B-12 - The Hidden Story

Rich, also I can not gain weight, I am thin, I eat and I continue to loose weight, scary. Tested years ago and was found to be sensitive to wheat, dairy, soy, and sugar. They called it leaky gut.

Lena

 

Hi Rich,

In the interests of understanding this whole thing, and gut issues in particular, I am glad to give you my story. It goes way back and I'll start at the beginning.

I was cow's milk formula fed from the beginning. From a very young age my mother used suppositories on me until my father stopped her at age 2. Whether this was due to an actual need or her obsession with her own bowel function I can't tell you. I had no real problem after she stopped at my age 2. She started restricting my access to meat and the more she did the fatter I got starting in 4th grade. By age fourteen I had IBS and it plagued me until 5 years ago, at 57. Decades later, after mb12, I found that I had an intolerance to milk and cheese. I always had a sensitive stomach and could not tolerate all sorts of things. Six years ago and prior I had a prescription to Compazine suppositories for nausea and I vomitted one or more times many days. Eating had become very difficult. I couldn't tolerate many foods.

I did several ellimination diets over the years and none ever made a difference or identified anything. I had occasional incidents of hives from childhood but never pinned down a cause. All this was pretty much ignored as a child because I had so many things wrong and was constantly sick with one thing or another for months on end. GI inflammation of varoius kinds are symtomatic of both mb12 and folate deficiencies decreasing the ability to absorb both in a kind of vicious feedback loop. There does not appear to be any way out of this cycle without getting enough nutrients including mb12 and methylfolate. This appears to be part of the epithelial inflammation and deterioration these deficiencies lead to. My mucous in general got thick and sticky, finally having the consistancy of a thick sticky jelly. I had difficulty coughing it up and when it did come up it came in huge globs and sheets. I had pneumonias every few years.

Every cold ended up in my lungs for months. After mb12 it thinned out and became fluid and "slick as snot" as the inflammation healed. After mb12 I tried the ellimnation diet again and positively identified milk and cheese as culprits and stayed off of them 100% for more than a year as a shorter period caused relapses of IBS and nausea even with lactase. Now, as long as I take lactase, I can eat them about once a week. I never drink milk any more. I use soymilk for cereal and such. I save my occasional dairy for cheeses mostly and occasionally icecream. However, if I eat them more often inflammation and IBS start returning.

In general now I can eat most anything I like. My digestive system is no longer "sensitive". It is completely normal as best I can tell after 40 years or more of problems. My skin also is no longer hypersensitive to chemical or physical irritants or anything else. My lungs are no longer hypersensitive. I haven't used any asthma medications or antihistamines for 6 years now. After a lifetime of those problems I no longer have them, all occurring about a year after starting the mb12 and improving again after the methylfolate. The brief stint with glutathione precursors restarted all sorts of inflmammatory responses and I had the worst hayfever I've had since starting the second year of mb12. 4800mcg of methylfolate with my usual mb12 and adb12 put a sudden end to those problems. I hope you find this helpful.

 

I have been doing a lot of reading lately (yes, I know it always seems to get me in trouble) about GI problems and b12/folate deficiencies. There seems to be a feedback loop for some reason. If a person gets an inflamed stomach and intestines, for whatever reason, the absorbtion of folate and b12 decreases. As these decrease the inflammation increases further decreasing absorbtion.

http://en.wikipedia.org/wiki/Atrophic_gastritis
Atrophic gastritis (also known as Type A or Type B Gastritis more specifically) is a process of chronic inflammation of the stomach mucosa, leading to loss of gastric glandular cells and their eventual replacement by intestinal and fibrous tissues. As a result, the stomach's secretion of essential substances such as hydrochloric acid, pepsin, and intrinsic factor is impaired, leading to digestive problems, vitamin B12 deficiency, and megaloblastic anemia. It can be caused by persistent infection with Helicobacter pylori, or can be autoimmune in origin. Those with the autoimmune version of atrophic gastritis are statistically more likely to develop gastric carcinoma, Hashimoto's disease, and achlorhydria.

Atrophic gastritis is a condition of chronic inflammation and atrophy (tissue destruction) affecting the stomach's mucosal lining. Over time, atrophic gastritis leads to a loss of the gastric glandular and chief cells, a subsequent breakdown of the mucosal lining, and an eventual replacement of the mucosa by intestinal and fibrous tissue. ​

Atrophic gastritis has two causes: 1) an autoimmune process targeting parietal cells or intrinsic factor and 2) environmental causes such as persistent infection with Helicobacter pylori bacteria or dietary factors. Recent evidence suggests that Helicobacter pylori can trigger the development of autoimmune atrophic gastritis through a process of molecular mimicry in which the bacterial organisms take on the appearance of parietal cells.

http://autoimmunedisease.suite101.co...phic_gastritis​

As there becomes more information on methylfolate this is implicated too. Atrophic gastritis decreases the absorbtion of methylfolate thereby increasing the inflammation.​

These are vicious self perpetuating feedback cycles.​

​

​

 

I just wanted to share another possible reason for improvment of gut function on Rich's or Freddds protocol. THis abstract shows that oxidative stress can lead to pancreatitis and Rich's protocol has been shown to raise glutathione in his study.

Superoxide dismutase and catalase: a possible role in established pancreatitis.
Guice KS, Miller DE, Oldham KT, Townsend CM Jr, Thompson JC.

The mechanism of cerulein-induced acute pancreatitis may involve the production of free radicals in excess of the capacity of endogenous intracellular scavengers. These radicals destroy the cellular membranes, releasing digestive enzymes and cellular proteins into the interstitium. Thereafter, a cascade of events, including polymorphonuclear infiltration and complement activation, leads to pancreatic destruction. The present study demonstrates that superoxide dismutase and catalase reduce the ultrastructural and biochemical injury associated with cerulein-induced acute pancreatitis in rats. Pretreatment with superoxide dismutase and catalase 30 minutes before injury did not appear to be protective, presumably because the half-life of intravenous superoxide dismutase is only 6 minutes. This and similar studies suggest a potential clinical role for free radical scavengers in acute established pancreatitis.

 

Mercy, Lena, no wonder you've been having nausea problems. I'm glad to hear you're still proceeding, and would be very interested to hear what's going on with you (even though at this point I know a lot of it will probably not be rosy. But I'm rooting for you.)

Rich, that was a very interesting think-aloud, I also appreciated your comment over on the gut thread. It occurred to me that using the sublingual B12s bypasses the digestive system, which may account for why velha and I have had good gut results on that protocol. But of course that's not the only variable here, and the other supplements in the protocol go through the digestive system. I'm wondering if, as you suggest, the amount of gut damage is one crucial factor. I've been sick for only about 2 years; although I was tinkering with my diet pretty early on, my gut only broke down (weight loss & ever-more-prevalent nausea, and other symptoms) in about the last year. I'd be curious, velha, to know what your own time trajectory on this is.

Don't know if this is helpful, but I noticed (and still notice) nausea coming up (perhaps that wasn't the best of phrases to describe it) when I start or increase dosages of methylB12 and methylfolate, but NOT with adenosylB12. I'd be curious to know if others have specific gut reactions to specific supplements on this protocol. Of course if you're starting out with nausea, it can be difficult to tell; I couldn't say for sure about my reactions to other supplements in the protocol, but the ones I've listed were (and are) very distinct for me.

 

Suzy, that's true: glutathione levels do come up when the methylation starts working again. This stuff is one big complicated puzzle.

 

Freddd, I think I was on page 100 before and somehow missed your posts. I'm interested to see that for you, and in at least some research, methylB12 and methylfolate are the big players in digestive issues. I'll be interested to see if my own gut issues straighten out over time. If I'm "healing backwards", it would make sense that the gut issues might be up front for me, because I've only had serious problems for the last year or so.

Lena, my own gut got better on this protocol, but only after something like 6 weeks to 2 months of constant nausea in with other bad crashiness. I didn't even have anything as severe as Freddd's disgestive problems, and yours sound severe to me as well; I originally started out with a cast-iron gut. Now my gut has healed some, I'm amazed at how much more present I am and I'm wondering too if this wasn't part of my lessening brain fog. I hadn't realized how much energy it takes to be nauseated all the time, and how it kind of puts a cloud of wooziness between you and your daily activities.

 

Hi Sunday,

It came as a complete surprise to me that my near lifelong GI issues turned out to be mb12 and folate related. I had almost 200 symptoms and signs in all affecting every system of the body. My docs all said that there was no way at all that they could all be related. The tendency was to divide me up amongst at least 5 or more specialists. I saw a gastroenterologist for the first time in my 20s along with urologist, internist, neurologist, ENT, psychiatrist, neurosurgeon, orthopedist and I don't remember what else. Most of my symptoms of 7 years ago traced back along a progression to earlier forms in my childhood. My history is a description of how these things develop and progress. At no point did anybody suggest that all my problems were related except for the car crash damages. And nobody had much success in dealing with them. Most of them wanted to say "it's all in your head" except the psychiatrist. He said while I had a not unusual assortment of minor problems that I had a clean psychiatric bill of health and didn't really need to be seeing anybody until I wanted to work on my "mother" (abusive psychotic) issues. She took it personally that I was sick so much and took it out on me. She found other excuses for my sisters.

After about a year on the mb12 I did another ellimination diet after several before. This time, unlike the previous times, one thing only stood out loud and clear, milk and cheese. I was as surprised as anybody. I never expected that at 61 I would have virtually all of my long lasting problems, most dating back to childhood in various forms, clear up. I haven't had a strep, a pneumonia, bronchitis, sinus infection, urinary infection, cold, flu or anything else in 6 years. I had one relatively minor allergic episode when traveling to Ohio in hay fever season where the pollen counts can go over 1000. I lost 80 pounds of excess water. My blood pressure dropped so that 106/75 is very common now. I can walk down the detergent aisle at the suppermarket without sufficating. Perfume from 4 rows away doesn't make me retreat from the symphony. My skin is smooth with no infected folicles. I still get ingrown hairs from shaving though. I have exercise tolerance, have rebuilt deteriorated muscles, have arobic endurance and normal skin sensation. I sleep 7-8 hours of restorative sleep a night after 30 years of 5 hours or less of lousy sleep. The change in my life is utterly total. I can't begin to represent it. It doesn't sound real it is so extreme. The doctors and all their interpretations of tests and treatments were 100% wrong except for hypothyroid, antibiotics to fight infection and a couple of broken bones.

 

I just have to wonder why the medical establishment in the USA has settled on the worst possible treatment that has any minimal effect for b12 deficiencies and defends it so vigorously?

 

Sunday,

My gut shut down at the same time I became very ill - July/August 09. Digestion just stopped. So, mine has been short term also.

It is hard to say what has helped my gut the most. I can say the I noticed no effect with increasing doses of mB12 and methylfolate (at least not immediate). My gut began to improve in late December. I did a number of things at that time, two being increasing my adB12 (to daily) and carnitine dosages (~4g/day).

Interestingly, I was reading about Trikatu and was considering purchasing it to 'stimulate' my own digestive process rather than replace it with (acid and enzymes) and I realized black pepper was one of the ingredients. I added some and had very noticable improvement. I have continued to eat fresh ground pepper as often as possible and I believe it is helping a lot...

Velha

 

Hi, Sunday.

I think this is interesting. Methyl B12 and methylfolate both support the methylation cycle, while adenosyl B12 helps to move some fuel into the Krebs cycle to make ATP. Lifting the partial methylation cycle block supports the entire sulfur metabolism. The detox system depends to a large degree on the sulfur metabolism. Perhaps the nausea is a detox symptom.

Best regards,

Rich

 

Suzy,

Thanks for posting this. One of the nice things about a hypothesis that involves glutathione depletion is that it can explain problems in so many different cells, organs and tissues, and something with broad implications like that is needed to explain all the problems we see in CFS. That was what attracted me to it when I first heard about it from Dr. Cheney and then studied to see what glutathione normally does for us.

I've got some papers that show that a problem in methylation fwill interfere with production of digestive enzymes by the pancreas. I don't think the mechanism or mechanisms are completely clear, but it does seem that glutathione depletion could be involved.

Rich

 

Hi, freddd.

Thanks for posting this detailed history. I'm sorry that you had to go through all of this agony for so many years. It's wonderful that you were finally able to figure out what to do, so that you can at least have healthy years now. The functions of B12 are so important to every cell of the body, and I think that explains the widespread symptoms affecting so many organs and systems in the body, including the digestive system.

As we've discussed before, your response to glutathione precursors is pretty unusual, and as I've written before, I think it suggests a genetic issue in the enzymes that operate in the pathways between glutathionylcobalamin and the coenzyme forms of B12. For some reason, in your case, once glutathione got hold of the cobalamin to form glutahionylcobalamin, your cells were not able to convert it to the coenzyme forms of B12. I haven't encountered another case like yours in this respect yet. Have you?

Best regards,

Rich

 

Hi Rich,

For some reason, in your case, once glutathione got hold of the cobalamin to form glutahionylcobalamin, your cells were not able to convert it to the coenzyme forms of B12. I haven't encountered another case like yours in this respect yet. Have you?

I have encountered a number of similar, but not identical cases. The similarity was the quick effect of being thrown into a folate and secondarily b12 deficiency. Of the closest matches 100% were taking the active b12s and methylfolate at the time. They all developed what are generally described as "glutathione detox" symptoms which are identical with folate deficiency with a bit of b12 deficiency thrown in. One was a vegan who came by his deficiencies slowly via diet and the others are of unknown casues. They all experienced the vastly increased visible cobalamin in their urine for the duration of the precursors or glutathione. There were various combinations of precursors or even direct glutathione infusions. Since then a number of people have shown up here and at another board who all had "glutathione detox" symptoms and experienced recovery with larger doses of methylfolate and both active b12s. The combination hasn't failed to produce improvment for anybody of which I am aware.

The major difference was the relative severity with the rapidly induced neurological deterioration startup I experienced and it's long duration after the discontinuance of the precursors, 6 months, until I increased the methylfolate to 4800mcg daily from 800mcg. Then it was 75% gone in 3 days and the balance cleared quite suddenly about 2 months following that. Nobody else had such a prolonged experience after discontinuance. Possibly nobody else waited six months to increase the methylfolate, which came from somebody on this board I beleive, or another one. That was the uniqueness. I'm still at 3200mcg.

If you go out to various forums and find people experiencing "glutathione detox" I would predict that like every one I know of who tried the active b12s and sizable methylfolate doses, they would have rapid relief of the symptoms. This is true for all the ones I have found (only a few) without exception.

 

Hi, freddd.

Thanks for this information. Maybe what happens in these cases is as follows:

The methyl B12 is given in such a way (sublingually or by injection in large dosages) that most of it is free (unbound to transcobalamin) in the bloodstream. Taking glutathione precursors causes the liver and the red blood cells to produce and export more glutathione to the blood plasma. The glutathione reacts rapidly with the free methyl B12 in the blood plasma, forming glutathionylcobalamin. Now, the glutathionylcobalamin may not be able to enter the cells. I'm not sure about this, because I don't know how B12 forms get into the cells when they are not bound to transcobalamin. It may be by diffusion, and maybe glutathionylcobalamin doesn't diffuse in as well as methyl B12 and adenosyl B12 do. Another possibility is that some people's cells can't convert glutathionylcobalamin to methyl B12 or adenosyl B12, because of genetic issues with the enzymes that do that.

Best regards,

Rich

 

Hi Rich,

Yes, I agree a lot. The glutathionylb12 hypothesis was my first approximation answer. As it progressed and the folate deficiency symptoms that predominated were not relieved by increased doses of mb12 and adb12 I modified it. First, the effect of methylfolate on urine. When I started 800mcg, the amount of mb12 I could inject to get a Just Noticable Difference in urine color for one occasion was 2.5mg. Within 8 hours of taking methylfolate I could increase to 4.4mg. Within a week, 5mg for the same JND of color shift. Within hours of glutathione precursors I had a urine color not seen except with 25mg injections previously, all day instead of just a few hours. After discontinuing glutathione precursors the color faded a bit but was still quite high, perhaps at a 15mg level. This continued unchanged despite 800mcg of methylfolate daily. After 6 months I took 4800mcg of methylfolate and the color disappeared 100% within 2 hours for almost a week. After a week or so color came back at a the JND level at 7.5mg injected (with 800mcg previously) with 10mg actually injected and stayed there. The amazing difference in coloration related to methylfolate is hard to ignore. The adb12 deficiency symptoms came back slowly, as if I wasn't taking any but no faster. The mb12 deficiency symptoms also came back at the rate of not being taken. The folate symptoms came on hard starting in hours, as if antagonized. There was no acne as I might find with hydroxyb12 or broken down mb12. Everybody had primarily folate deficiency symptoms with a smattering of b12 deficiency symptoms. After several weeks mood/personality changes came on hard. As we have been putting it at another forum, "Mr Hyde" came out as the kindly Dr Jeckyl went into hyding.

The reason this appeared confined to those taking mb12, adb12 and methylfolate was that these all represented return of symptoms previous relieved. Those not taking these items merely had some increased severity in existing symptoms and called it "glutathione detox symptoms". So which protocol, if either, a person was on determined their perception and naming of the symptoms increase.

 

Velha, that is so interesting! Since I got sick (actually, looking back, probably as it was coming on), I've been avid for fresh-ground pepper - something which I never had much taste for before.

 

Sunday,

I almost didn't mention the pepper thing, but I really think it is significant. I've been eating a completely controlled and predictable diet. I've been using betaineHCl and digestive enzymes with each meal. There were predictable consequences when I didn't. For that reason I was looking into Trikatu, an ayurvedic digestion stimulant. Black pepper is included (I believe).

On Christmas day I ate some food at a relatives that was not self prepared - it was what I usually eat with the exception that it was LOADED with whole black peppercorns. I forgot to take my betaineHCl or digestive enzymes and assumed I would have poor digestion as a result. To my surprise my digestion was improved over normal. I have been eating lots of pepper since...

I'm still considering the Trikatu, but for now - if there is something I can do that helps and does not involve another pill I'm very happy to include it in my regiment...
Velha

 

The major difference was the relative severity with the rapidly induced neurological deterioration startup I experienced and it's long duration after the discontinuance of the precursors, 6 months, until I increased the methylfolate to 4800mcg daily from 800mcg. Then it was 75% gone in 3 days and the balance cleared quite suddenly about 2 months following that. Nobody else had such a prolonged experience after discontinuance. Possibly nobody else waited six months to increase the methylfolate, which came from somebody on this board I beleive, or another one. That was the uniqueness. I'm still at 3200mcg.

Hey freddd/rich and all, I was just reading about "overmethylation" it says that some people are "folate deficient" with overmethylation. I'm interested is raising my does of methylfolate as freddd describes. I assume that would that be considered addressing the "folate deficiency" they are talking about in overethylation?

Another point. I am doing 2400 mcg a day of methylfolate and it does't seem to effect me, maybe I still need more as you reccommended fredd..... I'm just curious if anybody you know has tried a product called deplin http://www.deplin.com/ used for depression. I guessing this the same methylfolate we use here?