From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.med.nutrition,sci.med,misc.health.alternative,sci.med.pharmacy,
	sci.life-extension
Subject: Re: Folate and B12 tox (was: Vitamin C , 500mg, harmful !!!!)
Date: 17 Apr 1998 23:38:39 GMT

In <1998041719564900.PAA17682@ladder03.news.aol.com> lmg003@aol.com
(LMG 003) writes:

>Are you aware of any studies on B Vitamins and how they react with each
>other. I recall reading that taking a large dose of a single B can cause
>one of the other B's to be depleted. The same article suggested that B's
>should always be taken in a complex.

   That's one of those nutrition "myths" that I've never been able to
verify, sort of like the 2:1 calcium/mag ratio.  I don't know where
this stuff comes from.  Old Adele Davis books, or something (when Adele
"felt" something was right, she just wrote it...).

>  I have never been able to find a complex that incorporates
>the B's in any particular ratio.

    No, although a very common complex formula in the past had the same
milligram amounts of B1,B2,B3,"B5," (pantothenate) and B6.  That amount
was usually 50 mg.  Then often 50 micrograms of B12, for some reason
(perhaps so there would be another 50 on the label to make it look more
"balanced".)   Then the 400 ug folate allowed by law, and whatever
biotin the manufacturer could afford (often 50 micrograms also, if they
were cheap).  From there, perhaps a water soluable few non-vitamin
that have for some reason have traditionally been associated with the
B's (PABA, inositol, choline) might or might not be added in
insignificant amounts.  The megahorse-pill B complexes might have all
this, in proportionately larger amounts (75 or 100 mg or mcg).
Probably somewhere out there was (or still is) some giant company that
supplies something like the above in one single powder, to all the
little tableters and suppliers.

   No, none of this really makes any sense.  None of the ratios of dose
to RDA are really very similar in the above, except for the B1, B2, and
B6 ratios, since these all have somewhat similar RDAs.  The rest was
all over the map.

    Recently, a few supplement makers have started to put in B's at
something closer to the same Dose/RDA ratios for each, which makes at
least a bit more sense.  Although, of course, even there niacinamide
and pantothenate still get much lower ratios, biotin is still expensive
and not supplied in large amounts, and you still by law can't put in
more than 400 mcg of folate (except in prenatals, which never have the
others in megadose).

    B12 is also a sort of silly thing in B complexes, as its active and
passive effective dose ranges are so far appart that everybody in the B
complex business gets it wrong.  It simply doesn't make any sense to
put in more than about 5 mcg of B12, unless you are going to put in at
least 500 mcg.  But you usually see some dose in between, which just
wastes money.  As, of course, also does the homeopathic amounts of
PABA, choline, inositol, and so forth which you still see on
supplements trying to make themselves look "complete."

>This talk about a single B and toxicity triggers a bell. I wonder if the
>toxicity comes from losing one B as a result of taking a large dose of
>another one.

  Except I know of no evidence of that happening for any B vitamin!
They are all absorbed pretty specifically and independently and
actively (although there is non-active transport for some of them,
also).  This has effects on how much of each you can absorb at any one
meal.  For instance, you pretty much top out at 25 mg of B2, and
there's little point in putting more in a supplement, as twice the dose
only gets you a few mg more.  On the other hand, you can absorb much
larger amounts of the simpler B6 and niacin.   For thiamin and folate,
which have mixed active and passive mechanisms, you get intermediate
effects of going up in dose.  However, again, so far as I know, none of
this interfers with the others.  If you are short on B12/folate your
gut doesn't work well and absorbtion of all kinds of other nutrients
will be screwed up, but again, that really doesn't have anything to do
with giving large amounts of one B vitamin without the others.  There
are lots of places in metabolism where you need one vitamin to
metabolize another (example: you need B2 to get all your folate
metabolized, convert B6 to its coenzyme, tryptophane to niacin, etc,
etc), but again, this hasn't got anything to do with any danger of
giving one vitamin without the others as a supplement.

   Perhaps there is some literature on giving vitamins to animals who
are severely short of thiamin and which might suffer grave consequences
if metabolism is "goosed" in any way.  But surely none of this applies
to modern reasonably well B-vitamin nourished Americans, taking
supplements.  Perhaps if a thiamin depleted alcoholic took every B
vitamin BUT thiamin...?

                                   Steve Harris, M.D.

From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.med.nutrition
Subject: Re: Folate and B12 tox (was: Vitamin C , 500mg, harmful !!!!)
Date: 18 Apr 1998 07:47:34 GMT

In <2044.411T669T14204257@escape.ca> "Syd Baumel" <sgb@escape.ca>
writes:

>That's part of the theory -- too much of one vitamin leading to a
>relative deficiency of others, perhaps by competing unduly with them for
>absorption or transport within the body or by other means.

   I don't know whose "theory" this is, but I'm going to call it a
myth.  Or hypothesis, if you want to be respectable.  Theories are
generally supported by some evidence.

>For instance, some doctors believe their patients tolerate megdoses of B6
>well because they also take plenty of the other B vitamins -- and
>magnesium.

   They believe that, but I think, on faith.  Some people want to take
a lot of B6 for one reason or another, and need a talisman to ward off
evil.  But it's not at all clear why some people get neuropathies with
the "lower" doses of B6 (500 mg a day), and some don't get them even at
four times that.  I cannot find, for instance, any animal studies
showing that B6 toxicity is ameliorated by giving other vitamins.

> (B6 and magnesium team up very often in enzyme reactions within
>the body).

    Actually, I'm going to quibble with this, as it's probably another
Adele Davis myth.  "Very often"?  Okay, name THREE enzymic reactions
which require both Mg2+ and B6 as cofactors.  I'm rather astonished,
given the huge number of reactions for which each nutrient is needed
(literally hundreds, for each), that there isn't more overlap.  It
seems that ATP and nucleic acid reactions (the classic Mg2+
requirements) are rarely the same as all those nitrogen/protein
metabolism reactions which require B6.  Actually, I can't think of even
ONE, but then you know we doctors don't get much nutrition in medical
school, and I'm sure that's the reason.

>  The bottom line would seem to be that if you want to take a
>megdose of any nutrient(s), make sure your diet and supplements are
>supplying you with an ample intake of nutrients in general.

   That's the general mythology.  What I want are some specifics,
because I think it's just mythology.   It's sci.med.nutrition, and I
think we owe it to ourselves to clean out the mythology here, and get
down to what we really know, or have good evidence for.


                                  Skeptically Yrs,

                                  Steve Harris, M.D.

From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.med.nutrition,alt.nutrition
Subject: Re: Vitamin B dosage
Date: 18 Sep 1998 22:45:57 GMT

More like 1.4 mg a day-- so he's getting much more than RDA.  Still,
the stuff is non-toxic at these doses.  The only B vitamins which have
oral toxicity are B3 (niacin and niacinamide both), at more than
500-1000 mg a day (in a rare person), and vitamin B6 at doses around
200 mg a day (probably only the pyridoxine form, and usually it takes
grams a day for months to cause problems).  The worst thing about any
of the others is the diarrhea you can get from huge doses of B5, and
the dry mouth and eyes you can get after you stop B5 megadosing
suddenly.  Both temporary (cholinergic) effects.

                                         Steve Harris, M.D.

In <6ttedv$l5k$1@news.worldonline.nl> "Haarlemmer"
<hufri@worldonline.nl> writes:

>I guess not. These b-vitamins are water soluble and if you take more than
>your body needs it'll be peed out.  The RDA for vit. B1 is 14 mg a day so
>you don't take that much extra. Don't worry
>
>Frida
>armilius@rocketmail.com heeft geschreven in bericht
><6tsadg$8hc$1@nnrp1.dejanews.com>...
>>Is there any danger in taking this much of these vitamins daily?
>>
>>B1 - 19 mg
>>B2 - 20 mg
>>B6 - 21 mg
>>
>>Niacin - 114 mg

From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.med.nutrition,sci.med
Subject: Re: Vitamin B1 advise
Date: 5 Jan 1999 10:44:32 GMT

In <36910e5d.836202@news.annex.com> neutrino@annex.com (Daniel Prince)
writes:

>I am extremely Ill with CFS, NMH (Neurally Mediated Hypotension) and
>Hashimoto's Thyroiditis.  I think most of my symptoms are caused by
>one or more chronic infections.
>
>Someone advised me to take an additional 100 mg of Vitamin B1 (I
>already take a B complex and a multivitamin with a total of 75 mg of
>B1).  He said that it would give me more energy.  (I think my problem
>is more a lack of strength and a lack of stamina than a lack of
>energy.)
>
>Does this advice make any sense?


   No.


> How likely is it that taking an
>extra 100 mg of B1 will help me?


   Not likely. Biology's too complex to say impossible.  But not
bloodly likely.



> Is taking a large amount of just one
>B vitamin safe?  I have read that it can cause deficiencies in the
>other B vitamins.


    It's safe.  So far as I can tell, the idea you mention is an urban
myth.  I've been challenging anybody to come up with evidence of it for
years.  So far, nothing.  It's had to prove a negative, but the burden
here is on those asserting the effect.

From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.med.nutrition
Subject: Re: B-complex and iodine questions
Date: 30 Apr 1999 11:37:13 GMT

In <3728D4BC.8EAE6176@Mindspring.com> Jim <JDBarron@Mindspring.com>
writes:

>> >I do recall reading that the B vitamins are uptaken competatively, so
>> >that high levels of one may induce deficiency in others. Does anyone
>> >know if this is significantly true?
>>
>>    No, it's one of the great myths of nutrition.
>
>It's not *entirely* a myth.    *Some* people who take very large doses
>of ISOLATED B vitamins  (i.e. supplementing one without any of the
>others, not just "less than ideal balance") over a very long period of
>time developed problems (as best as I remember they were
>neurological). The effect was due to the VERY large relative
>imbalance.  But this was an effect from extreme forms of
>supplementation and showed up in only a few individuals.

    You've got your story wrong.  At least two B vitamins have shown
toxity when given in large doses: they are B3 (nictoninic acid and, in
animals, niacinamide) which can cause liver toxicity above 1000 mg a
day (human equivalent), and B6, which has caused neuopathy in doses as
low as 200 mg a day for some months.  Nobody has ever suggested from
either epidemiology or animal tox studies that these effects are due to
imbalances of these vitamins with others, or that they can be prevented
by taking megadoses of the others.  In fact, I think the idea is a
highly dangerous one.  The symptoms of toxity with B6 are very similar
to the symptoms of too little B6, not to the symptoms of any other
vitamin deficiency, and the most likely explanation is that B6 when
given as a provitamin (pyridoxine) interfers with *itself* (ie, its
active form, pyridoxal-5-phosphate), not some other vitamin.

>Taking any complex with amounts of the b complex in anything remotely
>near equal proportions is safe.


    You don't know that.  I suggest you experiment on yourself, if you
must, and refrain from such advice.

                                       Steve Harris, M.D.

From: sbharris@ix.netcom.com(Steven B. Harris)
Newsgroups: sci.med.nutrition
Subject: Re: B-complex and iodine questions
Date: 5 May 1999 23:23:02 GMT

In <372D0C2B.297B@netcom.ca> Tom Matthews <tmatth@netcom.ca> writes:

>Steven B. Harris wrote:
>
>> and B6, which has caused neuopathy in doses as low as 200 mg a day for
>> some months. Nobody has ever suggested from either epidemiology or
>> animal tox studies that these effects are due to imbalances of these
>> vitamins with others, or that they can be prevented by taking megadoses
>> of the others. In fact, I think the idea is a highly dangerous one. The
>> symptoms of toxity with B6 are very similar to the symptoms of too
>> little B6, not to the symptoms of any other vitamin deficiency, and the
>> most likely explanation is that B6 when given as a provitamin
>> (pyridoxine) interfers with *itself* (ie, its active form,
>> pyridoxal-5-phosphate), not some other vitamin.
>
>Since excess pyridoxal (PL) is irreversibly converted to pyridoxic acid
>(PIC) by either FAD (made from riboflavin) dependent aldehyde oxidases
>found in the liver and kidneys, or NAD (made from niacin) dependent
>aldehyde dehydrogenase found in all tissues, might not supplementing
>extra riboflavin and niacin decrease the toxicity of B6?

   That would depend, it seems to me, on whether the agent which is
toxic is pyridoxine or pyridoxal.   If it's pyridoxine that is toxic
the last thing you want to do is metabolize off your limited supply of
counterposing pyridoxal and P5P.  Tox studies on pyridoxal vs
pyridoxine are urgently needed, for this reason.  So far as I can tell,
no tox studies have been done on pyridoxal, even though pyridoxine is
not the most common vitamin in foods.  All human toxicity has been
reported by people taking pyridoxine, until recently the only
commercial form available in high doses.  (P5P, cleaved in the gut and
absorbed as pyridoxal, is now available.  I wonder if they make it from
pyridoxal and take all that time to stick on a phosphate on which just
has to be removed again, before the stuff is absorbed?)

   One of the B6 vitamers (pyridoxamine) is particularly interesting,
in that it seems to be far more efficacious in lowering homocysteine
and preventing atherosclerosis (in animals).  Tox studies are needed
for it also, for obvious reasons.  Might even be a product there.

From: Steve Harris <sbharris@ix.netcom.com>
Newsgroups: sci.med,sci.med.nutrition
Subject: Re: Large doses of B vitamins
Date: 3 Jul 2005 17:35:38 -0700
Message-ID: <1120437338.096418.252420@g43g2000cwa.googlegroups.com>

>>2) Is it possible to OD on the B vitamins or just make yourself ill by
taking a lot of them?  Does the stuff build up in your system, or do you
piss away the excess?  Do any metabolites of the B vitamins build up in
your system?  None of the bottles say anything about this, either. <<

COMMENT:

They all seem to be reasonably safe, and none of them build up at doses
below 100 mg a day. If you take less than that, the worst that happens
is you get riboflavin breath, in which your breath and sweat smell like
that smell you smell when you stick your nose into a bottle of
B-complex tabs. Riboflavin (B2) is also the stuff that makes your urine
that fluorescent yellow.

The only really toxic B vitamins are niacin(B3) and pyridoxine (B6).

B3 can cause liver problems at doses larger than 1 gram a day
(niacinamide, which is usually what's in B-complex, is actually a bit
more toxic than nicotinic acid).  Niacinamide at doses less than 500 mg
is pretty benign unless you have liver problems. Of course, there are
histaminic side effects from niacin as nicotinic acid, at doses as low
as 10 mg. But they rarely put this form in B-complex, due to the
unpleasantness of the skin effect (which feels like itch at low doses,
and looks and feels like wholebody sunburn at high ones, but doesn't
last and is harmless).

B6 can cause peripheral nerve damage in doses of grams/day, and there
have been reports as low as 200 mg/day.  I personally wouldn't take
more than 50 mg of the stuff a day. Even 25 mg is 10 times your RDI, so
that has to be overkill.

Some of the B-vitamins seem to have effects which are annoying more
than toxic. And they are person-specific, so I can't claim the
following will happen. Personally, I'm pretty sure than B5 taken in
high dose (500 mg a day) for a long time, then suddenly stopped, gives
me dry eyes for a while. How that works, I cannot say, but it soon goes
away.

Also, 2 B vitamins, B5 and biotin, cause me to have sensitive teeth for
some hours, to the point that I can tell which days I take a B-complex,
and which not. You may or may not find this happens to you. B5 has been
tried on arthritis, and some people complained it actually increased
joint sensitivity. This may be a cholinergic effect. It doesn't seem to
be an inflammatory one, and as noted, is more annoying than anything.
Lastly, something or other in B-complex also seems to be mildly
stimulating like caffeine, and I have more problems with insomnia if I
take it at dinner rather than in the AM.  Again this is mild and only
annoying. It's probably the reason people almost unconsciously tend to
take multivitamins in the AM, especially the megadose ones.


>>3) There's obviously a HUUUUGE discrepancy between the RDA for B
vitamins and what these "dietary supplement" manufacturers think you
should ingest.  All FUD, marketing hype and bullshit aside, what's the
*real* amount of B vitamin supplement that somebody should take? <<


COMMENT:

Nobody really knows. They've tried feeding rats a few times the
equivalent RDI for B-vitamins, and it doesn't lengthen their life span.
There are a few claims for HUGE supplemental doses of a few of the
B-vitamins on rat life span, but they seem to be unrepeatable, or else
everybody would be taking megadoses.

The amount of a lot of the B-vitamins you can absorb at one dose is
limited, though. For B1 and B2 it's around 10 to 20 mg. For B5 and B6
it seems to be larger, but nobody really knows. For most of these
things, absorbed levels are linear up to some limit of gut transporter
overload (like 20 mg) then go up in log fashion from there, probably
due to direct mass-action diffusion absorption.

SBH