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Role of Biotin in methylation

Messages
46
Hi,

One of the threads in the general treatment section asks people to list the supplements that they have found most effective. When I looked at it Biotin (which is a B vit) was commonly listed. Does anyone have a theory on how this links with methlation or doesn't it?

Don
 

richvank

Senior Member
Messages
2,732
Hi, Don.

I don't know of a link directly with methylation. If a person has HPU (hemopyrrollactamuria), this will deplete biotin as well as P5P and zinc, and it will also block methylation and associated pathways because P5P and zinc are needed as cofactors.

I do often see in urine organic acids panels from PWMEs that the marker for biotin is showing biotin deficiency.

Best regards,

Rich
 

brenda

Senior Member
Messages
2,262
Location
UK
Rich

Would you mind saying which is the marker for biotin deficiency? Thanks.

edit - Also, I am wanting to understand the results I have from my OAP because at the time I had it done, I was supposed to visit a doctor (in Germany) but I was too sick to make the journey and he would not do it over the phone, so I am looking for a site that can help me to work it all out so that I have valuable information to help me in doing the methylation protocol.

Brenda
 

richvank

Senior Member
Messages
2,732
Rich

Would you mind saying which is the marker for biotin deficiency? Thanks.

edit - Also, I am wanting to understand the results I have from my OAP because at the time I had it done, I was supposed to visit a doctor (in Germany) but I was too sick to make the journey and he would not do it over the phone, so I am looking for a site that can help me to work it all out so that I have valuable information to help me in doing the methylation protocol.

Brenda

Hi, Brenda.

It depends on which urine organic acids test you run.

Great Plains Lab OAT: Methylcitric

Genova Diagnostics Metabolic Analysis Profile: 3-Hydroxyisovaleric acid

Metametrix Organix: beta-hydroxyvalerate

A high value for one of these indicates low biotin.

I'm pretty swamped, but if you email your results at richvank at aol dot com, I will try to get to them when I can.

Best regards,

rich
 

rydra_wong

Guest
Messages
514
Hi, Brenda.

It depends on which urine organic acids test you run.

Great Plains Lab OAT: Methylcitric

Genova Diagnostics Metabolic Analysis Profile: 3-Hydroxyisovaleric acid

Metametrix Organix: beta-hydroxyvalerate

A high value for one of these indicates low biotin.

I'm pretty swamped, but if you email your results at richvank at aol dot com, I will try to get to them when I can.

Best regards,

rich

Very useful info - thanks Rich. I had a metametrix test via directlabs so no interpretation. I bought their little booklet but it didn't tell me that about biotin!

I read (posted elsewhere) that biotin helps govern whether to use the pyruvate cycle or the Kreb cycle (huge difference in energy produced) but I have no idea why -- I dont see it in the Kreb cycle...I wonder if it's true...
 

LaurieL

Senior Member
Messages
447
Location
Midwest
http://www.ncbi.nlm.nih.gov/pubmed/17182796

J Nutr. 2007 Jan;137(1):25-30.

Biotin deficiency inhibits heme synthesis and impairs mitochondria in human lung fibroblasts.

Atamna H, Newberry J, Erlitzki R, Schultz CS, Ames BN.

Source
Nutrition and Metabolism Center, Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA.

Abstract
Four of the 5 biotin-dependent carboxylases (BDC) are in the mitochondria. BDC replace intermediates in the Krebs [tricarboxylic acid (TCA)] cycle that are regularly removed for the synthesis of key metabolites such as heme or amino acids. Heme, unlike amino acids, is not recycled to regenerate these intermediates, is not utilized from the diet, and must be synthesized in situ. We studied whether biotin deficiency (BD) lowers heme synthesis and whether mitochondria would be disrupted. Biotin-deficient medium was prepared by using bovine serum stripped of biotin with charcoal/dextran or avidin. Biotin-deficient primary human lung fibroblasts (IMR90) lost their BDC and senesced before biotin-sufficient cells. BD caused heme deficiency; there was a decrease in heme content and heme synthesis, and biotin-deficient cells selectively lost mitochondrial complex IV, which contains heme-a. Loss of complex IV, which is part of the electron transport chain, triggered oxidant release and oxidative damage, hallmarks of heme deficiency. Restoring biotin to the biotin-deficient medium prevented the above changes. Old cells were more susceptible to biotin shortage than young cells. These findings highlight the biochemical connection among biotin, heme, and iron metabolism, and the mitochondria, due to the role of biotin in maintaining the biochemical integrity of the TCA cycle. The findings are discussed in relation to aging and birth defects in humans.

PMID: 17182796 [PubMed - indexed for MEDLINE]

http://www.vitamin-basics.com/index.php?id=52

So, with intestinal dysbiosis, biotin may be a critical co-factor in ones methylation protocol.

Laurie
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
Thanks Laurel for this article. I have known through personal use that biotin was helpful since about 1998. The implication from this article is that biotin may contribute both to increased energy and decreased oxidative stress. Bye, Alex
 

LaurieL

Senior Member
Messages
447
Location
Midwest
I knew we had discussed this last year. A link to the thread...lots of good info...

http://forums.phoenixrising.me/showthread.php?11176-Biotin-and-Methylation/page3&highlight=biotin

Post #30

Hi David,

I suspect that the results the first week were due to change because change is very visible. After it levels out the differences disappear. That doesn't mean it isn't doing what it needs to do, just that it has reached an equilibrium. Things can also fade when cofactors needed for it to work get used up and not replenished rapidly enough. This is they type of problem I had to work through over and over from the start with mb12. THis is why COMBINATIONS of cofactors and critical cofactors are so important, not single items. Maybe this is a clue though I don't know what cofactors it might need. Good luck.


Those combinations of co-factors would be, thiamin, riboflavin, niacin, lipoic acid, and pantothenic acid.

The amino acid conversion of luecine, isoluecine, and valine require those specific B vitamins in the conversion to a-keto's by way of the BCKA dehydrogenase. In the transamination and catabolism of those three amino acids, one will notice the role of adenosylcobalimin with methylmalonate, and the role of biotin with B-hydroxyisovalerate. Elevations in either methylmalonate or b-hydroxyisovalerate in the urine are sensitive indicators of B12 and biotin deficiencies. Without a balance of these afore mentioned B vitamins, the a-keto's cant be metabolized and end up in the urine.

Incidently, when looking into MMA, it is a form of metabolic acidosis in which I originally found the information concerning biotin treatments of 30mgs being effective.

The biochemical function of biotin-requiring enzymes is the
insertion of carboxyl groups to allow modification of metabolic
intermediates. The catabolism of the amino acid leucine is a highflux
process that offers a biochemical marker of biotin deficiency.
The product formed after the first three steps of the pathway, ?-
methylcrotonyl-CoA, requires a biotin-dependent carboxylation to
allow the flow to continue.

This compound accumulates if biotin
is deficient, and its hydrated product, ?-hydroxyisovalerate, spills
in urine. ?-Hydroxyisovaleric aciduria appears early in people who
are made biotin deficient by consuming the biotin-binding protein,
avidin. After starting avidin administration, elevated ?-hydroxyisovalerate
appears at the third day while serum biotin concentrations
remain in the normal range until the tenth day (Figure 6-8). The
effects are completely reversible.

Heritable disorders of biotin metabolism lead to the condition
called multiple carboxylase deficiency, in which the activities of
enzymes that have absolute requirements for biotin to carry out
carboxylation reactions are deficient [61]. ?-Hydroxyisovalerate
is a compound that is elevated in biotin deficiency and multiple
carboxylase insufficiency [62].

Biotin deficiencies of various degrees
have been shown to develop in normal pregnancies [63] and
in patients on long-term anticonvulsant therapy [64]. When ?-
hydroxyisovalerate was used to assess biotin in pregnant women,
biotin status was found to decrease during pregnancy, and out of
13 women studied were biotin depleted even in early pregnancy [65].

Symptoms of biotin deficiency include alopecia, skin rash, Candida
dermatitis, unusual odor to the urine, immune deficiencies, and
muscle weakness.

The enzymes that use biotin as a cofactor are called carboxylases,
because they use carbon dioxide to insert carboxyl groups into
substrates. Biotin from food or from intestinal microbial synthesis
is absorbed in the upper small intestine and transported to tissues
bound to several blood proteins. Cellular biotin must be incorporated
into the carboxylase enzymes by the action of other enzymes called
synthases (Figure 6-9). If these enzymes are not fully active, higher
biotin concentrations can increase enzymatic activity and enhance
the reaction rate.

The carboxylase enzymes have critical roles in
major pathways for the utilization of energy from amino acids (where
?-hydroxyisovalerate is formed), the synthesis of fatty acids for cell
membrane replacement, and the maintenance of blood glucose via
gluconeogenesis. At cell death, the biotin may be recovered if there
is sufficient activity of the enzyme biotinidase, which acts on the
biotin-peptide fragments called biocytin. All five of the major
factors (boxed text) in Figure 6-9 contribute to the maintenance of
active carboxylase enzymes.

Biotin deficiency can be caused by lack
of biotin-rich foods or genetic variations in the enzymes shown in
Figure 6-8. Antibiotic overuse can contribute to biotin insufficiency
by lowering the population of biotin-producing organisms and
favoring the overgrowth of non-biotin producing species.
Symptoms of ataxia, tremors,
loss of language development, gait disturbances, and eczematous
dermatitis cleared only after increasing biotin intake to 30 mg/day.
The data presented in Table 6-3 are from this report. After one year
of high dose biotin, the symptoms did not return and there was no
further progression of hearing loss but some attention disorder with
hyperactivity.

In addition to increased ?-hydroxyisovalerate, elevations of
lactate and alanine in urine and accumulations of odd-chain fatty
acids in plasma or red cell membranes have also been found in biotin
deficiency [61].

http://www.metametrix.com/files/lear...r-Medicine.pdf

Laurie