Candida, IL & biotin

[Kasper]

Saliva from Th17-deficient, but not Th1-deficient, mice exhibited reduced candidacidal activity. Thus, the Th17 lineage, acting largely through IL-17, confers the dominant response to oral candidiasis through neutrophils and antimicrobial factors.
http://jem.rupress.org/content/206/2/299

Interleukin-4 and -10 exacerbate candidiasis in mice.
http://www.ncbi.nlm.nih.gov/pubmed/7614983

IL-4 supresses TH-17.

[RRM]

Interleukins (IL) are signalling molecules inside the body, that 'spread a message' around
in one group of specific cells, or between various groups.
T cells regulate the cell-mediated immune response through T lymphocytes.
B cells regulate the humoral immune response through secreted antibodies.
IL-4, for example, is produced by T cells to activate B cells.
IL-17 is produced by 'memory' T cells, and induces an inflammatory response.

Kasper, what (if) are you trying to say with this post?

[Kasper]

Learning a little bit of immunology last couple of days.
I found this interesting, because Th17 cells seems to be very important in fighting Candida.
I think that therefore it's crucial to make sure that Th17 production is not impaired.
On the other hand, Th17 is also associated width autoimmune diseases.

IL-4, for example, is produced by T cells to activate B cells.

I learned that IL-4 main role is to promote pre-Th cells to become Th-2 cells. And inhibiting them to become Th-1 cells.
Overproduction of Th-2 cells is associated width overproduction of mucus, asthma and allergies.
Quite interesting stuff, as more and more people seem to be suffering from those.
A theory I have been studying a little bit is that those diseases are due to too high levels of prostaglandin D2.

For what I've read now, I think that overproduction of Th-2 cells is the main trigger that makes people suspectible for candida.

Just posting my thoughts a little bit, so I don't forget it myself.
And I hope it gives people stuff to think about...

[Kasper]

http://onlinelibrary.wiley.com/doi/10.1 ... x/abstract
Our results demonstrate that CMC patients have impaired cytokine production upon in vitro stimulation with Candida antigens resulting in low or absent IL-2, increased IL-6 and either absent or increased IFN-γ production.
Our studies support the hypothesis that Candida antigens trigger a predominantly Th2 instead of a Th1 cytokine response in patients with CMC.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC201074/
The most notable finding in CMC patients was the markedly impaired production of IL-12 in parallel with dramatically increased levels of IL-6 and IL-10 that occurred selectively in response to Candida.

[Kasper]

The antifungal activity of the IL-2-activated lymphocytes was exhibited against a number of clinical isolates of C. albicans and related fungal species.
IL-2-activated human peripheral blood lymphocytes also acquired the capacity to inhibit the growth of C. albicans.
http://iai.asm.org/content/60/3/853.full.pdf

I showed already that candida lowers IL-2 production.
How can we raise IL-2 production?
Zinc, vitamin B6 and biotin all seem to play important roles here.

Zinc
http://www.ncbi.nlm.nih.gov/pubmed/12389026
http://www.ncbi.nlm.nih.gov/pubmed/17162254

Vitamin B6
Plasma IL-2 concentration and in vitro production did not change throughout the study, although five of seven subjects showed increases with intakes of 2.1 and 2.7 mg B-6/d, respectively, compared with the 1.5 mg/d intake.
http://www.ncbi.nlm.nih.gov/pubmed/12421844

Biotin
1) Biotin-supplemented cells produce more IL-2 than biotin-deficient cells
2) Synthesis of IL-2Rγ correlates with biotin concentrations in human lymphoid cells. Effects of biotin on the expression of the IL-2Rγ gene are likely to be beneficial because IL-2Rγ plays a role not only in endocytosis of IL-2 (leading to degradation of IL-2) but also in triggering intracellular signaling pathways leading to growth and differentiation of immune cells in response to IL-2
http://ajpcell.physiology.org/content/284/2/C415.full
Intact IL2Rγ combats depressive-like behavior.
http://www.sciencedirect.com/science/ar ... 281000327X

[overkees]

So eating enough red meat, yolks and fish will do the trick.

[dime]

Yes, these minerals/vitamins seem to make a difference in people deficient in them, so if you're getting enough from diet, supplementation won't do much.

[Kasper]

I think higher 'theurapteutic' dosages could be helpfull here.

For vitamin B6, 2.1-2.7 mg was more effective than 1.5 mg for increasing IL-2.
For biotin, it's rumoured on the internet that dosages of 5-10 mg could have beneficial effects for candida, without any adverse effects.

A primary source of Biotin are the healthy bacteria colonies in the intestinal tract. Because these are often comprimised by a Candida Albicans overgrowth, candida sufferers are particularly prone to a Biotin deficiency. Yamaguchi reported that extensive mycelial formation of c. albicans when grown in a medium with a suboptimal concentration of biotin (0-1 ng/ml) as compared to primarily yeast cell growth in optimal levels of biotin.

Too high levels of zinc (over 50mg daily) is bad for immune sytem, and is not a good idea at all.
I think it's a good idea to follow at least the RDA when suffering from candida.

We induced in humans a mild deficiency of zinc by
restricting daily dietary zinc intake to 3–5 mg daily. The serum
thymulin activity (a zinc dependent thymic hormone) was
decreased within twelve weeks of zinc restricted diet. As a
result of mild deficiency of zinc, decreased T4+ to T8+ ratio,
decreased IL-2 generation and decreased NK cell lytic activity
were observed in mildly zinc deficient subjects [5]. These
changes were corrected after zinc supplementation.

[RRM]

Candida does not use zinc, B6 or biotin?

[dime]

The adequate intake for biotin (there's no RDA) is 30mcg.
Here's a table listing biotin content in various foods: http://www.ncbi.nlm.nih.gov/pmc/article ... /table/T1/
If you have candida due to biotin deficiency, I suppose you should have some of these symptoms at least? http://en.wikipedia.org/wiki/Biotin_deficiency

[Kasper]

If you have candida due to biotin deficiency, I suppose you should have some of these symptoms at least?

I have experimented a lot width biotin. I notice a lot more oil production in skin and hair width 5 mg biotin.
Which I like, because I have a little bit dry skin/hair normally.
I've started again width 5 mg biotin yesterday.

But I think using biotin for candida is not because people width candida are necessarily biotin deficient.
But because biotin helps fighting candida.
I regard the role of biotin for candida more as a medicine.

Candida does not use zinc, B6 or biotin?

I don't know, but at least for biotin there is some more direct evidence that high biotin levels helps controlling candida.

Yamaguchi reported that extensive mycelial formation of c. albicans when grown in a medium with a suboptimal concentration of biotin (0-1 ng/ml) as compared to primarily yeast cell growth in optimal levels of biotin.

I don't know how much biotin is needed to create this 'optimal' level of biotin. But on the internet people report having positive effects width high dosages like 5-10 mg. As biotin is one of the vitamins which doesn't seem to have adverse effects, I think this is a good 'medicine' to help against candida. When candida is under control, people might stop using biotin.

[RRM]

Candida does not use zinc, B6 or biotin?

I don't know, but at least for biotin there is some more direct evidence that high biotin levels helps controlling candida.

"Yamaguchi reported that extensive mycelial formation of c. albicans when grown in a medium with a suboptimal concentration of biotin (0-1 ng/ml) as compared to primarily yeast cell growth in optimal levels of biotin."

No, this study is about comparing how candida does in a biotin insufficient environment,
compared to when biotin levels are optimal.
This study is not about studying the effects of higher levels of biotin.
From this study we could conclude that people with candida should not be biotin-insufficient.
Thats not the same.
Candida (the yeast) actually contains an enzyme that activates biotin-dependent enzymes,
that are essential for the conversion of amino acids into glucose. (its main source of energy) Pendini NR et al
It has also been found that candida's ability to converse pyruvic acid in glucose, can be increased by an optimal concentration of B-vitamins, including biotin. Li Y. et al
On the other hand, growth of candida was observed in a high glucose, biotine free medium;
"At 5 g/L of glucose and without biotin very good growth was obtained...
Based on our results during the first 30 hours of growth, biotin has no influence on the yeast's growth." Vidotto V et al

I think this is a good 'medicine' to help against candida. When candida is under control, people might stop using biotin.

Be careful Kasper, and not too hasty, as up till now, all of this is still speculation.
We first need studies that show that biotin supplementation (beyond the normal optimal level),
reduces candida overgrowth.
Normally, candida growth is limited by our immune system and by other bacteria competing for the same locations in our body.
Indeed, candidiasis is not a biotin deficiency symtom.
Though it has been found that candida often can be cultured from biotin-deficiency skin lesions,
the candida infections might be the result of an impaired immune function, and contribute to the biotin deficiency skin lesions. Mock DM
In the passage between the yeast form and the mycelia form, only glucose concentration is of importance, and not biotin, amino acids or pH. Vidotto V et al


Regarding interleukins, "candida may have developed an ability to sense [host] IL-8. ...
this ability might help to keep the vulnerable hyphal tips away from areas with high concentrations of host IL-8 and [white blood cells killing candida]
...
... the IL-8-producing candidal cell body [has] a centrifugal growth pattern to facilitate host tissue penetration ... Ali A et al

[RRM]

Found this:

"Previous reports have indicated that many strains of Candida albicans and related species require biotin
for growth and that thiamine is stimulatory or essential for some strains (Schopfer and Guilloud, 1944;
Hijner, 1946; i\IcVeigh and Bell, 1951; Bona and Hedrick, 1952).
Later, Drouhet and Couteau (1954) and Drouhet and Vieu (1957) studied the detailed requirements of
over 100 strains in the genus Candida. Practically all of them required biotin; a few needed also
thiamine, vitamin B6, or nicotinic acid, either singly or in different combinations." Firestone et al

"Chlamydospore production by Candida albicans was investigated in rice cream decoction inoculated with a blastospore suspension...
The addition of biotin reduced the chlamydospore index (mean-number of mature chlamydospores produced)
at the concentrations tested (0.6 to 20 microgram/l)." Dujardin L et al

"The effect of biotin on the specific growth rate of Candida tropicalis was studied on media with various sources of carbon nutrition ...
The yeast was found to require 3--5 times less biotin on the medium with paraffin than on the medium with glucose and hexodecane,
and 3--4 times more biotin on the same substrate with an increase in temperature." Todosiĭchuk SR, et al

"The effect of thiamine and biotin on the processes of cell division, assimilation of glucose,
and accumulation of the biomass and nitrogen in the cells was studied with the Candida yeast.
The action of the vitamins depended on the source of nitrogen....
The vitamins did not favour the assimilation of nitrate nitrogen in species which were not adapted to this source of nitrogen." Makarova EN.

"A chemically defined medium composed of 6 amino acids, biotin, inorganic salts and glucose
for the growth of yeast and mycelial phases of Candida albicans at 25 degrees C and 37 degrees of C respectively
was developed based on the aminopeptidase(s) profile of the fungus.
This medium has proved successful in maintaining the growth characteristics of both phases during serial transfers" Lee KL et al

"When glucose was present in high concentration, Candida albicans formed filaments in a phosphate-buffered medium,
regardless of the nitrogen source. In lower concentrations of glucose, filamentation occurred only when various members of the glutamate,
succinyl, or acetoacetyl-coenzyme A families of amino acids were used as sole nitrogen sources.
Yeast morphology could be maintained either by replacing the amino acids in the medium
with ammonium chloride or by making the medium high in phosphate or biotin." Land GA et al

[Kasper]

A little bit more about the study btw:

A strain of Candida albicans in a chemically defined basal medium supplemented with biotin at optimal (10 ng/ml) and suboptimal (0.1 ng/ml) concentrations for growth developed predominantly into yeast (Y) and mycelial (M) phases, respectively. The M-phase thus grown showed an increase in alkali-insoluble glucan and a decrease in RNA and mannan as compared with Y- cells grown in biotin-optimal medium. Changes in the cell morphology as well as the chemical composition due to biotin insufficiency were almost completely restored by the supplementation of glyceryl mono-oleate to the medium. However, the supplementation of aspartie acid, accentuated both morphological and biochemical properties which were characteristic for biotin-insufficient cells. The correlation of morphology with the composition of major cellular constituents, especially cell wall polysaceharides, is discussed in relation to the casual role of certain biotin-participating metabolic processes in this fungus.
Read More: http://informahealthcare.com/doi/abs/10 ... 7485380461

No, this study is about comparing how candida does in a biotin insufficient environment,
compared to when biotin levels are optimal.
This study is not about studying the effects of higher levels of biotin.
From this study we could conclude that people with candida should not be biotin-insufficient.

You talk about biotin insufficient/sufficient (serum) levels as if those are defined somewhere. But I'm not aware of that.
I guess you mean width biotin sufficient, a lack of biotin deficiency symptoms.
Here a intresting study:

Serum biotin was 332 pg/ml (nl 520 +/- 220 pg/ml), and urine biotin was 5.22 ng/mg of creatinine (nl 4.3-95 with a mean of 30.2 ng/mg creatinine). The same parenteral nutrition regimen was contained and oral biotin was administered (10 mg/day). After 3 wk, serum and urine biotin levels were 650 pg/ml and 35.6 ng/mg creatinine, respectively. New hair growth was evident and all of her other symptoms resolved. Intravenous biotin was then provided (5 mg/day) for a month after which serum and urine biotin levels were 1316 pg/ml and 178 ng/mg creatine, respectively. The patient has been subsequently maintained on an intravenous multivitamin product containing 60 micrograms biotin per daily dose and remains free of signs and symptoms of biotin deficiency.

The candida study talks about a desirable 10ng/mL.
But this study shows that biotin deficiency symptoms already resolve at 0.650 ng/mL.
So just checking those deficiency symptoms is not sufficient to determine if you have the desirable 10ng/mL.
How much biotin is helpful stays speculation, I agree.
Reasons I believe to supplement width dosages around 5 mg for candida are:
- on various place on the internet such a dosage is recommend for candida
- people on the internet seem to have success width it
- there are no side effects known (and I can testify first hand that it can have positive effects for dry skin/har)
- IL-2 production is positively correlated width biotin

The adequate intake for biotin (there's no RDA) is 30mcg.

http://www.researchgate.net/publication ... _adult_men
Biotin, determined by bioassay with Ochromonasdanica, was significantly lower in the low fat diets (28 μg/day) than in the high fat diets (37–42 μg/day). Average serum biotin varied from 627 to 737 pg/ml with all diets,

Little chance that 30mcg biotin will give you 10ng/mL serum levels.

In the passage between the yeast form and the mycelia form, only glucose concentration is of importance, and not biotin, amino acids or pH.

... biotin helps controlling blood glucose levels, but still weird that they don't find any correlation in this study...

Found this:

I'm going to read it

[Kasper]

We first need studies that show that biotin supplementation (beyond the normal optimal level),
reduces candida overgrowth.

You might need that. I'm not going to wait for that study (cause I don't think it exist at this moment).
I want to do everything I think makes sense to cure my candida.

If there is some indication that 10ng/mL blood levels could help against candida, and there are no adverse effects, I go for it.
By the way. I found some information that serum biotin raises to 5,521 ng/L (5ng/mL) width 14 days of 1200 μg biotin supplementation in healthy subjects.
http://ec.europa.eu/food/fs/sc/scf/out106_en.pdf