REFEEDING SYNDROME - The clues to healing via induced deficiencies

[Freddd]

I want to start off here by thanking Rich VK, once again, for being very correct on his CblC disease suspicion about me, despite the research that verifies it not being published in many cases before he put the understanding together. And much more important, the PARTIAL METHYLATION, understanding. The partial methylation is much more “hard edged” than I think that Rich recognized. Partial methylation acts the way it does because of the “internal triage levels” as earlier researchers called it, that allows partial methylation, effective on some levels at the same time as having deficiency symptoms on other levels. And these levels or compartments are not what are expected so they all look like they don’t go with each other.


Using these understandings makes understanding what those weird problems with teeth and gums may originate from and that all those responses on the 3rd day or so following MeCbl/Mfolate startup that are not neurological brightening, to be “refeeding syndrome”. People wanted answers. Unfortunately for me, all the answers I’ve had have been gotten the hard way; CblC disease – adult onset, low potassium, copper deficiency, neurological damage, multi organ breakdown (kidney disease, heart muscle damage, from excess MMA (low AdoCbl/L-carnitine fumarate) and/or high HCY damge,heart disease, strokes, etc


For years I have talked about “startup” symptoms, because of the time of occurrence in relation to starting any of several supplements. Just which “startup” symptoms and what caused them was the subject of much speculation, trials, disagreements about hypotheses and so on. The last 5 years I have had the return of some symptoms in a different way and mix and severities than ever before and my gums were melting away and the dentist couldn’t stop it or even know why. I had to have all my uppers pulled and complete upper dentures now. I have been on the copper for almost 3 months now. When I started copper, it was apparent that it was perceived as working in hours. The sleep disorders were gone in 2 days. The perception of the demyelinations slowed to a stop in 3 days. On the third day my need for potassium increased noticeably by 400mg. Perceived recovery has been slow on the leg muscle strength. After 2-3 months the dentist can see a visible difference in my lower gums which with a lot of luck, might stop getting worse or even recover a little allowing me to keep my teeth.


I have heard this kind of question about teeth and gums a few times and never had an answer. Associated questions were lots of reoccurring tooth root cavities on the roots exposed by the gums melting away without gum infections. Associated with this can be sleep disorders and subacute combined degeneration type lesions causing problems relatively frequently occurring in the upper motor neurons and causes more perceived weakness than MeCbl/Mfolate caused lesions.


The copper deficiency symptoms were clear enough that my doctor agreed and ordered tests. Like so much else, my copper was at the low end of “in range” but I had rapidly worsening symptoms. Two days after seeing the doctor, before the results could be back, she called me to see how I was doing and I told her I started on the copper the previous day without waiting for results as I felt so bad, and it was already having a noticeable effect and gave the details on the copper I was using, the Solgar Copper amino acid chelate, which was used in UK case studies collection where there was no pharmacological copper supplement available.



In 1945 a new "syndrome" was named. "refeeding syndrome" after people who were starving started dropping dead from starting eating again. It turned out to happen typically about the third day after starting eating again. In the decades following, it was found that “refeeding syndrome” could occur from anorexia, 5 days of fasting or food deprivation, and even very specifically, specific vitamin and nutrient deficiencies whose lack causes lack of cell making. CyCbl was discovered to cause Hypokalemia on the third day following injection as cell formation (red blood cells assumed) progressed. Hypokalemia, low potassium, on the third day after starting the deficient nutrients, became the tip-off of “refeeding syndrome”. Basically almost any minerals needed could become deficient and be an induced deficiency. So copper is also a common induced deficiency but comes on far more slowly than potassium. Also, copper deficiency does damage over time rather than a person dropping dead quickly so it isn’t noticed the same way. In the CblC disease, a genetic form causing B12 and folate deficiencies, the disease is specified as having “unstable electrolytes”, like potassium, magnesium, calcium, copper, manganese and so forth. Whether that is an induced set of deficiencies from refeeding syndrome and hence inherent in treating CblC disease or inherent in CblC disease itself is undetermined. Further CblC disease has “low cellular folate” as a characteristic. Whether that is inherent in CblC disease or is there as part of methyltrap caused by treating it, again isn’t known. What a person can be sure of is a succession of induced deficiencies. Potassium and folate deficiencies are present almost always in refeeding syndrome and attempted recovery from CblC disease.


Many nutrients of which people can become specifically deficient can cause refeeding syndrome. It can be everything in general, i.e. caloric and multi nutrient deficiencies, or a single specific nutrient such as folate or B12. ANY vitamin or mineral or essential amino acid can become deficient and cause refeeding syndrome. However, only a few tend to at any given time. Instead what appears is that the main set of symptoms is those of the item that is most deficient, where the majority of “fails” to complete reaction occur.


If one looks at the lists of deficiency symptoms they have changed over time as knowledge changes over time. If one looks at the list of B12/folate responsive symptoms list let’s look at the people that respond with those symptoms in those patterns, and how those patterns change.


So what happens if somebody takes vitamins that have no effect? NOTHING! What happens if somebody takes vitamins and on the approximate 3rd day after starting they get all sorts of worsening symptoms, feeling maybe really sick, is likely “refeeding syndrome”. The two 3-4 day supplements that go low with intense symptoms are potassium and low l-methylfolate.


REFEEDING SYNDROME INDUCED DEFICIENCIES

Version 1.21 04/11/2015

Group 1 – Hypokalemia onset. Symptoms may appear with serum potassium as high as 4.3. May become dangerous if ignored. Considered “rare” with CyCbl (cyanocobalamin) it is very common with MeCbl (methylcobalamin) and AdoCbl (adenosylcobalamin) and less so with HyCbl (hydroxycobalamin).

There does not appear to be a clear order of onset. The order of onset varies widely from person to person but many appear consistent for each episode for any given person. There tend to be more and more intense symptoms as it gets worse. Some people have ended up in the ER because of not recognizing the symptoms.

IBS – Steady constipation, Nausea, Vomiting, Paralyzed Ileum,

Hard knots of muscle, Sudden muscle spasms when relaxed, Sudden muscle spasms when stretching , Sudden muscle spasms when kneeling, Sudden muscle spasms when reaching , Sudden muscle spasms when turning upper body to side, Tightening of muscles, spasms and excruciating pain in neck muscles, waking up screaming in pain from muscle spasms in legs. Muscle weakness

Abnormal heart rhythms (dysrhythmias), increased pulse rate, increased blood pressure

Emotional changes and/or instability, dermal or sub-dermal Itching, and if not treated potentially paralysis and death.


Group 2a - Both

IBS – Diarrhea alternating with constipation, IBS – Normal alternating with constipation


Group 2b – Either or both

Headache, Increased malaise, Fatigue


Group 3 - Induced and/or Paradoxical Folate deficiency or insufficiency

These symptoms appear in 2 forms generally, the milder symptoms that start with partial methylation block and the more severe symptoms that come on as partial methylation block gets worse or very quickly with methyltrap onset.

Edema - An additional thing I would like to mention. I would never have found it without 5 years of watching the onset of paradoxical folate insufficiency and trying to catch it earlier and earlier and to figure out what was causing it and to reverse it. For me the onset order goes back to the day of onset now with edema and a sudden increase of weight. I noticed that within 2 hours of taking sufficient Metafolin I would have an increase in urine output.

Old symptoms returning

Angular Cheilitis, Canker sores,

Skin rashes, acne like lesions potentially over whole body and potentially growing to the size of a 50 cent piece., Skin peeling around fingernails, Skin cracking and peeling at fingertips,

Increased hypersensitive responses, Runny nose, Increased allergies, Increased Multiple Chemical Sensitivities, Increased asthma, rapidly increasing Generalized inflammation in body, Increased Inflammation pain in muscles, Increased Inflammation pain in joints, Achy muscles, Flu like symptoms

IBS – Steady diarrhea, IBS – Diarrhea alternating with normal, Stomach ache, Uneasy digestive tract,

Coated tongue, Depression, Less sociable, Impaired planning and logic, Brain fog, Low energy, Light headedness, Sluggishness, Increase irritability, Heart palpitations,.

Longer term, very serious

Loss of reflexes, Fevers, Forgetfulness, Confusion, Difficulty walking, Behavioral disorders, Dementia, Reduced sense of taste, bleeding easily


Group 4 - Hydroxycbl onset, degraded methylcbl onset, methylcbl after photolytic breakdown onset.

Itchy bumps generally on scalp or face that develops to acne like lesions in a few days from start.


Group 3 symptoms, induced paradoxical folate deficiency or insufficiency are corrected quickly with titrated doses of Metafolin, methylb12 and adenosylb12. If glutathione (precursors) are the cause then larger doses of Metafolin, 7.5-15mg,or maybe more are needed. Different tissues are affected at different levels of methylfolate, it comes or goes in stages. Very strong dose proportionate characteristics are present. Serum folate levels may be high or even very high despite Metafolin responsive deficiency/insufficiency symptoms.

Group 1 symptoms respond readily to potassium. The symptoms and response to potassium may occur at a serum level of 4.3 or less.




With l-methylfolate only available for a bit more than a decade we don’t have a lot of information. So we look at the symptom. With people with those symptoms, a person receiving MeCbl, about 75% will have obvious symptoms changes in hours to days.


With partial methylation block one has a mix of MeCbl, AdoCbl and folate deficiency symptoms immediately. When one had severe MeCbl/AdoCbl deficiency symptoms, methyltrap occurs. Instead of B12 deficiency symptoms one has awful folate deficiency symptoms. That is because methyltrap causes the expulsion of methylfolate from the cell causing the biochemical fail at FOLATE and hence folate deficiency symptoms. Give the person a little b12 and suddenly the folate symptoms go away and the b12 deficiencies symptoms get far worse. Increase B1, B2, B3 or inositol above a certain level and folate deficiency symptoms get far worse rapidly increasing the need for more folate and more potassium. Add too much P5P and the hematocrit goes up too much causing a thicker blood. The same results as too much testosterone causes. However, the hematocrit goes down with less P5P even while testosterone remains the same. It is said that lack of methylation causes low testosterone. However, low copper causes non-methylation as does lack of MeCbl/mfolate and causes a drop of testosterone level. In my experience, after manifesting copper deficiency symptoms (subacute combined degeneration type) I I increased copper and suddenly my testosterone level increased dramatically, 300ng/L. Copper deficiency causes “sub acute combined degeneration” type lesions that are not exactly the same as low folate/B12. They take longer to heal and they cause more damage to the upper motor neurons causing more perceived weakness in the legs and arms. The copper lack also causes breakdown of connective tissue including spider veins, varicose veins, connective tissue breakdown, gum tissue breakdown and any number of problems not generally caused by lack of methylation. The copper deficiency is most distinguishable from methylation deficiency after the methylation is taken care of adequately, otherwise it is indistinguishable.


So in refeeding syndrome one does not have a simple single deficiency but rather a sequence of deficiencies that can go on for months or even years. I’m 12 years into healing and I was almost done when clobbered by glutathione (“catastrophic b12 deficiency” when a person has CblC disease). In recovering from that I got worse as the copper deficiency started up. I am in a process of going through all the micro mineral nutrients as those were specifically mentioned as being commonly induced deficiencies and unrecognized in refeeding syndrome.


And the number one most common and recognizable nearly immediately is potassium. Low folate (high histamine and inflammation symptoms, epithelial tissue breakdown and so forth, see the lists above) is the other very common and recognizable.


Interestingly, with the copper supplementation, my testosterone went up by 300ng/L in 6 weeks. My kidney function is the best it has been in 30 years. The copper has made a huge difference for me. Part of the problem is that the copper serum level was 74 (72 is bottom of range), still “in range” but not by much. And I was having neurological deterioration, sleep problems, fatigue problems and all that coming on very quickly. It was worsening noticeably by the day. My doc agreed that copper appeared likely and I tried copper. The difference was clear in less than 12 hours. The neurological deterioration stopped just like that, in hours.


So in an example of low speed starvation such as CFS/FMS with a whole lot of smaller miscellaneous deficiencies we might see an order of deficiencies such as the following. These are assuming that most of the basics have been taken care of in the basics otherwise everything becomes deficient along the way. It should come to nobody’s surprise how complicated this all looks.

1. MeCbl

2. Potassium

3. L-methylfolate

4. Potassium

5. AdoCbl

6. Potassium

7. L-carnitine fumarate

8. Potassium

9. SAM-e

10. Potassium

11. Zinc

12. Potassium

13. L-methylfolate

14. Potassium

15. Copper

16. Potassium

17. L-methylfolate

18. Potassium

19. Manganese

20. Biotin

21. Potassium

22. Etc.

One of the big problems is that often the only item that will respond immediately is that which is most deficient, that which is stopping the reactions right now. So often items have to be tested a number of times because they are not stopping the reaction, until it is.


Some people also just can’t metabolize LCF but rather must have ALCAR. 90% may require only LCF but 10% equally strongly require ALCAR. Another problem is MeCbl. The problem of MeCbl is that it isn’t a single simple thing. There is an unknown number of MeCbl variations; whether isomers, stereo isomers, bacterial and/or processing differences of MeCbl variations and only one or two versions are outright excellent and nobody knows which ones they are.

 

[Richard7]

Hi Freddd,

I just read the wikipedia article on refeeding ( to try to get up to speed).

In my case this seems to make a lot of sense. With onset I had the runs so was obviously not absorbing much. And I know that early pathology showed that I needed both betaine hcl and ox bile/ bile salts.

I was slightly aware of the problem of defficiency. I made a point of chewing or dissolving multivitamins in my mouth but knew nothing of fat soluble vitamins.

I could not obtain betaine hcl or bile salts in Australia (now I get them from the states) so I focussed the other parts of my doctors' and health professional;s' recommendations, which were often counterproductive.

So I probably had 12 years of malnourishment before I got betaine HCL at the beginning of the year.

Indeed I had a period before CFS where I was prescribed Zantac, probably incorrectly. Heartburn is often caused by stomach acid being too low to trigger the opening of the sphincter that flows into the duodenum.

So I probably had years of malnourishment caused by impaired digestion of what would otherwise have been a good diet.

I noticed that the refeeding article on wikipedia mentioned that one of the minerals that people might be deficient in is barium.

And that is kind of the point. If we are not digesting food properly we may be missing out on all sorts of things that are not in the multivitamins and whose absorption may not have even been studied.

 

[helen1]

Nice to have you back, @Freddd ! I've been wondering how you are and what you've been up to...

As far as your refeeding theory goes, are you saying that if we have a symptom a few days after starting to supplement a nutrient, it might be helpful if we check the deficiency symptoms for that nutrient? And if it coincides, then do what? Keep taking it?

Also I don't understand why refeeding syndrome happens. Why would giving missing nutrients cause deficiency symptoms? I don't get it. Please explain!

 

[Valentijn]

Unfortunately for me, all the answers I’ve had have been gotten the hard way; CblC disease – adult onset, low potassium, copper deficiency, neurological damage, multi organ breakdown (kidney disease, heart muscle damage, from excess MMA (low AdoCbl/L-carnitine fumarate) and/or high HCY damge,heart disease, strokes, etc

Do you have a mutation on the MMACHC gene?

 

[Mary]

Hi @Freddd - I've been wondering how you are too , and am glad to see you back, though am sorry things have been so rough for you, to put it mildly.

Your earlier posts about potassium were a godsend for me, and I've since found (in line with what you write above) that almost anything that increases my energy causes hypolakemia - methylfolate did when I first started it, and now thiamine is doing the same thing. Others things have too though I can't recall what they are right now.

Interestingly recently I've come across something called thiamine-responsive megaloblastic anemia. My MCV has been high (near the top of the normal range) for years and didn't come down after adding in folate (was already taking MB12). Anyways, I may have a variation of thiamine-responsive megaloblastic anemia, I responded very strongly to a relatively low dose of B1, with accompanying low potassium a few days later. I don't know about other induced deficiencies -

Thanks for your post!

 

[Freddd]

Do you have a mutation on the MMACHC gene?

Hi Valentijn,

At this point the number of different mutations is unknown. We are looking for a university based study who is interested in doing a 4 generation (maybe 5) family data collection.. One of the outstanding features of this is the "remarkable heterogeneity" these polymorphisms have. The medical system in this country is screwed beyond all reason making it not easily feasible to get testing of this sort and have it paid for. People not familiar with our lack of system are not familiar all the roadblocks and massive expense put upon the person.

For instance, I have an unusual, as has been pointed out many times, need for high dose MeCbl to keep my nervous system functioning. There is not a test available with any possible results that would cause my insurance to pay for 3x10mg injections of MeCbl daily. Nor is there a test that would have results causing insurance to pay for the 30 mg daily dose of Deplin (Metafolin) I also need. The studies done on Deplin do indicate that the 15 and 30mg doses were much more effective than 7.5 mg daily dose on the symptoms tested.

I have a hallmark symptom of adult onset CblC disease, rapid onset of catastrophic B12 deficiency from glutathione.

I would like to have "proof" and then have paid for therapy. Instead I can PAY for experimental tests. The pragmatically developed "treatment" for CblC disease adult onset is an occasional HyCbl injection, folic acid and ALCAR that does "poorly" at modifying the progress of this disease.. This "standard of care" "treatment" is dangerous and even deadly for me and is the ONLY one my doctors could give me for their safely (doc not be sued for going against "standards of care"). If I ever get put in a hospital here they might kill me with the treatment by giving me the allowed "standard of care" treatment and even that would not be paid for by insurance because they don't pay for "vitamins" or "medical foods".

My doctor knows all this. I was having a terrible time getting much worse very quickly from a mystery (low copper hypothesis, which worked quickly). And the copper which was tested was at the bottom end of "in range" so why am I having severe deficiency symptoms? My doctor was willing to go with my logic having studied my last 12 years of treatment (same office, new doc). The insurance paid for the test for the copper but as I had no "medically demonstrable need" (only symptoms) for more copper and getting it paid for. Besides copper is cheap enough, even the best, that the "copay" is more than the just buy it cost.

If I had Parkinson's, ALS, MS, SNP etc, I could get all sorts of expensive drugs that might slow down or increase some of the symptoms or kill me more or less quickly than what I am doing. However, no matter what the tests showed for the dreaded CNS disease(s) that I had there is no treatment of any kind that the insurance company would pay for with a copay less than the vitamins that work actually cost me.

That is one reason to find a study, so it is all paid for, and especially if they are willing to study the effectiveness of the MeCbl, AdoCbl, l-methylfolate and LCF instead of the HyCbl, folic acid and ALCAR, 100% of which don't work for me.

In the one year I have had my new doc she has seen my results for my proposed treatments of myself work every time. I fit the descriptions and responses and predictions of effectiveness of everything she has seen in the past year. The whole office has seen me look 20 years younger than I did 12 years ago, by blood tests normalized, by kidney performance has normalized, my blood pressure is in the best range, I have no edema instead of 85 pounds of excess water I had 12 years ago. I have discontinued almost all the medications I was on 12 years ago, I avoided a wheelchair.

Because of my gums melting away I have had $20,000 worth of dental work and not done yet. My lower gums have improved noticeably in 2 months of copper, a visible difference to my dentist. However, not soon enough to save my top teeth all 13 of which came out a few weeks ago. However, my doc and dentist have agreed to go over my tests and x-rays and such of the last 6 years and see what, if any, surrogate measurement that could be used to show lower versus higher copper levels and rate of gum shrinkage. Testosterone might be that surrogate. Six weeks of copper and my testosterone level went up by 300ng/L. That is a huge and fast increase. If the variability of the testosterone and the gums correlate usefully and then the eyeball tissue descriptions, it might be possible for some others here to not have to have all their teeth out because their gums melt away from low copper loss of connective tissue.

So far, as far as tests go, I had stage 2-3 kidney disease, diagnosed as a lying alcoholic because of the many peculiar blood test results. My serum B12 and folate was never "low" despite hundreds of active b12/folate responsive symptoms to both. I didn't "qualify" to have an HCY or MMA tests as a confirming test for low serum b12 so I was given decades of "blow-off" diagnoses such as CFS ("yuppie flu", FMS (an imaginary woman's disease"), a lying alcoholic (intolerant to alcohol like many of us), stocking and glove neuropathies as evidence of "its all in your head" "conversion disorder rather than B12 deficiency typical neuropathies and so on. I spent (self pay) $200,000 over 20 years trying to get answers and got poor and called names for having the wrong results

If you have any ideas of how to make our medical non-system functional and rational please don't keep it a secret. I will cooperate with extensively with any group doing real research into these things. However, everything based on CyCbl, HyCbl, folic acid and ALCAR are worse than useless as are the tests. I can't afford to pay for exploratory experimental tests and no matter what the answers of the genes, the treatment as they think it is at this time would disable or kill me quickly. Right now there are no winning choices in the USA for somebody like me. I can get called names, or treated for MS or Parkinson's or whatever they want to call it depending upon my 40 neurological symptoms of this week spending huge copays on drugs that work poorly or worse. Or I can work quietly with my doctor who is willing to consider nutritional items and is willing to go along with me as long as I have good results.

So at the oral surgeon I'm a "high risk" patient based on actual history. At my internist's I try to avoid all the drugs I can and she is surprised that after needing half a dozen rounds of antibiotics a year for most of my life and then zero for 12 years and then 3 rounds with dental work that I should find it odd to have an explosion of thrush after antibiotics as I'm 67 now. I take none of the expected drugs of somebody my age etc. No cholesterol drugs, no BP meds, no diabetes drugs, no heart or anything else medications. I take a thyroid med and some pain and anti spasm meds.

As far as symptoms and especially certain hallmark responses to glutathione, I have CblC disease adult onset. That is 100% predictive of what happens and what did happen. I found the superior variations of the same nutrients that the official research came up with except that they found the "poorly effective" inactive version and I found the highly effective active forms.

If I had been able to get a good diagnosis instead of being called names I would have been disabled in 1987 however, pain, yuppie flu, imaginary woman's diseases and such doesn't get anybody SSDI, especially in the 1980s before these were even valid diagnoses.

I'm satisfied that I have a diagnosis that fits ALL the symptoms for most of my whole life. I see hospitalization as being a life threatening situation. The only disagreement I had with Rich on the diagnosis was that with 3 known surviving adults institutionalized for neurological diseases with CblC disease and lots of dead children so how could that be me, as of the knowledge when I started reading and researching it, 1978.

So if you have some great ideas, let's hear them. For now I am trying to make the information more systematized and understandable to more people who need the information. And "refeeding syndrome" while having lots of causes also gives lots of clues so it isn't as much of a mystery. As a systems analyst I am seeing the SYSTEM inherent in refeeding syndrome, and the lack of system in the establishments research understanding of the diseases I have. "Refeeding syndrome" gives the outline that helps it make more sense to people reading it IF I can do a decent job of explaining it.

 

[Freddd]

Nice to have you back, @Freddd ! I've been wondering how you are and what you've been up to...

As far as your refeeding theory goes, are you saying that if we have a symptom a few days after starting to supplement a nutrient, it might be helpful if we check the deficiency symptoms for that nutrient? And if it coincides, then do what? Keep taking it?

Also I don't understand why refeeding syndrome happens. Why would giving missing nutrients cause deficiency symptoms? I don't get it. Please explain!

Hi Helen,

I apologize for not making my explanations more understandable. So let me start at the beginning.

"REFEEDING SYNDROME" is not a theory, and certainly is not mine. It is a very literal description of a syndrome, a collection of symptoms that might be from potentially dozens of causes. In 1945 when concentration camps and German and Japanese POW camps were liberated with millions dying of out and out starvation. When liberated the first thing the liberated prisoners did was start eating again. On about day 3 after starting eating again, the ex prisoners started feeling really bad and dropping dead. Pragmatically they found that if you do a food titration, giving them a fraction of the amount of food needed each day they didn't die. A little later they discovered that most of the people who died quickly died from hypokalemia, potassium being a major mineral in making cells of all varieties.

In the mid 1950's when CyCbl was ready for studies of injection and correcting megaloblastic anemia, hypokalemia was found to be induced. At 10 years after the end of the war they were not about to say that this Nobel prize winning vitamin caused refeeding syndrome. As they were giving 1 injection a month, after a while anyway, a titration of that speed was not fatal. I don't know if they ever had any fatal cases from induced by B12. They certainly didn't want to say that this new miraculous vitamin caused concentration camp disease. What they said was that it caused hypokalemia because it made cells (red blood cells specifically, to give it that very limited look) more quickly than the body could keep up with the nutrition needs. What they certainly didn't say was that lack of cell formation (partial methylation block slows cell formation) was that B12 deficiency caused a partial starvation and didn't make cells for that reason.

My mother (adoptive) had anorexia and starved herself to down below 70 pounds. She survived but without the help of potassium because her tendency was to not eat. Her final hospital stay was over when her doctor discovered she had B12 deficiency psychosis and she was started on vitamins. CyCbl and folic acid worked fine for her but for a while it was touch and go with getting enough potassium.

During the years, because it partly became more a part of nursing, delivering to a patient the right food in the right quantities until the person is able to put on weight without having a heart attack or other hypokalemia symptoms, and it was nurses who started pointing this out.

They discovered that the people they had to watch were these people with anorexia or bulimia, people who did fasts of 5 days or longer or who deprived themselves of certain nutrients for whatever reason and then were able to resume eating a full diet, that was when they had refeeding syndrome. So people who couldn't use vegetable folates and didn't eat meat and so couldn't get the sufficiency of l-methylfolate and couldn't get refeeding syndrome until L-methylfolate became available. Recovering from almost every deficiency disease was kind of dicey before 1945. If they had free access to food, they could die. That didn't happen with scurvy for instance since they didn't supply Vit C that turned on cell making in concentrated form until they supplied limes etc for entire voyages.. The whole diet was deficient of many items.

So looking at hypokalemia as part of refeeding syndrome, there is a definite delay after starting something , usually said as 3 days or 3rd day or after 3rd day. Just a few weeks ago I took a 3 week Diflucan prescription. I had additional hypokalemia from dose/day 1. So that appears to be not refeeding syndrome. Some things can cause more potassium to be excreted rather than used in cell formation.


To be continued ...

 

[Little Bluestem]

What is CblC disease?

 

[Valentijn]

At this point the number of different mutations is unknown. We are looking for a university based study who is interested in doing a 4 generation (maybe 5) family data collection.. One of the outstanding features of this is the "remarkable heterogeneity" these polymorphisms have.

A study might be somewhat unlikely, though it wouldn't hurt to contact the researchers who have published regarding Cblc Disease in the past. They also might be willing to share information with your treating doctor, and doctors can typically override the insurance company unless there's a specific limitation in your insurance policy saying that that treatment is not covered.

The other issue is that it would probably take a year or two for such a study to start, even if the researchers began planning it immediately. To some extent, you're a bit screwed because the treatments are vitamins and minerals, and largely unpatented outside of the high dose folic acid/B12 blends which probably aren't using the right forms of either. So there's no financial incentive for a pharmaceutical company to fund research into such a treatment for CblC Disease, which limits funding options for the researchers. But there are funds specifically for orphaned diseases now, from what I recall.

I would like to have "proof" and then have paid for therapy. Instead I can PAY for experimental tests. The pragmatically developed "treatment" for CblC disease adult onset is an occasional HyCbl injection, folic acid and ALCAR that does "poorly" at modifying the progress of this disease.. This "standard of care" "treatment" is dangerous and even deadly for me and is the ONLY one my doctors could give me for their safely (doc not be sued for going against "standards of care").

There are some suggestions that hydroxoB12 doesn't work for all, and that the problem can be a failure to convert B12 into the active co-enzyme forms (adenosylB12 and/or methylB12). When someone has a milder partial inability to produce an enzyme, increasing the precursor a lot can help increase production of the needed enzyme. But in other cases that is not expected to work - this should be a fairly straightforward concept which a doctor can understand and accept. But at any rate, a doctor should be fairly free to try what works, and billing might be a lot easier when there is a firm diagnosis. But yes, a bit of a catch-22 that they won't let you have the testing which would confirm such a diagnosis.

My general impression from reading the research summary ( http://www.omim.org/entry/277400 ) is that it's primarily diagnosed from the genetic angle, since most blood labs involving B12 issues can look relatively normal in the case of CblC Disease. That is, there's sufficient B12 floating around, and blood cells and volume can look normal, while still having grossly insufficient amounts of the active forms of B12.

So a couple things I'd suggest looking into:
1) Genetic testing of the MMACHC gene. On the Test Requisition form at https://www.genedx.com/test-catalog/available-tests/mmachc-gene-sequencing/ it looks like they offer relevant testing under "Inborn Errors of Metabolism" as "667 Methylmalonic acidemia, disorders of cobalamin metabolism and related disorders Next-Gen sequencing panel (16 genes)" on page 5 and more specifically as "274 Cobalamin C deficiency (MMACHC)" on page 6.

The MMACHC test looks at the exons of that one gene, which seems to be the only one associated with CblC Disease. The panel test is listed at http://www.genedx.com/test-catalog/disorders/methylmalonic-acidemia/ and includes MMACHC and 15 other genes closely involved in B12 issues. I'm not seeing many other options out there, though genetests.org might turn something up.

Genedx doesn't list prices, but there's an email to use for inquiring at the bottom of the URL given above. Typically testing genes thoroughly costs $100-200. It might not be much more for the 16 gene panel than for the MMACHC test alone, since a lot of the expense is in preparing the sample. If prices are going much higher than that, Whole Exome Sequencing of the coding sections of your entire genome can be done for $1,300. Then you can go through the relevant genes with a fine-tooth comb to look for the problems, if it's not already identified in the report.

LabCorp has the "Inheritest Carrier Screen" which includes screening for CblC Disease, but only detects 58% of cases, so probably is only testing a few SNPs per gene.

2) There might now be more specific lab tests which can reflect the amount of the active forms of B12. I'd also be pretty shocked if you can't get homocysteine tested, though I've no idea how your current B12 intake would be altering the results. But homocysteine is a very routine test done as part of yearly physicals.

At any rate, your doctor should be able to order the relevant tests if there's a good reason to think they're necessary. Insurance might issue an automatic denial, but the doctor can typically insist on the medical necessity of the test or treatment.

 

[ahmo]

@Little Bluestem
http://forums.phoenixrising.me/inde...fms-with-extreme-prejudice.35251/#post-553307
Cobalamin deficiency disease.

 

[Victronix]

I'd be interested to hear a little more on the symptoms of copper deficiency. Perhaps there is so much overlap with other symptoms, it's difficult to assess? In any case, sounds like it's worth a try to take a little extra copper and see. Glad to hear you figured that out.

FYI, receding gums are one symptom among many of estrogen deficiency, but not widely known. Very interesting about the testosterone relationship also.

 

[kangaSue]

Interesting you mentioning being accused of being a lying alcoholic, was that because they noted phosphate wasting in your renal tests as happens with alcohol abuse causing hypophosphatemia, abnormally low level of phosphate in the blood.

I see that Refeeding syndrome and malabsorption issues can also result in the same electrolyte imbalance
https://en.wikipedia.org/wiki/Hypophosphatemia

 

[garyfritz]

@Freddd, your description of adult-onset CblC is very interesting to me. I've been trying to understand why my B12 needs suddenly skyrocketed, and I wonder if that's what's going on. I had minor symptoms (occasional RLS, etc) for many years, but at about age 55 things got worse very suddenly. I stumbled onto B12 almost by accident, and by great luck I tried methyl B12. Over the last several years I've settled in on methyl B12, adenosyl B12, and folate as the key nutrients I need. Never got any results from LCF but maybe I should try ALCAR. My homocysteine levels are at the high end of the range.

I don't have full ME, thank God -- at least not yet. My symptoms seem to be more like acute B12 deficiency. Like you, I need large amounts of B12, currently 1.5mg mB12 and 4.5mg adB12 daily, injected equivalent.

I don't know about the copper. I show many symptoms (borderline low testosterone, low body temp, high cholesterol, kinky hair, hair loss (but at age 60 it may just be normal male-pattern baldness), etc. I had a recent hair-metal test that showed normal Cu levels, but who knows if I'm using it right. On my doctor's advice I'm taking Zinc, which can interfere with Cu absorption.

 

[kangaSue]

@Fredd, if you haven't seen this before, abnormal renal re-absorption of phosphate is a finding in Phosphate Diabetes in some patients with chronic fatigue syndrome.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360873/

There was a thread on it here
forums.phoenixrising.me/index.php?threads/phosphate-diabetes-in-patients-with-chronic-fatigue-syndrome.4494/

 

[Freddd]

Interesting you mentioning being accused of being a lying alcoholic, was that because they noted phosphate wasting in your renal tests as happens with alcohol abuse causing hypophosphatemia, abnormally low level of phosphate in the blood.

I see that Refeeding syndrome and malabsorption issues can also result in the same electrolyte imbalance
https://en.wikipedia.org/wiki/Hypophosphatemia

Hi KangaSue,

It looked more like multiple b-vitamin deficiencies, macrocytic anemia, low platelet counts, (I was asked about abnormal bleeding even more often. In the early 90s I had liver abnormalities for no known reasons. One of the reasons of suspicion was cultural. I lived in Utah. There were a lot of lying alcoholics there because you aren't even allowed to drink. in the local culture. Nothing else was mentioned and low phosphate was never mentioned. For instance, before any tests I'm being asked about alcohol usage (first exam, before tests). At that time I could barely tolerate alcohol at all. Wen asked I would start out "About a six pack worth..." interruption by a couple of docs who completed the phrase with "per night" and then I would finish it with my original intent "No,. per year. I almost don't drink as I can't tolerate alcohol." This was based on whatever cause them to jump to conclusions. Most of the ,many docs who failed utterly to figure out my situation said that at first glance they would have thought B12/folate deficiency but my use of CyCbl and folic acid make deficiency impossible. Then tests would b

I didn't have refeeding syndrome until I found MeCbl and the other effective nutrients, May 2003 to start with.

 

[Freddd]

A study might be somewhat unlikely, though it wouldn't hurt to contact the researchers who have published regarding Cblc Disease in the past. They also might be willing to share information with your treating doctor, and doctors can typically override the insurance company unless there's a specific limitation in your insurance policy saying that that treatment is not covered.

The other issue is that it would probably take a year or two for such a study to start, even if the researchers began planning it immediately. To some extent, you're a bit screwed because the treatments are vitamins and minerals, and largely unpatented outside of the high dose folic acid/B12 blends which probably aren't using the right forms of either. So there's no financial incentive for a pharmaceutical company to fund research into such a treatment for CblC Disease, which limits funding options for the researchers. But there are funds specifically for orphaned diseases now, from what I recall.

There are some suggestions that hydroxoB12 doesn't work for all, and that the problem can be a failure to convert B12 into the active co-enzyme forms (adenosylB12 and/or methylB12). When someone has a milder partial inability to produce an enzyme, increasing the precursor a lot can help increase production of the needed enzyme. But in other cases that is not expected to work - this should be a fairly straightforward concept which a doctor can understand and accept. But at any rate, a doctor should be fairly free to try what works, and billing might be a lot easier when there is a firm diagnosis. But yes, a bit of a catch-22 that they won't let you have the testing which would confirm such a diagnosis.

My general impression from reading the research summary ( http://www.omim.org/entry/277400 ) is that it's primarily diagnosed from the genetic angle, since most blood labs involving B12 issues can look relatively normal in the case of CblC Disease. That is, there's sufficient B12 floating around, and blood cells and volume can look normal, while still having grossly insufficient amounts of the active forms of B12.

So a couple things I'd suggest looking into:
1) Genetic testing of the MMACHC gene. On the Test Requisition form at https://www.genedx.com/test-catalog/available-tests/mmachc-gene-sequencing/ it looks like they offer relevant testing under "Inborn Errors of Metabolism" as "667 Methylmalonic acidemia, disorders of cobalamin metabolism and related disorders Next-Gen sequencing panel (16 genes)" on page 5 and more specifically as "274 Cobalamin C deficiency (MMACHC)" on page 6.

The MMACHC test looks at the exons of that one gene, which seems to be the only one associated with CblC Disease. The panel test is listed at http://www.genedx.com/test-catalog/disorders/methylmalonic-acidemia/ and includes MMACHC and 15 other genes closely involved in B12 issues. I'm not seeing many other options out there, though genetests.org might turn something up.

Genedx doesn't list prices, but there's an email to use for inquiring at the bottom of the URL given above. Typically testing genes thoroughly costs $100-200. It might not be much more for the 16 gene panel than for the MMACHC test alone, since a lot of the expense is in preparing the sample. If prices are going much higher than that, Whole Exome Sequencing of the coding sections of your entire genome can be done for $1,300. Then you can go through the relevant genes with a fine-tooth comb to look for the problems, if it's not already identified in the report.

LabCorp has the "Inheritest Carrier Screen" which includes screening for CblC Disease, but only detects 58% of cases, so probably is only testing a few SNPs per gene.

2) There might now be more specific lab tests which can reflect the amount of the active forms of B12. I'd also be pretty shocked if you can't get homocysteine tested, though I've no idea how your current B12 intake would be altering the results. But homocysteine is a very routine test done as part of yearly physicals.

At any rate, your doctor should be able to order the relevant tests if there's a good reason to think they're necessary. Insurance might issue an automatic denial, but the doctor can typically insist on the medical necessity of the test or treatment.

Hi Valentinj,

The "in range b12" preventing authorization of MMA, HCy tests was like 1970s, 1980s, and into the 90s. Such testing is totally irrelevant now and my doc did the serum Cbl and comes out "immeasurably high" now. That is of course to be expected due to my 30mg of injections daily with an estimated calculated daily range between 125,000 pg/ml to 200,000 pg/ml. As far as testing MMACHC the number of variations and what they mean is unknown at the present time. As they report, the symptoms are "extremely heterogeneous" and they have no idea what the many symptoms patterns are or what they mean. I have no Hcy or MMA symptoms and haven't in years. And if they tested high there is no treatment more effective than what I am doing in any case.

Of course HyCbl doesn't work for many folks with some of the variations, 1/3 are a complete miss. Prior to 1998 there was no choice. My problems were impossible to treat prior to MeCbl, AdoCbvl and L-methylfolate being available commercially. Active B12s were not available. HyCbl works poorly enough for most folks without problems. My doc knows exactly what I am taking, knows that I have to have MeCbl, AdoCbl, l-methylfolate and LCF because of the 3 items in the standard treatment, HyCbl, folic acid and ALCAR is a 3 strikes and I'm out for good, dead. They have no genetic based "better treatments". There is NOTHING to be learned right now by paying for tests as it won't influence my insurance coverage

Most all of these things are ancient history. My doc appears satisfied with a diagnoses from symptoms and characteristics and response patterns and is more than satisfied with my results as she has never seen better or even equal results.

The insurance company works from it's formulary and forbids "medical foods and vitamins" from coverage which protects pharmaceuticals who subsidize the cost of the drugs they want to push. They don't want to pay for Deplin. One of the recent CblC studies has the researcher stating that " it is outright foolish to restrict types or quantities of B12 for any reason for people with CblC disease". Try telling that to a pharmacy benefit company. They don't give a damn how that affects the rest of anybody's utilization, there is no incentive for them to pay attention.

These days one isn't even working with the insurance company, but rather a pharmacy benefit provider. In the 70s and 80s one was working with the insurer and could negotiate better than can be done now. The other problem is that injectable MeCbl is a compounding type deal. The new rules after that fungus infection at the New England compounding pharmacy a few years ago made the price go way up and almost impossible to get a months worth of MeCbl at a time.

Now copper is cheap and easy to buy. Only problem is that distinguishing copper deficiency symptoms is not easy until it gets bad enough. And again, test ranges don't necessarily indicate symptoms onset levels. Correcting copper deficiency can increase need for potassium. For me, it upped the my potassium daily need by 400 mg on the 3rd day after starting copper. It started affecting symptoms perceptively in several hours.

 

[Valentijn]

The insurance company works from it's formulary and forbids "medical foods and vitamins" from coverage which protects pharmaceuticals who subsidize the cost of the drugs they want to push.

A very nasty situation Vitamins are an essential part of health, and mega doses are required in various diseases - far more than what people can get from diet or even over the counter at a reasonable price. Health care really needs some major changes.

 

[Freddd]

A very nasty situation Vitamins are an essential part of health, and mega doses are required in various diseases - far more than what people can get from diet or even over the counter at a reasonable price. Health care really needs some major changes.

Hi Valentijn,

Proper use of vitamins in my case brought my pharmacy costs down over 90% after the first years. For me, as with a lot of people in the Deplin studies, the higher doses are more effective. I was in the benefits consulting business for decades and want to get a vitamin benefit plan put together but everybody and everything is against it, especially the pharmaceutical benefit plans unless they get to control it and do it like drugs. The FDA wants to change the rules and change any vitamin that is well studied into a drug by virtue of being studied. Then it is priced and dose controlled like a drug. Not being able to get the doses and kinds of vitamins I need can damage me quickly.

So far I have been able to get folic acid and HyCbl, CyCbl and folinic acid into my dangerous reaction drugs record. We don't know if that will stop "standards of practice" problems or not. I talked to by father's doctors when he was on IV nutrition and there is no way to get that without folic acid and CyCbl, no way to substitute the active forms. Again that was 10 years ago but that hasn't changed. Right now the "standards of care" are a potential death sentence for people like me. My father, with whom I worked in the consulting business, was on the Joint Commission Ambulatory Care Committee. Each organization had their representative who was largely there to keep their ox from being gored. Also, practicing according to the standards of care are generally law suite protection. With things as messed up as they are now and pressure to use results driven standards, things are even more difficult because that is when the bad research comes back and bites us.

With the active vitamins they have to learn how to deal with success, (refeeding syndrome) and take corrective action not treating like an undesirable side effect of a drug and say MeCbl is too dangerous to use because it turns on too much healing and causes low potassium. Also, since the active B12s and folates change how the other B vitamins interact so much research based on CyCbl and folic acid are just plain wrong for the active vitamins.

We need major changes to healthcare in so many ways. The mistaken Nobel prize for CyCbl (actually should have been MeCbl and AdoCbl) has caused all sorts of problems as has the partial effectiveness of folic acid, though that was the best they could do in 1942. Most young researchers don't know the history of B12 and the AMA and have no idea how much disease is caused by these outdated foundation research projects that have had their flaws forgotten in the mists of history. In the USA somehow health care became a political football that isn't about quality care as such. My vitamins cost me far more than the actual food I eat, but less than the pharmaceutical costs trying to fix hundreds of symptoms 1 or 2 at a time which never worked.

 

[Freddd]

I'd be interested to hear a little more on the symptoms of copper deficiency. Perhaps there is so much overlap with other symptoms, it's difficult to assess? In any case, sounds like it's worth a try to take a little extra copper and see. Glad to hear you figured that out.

FYI, receding gums are one symptom among many of estrogen deficiency, but not widely known. Very interesting about the testosterone relationship also.

Hi Victronix,

Estrogen and testosterone are both reduced by officially anyway, B12 and folate deficiencies. Some people when going to the active B12s, and some people with AdoCbl and some with MeCbl (methylation vs ATP) have their hormones restored and some don't. I had never seen it attributed to copper. But now, with a 300 ng./L, which is SIZABLE as increases go, I have to re-titrate with testing for just how much supplemental I need to take.

I'm going to describe this the best I can. I haven't had much feedback except that when it works it can be obvious. It affects the balance of most everything. For instance I have reported a top of effective range of dose for B1, B2, B3, inositol and maybe others wherein increased need for potassium and folate appears but actual healing appears to be decreasing because of the appearance of several "lack of methylation symptoms" in an odd combination. That might be because of the low copper being the most limiting factor and stopped by that at different from usual places . I can't say for sure yet as that is an additional trial set away.

The descriptions I have seen attribute "Sub Acute Combined Degeneration type lesions" given as the description affecting more heavily the upper motor neurons as the effects of low copper. However, it is a limited subset of the total symptoms, so that pattern itself could be a clue.

I think I can pin it down better than that. First, if the person hasn't achieved basic methylation and ATP startup with the deadlock quartet, and has all the symptoms, then there are any number of items that could get that basic startup with refeeding syndrome.

This brings up the idea of "most limiting factor". Basic methylation and ATP startup is a hostage to the deadlock quartet for about 90-95% of the people with a lot of the familiar symptoms. Vit D can provide about 5% with basic startup and then either basic startup or increase might happen with SAM-e, TMG, making sure of the active for you type of carnitine, Biotin and D-ribose, all together another few percent getting basic startup. If all that doesn't start it, and magnesium, zinc, etc are being taken, then copper might do that. It provided an increase in methylation for me amounting to +400 mg potassium on the 3rd day of a total of 2400mg of potassium.

Symptoms wise I had demyelination and rapid loss of nerve functions with very fatigued feeling legs and arms typical of upper motor neuron. Mood wise, depression, abnormal fatigue, sleep disorders and general personality/mood changes were very similar to the same results from lack of basic methylation startup. As copper deficiency symptoms they hit like a ton of bricks, more like loss of ATP startup or methyltrap than a slower partial methylation block. The spider veins and peripheral neuropathy symptoms came on slowly. The gums started shrinking like gangbusters 5 years ago, going from normal to no longer sufficient for teeth. The spider veins is also loss of connective tissue. I haven't studied up on connective tissue so much so I had no idea.

The catch is if basic methylation and ATP startup with some degree of refeeding syndrome appearing has started one can work to improve it. So copper, instead of 200 symptoms from lack of basic methylation and ATP, copper might only account for a dozen or so symptoms, similar but different pattern from the basic ones. If copper turns out to be the most limiting factor in general methylation/atp it will hit like a ton of bricks and could possible cause +2000mg or more of hypokalemia typically on the 3rd day.

The most limiting factor is what causes the symptoms that start correcting in hours to a day. That is what causes all the confusion about folate symptoms versus b12 deficiency symptoms. If there is a hard MeCbl deficiency then methylfolate is kicked out of cells (low cellular folate of CblC disease) causing not b12 deficiency symptoms but rather folate deficiency symptoms that can't be fixed by folate. However, given enough MeCbl to not cause methyltrap, then there will be folate deficiency symptoms that respond to l-methylfolate.

On the N=10 glutathione trial I was part of, methyltrap hit in about 2 hours causing body wide inflammation, return of allergies and asthma as well as all sorts of epithelial tissue problems; IBS, cheilitis, peeling and cracking fingertips, skin rashes, acne type lesions potentially growing to half dollar size in some people and a multitude of other problems with demyelination starting to become noticeably worse in about 2 weeks. Methyltrap folate deficiency symptoms don't respond to l-methylfolate, partial methylation block responds very well to l-methylfolate. The difference is the level of B12 available. And, because there are perhaps 8 "internal triage levels" for b12 and folate with causal link unknown. However, it is possible to have methyltrap on some levels, partial methylation block on some levels and active healing, even to the level of refeeding syndrome in some levels. This seemingly paradoxical response is difficult to unravel. Recognizing the patterns of partial methylation block versus methyltrap vs refeeding syndrome (folate, potassium).

The copper deficiency is most clearly defined when it it is spite of previously adequate amounts of MeCbl and l-methylfolate, AdoCbl and LCF. It is severe but more limited in symptoms range because it breaks the methylation in a way that only some things are susceptible to such breakage, ie the work copper containing enzymes does. Also, my nails and hair have become more brittle the past few years, again slow happening. slow noticing. My hair hardly needs cutting as it breaks off so easily. We shall see where it goes.

Paying attention to patterns and cycles of symptoms become the key to this. If I had been paying attention 5 years ago and recognized some of these patterns I might have saved my gums and teeth. It would have taken a larger earlier neurological effect to catch my attention and didn't realize the seriousness of the gum situation and where it was heading. Neither did my dentist. I was trying to do everything right in taking care of my mouth.

 

[trails]

@Freddd - I'm curious as to what type/dosaging of copper supplement you are using.