Acetaminophen (Tylenol) Depletes DHEA-S And Other Sulfated Steroids

Discussion in 'Scientific Studies' started by haidut, Feb 9, 2018.

  1. haidut

    haidut Member

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    It is well-known that in animal studies acetaminophen has a potent anti-androgenic and feminizing effect. In some animal models it also reliably causes autism-like symptoms. Given its widespread use and heavy marketing by hospitals, especially to pregnant women (due to its lack of effect on clotting) uncovering the mechanism behind these negative effects is very important.
    The study below discovered that acetaminophen lowers significantly the levels of sulfated steroids and especially DHEA-S. Steroids like pregnenolone sulfate (PS) and DHEA-S are the principal long-term storage forms for pregnenolone/DHEA and depleting them can lead to lack of precursors for vital steroidogenic functions in the placenta and fetus. It has also been shown that lowering of pregnenolone/DHEA is akin to accelerated aging, which is undoubtedly quite dangerous for both mother and fetus.

    http://www.ebiomedicine.com/article/S2352-3964(18)30037-9/fulltext
    "...
    • We use metabolome analysis of 3570 individuals to identify the effect of acetaminophen on metabolic processes.


    • Acetaminophen use is associated with decrease sulfation of sexual hormones.


    • These findings are relevant in the context of current debate on the use of acetaminophen during pregnancy
    Despite decades-long use of acetaminophen, there is an incomplete understanding of the mechanism of action, and of the potential for adverse metabolic effects. Recent epidemiological and animal work supports an effect of acetaminophen on reproductive processes and hormonal homeostasis. We observe a consistent and reproducible effect of acetaminophen use on the levels of sulfated sex hormones. This is relevant to the investigation of hormonal homeostasis during pregnancy – acetaminophen is the most commonly used analgesic by pregnant women. It also opens the door to investigating the role of sulfated hormones in pain management."
     
  2. Amazoniac

    Amazoniac Member

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    As a coincidence I was reading something related:

    Are we getting enough sulfur in our diet?

    "Methionine and cysteine are both required for protein synthesis by simple-stomached mammals and avian species [1]. For optimal growth, diets must provide these two amino acids, or methionine alone. The physiological requirements for cysteine can be met by dietary cysteine or by an excess of dietary methionine. The molar efficiency of trans-sulfuration, i.e. methionine sulfur converted to cysteine sulfur, is 100%. Cysteine can reduce the requirements of dietary methionine even though no cysteine is converted to methionine in higher organisms by sparing its utilization for essential processes. From the standpoint of the diet, methionine alone is capable of providing all the necessary body sulfur, with the exception of the two sulfur-containing vitamins, thiamin and biotin."

    "Sulfation is a major pathway for detoxificication of pharmacological agents by the liver. As already mentioned, certain drugs that play a key role in the treatment of cartilage anomalies, such as acetaminophen require sulfate for their excretion."

    "Sulfur amino acids contribute substantially to the maintenance and integrity of the cellular systems by influencing cellular redox state and the capacity to detoxify toxic compounds, free radicals and reactive oxygen species [16]. Cysteine and methionine are not stored in the body. Any dietary excess is readily oxidized to sulfate, excreted in the urine (or reabsorbed depending on dietary levels) or stored in the form of glutathione (GSH). Even in extreme situations, such as when tryptophane deficiency leads to a general catabolic effect, the organism tries to spare the loss of sulfur by continuing to store any available sulfur as GSH in the liver [17]."

    "Cartilage, less essential for survival, may not fare well under conditions of sulfur deprivation, explaining why dietary supplements containing sulfur (chondroitin sulfate, glucosamine sulfate, MSM (Methylsulfonylmethane), etc.) may be of benefit in the treatment of joint diseases [20]. Neither GSH nor GAG synthesis have been investigated in this context."

    "Even sulfurated water hydrotherapy, many times accompanied by the ingestion of such waters, and considered an empirical treatment for a variety of diseases, has been shown to involve the GSH related antioxidant cascade [21,22]." "Since all the dietary supplements investigated containing sulfate, including MSM [27] are readily metabolized prior or shortly after absorption to sulfate or small molecular weight intermediates, they should be able to spare losses of GSH associated with dietary deficiencies, increased utilization due to disease or altered immune function." "Reactive oxygen species (ROS) are generated during normal cellular activity and may exist in excess in some pathophysiological conditions, such as inflammation or preperfusion injury. These molecules oxidize a variety of cellular constituents, but sulfur-containing amino acid residues are especially susceptible [28]."

    "At low intracellular concentrations of methionine, remethylation of the metabolic product is favored over transsulfuration, and methionine is conserved. With increasing methionine intake, the transsulfuration pathway, which provides a substrate for GSH synthesis, is increased.

    Thus, under conditions of low SAA intake, protein synthesis will be maintained, and synthesis of sulfate and GSH will be curtailed. Changes in the availability of GSH are likely to influence in a negative fashion the function of the immune system and of the antioxidant defense mechanisms."

    "High dietary intakes methionine (5–6 g/day) on the other hand have been shown to raise plasma levels of homocysteine, despite adequate intakes of B vitamins [31-33]. This raises some concern as one does not want to activate the immune system at the cost of enhancing monocyte adherence to endothelial cells."

    "low intake of SAA causes antioxidant defenses to become compromised.

    A reduction in the levels of GSH, and consequently of antioxidant defenses, may increase the risk of damage to the host via transcription factor activation leading to up-regulation of proinflammatory cytokines, such as nuclear transcription factors and activator proteins, induced in turn by agents such as hydrogen peroxide, mitogens, bacteria, viruses, and UV and ionizing radiation.

    Oxidant damage to cells will give rise to a cascade of proinflammatory effects by the production of lipid peroxides."

    "Studies by Margalit et al [36] has provided clear evidence in mice that elevated levels of GSH inhibit PG [Procter and Gamble] production"

    "Our findings (Fig (Fig3)3) clearly demonstrate that S retention occurs during the consumption of low levels of protein. When less than 10 mmoles of sulfur derived from dietary proteins are consumed, supplementing the diet with 10 mmoles of L-methionine was accompanied by retention of this amino acid. At higher levels of dietary protein intake, when the requirements of sulfur are presumably met, essentially all the methionine added to the diet is excreted in the urine."

    "Consumption of sparkling mineral water containing 0.5 g of sulfate/liter (in this case San Pellegrino, one of the very few mineral waters that contains sulfate ions) throughout the day (2 liters containing approximately 10 mmoles) was accompanied by quantitative excretion of sulfate when dietary protein levels supplied 25 mmoles of SAA or more per day (Fig (Fig77)."
    "These findings support the observation, sometimes disputed, that inorganic sulfates are readily absorbed and excreted in urine, in spite of the osmotic effects that they can generate and which lead to their use as laxatives [11,41]."

    "The water in our studies, San Pellegrino, from an Italian source is stated in the label to contain .535 g sulfate ions per liter. We found experimentally that the batches used did not vary more than 5% from the stated value. Inorganic sulfates are only very minor components of our diet. Some processed or enriched foods contain minute amounts of sulfites as preservatives and certain additives included in flour, for instance, (ferric sulfate) can contain sulfate. Garlic, onions, and brussel sprouts contain significant amounts of sulfur."

    "In milk and dairy products the methionine/cysteine ratio is around 3/1. It is roughly the same in fishes such as canned tuna, which we used as a source of protein supplement in our studies, and in meats. In eggs, soy beans and other plant products it is around 4/3. The amount of protein in the various foods varies considerably, and the amount of SAA fluctuates. Chicken, fish and beef proteins contain an average of around 5% of SAA. Dairy products, milk, cheese, etc, contain lower levels, around 4%, primarily due to the lower content of SAA in casein. The whey protein fraction, accounts for about 20% of the milk proteins (rich in lactoglobulins) contains more SAA, and is used therapeutically or as a dietary supplement. Plant proteins, in addition to be present in lower amounts, are relatively low in SAA, averaging below 4%. The highest content of SAA is found in egg products, the egg white containing around 8% of SAA."

    "Finally it may be relevant to conclude this review with a statement taken from Sir Stanley Davidson and Passmore's classic textbook of Human Nutrition and Dietetics [61] who suggested that "it is not unlikely that some of the effects of protein deficiency are in fact due to failure of sulfur containing intermediates or even to sulfur containing polysaccharides. It is even possible that the ancient nostrum of 'brimstone and treacle' (sulfur and molasses) had nutritional value unsuspected by modern knowledge"."
     
  3. Wagner83

    Wagner83 Member

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    DMSO anyone?
     
  4. Amazoniac

    Amazoniac Member

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    It's so bizarre to review sulfur in humanoids and not mention taurine a single time.
     
  5. Wagner83

    Wagner83 Member

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    I'm sorry.
     
  6. Amazoniac

    Amazoniac Member

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    ?
     
  7. OP
    haidut

    haidut Member

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    I guess this may be one reason it helps the liver - provide the sulfur needed for sulfation and excretion of so many toxins (including acetaminophen).
     
  8. OP
    haidut

    haidut Member

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    Taurine, thiamine and biotin have all been shown to benefit liver health, increase excretion of estrogen, and protect from heavy metal toxicities (excretion of some of which also depends on sulfur). I guess now we know part of the reason.
    I wonder if they also raise steroid levels. We know taurine does, so now I am wondering if the body would synthesize only as much steroid from a certain group as the amount of the available sulfur for sulfation. So, sulfur deficiency could lead to low levels of DHEA-S for example even though DHEA levels may be normal.
     
  9. Murtaza

    Murtaza Member

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    @haidut
    “Increased mean levels of DHEA sulfate is significantly associated with increased clinical severity of male pattern androgenic alopecia.”[1]

    “Increasingly, in both sexes, it appears that DHEA may rise during stress as a result of a deficiency of thyroid, progesterone, and pregnenolone.”[2]

    “These data show that DHEA sulfate concentrations increase in response to both acute and chronic (repeated) stress and provide another measure of HPA activity that parallels cortisol during acute responses to stress but diverges in chronic or repeated stress.”[3]

    "These data suggest that prolactin modulates the secretion of DHEA sulfate: an increase in plasma levels of prolactin is correlated with elevated concentrations of DHEA sulfate, whereas a decrease in prolactin is followed by a fall in DHEA-sulfate.”[4]

    "A dose-response relationship between serum prolactin and DHEA sulfate was found in hyperprolactinemic patients." "In summary, we found a direct synergistic effect of prolactin on adrenal androgen secretion.”[5]

    "Eighteen men aged 18 to 32 with rapidly progressive male pattern baldness had serum DHEA sulfate and testosterone measured. DHEA sulfate levels were elevated in all patients, ranging from 340 to 730 micrograms/dl. The patients were otherwise healthy and serum testosterone levels were within normal limits. A control group of men of similar age without hair loss had lower DHEA sulfate levels ranging from 124 to 300 micrograms/dl. The biochemistry of androgens, particularly DHEA sulfate, suggests that adrenal hyperactivity may initiate alopecia in young men who are genetically susceptible.”[6] - The Danny Roddy Weblog

    thoughts?
     
  10. Wagner83

    Wagner83 Member

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    For the record Sea posted information (which I already linked to) on how it could affect liver health negatively, but from what I remember Dmso has quite the anecdotical feedback on treating joint health, arthritis etc... Garlic (for various reasons) and onions could be worth adding to the diet.
     
  11. Amazoniac

    Amazoniac Member

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    2005 Patent For Topical Magnesium Chloride To Raise DHEA-S Levels
    The guru discusses in brief why he used chloride instead of sulfate, the levels still increased.
     
  12. paymanz

    paymanz Member

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    That requires molybdenum(to activate Sulfite oxidase) to work i believe.
     
  13. Sucrates

    Sucrates Member

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    Is the assumption that acetaminophen detoxification depletes sulfur, leading to lower levels of sulfated steroids?

    Would the substances used to protect the liver from acetaminophen be expected inhibit the lowering of sulfated steroids also? (Vitamin C, anything that increases glutathione, various herbs?)

    @Amazoniac , @haidut
     
  14. Amazoniac

    Amazoniac Member

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    Zeus, why some people react to those from supplements but I assume not from foods?

    --
    @Sucrates - I didn't know what to reply.
     
  15. OP
    haidut

    haidut Member

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    I think taurine can be very easily contaminated. Same with biotin. Seem to be a waste product of some industrial process. Thiamine seems to be a lot safer, at lest the regular Hcl variety.
     
  16. Vinero

    Vinero Member

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    I experienced that, contaminated taurine. I ordered some cheap taurine powder that was supposed to be 100 % taurine with no added fillers.
    I felt sick immediately after consuming one dose of it.
    I also felt poisoned one time after taking a l-theanine supplement (which took me a week to recover from), which I had ordered and used a few times before without issues, so I assume they changed the ingredients or something.
    I am kind of scared to try out most commercial supplements.
    Just because it comes from a bodybuilding website doens't mean its high quality.
    I stick to a couple of redbulls if I want some taurine, that is way safer in my experience.
     
  17. raypeatclips

    raypeatclips Member

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    Theanine made me feel ******* weird, which last 3-4 days after I took it. Didnt feel like I was with it, felt derealized.

    I'm worried about trying supplements out too now after several bad reactions, and pretty much no good reactions I can think of. I wondered if a poor gut was causing negative reactions to things that would otherwise benefit me.
     
  18. Vinero

    Vinero Member

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    It makes me wonder what could be causing that.
    It's probably made in china were all sorts of quality controls lack, causing heavy metal contamination and other very bad stuff..
    I literally felt poisoned when I took theanine, and took a week to recover from.
     
  19. Amazoniac

    Amazoniac Member

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