Problems With Sulphur

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"One significant function of Mn is its effect on proteoglycan (PG) and glycosaminoglycan (GAG) metabolism (Leach 1971). Manganese functions as a specific activator of glycosyltransferases, enzymes involved in the elongation and polymerization of GAG chains in connective tissue (Leach et al. 1969). Manganese deficiency affects GAGs biosynthesis and results in decreases in total and individual GAGs, especially chondroitin sulfate (CS) in chick cartilage and rat skin (Leach et al. 1969; Bolze et al. 1985; Leach 1986; Shetlar & Shetlar 1994). Manganese also effectively activates sulfotransferases, enzymes involved in GAG sulfation and synthesis (Gundlach & Conrad 1985)."​

It's worth observing if having adequate manganese makes a difference on how sulfate is metabolized. Manganese follows (for the most part) the fat-soluble route of excretion through feces, whereas sulfate is eliminated mainly in urine, like other water-soluble toxins. If sulfate is applied on the skin at the same time that a meal rich in manganese is consumed, by the time that it gets digested, sulfate may already be on its way out.
There was one study about excessive salt in the diet being soaked up by organs, especially skin. In the study, they said the excess sodium could be held in the skin without causing edema as osmotically inactive, by binding to these glycosaminoglycans. Since manganese can increase the amount of these substances, could it help to explain in part of the reason why some people can avoid increases in blood pressure after a big salt dose, while others get high blood pressure?
 

Serene

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I think I am having this issue and just had a consultation with a practitioner.

Incidentally, I got Dr. Nigh's low-sulfur protocol. It's basically a torturous anti-thyroid vegan diet for a few weeks, but there is some good information in here that might be helpful if anyone would like it. Dr. Nigh talks about structured water and stuff like that so overall I tend to like his work. The diet is just temporary to help clear the sulfur from the body.
 

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Amazoniac

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There was one study about excessive salt in the diet being soaked up by organs, especially skin. In the study, they said the excess sodium could be held in the skin without causing edema as osmotically inactive, by binding to these glycosaminoglycans. Since manganese can increase the amount of these substances, could it help to explain in part of the reason why some people can avoid increases in blood pressure after a big salt dose, while others get high blood pressure?
If that's not related to the space between cells taking up water to help normalize other compartments, it's something new to me. Saving for later..
- Regulation of Fluid Volume From the Outside: A Role of Glycosaminoglycans in the Skin Interstitium?

I think I am having this issue and just had a consultation with a practitioner.

Incidentally, I got Dr. Nigh's low-sulfur protocol. It's basically a torturous anti-thyroid vegan diet for a few weeks, but there is some good information in here that might be helpful if anyone would like it. Dr. Nigh talks about structured water and stuff like that so overall I tend to like his work. The diet is just temporary to help clear the sulfur from the body.
Nice, it's a decent approach, the best one that I've come across so far. At first glance it seems well-rounded, but it's incomplete.

He's reducing problems with sulfur to a molybdenum deficiency and assuming that the surge in hydrogen sulfide from the gut is only in response to a shortage of sulfate. Consider this: if the body sensed that there isn't enough sulfate and has no means to convert sulfite (it's building up in cell and wreaking havoc), why would it fuel an impeded pathway?

Sulfur-containing amino acids → ↑sulfite -/→ ↓sulfate​
Sulfur-containing amino acids + hydrogen sulfide → ↑↑sulfite -/→ ↓sulfate​

It can be argued that the regulatory signal is downstream, past the impaired step, but at least for me it's enough to make me look up for more factors. What about the people who already consume plenty of morbydenum and still experience the same issues? How can we expect that an approach that relies essentially on morbydenum and fartate is going to be fixing for them?

Morbydenum is only one factor that can be missing when there are problems with sulfur, the approach can't revolve on it. Maybe the intestine is injured and that's the hormonal drain. This in turn can affect cholesterol metabolism, coupled with extensive losses of tyrosine/phenylalanine may get in the way of proper synthesis of ubiquinone. If sulfite is odorless, why are people stinking? It isn't supposed to cross the intestial barrier without being oxidized, otherwise it should be rapidly cleared.

What if the person has a chronic lack of pyridoxine that leads to antioxidant deficiency that's alleviated with hydrogen sulfide? There's the sulfate-autism relationship, but it has to be accounted that pyridoxine is very important in sulfur and tryptophan metabolism.

Therefore, morbydenum is not a magic pill and there can be complications from its use. One of the concerns is that (similar to pyridoxine) it might contribute to virulence.
- Molybdenum Enzymes and How They Support Virulence in Pathogenic Bacteria

There are publications of this kind for most nutrients, but in the case of morbydenum, what bothers is that although some sulfidogenic microbes are inhibited by it, others will thrive in its presence, I guess they use it to metabolize sulfur, from the amino acids for example.

It's absorbed early in the small intestine in an efficient process, but there's always a small fraction that is not. Surprisingly, this fraction that escapes absorption was found in an experiment to decrease as the dose increased. Nevertheless, a tiny fraction of a large dose is going to be a great amount that can't be overlooked. The starting point for morbydenum to be promoting should be lower than for inhibition.

The morbydenum supplement suggested appears to be a neat option, I have been looking for something similar for a while, wasn't aware of its existence and thought that it could be worth for the lion to offer it. Advantages of supplemental morbydenum are that absorption should be superior than with foods and that it's easy to take it away from meals with ingredients that are potentially problematic.

Another concern with morbydenum is the multiple nutrient deficiencies that tend to occur in this syndrome (ubiquinone, copper, pyridoxine, ascourgic acid, and so on), some can be made worse with its isolated supplementation. In reading reviews of morbydenum supplements, you can find bizarre reactions that could have been caused by induced deficiencies.

Boosting detoxification through saunas may aggravate the situation above. If I had to choose between the sauna options, I would keep the heat therapy for being less depleting than having the additional light. The priority is to normalize the sulfur metabolism, detoxification can be postponed. When all factors are covered, microbes are no longer needed to supply what's missing, they have to be cleared and the transition can be conflictual since there are no longer interests in common. The idea is to promote hyperthermia in a conserving way so that the immune system has what it needs to address the trouble.

Stuffing yourself with sulfate while depriving of other sources of sulfur may be a bad idea if it's admitted that the condition is a purposeful adaptation, the body will seek means to recover sulfur. Even though transdermal sulfate is safer in terms of not fueling infections, this route is less regulated than ingested, making it prone to worsen imbalances and possibly taking out other nutrients as it's eliminated. Mucus integrity can be compromised due to ongoing inflammation and malnutrition, with microbes taking over. Any measure that happens to enrich mucus with sulfur in a disorganized way may be exploited by the microorganisms, which may bloom. This may even happen intentionally to make up for the restriction: it's a temporary measure, but the body doesn't know for how long it will last. It was mentioned in one of the publications posted that some people are bad responders to sulfate in spite of it being used transdermally.

Hydroxocobalamin is a good measure, it's preferable to avoid ingesting large doses.

Too much futhilamine when dealing with sulfur issues stemming from the gut can make the temporary strict regimen futile and defeat its purpose. Makes no sense to be meticulous in excluding items from the diet while advocating 2x 200 mg of futhilamine a day.

All fats deserve attention if the person is synthesizing taurine normally.
On dairy and coconut fats, they're likely healthier when raw, but I expect them to be more prone to trigger sulfur issues in such state because heat may degrade the reactive sulfur compounds, just like the alium foods are rendered milder after cooking.

The potential issues from activated charcoal were mentioned in this thread.

Despite these concerns and the seneffiosis, I think that overall it's good and will probably move people on the right direction towards recovery.
 

Amazoniac

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- Effect of Molybdate on Sulfide Production from Methionine and Sulfate by Ruminal Microorganisms of Sheep
- What Is "adequate Protein"?


In case you notice that certain traditional cheeses are particularly beneficial, this can be one of the reasons:
- Copper in Parmesan and other Cheese

Copper kitchenware can replace steel, but to avoid arbitrary ingestion, it's better to rely on supplemental powder. By the way, the cropotol above will possibly induce a copper deficiency, even more so now that apparently they've added zinc to it. :banghead:
 

Amazoniac

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'Sulfate':


- Alleviation of Metabolic Syndrome with Dietary Egg White Protein

"[..]the use of egg white is challenging in dietary therapy because of its hydrogen sulfide odor. To address this issue, lactic-fermented egg white (LE) has been developed[28]. LE is easier to consume because the hydrogen sulfide level of LE is lower than that of egg white. Ovalbumin and lysozyme in egg white are stable after the fermentation treatment (data not shewned)."​


This sugar was brought up somewhere in this thread:

- Sulfoquinovose is a select nutrient of prominent bacteria and a source of hydrogen sulfide in the human gut

"Here, we explored for the first time microbial metabolism of sulfoquinovose (6-deoxy-6-sulfoglucose, SQ) in the human gut. SQ is the polar head group of sulfoquinovosyl diacylglycerol (SQDG), a ubiquitous sulfolipid in the photosynthetic membranes of all land plants, algae, dinoflagellates, and cyanobacteria. SQDG is one of the most abundant organic sulfur compounds in the biosphere and can represent greater than 25% of the total lipids in common dietary, leafy green vegetables such as spinach, lettuce, and green onion [9, 10]. Studies on the catabolism of dietary SQDG by animals are scarce; in guinea pigs SQDG is deacylated via host-derived lipases to sulfoquinovosyl glycerol (SQG) [11]. It is not known whether host tissues are able to metabolize SQG or SQ. Some Proteobacteria can catabolize SQDG/SQG and SQ analogously to the Embden–Meyerhof–Parnas (EMP) and the Entner–Doudoroff (ED) glycolytic pathways, hence, either via the sulfo-EMP (e.g., commensal and pathogenic Escherichia coli) or the sulfo-ED pathway (e.g., Pseudomonas putida) [12,13,14]. Recently, a third pathway for SQ degradation via a novel 6-deoxy-6-sulfofructose transaldolase (SFT) was described in the aerobic Bacillus aryabhattai isolate SOS1 [15] and Bacillus megaterium DSM 1804 [16]. The intestinal strains of the Firmicutes species Enterococcus gilvus, Clostridium symbiosum, and Eubacterium rectale also expressed SFT pathway genes during anaerobic, fermentative growth with SQ [15]. Bacterial SQ-degradation products are the excreted C3-organosulfonates 2,3-dihydroxypropane-1-sulfonate (DHPS) or 3-sulfolactate, which can serve as sources of sulfite via diverse catabolic pathways of specialized sulfite-respiring and H2S-producing Desulfovibrionaceae species [17, 18]. Although mammalian cells also produce H2S in the cytoplasm and in mitochondria [19], bacteria that anaerobically respire sulfite derived from sulfate or taurine are considered the main sources of H2S in the intestine [20, 21]. Because SQDG is a frequent compound in a vegetarian diet and some gut bacteria have the catabolic potential for complete degradation of SQ to H2S via interspecies cross-feeding of 3-sulfolactate or DHPS, SQ could be a so far overlooked green-diet-derived source of H2S in the gut."

Here they tried without having it purified as well:

- Impact of dietary sulfolipid-derived sulfoquinovose on gut microbiota composition and inflammatory status of colitis-prone interleukin-10-deficient mice

"Consumption of high amounts of green vegetables or cyanobacteria such as Arthrospira platensis (commercially known as Spirulina) as dietary supplements may increase the availability of sulfonates in the intestinal tract of humans."

"While utilization of taurine by B. wadsworthia has been known for a long time (Laue et al., 1997), degradation of DHPS by this bacterium and the enzymes involved have been reported only recently (Liu et al., 2020b). Sulfonate-dependent stimulation of growth of these sulfite-reducing bacteria may promote intestinal inflammation, either owing to their cell-based immune-activating properties or the increased production of hydrogen sulfide (H2S) in the colon (Fig. 1)."

"B. wadsworthia has been linked to various types of inflammation since its discovery by Baron et al. in 1989, as it was isolated from appendicitis, abscesses and other inflamed tissues (Baron et al., 1989; Finegold et al., 1992). The potential of B. wadsworthia to induce a T helper 1 (Th1) cell-mediated inflammatory response, metabolic dysfunctions and even systemic inflammation in its host has been described earlier (Devkota et al., 2012; Feng et al., 2017; Natividad et al., 2018), but the underlying mechanisms have not been elucidated."

"The intestinal microbiota of the conventional IL-10-/- mice used in our study was demonstrated to metabolize both SQ and TC with subsequent formation of H2S. The degradation of SQ to H2S was reported to involve at least two bacterial species, the first of which converts SQ to DHPS (e.g., E. coli) and the second degrades DHPS to H2S (e.g., B. wadsworthia, Desulfovibrio sp. strain DF1) (Burrichter et al., 2018; Denger et al., 2014; Liu et al., 2020b). TC can be deconjugated by bile salt hydrolase (BSH) present in several gut bacteria (Urdaneta and Casadesús, 2017) and the resulting taurine degraded to H2S by B. wadsworthia (Laue et al., 1997; Xing et al., 2019)."

"Conventional IL-10-/- mice were fed a diet supplemented with the SQDG-rich cyanobacterium Arthrospira platensis (Spirulina)." "The results regarding effects of the sulfonates presented here focus on the cecum, as the cell density of B. wadsworthia was higher in cecal content and the observed effects were stronger than in the colon (data not shown). Feeding IL-10-/- mice the diet supplemented with 20% Spirulina led to a consumption of approximately 23 g of this cyanobacterium per kg body weight (!). This corresponds to an estimated daily intake of 200 mg SQDG per kg body weight, based on the given lipid content of the Spirulina supplement and literature data on the percentage of SQDG in the lipid fraction of A. platensis (Xue et al., 2002)." "SQ or TC were orally applied to conventional IL-10-/- mice and gnotobiotic IL-10-/- mice harboring a simplified human intestinal microbiota with or without B. wadsworthia. Analyses of inflammatory parameters revealed that none of the sulfonates induced severe colitis, but both, Spirulina and TC, induced expression of pro-inflammatory cytokines in cecal mucosa. Cell numbers of B. wadsworthia decreased almost two orders of magnitude by Spirulina feeding but slightly increased in gnotobiotic SQ and conventional TC mice. Changes in microbiota composition were observed in feces as a result of Spirulina or TC feeding in conventional mice. In conclusion, the dietary sulfonates SQDG and their metabolite SQ did not elicit bacteria-induced intestinal inflammation in IL-10-/- mice and, thus, do not promote colitis."

"In our study, Spirulina-fed mice harbored two orders of magnitude lower cecal cell numbers of B. wadsworthia than control mice, which corresponds to the lower relative abundance of Desulfovibrionaceae OTUs observed in cecal contents. Such a strong depletion of this pathobiont has not been described in the literature so far and adds to the reported beneficial effects of Spirulina. A general impact of Spirulina feeding on β-diversity of gut microbiota as observed in the present study was already described for mice previously (Hu et al., 2019; Rasmussen et al., 2009). However, the observed effects appear to be caused by bioactive compounds other than SQDG contained in Spirulina, which is also in line with the outcome of the SQ application experiment."

"Regarding transferability of results from mice to humans, it has to be pointed out that the murine and human bile acid composition differs considerably, which also includes the ratio of taurine- and glycine-conjugated bile acids (Ridlon et al., 2016)."

Related to Rafael's last post:

- The Pros and Cons of Using Algal Polysaccharides as Prebiotics

"Unlike terrestrial plants that contain PS [PlayStation] with the same sugars, many algae PS are sulfated (fucoidan, agar, carrageenan, ulvan), which contributes to their structural diversity and gives them specific properties. The reason why seaweed PSs are sulfated is unclear. Though sulfated PS are absent in glycophytes (salt-intolerant) plants, they are present in halophytes plants growing in high salinity soils. The concentration of sulfated PS and their degree of sulfation correlate with the concentrations of salt in the ecosystem, suggesting that sulfated PS reflect a convergent adaptation of algae and halophytes to high-salt environments (8). It has been proposed that sulfated PS work as polyanions generating higher Donnan potential by increasing ion density in the vicinity of the plant cell wall and facilitating ion transport at high salt concentrations (8). Sulfated PS might also prevent desiccation and osmotic stress at low tide, by scavenging water and ion in the extracellular matrix. On the other hand, the exposition of the green microalga Chlamydomonas reinhardtii to sodium nitrate enhances the concentrations and sulfation degree of its PS. This phenomenon promotes the anti-microbial and antioxidant properties of the PS, improving algal protection (9). Finally, sulfated PS also sequester heavy metals, being alginate more efficient than carrageenan and agar (10). It is unclear whether this activity facilitates metal absorption from the saline environment or reduces the deleterious effects of the heavy metals in the algal cells. These reasons probably explain why fucoidans are also found in some marine animal species such as Holothuroidea (sea cucumber), a class of echinoderm (11)."

"The colonic supply of free sulfate depends on dietary intake through water and foods, and the in situ microbial degradation of sulfated compounds including sulfomucins, heparan sulfate, or chondroitin sulfate (42, 43). Fucoidan, agar, carrageenan and ulvan are highly sulfated PS and their eventual degradation by the microbiota might contribute to increase the levels of free sulfate in the colon. Some Bacteroides species express exo- and endo-sulfatases capable of desulfating simple and complex carbohydrates (44). The released sulfate may be cross-fed by sulfate-reducing bacteria (SRB) such as Desulfovibrio, a member of the Proteobacteria phylum, conducing to the formation of hydrogen sulfide (H2S) (42, 43). H2S is the sole inorganic substrate used by the colonocyte mitochondria (32, 45). In low concentrations, H2S is detoxified by the mitochondrial sulfide oxidizing unit while in high concentrations, it inhibits the mitochondrial complex IV, reducing butyrate oxidation and oxygen consumption. This favors the diffusion of oxygen to the lumen, lowering the local anaerobiosis and contributing to the overgrowth of facultative anaerobic Enterobacteria, known to be involved in the development of mucosal inflammatory processes. Interestingly, sulfatase genes from B. thetaiotaomicron are essential to trigger colonic inflammation in genetically susceptible mouse model (46) and increased sulfatase activity and H2S concentrations have been detected in fecal samples from patients with ulcerative colitis, suggesting that this compound is involved in the initiation and/or maintenance of this disease (43, 47).

Globally, these findings suggest that it is probably important to control the abundance of sulfatase-expressing bacteria, sulfate-reducing bacteria as well as the levels of H2S in studies carried out with highly sulfated PS. Notably, some prebiotic compounds have been shown to reduce H2S production by the GM (48)."

"Our results, summarized in Figure 1, suggest that non-sulfated PS are more fermentable by the GM [General Motors], promoting SCFAs formation, and Bacteroides, Bifidobacterium, Lactobacillus and butyrate-producing bacteria growth, whereas attenuating the production of harmful putrefactive compounds."


- Enhanced Synthesis and Diminished Degradation of Hydrogen Sulfide in Experimental Colitis: A Site-Specific, Pro-Resolution Mechanism (endogenous)

Abstract said:
Hydrogen sulfide (H2S) is produced throughout the gastrointestinal tract, and it contributes to maintenance of mucosal integrity, resolution of inflammation, and repair of damaged tissue. H2S synthesis is elevated in inflamed and damaged colonic tissue, but the enzymatic sources of that synthesis are not completely understood. In the present study, the contributions of three enzymatic pathways to colonic H2S synthesis were determined, with tissues taken from healthy rats and rats with colitis. The ability of the colonic tissue to inactivate H2S was also determined. Colonic tissue from rats with hapten-induced colitis produced significantly more H2S than tissue from healthy controls. The largest source of the H2S synthesis was the pathway involving cysteine amino transferase and 3-mercaptopyruvate sulfurtransferase (an α-ketoglutarate-dependent pathway). Elevated H2S synthesis occurred specifically at sites of mucosal ulceration, and was not related to the extent of granulocyte infiltration into the tissue. Inactivation of H2S by colonic tissue occurred rapidly, and was significantly reduced at sites of mucosal ulceration. This correlated with a marked decrease in the expression of sulfide quinone reductase in these regions. Together, the increased production and decreased inactivation of H2S at sites of mucosal ulceration would result in higher H2S levels at these sites, which promotes of resolution of inflammation and repair of damaged tissue.


- Excess hydrogen sulfide and polysulfides production underlies a schizophrenia pathophysiology
 

Serene

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Messages
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If that's not related to the space between cells taking up water to help normalize other compartments, it's something new to me. Saving for later..
- Regulation of Fluid Volume From the Outside: A Role of Glycosaminoglycans in the Skin Interstitium?


Nice, it's a decent approach, the best one that I've come across so far. At first glance it seems well-rounded, but it's incomplete.

He's reducing problems with sulfur to a molybdenum deficiency and assuming that the surge in hydrogen sulfide from the gut is only in response to a shortage of sulfate. Consider this: if the body sensed that there isn't enough sulfate and has no means to convert sulfite (it's building up in cell and wreaking havoc), why would it fuel an impeded pathway?

Sulfur-containing amino acids → ↑sulfite -/→ ↓sulfate​
Sulfur-containing amino acids + hydrogen sulfide → ↑↑sulfite -/→ ↓sulfate​

It can be argued that the regulatory signal is downstream, past the impaired step, but at least for me it's enough to make me look up for more factors. What about the people who already consume plenty of morbydenum and still experience the same issues? How can we expect that an approach that relies essentially on morbydenum and fartate is going to be fixing for them?

Morbydenum is only one factor that can be missing when there are problems with sulfur, the approach can't revolve on it. Maybe the intestine is injured and that's the hormonal drain. This in turn can affect cholesterol metabolism, coupled with extensive losses of tyrosine/phenylalanine may get in the way of proper synthesis of ubiquinone. If sulfite is odorless, why are people stinking? It isn't supposed to cross the intestial barrier without being oxidized, otherwise it should be rapidly cleared.

What if the person has a chronic lack of pyridoxine that leads to antioxidant deficiency that's alleviated with hydrogen sulfide? There's the sulfate-autism relationship, but it has to be accounted that pyridoxine is very important in sulfur and tryptophan metabolism.

Therefore, morbydenum is not a magic pill and there can be complications from its use. One of the concerns is that (similar to pyridoxine) it might contribute to virulence.
- Molybdenum Enzymes and How They Support Virulence in Pathogenic Bacteria

There are publications of this kind for most nutrients, but in the case of morbydenum, what bothers is that although some sulfidogenic microbes are inhibited by it, others will thrive in its presence, I guess they use it to metabolize sulfur, from the amino acids for example.

It's absorbed early in the small intestine in an efficient process, but there's always a small fraction that is not. Surprisingly, this fraction that escapes absorption was found in an experiment to decrease as the dose increased. Nevertheless, a tiny fraction of a large dose is going to be a great amount that can't be overlooked. The starting point for morbydenum to be promoting should be lower than for inhibition.

The morbydenum supplement suggested appears to be a neat option, I have been looking for something similar for a while, wasn't aware of its existence and thought that it could be worth for the lion to offer it. Advantages of supplemental morbydenum are that absorption should be superior than with foods and that it's easy to take it away from meals with ingredients that are potentially problematic.

Another concern with morbydenum is the multiple nutrient deficiencies that tend to occur in this syndrome (ubiquinone, copper, pyridoxine, ascourgic acid, and so on), some can be made worse with its isolated supplementation. In reading reviews of morbydenum supplements, you can find bizarre reactions that could have been caused by induced deficiencies.

Boosting detoxification through saunas may aggravate the situation above. If I had to choose between the sauna options, I would keep the heat therapy for being less depleting than having the additional light. The priority is to normalize the sulfur metabolism, detoxification can be postponed. When all factors are covered, microbes are no longer needed to supply what's missing, they have to be cleared and the transition can be conflictual since there are no longer interests in common. The idea is to promote hyperthermia in a conserving way so that the immune system has what it needs to address the trouble.

Stuffing yourself with sulfate while depriving of other sources of sulfur may be a bad idea if it's admitted that the condition is a purposeful adaptation, the body will seek means to recover sulfur. Even though transdermal sulfate is safer in terms of not fueling infections, this route is less regulated than ingested, making it prone to worsen imbalances and possibly taking out other nutrients as it's eliminated. Mucus integrity can be compromised due to ongoing inflammation and malnutrition, with microbes taking over. Any measure that happens to enrich mucus with sulfur in a disorganized way may be exploited by the microorganisms, which may bloom. This may even happen intentionally to make up for the restriction: it's a temporary measure, but the body doesn't know for how long it will last. It was mentioned in one of the publications posted that some people are bad responders to sulfate in spite of it being used transdermally.

Hydroxocobalamin is a good measure, it's preferable to avoid ingesting large doses.

Too much futhilamine when dealing with sulfur issues stemming from the gut can make the temporary strict regimen futile and defeat its purpose. Makes no sense to be meticulous in excluding items from the diet while advocating 2x 200 mg of futhilamine a day.

All fats deserve attention if the person is synthesizing taurine normally.
On dairy and coconut fats, they're likely healthier when raw, but I expect them to be more prone to trigger sulfur issues in such state because heat may degrade the reactive sulfur compounds, just like the alium foods are rendered milder after cooking.

The potential issues from activated charcoal were mentioned in this thread.

Despite these concerns and the seneffiosis, I think that overall it's good and will probably move people on the right direction towards recovery.
Thanks for the thoughtful answer.

I am working with Dr. Rostenburg's clinic right now - they "specialize" in this issue, which is related to oxalates.

Been watching/reading all I can about it.

My understanding so far is:

- high oxalates can be vitamin K/calcium/vit D deficiency
- a single round of any of the tetracycline antibiotics can kill off the Oxalobacter sp. that degrade oxalates in the gut

The body adapts by storing the Ca it can't use into calcium oxalate crystals throughout the body.

- Oxalate degrades sulfur, so bacteria in the gut that make hydrogen sulfide start to overgrow to try and give sulfur to the body, causing more issues.


- Of course congested gall bladder/liver involved as well. Leaky gut from glyphosate can induce a B6 and glycine deficiency which makes the gut even leakier, and lets the sulfide/oxalate into the bloodstream - can't detoxify. Probably multiple mineral/nutrient deficiencies overall.

This makes total sense to me and seems to be what is happening with me. Just did a DUTCH hormone test and waiting to receive the urine OAT test to see what's going on metabolically for me.

As far as Dr. Nigh's protocol, I have been taking small amounts of molybdenum (25-50mcg) a few times a day. I don't believe that megadosing with a single nutrient is going to fix the problem. I initially took 50mcg and it made my head hurt, so I am going low and slow. I found this blog with some possibly dangerous advice - 1500mcg of molybdenum BID!

I have been taking taurine, B6 and a b-complex as well (health natura 15 drops BID), magnesium glycinate. Taking the butyrate, gave me loose/thin stools at first but they seem to be normalizing now. I tried doing the high-dose thiamin and had what I would call an oxalate dump that sent me to the ER. (woke up shaking uncontrollably and sweating profusely with the worst headache I have ever had).

Epsom salt baths (4 cups) every couple days are awesome and think are really helping. I did a pretty low protein/sulfur diet for about a week, which is all my body could handle. I don't do well on low protein, as I think I have been running on cortisol and adrenaline for a while and have minor muscle wasting I think. I was STARVING after that. Wolfed down a whole chicken. LOL :) Now I have been able to add meat (although I am doing smaller portions than before). I have just cut out eggs - of which I was eating 2-3 every day before, and cut out the sulfur veggies which I was eating kind of frequently (cauliflower, brussels sprouts, and asparagus). I haven't tried the b12, ginseng, or capsaicin.

So far my clinician has recommended daily coffee enemas to clean out my GB/liver, but I have to wait to do the OAT before starting the protocol. Then taking binders at night. I am pretty sensitive to probiotics (hives/itchy/erythema) so have not started those consistently yet.

I don't know how I feel about saunas, I have heard mixed things. I just alternate between my red light (which has IR) and the good ole' red chicken lamp.

Thanks again for the input.
 

Dr. B

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Avoid high sulfur foods for a while, primarily: Brassica, Eggs, Beans, Alliums, Dairy. Easy way to remember is B.E. B.A.D., as in 'them sulfur containing foods be bad for my gas'. Take plenty of supplemental molybdenum (key to optimal sulfuration pathways), and also get lots of pepto-bismul (this will help to eliminate excess sulfur from the gut) and also make iron less available to gut bacteria. I have been reading about this lately, I think it explains why I always feel bloated after eating, and burp excessively - even after having done all I can otherwise to keep from having any SIBO symptoms, (enzymes, acv, hcl, etc etc). I think this also explains why I respond so well to DMSO - I think it gives me relief as it is getting sulfur to places that are sulfur deficient (this supports the idea that I have some poor handling of sulfur). What I have gathered is, if the sulfur pathways are not running well, then to compensate, the gut will support more hydrogen sulfide producing bacteria - which over time creates poor health effects and is agitated by taking in more sulfur. Apparently people have a good success rate of correcting this problem simply by taking a break from high sulfur foods for several weeks, and increasing molydenum etc. I am trying this out as of just a few days ago. I realized I have been eating a lot of high sulfur foods for most of my life, and generally have always felt bloated, so I am interested to see if this fixes my bloat. I have always been bloated to the extent that if I lose weight it is hardly noticeable as my gut will just take up the extra slack through bloat.
does milk have significant sulfur? milk itself has like 22mcg molybdenum per serving. shouldnt that balance it out?
I seem to have problems with sulphur--both in terms of food and supplements.

I am continual problems with low copper and low selenium, to the point that my thyroid swells if I do not consume enough and I get very strong low copper symptoms. If I eat high sulphur foods, it is a constant struggle to get enough selenium and copper. My experiments with whey protein have had me feeling like my memory is completely going. I am only 28.

I am a rock climber and train 4-5 times a week. Whenever I have consumed taurine I end up with quire severe finger tendon injuries. I react poorly to garlic, b1, cruciferous veg, egg (very bad). I often can have gas that is very smells strongly of sulphur.

Any ideas, solutions, recommendations? I am vaguely familiar with concepts such as CBS mutation, methylation but there are many schools of thought that dismiss CBS mutations as false.

I really need to keep my selenium and copper high. My thyroid really suffers otherwise.

why b1? is thiamine a sulfur based vitamin? do you have issues with taurine? have you tried organic grass fed milk? beef liver?
 

Amazoniac

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Thanks for the thoughtful answer.

I am working with Dr. Rostenburg's clinic right now - they "specialize" in this issue, which is related to oxalates.

Been watching/reading all I can about it.

My understanding so far is:

- high oxalates can be vitamin K/calcium/vit D deficiency
- a single round of any of the tetracycline antibiotics can kill off the Oxalobacter sp. that degrade oxalates in the gut

The body adapts by storing the Ca it can't use into calcium oxalate crystals throughout the body.

- Oxalate degrades sulfur, so bacteria in the gut that make hydrogen sulfide start to overgrow to try and give sulfur to the body, causing more issues.


- Of course congested gall bladder/liver involved as well. Leaky gut from glyphosate can induce a B6 and glycine deficiency which makes the gut even leakier, and lets the sulfide/oxalate into the bloodstream - can't detoxify. Probably multiple mineral/nutrient deficiencies overall.

This makes total sense to me and seems to be what is happening with me. Just did a DUTCH hormone test and waiting to receive the urine OAT test to see what's going on metabolically for me.

As far as Dr. Nigh's protocol, I have been taking small amounts of molybdenum (25-50mcg) a few times a day. I don't believe that megadosing with a single nutrient is going to fix the problem. I initially took 50mcg and it made my head hurt, so I am going low and slow. I found this blog with some possibly dangerous advice - 1500mcg of molybdenum BID!

I have been taking taurine, B6 and a b-complex as well (health natura 15 drops BID), magnesium glycinate. Taking the butyrate, gave me loose/thin stools at first but they seem to be normalizing now. I tried doing the high-dose thiamin and had what I would call an oxalate dump that sent me to the ER. (woke up shaking uncontrollably and sweating profusely with the worst headache I have ever had).

Epsom salt baths (4 cups) every couple days are awesome and think are really helping. I did a pretty low protein/sulfur diet for about a week, which is all my body could handle. I don't do well on low protein, as I think I have been running on cortisol and adrenaline for a while and have minor muscle wasting I think. I was STARVING after that. Wolfed down a whole chicken. LOL :) Now I have been able to add meat (although I am doing smaller portions than before). I have just cut out eggs - of which I was eating 2-3 every day before, and cut out the sulfur veggies which I was eating kind of frequently (cauliflower, brussels sprouts, and asparagus). I haven't tried the b12, ginseng, or capsaicin.

So far my clinician has recommended daily coffee enemas to clean out my GB/liver, but I have to wait to do the OAT before starting the protocol. Then taking binders at night. I am pretty sensitive to probiotics (hives/itchy/erythema) so have not started those consistently yet.

I don't know how I feel about saunas, I have heard mixed things. I just alternate between my red light (which has IR) and the good ole' red chicken lamp.

Thanks again for the input.
If it was only an issue of poor handling of dietary oxalate, it would be easier to prevent.


"Most of body oxalate is a metabolic end-product generated largely in the liver and represents 85 % to 90 % of the total oxalate circulating in blood (endogenous oxalate). An unknown proportion of the liver-produced oxalate is removed via bile secretion. The remainder (10 % to 15 %) of blood oxalate (exogenous oxalate) originates from the absorption of food in the gastrointestinal tract (11-13). The ratio between liver-generated and absorption-related sources depends on oxalate content in ingested food (11). Both sources have a potentially important role in increasing oxalate concentrations in plasma and urine."​


On morbydenum dosing, the range that you're supplementing is what I would take as well.


1618964265613.png

The highlighted represents movement from bile to gut.
 

Amazoniac

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On the previous post, I forgot to mention that a great deal of morbydenum poured in bile is recovered (gut to plasma) with little leaving in faeces. The amount that passes through the gut daily increases proportionally to the dose, the recovery may occur at a site of the small intestine that may be infested, leading to trouble just like it happens with taurine in bile.



There was a guy on another thread complaining of issues with morbydenum supplementation, these adverse reactions aren't rare.

Since it's not inherently toxic (like poison A) and a serving of variety of foods can provide more than what's enough to trigger the adversities when supplemented, it has to be a conditional toxin, the effects are different depending on the context.

Morbydenum is knowned to interact with copper and sulfur. I would make sure that both are being covered. In terms of copper, despite its involvement in some functions that require morbydenum (such as in sulfite oxidation), the nature of the reactions noted doesn't seem to make concomitant use of copper the most likely preventive measure, it might actually make them worse if consumed along in a purified form. If it happens to mobilize copper in a disordered way, an antioxidant appears to be more appropriate. Due to this and regarding sulfur, cysteine may help, but I wouldn't discard taurine and sulfate. Ingesting morbydenum with meals that are the richest in them is worth a try.

Its enzymes are usually 'morbydoflavoproteins', taking it in isolation may lead to problems. Also, in the case of xanthine and aldehyde oxidation, the reaction is cleaner in the presence of NAD+. Without it to accept electrons, oxidation takes place with oxygen as a final acceptor, yielding some reactive oxygen specie (such as hydrogen peroxide). Therefore, niassassin and ripofflavin may be supportive. I would include pitytoxine as well, given its importance in moving sulfur in the body.

I don't expect bidiotin to remain in the gut for long around microbes that are gobbling down sulfur. Inappropionate in excess may aggravate an insufficiency. I can't think right now of an interaction with morbydenum, but assume that it's low and wouldn't be surprised if it helped to ease the negative effects.

Someone suggested chromium, off the top of my head, I would watch out for manganese and vainadium.
- "The Fallacy Of Administering Mixtures Of Crystalline Vitamins Alone In Nutritional Deficiency"

But it makes no sense for them to treat morbydenum as the ultimate solution when it's only one factor in many that can affect sulfur metabolism.

- The Cysteine Dioxygenase Knockout Mouse: Altered Cysteine Metabolism in Nonhepatic Tissues Leads to Excess H2S/HS− Production and Evidence of Pancreatic and Lung Toxicity (between cysteine and taurine/sulfate, an impairment won't even allow you to build up sulfite unless it's obtained through alternative means; can explain the detectable elevation of cysteine levels in disease and the positive response not just to sulfate, but to taurine)

If this issue is chronic, it's not good to be fixated on normalization of sulfur metabolism, there can be structural damage and attention has to be given to tissue repair as well.



Motif, if nothing suggested works, clothespin on nose.
 

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It makes no sense for those practitioners to be fixated on morbydenum, a lot of factors are capable of impairing sulfur metabolism.

The figure below has details added to a simpler version posted in this thread.

- CoQ deficiency causes disruption of mitochondrial sulfide oxidation, a new pathomechanism associated with this syndrome

"Sulfide:quinone oxidoreductase catalyzes the first step in the mitochondrial sulfide oxidation pathway. In this reaction, H2S is oxidized by SQR, forming a protein‐bound persulfide. Two electrons from the oxidation of H2S are transferred via flavin adenine dinucleotide to CoQ and then to the electron transport chain. The SQR‐bound persulfide is transferred to an acceptor such as glutathione (GSH) or sulfite, resulting in the generation of GSH persulfide (GSSH) or thiosulfate, respectively (Fig 1). The persulfide group from GSSH is oxidized to sulfite by a sulfur dioxygenase (EC 1.13.11.18; SDO) (also known as ETHE1 or persulfide dioxygenase). Sulfite can then either be oxidized to sulfate by sulfite oxidase (EC 1.8.3.1; SO) or converted to thiosulfate via addition of a persulfide catalyzed by the thiosulfate sulfurtransferase or rhodanese (EC 2.8.1.1; TST). The sulfane sulfur from thiosulfate can be remobilized by another sulfurtransferase called thiosulfate reductase (EC 2.8.1.3; TR) (Hildebrandt & Grieshaber, 2008; Kabil et al, 2014; Libiad et al, 2014; Di Meo et al, 2015)."

1620222718765.png

We have an oxygenase in the classic pathway (cysteine dioxygenase) between cysteine and sulfate/taurine, there's also one here (sulfur dioxygenase) between hydrogen sulfide and sulfate/thiosulfate.

- Loss of ETHE1, a mitochondrial dioxygenase, causes fatal sulfide toxicity in Ethylmalonic Encephalopathy


- Decreased Mucosal Sulfide Detoxification Capacity in Patients With Crohn's Disease

"[..]we provide evidence that the expression of the sulfide detoxification gene TST is not only downregulated in UC but also in CD. Inflammation is clearly associated with the observed deficiency in CD. An upregulation of the expression levels after anti-inflammatory therapy was observed in responders to infliximab therapy with complete mucosal healing suggesting that, similar to that in patients with UC, the effect is secondary to inflammation."​
 

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"The combination of transmethylation and remethylation pathways comprises the methionine cycle which occurs in most cells. However, the trans-sulfuration pathway has a limited tissue distribution and is restricted to the liver, kidney, intestine, pancreas and adrenals (3, 11)."

"Although the liver is usually considered as one of the major organs in the body that metabolises sulfur amino acids, the gastrointestinal tract (GIT), and especially the intestine, appears to be also a significant site of dietary sulfur amino acid metabolism. Several reports indicate that intestinal sulfur amino acid metabolism is nutritionally important for normal gut function and intestinal mucosal growth. Dysregulation in the intestinal sulfur amino acid metabolism leads to numerous complications and diseases."

"[..]serine is the predominant one-carbon donor for homocysteine remethylation in healthy females with adequate folate, vitamin B12 and vitamin B6 nutritional status."

"In 1965, Mudd et al. (42) were the first to show significant levels of three enzymes involved in the trans-sulfuration pathway, i.e. methionine adenosyltransferase (MAT), CBS and cystathionine γ-lyase, in rat small intestine mucosa, but at lower activities for one or more enzymes compared with the liver, pancreas and kidney. In 1972, Stegink & Den Besten (43) then showed that splanchnic organs are an important site of transmethylation and trans-sulfuration of dietary methionine for the synthesis of cysteine in human adults. They found a twofold higher plasma cystine concentration in adults given a continuous cyst(e)ine-free nutrient solution for 2 weeks via the nasogastric route compared with the intravenous route. Since then, others studies have shown that total parenteral nutrition without cysteine results in low circulating levels of cystine in newborn infants (44) and neonatal piglets (45). In agreement with the study from Stegink & Den Besten (43), plasma cystine concentrations were higher in enterally than parenterally fed piglets administered methionine as the sole sulfur amino acid source(45). These data suggest that the first-pass splanchnic metabolism is important for the synthesis of cysteine in neonates as well as adults."

"Significant advancements in our understanding of splanchnic amino acid metabolism were derived from in vivo measurements of splanchnic organ balance (46). Pig models have been extensively utilised to study human nutrition since they have similar physiology to man, especially gut physiology. Our studies in piglets showed that the net portal absorption of several indispensable amino acids, including methionine, was significantly less than 100 % of the dietary intake, ranging from 40 to 70 % (47). The importance of the gut was also demonstrated in studies where the whole-body methionine requirement was 30 % greater in enterally fed than parenterally fed piglets (45, 48). Our recent study in infant piglets using the Storch et al. isotopic model indicates that the GIT metabolises 20 % of dietary methionine intake which is mainly transmethylated to homocysteine and trans-sulfurated to cysteine (49). The GIT accounts for about 25 % of whole-body transmethylation and trans-sulfuration (49)."

"However, recent studies in pigs found negligible catabolism of methionine in enterocytes (53, 54), suggesting that the metabolism of methionine in the intestine may result from the action of non-epithelial cells or luminal microbes in the intestinal mucosa."

"As regards cysteine in the GIT, studies in pigs indicate that less than 100 % of dietary cysteine appears in the portal blood, suggesting intestinal utilisation of cysteine (47, 58). The first step in cysteine catabolism is its conversion to cysteine sulfinate via the enzyme cysteine dioxygenase (CDO) (Fig. 1). The cysteine sulfinate is then either decarboxylated via cysteine sulfinate decarboxylase to produce hypotaurine, which is further oxidised to taurine via a poorly understood mechanism, or transaminated to the putitative intermediate β-sulfinylpyruvate that spontaneously decomposes to pyruvate and sulfate (59) (Fig. 1). Rodent studies with 14C-labelled cysteine showed significantly higher oxidation when given via the intragastric (70 %) than the intraperitoneal (41 %) route, suggesting that nearly half of the whole-body cysteine oxidation occurs in splanchnic tissues (60). More importantly, subsequent work demonstrated that rat enterocytes extensively metabolise cysteine via CDO to cysteine sulfinate (61). This is in accordance with the expression of the murine CDO gene in the small intestine (62). In contrast to rodent studies, our recent studies in infant pigs showed that the fractional whole-body oxidation of enteral cysteine (22 %) is lower than parenteral cysteine (35 %)(63). We also found that splanchnic tissues (liver and gut) utilise about 40 % of dietary cysteine intake in first-pass metabolism (63). Intestinal absorption was the major metabolic fate of dietary cysteine, representing 75 % intake, indicating that the gut utilises 25 % of the dietary cysteine intake (63). We also determined that cysteine gut uptake represents about 65 % of the splanchnic first-pass uptake (63). In addition, our results in pigs suggest that gut tissues consume a substantial proportion of dietary splanchnic cysteine metabolism via non-oxidative pathways (63). We postulate that glutathione synthesis is a major non-oxidative metabolic fate for cysteine in the gut. Consistent with this, in vivo rodent studies with intravenous infusion of [15N]cysteine indicate that an important metabolic fate of cysteine in the gut is incorporation into glutathione (64)."

"Taurine is also another endproduct of cellular cysteine catabolism(1) (Fig. 1) and we recently found that taurine is produced by the small intestine in piglets (52). Along with glutathione and cysteine, taurine plays an important role in the antioxidant function in the body (65), especially in the intestine which is constantly exposed to endogenous and exogenous diet-derived oxidants. Moreover, among the numerous other physiological functions of taurine (i.e. osmoregulation, retinal and cardiac function, diabetes modulator, hepatoprotection, neuroprotection (66, 67)), taurine is also involved in bile acid conjugation (67). Bile acids are essential for intestinal digestion and absorption of lipids. In a recent study in adult patients with short-bowel syndrome (68), long-term parenteral nutrition was associated with an impaired tauro-conjugation of bile acids (enterohepatic pool) and a low biliary taurine concentration despite the long-term taurine intravenous supplementation, suggesting a partition between the systemic and the enterohepatic taurine pools. This finding suggests that the intestine plays an important role in providing taurine to the liver. Besides the fact that the majority of the intestinal taurine pool is derived from the diet and absorbed by the gut, some taurine might also come from endogenous synthesis in the gut from cysteine since CDO expression has been found in rodent small intestine (59, 62). Moreover, we also found a decrease in taurine concentration in the ileum of piglets enterally fed a sulfur amino acid-free diet compared with a complete diet (52), suggesting an intestinal synthesis of taurine from methionine and cysteine."

"The intestinal epithelium is one of the most dynamic sites of cell turnover in mammals (93). Its growth status can be modulated by various stimuli, accompanied by corresponding changes in subepithelial mucosa. Total parenteral nutrition is commonly associated with a decrease in crypt cell proliferation and epithelial renewal rate (94). Our results in piglets indicate that the minimal enteral nutrient intake necessary to increase mucosal mass was 40 % of total nutrient intake, whereas 60 % of enteral nutrition was necessary to sustain normal mucosal proliferation and growth (95). We recently demonstrated that a sulfur amino acid-free diet administered enterally to piglets for 7 d led to a reduced intestinal mucosal growth associated with villus atrophy, reduced epithelial cell proliferation, lower goblet cell number and diminished small-intestinal redox capacity (52). Moreover, using [1-13C-methyl-2H3]methionine and [15N]cysteine tracer approaches, we also found an alteration in methionine metabolism under sulfur amino acid-deficient conditions at both whole-body and intestinal levels, where the methionine pool was preserved for protein synthesis by up-regulation of homocysteine remethylation and suppression of trans-sulfuration (52). The suppression of trans-sulfuration contributed to the diminished cellular cysteine and glutathione concentrations and increased oxidant stress, which seemed to preferentially affect intestinal growth, especially in the jejunum (52)."

"Maintaining normal GSH concentration is essential to most tissues, especially the intestine, which is constantly challenged by luminal toxins and oxidants derived from the diet as well as endogenous generated reactive oxygen species. Indeed, a marked depletion of GSH, induced by buthionine sulfoximine, was shown to result in severe degeneration of jejunal and colonic epithelial cells in mice and this intestinal damage seemed to be prevented by concomitant GSH administration (102). However, the notion of an essential need of GSH for cell growth appeared to be controversial (103). Changes in the extracellular cysteine/cystine redox status per se have been shown to mediate proliferative signalling that is independent of the intracellular GSH/GSSG in colon cancer cells (104, 105). Thus, all these findings strongly suggest that sulfur amino acids methionine and cysteine play a key role in intestinal mucosal growth associated with a regulated redox status, and intestinal epithelial cell function."

"Besides its role as a constitutive precursor for protein synthesis, the role of methionine as a precursor for SAM synthesis may have greater regulatory importance for cell function and survival given its singular role in methylation reactions and control of gene expression. Once SAM is produced, it can be processed via two pathways, namely transmethylation or polyamine synthesis (Fig. 4). SAM is the major biological methyl group donor for a variety of methyltransferases, resulting in the methylation of substrates such as nucleic acids (DNA, RNA), proteins and lipids (112), as well as the synthesis of small molecules (for example, creatine, phosphatidylcholine, adrenaline), modification of xenobiotics (for example, thiols, arsenite) and inactivation of neurotransmitters (for example, adrenaline, noradrenaline, dopamine) (113). DNA methylation is a major epigenetic modification of the genome that regulates crucial aspects of its function during development and in adults, including imprinting and X-chromosome inactivation (114). In mammalian cells, DNA methylation occurs mainly on cytosine residues at the C5 position within CpG dinucleotides to form 5-methylcytosine and this reaction is carried out by two important classes of DNA methyltransferases (DNMT). DNMT1 is essential for maintaining DNA-methylation patterns in proliferating cells, whereas DNMT3a and DNMT3b, two members of the second class of methyltransferases, are required for de novo methylation during embryonic development (115). Few studies have examined the epigenetic mechanisms underlying normal gut development. Most of our knowledge on epigenetic involvement, especially methylation reactions, in intestinal metabolism and physiology comes from epigenetic dysregulation in gastrointestinal carcinogenesis, such as in colorectal cancer."

"In addition to its role in methylation, SAM is also involved in the synthesis of polyamines (Fig. 4) which are known to play a key role in cell proliferation by regulating the expression of various growth-related genes (116, 117). The intestinal epithelium is one of the most rapidly proliferating tissues in the body and, therefore, has a high demand for polyamines (118). Several studies have demonstrated that polyamines stimulate normal intestinal epithelial cell proliferation and are required for the maintenance of mucosal integrity (118, 119). Very few studies have investigated the role of SAM in intestinal cell growth related to polyamine synthesis. SAM has been widely studied in hepatocytes since the liver is the major site of SAM synthesis and degradation (4). A physiological increase in SAM has been reported to stimulate growth in liver cancer cells whereas a pharmalogical dose of SAM exerted a growth-inhibitory effect (120). The effect of SAM at pharmalogical doses may be mediated by its metabolite MTA. SAM is very unstable and converts spontaneously to MTA in the polyamine synthesis (Fig. 4). In contrast to SAM, MTA has been shown to inhibit transmethylation and polyamine synthesis (121). The removal of MTA by MTA phosphorylase is necessary both for the resynthesis of methionine (Fig. 5) and for polyamine synthesis, since MTA is a strong inhibitor of both spermine and spermidine synthases (122). In colon cancer cells, 6 h of MTA treatment (1 mm) was shown to reduce polyamine level (111). In addition, it was recently reported that SAM and MTA are able to induce apoptosis in colon cancer cell lines but not in normal colon epithelial cells (123). These opposing effects of SAM and MTA on apoptosis in normal v. cancer cells have been also previously reported in hepatocytes (120). However, the molecular mechanism of SAM and MTA on cell growth between colonocytes and hepatocytes may be different due to the presence of the MAT1A gene in hepatocytes that is absent in intestinal cells and which is differently regulated by SAM (Table 1)(4). Interestingly, the proapototic effect of MTA was not blocked by increased doses of polyamines in colon cancer cells RKO (123). Polyamine depletion has been shown to both enhance and protect against apoptosis in a cell line- and stimulus-dependent manner (124). Thus, all these data suggest that the concentration of SAM plays an important role in intestinal cell growth and apoptosis. A decrease in methionine intake or a deficiency in folate may disrupt methionine metabolism and have an impact on intestinal SAM pool and hence polyamine synthesis, which clearly emphasises the importance of dietary sulfur amino acid intake to maintain a normal intestinal growth."

"Because homocysteine methylation by betaine via betaine-homocysteine methyltransferase activity is confined to the liver and the kidney (3), choline and betaine dietary intake may have less impact on the methylation of homocysteine in the colon than folate since methionine synthase that methylates homocysteine to methionine using 5-methyltetrahydrofolate as a methyl donor is ubiquitously distributed (3). One of the consequences of folate deficiency is SAM deficiency since folate is involved in the remethylation of homocysteine to methionine, the precursor of SAM (Fig. 1). However, folate supplementation can either prevent or exacerbate intestinal tumorigenesis, depending on the timing and dose of folate intervention (126). This may be explained by the function of folate in nucleotide synthesis (Fig. 1) where rapidly proliferating tissues, including tumours, have an increased requirement for nucleotides. At present, based on lack of compelling supportive evidence on the potential tumour-promoting effect and presence of some adverse effects (127, 128), a recent review concludes that folate supplementation should not be recommended as a chemopreventive measure against colorectal cancer (129)."

"Interestingly, a low methionine intake, which decreases SAM levels and increases SAH levels, stimulates methylenetretrahydrofolate reductase (MTHFR) to irreversibly convert 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate (Fig. 1) (130)."

"[..]SAM and its metabolite MTA, at pharmacological doses, are able to down-regulate MAT2A expression and to block the ability of growth factors (leptin, insulin-like growth factor-1 and epidermal growth factor) to induce MAT2A expression and exert their mitogenic response in colorectal cancer cells HT-29 and RKO (111). They also observed similar results in vivo in wild-type mice where SAM and MTA supplementation in drinking water for 6 d decreased MAT2A expression in proximal small intestine by 20 % (111). The increased levels of intracellular SAM in cancerous colonocytes are likely to support polyamine synthesis required for growth and differentiation. However, high-dose SAM treatment was shown to inhibit growth and the effect is mediated by MTA (111). Indeed, in contrast to SAM, MTA inhibits methylation and polyamine synthesis(138). Therefore, like for folate, the dose of SAM supplementation may be a critical determinant in colorectal cancer susceptibility. In addition, due to their proapoptotic effect in colon cancer cells (123), SAM and MTA may be attractive agents in the chemoprevention and treatment of colon cancer."

"Homocysteine has been associated with the pathophysiology of inflammatory bowel disease (IBD). The two major forms of IBD, Crohn's disease and ulcerative colitis, represent chronic inflammatory disorders characterised by progressive destructive inflammation in the GIT. Hyperhomocysteinaemia has been consistently found in patients with IBD, as well as an increased level of homocysteine in colonic mucosa (139, 140). Elevated plasma and intestinal mucosal homocysteine concentration can result from either genetic defects affecting either the trans-sulfuration or remethylation pathways of homocysteine such as CBS deficiency or a polymorphism in MTHFR, or nutritional deficiencies of the vitamin cofactors (folate, vitamin B12 and vitamin B6) required for homocysteine metabolism (Fig. 1) (139, 140)."

"Several studies suggest that homocysteine may promote inflammatory processes through oxidative stress (141) and contribute to the inflammatory state of the mucosal endothelium through endoplasmic reticulum stress (142). Although the aetiology of Crohn's disease and ulcerative colitis remains unknown, gut tissue injury is the result of an abnormal immune response and involves multiple non-immune cellular systems, including intestinal microvascular endothelial cells (143, 144). Whether increased circulating or local homocysteine is involved in these phenomena warrants further study."


"The importance of the gut was also shown in piglet studies designed to estimate the whole-body amino acid requirements by indicator amino acid oxidation in enterally and parenterally fed neonatal piglets (11,17–19). These studies indicated that the whole-body requirements for threonine, BCAAs, and methionine were significantly higher in enterally fed than in parenterally fed piglets. The methionine requirement was 30% greater in enterally fed than parenterally fed piglets fed methionine alone or in combination with excess cysteine (11,19). These data suggest that intestinal metabolism of dietary methionine is nutritionally relevant."


"[..]recent evidence supports the view that tissues of the intestine capture, transform, and degrade absorbed AA before their entry into portal circulation (Fang et al. 2009, 2010a; Riedijk and van Goudoever 2007; van Goudoever et al. 2006) and thus form a critical first line of defense against the vagaries of the dietary AA supply (van Goudoever et al. 2008), acting as a "gatekeeper" to defend the organism against AA toxicity (Baracos 2004)."

"[..]recent studies (Chen et al. 2007, 2009) in vitro with isolated enterocytes seem contradictory to the view that the gut may be quantitatively important site for conversion of dietary methionine to both homocysteine and cysteine. In the studies conducted by Chen et al. (2009), enterocytes isolated from the jejunum of 0-, 7-, 14-, and 21-day-old piglets were incubated in Krebs buffer containing plasma concentrations of AA and one of the following tracer AA plus tracers: lysine, methionine, threonine, tryptophan, histidine, phenylalanine, and branched-chain AA (BCAA) including leucine, isoleucine and valine, to test whether the mucosal cells of the neonatal small intestine could degrade nutritionally indispensable AA. The results indicated that BCAA were extensively transaminated and 15–50% of decarboxylated branched-chain a-ketoacids were oxidized to CO2 depending on the age of piglets. In contrast to BCAA, catabolism of methionine and phenylalanine was negligible and that of other indispensable AA was absent in enterocytes from all ages of piglets due to the lack of key enzymes. The authors (Chen et al. 2009) concluded that previously observed extensive in vivo catabolism of methionine, histidine, lysine, phenylalanine, threonine or tryptophan by the small intestine (Stoll et al. 1998) may result from the action of luminal microbes in the intestinal mucosa (Blachier et al. 2007). In agreement with this notion, recent evidence demonstrated that dietary and endogenous AA were the main contributors to microbial protein in the upper gut of normally nourished pigs (Libao-Mercado et al. 2009), which means that microbial protein, if subsequently not digested and absorbed, may make a net loss to the host’s AA supply. However, it is also possible that 13C-methionine oxidation reported in vivo in pigs occurs by other cell types and tissues with the PDV ['Portal-drained viscera'], such as lymphocytes, fibroblast, [intestine,] pancreatic tissue, spleen tissue, or stomach as they all drain into the portal vein. In support of this view, Riedijk et al. (2007) demonstrated that 20% of dietary methionine intake was metabolized by the intestine and 40% of this was oxidized to CO2. One demand for intestinal methionine oxidation may be for synthesis of cysteine-rich mucins secreted by goblet cells involved in innate immune function (Van Klinken et al. 1998). Similarly, the observation that 14C radioactivity in the pancreas was about twice that in the intestine after administration of L-1-14C-methionine (Saunderson 1985) may imply the significant role of pancreas in the metabolism of dietary methionine, which remains to be defined."

"[..]recent evidence (Riedijk et al. 2007) suggests that the high rate of methionine transsulfuration in the gut is driven by cysteine needs for glutathione synthesis because of the oxidant stress associated with the high metabolic activity of proliferating epithelial cells."

"[..]a single meal of free AA mimicking casein composition compared with a single meal of slowly digested casein induced a stronger, more rapid and transient increase of AA oxidation. Therefore, the existing status (AA vs. protein) of nutrients used in the in vitro and in vivo studies combined with the dynamic access rate (fast vs. slow) of enterocytes to these nutrients may also result in difference in methionine metabolism between in vitro and in vivo studies. Thus, the relative contribution of PDV tissues and luminal microbes to the metabolism of dietary methionine remains to be elucidated."

"On the basis of that the small intestinal capacity to digest and absorb protein and AA is substantially greater than possible dietary inputs (Burrin et al. 1999), much of this organ’s demand for AA for maintenance may be an unnecessary burden (Bertolo et al. 2005). This raises a possibility that lowering intestinal AA metabolism without compromising gut absorptive capacity or protective functions may be promising for improving AA nutritional efficiency (Fang et al. 2010a). To test this hypothesis, Peng and co-workers (Fang et al. 2009, 2010a, b) conducted a series of studies with piglets implanted with arterial, portal and mesenteric catheters as the animal model and with DL-HMTB and DL-MET taken as the potential paradigms for ‘‘more’’ and ‘‘less’’ bypass-the-intestine AA, respectively. The results indicated that despite the difference in methionine sources, the first-pass utilization of dietary methionine by the intestine remained at ~30% of intake (Fang et al. 2010a). Similar results in piglets fed milk protein have been obtained in a previous study (Bos et al. 2003), in which dietary methionine intake is about 1.5-fold that administered by Fang et al. (2010a). These results suggested that the fraction of methionine might be more constant than the absolute amount of methionine that extracted by the intestine in its first-pass. It would appear that the more the local availability of dietary methionine absorbed into enterocytes, the more the absolute amount of methionine that metabolized by the intestine."
 

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White carrots are difficult to find, but the dark ones are less so. They're likely a better option than the orange for people dealing with gut sulfur issues, the pigments should be protective. There are varieties that have a sinister coloration, almost pitch-black on the exterior and interior. Interestingly, below they report that some of them are low in macabrotenes, these are not just hidden.

- Carrot Anthocyanin Diversity, Genetics, and Genomics
- Bioactive Compounds and Antioxidant Capacity in Anthocyanin-Rich Carrots: A Comparison between the Black Carrot and the Apulian Landrace “Polignano” Carrot

- Comparing carotene, anthocyanins, and terpenoid concentrations in selected carrot lines of different colors

1622246699301.png



1622246708865.png
 

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"The factors responsible for inducing a deficit in CoQ10 status in secondary CoQ10 deficiencies are currently not completely understood, but in some cases may be disease-specific, for example the inhibition of the mevalonate pathway by high phenylalanine concentrations in PKU, or the low blood levels of vitamin B6 reported in MPS patients—the active form of vitamin B6, pyridoxal 5-phosphate, is an important cofactor required by the CoQ10 biosynthetic pathway [47].

OS-induced degradation of CoQ10 has been suggested as a possible contributory factor to the deficit in the level of this isoprenoid reported in certain diseases, although this has yet to be confirmed or refuted [49]. In addition, the possibility arises that OS may also inhibit the enzymes of the CoQ10 biosynthetic pathway, which may also cause a diminution in cellular CoQ10 status, although this putative mechanism has yet to be investigated. Figure 4 outlines the possible causes of secondary CoQ10 deficiency in PKU, MPS and METC disorders."​
 

Amazoniac

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- Dealing with moles and the significance of avocado

Molecular mass:

- Methionine: 149 g/mol
- Cysteine: 121 g/mol
- Sulfate: 96 g/mol​

They simplify in considering that both amino acids are consumed equally. Therefore..

149 g/mol + 121 g/mol = 270 g/mol ÷ 2 = 135 g/mol​

Relativizing these toxins:

- 135 g/mol of SAAs = 100%
- 96 g/mol of sulfate = ?

96 g/mol ÷ 135 g/mol ≈ 70%​

If the amino acids are oxidized to sulfate, the differences in molecular mass will show up in the yield, that should only be 70% of the starting weight, or 0.7 g of sulfate/1.0 g of sulfur amino acids as found in the table.

They assume an intake of 4 g of SAAs/d, which should result in 2.8 g of sulfate.


It's only the first value that has to be compensated if the impairment is in metabolizing the amino acids, preformed sulfates can be disconsidered. A teaspoon of magnesium sulfate provides about 2 g of sulfate, so, 1.5 tsp could make up for it.

However, 4 g of SAAs/d is beyond needs when the person isn't wasting sulfur. If 3 g/d are enough, that would require about 2 g of sulfate, which is the amount contained in a teaspoon of magnesium sulfate.
 

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