Vitamin A and its Interactions (Split From Vitamin D Sensitivity Thread)

aaron_c

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Update:

Within a day or two of my last post I discontinued the vitamin A and cod liver oil entirely, mostly because of concentration problems and poor sleep. In spite of stopping these supplements the pre-migraine sensation stayed steady and three nights ago after a day without coffee (I have recently been drinking about an ounce of decaffeinated espresso twice daily) I woke to a full-blown migraine that neither magnesium nor citicoline mitigated in any way. I took the pharmaceutical rizatriptan benzoate (10 mg) and that was, luckily, successful in stopping it. Since then I have made sure to take espresso as I did before, and the pre-migraine sensation backed off to what I described in the prior post.

In the past week in particular I have also experienced a heat sensation that is most pronounced in my arms, as well as nausea and a weak appetite. On the other hand my daily diarrhea has disappeared, to be replaced by normalish stool, although this only happened after I discontinued the cod liver oil (perhaps my guts also do not like the cinnamon?) and has returned to diarrhea in the past two or so days.

The sleep problems were the kind where I can't fall asleep easily, and although extra phosphatidylserine and citicoline helped a little, the sleep quality felt poor, and after a few days my concentration, as I mentioned above, began to suffer. In addition to this, my heart began to experience a burning sensation. The way that sleep worsened (and the burning sensation in my heart) felt very much like when I could not eat my raw beef (see this thread), a sensation I came to the conclusion was caused by taurine deficiency in my cells. I began taking taurine at about .8 grams with meals and also at night before bed. The first day or so I was somewhat nauseous, but this stopped and hasn't returned since. My sleep has returned to normal, however my concentration did not improve immediately, and I doubt that taurine deficiency was the only issue causing concentration issues (see below).


Iron Deficiency

As I mentioned last time, one of my chief suspicions as to the source of my (and @Gondwanaland 's and @Lou 's) adverse reactions to vitamin A has been that Vitamin A somehow changed iron metabolism. Gondwanaland indicated that hair loss in the past was helped by iron supplementation, which has led me to change my mind and agree with her that Vitamin A at the very least probably decreased iron transport to her scalp. Although I cannot now find the web site where I read this, I also read that heat sensations, particularly in the...arms or extremities, was a symptom of iron deficiency. Other symptoms include brain-fog, heart palpitations, insomnia, and all of the symptoms that go along with anemia (hard for us to differentiate from every-day fatigue). On the other hand iron toxicity appears to cause joint pain and problems regulating blood sugar, neither of which I experience. Finally, I found this chart about left-side vs right-side migraines. Essentially, things from one group will help one type of migraine but will do nothing or even exacerbate the other type.

Group A
Calcium
Iron
Chromium
Potassium
Vit B1
Vit B6 *
Vit C
Vit B15
Lecithin
Cat's Claw
Apple cider vinegar with water
Caffeine
Decrease oxygen


Group B

Magnesium
Manganese
Copper *
Zinc
Vit B2
Vit PABA
Vit E
Vit B12
Choline
Turmeric
Baking soda with water
Alcohol
Increase oxygen


I assume the comments about oxygen indicate that Group A generally decreases oxygen to the brain while Group B generally increases oxygen supply to the brain.

For the past year or so skipping magnesium and/or manganese generally would cause a migraine, and taking magnesium would improve migraine symptoms noticeably. Since this no longer seemed to be the case and my migraine coincided with a day off of decaffeinated coffee, I thought I would try taking things from Group A instead. Notice that iron is the second item in Group A. If you google around, you should also find web sites like this, suggesting iron as a cure for migraines. Two days ago I also discontinued the 3 mg of manganese that I had been taking daily, mostly based on its presence in the "wrong" column. I plan to experiment with this later.

This morning my migraine sensation has gone entirely, and I am able to concentrate again. However, I am unsure how much of this is due to taking iron and how much is due to taking some calcium hydroxyapatite (about 100 mg last night and 100 mg this morning.) The warmth sensations have also decreased, and these did so before the calcium but after taking iron, so I suspect they were related to iron deficiency. The nausea and poor appetite have also both improved, also prior to the calcium but after the iron, suggesting that iron deficiency may have been the cause.


Iron and Vitamin A

All of this has led me to think that the vitamin A has caused what may have been already low iron levels to drop even lower. Assuming I am correct, I have two questions, the first of which is why would a male (myself) who every day eats about 2 ounces of raw beef (rich in heme-iron, the most bio-available form) be deficient in iron? I have three answers. First, vitamin A, which I appear to be deficient in, might increase iron absorption through supporting gut health--which has been lacking for me. Secondly, for much of the past year I have taken a teaspoon of turmeric with each meal. According to this paper, turmeric appears to be rich in tannins, which can inhibit iron absorption. Of course, I am not entirely sure that I was iron deficient, and I am not sure that pre-existing iron deficiency is necessary for vitamin A to cause a more acute-type iron deficiency. Finally, according to the US Department of Agriculture 2 ounces of beef should have a little more than one milligram of iron, while the Linus Pauling Institute says the RDA for a grown man is 8 mg per day to avoid deficiency. Although our bodies can adapt to absorb more iron when we are lacking, perhaps it could not adapt enough.

The second question needs to be answered is why would vitamin A, which increases ceruloplasmin and therefor transferrin and ferritin saturation appear to cause iron deficiency? Also remember that vitamin A together with vitamin D prevented diarrhea, which seems likely to have improved iron absorption (one risk factor for iron deficiency is Irritable Bowel Syndrome). Even assuming I was iron deficient before, at first glance taking vitamin A should improve this situation, not make it worse.

The best answer I can currently come up with is that vitamin A may be increasing production of cytochrome c (a heme-containing protein involved in the electron transport chain). This study confirms that vitamin A deficient rat livers and hearts have about 71% of the cytochrome c of vitamin A sufficient rats. Cytochrome c is almost entirely found within the inner mitochondrial membrane attached to cardiolipin. Cardiolipin, which appears mostly in the inner mitochondrial membrane, is decreased by vitamin A deficiency, so perhaps the link between vitamin A deficiency and cytochrome c has something to do with this. In any case, increasing vitamin A might suddenly increase the body's need for iron, as it is suddenly able to attach more cytochrome c to cardiolipin within our mitochondria.


Iron and Taurine

Since taurine helped me sleep following vitamin A supplementation, and because the symptoms of iron deficiency include insomnia and heart palpitations--just like taurine deficiency--I suspect that iron deficiency somehow reduced the taurine available to my cells. This study found that taurine and iron together were more effective at treating iron-deficient anemia, so there does seem to be some kind of connection.


Iron, Molybdenum, and Sulfites

Iron and molybdenum are both necessary to form the Sulfite Oxidase (SUOX) enzyme, which converts toxic sulfites into helpful sulfates. Specifically, SUOX requires cytochrome b5, which is formed from protoheme (heme) as well as a molybdenum cofactor (MoCo). This is why people with Protoporphyria are sensitive to sulfites (thank you again Rich VanK). Protoporphyria is literally a high level of protoporphyrin IX. Protoporphyrin IX is basically protoheme without iron. Rich wrote that mercury, lead, or a genetic defect can all induce Protoporphyria, however the Mayo Clinic notes that "iron-deficiency anemia is the most common cause of increased RBC protoporphyrin," although when this happens I believe it is referred to as iron-deficient anemia and not protoporphyria.

For perhaps two years I have taken a fairly high dose of molybdenum. I now suspect that this has helped me cover for low iron in two different ways: First, it has helped push up the nunbers and function of the sulfite oxidase enzymes. This was, in fact, why Yasko and others suggest it. Secondly, xanthine oxidase, another molybdenum-containing enzyme, appears to help attach iron to its transport proteins (what we normally think of as ceruloplasm's job). I have some concern that my high levels of molybdenum might be increasing xanthine oxidase activity, which might work with the increased ceruloplasm from the Vitamin A to over-attach iron to its transport proteins. Could this make iron difficult for the body to use, or else could it change Iron transport patterns sufficiently to cause problems as I attempt to normalize vitamin A? Does molybdenum increase xanthine oxiddase activity enough to make any difference at all to transferrin/ferritin saturation? I am not sure.

In any case, I think it is possible that increasing iron (and Vitamin A) could reduce my sulfite sensitivity.


Unanswered Questions

How did vitamins A and D contribute to a functional calcium deficiency?
How does iron play into taurine transport, synthesis and/or use?
Is manganese involved, and will supplementing 3 mg per day cause problems?


In Summary

Vitamin A (and possibly vitamin D) appear to have induced functional deficiencies of iron, calcium, and (probably indirectly) taurine. Taking them and/or stopping manganese appears to be helping. I also wonder if somewhat mild iron deficiency might impact either synthesis or function of sulfite oxidase, and if iron supplementation might improve my sulfite sensitivity.
 

Gondwanaland

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@aaron_c you just explained why my hair loss worsened last year from taking B2. Can't exclude low copper though, b/c my iron and ferritin levels are always in the top of the range:confused:
I remember that my transferrin was very low many years ago when I supplemented with iron, but drs don't order that test frequently.

Also I am trying to find out what is wrong with my husband and I think it has something to do with what you posted above.

He took a Zn supplement for about 2 months and got daily diarrhea, which stopped when I gave him a multimin containing copper (no iron since his iron levels have always been way above the top range).

TMI alert

His diarrhea was liquid and black, so I think the Zn caused him to dump A LOT of iron.

Also we get this strange symptom from taking Milk Thistle, which I believe is associated with its iron mobilizing/lowering effects. DH had it again from B2 this past week. o_O

We have been avoiding high vitamin C fruits with fear to turn it into oxalates, but I think some fruit with meat and salads is a good move now to increase iron absorption. Just a few weeks ago I was craving star fruit, which is high in vit C (and oxalates? or oxalate converting potetial? @alicec ?) and noticed only good effects from it.
 

aaron_c

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Summary

Test results show I have moderately high iron in my blood, so I stopped taking iron for now. I also think I have been taking too much vitamin A in relation to vitamin D, and I have begun experimenting to see if the vitamin A relieved the "vitamin D fatigue" by preventing the use of various nutrients for bone growth. Finally, I have a new idea as to why cod liver oil seems to have increased my need for taurine.


Iron


I had an iron panel done, and the results came back showing somewhat high iron (not low, as I had predicted):

Reference ranges in brackets.

Ferritin: 128 [22-322] ng/mL
Iron: 163 [35-140] ug/dL
UIBC (Unsaturated Iron Binding Capacity): 160 [130-300] ug/dL
Iron Saturation: 50 [15-50] %
TIBC (Total Iron Binding Capacity): 323 [220-390] ug/dL

The results could look like some lesser degree of iron poisoning or hemolytic anemia (anemia from B12 deficiency), as far as I can tell. In any case, I have stopped taking iron for now.

Although I am not sure that I am wrong about vitamin A somehow preventing Iron usage by some parts of the body, I am also much less confident that I am right, and even less confident that taking iron is the best way to fix the problem if it does exist.


Was I Half-Wrong About Vitamin A?

I found this extensive article from 2006 on Vitamin A from Chris Masterjohn, which references many of the studies that Sally Fallon referenced in the Weston A Price Foundation post I linked to above. While Sally Fallon accepts the conclusion of one of the study authors that food-based vitamin A is safe but synthetic vitamin A is not, Chris Masterjohn digs into the details of the studies and produces what I see as a much more compelling conclusion: That the toxicity of vitamin a is found in a U-shaped curve. He suggests that low and high amounts of vitamin A are toxic, and because food-based (almost always fat-soluble) vitamin A is less potent than water-miscible forms like retinyl palmitate, the middle of the U-shaped toxicity curve for food-based vitamin A is farther up the graph than it is for the average supplemental vitamin A. Thus, the apparent increase in toxicity for vitamin A supplements.

Like Sally Fallon, he also very much stresses that vitamin A toxicity is negated by vitamin D intake and visa-versa. Because of this, he suggests taking vitamins A and D (and K) in a ratio that has yet to be determined. The 2006 article suggests that cod liver oil is an ideal supplement when sunlight is limited, and that it has a 10:1 vitamin A to D (IUs) ratio. Masterjohn's 2010 update on vitamins A and D, however, suggests somewhere between 4:1 and 8:1 vitamin A to D (IUs?) to be ideal. In any case, by using vitamin a to "fix" my vitamin D fatigue, I was pushing the vitamin A : D ratio way over what he is suggesting*. If he has suggested a vitamin K dosage in relation to vitamins A and D I haven't found it.

After seeing this, I began to suspect that the vitamin D fatigue might be caused by my body's use of some material for bone-building, leaving the rest of my body deficient of this nutrient, and thus tired. As I understand it, although vitamins A and D work together to build healthy bones, by itself vitamin D will try to increase bone growth and vitamin A will inhibit this at least by reducing the amount of calcium that vitamin D invites into the body. If I am right, vitamin A fixed my fatigue by preventing vitamin D from importing calcium and starting bone-building, thus preventing vitamin D from causing my body to use up...something.

In looking for this something, I have experimented with supplementing a number of minerals necessary for bone growth. My results so far:

Calcium: Not taking this may have contributed to the migraines that I mentioned before. It seems to prevent them something like the iron did.

Magnesium: I haven't changed my magnesium intake. I still take 1/8 teaspoon of magnesium three times a day. Nonetheless, I imagine it is an important part of this.

Phosphate: Taking sodium phosphate in water may have reduced my fatigue. Iron deficiency seems to induce phosphate diabetes (excessive urinary excretion of phosphates) in genetically susceptible and possibly metabolically susceptible (ie kidney disease) populations. But I am far from sure that this is the main issue, if it even is one in the first place. As I alluded to above, I am not sure what, if anything, is going on with my iron.

Manganese: Taking about 3 mg of this improved fatigue.

Copper: Taking a second cunemuspir pill (with .85 mg copper) in it today appears to have improved my fatigue markedly.

Boron: Taking 3 mg yesterday removed my brain fog, which is still gone today (I haven't taken any Boron). 3 mg might be too high for daily use. Boron appears to inhibit the breakdown of active vitamin D, and indeed, following Boron ingestion I felt the beginnings of a migraine followed by a redoubling of the "vitamin D fatigue."

Vanadium: Yesterday I doubled the 50 mcg I usually take. I didn't notice any effect. I also took Boron yesterday, and I ascribe the improvement in my brain fog to Boron both because I read that it can do that and because the improvement occurred closer to when I took the Boron than the Vanadium.​

Over the last week or so my insomnia has also worsened--the kind where I have difficulty getting to sleep, but once I fall asleep sleep decently. Last night I was sleepy much earlier, which I cautiously ascribe to Boron--it appears to help some people with insomnia. The night before last I took maybe 15-21 mg of vitamin K-2 (MK-4), which is more than the 7.5 mg I usually take each day. This also helped me get to sleep.

In summary: Although I haven't yet "perfected" how much of each mineral I need to take along with my cod liver oil, I think that the "hungry bone" theory of Vitamin D fatigue is showing promise.

Taurine

Finally, I found more information on taurine. It seems that high extracellular calcium increases taurine transport into osteoblasts, which in turn increases the concentration of Magnesium ions in the osteoblasts. I imagine this would be a necessary first step in incorporating magnesium into the bone matrix. Perhaps increased bone mineralization is responsible for my sudden need for taurine since taking cod liver oil?



*Assuming one tablespoon of cod liver oil has 1000 IU of vitamin D and 10,000 IU of vitamin A, taking an extra 12,500 IU of vitamin A every day pushed the Vit A : D ratio to 22:1.
 
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Gondwanaland

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@aaron_c you seem to be overlooking all other effects of vit D. Right now I can add from the top of my head dopamine and thyroid hormone (T4? T3? don't remember which one) formation.

Boron helps with brain fog because it interacts with dopamine and testosterone, and since you have too much circulating vit D, some additional Boron will balance that.

Cu and Mn are helping to balance excess Fe.
 

Little Bluestem

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I have osteopenia/osteoporosis. Along with the things you list, the supplement my physician recommended contains vitamin K1, vitamin K2, folic acid (should be folate), selenium, and molybdenum.
 

aaron_c

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Thanks @Gondwanaland,

I appreciate your input. I wasn't aware of a thyroid hormone link with vitamin d...I see now that they both activate the steroid hormone receptor. I posted the last not because I had all of my ducks in order but because the direction I was going in (and the test results) appeared to be counter to my prior direction, and thought I had better not wait.

Boron helps with brain fog because it interacts with dopamine and testosterone, and since you have too much circulating vit D, some additional Boron will balance that.
I understand (and agree) with the first part about boron and brain fog, but I am not sure how boron would balance excessive vitamin D. As I wrote above, I am under the impression that boron will increase the amount of active vitamin D.

@Little Bluestem : Yes, thank you. I also take vitamin K-2 (MK-4) daily. I mentioned it in relation to vitamins A and D above, but didn't single it out in the lower portion...I was so excited about it a year ago and by now I sometimes forget to mention it, but if the Weston A Price people are to be believed (and I obviously want to believe them) it is essential as well.

I haven't heard of molybdenum or selenium for bone growth before.

Last night I had insomnia, and tonight it is worse. I suspect that some combination of the copper (1.7 mg), manganese (10 mg), and/or boron (1 mg) might have done it. Today I took none of either, so it is puzzling that my insomnia has only gotten worse.
 

Gondwanaland

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I understand (and agree) with the first part about boron and brain fog, but I am not sure how boron would balance excessive vitamin D. As I wrote above, I am under the impression that boron will increase the amount of active vitamin D.
Yes, it is a synergistic effect in activating neurotransmitters and hormones.

10mg of Mn? It will increase estrogen and make you gain weight around the waist line - among other things.

Edited to add - beware of metals. You might be deficient, but at some point you can turn it into toxicity, just like with everything else.
 

Gondwanaland

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I don't know if this has already been covered here, but I was looking into vit A myself about how it can help me to recover from anemia. Vit A will increase transferrin facilitating iron transport for erythropoiesis.

And this is an awsome resource on iron: http://patient.info/doctor/non-anaemic-iron-deficiency
Possible signs of iron depletion (although more usually seen in IDA) are:
  • Angular cheilitis or angular stomatitis.
  • Atrophic glossitis.
  • Nails which may show brittleness, ridging or koilonychia (spoon-shaped nails).
  • Poor condition of skin or hair.
So when someone takes too much folate or B2 it will cause angular cheilitis due to the iron lowering effect :bulb:
 

Lou

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Does the person then need less folate/B2 or more iron?
Good question, doesn't seem it was actually answered. I've had a difficult time figuring if I'm low on iron or have excess stored which is bio-unavailable.

I was unfamiliar or have forgotten excess folate may cause low iron. Am thinking since I'm mthfr 1298 maybe I just don't need the extra folate and so stopping it for now and see what happens, if anything. Will let you know if this provokes noticeable response.
 

Gondwanaland

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I was unfamiliar or have forgotten excess folate may cause low iron.
It seems to be largely ignored here at the boards that B vitamins promote blood cell synthesis and that iron and copper will be largely mobilized/needed.

Other important factor is their (and potassium's) role in insulin sensitivity.
 

mariovitali

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@Gondwanaland

I would be particularly cautious about taking Vitamin A. According to my hypothesis (which you know already but just adding here for people reading this Thread ) Liver disease is the main culprit for our condition and High doses of Vitamin A should be avoided in case of Liver disease.

Apart from this, Iron should be avoided as it is commonly found elevated in case of Liver disease.
 

Gondwanaland

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@Gondwanaland

I would be particularly cautious about taking Vitamin A. According to my hypothesis (which you know already but just adding here for people reading this Thread ) Liver disease is the main culprit for our condition and High doses of Vitamin A should be avoided in case of Liver disease.

Apart from this, Iron should be avoided as it is commonly found elevated in case of Liver disease.
Mario, I don't have enough iron in my system to support high/frequent vitamin A supplementation. I take it once in a blue moon, when I am going thru an oxalate problem for instance...
 

Johnmac

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@Gondwanaland, sorry to come in on this conversation a year late.

I am wondering if I have copper deficiency, after a year of supplementing 25-150mg/day of zinc for pyroluria: in recent months, fatigue, staph infections (including boils that take forever to heal), huge cold sore, crabby & irritable mood, blacking out when standing - not stuff I normally get. No hair loss.

I have low-normal zinc, & my copper & ceruloplasmin were mid-normal - however I was supplementing copper the day of the test & a few days before, so these results may be invalid (?).

Do the symptoms sound like -Cu to you?