Food sensitivities and PST

[Gondwanaland]

I recently experienced salicylate sensitivities and recovered my ability to detox phenols by supplementing magnesium oxide and Saccharomyces boulardii.

These were the pieces of my puzzle:

• urea and uric acid above range in blood
• urine pH low (4.5 - 5.0)
• magnesium in urine very low below range

I would like to paste here the references that helped me most:

THE LANCET, MARCH 20, 1982, P. 691

WHAT DOES PHENOLSULPHOTRANSFERASE DO?

SIR,- Your interesting editorial on phenolsulphotransferase
(Feb. 27, p. 490) states that this enzyme has no clear physiological
function. In view of the widespread distribution of this enzyme in
gut mucosa, liver, platelets and brain,(1) it is surely reasonable to
conclude that its function is to render phenols non-toxic.

Indeed Miller at al.(2) demonstrated this in the cat, an animal that is highly
susceptible to phenol poisoning because it lacks a glucuronidation
mechanism. There may be some humans who are sensitive to phenol
poisoning.(3)

Phenols occur in tea, coffee, and various foods and are
produced by gut bacteria, and the body has to inactivate 300 mg
phenols every day. Their potential toxicity is great. The quinols can
cause uncoupling of oxidative phosphorylation. Phenols are known
to cause convulsions and coma.(4)

It is likely that the enzyme is especially important in patients with acute
hepatic damage and in uraemia. Free phenols can appear in hepatic
coma and they inhibit a variety of enzymes and mechanisms, such as
sodium-potassium ATPase, (5) aminolaevulinic acid dehydratase, malic
and a-ketoglutarate dehydrogenase and the uptake of phosphate by
cells. Their ability to chelate magnesium ions and to interfere with
Mg-ATP and phosphate transfer may be especially important for
neurones.

A rather more restricted set of phenols appear to make
some contribution to uraemic toxicity.(6)

It may be disappointing that no specific role in cerebral function has yet
been identified, but the enzyme nevertheless has general biological importance.

E. N. WARDLE
33 Hawthorn Gardens,
Kenton, Newcastle upon Tyne NE3 3DE

(1) Anderson RJ, Weinshilboum RM Phenolsulphotransferase in human tissue. Clin Chim Acta 1980; 103: 79-90.
(2) Miller JJ, Powell GM, Olavesen AH, Curtis CG. Metabolism and toxicity of phenols in cats. Biochem Soc Trans 1973; 1: 1163-65.
(3) Caldwell J, Davies S, Smith RL. Individual differences in the conjugation of paracetamol with glucuronic acid and sulphate. Br J Pharmacol 1980, 70: 112P.
(4) Matsumoto J, Kiyano S, Nishi H, Kioki J, Ichohoshi T. The convulsive mechanism of phenol derivatives Med J Osaka Univ 1963; 13: 313-24.
(5) Wardle E. N. Phenols, phenolic acids and ATPases. J Mol Med 1978; 3: 319-27.
(6) Niwa T. A. GC-MS analysis of phenols in uraemic sera. Chn Chim Acta 1981; 110:
51-57.

This reference is also useful because at the same time I experienced intermittent goiter:

13- Dietary Minerals and Drug Metabolism, Pages 371-398, GEORGE C. BECKING
Nutrition and Drug Interrelations edited by John Hathcock, Elsevier, 1978, p.376

The following unpublished, preliminary experiments indicate that the
effects of magnesium depletion on drug metabolism are more complex
than previously described by Becking and Morrison (1970b).

A possible interplay between dietary magnesium and the thyroid, and perhaps
phospholipid metabolism, is slowly emerging.

Plasma thyroxine levels in magnesium-depleted animals have been shown
to be significantly lower than controls, as expected from earlier studies of
Humphrey and Heaton (1972).

Thyroxine values of 4.3 µ /100 mL were found in deficient
animals compared to control values of 7.3 µ /100 mL.

Kato and Takahashi (1968) reported decreased drug metabolism
in thyroidectomized male rats. Unlike thyroidectomized animals,
magnesium deficient rats exhibit unaltered barbiturate oxidase and
nitroreductase activities.

Thyroid hormone levels in magnesium-depleted animals are
probably only a part of the reason for the noted changes in drug
metabolism.

You can read all about magnesium here, here and here. Especially here, including warnings and toxicity.
Free download booklet: the 2nd chapter includes a list of magnesium depleting drugs and the last chapter mentions allergies related to magnesium deficiency.
Mercola recently stated that Clostridia helps prevent sensitization to food allergens. In this case beware of overdoing S. boulardii, which is recommended to fight Clostridia strains.

Since I don't know my SNPs, I am navigating through symptoms.

I hope this info can help someone.

izzy

 

[Gondwanaland]

Just found out that I have a series of impairments with the PST enzymes. My husband, OTOH is all clear for this gene.
SULT1A1 28617057 rs1042157 A or G AG
SULT1A1 28617448 rs35728980 G or T GT
SULT1A1 28617514 i6018900 C or T CT
SULT1A1 28617574 rs4149394 C or T CT
SULT1A1 28617595 rs4149393 A or G no call
SULT1A1 28618933 rs2925628 C or T CT
SULT1A1 28632021 rs2411453 G or T GT

From here on DH also has some +/- and no calls, not the same ones as mine
SULT1A2 28603655 rs1059491 G or T GT

SULT1B1 70592790 rs2292092 G or T GT
SULT1B1 70599073 rs1847366 C or T CT
SULT1B1 70611119 rs1604741 A or G AG
SULT1B1 70612712 rs11727948 A or G AG
SULT1B1 70614259 rs1604747 A or G AG
SULT1B1 70616322 rs1354360 A or G AG

SULT1C2 108912150 rs12990757 A or G AG
SULT1C2 108912673 rs13410305 A or C AC
SULT1C2 108916044 rs4149423 A or G AG
SULT1C2 108925572 rs11689841 A or G AG
SULT1C2 108926033 rs17821546 A or G AG

SULT1E1 70709023 rs1238574 C or T no call
SULT1E1 70718282 rs3775775 A or G AG
SULT1E1 70719238 rs3775774 C or T CT
SULT1E1 70725821 rs3736599 C or T CT

SULT2A1 48377519 rs4149452 C or T CT

SULT2B1 49061724 rs3848542 A or G AG
SULT2B1 49070392 rs2665601 A or G AG
SULT2B1 49071756 rs2544800 A or G AG
SULT2B1 49077667 rs3760808 C or T CT
SULT2B1 49079246 rs2544794 C or T CT
SULT2B1 49098750 rs12460535 A or G AG
SULT2B1 49102399 rs1132054 C or T CT

SULT4A1 44225888 rs2285158 A or G AG
SULT4A1 44236864 rs4149442 C or T CT
SULT4A1 44248601 rs2285161 C or T CT
SULT4A1 44250570 rs138097 A or G AG
SULT4A1 44251326 rs2285168 A or G AG
SULT4A1 44255332 rs739230 C or T CT
SULT4A1 44255832 rs138105 A or G AG

 

[melamine]

Good sleuthing, Gondwanaland!

 

[Gondwanaland]

Thanks, @melamine ! This reminds me, I found a review about SULT
Human Sulfotransferases and Their Role in Chemical Metabolism
It brings an interesting table:

 

[Gondwanaland]

Looking further into glucuronidation:

Metabolism of xenobiotic compounds consists of phase I and a phase II biotransformation reactions, being compound modification and conjugation reactions respectively. In phase I biotransformation, the compound is modificated via oxidation, reduction, hydrolysis, or other minor reactions, to reveal a reactive group to which a conjugation molecule can react to. In phase II, a small conjugation molecule reacts with the phase I modified molecule, producing a much more water-soluble molecule that can be excreted more easily. Glucuronidation is a phase II biotransformation reaction in which glucuronide acts as a conjugation molecule and binds to a substrate via the catalysis of glucuronosyltransferases. First, in a series of reactions the cosubstrate uridine diphosphate glucuronic acid (UDPGA) is formed. The glucuronosyltransferases (UGTs) then catalyze the transfer of glucuronic acid from UDPGA to a substrate resulting in a glucuronidated substrate and leaving uridine 5'-diphosphate. UGTs are a very broad and divers group of enzymes and count as the most significant group of conjugation enzymes in xenobiotic metabolism, qualitatively because glucuronic acid can be coupled to a large diversity of functional groups and quantitatively because of the large and divers number of substrates that are formed.

Detoxification of Phenols by Sulphate Conjugation: An Alternative to Glucuronidation in an Enzymatic Liver Support System (no full access)

Hepatology. 2004 Apr;39(4):970-7.
Variation of hepatic glucuronidation: Novel functional polymorphisms of the UDP-glucuronosyltransferase UGT1A4.

Abstract
UDP-glucuronosyltransferases are a family of drug metabolizing enzymes contributing to hepatic drug metabolism and protection against environmental toxins. The aim of this study was to identify polymorphisms at the human UGT1A gene locus and to characterize their function and potential association with hepatocellular carcinoma (HCC). Genomic DNA from the blood of 363 subjects (128 patients with HCC, 235 blood donors) was analyzed for polymorphisms of the UGT1A3, UGT1A4, UGT1A8, UGT1A9, UGT1A10 genes using polymerase chain reaction, sequencing analysis. Recombinant variant UGT protein was analyzed by activity assays. In the UGT1A8 gene an A173G variant and a conserved G to A exchange at position 765 were detected in 25% and 15%. UGT1A9 exhibited two variants C3Y and M33T in 1% and 3%. UGT1A10 exhibited conserved nucleotide exchanges (128 G-->A and 696 C-->T) in 2% and 13%. In the UGT1A3 gene a W11R, a V47A variant, and a conserved G to A exchange at position 81 with an incidence of 65%, 58%, and 65%, respectively, were identified. UGT1A4 exhibited a P24T and an L48V variant in 8% and 9%. UGT1A SNPs were not associated with HCC. UGT1A4 P24T and L48V exhibited reduced glucuronidation activities: beta-naphthylamine 30% and 50%, and dihydrotestosterone 50% and 0%, respectively. In conclusion, the high prevalence of SNPs throughout the human UGT1A gene locus illustrates a genetic basis of interindividual variations of hepatic metabolism. Two polymorphisms of the hepatic UGT1A4 protein show a differential metabolic activity toward mutagenic amines and endogenous steroids, altering hepatic metabolism and detoxification.

Next step: look up the UGT SNPs on 23andMe.

 

[jason30]

Thanks, @melamine ! This reminds me, I found a review about SULT
Human Sulfotransferases and Their Role in Chemical Metabolism
It brings an interesting table:
View attachment 9380

A bit old post, but very interesting to read! Thanks for that!

I am looking into SULT at this moment, as I have:
SULT2A1 G9598T +/+ AA
SULT2A1 G9696A +/+ TT

In the table, by SULT2A1, they say DHEA by endogenous substrates.
I have no clue how to interpret this, but when someone have a Homozygous mutation, does this mean that DHEA is less made in the body or?

 

[Gondwanaland]

In the table, by SULT2A1, they say DHEA by endogenous substrates.
I have no clue how to interpret this, but when someone have a Homozygous mutation, does this mean that DHEA is less made in the body or?

I think it doesn't affect DHEA production, but it affects subsequent DHEA pathways (?)

 

[jason30]

Thanks, I keep an eye on this gene.