PUFA And Endotoxin (LPS) Inhibit Vitamin D And Thyroid Transport / Activity

Discussion in 'Scientific Studies' started by haidut, Mar 14, 2018.

  1. haidut

    haidut Member

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    The "good" news for PUFA and endotoxin just keep on coming. I already posted a few studied showing that PUFA inhibits binding of androgens to their receptor and increases binding of estrogens to their receptor. This new study shows that PUFA and endotoxin inhibit the binding of vitamin D to the...vitamin D binding protein (DBP), which results in impaired transport of vitamin D from skin to the liver, liver to kidneys and ultimately impaired cellular uptake of vitamin D. The same study also mentions that PUFA inhibits binding of thyroid hormone to the carrier protein, which combined with the DBP inhbition wreaks systemic havoc on metabolism/health of every cell. Perhaps just as importantly, the study states that physiological concentrations of PUFA are capable of interfering with thyroid binding and causing "complex abnormalities" in thyroid hormone metabolism and effects. And as usual, saturated fatty acids were devoid of such detrimental effects.

    https://www.ncbi.nlm.nih.gov/pubmed/1525046
    "...The transport of vitamin D metabolites in the plasma of vertebrates is mediated by a specific protein, vitamin D-binding protein (DBP) or group-specific component (Gc)[1-4]. DBP has also been reported to bind G-actin [5], endotoxin[6] and fatty acids[7]. Ena et a/.[8] reported that human DBP purified from serum, bound fatty acids (0.4 tool per mol of protein), whereas it contained only about 0.04mol of combined vitamin D metabolites [8]. Several drugs interfere with the binding of thyroid hormones to thyroxine-binding globulin (TBG) and free fatty acids (FFA) can also compete with the binding of steroid or thyroid hormones to their plasma-binding prorein [9-11]. Polyunsaturated but not saturated fatty acids were able to decrease the binding of thyroxine to TBG [9] and similar observations were made for the interaction of estradiol with sex hormone-binding globulin [10, 1 I]".

    "...Cairo and Ena [12] similarly observed that arachidonic but not palmitic acid decreased the binding of 25-hydroxyvitamin D3 (25-OHD3) to human DBP [12]. We therefore evaluated the effects of FFA and prostaglandins on the binding of 25-OHD3 and l~,25-dihydroxyvitamin D3 [I,25- (OH)2D3] to purified human DBP. We found that polyunsaturated but not saturated fatty acids or prostaglandins markedly decreased the affinity of vitamin D metabolites for DBP."

    "...Among the unsaturated fatty acids, the inhibitory potency was linoleic acid (18 : 2) > oleic acid (18 : 1) > arachidonic acid (20 : 4) > linolenic acid (18 : 3) > erucic acid (22: 1). The degree of unsaturation, therefore, did not markedly influence the inhibitory potency. The inhibitory effect of linoleic acid on the binding of [‘H]25-OHD, to DBP could be blocked by a large molar excess of human albumin but not under circumstances of a physiological albumin:DBP ratio (Fig. 2)."

    "...Arachidonic acid at 26 PM final concentration displaced 50% of [‘HI 1 ,25-(OH&D3 whereas that concentration of oleic, linoleic, linolenic and erucic acid displaced about 38, 34, 27 and 18%, respectively (Fig. 3). The molar ratio of unsaturated FFA: DBP necessary to decrease the binding of 25-OHD3 for DBP by 20% varied between 1.5 and 3.6 x lo4 for linolenic and arachidonic acid, respectively (Fig. 1). However, much smaller molar ratio’s were able to decrease the binding of 1,25-(OH&D, to DBP. Indeed, a molar excess of 25 (arachidonic acid), 45 (oleic acid) or 84 (linolenic acid) significantly decreased the binding (- 20%) of 1,25-(OH)2D3 to human DBP (Fig. 3)."

    "...The stereospecificity of this interaction could be demonstrated by the lack of effect of saturated fatty acids (stearic and arachidic), cholesterol and cholesterol esters. The degree of unsaturation was, however, not crucial as the effect on 25-OHD3 binding was greater for linoleic (18:2) than for oleic (18:1) or linolenic acid (I 8: 3). Moreover, arachidonic acid (20: 4) greatly decreased the binding of vitamin D metaboHtes to DBP but its further cyclic unsaturated metabolites (prostaglandin Ai and E~) did not influence the ligand DBP interaction. Unsaturated FFA esterified to glycerol or cholesterol, however, largely lost their effect on interfering vitamin D-DBP binding (Figs 1 and 3)...A physiological albumin:DBP ratio (addition of 1/~g albumin/ml) did not impair the inhibitory effect of linoleic acid and even a 200-fold molar excess could only partially impair the interaction (Fig. 2), indicating that the effect of FFA on 25-OHD3 binding might be of physiological importance in vivo."

    "...In non-thyroidal illness, however, high concentrations of FFA were probably responsible for most of the abnormal thyroxine-binding to TBG[20-22]. Indeed, in this situation a serum concentration of 1.3___0.32 and 0.72+0.34mM oleic and lineoleic acid, respectively, was capable of decreasing thyroxine-binding. This enhanced the metabolic clearance and/or cellular access of thyroxine and resulted in complex abnormalities in thyroid hormone concentration and metabolism[20-22]. Such high concentrations of unsaturated fatty acids would be sufficient to alter DBP-binding to vitamin D metabolites but the availability of these FFA for DBP may be limited by their binding to albumin."
     
  2. Vinero

    Vinero Member

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    If PUFA prevent Vitamin D from binding to it's receptor, then people who eat high-PUFA need more vitamin D.
    This means vitamin D requirements decrease for those eating mainly saturated fats like Butter, Cocoa-butter, Beef-tallow, and Coconut oil.
    In other words Saturated fats spare vitamin D and PUFA wastes it.
    Oily fish is often claimed to be a good source of dietary vitamin D, but if the fat is mainly PUFA than maybe oily fish isn't a good source of Vitamin D, as the PUFA interfere with vitamin D from binding to its receptor.

    Ray has written that animals that eat sucrose as their main carbohydrate source don't show signs of a vitamin D deficiency when fed a vitamin D deficient diet,
    whereas animals that were fed the same vitamin D deficient diet but were fed starch as their main carbohydrate, showed impaired growth or other bad effects.

    "An older experiment compared two groups with an otherwise well balanced diet, lacking vitamin D, containing either 68% starch or 68% sucrose. A third group got the starch diet, but with added vitamin D. The rats on the vitamin D deficient starch diet had very low levels of calcium in their blood, and the calcium content of their bones was low, exactly what is expected with the vitamin D deficiency. However, the rats on the sucrose diet, also vitamin D deficient, had normal levels of calcium in their blood. The sucrose, unlike the starch, maintained claim homeostasis. A radioactive calcium tracer showed normal uptake by the bone, and also apparently normal bone development, although their bones were lighter than those receiving vitamin D." -Ray Peat
     
  3. Hans

    Hans Member

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    Would this mean that PUFAs increase free estrogen?
    Increased metabolic clearance is good for excess estrogen, yet increased cellular access is very unwanted. SHBG is protective against estrogen, yet decreases metabolic clearance then?
     
  4. OP
    haidut

    haidut Member

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    Possibly yes. PUFA also increases estrogen binding to "receptors" so it increases its effects.
     
  5. OP
    haidut

    haidut Member

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    All good points. Also, since SFA makes the cell more lipophillic and vitamin D is a lipohillic steroid, SFA also help vitamin D uptake into the cell. PUFA does the opposite, by making the cell more hydrophillic.
     
  6. tca300

    tca300 Member

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    Great.. so Chris Masterjohn was at least somewhat accurate when he mentioned oleic acid can also inhibit thyroid.
     
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