic here is to allow myself to get much worse in the hopes that it'll help them figure out what's going on..

I also received the glisodin today, and I did feel that energy boost and a warm, euphoric feel..almost like I was giving my body something it craved badly.

Edited by Lufega, 16 April 2009 - 08:54 PM.

[Lufega]

These is my white blood cell count dated 4/4/2009

White Blood cells............K/uL........ 4.82 [* ] 4.80 10.80
Red blood cells..............M/uL........ 4.91 [* ] 4.70 6.00
Hemoglobin.................g/dL........ 14.50 [* ] 14.00 18.00
Hematócrit.................%........... 41.50 *[ ] 42.00 52.00
Platelets...................K/uL........ 243.00 [* ] 150.00 450.00


Neutrófilos.................K/uL........ 2.69 [* ] 2.00 6.90
Neutrófilos %...............%........... 55.80 [ * ] 40.00 70.00
Linfocitos..................K/uL........ 1.64 [ * ] 0.60 3.40
Linfocitos %................%........... 34.00 [ * ] 20.50 45.50
Monocitos...................K/uL........ 0.38 [ * ] 0.00 0.90
Monocitos %.................%........... 7.90 [* ] 5.50 13.50
Eosinófilos.................K/uL........ 0.10 [* ] 0.00 0.90
Eosinófilos %...............%........... 2.10 [* ] 0.00 9.00
Basófilos...................K/uL........ 0.01 [* ] 0.00 0.20
Basófilos %.................%........... 0.20 [* ] 0.00 2.00

These are the results as of 4/16/09 after a single 4.5 mg dose of Low Dose naltrexone:

White blood cells............K/uL........ 6.87 [ * ] 4.80 10.80
Red blood cells..............M/uL........ 4.61 *[ ] 4.70 6.00
Hemoglobin.................g/dL........ 13.60 *[ ] 14.00 18.00
Hematócrit.................%........... 39.10 *[ ] 42.00 52.00
Platelets...................K/uL........ 214.00 [* ] 150.00 450.00



Neutrófilos.................K/uL........ 4.29 [ * ] 2.00 6.90
Neutrófilos %...............%........... 62.40 [ *] 40.00 70.00
Linfocitos..................K/uL........ 1.91 [ * ] 0.60 3.40
Linfocitos %................%........... 27.80 [* ] 20.50 45.50
Monocitos...................K/uL........ 0.57 [ * ] 0.00 0.90
Monocitos %.................%........... 8.30 [ * ] 5.50 13.50
Eosinófilos.................K/uL........ 0.08 [* ] 0.00 0.90
Eosinófilos %...............%........... 1.20 [* ] 0.00 9.00
Basófilos...................K/uL........ 0.02 [* ] 0.00 0.20
Basófilos %.................%........... 0.30 [* ] 0.00 2.00

White blood cells in general increased. I was most impressed with the number of neutrophils that changed. These always show low normal. Low neutrophils are seen in copper deficiency. I'll repeat my CBC after a few weeks on LDN.

I complained to the Doc. about having NO muscle mass and general weakness and he had me test creatine phosphokinase which came back high. This implies active destruction of muscle mass. Makes sense. I can work out and put on a few pounds of soft muscle only to lose it almost as soon as I stop working out. Now I see why I bulked up so much when I used creatine back in the days.

Edited by Lufega, 17 April 2009 - 04:26 AM.

[Lufega]

Just came back from the Cardiologist. He trained in Europe and seems to be very knowledgeable in traditional medicine. My Eco shows that everything is normal even though I have regurgitation in the both the mitral and tricuspid. He claims this is normal. It could be right. It could be that dosing magnesium for the last couple of years really did reverse the prolapse, as some research articles pointed out. He ruled out any problem of cardiac origin. If I still feel symptoms, these are probably secondary to some systemic problem. He also asked if I had a traumatic childhood. Any idea where this is going? He toyed with the idea that I was somaticing all my problems because my symptomatology is so varied but I denied any emotional or childhood problems. He simply did not know what was going on and wanted to rule me out as a hypochondriac. The eco negates the findings seen in the Chest X-ray and EKG and he concludes they are false positives. I still don't understand how that works but if it means I have no heart problems....then great!!!!! But I'm getting a second opinion..

It's funny though how many of my test show "false positives" for organic problems like the brain MRI, thoracic CT, EKG, chest X-ray. These all show "something" but this something falls out of their known interpretation. Or simply, they said the tests use bad technique. Even my lab values that are all over the chart, they had the balls to dismiss as normal. I would understand one or two lab values, but MOST are either high, low or off-the charts in either direction. There is obviously something there but they just cannot interpret it. I went back to my Dr. House and he's with me. There's something there and he's set to find out what it is. I like him a lot. Additionally, we share a common idea. Most "congenital" problems are caused by nutritional deficiencies the mother had during pregnancy.

Today ended well though. I was sitting in a room with the top radiologist of the hospital. Someone mentioned that magnesium was good for you and even though most of them dismissed it as rubberish, something came over me and I started to lecture everyone on how awsome magnesium is. The teachers became the students and I think I left an impression. For those few minutes, I felt empowered and important. Then again, this is MY field of knowledge and magnesium is my favorite supplement! As I was leaving, most of them, some of whom are or will be professors or mine, chased me down the hall asking where they can get some.

[nameless]

Good news on the echo. I assume the cardiologist also looked over the EKG and x-ray results too. Did he give an opinion on why the previous diagnosis was incorrect? How can an EKG or chest x-ray be 'false positive'? They just show what they show... unless whoever stated there was a problem made a mistake reading them?

Besides the size of the heart, I'm not sure what sort of diagnosis (or who would give a diagnosis) off a chest x-ray alone anyway -- so the echo is the best test to go by.

Again, minor or trace regurgitation usually isn't a big deal. It's quite common in people, but they don't even know it because they don't regularly get echos.

Have you had the Igenex testing done yet? Lyme or some type of co-infection is still a possibility, and could explain a lot.

[Lufega]

The cardiologist I saw was more predisposed to call me a hypochondriac than he really was interested in diagnosing me. I mean, he did not even bother to auscultate me. I would go as far as to say he saw me coming. Someone told him about me and he just brushed me off. I guess it didn't take long before I developed a reputation. I wasn't satisfied with this visit today. How can 2 consecutive chest X-ray and EKG show something that isn't there? There seem to be too many coincidences, too many "false-positives" and "bad techniques". My brain MRI showed increased space in the sulci, a sign of brain atrophy (per one of the radiologists) such as seen in Alzheimer's and they dismissed it as bad technique. Even though I'm complaining of cognitive problems.

I think I'm just going to send the Igenex either way. I was going to wait, and boost my immune system but I don't think it's going to make a big difference. I seem to be producing antibodies to everything else I've tested so I should be ok. Lyme is still high in my differentials. I wanted to mention Lyme carditis today and even brought some articles for him to read but he really did not seem interested in treating something he couldn't just prescribe something for.

Now I'm afraid of taking ANY supplements because these seems to be giving out false negatives in my tests and evaluations. I really want the Doc's to see what's there. Next week I'm seeing gastro, endo, liver biopsy and a few others. I'm going to take a break from my supplements for a few weeks and see what happens...

Edited by Lufega, 17 April 2009 - 10:14 PM.

[notlupus]

It's funny though how many of my test show "false positives" for organic problems like the brain MRI, thoracic CT, EKG, chest X-ray. These all show "something" but this something falls out of their known interpretation. Or simply, they said the tests use bad technique. Even my lab values that are all over the chart, they had the balls to dismiss as normal. I would understand one or two lab values, but MOST are either high, low or off-the charts in either direction. There is obviously something there but they just cannot interpret it.

Welcome to modern medicine. At least in my experience, unless all your symptoms are perfectly explained by a single problem you are labeled a hypochondriac. Stick with the one doc that wants to figure this out.

I wish I could provide some sort of deep insight, but right now I think I'm starting to herx thanks to the diflucan and my brain is turning into mush. Glad you had a chance to mention supplements. It's sad what a small minority we are in, wanting to use something that's not got a fancy name and comes from the pharmacy at an unreasonable price.

[k10]

If you get tested for lyme please get tested for bartonella as well. I'm skeptical about the lyme since you didn't have any sort of response to doxycycline... but it would make sense if bartonella is what is causing your problems.
Check this article out:
http://www.publichea.....0and die.html

Edited by k10, 20 April 2009 - 06:46 AM.

[Lufega]

If you get tested for lyme please get tested for bartonella as well. I'm skeptical about the lyme since you didn't have any sort of response to doxycycline... but it would make sense if bartonella is what is causing your problems.
Check this article out:
http://www.publichea.....0and die.html

Thanks for this info. Seems like only accurate test is this one:

"The patient was ordered a Bartonella henselae IgG and IgM along with other lab testing which was negative, including a PCR test for Bartonella. However, the Fry Blood Smear Test came back as positive."

Any idea here I can get this doe??

[nameless]

"The patient was ordered a Bartonella henselae IgG and IgM along with other lab testing which was negative, including a PCR test for Bartonella. However, the Fry Blood Smear Test came back as positive."

Any idea here I can get this doe??

http://www.frylabs.com

Looks like it has to be ordered from a physician (under their FAQ for getting results mailed).

Are there any good Lyme doctors in your area? Alternative I guess would be Lyme/co-infection test from local lab or Igenex, and hope it's accurate.

[k10]

If you get tested for lyme please get tested for bartonella as well. I'm skeptical about the lyme since you didn't have any sort of response to doxycycline... but it would make sense if bartonella is what is causing your problems.
Check this article out:
http://www.publichea.....0and die.html

Thanks for this info. Seems like only accurate test is this one:

"The patient was ordered a Bartonella henselae IgG and IgM along with other lab testing which was negative, including a PCR test for Bartonella. However, the Fry Blood Smear Test came back as positive."

Any idea here I can get this doe??

I would first get tested for Bartonella Henselae IgG/IgM as you can get this done at any lab where you live and get an accurate result. If it comes back negative I would recommend Clongen labs as they offer an excellent Bartonella Species PCR test which looks for 20 different species of bartonella.
http://clongen.com/m...diagnostics.php

The blood smear is the one offered by Fry Labs here:
http://frylabs.com/services.php

88342 Stained smear with photo documentation of findings (2 photos). Looks for anything abnormal such as a blood-born pathogen or bacteremia.

Edited by k10, 21 April 2009 - 07:25 AM.

[Lufega]

I had the liver biopsy yesterday. It was a fun experience. I must say that supplementing with Vitamin K helped. I used it for two months then stopped for two weeks. My prothrombin time was still a little high but not enough to deter the procedure. After the biopsy, I took another dose unknown to the nurses. I did it to minimize any complications of bleeding associated with the biopsy. The only problem was, every time they drew blood to check my stats, it kept coagulating.

I will know the results tomorrow.

[youandme]

I had the liver biopsy yesterday. It was a fun experience. I must say that supplementing with Vitamin K helped. I used it for two months then stopped for two weeks. My prothrombin time was still a little high but not enough to deter the procedure. After the biopsy, I took another dose unknown to the nurses. I did it to minimize any complications of bleeding associated with the biopsy. The only problem was, every time they drew blood to check my stats, it kept coagulating.

I will know the results tomorrow.

Hi Lufega

Wow , Y'know Ive had high Liver LFT's (GGT) for now 3 years..yet not once did they say I have should have a Liver Biop....
Make sme wonder if I have the right Doc's looking at my case...my lot of Doc's prefer to watch n wait.

That Biop is as heavy as it gets..pencil sized needles are no fun any way you think apout it...power to you for coming through it.

From it I do hope they can figure some things out.