B2 I love you!

[Blossom1]

5-10mg manganese is 250-500% of the RDA. It might simply be too much for many people.

I had been taking 5mg for some months, until a blood test showed my hemoglobin to be very low. I was feeling increasingly weak and cold. Since manganese inhibits the absorption of iron, and iron builds hemoglobin, I have stopped the manganese and started supplementing iron. I feel much better now.

It is my understanding that you are supposed to take b2 to "encourage" your liver to release iron. I can't see any reason why a person who eats meat and/or lives in a country where food is plentiful would need to supplement with iron. It seems to me to be more a matter of getting your liver to release it into your blood and/or storing it in your tissues rather than absorbing it from food or supplements.

I took manganese by itself for almost 2 weeks and had cold extremities and chills; they stopped when I added in small amounts of b2 as well as small amounts of b12 (blood building vitamins). This also increased my serum iron levels by a small amount (67 to 77) and caused my ferritin levels to increase from 3 to 14 in less than 2 months.

 

[adreno]

It is my understanding that you are supposed to take b2 to "encourage" your liver to release iron. I can't see any reason why a person who eats meat and/or lives in a country where food is plentiful would need to supplement with iron. It seems to me to be more a matter of getting your liver to release it into your blood and/or storing it in your tissues rather than absorbing it from food or supplements.

There is no evidence to support the idea that B2 releases iron from the liver.

Anyway, I was taking B2 at the time, and it didn't make a difference for me.

 

[Asklipia]

Sunbathing but no tan!

This is a new result of the B2/Manganese supplementation (8-9 weeks on).
For the last two months I have been swimming and sunbathing every other day (at least 40 mns in the sun, which is very bright and hot at the moment - 35°C all this last week). But my skin stays the same colour! Vaguely apricot-gold. With no defined delineations at the edges of the swimming suit.

I wonder if this is not a sign of my body manufacturing more glutathione?

I know glutathione pills are all the craze in Japan, and are supposed to stop you getting darker in the sun.
For example :
http://herroyalbleakness.blogspot.gr/2010/08/glutathione-war-tathion307-vs-ph338.html
http://www.superwhiteningpills.net/

Is the same thing happening to you too?

Be well!
Asklipia

 

[richvank]

Hi, Asklipia.

I think this is fascinating! I have been aware of the use of glutathione for skin lightening in the Asian countries, but didn't know that the same effect could be achieved with B2 and manganese. I'm guessing that both are involved in this effect, because B2 supports glutathione reductase, which recycles glutathione when it becomes oxidized, and manganese supports the mitochondrial version of superoxide dismutase, which will convert the superoxide free radicals to hydrogen peroxide, which glutathione peroxidase will then convert to water. Together, they should help to prevent oxidation of tyrosine, which produces melanin and skin darkening.

Something that I think is really cool about all of this is that this whole motivation to raise glutathione to make oneself look better (at least in the view of the cultures where people are doing this) is actually serving to promote health and longevity at the same time! Too often, I think that what people do to try to make themselves look better is actually working counter to their overall health, but this is a happy situation in which it's good both ways!

Meanwhile, we have some of the paler people of the world paying to go to tanning booths to darken their skin! What's wrong with this picture?

Best regards,

Rich

 

[Asklipia]

Vitamin D connection?

Hi Rich!
I wonder if this is not related to Vitamin D.

Paler skin would allow for more Vitamin D formation in the skin I suppose. I feel the kick of the Vitamin D starting when I sunbathe, but it is not vaguely unpleasant and nauseating as it used to be before B2/manganese supplementation. It is now as though my body was hungry for the sun just as it was when I was 20 (that is 40 years ago!).

I suspect my low levels of Vitamin D (a couple of years ago - normalized now) were an adaptation reaction to something, low glutathione levels or something else.

I wonder if the manganese is helping the vitamin K. Low levels of vitamin K induce vitamin D toxicity I think. I do take 15mg MK-4 daily and have no problems in the sun, but it seems B2/manganese has improved things further!!!!

Best regards,
Asklipia

 

[Vegas]

There is no evidence to support the idea that B2 releases iron from the liver.

I don't think this connection can be so readily dismissed. The primary enzymes involved in the release of iron from ferritin require FAD & FMN, which comes from Riboflavin, and NADH, which is converted from Niacin. There is also a xanthine reaction that liberates iron. I believe the liver is the primary storage site of iron. It stands to reason that in a patient with a marked riboflavin deficiency upon induction of these oxidoreductase enzymes could rather dramatically "dump" iron from the liver. Obviously taking B2 doesn't necessarily liberate large amounts of iron, but in a patient with very poor B2 status and high amounts of oxidative stress where sequestration of iron would be desirable to further limit ROS, I believe this is very plausible. Not sure about xanthine status in ME/CFS, but it is easy to predict chronic deficiencies in these reactions based upon the other cofactors which dictate how much iron is released from ferritin.

Also, when I looked at these enzymes a few months ago I noticed something interesting. I encountered a number of studies wherein B2 supplementation did not restore B2 levels and others studies where it did. In those where status did not improve, a B-complex was used whereas improvement in these levels was associated with B2 singularly supplemented...unfortunately this was not evaluated in the studies and the sample size is very small.

 

[Blossom1]

7 weeks into B2/Manganese

Now taking 37.5 to 50 mg B2 and 20 mg Manganese chelated every day.
No other supplements except :
- daily: 15 mg Menatetrenone (MK-4) with breakfast; Melatonin 3 mg + Zinc 8.7 mg + Selenium 50 mcg (these last three in the same preparation at night). I know that MK-4 must be depleting B2 but I feel much better taking it. Same goes for the Melatonin pill (because of zinc) but otherwise my eyes don't feel right and my sleep is less relaxed.
- on Sundays : 1 mg mb12 or 3 mg adb12 (supposed to lower B2 but I have some left-overs from trying the methylation protocol and I don't feel any bad effect when taking them. I figure once a week can't be that bad).

What I notice compared to 2 weeks ago when I was 5 weeks into this protocol:

-
- short term memory loss by bursts, much less;
- irritation of the eyes in the morning on waking up only;
- dry mouth (not too bad) on waking (was worse before - not sure as it comes and goes);
- Today I shall stop all supplements just for one day.

Best wishes and good luck to all.
Asklipia

Askilipia,

Have you tried taking b12 every day? I started taking b2/manganese after a bad crash following the methylation protocol and upping my methylfolate dose. I could hardly tolerate any b2 and Christine suggested that I go off of it for a bit and just take manganese until I could tolerate more b2 and then add in b12 when my tongue started to itch/sting or other symptoms of b12 deficiency showed up. This happened quickly after adding tiny amounts of b2, but I found that the small amounts of cyanocobalamin did nothing for me, and I had to take small amounts of the methyl form for the tongue issues to go away. I also get red, itchy or watery eyes in the morning that is helped by taking b12 with b2, and I was wondering if your eye irritation goes away when you take b12 or if anyone else has had this problem.

 

[adreno]

I don't think this connection can be so readily dismissed. The primary enzymes involved in the release of iron from ferritin require FAD & FMN, which comes from Riboflavin, and NADH, which is converted from Niacin. There is also a xanthine reaction that liberates iron. I believe the liver is the primary storage site of iron. It stands to reason that in a patient with a marked riboflavin deficiency upon induction of these oxidoreductase enzymes could rather dramatically "dump" iron from the liver. Obviously taking B2 doesn't necessarily liberate large amounts of iron, but in a patient with very poor B2 status and high amounts of oxidative stress where sequestration of iron would be desirable to further limit ROS, I believe this is very plausible. Not sure about xanthine status in ME/CFS, but it is easy to predict chronic deficiencies in these reactions based upon the other cofactors which dictate how much iron is released from ferritin.

Also, when I looked at these enzymes a few months ago I noticed something interesting. I encountered a number of studies wherein B2 supplementation did not restore B2 levels and others studies where it did. In those where status did not improve, a B-complex was used whereas improvement in these levels was associated with B2 singularly supplemented...unfortunately this was not evaluated in the studies and the sample size is very small.

I am sure that we can think of many nutritional deficiencies that will cause havoc for the human body. But the more important question is: do you believe ME/CFS can be reduced to a nutritional deficiency?

Here are 3 studies that all show that riboflavin deficiency leads to reduced liver contents of iron:

http://www.ncbi.nlm.nih.gov/pubmed/9197927
http://www.ncbi.nlm.nih.gov/pubmed/15539220
http://www.ncbi.nlm.nih.gov/pubmed/3676194

Now, if riboflavin deficiency leads to reduced liver contents of iron, wouldn't it make sense to conclude that riboflavin repletion would increase liver stores of iron?

 

[Asklipia]

But the more important question is: do you believe ME/CFS can be reduced to a nutritional deficiency?

Hi Adreno,
There is in my opinion a big difference between the reason for the onset of a particular health condition and the means to cure it.
Nobody would suppose an infectious disease like typhoid to be due to a lack of chloramphenicol! But chloramphenicol is indeed the cure.

Personally I would not propose that ME/CFS is due to a nutritional deficiency. It feels on the contrary like some kind of poisoning!!!
Whatever the cause of it (and I am sure we shall live to find out), ignorance of this cause is not a reason to stop looking for a cure. This would not be the first time in medical history that a cure is found before we understand what is really going on.
I am optimistic today!
Be well!
Asklipia

 

[Vegas]

I am sure that we can think of many nutritional deficiencies that will cause havoc for the human body. But the more important question is: do you believe ME/CFS can be reduced to a nutritional deficiency?

Here are 3 studies that all show that riboflavin deficiency leads to reduced liver contents of iron:

http://www.ncbi.nlm.nih.gov/pubmed/9197927
http://www.ncbi.nlm.nih.gov/pubmed/15539220
http://www.ncbi.nlm.nih.gov/pubmed/3676194

Now, if riboflavin deficiency leads to reduced liver contents of iron, wouldn't it make sense to conclude that riboflavin repletion would increase liver stores of iron?

-------------------------------------------------------------------------------
No, I don't think that ME/CFS is caused by nutritional deficiencies, but nutritional deficiencies develop in a majority of patients and these increase the severity of the condition.

I didn't say that riboflavin deficiency led to increased iron stores in the liver, although I think this is also possible despite the abstracts you posted. My point related to the liberation of iron from ferritin, and specifically that riboflavin catalyzes enzymatic reactions in the liver. These reactions need flavin nucelotides to free the iron contained in the ferritin molecule, and it is easy to conclude that an ME/CFS population is deficient of this nutrient.

I also think that the studies you linked don't take into account the fact that the ME/CFS population is marked by a redox problem and experience the associated biochemical consequences of the chronicity of the condition. Chronic nutrient deficiency can produce different consequences than a more acute deficiency. Also, the intracelluar redox environment has to be taken into consideration. Low intracellular cysteine and glutathione, which are obviously common findings among the ME/CFS population, also inhibit the release of iron from ferritin. So, yes, I continue to believe that riboflavin can induce significant releases of iron from ferritin, and this is likely to be more pronounced in those with ME/CFS.

 

[Blossom1]

I am sure that we can think of many nutritional deficiencies that will cause havoc for the human body. But the more important question is: do you believe ME/CFS can be reduced to a nutritional deficiency?

Here are 3 studies that all show that riboflavin deficiency leads to reduced liver contents of iron:

http://www.ncbi.nlm.nih.gov/pubmed/9197927
http://www.ncbi.nlm.nih.gov/pubmed/15539220
http://www.ncbi.nlm.nih.gov/pubmed/3676194

Now, if riboflavin deficiency leads to reduced liver contents of iron, wouldn't it make sense to conclude that riboflavin repletion would increase liver stores of iron?

Adreno,

This is very interesting. It seems that weagree that b2 is needed to increase iron, however whether the liver is low in iron and needs b2 to help store it or high in iron and needs b2 to release it is something I don't know. Christine obviously thinks the liver is high in iron. Unfortunately, she has not published a paper fully explaining her theory. I would think the ideal way to solve this question is with liver biopsies, and since Christine has done quite a few liver biopsies on dogs with what she said had similar problems to humans, I'm assuming she found high contents of iron in their livers. However this is just an assumption; I don't think she has explicitly said that.

To specifically address those studies, I would guess that the rats were perfectly healthy to begin with and had good mineral/vitamin balances. It would be better if they ate a SAD first which has high amounts of non-heme iron in cereals and white flour and low manganese. Then their livers could be checked for iron levels before and after a specifically riboflavin deficient diet is started. Also, there are several studies saying that non-heme iron decreases manganese levels. Christine thinks that manganese is vital to proper formations of the ER structures that store iron. So is it possible that there is a lot of iron being stored incorrectly? In other words, I'm not sure that the studies can support the jump in reasoning that our livers are low in iron. At the same time you may be correct; I just don't know. I think it would be helpful to know if to "cure" the rats, the investigators added back b2 or iron or both?

To give a little bit of personal experience to add to the collective database of knowledge , my 2.5yo started becoming extremely aggressive, would "lose" words (start saying a couple phrases and then never say them again until at points he just never said any words), and would nap for 4-5 hours without having restorative sleep--wake up very tired, stay very grouchy for 2-3 hours after waking up, circles under eyes, etc. I started him on the children's dose size recommended on the WaterOZ manganese bottle as well as b2 in the dosage recommended in the multivitamin his doctor had suggested and tiny amounts of b12 less than the dosage recommended for his age. These were his only supplements (I stopped the multivitamin since after 6 months, it did not help in any obvious way). Within 2 days he was counting to six and every day since he has added a new entire phrase (I love you, what is that, etc) to his vocabulary. He does not hit, bite or throw things anymore and he sleeps only 2.5 hours a day and wakes up easily and happily. This vitamin combination has done wonderful things for me too. Therefore, I think a lot of what Christine says has merit, but that obviously does not mean everything is correct. I have eliminated cereals and foods with added iron (non-organic white flour and rice), but we both eat meat, whole grains, chocolate and food cooked in cast iron pans so our diets do still have iron in them. Since starting this, my son does crave oatmeal which has quite a bit of natural iron and he does not like dairy which can inhibit the absorption of iron (I don't know if it also inhibits the absorption of Mn too). As I mentioned earlier, my ferritin levels are increasing without taking any iron supplements. However, I do not see anything in my personal experience to contradict the low iron storage theory.

Since Christine cannot contribute, the continuation of this thread is a great way to explore/test/discuss what little we know of her theories.

 

[adreno]

-------------------------------------------------------------------------------
No, I don't think that ME/CFS is caused by nutritional deficiencies, but nutritional deficiencies develop in a majority of patients and these increase the severity of the condition.

I didn't say that riboflavin deficiency led to increased iron stores in the liver, although I think this is also possible despite the abstracts you posted. My point related to the liberation of iron from ferritin, and specifically that riboflavin catalyzes enzymatic reactions in the liver. These reactions need flavin nucelotides to free the iron contained in the ferritin molecule, and it is easy to conclude that an ME/CFS population is deficient of this nutrient.

I also think that the studies you linked don't take into account the fact that the ME/CFS population is marked by a redox problem and experience the associated biochemical consequences of the chronicity of the condition. Chronic nutrient deficiency can produce different consequences than a more acute deficiency. Also, the intracelluar redox environment has to be taken into consideration. Low intracellular cysteine and glutathione, which are obviously common findings among the ME/CFS population, also inhibit the release of iron from ferritin. So, yes, I continue to believe that riboflavin can induce significant releases of iron from ferritin, and this is likely to be more pronounced in those with ME/CFS.

Ok, it seems we are mostly in agreement after all. It is my understanding that B2 enhance the absorption, storage and utilization of iron. I stumpled upon this interesting study:

Int J Vitam Nutr Res. 2007 May;77(3):217-23.

Influence of infection/inflammation, thalassemia and nutritional status on iron absorption.

Lynch S.

Source
Eastern Virginia Medical School, USA.

Abstract
Iron balance in human beings is maintained by the control of absorption. Recent observations have demonstrated that a peptide hormone, hepcidin, is the principal regulator of iron homeostasis. It is produced in the liver in response to increasing iron stores. It is also induced by interleukin-6 (IL-6) in infectious and inflammatory diseases. Hepcidin restricts both iron absorption and iron release from stores. Disorders that affect the duodenum or stomach directly, particularly gluten enteropathy and H. pylori infections, also impair iron absorption by damaging enterocytes or reducing gastric acid output. Hepcidin secretion is suppressed by accelerated erythropoiesis even when iron stores are increased. This appears to account for the contribution that excessive absorption makes to the iron overload seen in patients with iron-loading anemias such as thalassemia major. There is some evidence suggesting that two nutritional deficiency disorders (deficiencies of vitamin A and riboflavin) lead to impaired iron absorption or utilization, but further research is needed to reconcile conflicting experimental observations.

PMID: 18214023

It is noteworthy that B2 inhibits IL-6. But then again, so does B12, vitamin E and likely many other nutrients.

 

[Asklipia]

It is noteworthy that B2 inhibits IL-6. But then again, so does B12, vitamin E and likely many other nutrients.

Hi Adreno,
I find this very interesting, because it could be one of the ways in which B2 has brought me even further in my healing.
I have been supplementing with 45 mg K2 (MK-4) for two years until last September, with nearly no inflammation left. (Now on 15 mg a day). Nearly is the word. Something(s) was missing.
With B2, no inflammation left whatsoever.
Since MK-4 does not seem to affect IL-6, it seems the B2 was the missing piece.
Be well,
Asklipia

 

[adreno]

With B2, no inflammation left whatsoever.

How do you know you have no inflammation left?

 

[Asklipia]

How do you know you have no inflammation left?

Feeling cool and fresh all over.
No more rashes, itching in any place. Gums feeling tight and closer to the teeth. Finger rings slipping off the fingers.
It is a general feeling. Before B2 when on K2 alone I did not feel bad, but I don't recall having felt this "no-inflammation" state for years. Even when I was a child it was rare I realize!
This inflammation might have gone on for longer that I thought previously. That is, it predates the onset of serious problems.

 

[adreno]

Feeling cool and fresh all over.
No more rashes, itching in any place. Gums feeling tight and closer to the teeth. Finger rings slipping off the fingers.
It is a general feeling. Before B2 when on K2 alone I did not feel bad, but I don't recall having felt this "no-inflammation" state for years. Even when I was a child it was rare I realize!
This inflammation might have gone on for longer that I thought previously. That is, it predates the onset of serious problems.

I find it a bit of a stretch to conclude that because you're feeling better on B2, it is because of it lowering inflammation, and more specifically lowering IL-6. There really is no way of knowing this without testing. And B2 have many other actions other than inhibiting IL-6. Besides, as I said, many other nutrients inhibit IL-6.

 

[Asklipia]

I find it a bit of a stretch to conclude that because you're feeling better on B2, it is because of it lowering inflammation, and more specifically lowering IL-6. There really is no way of knowing this without testing. And B2 have many other actions other than inhibiting IL-6. Besides, as I said, many other nutrients inhibit IL-6.

Hi adreno,
I am not trying to prove anything, just offering my personal experience for others to ponder as they like. Fuel for someone with skills different from mine who may be able to take us all further towards a solution.

As to there being no way of finding out what goes on without testing, it seems farfetched to me. Certainly the feel good or feel bad experience is a symptom, and as such has a meaning. You would never go to the doctor to get tested (not that they always do that anyway!) if you did not feel bad.

You could never test hypotheses on clinical trials if you did not formulate these said hypotheses in the first place. Trying to understand what you intuitively think might be true.
Being right is not possible every time.
If you don't formulate hypotheses, you don't even get the possibility of being right from time to time. Science is not only in the testing, but also in the curious and imaginative mind.

I am grateful for the IL-6 idea!!!! I see you regret this already!!!
I only wrote : it could be one of the ways in which B2 has brought me even further in my healing.
Nothing to worry about! It is in no way a firm conclusion.
For the moment anyway!
Be well and with thanks,
Asklipia

 

[Asklipia]

9 weeks into B2/Manganese
Update from post #454 in bold the new observations

Now taking 37.5 to 50 mg B2 and 20 mg Manganese chelated every day. (no change)
No other supplements except :
- daily: 15 mg Menatetrenone (MK-4) with breakfast; Melatonin 3 mg + Zinc 8.7 mg + Selenium 50 mcg (these last three in the same preparation at night).
- on Sundays : 3 mg adb12
- on Tuesdays and Fridays 1 mg mb12 (started this around week 8)

What I notice compared to 2 weeks ago when I was 7 weeks into this protocol:

- good energy; a little bit better
- sleep = more dreams (not very nice ones but not that bad). Waking up a bit earlier than before. Sometimes irrepressible need to sleep after lunch. Feeling a very slight tension in my sleep;
This is changed : good sleep with no tension. No dreams at all.
- no bouts of sadness/depression/feeling overwhelmed; same
- less affected by other people's depression!!!!!! Much less empathy!!! same
- no nausea at all. Vague feeling sometimes in the stomach which I take maybe manganese induced. Nothing either painful or worrying, just a feeling, not getting worse at the moment;
No more queasy feelings in stomach.
- since the beginning of supplementation, very easy and slippery bowel movements. Transit was never a problem in the last year but now it seems there is a lot of lymph (or something oily) coating the matters. Colour normal, not very dark though; same
- pee is back to absolutely normal colour; same
- no more stuff coming out of my scalp and ears; same
- Lots of new hair growing I think; I see them around the hairline babies 1 cm long; not sure; I don't see new hairs.
- hearing more or less back to normal, with sometimes lower accuracy for a couple of hours; same
- tiny improvement in blurry vision (so tiny I am not really sure this will last); no improvement
- one shoulder hurting sometimes, much less; even less pain there
- short term memory loss by bursts, much less; even less forgetfulness
- irritation of the eyes in the morning on waking up only; not at the moment
- dry mouth (not too bad) on waking (was worse before - not sure as it comes and goes); not dry anymore, a bit pasty
- some mucous since last week coming out of my lungs which I have to spit out from time to time; gone
- sometimes a slight pain in the throat that does not last (gone next day); none
- sometimes a lot of mucous coming out of my sinuses - this stops after a couple of hours; none
- strange sharp pains that last only a couple of seconds = in my left ear deep inside, in my head at the back, behind one eye; generally followed by need to spit; none
- hair getting greasy after a couple of days; same
- even more easily satisfied by what I eat (appetite is still good) same
- sunbathing but no tan!!! see my post #463

Best wishes and good luck to all.
Asklipia

 

[SJB944]

I have recently found that my serum Ferritin has increased quite dramatically since starting to take b2. Now I can't be definitive that it is B2 but it is the only thing I have changed since my last test.

What I don't know, is what this means?

 

[Asklipia]

No more Stretch Marks!!!!

This is a new result of the B2/Manganese supplementation (10-11 weeks on).

I am not sure this is due to the above, but it has happened on their watch.
I had stretch marks on my breasts that have been there for 46 years. My husband noticed yesterday that they were gone. So I looked for his (on hips for the last 38 years) and they are gone too!!!!!!

Another sign of our bodies manufacturing more glutathione?
What is going on?
Apart from that, all is well.
Best wishes,
Asklipia