Bad Experience - Vitamin A / Pregnenolone Experiment

Discussion in 'Testimonials' started by zanolachino, Apr 25, 2013.

  1. zanolachino

    zanolachino Member

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    Hi, everyone. This is my first post here.

    A few days ago, I experimented with vitamin A (InterPlexus NutriSorb A) to see what effect it might have on my skin problems: acne, dandruff, some eczema. In general, I resist supplementation, but weekly or even twice-weekly liver has not helped my skin. (As for the zinc issue discussed on the recent vitamin A and acne thread, I eat oysters about every other day.)

    I used 15,000IU per day, topically, for four days -- a small dose by this community's standards. I had no idea whether it would help, but I figured that the worst that would happen was that it would exacerbate the skin problems.

    It was a disaster, on a much deeper level. After struggling for over two years to calm my nervous system and restore restful sleep, I am suddenly back to where I started. My brain is on fire, and insomnia, which I thought I had banished for good, has returned.

    Given how stable I had been for months prior, it seems almost certain that it was the vitamin A. But how could vitamin A have this effect? Is 15,000IU for four days really enough to blast the thyroid? Could it have something to do with liver function, which I suspect is compromised?

    That's my question in a nutshell, but for anyone interested in more background, here are a few other points which may or may not be relevant:

    1. A week earlier, I tried pregnenolone for the first time. I find it hard to believe that this could be involved, as I was taking only 15mg per day, transdermally, for just one week, but now I do regret changing more than one variable so quickly.

    2. I seem to respond very badly to more than one of the canonical Peat supplements. The few times I tried them, gelatin and niacinamide also sent my nervous system into a state of extreme agitation. This all seems very significant, but I have not been able to get to the bottom of it.

    3. Conversely, one of the few supplements ever to have a noticeably positive effect is magnesium. Indeed, it is hard for me to get as much magnesium as I would like, as the common delivery routes result in bowel or skin intolerance beyond a certain point.

    Finally, since I am new here I should say that I have been following a diet which is 100% pure Peat, in terms of the foods eaten and avoided, for about two years. The majority of my calories are from dairy, and milk has done more than anything else to calm my system. However, I eat less carbohydrate than is ideal, because of mysterious blood sugar problems.

    Sorry, this was much longer than I intended. Thanks for reading!
     
  2. j.

    j. Guest

    Re: astonishingly bad experience after vitamin A

    If your vitamin D level is good I think you're less likely to suffer from vitamin A toxicity.
     
  3. Edward

    Edward Member

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    Re: astonishingly bad experience after vitamin A

    In some people too much retinol can also induce oxidative stress. Some people can react to pregnenolone even at low doses, and the symptoms often take a few days or more to appear, I've seen anecdotal accounts of this before. There are some people who have mutations in the Cytochrome P450 CYPxxxx series of genes. Those genes are responsible for steroid hormone synthesis and exogenous pregnenolone can interfere with this.

    Reduction of thyroid hormone may participate in the modulation of cytochromes P450 2C11 and 3A2 by retinol
    http://www.sciencedirect.com/science/ar ... 0598005165

    “Both hypothyroidism and retinol supplementation in rats induce CYP 3A2 and suppress CYP 2C11. Therefore studies were performed to evaluate the role of thyroid hormones in the modulation of P450 expression by retinol. Adult male Sprague-Dawley rats were given retinol as a single oral dose of 75 . Rats were killed and hepatic microsomes prepared at 24, 48, 72, and 96 hr following treatment. The catalytic activity of 2C11 was reduced maximally by retinol at 48 hr (by 30%) whereas 3A2 activity was elevated maximally at 24 hr (by 30%). The serum concentration of testosterone was not altered at any time point. However, retinol produced a decline in the concentration of thyroxine by 35% and 43% at 24 and 48 hr, respectively. These data suggest that administration of large doses of retinol may alter hepatic microsomal enzyme expression by perturbation of plasma thyroid hormone levels.

    Transient receptor potential M3 channels are ionotropic steroid receptors in pancreatic β cells
    http://www.nature.com/ncb/journal/v10/n ... b1801.html

    “Transient receptor potential (TRP) cation channels are renowned for their ability to sense diverse chemical stimuli. Still, for many members of this large and heterogeneous protein family it is unclear how their activity is regulated and whether they are influenced by endogenous substances. On the other hand, steroidal compounds are increasingly recognized to have rapid effects on membrane surface receptors that often have not been identified at the molecular level. We show here that TRPM3, a divalent-permeable cation channel, is rapidly and reversibly activated by extracellular pregnenolone sulphate, a neuroactive steroid. We show that pregnenolone sulphate activates endogenous TRPM3 channels in insulin-producing β cells. Application of pregnenolone sulphate led to a rapid calcium influx and enhanced insulin secretion from pancreatic islets. Our results establish that TRPM3 is an essential component of an ionotropic steroid receptor enabling unanticipated crosstalk between steroidal and insulin-signalling endocrine systems.”

    Given your symptoms it is possible that you have a mutation in one of your CYP genes. It’s not a bad thing, some people are thrifty with vitamin A and steroid hormone synthesis and so they need less. Are you experiencing an increased appetite?
     
  4. Wilfrid

    Wilfrid Member

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    Re: astonishingly bad experience after vitamin A

    15 mg of preg transdermally is really unlikely to give you any side effect.....
    The absorption via the skin is way more less efficient than by mouth...At worst, you are putting in your system between 1 to 3 mg of preg comparing this amount with your weight and you are probably taking homeopathic dose of it.
    There is very few studies made with transdermal vitamins....most of them were made on rodents (mostly for the vitamin A) and even less for vitamin D (few of those were on humans and mostly for children....)
    Yet the toxicity via transdermal route is, of course like Edward said, possible and this toxicity vary with the dosage... But yet 15 000 UI of A it's at worst around 3000 UI taken effectively or at "best" around 1500 UI.....and you seem to tolerate a pretty good amount of retinol ( you said that you're eating liver one or twice weekly and apparently you didn't have any side effects from it...) so it may be wise to stop the nutrisorb but if I were you, I will keep an eye more closely on any lacking nutrient (may be via blood test) and steroid synthesis ( like Edward suggest).
     
  5. Edward

    Edward Member

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    Re: astonishingly bad experience after vitamin A

    Mutations in P450 are common. P450 expression varies from population to population. I'm Okinawan and typically we need little retinol and fare better with higher carbohydrate diets particularly starch, we are quite thrifty with retinol. My wife is thoroughbred Norwegian, consumes more vitmain A than me, and she does extremely well with oats and milk and consumes more meat. On the other hand if I eat oats I swear my hair gets thinner and if I consume more than my typical ration of vitamin A my skin gets dry. I can sit and eat 3-4 cups of white rice (uncooked measurement) where as she will get small breakouts. I seem to have good beta-carotene conversion I can sit and eat a large portion of sweet potato and am fine, but if I consume too much retinol my palms turn orange. Some people can metabolize nicotine or alcohol faster than others, mutations in CYP2A6 impact nicotine metabolism, Europeans metabolize nicotine faster than most pacific populations. That is just one example, there are many variation possibilities in P450. It's also the reason some people will tolerate a drug and others will react badly, xenobiotic metabolism varies greatly.

    Gene expression isn't set in stone, expression can change, how much impact can changing a diet impact gene expression? A lot. But we still don't know to what extent. But what we do know is that you can't take a poodle feed it meat and it will change into a wolf. You can't take a tame silver fox and return it to it's more aggressive behavior and make his ears stand back up simply with diet. So some things genetic are just that, genetic. There are some genetic mutations such that manifest in what is called Zellweger syndrome which is a peroxisomal disorder (http://amzn.com/0748400532). People with this syndrome cannot eat long chain fats. No amount of fat feeding changes that. MCAD (medium-chain acyl-CoA dehydrogenase) deficiency is another one and a characteristic symptom is hypoketotic hypoglycemia. Essentially people with MCAD deficiency can't fast because they can't produce sufficient ketones. I've seen numerous examples in low-carbohydrate dieters where they exhibit strangely similar symptoms whereas some low-carbohydrate dieters seem to do just fine. You can also have a hepatic fructose-1, 6-diphosphatase deficiency which can induce lactate acidosis similar to what is experienced in elite middle distance running. You literally feel exhausted at most times. Dietary fructose can resolve the symptoms.

    If you have a symptom that is brought on from a new substance you are experimenting with if it doesn't work for you it doesn't work, don't fret over it and don't over think it too much, it doesn't mean something is wrong with you per se. For example, some people are completely convinced of low-carbohydrate dieting yet they exhibit symptoms that say otherwise, they will insist if they just do it long enough, or restrict carbohydrates more, or eat more salt, etc., that things will get better, and slowly as they insist, over time, they continue to deteriorate. Max Weber the German sociologist described in the context of religion a process called "rationalization" this principle transfers to nutritional culture and individual psychology, it is when a dogma creates a dilemma that conflicts with reality and instead of looking at things form a pragmatic and rational way the individual or culture looks for deeper meaning that only creates more confusion and more abstraction of reality.
     
  6. fabiomln

    fabiomln Member

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    Re: astonishingly bad experience after vitamin A

    I had similar simpotms taking for several weeks 10.000 - 25.000 ui of vitamin A.
    I woke up in the night as having high level of adrenaline.
    Lowering the dose every simptom disappared.

    fabio
     
  7. MyUsernameHere

    MyUsernameHere Member

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    Re: astonishingly bad experience after vitamin A

    I've never experienced anything bad with getting my Vitamin A from liver. I believe ate up to 100.000 IU in one sitting without any ill effects (or any good effects for that matter).

    I guess the synthetic supplementation might be problematic.
     
  8. OP
    zanolachino

    zanolachino Member

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    Re: astonishingly bad experience after vitamin A

    A very belated thank you to everyone who replied. I am especially grateful to Edward for all the thought and research he put into his responses.

    It took my system about a week to settle down from the misadventure detailed in my original post. In the two months since, I have conducted better-controlled experiments with both vitamin A and pregnenolone. The upshot, which I can now state with confidence:

    It was not the vitamin A which screwed me up. It was the pregnenolone.

    More details to come on the pregnenolone thread.
     
  9. j.

    j. Guest

    Re: astonishingly bad experience after vitamin A

    hahahha, same thing happened to me with pregnenolone and vitamin k. first I thought it was vitamin k, then I thought it was pregnenolone, and now again I think it was vitamin k.
     
  10. Swandattur

    Swandattur Member

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    Re: astonishingly bad experience after vitamin A

    I wonder if it's possible my son might have MCAD deficiency, because he gets very moody and irritable when he goes too long without food.
     
  11. Swandattur

    Swandattur Member

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    Re: astonishingly bad experience after vitamin A

    I know a lot of people have what seems to be reactive hypoglycemia, but my son has such extreme symptoms, that it makes me wonder if it could be this deficiency.
     
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