I'm interested in info abt supplementing with B12 forms, that may actually bring about noticeable, & sustained improvement of a whole range of symptoms. (Can understand when these bring about little or no improvements, people will resort to injections, including on self !).
Ignoring the synthetic, lower cost & faster dispelled cyano-, the 3 natural forms are, methyl-, adenosyl- ... & hydroxo- cobalamins. I suspect different pple have had, & will have, varying experiences with these forms. And what daily doses & frequencies (per day!) have pple tried?
Seems for some, even a daily dose of 1+mg B12 ( - of a particular form, so 1000+ug) over several months may not be enough to bring about noticeable benefit, in part bcos being water soluble, it tends to be expelled rather readily! What maximum daily amount taken, & in how many doses, have pple have tried, ... or come across? And which forms? The timing of these, especially relative to meals, may be an important consideration too, surely?
[ Interestingly, more products are becoming available with the two ( - said to be 'active') methyl- & adeno- forms! Some of these products are also pretty good value now, with packs of 365 tablets, . . . for ( -'up to', ... for present consideration!) a year's supply !].
All thoughts, info & personal experiences appreciated. Am wondering if only supplementing with one form cld be a major factor in seeing N⛔ discernable benefit, . . . & not just the daily dose, & frequency!
AtB,
Sid 😑,
Saturday 27 May 2023, . . . on a 🌞nny summer's day !
Forget tablets. Too little get absorbed. Oral B12 supplements can only be absorbed passively and only about 1% of the B12 supplement will make it into the blood. The body can only efficiently absorb a small amount of B12 within a given period of time. In order to help B12 absorption it is recommended that you divide the dose over the course of the day. So I dilute B12 liquid and drink it. It gives my intestines a larger volume of B12 so it is able to absorb more. I also takes lots (15000mcg daily).
Taking B12 this way means I can tailor my daily dose and that gives me more control over my situation. For example if I exercise a lot or have a stressful day I find my B12d symptoms returning. So I take more B12 to correct this
I did try the adeno form thinking I was missing a trick but I didn't notice any benefit. My B12 liquid is cyanocobalamin. It is supposed to be absorbed slightly better within the body than methylcobalamin. Methylcobalamin is retained in the body longer but that doesn't matter to me as I am drinking B12 all day long.
What matters to me is that it works. I was in a terrible state before and now I am almost 'normal'.
I dilute high strength sublingual B12 in water ( one dropper full in approx 8 oz water) and drink it through the day. It also makes sure I drink enough water.
the 15000 is indeed interesting. I am currently on approx 9000 mcg daily in divided doses of different types - a methyl 1000mcg tablet first thing, three doses of methyl liquid and the balance in between as sublinguals - methyl/adenosyl 500/500 and hydroxo 1000. Might try increasing and adding liquid to a larger quantity of water as per charks.
Your link (below) is really interesting, but you have to wonder why they only used folic acid to increase folate and say that MTHFR issues "are associated with requirements for higher doses of folic acid". What about folate/methyltetrahydrofolate as an alternative? They say that many have SNPs affecting processing and that some are poor folic responders but give no study trying an alternative (although they use the methyl or active forms of B12). Unless I'm missing something of course. I didn't do well with folic but got a significant 'jump' of improvement with folate, and not at high dose - just a moderate amount did the job, which would surely be preferable to having the risk of unmetabolised folic acid in those folk who can't use it, or not use it well.
. . . think that it was 'a cross-sectional survey' . . . rather than a clinical trial, . . . may have something to do with it ? Pple were already taking, what they were taking, . . . rather than being given it from the start of a trial ? And probably taking 'folic acid' . . . knowing no better, given its greater availability at the ⏳, . . . up to date of 2015 paper ?
(( Something darn strange going on with this cobalamin biochem in the chronically unwell, . . . given the RDA ( - for the healthy!) . . . is said to be ~2.4 ( - two point four!)ug/day, . . . & the body can have stores of a year, . . . or, much more depending on the source of info one cites !
This MUST BE the FIRST ⏳ in HISTORY that so many pple hv been taking such huge . . . 'supra-physiologic' doses . . . in order to gain relief from symptoms of long term conditions, . . . - & in most cases, . . . indefinitely ??❓Yes, they reduce certain classes of toxins effectively, . . . which can result in symptom-reduction, . . . but the underlying pathology remains, . . . just feeling less unbearable ??❓)).
AtB,
Sid 😑,
Tuesday 30 May 2023, ... after a 3rd May Bank Holiday, uniquely ! 😊
I agree that they were taking what they were taking, but they were being prescribed it, and in increasing doses, and the study of the paper's own group of ME patients still states that they need to increase folate by giving more folic. It is very sad and short-sighted. Methylfolate is the only form which crosses the blood brain barrier and it was regularly in use (from a quick search) by 1990 for enhancement of recovery from psychiatric illness and discussed in neuropsychiatry of megaloblastic anemia in 1980.
It is good that they touch on toxins such as mercury though, but no mention of lead which is especially B12 dependant.
Body stores are basically irrelevant, because you cannot store what you cannot produce and absorb normally. We are only taking in enough for basic immediate needs (and excreting excess and/or it becoming 'inactive') and our deficiency will quickly deplete any useable stores which we might have been able to accumulate when less unwell. Some people may be able to store and access the stuff, but not all of us. If the series of processes involved in the very complex folates cycle are not working effectively, we will most likely need to support that indefinitely (and not only with B12 and B9 in the appropriate vitamers for us personally).
. . . well, at least we hv a clearer idea of what levels of B12 & B9 seem to bring abt meaningful ( - 'mild' or 'much') improvements ( - in one small sample!) ! 😊
Note the B9 levels are MUCH higher than one would usually consider as 'adequate' . . . ??! Hmmm, . . . - so wondering if 600ug/day wld be enough ( - as methyl folate) . . . but d⛔n't seem to be feeling the effects since started ! Cld there be a ⏳-delay, . . . of up to 2+wks, . . . in feeling the benefits, tho' . . . even with the actual ( - supra physiologic seeming!) adequate doses ??!
Alternatively, . . . is one of the other B vits . . . actually more involved in the 'rate limiting' step to feeling better . . . ? D⛔n't know . . . yet !
AtB,
Sid 😑,
Tuesday 30 May 2023, ... after a 3rd May Bank Holiday, uniquely ! 😊
Enjoy yours - its 'a gift', . . . also called 'a present' 🎁 ! 😊
Absolutely - it is not just about B12 and B9, nor even B6, but all of the B vits together, and not about homocysteine either. Have a look at mdpi.com/2072-6643/8/2/68, especially Fig 2 (methionine/folate cycles).
High folate should not be necessary for most. I did get as far as approx 1000mcg briefly but read that less should be enough so settled on c 400 mcg in three divided doses daily.
Great post and I am on a similar journey to try to maximise my good health and minimise symptoms.
I have been increased to self injecting subcutaneous 1500ug DAILY for about two months now and I have noticed a big improvement in the quality of my life.
As expected, as I feel better I do more physically but if I am more active and have fewer symptoms I must be going in the right direction for me.
I have noticed that if I have a busy day my urine appears to contain more B12 as it has a stronger yellow/green hue and brain fog and irritability creep in towards the end of the day. However, when I have a physically more restful day, my urine appears much lighter in colour and I have no symptoms.
Now I am wondering what this may suggest as a non medic and purely so I can rationalise what my body is doing. I am thinking that my body priorities the B12 to provide physical energy I need over healing. When providing physical energy less B12 is used than when healing.
This may explain why after consecutive busy days I begin to feel unwell and emotionally low - as too little B12 was used for healing?
I am finding that I am improving with a rest day after two days of busy although I can extend to more busy days but the recovery is not comfortable.
I am currently also trialling a B12 injection in the morning followed by four hours physical resting before activity in the afternoon. This combo is also having positive results and my urine is a very light hue suggesting more B12 has been used.
I know this is not very scientific but it may give you an insight into how to tailor your self treatment 🤗🤗
. . . your clear observations are VERY scientific, . . . certainly ! 😊
. . . an alternative (potential) 'explanation', hypothesis/conjecture abt yr experience is that on y/our busier days, you/we produce more of the waste products ( - homocysteine, MMA etc?) which the B12 compounds are S🍥 g🍒d at moping up ? Wonder if that sounds to you ? This suggests adequate amounts of rest & relaxation are required to 'detoxify' the body, . . . which has (at least) two sides - less waste produced, . . . & more energy for the body to remove those that have accumulated, . . . from the preceding activities. The PEM - post exertional malaise - common in CFS/ME, & also fibroM, would seem to be adequately enough explained by a (delayed) build up of such , . . . in the first instance ??!
Thanks for taking the ⏳ to sharing your valuable experience. Not sure what though you've given to the MUX of the 3 B12 natural forms.
AtB,
Sid 😑
Sunday 28 May 2023 ... - on a quiet a.m. w' Desert Island Discs on ! 😊
I guess though not scientific, but it’s a reality that B12 deficiency recovery is not still that scientific that we have to go by symptoms. I feel the same more or less as some days I feel energized and happy than the other days as in which I have more physical activity ( just normal physical activity and I still can’t work out yet) or I have some stressful days so I need to rest more and calm myself down to be back on the track! Good point about the urine color which I haven’t noticed, but I would also consider tracking it. What I realized in general that my urine color is whiter than before starting my B12 injections generally.
. . . seems folate/folic acid may be important, . . . as well as vit B6, as P5P, rather than pyridoxine ( - not mentioned in the paper?) ! 😊
Pleased to know you've made g🍒d progress, . . . descending yr Mt 🗻 Sickness, as I think of it ! Feel my descend has barely commenced . . . finally, . . . yet precisely on ⏳ . . .❓❓❗
AtB,
Sid 😑,
Saturday 27 May 2023, . . . on a 🌞nny summer's day !
Here's a portion of the text of that 2015 paper cited above, for convenience ( - & hope I'm n⛔t inadvertently infringing copyright!):
Logo of plosone
PLoS One. 2015; 10(4): e0124648.
Published online 2015 Apr 22. doi: 10.1371/journal.pone.0124648
PMCID: PMC4406448PMID: 25902009
Response to Vitamin B12 and Folic Acid in Myalgic Encephalomyelitis and Fibromyalgia
Björn Regland,* Sara Forsmark, Lena Halaouate, Michael Matousek, Birgitta Peilot, Olof Zachrisson, and Carl-Gerhard Gottfries
Abstract
Background
Patients with myalgic encephalomyelitis (ME, also called chronic fatigue syndrome) may respond most favorably to frequent vitamin B12 injections, in vital combination with oral folic acid. However, there is no established algorithm for individualized optimal dosages, and rate of improvement may differ considerably between responders.
To evaluate clinical data from patients with ME, with or without fibromyalgia, who had been on B12 injections at least once a week for six months and up to several years.
38 patients were included in a cross-sectional survey. Based on a validated observer’s rating scale, they were divided into Good (n = 15) and Mild (n = 23) responders, and the two groups were compared from various clinical aspects.
Good responders had used significantly more frequent injections (p<0.03) and higher doses of B12 (p<0.03) for a longer time (p<0.0005), higher daily amounts of oral folic acid (p<0.003) in good relation with the individual MTHFR genotype, more often thyroid hormones (p<0.02), and no strong analgesics at all, while 70% of Mild responders (p<0.0005) used analgesics such as opioids, duloxetine or pregabalin on a daily basis. In addition to ME, the higher number of patients with fibromyalgia among Mild responders was bordering on significance (p<0.09). Good responders rated themselves as “very much” or “much” improved, while Mild responders rated “much” or “minimally” improved.
Frequent injections of high-concentrated vitamin B12, combined with an individual daily dose of oral folic acid, may provide blood saturations high enough to be a remedy for good and safe relief in a subgroup of patients with ME/FM. Moreover, we suspect a counteracting interference between B12/folic acid and certain opioid analgesics and other drugs which have to be demethylated as part of their metabolism. Furthermore, it is important to be alert on co-existing thyroid dysfunction. These issues should be considered when controlled trials for ME and fibromyalgia are to be designed.
I use a sublingual spray and I have found that really effective when I get my levels tested I am always extremely over supplementing . I use 4 sprays a day . You don’t have to worry about when or on an empty stomach . I tried the skin patches too but not for long enough to know if they work but a friend says she has found them good she also uses the rub in cream too . Sublingual and transdermal avoids the issue of metabolism
I use the better you spray I tried others but for example the Aldi one tests funny . It has to be sprayed under the tongue so I don’t get it on my teeth usually and if I do i can’t say I notice any sensitivity and my teeth are sensitive
5 mg SL liquid methylcobalamin/adenasolcobalamin 66%/33% three times a day at the same time as injections and extra as needed.
Pyridoxal-5-Phosphate .25 mg liquid in water twice a day.
“Simple Spectrum ” 1/2 scoop 2.4 g in juice twice a day in lieu of B-complex. Which includes 20 mg of B6 in the form of Pyridoxal-5-Phosphate and .35mg of B12 in the form of methylcobalamin.
6 mg Adenasoyolcabalamin three times a day SL tablet.
Wow! That's a lot of B12. It must be costing you a fortune. When do you think you will start reducing. Or will you play safe and continue your regime for ever.
. . . g🍒d for you - use what works, . . . seems to work & review regularly, . . . makes sense ! 😊
. . . however, I've just come across the IF needed to absorb the B12 into the bloodstream being/becoming the 'rate limiting' factor - suggesting that smaller doses every few hours, up to a point ( - in ug) wld be better absorbed that one/fewer doses per day. This points to the far greater effectiveness of admin by 💉s !
AtB,
Sid 😑
Sunday 28 May 2023 ... - & gently into a 🌞nny pm ! 😊
Intrinsic factor is the natural human mechanism for B12 absorption. If you have PA, you typically have no (or almost no) effective intrinsic factor, this is why those with PA become B12 deficient. The only available oral absorption route for B12 at that point is passive absorption which occurs at 1% of the dose. I have not read anything that suggests passive absorption can be saturated. It's not the "natural" way the body expects to receive B12 but it does work, at least in theory even with PA, because it doesnt require intrinsic factor at all and is thus not subject to that mechanisms saturation limit. But in reality, most seem to find injections are necessary and oral doses not matter how high, do not adequately treat symptoms.
. . . yes its useful to have a feel for REALISTIC absorption rates, whether with IF* thru the gut, . . . or directly, say sub-lingually !
Know I felt N⛔ discernable difference with B12 patches, as I believe many haven't ( - & others report they do ! 😯❗).
Liquids, as drops COULD be absorbed better than tabs & capsules, for those w'n⛔ IF issues . . . as a general rule??❓ That's the feeling I get, but don't recall seeing any hard comparative data. But then, the liquids ( - & sprays) may be more unstable, require refrigeration, or contain more presevative, like glycerol ( - not sure if there's any issue with small daily doses of glycerol, whether of veg origin or other!).
D🎯 think IF* - as the 'boat' to carry the B12 into the bloodstream - can be limited in those with no known IF* issues ( - therefore, this being the rate of absorption limiting factor, when LARGE B12 doses are taken orally. S📀, . . . large doses spaced thru the day may well be more effective ( - by a bit?) than fewer even larger doses, in those with normal IF* function.
A 1% or so, absorption rate for drops/sprays ( - direct absorption, ... w' N⛔ IF*) would mean for every 1000ug dose, . . . only ~10ug of B12 is being absorbed - which even taken several ⏳s a day, compares poorly to say getting 500ug-1500ug doses by 💉.
Therefore, inclined to agree that "most seem to find injections are necessary" . . . & this may well be the case for those with even N⛔ known/apparent IF* issues ! (When will the NHS & NICE recognise this, . . . as clearly, we cld wonder ??!).
AtB,
Sid 😑
Tuesday 30 May 2023 ... - & gently into the evening pm ! 🌓 😊
*IF - intrinsic factor, ... for absorbing the B12 into the bloodstream.
I started SI-EoD with Cyno in the first week of April and at the same time, I was taking sublingual meth every day since I had neurological symptoms like numbness, tingling, muscle stiffness, fatigue, etc. My symptoms started to improve, and I felt more energized and happy then a few days ago I stopped taking sublingual just to see how my body reacts, and I shifted from Cynoto Hydro all of a sudden and I heard it last longer in body. So first I only tested Hydro one shot so I can’t tell the difference yet and second after stopping the sublingual, I feel I have some symptoms back like neck pain and muscle stiffness (of course, not as severe as before) in the last three days but I also was stressful so again I can’t tell it’s because I stopped sublingual or it’s because I was stressful but I think reducing the dose is the main reason. I want to stay on Hydro EoD, and perhaps within 10 days or so, I can say if I fill differently from Cyno. The symptoms tracking is a bit weird in the sense that one week you feel strong and symptom-free and then again when you don’t expect some symptoms show up and then make you a little bit frustrated but I think it’s the same path for everyone and as I have not started so long ago, I would expect some flare-ups on the way, but I want to stay positive and hopeful and find the best recovery path. BTW I would recommend stopping taking alcohol for a while as it harms your recovery.
. . . yes, staying '➕ve & hopeful' . . . can help, . . . - & perhaps related to this, . . . reducing identifiable 'awfulising & catastrophising' can be helpful habits to ponder on, & practice, practice, . . . & erm, . . . PRACTICE. This 'is' the psychological, cbt, . . . or REBT side - found valuable by many !
. . . the alcohol is already NIL, . . . as decades ago, I became intolerant to it ( - a significant sign of being metabolically unwell, perhaps ?!!). 😊
Hello! I am in full remission on weekly self intramuscular injections of hydroxo under doctor’s direction. Diagnosis was 7 years ago but getting adequate injections was a journey. I would say it took a couple of years of weekly injections to finally achieve where I am today.
Weeklies appear to be my adequate maintenance dose to prevent reoccurrence of symptoms—and I pretty much had them all. I discontinued injections early on and went with high daily doses of methyl and became the sickest I have ever been in my life in only 3 months.
I never received loading doses. Monthly at first and then weekly after no injections. Weeklies were cut back to every other week when bloodwork showed levels over 2000. I could never get better on every other week injections.
My diagnosis was age 44 but I had suffered early symptoms for many years leading up to the discovery. I began suffering gastrointestinal problems in my 20’s and think it’s possible I may have been suffering deficiency symptoms as early as then.
Best of luck to you and I hope you feel better soon!
You said: 'I discontinued injections early on and went with high daily doses of methyl and . . . ' - do you mean you changed to tablets or drops by this . . . ?
. . . & were/are yr 💉s of hydroxocobalamin ?
Hv you tried supplementing, in addition to your 💉 s ?
Yes,. I took 3-5,000 daily units methyl sublingual tablets. I also tried liquid Adenosly/hydroxo as I got sicker and believed it was the form of b12 I was supplementing not the obvious that I needed injections—so I changed. It think it was 5,000 units? It took me a while to realize I might need injections as my mind was not working properly.
My severe anxiety was non-stop and I could barely drive to the doctor when I finally realized what it might be. I still was not sure but my primary care doctor gave me an injection and I was significantly better within 3 days so I knew we were on the right track.
I did take Adenosly liquid with injections also but there seemed to be no difference in symptoms. I played around with the dosage to see if it made a difference. My doctor and I agreed it was not working and was a waste of money. I had hoped to reduce the number of injections by using it and to help me feel better as I was never free of symptoms on every other week injections. There was no change when I discontinued oral supplements, relying solely on injections.
My gastro doctor found the deficiency. He rechecked my blood after two monthly injections and I was also supplementing daily 1,000 units—might have been cyano —I don’t remember—because a week after an injection, I was crashing. The numbers didn’t rise as they should’ve with both injections and daily sublingual. He realized this and told me that he thought I was going to have to go back on injections.
Problem is that he did not explain this to me so I didn’t think it was a big deal and I believed in my mind that I could just supplement orally. I did not know that the reason I needed to go back on injections was because I wasn’t absorbing the oral b12. I had zero understanding of b12 deficiency at the time.
I have been on hydroxocobalamin since the fall of 2016. It is not common in the US, but I started using it at a private clinic that offers b12 injections without rx as I was not receiving adequate treatment and was very symptomatic. I was doing so well on it that I asked my doctor to change my rx from cyano to hydroxo when I went back to see her again. I was starting a new job and had to learn to self inject because I wasn’t going to be able to take off work for weekly injections that I was receiving at the time.
I was subsequently cut back to every other week injections based on lab results. I suffered a significant setback and resumed weekly injections. I have been on weekly hydroxo injections for nearly three years straight. Though it has taken a long time, I consider myself to finally be in full remission. Had I received loading doses in the very beginning and remained on weekly injections, I know that I would’ve recovered years sooner.
The bottom line is that some people are able to absorb some while others are not at all. I wish that I was one of the ones who could but unfortunately for me-it is lifetime injections. I hope this helps you!
. . . that, MicroWoo, . . . REALLY is a FAB reply ! 😊 Thank y💞u . . . very much ! This reply's very clear & helpful !
As well as being of interest to me, . . . I think it'll be of use to MANY others.
. . . & very pleased to know you're now 'in full remission' . . . albeit belatedly ! Sadly, such delays in getting the right treatment remain too common, . . . - & usually for no acceptable reasons . . . ! 😕
AtB,
Sid 😑
Sunday 28 May 2023 ... - & gently into the pm (at Brit ⏳ - BST!) 😊
Indeed, while I wish that it had not taken so long to get better, I am forever grateful to the doctor who found my deficiency and to the doctor who did the research on PA to adequately treat me. I am just grateful to be where I am today without permanent damage. While I suffered unnecessarily, I did learn a lot about PA along the way and I have a full appreciation of how destructive B12 deficiency can be to the body and mind.
. . . yeah, the bottom line seems to be you survived your longer term medical mishaps/failures of an apt diagnosis . . . & now from a better place are willing to share the benefits of your experience with others, including here on HU ! 😊
Pleased to hv yr contributions, MicroWoo ! 😊
AtB,
Sid 😑
Sunday 28 May 2023 ... - & gently into a 🌞nny later pm ! 😊
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B12 Deficiency getting worse with supplementation?
Loading doses b12
Adenosylcobalamin
