Discussion in 'Diagnostic Guidelines and Laboratory Testing' started by seethatlake, Jul 17, 2017.
Was that active B12 holo-transcobalamin?
As per @Asklipia 's hints, I have been reading more of dr. Lonsdale's work (he is 93 yo!). I found a mention to an experimental veterinary study (enclosed) which used Nicotinic Acid (B3) to activate thiaminase (which destroys thiamin). I wonder if and how this applies to humans. Would this explain my Niacin intolerance? (Nicotinamide is even worse). However, I feel benefits if I stimulate Tryptophan breakdown into B3.
I don't know. Just says Active B12. Can you explain how it makes a difference please?
I could check with the lab to find out.
Usual serum cobalamin with my lab has a range of 187 - 883 pg/ml. Mine in average has been 1637.
Holo-transcobalamin with my lab has a range of > 50 pmol/l. Mine has been >128.
So I wondered if they were in any way comparable.
Despite high enough holo-transcobalmin, B12 serum, and B6, B9 serum and whole blood levels and supplementing sufficient TMG and choline too, my homocysteine levels haven't been consistently optimal yet. So at least holo-transcobalamin obviously doesn't tells the whole story.
Interesting, thank you. My test was done by Doctors Laboratory, London. Is this all to do with methylation problems or is it something else?
Interesting. I had assumed that niacin depletes thiamine by increasing its utilisation. Thiaminase activation could be another avenue, although my search on the internet only showed this as a problem for ruminant animals, nothing mentioned about humans.
Maybe you need to resort to transdermal B3.
I will try that, thanks for the suggestion, but I am afraid this will cause me the same intolerance I have to transdermal progesterone and haven't found the explanation to it yet ( @jjxx ).
If I recall correctly, I didn't have the article saved about tryptophan is diverged to produce B3. And if you are still looking for it, I did find another source which is more reliable than the original article I mentioned;
Excerpts from Linus Pauling Institute website:
In addition to its synthesis from dietary niacin, NAD can be synthesized from the dietary amino acid tryptophan via the kynurenine pathway (see Figure 2 below). The relative ability to make this conversion varies greatly from mice to humans. The first step is catalyzed by the extrahepatic enzyme indoleamine 2,3-dioxygenase (IDO), which is responsible for the oxidative cleavage of tryptophan. The chronic stimulation of tryptophan oxidation, mediated by an increased activity of IDO and/or inadequate niacin levels, is observed in a number of diseases, including human immunodeficiency virus (HIV) infection (see HIV/AIDS). In healthy individuals, less than 2% of dietary tryptophan is converted to NAD by this tryptophan oxidation pathway (14). Tryptophan metabolism plays an essential regulatory role by mediating immunological tolerance of the fetus during pregnancy (15). It is now understood that tryptophan oxidation in the placenta drives a physiologic tryptophan depletion that impairs the function of nearby maternal T-lymphocytes and prevents the rejection of the fetus. However, the synthesis of niacin from tryptophan is a fairly inefficient pathway that depends on enzymes requiring vitamin B6 and riboflavin, as well as an enzyme containing heme (iron). On average, 1 milligram (mg) of niacin can be synthesized from the ingestion of 60 mg of tryptophan. The term "niacin equivalent" (NE) is used to describe the contribution to dietary intake of all the forms of niacin that are available to the body. Thus, 60 mg of tryptophan are considered to be 1 mg NE. However, studies of pellagra in the southern US during the early twentieth century indicated that the diets of many individuals who suffered from pellagra contained enough NE to prevent pellagra (10), challenging the idea that 60 mg of dietary tryptophan are equivalent to 1 mg of niacin. In particular, one study in young men found that the tryptophan content of the diet had no effect on the decrease in red blood cell niacin content that resulted from low dietary niacin (16).
Thanks. I found out that Biotin is also a limiting factor because BCAAs can impair Trp metabolism (and Biotin is needed in BCAAs metabolism).
What do you do to successfully stimulate the tryptophan to B3?
Trp food at dinner and B2 + B6 + B7 (+ B5 for melatonin) at bedtime
Lonsdale did indeed find a connection between B12/folate and B1 -- he talks about several different case histories in his book, including one where a six year old kept getting high fevers, swollen glands, sore throats, etc.. His curiosity was piqued when the mother asked him to test his B12/folic acid levels, as apparently they had been high the last time he had an 'attack'. Sure enough, they were high:
"I found that he had definite evidence of vitamin B1 deficiency and started giving him this vitamin. He was sent home form the hospital, and when I saw him again in a month or so he had not had any more of his attacks and was well in every way. I measured the two B vitamins in the blood again; they were now in the normal range."
He then got permission (reluctantly) from the mother to stop the B1, and within 2-3 weeks the fever and swollen glands returned, and his blood levels of B12 and folic acid were again elevated. He repeated the 'large doses of B1', and he was 'well again within five days' -- and B12 and folic were 'close to being normal again'.
Lonsdale's conclusion was the B12 and folic acid were elevated because:
"They must be activated in the body, a complex biochemical process which requires energy. Since his requirement for vitamin B1 had not been met, he was deficient in this energy and the two vitamins were not being activated. They were present but not biologically activated and were simply piling up in the blood."
You could be right about that.
I have run into a lot of trouble and presume I have unbalanced something else - not surprising and not unexpected given the large doses of benfotiamine.
Actually things have become so intolerable that I have stopped the benfotiamine and just continued with 50 mg allithiamine.
With the benefit of hindsight there have been some suggestions of this before I embarked on the benfotiamine experiment but it was hard to pin down. Now there has been a variety of symptoms which have been very obvious and getting worse - headache, nausea, anxiety, sleep disturbance, generally feeling hyped up.
I cut back the benfotiamine considerably then stopped altogether while I rethought.
I have been experimenting with 100-200 mg doses of niacinamide taken several times a day and it has definitely settled things down a lot.
I'm missing the benfotiamine a bit - think I still need some though not nearly as much as previously and will reintroduce once I have stabilised things with the niacinamide.
How about Niacin? I suppose the body can convert it to Niacinamide but can't convert Niacinamide back to Niacin.
Obviously it is a personal response, but I feel no benefits from Niacinamide (all I get is a decreased tolerance to smells) while I get an energy boost from Niacin (I just wish I tolerated it without flaring symptoms of high uric acid).
I have had problems with niacin in the past but have always found a dose of 50-100 mg niacinamide at night is very calming and helpful to sleep.
I do intend to try niacin again as part of this experiment.
I was severely depleted of B12, but homocysteine was 3. Turns out I was depleted in methionine so couldn't make homocysteine to recycle to methionine. Sort of a vicious cycle.
Very interesting. So this is like the next stage of severity.
Yes, it is. My doctor was quite surprised...
Taking methionine brought it up to 6.
Can anyone comment on these results?
My active (holo-transcobalamin II) B12 levels are just slightly exceeding the high side of normal, but nearly 50% of total B12, which is low-ish normal. Serum folate is deficient.
Based on my limited understanding active B12 is generally between 10 and 30% of the total. What does it mean to have such a high proportion? (My mum got similar results back but her active is even higher at 60% of total.)
Total Vitamin B12: 352 pmol/L
(Deficient <140 / Insufficient 140 - 250 / Consider reducing dose >725)
B12-Active: 167.9 pmol/L
(25.1 - 165)
Serum Folate: 4.25 nmol/L
(8.83 - 60.8 nmol/L)
No obvious signs of anaemia or abnormal red blood cells.
Tingling in feet, poor sense of balance, twitchy muscles, tinnitus but all these have been present for years. Recently, walking is becoming increasingly awkward in that it feels stilted and I almost trip up quite frequently.
You can also try a Google Site Search
Separate names with a comma.