Problems With Sulphur

[Amazoniac]

You are a very bad poet. Continue focusing on witty word plays instead.

OHHH H HHHHH O HHHHHHH
HHHHH H HHHHH H HHHHHHO
OHHHHH H HHHHH H HHHHH
HHHHHHH O HHHHH H HHHHO

No, not really. Why?

His experience with dairy fat was negative and it can be justified, it has to be somehow. If I remember it right, there was no previous interest from his part to switch to other fats, he wased determined to make them work.

The problem when you keep rehashing the virtues of these fats or recruit semi-gods to praise them along, the discussion is geared towards explaining how such events are unlikely and downplay adverse experiences.

The primary impact of the saturated milk fat lies in the unique fatty acid composition consisting of high levels of hydrophobic stearate that places demand on the host for efficient emulsification by bile salts. The body adapts and shifts the composition of bile toward a greater taurocholate:glycocholate ratio— taurocholate being the much more efficient emulsifier for hydrophobic fats.

That's confusing, there's something else to the story.

Supplementary Table Ein from their first publication posted:

Spoiler

If long-chain fats indeed have such effect on bile composition..

Dietary fat-induced taurocholic acid production promotes pathobiont and colitis in IL-10−/− mice​

..why only milch fat allowed them to thrive in the immunodysfunctioned gurus?

Supplementary Figure Zwei:

Spoiler

- Differential effects of coconut versus soy oil on gut microbiota composition and predicted metabolic function in adult mice

"Cecal contents from HFC [coconut oil] fed mice had a higher abundances of the class Deltaproteobacteria compared to HFS [soybean oil] mice. The increase in Deltaproteobacteria has been described for mice fed a lard-based HF diet [3]; in addition, a significant bloom in Bilophila wadsworthia, a member of the Deltaproteobacteria has been found in mice administered a diet rich with saturated milk fat [5]. In the work by Caesar et al [6], Deltaproteobacteria were increased in fish-oil-fed mice. An increased prevalence of Proteobacteria has been proposed as diagnostic signature of gut dysbiosis and risk of disease [20]."​

These fats might exert all their protective effects in spite of the inconvenient in susceptible people.

 

[Kartoffel]

His experience with dairy fat was negative and it can be justified, it has to be somehow. If I remember it right, there was no previous interest from his part to switch to other fats, he wased determined to make them work.

In my discussion with him, he was all about coconut oil. I ate lots of coconut oil, it made me feel bad. Here, see, just eating it once drastically increases your endotoxin. If one-time feedings increase endotoxin that can hardly be explained be increased proteobacteria.

"Cecal contents from HFC [coconut oil] fed mice had a higher abundances of the class Deltaproteobacteria compared to HFS [soybean oil] mice. The increase in Deltaproteobacteria has been described for mice fed a lard-based HF diet [3]; in addition, a significant bloom in Bilophila wadsworthia, a member of the Deltaproteobacteria has been found in mice administered a diet rich with saturated milk fat [5]. In the work by Caesar et al [6], Deltaproteobacteria were increased in fish-oil-fed mice. An increased prevalence of Proteobacteria has been proposed as diagnostic signature of gut dysbiosis and risk of disease [20]."

So when we take these results and the result from the initial study, the only conclusion we can arrive at is: Everything increases proteobacteria. Butter, Lard, Fish-oil...it seems to randomly vary between studies.

The problem when you keep rehashing the virtues of these fats or recruit semi-gods to praise them along, the discussion is geared towards explaining how such events are unlikely and downplay adverse experiences.

Well, kind of, but the fact remains. You can't just ignore all the evidence showing that they cause the opposite of dysbiosis in most instances. That isn't the same as to say that studies as this one are impossible. The interesting thinh is find out how these results happen. When the explanations of the authors don't make sense there is clearly something else we have to find out.

In this study they compared a butter diet to virgin olive oil. They also found higher levels of proteobacteria in the butter mice, but the difference was small.

Influence of a diet enriched with virgin olive oil or butter on mouse gut microbiota and its correlation to physiological and biochemical parameters related to metabolic syndrome

However, the also found a significant increase of sulfate reducing bacteria, and the difference in food intake and weight gain were striking between olive oil and butter rats. They have some alternative explantions for the differences.

"However, the diet enriched in butter showed a clear, significant increment in the presence of Desulfovibrionaceae, which was consistent with significantly higher levels of Desulfovibrio and its key species D.desulfuricans. In this respect, not only did the EVOO diet have significantly lower levels than those of the butter group but these values were also lower, although not significant, than those found in the standard diet at the three taxonomical levels.

Desulfovibrionaceae are sulfate-reducing bacteria that could be sustained by butter sulfate sources, in part via cross-feeding mediated by Bacteroides-encoded sulfatases, since chondroitin sulfate, a common dietary supplement of animal origin, has been shown to stimulate Desulfovibrio intestinal growth.​

The lower levels found in the EVOO diet, even with respect to the SD diet, could be explained by the elevated presence of polyphenols in this type of fat. In fact, another high polyphenol food, such as table grapes, has been shown to decrease the intestinal abundance of sulfidogenic (Speaking about benefit of whole foods and all its' components) Desulfobacterspp. and the Bilophila wadsworthia-specific dissimilatory sulfite reductase gene

[About endotoxin] Being part of the Proteobacteria and therefore Gram-negative bacteria, which present LPS in their outer membrane, Desulfovibrio fits this physiological effect. However in this study the correlation is not extended to the whole phylum neither to other proteobacterial taxa with significant differences between diets. Therefore, it is reasonable to consider other factors specific to this taxon affecting the LPS translocation through the tight junctions. One of these factors could rely on its sulfidogenic ability, since both sulphite and hydrogen sulphide have been implicated in intestinal toxicity and ultimately in the breakdown of the colonic epithelial cell barrier and the genesis of inflammation

On this subject, Patterson et al. [29] obtained significant differences both at the family and genus level when comparing palm, safflower, fish and olive oil with low
fat diets, being olive oil the diet with the highest value. Bacteroides is a bile resistant strict anaerobe [30, 31] so this could be a reason for its specific increment after an olive oil diet, well known for its cholagogue [what a fancy, old word] effects [32], provoking a microenvironment that would give an adaptive advantage to the genus. In the same way, the presence of antioxidant polyphenols in virgin olive oil could protect anaerobic growth from oxygen microenvironments and this would explain as well the light increase of this genus in a safflower oil supplemented diet [29], also rich in polyphenols.
​

Maybe it's not so much about the type of fatty acid but about what is missig from an artifical diet. Maybe the amount of polyphenols in most oil is not enough to discourage the production of proteobacteria, at least for some time.

 

[Amazoniac]

Well, kind of, but the fact remains. You can't just ignore all the evidence showing that they cause the opposite of dysbiosis in most instances. That isn't the same as to say that studies as this one are impossible. The interesting this is find out how these results happen. When the explanations of the authors don't make sense there is clearly something else we have to find out.

In this study they compared a butter diet to virgin olive oil. They also found higher levels of proteobacteria in the butter mice, but the difference was small.

Influence of a diet enriched with virgin olive oil or butter on mouse gut microbiota and its correlation to physiological and biochemical parameters related to metabolic syndrome

However, the also found a significant increase of sulfate reducing bacteria. They have some alternative explantions for the differences.

"However, the diet enriched in butter showed a clear, significant increment in the presence of Desulfovibrionaceae, which was consistent with significantly higher levels of Desulfovibrio and its key species D.desulfuricans. In this respect, not only did the EVOO diet have significantly lower levels than those of the butter group but these values were also lower, although not significant, than those found in the standard diet at the three taxonomical levels.

Desulfovibrionaceae are sulfate-reducing bacteria that could be sustained by butter sulfate sources, in part via cross-feeding mediated by Bacteroides-encoded sulfatases, since chondroitin sulfate, a common dietary supplement of animal origin, has been shown to stimulate Desulfovibrio intestinal growth.
The lower levels found in the EVOO diet, even with respect to the SD diet, could be explained by the elevated presence of polyphenols in this type of fat. In fact, another high polyphenol food, such as table grapes, has been shown to decrease the intestinal abundance of sulfidogenic (Speaking about benefit of whole foods and all its' components) Desulfobacterspp. and the Bilophila wadsworthia-specific dissimilatory sulfite reductase gene

[About endotoxin] Being part of the Proteobacteria and therefore Gram-negative bacteria, which present LPS in their outer membrane, Desulfovibrio fits this physiological effect. However in this study the correlation is not extended to the whole phylum neither to other proteobacterial taxa with significant differences between diets. Therefore, it is reasonable to consider other factors specific to this taxon affecting the LPS translocation through the tight junctions. One of these factors could rely on its sulfidogenic ability, since both sulphite and hydrogen sulphide have been implicated in intestinal toxicity and ultimately in the breakdown of the colonic epithelial cell barrier and the genesis of inflammation

On this subject, Patterson et al. [29] obtained significant differences both at the family and genus level when comparing palm, safflower, fish and olive oil with low
fat diets, being olive oil the diet with the highest value. Bacteroides is a bile resistant strict anaerobe [30, 31] so this could be a reason for its specific increment after an olive oil diet, well known for its cholagogue [what a fancy, old word] effects [32], provoking a microenvironment that would give an adaptive advantage to the genus. In the same way, the presence of antioxidant polyphenols in virgin olive oil could protect anaerobic growth from oxygen microenvironments and this would explain as well the light increase of this genus in a safflower oil supplemented diet [29], also rich in polyphenols.

Great find, thanks to you. This shift appears to be consistent in experiments.

Desulfovibrionaceae are sulfate-reducing bacteria that could be sustained by butter sulfate sources

- Sulfate content of foods and beverages

It's curious that the butter the content is about 14.5 mg sulfate/100 g, which is low in comparison to other foods.

In my discussion with him, he was all about coconut oil. I ate lots of coconut oil, it made me feel bad. Here, see, just eating it once drastically increases your endotoxin. If one-time feedings increase endotoxin that can hardly be explained be increased proteobacteria.

- What Is "adequate Protein"?

 

[Kartoffel]

- What Is "adequate Protein"?

How much protein does an Amazoniac eat on average?

 

[Amazoniac]

How much protein does an Amazoniac eat on average?

I don't track but it's on the lower side.


- Bilophila wadsworthia Bacteremia in a Patient with Gangrenous Appendicitis

"Bilophila wadsworthiais a slow-growing, non-spore-forming, gram-negative, obligate anaerobe whose growth is stimulated by bile and pyruvate. The organism forms small, low, convex, black or opaque colonies or circular translucent colonies with dark black centers when grown on Bacteroides bile esculin (BBE) agar. It is strongly catalase-positive, oxidase-negative, and, usually, urease- and b-lactamase-positive. B. wadsworthia is nonmotile and reduces nitrates but does not reduce sulfates [16]."

"B. wadsworthiawas first isolated in 1989 in a study of peritoneal fluid and tissue samples from patients with gangrenous and perforating appendicitis and was subsequently isolated in fecal specimens from healthy individuals [1-4]. Since then, B. wadsworthia has been isolated from several other human specimens, including hepatic abscesses, pus from a scrotal abscess, pleural fluid, pericardial fluid, joint fluid, blood, bloody vaginal discharge, and skin wounds; it has also been isolated from patients with osteomyelitis and hidradenitis suppurativa [4, 5, 7]."

"The biochemical properties ofthe organism were determined. Growth was stimulated by bile and pyruvate. The organism reduced nitrate but was negative for production of catalase, urease, and oxidase and did not ferment carbohydrates or hydrolyze esculin. It was also nonmotile."

"Antibiotic susceptibility testing was performed with use of E-test (AB Biodisk, Solna, Sweden) on Fastidious Anaerobe Agar (Lab M, Bury, UK), which is a pyruvic acid-containing medium supplemented with 5% sheep blood. The MICs for the organism were as follows: penicillin, 6 mcg/mL; metronidazole, 0.032 mcg/mL; amoxycillin/clavulanic acid 1 mcg/mL; and clindamycin, 0.125 mcg/mL. Thus our isolate, like most other Bilophila isolates, was resistent to penicillin and susceptible to metronidazole, amoxycillin/clavulanic acid, and clindamycin [4, 6-10]."

"Since B. wadsworthia is the third most frequently isolated anaerobe in recent studies on gangrenous and perforating appendicitis [2-4], it might be a pathogen whose importance has been underestimated because it is difficult to recover."​

So they're found in wealthy people and are far from being the main concern. If these yerms have invaded the protective layer of the intestine, are thriving on sulfated mucus and steal some sulfur from (or compete for nutrients with) the compromised host, it's possible that the availability is decreased in a time of increased needs. Anything that compromises the barrier must lead to further inflammation and then eventually atrophy.

Occasional magnesium sulfate baths if the diet provides plenty of copper is worth trying for gurus struggling with this issue. If I'm not wrong, elimination of excess is through pee.

Lack of enough sulfur and the inability to metabolize it to sulfate is harmful. Sulfation of steroid hormones (including venom D) is curious..
- Steroid sulfation research has come a long way (for references)

 

[Kartoffel]

So they're found in wealthy people and are far from being the main concern.

It seems so. Only rich moms can afford fish oil supplements.

Gut Microbes. 2015; 6(1): 24–32.
Maternal exposure to fish oil primes offspring to harbor intestinal pathobionts associated with altered immune cell balance
DL Gibson,2,* SK Gill,2 K Brown,2 N Tasnim,2 S Ghosh,2 S Innis,1 and K Jacobson1

Our previous studies revealed that offspring from rat dams fed fish oil (at 8% and 18% energy), developed impaired intestinal barriers sensitizing the colon to exacerbated injury later in life. To discern the mechanism, we hypothesized that in utero exposure to fish oil, rich in n-3 polyunsaturated fatty acid (PUFA), caused abnormal intestinal reparative responses to mucosal injury through differences in intestinal microbiota and the presence of naïve immune cells. To identify such mechanisms, gut microbes and naïve immune cells were compared between rat pups born to dams fed either n-6 PUFA, n-3 PUFA or breeder chow. Maternal exposure to either of the PUFA rich diets altered the development of the intestinal microbiota with an overall reduction in microbial density. Using qPCR, we found that each type of PUFA differentially altered the major gut phyla; fish oil increased Bacteroidetes and safflower oil increased Firmicutes. Both PUFA diets reduced microbes known to dominate the infant gut like Enterobacteriaceae and Bifidobacteria spp. when compared to the chow group. Uniquely, maternal fish oil diets resulted in offspring showing blooms of opportunistic pathogens like Bilophila wadsworthia, Enterococcus faecium and Bacteroides fragilis in their gut microbiota. As well, fish oil groups showed a reduction in colonic CD8+ T cells, CD4+ Foxp3+ T cells and arginase+ M2 macrophages. In conclusion, fish oil supplementation in pharmacological excess, at 18% by energy as shown in this study, provides an example where excess dosing in utero can prime offspring to harbor intestinal pathobionts and alter immune cell homeostasis.

 

[Amazoniac]

- A case of sulfhemoglobinemia in a child with chronic constipation

"In constipated patients there is a dysbiosis of intestinal flora with a 10–100-fold increase in sulfate-reducing bacteria leading to an increase in hydrogen sulfide [5]. Further, the increased colonic transit in constipated individuals leads to increased bacterial breakdown of amino acids that leads to release of hydrogen sulfide [6]."​

⬑ [5] Functional dysbiosis within the gut microbiota of patients with constipated‐irritable bowel syndrome

"Lactate and H2 are two of the main intermediate metabolites in the gut that support growth of various lactate-utilising and H2-consuming microorganisms. Among these microbial communities, SRB represent a group of bacteria that is able to use sulphate as terminal electron acceptor to form H2S with a wide range of substrates as electron donors, including lactate and H2. SRB are known to compete efficiently for utilisation of these two substrates in the human gut.[36, 37] Lactate is quickly metabolised by specific bacterial species in the healthy gut microbiota into butyrate or propionate.[15, 22, 38] The number of these lactate-utilising bacteria was decreased 10-fold in the faecal microbiota of C-IBS patients compared with healthy ones. Concomitantly, the number of lactate-utilising SRB was increased by a 2 log-order in IBS compared with healthy subjects. This represents a major shift in the composition of the lactate-utilising community which is likely to be accompanied by a major shift in fermentation products."

Spoiler: Table 1

Spoiler: Table 2

Spoiler: Table 3

 

[Amazoniac]

It's akin to reading an (interesting) article on nitric oxide:

- Hydrogen Sulfide in Physiology and Pathogenesis of Bacteria and Viruses

"Early life forms first appeared on an anoxic earth in the Archean eon, approximately 3.8 billion years ago (1,2). Among them, were the dissimilatory sulfate-reducing bacteria which constitute one of the oldest forms of bacterial life on earth. These bacteria utilized inorganic sulfur substrates and produced hydrogen sulfide (H2S) as the end product of anaerobic respiration (3). Before the “great oxidation event” which occurred 2.5 billion years ago leading to an increase in atmospheric oxygen, H2S remained the most abundant and versatile chemical on the primitive earth (4,5). In fact, H2S is widely believed to be the primordial sustainable energy source (6). Primitive photolithotrophs used sulfide as the terminal electron acceptor, similar to today’s green and purple sulfur bacteria. Therefore, sulfide-based metabolism may have preceded the present, oxygen-based life on the planet by billions of years (7–9)."

"In sharp contrast to its pivotal role early in the evolutionary timeline, H2S is known mostly for being a foul smelling poisonous gas, associated with sewers, septic tanks, and as a weapon of chemical warfare during the First World War. Consequently, majority of the research pertaining to this gas has been conducted from a toxicology point of view (10,11). With studies published as long back as 1803 highlighting the detrimental effect of H2S on animals, along with the recent gene expression data, H2S was condemned as a respiratory and metabolic poison (12)."

"It was not until the 1940s that the “transsulfuration” pathway involving the production of H2S by interconversion between cysteine, homocysteine via cystathionine was described for the first time in liver homogenates (13,14). Further studies led to detailed biochemical characterization of the enzymes cystathionine beta synthase (CBS) and cystathionine gamma lyase (CSE) involved in the transsulfuration reaction. Later, another enzyme, 3-mercaptopyruvate sulfurtansferase (3-MST) was identified as a part of H2S biogenesis pathways (15–18). However, the functional implication of the H2S biogenesis remained elusive for a long time. First glimpse of H2S involvement in cellular physiology emerged from the studies demonstrating measurable levels of endogenous H2S within brain tissues of healthy individuals (0.65–0.73 mg/g) and animals (1.57 ± 0.04 μg/g) (19–21). Along these lines, higher levels of neuronal H2S was found to be due to greater expression of CBS in the brain tissues. Additionally, H2S production in the brain tissue was efficiently reduced using pharmacological CBS inhibitors (hydroxylamine and amino-oxyacetic acid). Further studies proposed that H2S facilitates the induction of hippocampal long-term potentiation (LTP) by enhancing the activity of N-methyl d-aspartate (NMDA) receptors (22). Later, H2S was found to relax vascular smooth muscle by activating ATP-sensitive K+, intermediate conductance Ca2+ sensitive K+, and small conductance Ca2+-sensitive K+ channels (23–25). Importantly, H2S was identified to protect from oxidative stress and ischemia-reperfusion injury by multiple mechanisms such as restoring the levels of GSH and direct scavenging of mitochondrial ROS (Fig. 1) (26,27). These discoveries further led to the disclosure of mechanisms by which H2S protects various organs, including the heart and kidney from oxidative stress and ischemia-reperfusion injury (28). Based on these studies, H2S was inducted as the newest member of the family of small molecule gaseous transmitters or “gasotransmitters” alongside nitric oxide (NO) and carbon monoxide (CO) (29). Along this line hydrogen gas (H2) has also emerged as a potential gaseous signaling molecule with therapeutic antioxidant function (30,31). Recently, H2S was found to have a protective role in airway epithelial cells infected with respiratory syncytial virus (RSV) demonstrating for the first time that this molecule might be used as a therapeutic agent. Needless to say, the role of H2S has permeated to areas of metabolism, redox physiology, neurophysiology, apoptosis, angiogenesis, ageing, inflammation, atherosclerosis, pulmonary diseases among others with a whole spectrum of physiological implications (32–34)."

"H2S producing bacteria were discovered way back in 1877. Many investigators demonstrated bacterial production of H2S by its rotten egg smell and its ability to react with lead acetate resulting in the blackening of paper strips impregnated with lead acetate (12,35). In fact, lead acetate test was successfully exploited to distinguish between the paratyphoid and enteritidis groups and still remains an indispensable diagnostic tool (36). In the area of marine microbiology, H2S emitted from deep sea vents is often referred to as the “sunlight of the deep ocean” (37,38). H2S forms an important source of metabolic energy for the microorganisms inhabiting such niches, reminiscent of the primordial earth (6). Many bacterial species were demonstrated to possess orthologs of the transsulfuration pathway enzymes (CBS and CSE) and of 3-MST (36,39–41). However, the significance of H2S biogenesis in bacteria remained poorly characterized. In 1960s, co-culture experiments with Desulfovibrio desulfuricans/Pseudomonas aeruginosa and Escherichia coli/Staphylococcus aureus provided the first evidence of a possible “protective” role of H2S in bacteria. H2S produced by D. desulfuricans was demonstrated to be the “diffusible” factor responsible for imparting pseudomonads the ability to resist heavy metal (e.g., mercury) toxicity (42). Similarly, H2S produced by E. coli protected S. aureus from merbromin and mercuric chloride (43). Surprisingly, it took more than four decades to discover additional roles of H2S in protecting diverse bacterial species from oxidative stress and antibiotics (44). Similar reports of protective influence of H2S have emerged in plants and nematodes, however, they are beyond the scope of this review. Altogether, it appears that H2S is an important biological effector molecule with diverse roles in organisms ranging from bacteria to mammals."

Pathways involved in enzymatic biogenesis of H2S.

"H2S gas was discovered in 1777, by Carl Wilhelm Scheele, and was largely considered as a toxic gas for over hundred years (59). Based on toxicological studies, the permissible exposure limit of H2S is 10 ppm and 800 ppm exposure for 5 min is the lethal concentration for 50% of humans (LC50) (60,61). Much of its toxicity is owed to the fact that H2S is known to inhibit respiration thereby acting as a metabolic poison. When present at higher concentrations it causes reversible inhibition of cytochrome c oxidase (complex IV), thereby perturbing mitochondrial respiration and oxidative phosphorylation (46). This is further exemplified by the observations that H2S induces a state of “suspended animation” with consequent lowering of metabolic rate and body temperature in mice (61)."

"The standard two electron redox potential of H2S/S0 couple, −0.23 V (noted +0.140 value in acidic condition) at pH 7 (versus the standard hydrogen electrode) is comparable to that of major cellular antioxidant buffers, glutathione disulfide/glutathione (E°′= −0.262 V) and cystine/cysteine (E°′= −0.245 V) redox potentials (62–65). While the physiological concentration of H2S is a matter of ongoing controversy, it seems that low nM concentrations are most likely (66). Only in case of aorta, the reported concentration of free H2S is ~ 20–100 fold higher than that of other tissues (67). Interestingly, the flux of sulfur into H2S is comparable to that of GSH, indicating that the low nM levels are maintained as a consequence of higher sulfide clearance rate (59,68). The low steady-state concentration of H2S than GSH (~10 mM) precludes its involvement in counteracting oxidative stress by acting as an antioxidant buffer (46). Alternatively, it is proposed that H2S can modulate intracellular redox signaling by modifying cysteine thiols of the various cellular proteins (S-persulfidation) coordinating redox homeostasis. However, since a direct reaction of H2S with thiols is unlikely, the mechanism by which persulfides are formed intracellularly is poorly understood (69,70)."

"H2S is lipophilic and is known to permeate freely through biological membranes without any assistance from membrane channels (lipid bilayer permeability PM ≥ 0.5 ± 0.4 cm/s) (71). Being a weak acid, it dissociates immediately and equilibrates with its anion HS– and S2– in aqueous solution as shown in Eq. (1)."

"The pKa1 for H2S dissociation ranges from 6.97 to 7.06 at 25 °C, while pKa2 is estimated to be between 12.20 to 15.00 at 25 °C (72). Based on these values it is calculated that the ratio of HS–:H2S is 3:1 at physiological pH of 7.4 (72). Nevertheless, total intracellular H2S levels is referred to as total free sulfide pool (i.e., H2S + HS– + S2–). Based on its chemical features, H2S can influence cellular redox physiology via four mechanisms: (1) scavenging of ROS and RNS, (2) reaction with metal centres, (3) modulation of cellular respiration, and (4) reaction with protein cysteine thiols to generate persulfides (S-persulfidation- an oxidative posttranslational modification [oxPTM]) (69,73)."

"H2S acts as a cytoprotective molecule and has the ability to directly scavenge free radical species (74). Owing to its nucleophilic properties, H2S has been shown to react with oxygen (O2), ROS, peroxynitrite (ONOOH/ONOO–), and hypochlorite (HOCL/–OCL) (65,75). The apparent second-order rate constants of H2S with various oxidants have been summarized in Table 1. While these studies indicate a direct scavenging of oxidants by H2S in vitro, the low concentrations of H2S (10 nM to 3 μM) compared to other antioxidants (GSH; 1–10 mM) in vivo raised substantial concerns about its role in remediating ROS/RNS under biologically relevant conditions (66,76–79). Alternatively, H2S has been shown to increase GSH production by enhancing the inward transport of cystine and inducing the expression of GSH-biosynthetic enzyme, GCL (γ-GCS) (80,81). This increase in intracellular GSH could be another mechanism by which H2S indirectly participates in protection from oxidative stress."

"The interaction of H2S with metals falls into two categories: (i) electron-transfer reaction and (ii) coordinate complex formation (65). In the first category, complete electron transfer occurs between the sulfide species and the metal, whereas coordinate complex formation involves binding of the sulfur species to the metal ligand (65). These reactions are predicted on the basis of chemical properties of H2S to act as a nucleophile. Interestingly, a wine-like model was used to study the reaction mechanism of metals with H2S. Sulfidic off-odors encountered during wine production are due to the presence of H2S and low-molecular-weight thiols (82). These off-odors are usually removed in a process called Cu fining, wherein Cu (II) is added to selectively and rapidly form ~1.4:1 H2S/Cu and ~2:1 thiol/Cu complexes, resulting in oxidation of H2S and reduction of Cu (II) to Cu (I) (82). The CuS precipitate formed is than subsequently removed from the wine by racking and/or filtration (82)."

"In a biological setup, interaction of H2S with the mitochondrial heme protein-cytochrome C oxidase (CcO) is extensively studied. It has been demonstrated that high concentrations of H2S competitively binds to CcO, resulting in inhibition of O2 binding (83–85). H2S interacts with CcO through the O2-binding copper (CuB)/heme (a3) iron binuclear site in oxidized state (Cu2+/Fe3+) and reduces the enzyme (86). The Ki for this reaction is 0.2 μM with purified CcO (86). Most of the studies demonstrating inhibitory effect of H2S on respiration via interaction with CcO were done using very high/nonphysiological concentrations of H2S. However, it was shown that the liver mitochondria of H2S treated rats show biphasic respiration profile (87). Low concentrations (0.1–3.0 μM) of H2S induces respiration whereas higher concentrations (30–100 μM) inhibits (87). At lower concentrations, H2S acts as a mitochondrial electron donor and stimulates electron transport chain (87,88)."

"Other than CcO, H2S is known to covalently modify ferryl/peroxo heme within hemoglobin and myoglobin resulting in the formation of green colored sulfhemoglobin and sulfmyoglobin species, both of which are indicators of H2S poisoning (89). Additionally, H2S can react with nonheme iron present in iron-sulfur cluster containing proteins to generate insoluble precipitates (65). Lastly, H2S is reported to react with a copper-containing protein (Cu—Zn—SOD) (90). This reaction involves copper-catalysed reduction of O−2 to H2O2 Oxidation of H2C to S(0) (90)."

"The effects of H2S on cellular bioenergetics are largely derived from examining mitochondrial function. The effect of H2S on mitochondria is complex, exhibiting two opposing effects; inhibition and stimulation of mitochondrial bioenergetics (88). Oxidation of H2S by mitochondrial inner membrane localized Sulfide-Quinone oxidoreductase (SQR) leads to transfer of electron from H2S to ubiquinone and increases the flux of electron transport to mitochondrial respiratory complex III and IV, thereby leading to enhanced oxygen consumption and cellular respiration (91,92)."

"While the initial co-culture experiments described earlier provided a valuable clue with regard to potential of H2S in protecting bacteria from toxic compounds, in depth examination of these findings was never attempted (42,43). It was only in 2011 that a study highlighted the importance of H2S in protecting bacteria from antibiotics and oxidative stress (44). In this context, H2S has been termed as a “double edged sword” mitigating not only the effects of antibiotics but also the resulting oxidative stress caused by them. To ascertain the role of H2S in E coli, the authors compared wild type and 3-MST deficient E. coli by a phenotypic microarray. While these strains showed no difference with respect to growth defects in vitro, the 3-MST deficient strain became highly susceptible to structurally and functionally different classes of antibiotics. Similar results were obtained for CBS/CSE deficient strains of P. aeruginosa, S. aureus, and B. anthracis, establishing the protective role of H2S across gram negative and gram-positive bacteria. Overexpression of 3-MST led to enhanced protection against spectinomycin whereas chemical inhibition on 3-MST, CBS, and CSE rendered them highly susceptible to a variety of antibiotics. NaHS, an H2S donor chemically complemented these mutant strains establishing the role of endogenously generated H2S as a protective mechanism against antibiotics."

"The association of H2S and drug resistance is not new. Nearly 40 years ago, several studies have reported the presence of plasmid-borne genetic elements enhancing both basal H2S production and antibiotic resistance in multidrug-resistant strains of E. coli isolated from patients suffering from urinary tract infection (146,147)."

"The effect of H2S on intracellular human pathogens such as Mycobacterium tuberculosis (Mtb) is largely unknown. However, a recent study aimed at identifying genetic components involved in protection from oxidative stress showed that H2S donor (NaHS) can complement the defects in recycling of the major mycobacterial antioxidant, mycothiol (MSH) (148)."

"Host-derived H2S has a marked effect on the outcome of bacterial and viral infections. Blocking the host transsulfuration pathway in macrophages by propargylglycine increased the viability of Mycobacterium smegmatis. This impairment in bacterial clearance was shown to be due to defects in the phagolysosomal fusion during infection. Treatment with N-acetylcysteine (NAC), which is known to increase cysteine flux through H2S biogenesis pathway, significantly increased the phagolysosomal fusion resulting in vacuolar acidification and killing of mycobacteria (170). H2S was found to inhibit the induction of an inflammatory response on infection with Mycoplasma fermentans. Underlying mechanism revealed that H2S inhibited the activation and nuclear translocation of a redox sensitive transcription factor NF-κB, thereby diminishing the transcription of proinflammatory genes (171,172). One of the mechanism by which H2S affects the activity of a global transcriptional regulator, NF-κB, is by persulfidation of Cys-38 residue in the p65 subunit (131)."

"H2S production by gut microbiota presents itself as an interesting line of study to explore the effect of bacteria-derived effector molecules affecting host physiology and pathophysiology. Sulfide reducing bacteria (SRB) represent a major class of the normal gut microbiota (173). The predominant genera residing in gut are Desulfovibrio, Desulfobacter, Desulfolobus, and Desulfotomaculum. SRBs are the major contributors of nonenzymatic H2S produced in the human body (174). Some of the initial studies to explore the significance of gut microbiota-derived H2S came from experiments done on germ free animals. It was observed that fecal samples of germ free mice contained half the H2S as compared to control mice (175). In addition to this, free H2S levels in inferior vena cava, blood plasma and in gastrointestinal tissues, were shown to be diminished in germ free mice. Apart from this, sulfane sulfur levels of plasma, adipose, and lung tissues were also found to be lower in such mice. This implicated the gut microflora as a potential source of circulating H2S for the host (176). Recent studies have also shown that colonocytes are capable of using H2S as an energy source (177)."

"Gut bacteria-derived H2S has been shown to have both protective and detrimental effects on colonic health. Increased fecal sulfide levels have been found in patients with ulcerative colitis (UC) (178). Furthermore, it has been suggested that epithelial damage associated with UC is due to increased availability of dietary sulfate for SRBs (179). In contrast, using animal models of colitis, it was demonstrated that scavenging bacterial H2S by bismuth did not ameliorate the symptoms of colitis (180). In fact, the condition was shown to improve on exogenous H2S administration (181). The ability of luminal H2S to modify secreted defensive proteins like trefoil factor 3 (TFF3) by reduction of the disulfide bond is believed to be a potential mechanism of the anti-inflammatory role of H2S. TFF3 plays an important role in mucosal repair and regeneration (182)."

"RSV [Respiratory Syncytial Virus] infection resulted in downregulation of expression and impaired activity of H2S biosynthesis enzymes. As a consequence, the endogenous levels of H2S were diminished in RSV infected cells (183). Pharmacological inhibition or genetic silencing of CSE (cystathionine gamma-lyase) enhances RSV multiplication and exacerbates disease condition, airway dysfunction, and pulmonary inflammation (186,187). Consistent with these findings, exogenous administration of H2S reduces the secretion of viral induced chemokines and cytokine through inhibition of NF-κB mediated activation of genes encoding proinflammatory cytokines (183)." "Moreover, H2S treatment significantly improved clinical disease parameters and pulmonary dysfunction on RSV infection (186). Similarly, H2S also exerts antiviral and anti-inflammatory effects on the viruses in the family of Paramyxoviridae; human metapneumovirus (hMPV) and Nipah virus (NiV) (183)."

"H2S has also been shown to affect replication of highly pathogenic enveloped RNA virus from Ortho-, Filo-, Flavi-, and Bunyavirus families (Fig. 6) (188). FDA approved antiviral treatment is available for influenza virus (Orthomyxoviridae), whereas there is no vaccine or therapeutic interventions to target Ebola virus (Filoviridae), Far-eastern subtype tick-borne flavivirus (Flaviviridae), Rift valley fever virus and Crimean-Congo hemorrhagic fever virus (Bunyaviridae) (189). H2S was shown to significantly reduce replication of all the above families of viruses (188)."

"Lastly, H2S has been recently shown to modulate Coxsackie virus B3 (CVB3) infection induced inflammatory response, which is a predominant cause of human myocarditis and ultimately leads to heart failure (190). Treatment of CVB3 infected rats with H2S significantly resulted in downregulation of proinflammatory mediators, reduces myocardial injury, and alleviates damage of myocardial cells (191)."​

 

[Amazoniac]

- Role for diet in normal gut barrier function: developing guidance within the framework of food-labeling regulations

"There is some epidemiological evidence showing an increased risk of developing inflammatory bowel disease in subjects with a high protein intake, specifically with meat protein [reviewed by Kakodkar and Mutlu (107)]. A mechanism that may help explain this association lies in the interactions between high protein levels reaching the colonic microbiota and the fermentation by these microbes, which releases toxic compounds such as ammonia, phenols, branched-chain amino acids, and hydrogen sulfide (127, 233). An elegant study examining effects of altering diet composition on intestinal permeability and colitis development in mice clearly demonstrated that increasing protein in the diet increased gut permeability and also the severity of colitis in a microbiota-dependent and microbiota-independent manner (129)."​

- Diet as a therapeutic option for adult inflammatory bowel disease

"Protein derived from meat, cheese, milk, fish, nuts and eggs provides colonic bacteria with sulfate and sulfite which are fermented to form hydrogen sulfide. This may have a negative effect on colonocytes by inhibiting butyrate oxidation. The association between protein intake and development of IBD has been studied: In a study published by Reif et al using a pre-illness dietary questionnaire in newly diagnosed IBD patients in Israel did not show a statistically significant association with total protein intake [21]. Consumption of eggs did show a positive association with UC but not for CD, and there was no association with fish and both types of IBD. Another epidemiologic analysis of CD incidence in Japan showed a positive correlation with animal and milk protein intake but there was no correlation with fish protein. There was a negative correlation with vegetable protein [22]. A prospective cohort study of middle-aged French women showed an association between risk of IBD and total protein intake, specifically with meat and fish but not eggs or dairy [23]."​

 

[Amazoniac]

Stephanie Seneff is a broscientist magnet, we don't just repeat her speculations, we develop and ramify them into an unfounded mess. Not her fault: she's always made it clear that they're suppositions, but we prefer to skip this part.

I've read not long ago (outside of the forum) one of us elaborating on her ideas (without crediting) that sunlight gets rid of sulfur intolerance (with an infectious component) because it does something mystical to it.

In the general, taking supplements on empty stomach isn't a good practice because you're missing a chance to include them in a meal with the synergistic nutrients and the bulk of it prevents the absorption of impurities. However, for those with gut infections, trying a couple of times with just water can be interesting, later on, favoring its use with simpler meals that can't ferment or can into something safe should be better. It also applies to some troubling foods.
It's possible that they're already habituated with your diet (when not specialized), therefore in the same way that having it plain makes it less utilizable for you, it should also be for them, but it gets advantageous when they have to get out of the defensive hibernating mode to acquire resources that will be incomplete: they can't thrive while the immune system can act when revealed.

The sulfur intolerance disappearing after sun exposure may be that the problematic event signals what has to be done and the immune boost takes care of it. Some oxidative stress might help to counteract the antioxidative state that makes them prosper, which you can't get from a pill. No need to invoke those and propagate variations when even the author is yet unsure of them.

 

[Amazoniac]

A gut microbiota-targeted dietary intervention for amelioration of chronic inflammation underlying metabolic syndrome

"[..]the abundance of lipopolysaccharide-producing bacteria Escherichia/Shigella, Klebsiella, and Citrobacter, in the family Enterobacteriaceae, was significantly reduced. We also found a decrease in the abundance of sulfate-reducing bacteria of the family Desulfovibrionaceae, another potentially important group of endotoxin producers. Lipopolysaccharide produced by bacteria in these two families has potent inflammation-inducing capacity, usually 100- to 1000-fold higher than lipopolysaccharide from Bacteroides spp. (Lindberg et al., 1990; Hakansson & Molin, 2011). Taken together, the increase in gut barrier-protecting bacteria and decrease in opportunistic lipopolysaccharide-producing pathogens should eventually lead to reduction in antigen load to the host, which may help alleviate inflammation (Van der Waaij, 1989)."

Spoiler: Method

"We adopted the self-control design and allocated all recruited volunteers into intervention group (Fig. 1), which received the diet intervention consisting of an intervention (9 weeks, Phase I) and a maintenance period (14 weeks, Phase II)."

"During Phase I, volunteers were prescribed customized menus. Three (for female) or four (for male) cans of gruel as staple food per day were recommended."

"Formula No. 1 was a precooked mixture of 12 component materials from whole grains and TCM food plants that are rich in dietary fiber, including adlay (Coix lachrymal-jobi L.), oat, buckwheat, white bean, yellow corn, red bean, soybean, yam, big jujube, peanut, lotus seed, and wolfberry, which was prepared in the form of canned gruel (370 g wet weight per can) by a contract food manufacturer (Shanghai Meilin Meida Food Co., Ltd., Shanghai, China). Each can contained 100 g of ingredients (59 g carbohydrate, 15 g protein, 5 g fat, and 6 g fiber) and 336 kcal (70% carbohydrate, 17% protein, 13% fat)."​

"The suggested dose of formula No. 2 was 40 g reconstituted with warm water in two divided doses taken orally, before breakfast and dinner."

"Formula No. 2 was a powder preparation for infusion (20 g per bag) containing bitter melon (Momordica charantia) and oligosaccharides, which included fructo-oligosaccharide and oligoisomaltose, and totally accounted for 34% of the formula No. 2."​

"One bag of formula No. 3 was taken with more than 800 mL water once a week before breakfast."

"Formula No. 3 contained soluble prebiotics, including guar gum, pectin, konjac flour, other fermentable dietary fiber (Fibersol 2, resistant starch, hemicellulose), and oligosaccharides, and was administered in the form of powder for infusion (50 g per bag)."​

"The two infusion formulas were designed to facilitate the modulation of gut microbiota with a mild antibacterial effect and gas-producing function (Fei & Zhao, 2013)."

"Appropriate amounts of vegetable, fruit, and legume products could be consumed everyday according to the dietitian’s guidance to ensure complete nutrition. The diet contained 1000–1600 kcal, and the volunteers were allowed to consume enough of this diet to avoid hunger pangs."


"In Phase II, formula No. 1 was not supplied, and volunteers were required to prepare the staple diets with high-fiber, low animal source foods at home by themselves under a dietitian’s guidance. The intake of meat (or fish or shrimp) was < 50 g each day. The dosage and administration of formula No. 2 were the same as in Phase I, but the dosage of formula No. 3 was reduced to 50 g every 2 weeks."

Spoiler: Changes on the degree of seneffiosis

 

[Amazoniac]

- Cysteine-derived hydrogen sulfide and gut health: a matter of endogenous or bacterial origin

"Several studies revealed that modifications of the production of this fascinating gaseous compound by either the colonic bacteria or by the colonocytes are protective or deleterious toward the colonic epithelium in different physiological and pathological contexts."

"Dietary and endogenous proteins are generally highly efficiently digested in the gastrointestinal tract. However, a significant proportion of luminal undigested or partially digested protein are transferred from the small to the large intestine, representing between 6 and 12 g of proteins [6]. These proteins are degraded by the intestinal bacteria which release amino acids, including cysteine, which are used for bacterial protein synthesis and/or for amino acid metabolism with synthesis of intermediary and final metabolites [7]. Amino acids, except in the neonatal period, are not absorbed by the mammalian colonic mucosa to any significant extent [8], but several of the amino-acid-derived bacterial metabolites can enter the colonic epithelial cells, be metabolized there, and then be released together with cometabolites (i.e., bacterial metabolites modified by the host) in the portal vein."

"In the colonic luminal content, several bacterial species can transform cysteine into H2S [9]. In fact, numerous bacterial groups (Fusobacterium, Clostridium, Escherichia, Salmonella, Klebsiella, Streptococcus, Desulfovibrio, and Enterobacter) convert cysteine to H2S, pyruvate, and ammonia by cysteine desulfhydrase activity [10,11,12]. From experiments performed with fresh fecal samples from healthy or irritable bowel syndrome study participants, it has been shown that sulfite respiration and cysteine degradation are the dominant sulfidogenic processes compared with bile acids or taurine-based H2S production [13]. In addition, cysteine-fermenting bacteria belonging to Clostridium cluster XIVa (that express cysteine desulfhydrase) are highly predominant in the high H2S-producing microbial communities present in the feces [13]."

"In mammalian cells, although the respective roles of the different metabolic pathways for the synthesis of H2S from cysteine in the different cell phenotypes are not clear yet, several operating metabolic pathways have been described [15,16] (Fig. 1). Cystathionine b-synthase (CBS) appears to be a versatile enzyme as it can convert cysteine to H2S and serine but can also convert two molecules of cysteine into H2S and lanthionine. In addition, CBS can convert cysteine and homocysteine into H2S and cystathionine. CBS is not the only enzyme involved in H2S production from cysteine. Indeed, cystathionine g-lyase (CSE) converts cysteine into H2S, NH3, and pyruvate, and cysteine and homocysteine in H2S and cystathionine. Lastly, by the sequential activity of cysteine aminotransferase and 3-mercaptopyruvate sulfurtransferase (3-MST), cysteine can give rise to H2S production."

Effects of exogenous and endogenous hydrogen sulfide and energy metabolism in colonocytes

"In colonocytes isolated from the rat colon, 20 and 40mM NaHS, used as a rapid H2S donor, increase instantaneously the cell oxygen consumption by entering the mitochondrial respiratory chain at the level of the sulfide quinone reductase (SQR) (Fig. 2) [14]. This enzyme oxidized H2S by transferring electron equivalents to quinones with the intervention of reduced glutathione, and then to the mitochondrial complexes III and IV (cytochrome c oxidase). In the meantime, the persulfide dioxygenase (ETHE1) allows the synthesis of sulfite, which is converted to thiosulfate by rhodanese, an enzyme characterized by its sulfur transferase activity [17]. Oxygen consumption by colonocytes is associated with an inner mitochondrial membrane energization and ATP synthesis. Thus, the detoxification of H2S by the sulfide-oxidizing unit allows energy production by the colonocytes. In contrast, at concentrations above 65mM, NaHS severely inhibits colonocyte oxygen consumption by inhibiting the mitochondrial cytochrome c oxidase activity [14] (Fig. 3)."

Spoiler

"Interestingly, inhibition of the mitochondrial cytochrome c oxidase activity in human colon cancer cells by high (millimolar) concentration of NaHS results in a spectacular increase of the capacity of these cells to utilize glucose in the glycolytic pathway [17]. Thus, the high capacity of colonocytes for H2S oxidation should be considered as a way for these cells to detoxify this bacterial metabolite and as a way to recover energy from it. The fact that colonocytes are among the most efficient cells for H2S disposal is not surprising taking into account that these cells face the highest H2S concentrations in the body [12]."

"Regarding the effects of H2S produced endogenously within colonocytes, although little has been investigated regarding this aspect, it appears unlikely, notably in regards to what has been shown in other cell types [16], that the endogenous production of H2S would reach a rate of production that would inhibit mitochondrial ATP synthesis in colonocytes."

"Recently, it has been hypothesized that H2S could modulate intestinal inflammation through interactions with the protective mucus layer that limits direct interaction between bacteria and epithelial cells. Ijssennagger et al. [23] proposed that microbiota-generated H2S could destabilize the protective mucus layer through the reduction of disulfide bounds linking the mucin 2 network. In contrast, endogenous H2S production by CSE contributes to the segregation between luminal bacteria and the mucosa through the production of mucus [20]."

"The microbiota of new-onset pediatric Crohn’s disease patients is characterized by a high abundance of Atopobium, Fusobacterium, Veillonella, Prevotella, Streptoccocus, and Leptotrichia, members of those genus being known to produce H2S through the fermentation of sulfur-containing amino acids [24]. Interestingly, in this cohort, the abundance of H2S producers predicted inflammation severity and this observation was specific to cysteine degraders and not sulfate reduction. To investigate the causal-to-effect relationship between cysteine degrading bacteria and intestinal inflammation, the authors colonized IL10−/− mice with the H2S producer Atopobium parvulum and observed a worsening of colitis, whereas this effect was attenuated by the administration of bismuth, an H2S scavenger."

"Interestingly, in the same human cohort, the colonic mucosal biopsies from Crohn’s disease patient displayed decreased expression of the proteins involved in the mitochondrial H2S detoxification (ETHE1, thiosulfate sulfurtransferase, SQR) [24]. These latter results suggest that the impairment of H2S detoxification system might amplify the toxic effects of the observed overproduction of H2S by the microbiota from cysteine degradation."

"Interestingly, the consumption of a high-protein diet in the rat model which increases the colonic content of H2S coincides with an increased expression of the gene corresponding to SQR, the first and rate-limiting enzyme for H2S detoxification [14], thus suggesting that the H2S-detoxifying enzymatic system can adapt, up to a certain extent, to an increased amount of this bacterial metabolite within the colonic content."

"Recently, it has been shown that proanthocyanidin-containing polyphenol extracts originating from various plants can largely prevent the inhibitory effects of NaHS on human colonocyte oxygen consumption [18]. As proanthocyanidins are little absorbed in the small intestine, this result raises the possibility to reduce the concentration of H2S in the large intestine by unabsorbed dietary compounds, thus avoiding the deleterious effects of this bacterial metabolite when present in excess in the luminal content."

"Thus, it should be feasible to control the intraluminal concentration of H2S by dietary managements in situation of excessive production by the intestinal microbiota (Fig. 4) and thus to reduce its deleterious effects on the colonic mucosa."

Spoiler

 

[Kvothe]

"There is some epidemiological evidence showing an increased risk of developing inflammatory bowel disease in subjects with a high protein intake, specifically with meat protein [reviewed by Kakodkar and Mutlu (107)]. A mechanism that may help explain this association lies in the interactions between high protein levels reaching the colonic microbiota and the fermentation by these microbes, which releases toxic compounds such as ammonia, phenols, branched-chain amino acids, and hydrogen sulfide (127, 233).

Casein is used in most of the protein studies to demonstrate the detrimental effects of animal protein with regards to the sustances released during putrefaction. It seems a little unfair since most healthy vegetable proteins such as soy and corn seem to promote putrefaction to a much larger degree.

 

[Amazoniac]

There's a lot of discussion here on carbon and nitrogen monoxide, but not so much on hydrogen sulfide. One modulates the other and can't be considered in isolation. It's important to know first why they was elevated because it can be compensatory, organs that are in better shape could be taking the hit for those that may benefit from the least harmful alternative. For example, dietary restriction that left you deficient in sulfur may lead to an overgrowth of bacteria that can maximize its use and deliver it through diffusion to tissues that are under stress. It must eventually promote Raj's antioxidative stress and death. Dangerous, should be cared as drugs.

- Oxidation States of Sulfur and Phosphorus | slideplayer.com/slide/3514202/

Spoiler

- Oxidation state - Wikipedia

Related:
- "The Primary Sources Of Acidity In The Diet Are Sulfur-containing AAs, Salt, And Phosphoric Acid" (last spoiler)

- Hydrogen sulfide and nitric oxide interactions in inflammation

"˙NO and H2S share several of the common features of gaseous mediators: they are small gaseous molecules; they are freely permeable to cell membranes and do not rely on membrane receptors to exert their functions; they are endogenously and enzymatically generated; their production is finely regulated [and] they have well-defined functions at physiologically relevant concentrations (8). Besides these characteristics, ˙NO and H2S seem to regulate the same physiological functions through similar reaction mechanisms (Figure 1) (9), in the cardiovascular and nervous systems and in inflammation. Experiments have suggested that these similarities do not rely only on “parallel” functions exerted by ˙NO or H2S, but that either molecule can also alter the functions (or levels) of the other (10-17). Therefore, alongside studying the effects that ˙NO and H2S exert singularly, effort should be put into investigating the interplay, or so-called “cross-talk”, between these molecules (9, 18, 19)."

Spoiler

"The five clinical signs of inflammation are redness, heat, swelling, pain, and eventually loss of function of the injured tissue (20)."

"Both ˙NO and H2S have roles in inflammation and both pro- and anti-inflammatory effects have been reported for each of these molecules."

"H2S has been suggested to regulate ˙NO bioavailability (11, 12, 61) and it has also been shown to cause ˙NO release from nitrosothiols (62-64)."

"Similarly to ˙NO and CO, H2S is also known to interact with heme-containing enzymes and it is thought to inhibit cellular respiration by inhibiting cytochrome c oxidase, via reaction with its copper centre. This mechanism has been implicated in some of the cytotoxic effects which have been reported for H2S, as well as in the induction of suspended animation state [Stephanie's nirvana mentioned previously] in mice (43, 67, 68)."

"Both cytotoxic and cytoprotective effects have been reported for H2S. H2S is known to be an efficient reducing molecule; therefore it could exert direct antioxidant effects on cells, protecting them from oxidative stress. For example, H2S at concentrations between 25 and 250 µM has been shown to protect SH-SY5Y cells against ONOO- and hypochlorous acid induced-cell death (57, 69, 70). In addition, many studies in vitro have shown the ability of H2S to reduce several biological oxidants (71-75), but, due to the kinetics involved, it does not appear that H2S would be the preferential target for these molecules in vivo (74). Therefore, it appears that the simple reduction of oxidants cannot explain in full the cytoprotective effect of H2S in vivo. At the same time, H2S concentrations between 200 and 500 µM have been shown to cause apoptosis in human aortic smooth muscle cells (76). In general, it is possible to point out that at low micromolar concentrations several studies have demonstrated cytoprotective effects for H2S, while higher exposures tend to be cytotoxic (57)."

"H2S levels have been found to be disrupted in several disease states, such as hypertension and diabetes and also in chronic inflammation and several models of acute inflammation (22, 57). Most of the assays used currently to detect H2S levels in cells, tissues or biological fluids do not actually detect “free” H2S, but give a value for the general sulfide levels in the sample (H2S, HS-, bound sulfane sulfur etc.) which is generally referred to as H2S. Despite the lack of specificity in determining which is the “active” species, it is clear that in several disease states or models H2S synthesis is perturbed (57, 81, 82). As for ˙NO, several studies have reported both pro- and antiinflammatory roles for H2S, and although there is considerable evidence that H2S is a mediator of inflammation its exact role is unclear."

"The observed effects of H2S in the gastrointestinal system (e.g. reduction of leukocyte adherence and chemotaxis), together with the induction of apoptosis in neutrophils, led many research groups to hypothesize a role for H2S in the resolution of gastrointestinal inflammation (21, 92)."

"There is increasing evidence that all three gasotransmitters, ˙NO, CO and H2S interact with each other, affecting their bioavailability and reactivity. However, the nature of the interaction is still unclear and is likely to depend on the system studied (19)."

"˙NO and H2S appear to interact at different levels: they seem to affect each other’s enzymatic production and/or alter the expression of their respective synthesizing enzymes, but they can also interact further downstream, at the level of their metabolites (63, 100-102)."

"[..]despite the effects described [] (H2S and ˙NO inhibiting each other’s synthesis), it has been found that the two molecules can enhance their respective production via several mechanisms. ˙NO has been shown to increase H2S endogenous production by elevating CSE and CBS expression in vascular smooth muscle cells (87, 103). In a similar way, NaSH has been shown to enhance ˙NO production by increasing IL-1ß-induced iNOS expression (104), in rat vascular smooth muscle cells. Additionally, in bovine arterial endothelial cells, H2S has been shown to increase eNOS activation either by inducing its phosphorylation on Ser 1177, by an Akt-dependent mechanism (105) or by directly inducing Ca2+ release from the intracellular storage in the endoplasmic reticulum (14). These findings were also confirmed in human umbilical vein endothelial cells (16), where it was also found that L-cysteine supplementation stimulated ˙NO production, while inhibition of CSE blocked it. Additionally, the authors showed that CSE knockdown inhibited ˙NO production, while CSE overexpression increased it (16), suggesting that there is a clear correlation between H2S and ˙NO enzymatic synthesis."

"It is therefore evident that ˙NO and H2S can affect each other’s synthesis, but it has also been suggested that ˙NO (or ˙NO donors) and H2S can directly interact to form novel molecular entities, which could, in turn, modulate ˙NO and H2S biological effects and bioavailability. For example, it appears that the interaction of SNP and H2S can form a nitrosothiol-like species, which has shown physiological effects similar to those of ˙NO (61)."

"Often H2S is able to regulate ˙NO bioavailability by multiple mechanisms at the same time."

"Investigations on ˙NO-H2S cross-talk in inflammation have been less extensive, than the studies conducted on the vasculature. Also, the interaction of ˙NO and H2S in inflammatory states could be significantly different from what has been found and described [] for the vasculature, as evidenced by various studies. Anuar et al. (2006) have shown that ˙NO reduces the formation of H2S in LPS-treated rats (116)."

"Oh et al. (2006) showed that H2S (as pure H2S gas or NaSH) was able to inhibit ˙NO production and iNOS expression via heme oxygenase 1 (HO-1) expression in RAW264.7 macrophages treated with LPS. NaSH and H2S gas both induced HO-1 expression through the activation of extracellular signal-regulated kinase (ERK). This led to a reduced iNOS expression, which was additionally depressed by the addition of L-cysteine (substrate for H2S production) (117). NF-kB activation was also reduced when LPS-treated macrophages were pre-incubated with H2S, and interestingly the same result was also achieved by treating the challenged macrophages with CO. This last observation corroborates the hypothesis of a “gaseous” cross-talk in inflammation, involving not just ˙NO and H2S, but CO as well (19)."

"In a model of inflammatory lung disease (ovalbumin-challenge model of asthma in mice), CSE expression and pulmonary tissue H2S levels were found to be decreased (22, 118). The exogenous administration of NaSH reduced inflammation, neutrophil infiltration and inactivated iNOS, similarly to that described previously for LPS-treated macrophages."

"Despite the benefits observed (reduction of inflammation), because of basal iNOS overexpression in the disease process, H2S administration did not completely improve the animals’ survival rate (119). Once again this proves how extremely important the mutual levels of H2S and ˙NO are, in both physiological and pathophysiological settings."​

- Regulation of carbohydrate metabolism by nitric oxide and hydrogen sulfide: Implications in diabetes
- The dichotomous role of H2S in cancer cell biology? Déjà vu all over again
- Thionitrous Acid/Thionitrite and Perthionitrite Intermediates in the “Crosstalk” of NO and H2S
- H2S-induced thiol-based redox switches: Biochemistry and functional relevance for inflammatory diseases
- Revisiting the systemic lipopolysaccharide mediated neuroinflammation: Appraising the effect of l-cysteine mediated hydrogen sulphide on it
- Regulation of vascular tone homeostasis by NO and H2S: Implications in hypertension
- An Update on Hydrogen Sulfide and Nitric Oxide Interactions in the Cardiovascular System
- Hydrogen Sulfide (H2S) Based Therapeutics for Bone Diseases: Translating Physiology to Treatments

 

[Amazoniac]

- The Role of Sulfide Oxidation Impairment in the Pathogenesis of Primary CoQ Deficiency

"Hydrogen sulfide [] participates in the relaxation of blood vessels by opening ATP-sensitive K+ channels in vascular smooth muscle (Yang et al., 2008), in inflammatory modulation (Yang et al., 2013) and in the production of reactive oxygen species (ROS; Eghbal et al., 2004). Accumulation of H2S in the nervous system induces increase in the concentration of serotonin and a decrease in GABA, aspartate, norepinephrine, and glutamate (Skrajny et al., 1992; Roth et al., 1995). One mechanism of action of H2S is through modification of cysteine residues of target proteins by S-sulfhydration (sulfhydration, persulfhydation). Oxidative post-translational modifications of Cys residues in proteins are important for regulation of different cell functions. S-sulfhydration usually affects proteins function exerting opposite effects of nitrosylation, therefore enhancing their function (Mustafa et al., 2009; Paul and Snyder, 2012)."

"In mammals, CoQ is a lipid-soluble present in all cell membranes and is involved in multiple metabolic functions. One of these functions is to shuttle electrons in the first reaction of the H2S oxidation pathway, catalyzed by SQOR (Figure 1). Our studies in human fibroblasts confirm that low levels of CoQ cause decrease of SQOR protein levels, proportionally to the degree of CoQ deficiency (Luna-Sanchez et al., 2017; Ziosi et al., 2017)."​

- Hydrogen Sulfide Oxidation: Adaptive Changes in Mitochondria of SW480 Colorectal Cancer Cells upon Exposure to Hypoxia

"The first step of sulfide breakdown [shown above] is catalyzed by the membrane-associated sulfide:quinone oxidoreductase (SQR). This flavoprotein transfers electrons from H2S to coenzyme Q in the mitochondrial electron transfer chain, thus making H2S the first inorganic substrate that is able to sustain mitochondrial respiration [15]. Concomitantly, SQR transfers the H2S sulfur atom to an acceptor, leading to the formation of glutathione persulfide (GSSH) [16, 17] or, less likely, S2O3(2-) [18, 19]. Differences in the SQR substrate specificity were recently reported comparing the soluble with the nanodisc-incorporated enzyme [20]. Three additional enzymes, persulfide dioxygenase (ETHE1), thiosulfate sulfurtransferase, and sulfite oxidase, cooperate with SQR in the mitochondrial sulfide oxidation pathway, to oxidize H2S into SO4(2-) and S2O3(2-). To process 1 H2S molecule, mitochondria overall consume ~0.75 O2 molecules (0.25 by CcOX plus 0.5 by ETHE1, [21]). Besides being metabolized through the mitochondrial sulfide-oxidizing pathway, H2S can be oxidized by several metalloproteins such as globins, heme-based sensors of diatomic gaseous molecules, catalase, and peroxidases (see [8] and references therein) or be catabolized by the cytosolic thiol methyltransferase [22]."

"Upon prolonged exposure to hypoxia, mitochondria become less abundant, but enriched in sulfide:quinone oxidoreductase (SQR). Consistently, their maximal sulfide-oxidizing activity increases, while overall decreasing in the cell. These changes are proposed to occur to prevent H2S inhibition of cytochrome c oxidase (CcOX) and thus protect cell respiration from H2S poisoning."​

- Hydrogen Sulfide and Persulfides Oxidation by Biologically Relevant Oxidizing Species

"In addition to hemeproteins, CuZn and Mn superoxide dismutases are able to catalyze the oxidation of H2S by oxygen [114,115]."

"H2S shows nucleophilicity and is analogous to thiols, albeit weaker [27,28]. Among some possible targets in cells, H2S can react with metallic centers (iron, copper, zinc, molybdenum) producing coordination complexes and, in some circumstances, donating electrons. H2S is also able to react with oxidized forms of protein thiols such as disulfides (RSSR) or sulfenic acids (RSOH), thus leading to the formation of persulfides (RSSH/RSS–) [28,29]."

"The recommended names by IUPAC are dihydrogen sulfide and sulfane for H2S, and sulfanide or hydrogen(sulfide)(1–) for HS– [20]."

"H2S may be considered at first sight to be similar to water, but there are several important differences that lead to dissimilar physical and chemical properties. Sulfur is larger than oxygen (van der Waals radii of 1.80 and 1.42 Å, respectively) [50], has a lower electronegativity (2.58 and 3.44 in the Pauling scale, respectively), and is more polarizable [51]. Hence, the dipole moment of H2S is lower than that of water, and hydrogen bonds in H2S are not formed at room temperature [51]; this explains why H2S is a gas at ambient temperature and pressure. H2S can dissolve in water with a relatively high solubility (101.3 mM/atm at 25 °C) [52], and the solvation is dominated by dispersive forces with no hydrogen bonds with water [51]. The slightly hydrophobic character of H2S is further supported by its twice higher solubility in organic solvents such as octanol and hexane than in water [12]."

"The hydrophobic character of H2S results in a higher solubility in membrane lipids than in water that results in a rapid diffusion through cell membranes without assistance by protein channels [11,12,13]."

"The oxidation state of sulfur in H2S and in HS– is –2. Thus, H2S can only be oxidized; it cannot act as an oxidant. Therefore, the statements in the literature regarding H2S oxidation of protein cysteines to persulfides are not correct; either the thiol or H2S need to have undergone previous oxidation for cysteine persulfide formation to occur. Oxidation of H2S can lead to various products in which the sulfur can have oxidation numbers up to +6. The oxidation products include sulfate (SO4(2−)), sulfite (SO3(2−)), thiosulfate (S2O3(2−)), persulfides (RSS(−)), organic (RSSnSR) and inorganic (HSSnS(−)) polysulfides, and elemental sulfur (Sn)."​

- Roles of Hydrogen Sulfide in the Pathogenesis of Diabetes Mellitus and Its Complications

 

[Amazoniac]

This is pretraining sulfate-reducing bactaeria:

- Metabolism of dietary sulphate: absorption and excretion in humans

"Sulphate reduction does not occur in mammalian cells. It does occur in bacteria, and in particular, in sulphate reducing bacteria, which can couple oxidative phosphorylation with reduction of sulphate (replacing oxygen in conventional aerobic respiration) to produce hydrogen sulphide.[1]"

"Sulphate reducing bacteria oxidise a range of readily available organic compounds in the colon (short chain fatty acids, hydrogen, succinate, lactate, ethanol, pyruvate) and are likely to be growth limited not by substrate, but by availability of the terminal electron acceptor, sulphate. Large numbers of sulphate reducing bacteria are found in the colon especially in people who do not excrete methane in their breath,[5] and experiments in vitro[6] and in vivo[7] have suggested that these bacteria might outgrow methanogenic bacteria when there is an adequate supply of sulphate."

"Sulphate is believed to be poorly absorbed by the human gastrointestinal tract.[9,10] Hence the basis for its use as an osmotic laxative, and as a non-absorbable anion in absorption studies.[11,12] Sulphate excretion in urine has been ascribed entirely to the oxidation of sulphur in sulphur amino acids.[13] On the other hand, animal studies indicate that appreciable absorption of sulphate is possible by the upper gastrointestinal tract of a variety of monogastric mammals.[14-16] Also, in humans, tracer doses of radioactive sulphate given by mouth are well absorbed,[17,18] with more than 80% of radioactivity being recovered in urine over 24 hours.[18]"

"We have therefore measured the amount of sulphate passing into the colon from the upper gastrointestinal tract from dietary and endogenous sources by feeding ileostomy subjects diets containing variable amounts of sulphate and measuring sulphate excretion in ileostomy fluid and urine. Sulphate in cooked food is mainly in the free anionic form.[19] On the other hand, sulphate from intestinal secretions is esterified with glycoproteins (mainly mucin) and to a lesser extent with steroids and glycolipids.[20] Because there is little sulphatase activity in the mucosa of the gastrointestinal tract,[21] the free sulphate in ileal effluent is likely to be of dietary origin, whereas bound sulphate is largely endogenous. Sulphate losses in ileal effluent are assumed to be the same as the sulphate which reaches the caecum in the intact gut."

"Intakes of dietary sulphate varied over a 75-fold range from 2.1-15.8 mmol/day. Although the ileostomy diets were experimental, they comprised normal food constituents and had nutritional contents broadly similar to those of typical British diets.[24]" "

Spoiler

"These experiments show net absorption of dietary sulphate and its excretion in urine over 24 hours in human subjects fed a range of sulphate in diets broadly in keeping with British eating habits. Maximum net absorption by the upper gastrointestinal tract plateaued at 5 mmol/day with dietary intakes of 7 mmol/day and above."

Spoiler

"[A] possible fate for sulphate in the colon which merits consideration is that it is first reduced to hydrogen sulphide by bacteria, then absorbed and reoxidised to sulphate." "[..]this gaseous compound is very water soluble (2000 ml/l water at 37°C, compared with solubilities of 18 ml/l water for hydrogen, and 570 ml/l water for carbon dioxide) and is mainly in a nonionic form at faecal pH (pKal= 7.04).[45] Therefore, if not consumed by chemical or enzymatic reactions in the gut lumen, hydrogen sulphide is likely to be readily absorbed."

"It is unlikely that an appreciable reduction of sulphate occurred in our subjects, who had no sulphate reducing activity in vitro. The sulphur requirement of faecal bacteria if sulphate reducing bacteria are not present is not more than 1-2 mmol/day. Most of this requirement would be met by cysteine and methionine from protein degradation. Bacterial assimilation of sulphate to produce hydrogen sulphide for sulphur needs is a process requiring adenosine triphosphate whose pathway is repressed when bacteria are grown with cysteine.[53,54] Making the unlikely assumption that non-sulphate reducing bacterial sulphur needs are all met by sulphate, and assuming an average bacterial faecal dry mass of 14.7 g, and bacterial nitrogen content of 0.88 g (calculated from Stephen and Cummings,[55]) and a nitrogen to sulphur ratio of 16, then the sulphate assimilated for bacterial sulphur needs would amount to only 1.7 mmol/day. Moreover, the sulphate requirement for bacterial sulphur would be considerably less in ileostomy subjects, whose gut bacterial load is many orders of magnitude smaller than that of normal subjects."

"In this study we were able to estimate for the first time net endogenous sulphate secretion by the human upper gastrointestinal tract, 0.96-2.6 mmol/day [⇈]. Some of the bound sulphate is esters of steroids, phenols, glycoproteins, chondroitin, and glycolipids, but most is probably in mucin. By assuming all bound sulphate to be from mucin and 3.4% sulphate in the carbohydrate portion of small intestinal mucin,[56] then the daily carbohydrate contribution from mucin secretion by the upper gastrointestinal tract is estimated to be 2.7-7.3 g/day in our subjects. This calculation is in approximate agreement with estimations of mucin secretion based on measurements of hexosamines in ileostomy fluid[57] (3.4 g/day) or of total carbohydrate in the ileostomy fluid of subjects on a polysaccharide free diet[58] (2.3 g/day)."

"Diet and intestinal absorption are the principal factors determining the size of the colonic sulphate pool in this study. Because the magnitude of this pool is likely to be a major determinant of sulphate reducing bacteria carriage and activity, it therefore follows that the epidemiology of human methanogenesis, which is inversely related to the carriage of sulphate reducing bacteria,[5] should be determined at least in part by the quantity of sulphate ingested." "[We has] measured the sulphate in a composite rural African diet from a predominantly methanogenic population[62] and found it to be only 2-7 mmol/day (unpublished results), despite a large beer intake. By contrast, the high dietary sulphate consumed by the British population is associated with the carriage of significant sulphate reducing bacteria.[5] Furthermore it is possible to stop methanogenesis in some subjects fed inorganic sulphate.[7]"​

 

[Amazoniac]

Just because there's no odor, it doesn't mean that there's no issue. Some cases:

1. Intact defenses, minor insults.
   
2. Intact defenses, major insults.
   
3. Compromised defenses, minor insults.
   
4. Compromised defenses, major insults.

It should be detectable in the last two, but the second case may also experience brain fog, fatigue, and so on, since detoxification systems can be taxed and nutrients being diverted for this purpose. Given that most people carry these bacteria, cases 1 and 3 should be the commonestest.

Light therapy can be overdone because you may already be running low in nutrients. By unclogging mitochondrial cytochrode c oxidase, the bright (tut) side is that it's at the last steps of cellular respiration, therefore flooding a limiting step should not be a problem. On the dark side, by stimulating and making it unimpeded, you'll be increasing the rate of the processes before it, so you could also be increasing your demand further when you can't afford doing so.

- Red Light Therapy, Lights, Supplemental Lighting​

An example would be ubiquinode. Since it's involved in detoxification of hydroged sulfide, the person could be insufficient in it, and the light boost must eventually drop it to deficient levels. Sunlight has the advantage of shaping immunity and the oxidative stress must counteract the antioxidant effect from excess hydrogen sulfide, yet it does deplete a lot of nutrients.

If you don't want to risk nutrient depletion or wastage, the surest way is to get extra and close to the light session. That's because if you take in advance, it may be impeded where light acts; if it's taken after, there's enough time for you to run out of them, lead to stress, trigger an adaptive response, and if you supplement later you'll be adding when ready to conserve them.
Has anyone tried methylene blue right after the end of a light session?

Given that celery stalk is helpful, carrot top may be too. They's from the same family.

There's the idea that bad effects after a meal are not necessarily from the current one, that it can be due to the previous moving to a compromised region of the intestine. However, another possibility is having the intestinal lining breached, infected and pathogens responding to the meal changes inside the body rather than the lumen. I don't know how severe it has to get for this occur, yet invasiveness should make it conceivable of being affected this way.

Nutrients that tend to be problematic can be taken with a mad dose of killcium, preferably as the last meal of the day to prevent interaction with other ones that might fuel the issue, there will be plenty of time until the next. As Raj mentioned, killcium will prevent microbial action, so sleep must not be disturbed from this.

 

[Amazoniac]

- Nutrient Metabolism: Structures, Functions, and Genes - Martin Kohlmeier

"The least oxidized simple sulfur-containing molecule is hydrogen sulfide (H2S). Hydration of sulfur dioxide (SO2) gives rise to sulfurous acid (H2SO3) and the hydrogen sulfite (bisulfite, HSO3(−)) and sulfite (HSO3(2−)) ions. Sulfur trioxide (SO3) is the precursor of sulfuric acid (H2SO4) and the bisulfate (HSO4(−)) and sulfate (SO4(2−)) ions. Dithionate (S2O6(2−)), disulfite (metabisulfite, S2O5(2−)), dithionite (S2O4(2−)) , and thiosulfate (S2O3(2−)) are the ions of related sulfur oxides. Thiocyanate (SCN(−)) is an oxygen-free mixed sulfur ion. Numerous complex organic compounds, including the amino acids methionine, cysteine, and taurine, the vitamins thiamin and biotin, and the metabolic cofactor lipoic acid contain sulfur in various configurations."

"The sulfur amino acids methionine and cysteine are necessary for the synthesis of proteins and serve as precursors of important cofactors and metabolites. Development and maintenance of brain and nerves, spermatogenesis, joint repair, hormone action, and many other body functions are critically dependent on undisturbed sulfate metabolism. Sulfate is an essential constituent of many proteins, glycans, and glycolipids, and plays an important role in the activation and elimination of hormones, metabolites, phytochemicals, and xenobiotics. Various other sulfurous compounds, such as taurine, thiamin, biotin, and thiosulfate, have specific functions in the body."

Spoiler

"Most utilizable sulfur comes with sulfur amino acids in proteins of animal and plant origin. Much smaller amounts are consumed as sulfate. Some sulfur compounds, such as the potentially toxic hydrogen sulfide, arise when bacterial in the distal intestine act on nonabsorbed amino acids."

"Since symptoms of methionine and cysteine deficiency will occur with inadequate intake, the consequences of isolated sulfur deficiency cannot be determined. Experience with the rare patients with defective sulfate transporters indicates a particular vulnerability of the brain and connective tissue."

"Excessive sulfate intake may accelerate bone mineral loss and increase the risk of osteoporosis. Exposure of sensitive individuals to large doses of sulfite (>100 mg) can trigger asthma attacks, urticaria, and related symptoms."

"The catabolism of the sulfur amino acids methionine, cysteine, cystine, and taurine [?] generates significant quantities of sulfite, most of which is rapidly converted to sulfate. Typical combined intake is in excess of 40 mg/kg, and most of this is eventually broken down. Thus, more than 75% of ingested methionine is converted to sulfate within a few hours (Hamadeh & Hoffer, 2001)."

"Cysteine is broken down in successive steps catalyzed by cysteine dioxygenase (EC1.13.11.20, contains iron and FAD), cytosolic aspartate aminotransferase (EC2.6.1.1, requires PLP) to beta-sulfinylpyruvate. This intermediate spontaneously releases sulfite and pyruvate. Aspartate 4-decarboxylase (EC4.1.1.12) can generate sulfite from cysteinesulfinate."

"Many sulfur compounds, including inhaled hydrogen sulfide, are toxic. Only a few of the numerous sulfur compounds in nature serve as significant precursors for human sulfur homeostasis. Among these the amino compounds methionine, cysteine, homocysteine, and taurine are most notable, because they contribute to the synthesis of the sulfate donor 3′-phosphoadenosine 5′-phosphosulfate (PAPS) on top of their function as precursors for proteins and other specific compounds."

"Sulfites are added to some foods (especially wines and dried fruit) as preservatives, antioxidants, and bleaching agents. US regulations allow the use of sulfur dioxide, sodium sulfite, sodium bisulfite, potassium bisulfite, sodium metabisulfite, and potassium metabisulfite for food preservation. Numerous pharmaceutical products contain significant amounts of sulfites (Miyata et al., 1992). Wine and cider drinkers in France in one survey consumed an average 31.5 mg/day sulfite; those who did not drink alcoholic beverages had an average intake of 2 mg/day (Mareschi et al. 1992)."

"Some sulfate, including glucosamine sulfate and the food additive sodium dodecyl sulfate, is consumed directly. The sulfate content of bread is 1.5 mg/g, potatoes contain 0.3 mg/g, broccoli 0.9 mg/g, and wine 0.36 mg/g. Sulfate concentration in tap water varies widely, typically between a few milligrams to a few hundred milligrams per liter. The content of sulfate in bottled waters varies hugely. The mineral waters with especially high sulfate concentration include Eptinger (1630 mg/l) ☠, Valser (990 mg/l), Aproz (934 mg/l), Vittel, Hepar, San Pellegrino, Rietenauer, and Contrex."

"Epsom salt is magnesium sulfate concentrate derived from the waters of the Epsom spa that has traditionally been used for medicinal purposes."

"Glycosinolates from brassica species (cauliflower, broccoli, Brussel sprouts, cabbages, watercress, mustards, horse radish, and radishes) and from allium species (onions, garlic, leeks, and chives) release various sulfur compounds with a strong sulfurous odor. These relatively volatile odorants, such as methanethiol, dimethyl sulfide, and dimethyltrisulfide, do not contribute significantly to total sulfate intake."

"While a low-sulfate diet may provide as little as 1.6 mmol/day, most people get much more. The amount of all sulfur compounds combined that reach the colon may be as much as 7 mmol/day (Florin et al., 1991)."

"Nearly one of two healthy adults has sulfate-reducing bacteria (SRB, Desulfovibrio desulfuricans) in the colon, which generate sulfide (Pitcher et al., 2000). Colonic sulfide production competes with methane production for hydrogen. High sulfide production from sulfur amino acids may explain the absence of CH4 in the breath of many people in western populations (Pitcher et al., 1998). SAM-dependent conversion of 2-mercaptoethanol to S-methyl-2-mercaptoethanol is mediated by thiol methyltransferase (EC2.1.1.9, Pitcher et al., 1998)."

"Sulfate is the fourth most abundant anion in human plasma, with fasting concentrations around 300 μmol/l (Hamadeh & Hoffer, 2001). Intake of sulfur amino acids or sulfate can increase plasma levels nearly twofold. Typical sulfite concentrations in serum are around 5 μmol/l with a reference range of 0–10 μmol/l (Ji et al., 1995)."

"Several transporters with diverse tissue expression patterns mediate the transfer of sulfate into or out of cells. Erythrocytes, leukocytes, fibroblasts, vascular smooth muscle, liver, and other tissues take up and release sulfate along with a proton in exchange for a chloride ion via SLC4A1 (band 3 protein), which otherwise mediates exchange of chloride and bicarbonate (Gimenez et al., 1993; Jennings, 1995; Chernova et al., 1997)."

"The sulfate transporter SLC26A2 is critical for the production of sulfated proteoglycans in cartilage matrix (genetic defects cause a clinical phenotype of diastrophic dysplasia). Sulfate transporter 1 (SUT1, SLC13A4) is a sodium-dependent system in a few specialized tissues, including the heart, testes, and placenta. Its abundant presence in high endothelial venules is closely linked to the accumulation of sulfate at these vascular sites associated with lymphocyte extravasation into the extravascular space and lymphatic vessels. Sulfate is also supplied to these endothelia via the sulfate anion exchanger SLC26A7 (Vincourt et al., 2002)."

"Hydrogen sulfide: This small molecule is a key mediator and its tissue concentrations are tightly regulated (Kimura, 2014). The reactions catalyzed by cystathionine β-synthase (CBS, EC4.2.1.22), cystathionine γ-lyase (CSE, EC4.4.1.1), and 3-mercaptopyruvate sulfurtransferase (3MST, EC2.8.1.2) generate hydrogen sulfide. A series of other reactions in mitochondria metabolize hydrogen sulfide to a rich spectrum of compounds, including polysulfides, thiosulfate, and sulfate. Sulfide:quinone oxidoreductase (SQR, EC1.8.5.4) binds the sulfide and oxidizes it while transferring two electrons to the ubiquinone. Sulfur dioxygenase (EC1.13.11.18) then acts on the SQR-bound persulfide and oxidizes it to sulfite. Thiosulfate sulfurtransferase (rhodanese, EC2.8.1.1) finally combines the SQR-bound persulfide with sulfite and releases it as thiosulfate."

"Sulfide quinone oxidoreductase (SQR, EC1.8.5.4) can generate polysulfides, which are compounds with 2–8 sulfur atoms in sequence: n HS- + n quinone ⇌ polysulfide + n quinol . The polysulfide with 8 sulfur atoms forms a ring and does not accept additional sulfides."

"SQR can also reduce sulfide to sulfur (sulfide + ubiquinone-1 ⇌ sulfur + ubiquinol-1). The addition of sulfite to the sulfide molecule generates thiosulfate (sulfide + sulfite + ubiquinone-1 ⇌ thiosulfate + ubiquinol-1). All of these SQR-mediated reactions occur in the mitochondria."

"Thiocyanate: SQR catalyzes the condensation of sulfide with cyanide, which generates thiocyanate (sulfide + cyanide + ubiquinone-1 ⇌ thiocyanate + ubiquinol-1). The mitochondrial enzyme thiosulfate sulfurtransferase (rhodanese, EC2.8.1.1) adds a sulfur group from thiosulfate to cyanide and thereby generates sulfite and thiocyanate.
These reactions are important for the detoxification of cyanide, especially in the case of high dietary exposure (Spencer, 1999)."

"The flavoprotein sulfite oxidase (EC1.8.3.1) uses oxygen and water to oxidize sulfite to sulfate. The reaction releases hydrogen peroxide and relies on cytochrome c as the electron acceptor. The enzyme, which contains molybdenum cofactor and heme, resides in the mitochondrial intermembrane space and is thus readily accessible for cytosolic sulfite."

"Reactions that attach sulfate to proteins or other complex molecules use PAPS as a sulfate donor. PAPS synthesis proceeds in two distinct steps. Sulfate adenylyltransferase (EC2.7.7.4) links sulfate to the adenylyl phosphate moiety of ATP and releases pyrophosphate. Adenylylsulfate kinase (EC2.7.1.25) then adds a phosphate in the 3′ position. In humans, both activities are combined in the bifunctional proteins 3′-phosphoadenosine 5′-phosphosulfate synthethase 1 (PAPSS1; highly active in the brain) and 2 (PAPSS2; in the liver). PAPSS1 localizes strongly to the cell nucleus. Adenylylsulfatase (EC3.6.2.1) and phosphoadenylylsulfatase (EC3.6.2.2, manganese-dependent) reverse these synthesis steps and release sulfate again."

"Small amounts of sulfate are stored in tissues as ascorbate sulfate. Alcohol sulfotransferase (EC2.8.2.2, requires divalent iron, manganese, or cobalt for activation) uses PAPS to modify ascorbate. Arylsulfatase A (EC3.1.6.1) releases sulfate from ascorbate sulfate."

"Fecal losses of sulfur compounds are small (<0.5 mmol/day) compared to urinary excretion (Florin et al., 1991). Typical total sulfur excretion via urine is around 1.3 g/day (Komarnisky et al., 2003) but may be more with high intake. About 15% of the urinary losses are in the form of organic sulfate esters (e.g., hormones, flavonoids, and xenobiotics). Most of the remainder is excreted as sulfate (Hamadeh & Hoffer, 2001)."

"More than 5 g of sulfate is filtered daily in the kidneys. The renal proximal tubules recover most of this amount through the sodium/sulfate symporter (SLC13A1, NaSi1) in the brush border membrane of epithelial cells of proximal tubules (Puttaparthi et al., 1999). Vitamin D status influences sulfate uptake from the proximal tubular lumen (cf. P.1522, Markovich, 2001). The sodium dicarboxylate/sulfate transporter 2 (SDCT2) then extrudes sulfate across the basolateral membrane into the perivascular space in exchange for succinate or citrate plus sodium (Chen et al., 1999)."


Functions summarized

"Hydrogen sulfide: This small molecule is an important signaling compound that affects neuronal function, cellular integrity, modulation of inflammatory reactions, vascular tone, and other key homeostatic functions (Kimura, 2014)."

"Polysulfides have recently gained attention for their importance in the brain and other tissues, where they activate transient receptor potential channels even more potently than hydrogen sulfide. They also promote the expression of numerous genes. An important example is the sulfide-dependent sulfuration of Kelch-like ECH-associated protein 1 (Keap1), which in turn releases Nrf2 and thereby promotes the expression of antioxidant genes (Kimura, 2014)."

"Cyanide detoxification: Small amounts of cyanide are consumed with certain glycosides in food that are cleaved during digestion by beta-glucosidase (EC3.2.1.21). Various seeds contain amygdalin, prunasin, and other cyanogenic glycosides (Bolarinwa et al., 2015). Examples include bitter almonds and apple seeds. The only commonly consumed food with cyanogenic glycosides in significant amounts is cassava (Manihot esculenta). This tuber contains linamarin, from which cyanide can be released by hydroxynitrile lyase (EC4.1.2.47) from the plant itself or by bacterial beta-glucosidase (EC3.2.1.21) during food fermentation or intestinal digestion."

"Sulfide quinone oxidoreductase (EC1.8.5.4) in mitochondria combines cyanide with sulfide and reduces the aggregate to thiocyanate. Thiosulfate sulfurtransferase (rhodanese, EC2.8.1.1) is another mitochondrial enzyme that chemically sequesters cyanide. In this case, thiosulfate is bound to cyanide and thiocyanate plus sulfite are then released. Yet another enzyme, 3-mercaptopyruvate sulfurtransferase (3MST, EC2.8.1.2), combines cyanide with 3-mercaptopyruvate and generates thiocyanate plus pyruvate."

"Thiocyanate: Thiocyanate (H2S2O3) selectively promotes the action of glutamate at neuronal glutamate receptors of the (RS)-alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) subclass. Myeloperoxidase (EC1.11.2.2) and other peroxidases use thiocyanate to generate the potent free radical hypothianate (OSCN−) for antimicrobial defense and in inflammatory environments (Rees et al., 2014)."

"Increased thiocyanate production in excess of an individual’s capacity for its removal by excretion or metabolism may be responsible for persistent spastic weakness of the legs and degeneration of corresponding corticospinal pathways (konzo, which means “tied legs” in English) in people with habitual consumption of cyanogenic plants such as cassava (Boivin et al., 2013)."

"Glycans: Sulfate groups endow various complex sugar polymers with their characteristic properties. Chondroitin (in cartilage and many other tissues) contains sulfite groups linked to the 4 or 6 position of the N-acetyl galactosamin (GalNAc) moieties."
"In heparan sulfate (in skin, arterial endothelium, and other sites), the sulfur group resides at position 2 of the acylated glucose moieties and at position 2 of l-iduronic acid. The closely related heparins (in mast cells) contain an even higher proportion of sulfate-substituted sugars. Keratan sulfates (present in cartilage, cornea, and numerous other tissues) are substituted at position 6 of both their glucose and N-acetylglucose constituents by keratan sulfotransferase (EC2.8.2.21)."

"Arylsulfatase E (EC3.1.6.1) in bone and cartilage removes the sulfate groups again from these polymers (Daniele et al., 1998). Another important enzyme with detoxifying, antioxidant properties is triglucosylalkylacylglycerol sulfotransferase (EC2.8.2.19)."

"Sulfolipids: Brain and nerve tissues contain a rich assortment of sulfoglycolipids. Sulfatides (galactosylceramide 3-sulfates) and seminolipids (monogalactosylalkylglycerol 3-sulfate) are two distinct types within this class of complex compounds (Honke et al., 2002). The vitamin K–dependent enzyme galactocerebroside sulfotransferase (EC2.8.2.11) mediates the sulfate transfer from PAPS to both types, while arylsulfatase (EC3.1.6.1, also vitamin K-dependent) catalyzes the release of the sulfate group (Sundaram & Lev, 1992). An important product of such reactions is galactocerebroside 3-sulfate."

"Cell adhesion proteins: Various cell surface antigens interact with their targets only when they are sulfated. Examples are 6-sulfo N-acetyllactosamine glycoconjugates such as the lymphocyte homing receptor l-selectin and the blood group compound 6-sulfo sialyl Lewis X."

"Catecholamines: The activity of catecholamines is modified by sulfation."

"Steroid hormones: Estrone sulfotransferase (EC2.8.2.4), steroid sulfotransferase (EC2.8.2.15), cortisol sulfotransferase (EC2.8.2.18), and to some extent less specific sulfotransferases mediate the modification of a wide range of endogenous and synthetic steroid hormones and metabolites using 3′-phosphoadenylylsulfate as a sulfate donor."

"Bile acids: Both conjugated (to glucuronate, taurine, or glycine) and free bile acids can be sulfated by bile-salt sulfotransferase (EC2.8.2.14)."

"Modification of xenobiotics: A wide range of endobiotics, heterocyclic amines, and other complex molecules are sulfated upon uptake into the small intestinal epithelium. For instance, about 10% of the soy isoflavone genistein is sulfated and appears to be the most effective biological form. The phenolsulfating phenol sulfotransferase 1 (SULT1A3, EC2.8.2.1) uses 3′-phosphoadenylylsulfate to convert phenols into arylsulfates."

"Gastrointestinal effects: Sulfate-rich waters have been used in spas for the treatment of ailments of the digestive tract. Ingestion of sulfate-rich water appears to stimulate the emptying of the gallbladder (Gutenbrunner et al., 2001)."

"Renal effects: High sulfate intake with certain natural mineral waters may induce diuresis and has been suggested as a mild adjunct to the treatment of urolithiasis and pyelonephritis. Urinary sulfate may inhibit uric acid crystallization, thereby reducing the risk of kidney stone formation."

"Skeletal effects: High intake of sulfur-containing amino acids and sulfate (mineral water) has been linked to accelerated bone mineral loss."

"Sulfite toxicity: Exposure of sensitive individuals to several hundred milligrams of sulfite can trigger asthma attacks with airway constriction, nasal congestion, urticaria, vasculitis (Wuthrich, 1993), and other skin manifestations. Sulfites readily react with nitric oxide and related compounds (Harvey & Nelsestuen, 1995). The resulting nitric oxide depletion may interfere with its signaling function, thereby causing some of the toxic effects of sulfite."

- Hydrogen sulfide abrogates heart valve calcification: Implications for calcific aortic valve disease

 

[berk]

Hello, i have a sulfite intolerance and sulfate foods give me big inflammation in all my joints.
Because all protein have high amount sulfate i consume all my protein before bed so it don't bother me.

I got lost halfway this topic, to much stuff in it, to technical what i don't understand.

So lets wrap up what in the conclusion that can heal sulfur intolerance?

 

[Amazoniac]

Hello, i have a sulfite intolerance and sulfate foods give me big inflammation in all my joints.
Because all protein have high amount sulfate i consume all my protein before bed so it don't bother me.

I got lost halfway this topic, to much stuff in it, to technical what i don't understand.

So lets wrap up what in the conclusion that can heal sulfur intolerance?

You mean problems with sulfur once it's absorbed?
- Molybdenum, Hard To Pronounce, Harder Still To Obtain


If it involves gut imbalances and it's the constipation type, vigorous intestinal activity is the priority; if you correct it, the rest might follow, and if there hasn't been much time since initiation, it shouldn't be rooted and harmful microbes should be outcompeted. The diarrheal types tend to be more complicated to solve because microbes aren't merely overgrowing due to a favorable conditions, you would have to attempt to modulate it somehow, larger doses of killcium should help to control it.


The things that have been suggested:

- Acidification with safe fermentable carbs.
- Sun exposure.
- Ubiquinone. Should we call mk-4, MeQ4; or CoQ10, uq-10? Confusing and dangerous. Again, IUPAC/FAO/WWF/FDA (Lemonoil, 2020) to it.
- Methylene blue. [C16H18ClN3S]
- Extra ascourgic acid (if I'm not wrong, Raj suspected industrial sulfur residues in some supplements).
- Creatine/choline/cobalamins (preferably together with protein, collagen and adequate magnesium). They can worsen the state in case of existing nutrient deficiencies.
- Hydrolyzed collagen instead of gelatin.
- Troubling supplements can be consumed at a higher dose less often, or topically.
- Topical B-vitamins, magnesium, and vitamin E with K2.
- Anthocyanin-rich foods.
- Sodium 'hydrogen carbonate' before meals (waiting until appetite returns).
- Vinegar (neutralized or not).
- Trace minerals: copper, molybdenum, manganese, zinc, selenium (inorganic forms may be alternatives, probably unnecessary and fatal), boron, silicon.
- Problematic foods at the end of the day with a hefty killcium dose. Roughage with meals depends on the type of condition, but more at evening if you want to encourage fermentation and acidification.
- Trying problematic foods on their own (for the sake of experiment) and avoid starting your day with them.
- Combining troubling ones with nitrate-rich foods (celery root/stalk, beetroots, and so on; depends on what you're dealing with, check out text below).
- Dark leafy greens mixed.
- Venom D with meals (prevents microbial action).
- Green apple (or its juiceless fiber added to other recipes).
- Custard apple family fruits (even soursop).
- Berries.
- Edible fruit skins (may try supplemental lactose with them).
- Incidental resistant starch.
- Bell pepper.
- Ginger, cinnamon, hibiscus, pepper, (dried) herbs (some are sources, such as oregano, cooking helps, but the only spice that's really concerning in terms of fueling the problem is turmeric).
- Beneficial fats such as butter and coconut can be inducers: better consumed with complex meals that make their impact in this regard negligible.
- Walking (moderate activity) sipping magnesium water (improves its utilization).
- Counteracting the stress response to troubling foods with as much clothing as it's necessary to keep you comfortable (putting on or taking out).
- Cascara sagrada for relief.


Limiting the intake of the most troubling foods is advisable, but excluding all potential sources not only is impractical, but won't work. This toxin is everywhere:
- Organosulfur compounds - Wikipedia
- Volatile sulfur compounds in tropical fruits

Foods are complex enough to not justify restriction of any without being sure that the one in question is doing more harm than good. It may contain enough reasons to be contraindicated, yet it ends up not being detrimental in practice because there's something else in it that's protective. Dairy, pineapple, cocoa/chocolate and cruciferous vegetables are examples that may have more valuable compounds in them than the potential troubling ones. Their quality also varies a lot, it's a the worth exploring your available options. For example, cheeses might behave differently, there are ones whose proteins are easy to digest, provide a lot of salts that will be protective; white and opaque pineapples are harsh, the others are not; some dark chocolate bars have a fart.. taste, others are naturally sweet; a mild fermentation of cruciferous vegetables can be advantageous; and so on.

In general, it's the indigestible sulfur-containing compounds in high concentrations that are fueling.

Some traditional condiment recipes call for complementary ingredients with balancing fibers, it's rarely just one class.

The major source of sulfur in the diet are the amino acids containing them (not a reason to restrict them, it's not necessarily proportional to content). If I remember it right, about 25% of their weight is sulfur. Requirements vary, but you can use the RDA as guide to be sure that the intake of sulfur is decent.


It's possible to be dealing with acetate consumers that block butyrate utilization, nice.

- Hydrogen sulfide toxicity in the gut environment: Meta-analysis of sulfate-reducing and lactic acid bacteria in inflammatory processes

Spoiler

"SRB are [] present in the gastrointestinal tract of humans and animals [3–7]. They can significantly influence the gut environment since they are producing hydrogen sulfide and at the same time they are competing for nutrients. Hydrogen sulfide interferes in the colonocytes with metabolic processed and it damages the intestinal mucosa [8–11]. Consequently, SRB can be a cause for the initiation of the inflammation that can lead to bowel diseases such as ulcerative colitis (UC) [12–16]." "On the other hand, ulcerative colitis is considered a multifactorial disease with unclear etiology."

"Several pathological findings are related to ulcerative colitis: oxidative stress, specific inflammatory mediators increase, higher concentrations of glycosaminoglycan in the mucosa, short chain fatty acids reduced oxidation, higher intestinal permeability, higher sulfide production and lower level of methylation. Geographical region, lifestyle and diet habits also affect the prevalence of UC. Developing countries have lower incidence rates in comparison with developed nations. USA, UK, Canada and Scandinavia are the countries with the highest incidence of UC (the prevalence: 1/1000). The lowest UC prevalence is in Africa. In Africa methanogens are the most dominant gut microorganisms among populations [38–40]."

"UC can be grouped according to the occurrence place: proctitis (distal part), distal colitis (descending colon) and pancolitis (the whole colon). Symptoms are abdominal cramping, stool loosening and diarrhea. When the disease is more progressive, affected individuals lose weight, feel fatigued, appetite loss, rectal bleeding, fever and anemia [42]. Higher counts of SRB and increase amounts of H2S are in correlation with UC formation. Hydrogen sulfide concentrations in healthy adult individuals range from 0.3 to 3.4 mmol/l. The free penetration of hydrogen sulfide through the cell membrane is possible due to its solubility in lipophilic solvents. Adenosine 5'-triphosphate-dependent potassium channels, DNA integrity, and activity of cytochrome c oxidase and carbonic anhydrase are influenced by H2S [8,36,37,43]."

"H2S is prohibiting butyrate oxidation. Colonocytes are getting 70% of energy from the butyrate derived from intestinal substrates fermentation by gut microbiota [44]. That is the reason why energy deficiency is often connected with the prevalence of UC [10,11,45]."

"Anoxic habitats are environments where sulfate-reducing bacteria (SRB) are often found [46]. SRB are able to reduce sulfate to hydrogen sulfide and from this their ability is also derived their name. They use sulfate in the same way as aerobic microorganisms oxygen (terminal electron acceptor) [47–50]."

"Biologically, SRB are quite unrelated to each other (they differ in shape and optimal growth conditions), beside ability to perform dissimilatory sulfate reduction [51]."

- Definition and distinction between assimilatory, dissimilatory and respiratory pathways

"In general, a redox process can be consideredas assimilatory if reducing equivalents, mainly NAD(P)H,are used to generate a molecule that is further incorporated into cell material, as respiratory if the electron flowis coupled to a proton-translocating complex to allow ATP generation or as dissimilatory if electrons are transferred, without the generation of a proton motive force, to dissipate the excess of reducing power."​

"SRB use hydrogen as an organic matter and obtain energy by oxidation. In sulfate reduction, electron donors are lactate, pyruvate, malate, succinate and acetate [57]. Some strains of SRB can grow on short-chain fatty acids (including acetate), long chain fatty acids and aromatic compounds (benzoate and phenol) [48]. There is a difference among SRB in their organic compounds degradation since some of them degrade organic compounds to carbon dioxide (total degradation) and others degrade it only to acetate [51]. Sulfate is the terminal electron acceptor, but fumarate and dimethylsulfoxide can be used by some marine strains, same as sulfonates by Desulfitobacterium [58–61]."

"Gram positive (that are exceptions) SRB are spore forming (Desulfotomaculum), while the majority are gram negative [63]. The majority of SRB are motile (they usually have a single or polar and multiple flagella. SRB can also lose their motility by losing their flagella if they are treated roughly [51]. High concentrations of hydrogen sulfide are another factor affecting the motility of Desulfovibrio [5,51]."

"SRB are declared anaerobes, though they can tolerate some oxygen during a period of time [64]. The oxygen tolerance is species dependent [65]."

"Medium for SRB growth usually contains lactate (the most commonly utilized electron donors in SRB metabolism [6,68,70–72]. SRB are used as significant reducers for the elimination of the environmental pollution, since various SRB can oxidize toluene, ethylbenzene, benzene and xylene (the major compounds in aromatic fuel hydrocarbons) [47]."

"Different substrates can be utilized by SRB in the human colon. The major electron donors are fatty acids (acetate, propionate and butyrate), amino acids (glutamate, serine and alanine), ethanol and organic acids (succinate, pyruvate ad lactate). Hydrogen can be also utilized by Acetogens (Clostridium, Ruminococcus, Blautia) and methanogens (Methanobrevibacter, Methanosphaera). Sulfite (with very low pH: pKa = 7.04) is released into the colonic environment and biologically active free H2S is in the process of HS hydrolysis [9,26,40]. SRB cannot survive in environments with low sulfate concentrations, since they have a limited capacity to degrade carbon compounds. SRB has to compete for the hydrogen with methanogenic bacteria that use it more efficiently. Consequently, in human feces can be only one of these two bacteria [8]."

"There is a higher prevalence of SRB in patients with UC than in healthy persons. Certainly, that the presence of sulfate is influencing SRB counts. The studies that conducted experiments including feeding of animals (guinea pigs with developed UC) with sulfated polysaccharides (carrageenan and amylopectin sulfate) indicated the progression of colitis like conditions. Specific fatty acids (derived during sulfur metabolism) can also induce colitis due to their influence on colonic epithelial cells [40]."

"Superoxide radicals and peroxides are formed in the process of sulfide reduction. The formation of aggregates is helping SRB to survive oxygen exposure or even to conduct an oxygen reduction [67]."

"Sulfur can be utilized only in its reduced form and that is the reason why the process of sulfate reduction is very important in nature [51]. It means that sulfates, thiosulfates and sulfites are essential for life on Earth [2]. Many microorganisms can perform an assimilatory sulfate reduction, but only a few microorganisms can perform a dissimilatory sulfate reduction [78]. The final product of sulfate reduction is hydrogen sulfide (H2S) (requiring 8 electrons) [2]. There are more than hundred compounds that can be potential electron donors for SRB [1]."

"Lactate or acetate, electrons and hydrogen ions are formed in the process of carbon sources oxidation [23]. Subsequent metabolism utilizes these ions. SRB reduce sulfate to hydrogen sulfide, same as aerobes reduce oxygen to water."

"Beside sulfur containing compounds, SRB are also able to use other molecules from the environment as terminal electron acceptors, including nitrite and nitrate (some strains of Desulfovibrio)."

"Following strains can utilize nitrite and nitrate: Desulfovibrio, Desulfobulbus, Desulfotomaculum, Desulfobacterium and Thermodesulfovibrio [1]. In certain occasion they can even prefer them over sulfate [74]. Ammonium is the final product of nitrate by sulfate and sulfur reducers [64]."

"Spontaneous relapsing inflammation of the gut is the characterization of inflammatory bowel diseases (IBD), such as ulcerative colitis (UC) and Crohn’s disease. Crohn’s disease can influence each part of the digestive system, oppositely from the ulcerative colitis that affects only the large intestine [82]. The reason for this is probably acidic pH of the stomach (unfavorable environment for the SRB), while colon has a pH lower than 5.5, but in the distal part of the colon pH is neutral that is considered the optimal condition for SRB growth [23]."

"The correlation between IBD and SRB presence in the gut has been found, but they are still considered an ordinary component of the normal intestinal flora (SRB is found in the digestive system of healthy people too). Healthy population has prevalence of SRB in the gut, according to literature, from 12% to 79% [8,14]."

"SRB cannot be considered direct pathogens, but only a possible contributing factor in ulcerative colitis development. An inappropriate response to a luminal agent is the cause for IBD [83]. During inflammation the barrier epithelium function is damaged and translocation of toxins and antigens further promotes immune response [23]."

"Cells are starving due to the inhibition of butyrate oxidation that is caused by hydrogen sulfide damages on gut mucosa [42]. The experiments, including human colonocytes showed butyrate oxidation by hydrogen sulfide of 75% and 43% in the distal colon and ascending colon, respectively [11]. Decreased oxidation of short chain fatty acids is influencing gut inflammation, since studies confirmed lower butyrate oxidation levels in patients with UC than in patients within remission. The fact is also supported by the fact that 3 patients with inactive disease faced relapsed in a few weeks, had decreased butyrate oxidation [91]."

"Food commodities containing more than 80 mg/100 g of sulfate are cow milk, cheese, eggs and cruciferous vegetables [10]."

"The oxidation of sulfur dioxide (present in cheese, beer, canned and pickled products serving as a conservator) can be also the source of sulfate. Mucins, secreted by goblet cells of the gastrointestinal tract, and chondroitin sulfate in mammalian tissues are other sulfate sources [2]. SRB are dependent on saccharolytic bacteria in the gut, since they cannot utilize mentioned sulfate sources. Saccharolytic bacteria can disengage the bound sulfate through depolymerization and desulfatation of glycoproteins [40]."

"SRB belong to methylation bacteria and they are capable of inorganic mercury transformation to more toxic organic form of mercury (methyl mercury) [104]. The studies indicated that SRB are the main Hg methylators in soil and sediments (anaerobic environments) [105] (Hsu-Kim et al., 2013). Molybdates are used for the SRB inhibition in soil [104]. Though, not all SRB can methylate mercury, this property depends on the strain rather than genus or species [105]. Methyl-cobalamin compounds and acetyl-coenzyme A (acetyl-CoA) pathway are responsible for the methylation of inorganic mercury. The exceptions have been also found, since some SRB without acetyl-coenzyme A were detected to produce methyl mercury [106]."

"Colorless aromatic amines are formed by the ability of hydrogen sulfide to degrade the N≡N bond."

"Lactic acid bacteria can inhibit certain microorganisms due to its ability to penetrate the cytoplasmic membrane in undissociated form. This is resulting in diminished intracellular pH and at the same time disruption of the proton motive force transmembrane. Lactic acid change outer membrane permeability due to its ability to gain access to the periplasmic space of gram-negative bacteria (via the porins present in the outer membrane). This process is not considered bactericidal. The penetration of other compounds such as bacteriocins, antibiotics or lysozymes to the cell occur due to the outer membrane disruption. In this way cellular metabolism can be affected may result in cell death [120]."

"The benefit of LAB is that they are forming conditions not adequate for pathogenic microorganisms such as: low pH and oxidation-reduction potential, antimicrobial compounds production, or lack of nutrients due to competition [122]."

"Various enzymes are released into the intestinal environment by lactic acid bacteria, resulting in synergistic impacts on digestion, malabsorption symptom reduction, and lactic acid production, leading to the decrease of the intestinal pH and so inhibition of invasive pathogens. Due to the bacterial enzymatic hydrolysis, bioavailability of protein and fat may be enhanced. This process can lead to higher production of free amino acids. The short chain fatty acids (SCFA) released into the intestinal environment as the end-product of fermentation, when absorbed, contribute to the available energy of the host and can increase the protection against pathological changes in the colonic mucosa. Certain SCFA concentration may also help to keep a suitable pH in the colonic lumen. This is crucial in the expression of many bacterial enzymes as well as in the carcinogen metabolism in the gut [131,134]."

- CoQ10 supplementation rescues nephrotic syndrome through normalization of H2S oxidation pathway (!)

Nephrotic syndrome (NS), a frequent chronic kidney disease in children and young adults, is the most common phenotype associated with primary coenzyme Q10 (CoQ10) deficiency and is very responsive to CoQ10 supplementation, although the pathomechanism is not clear. Here, using a mouse model of CoQ deficiency-associated NS, we show that long-term oral CoQ10 supplementation prevents kidney failure by rescuing defects of sulfides oxidation and ameliorating oxidative stress, despite only incomplete normalization of kidney CoQ levels and lack of rescue of CoQ-dependent respiratory enzymes activities. Liver and kidney lipidomics, and urine metabolomics analyses, did not show CoQ metabolites. To further demonstrate that sulfides metabolism defects cause oxidative stress in CoQ deficiency, we show that silencing of sulfide quinone oxido-reductase (SQOR) in wild-type HeLa cells leads to similar increases of reactive oxygen species (ROS) observed in HeLa cells depleted of the CoQ biosynthesis regulatory protein COQ8A. While CoQ10 supplementation of COQ8A depleted cells decreases ROS and increases SQOR protein levels, knock-down of SQOR prevents CoQ10 antioxidant effects. We conclude that kidney failure in CoQ deficiency-associated NS is caused by oxidative stress mediated by impaired sulfides oxidation and propose that CoQ supplementation does not significantly increase the kidney pool of CoQ bound to the respiratory supercomplexes, but rather enhances the free pool of CoQ, which stabilizes SQOR protein levels rescuing oxidative stress.

Spoiler

"As CoQ10 deficiency has been shown to cause impairment of H2S oxidation [18,33], we assessed effects of CoQ10 supplementation on levels of the enzymes involved in the H2S oxidation pathway, sulfide quinone oxido-reductase (SQOR), thiosulfate sulfurtransferase (TST), persulfide dioxygenase (ETHE1) and sulfite oxidase (SUOX)."

- Problems With Sulphur​

"Here, we show that abnormalities in the H2S metabolism pathway [when synthesis of ubiquinode is impaired are] early events, occurring in pre-symptomatic stage of disease. We have observed that CoQ10 supplementation rescues survival and prevents kidney failure in mutant animals, but does not correct respiratory chain enzymes activities. On the contrary, CoQ10 administration improves oxidative stress and rescues H2S oxidation proportionally to the duration of the supplementation and increases mitochondrial mass. These results support the hypothesis that H2S oxidation impairment and oxidative stress together contribute to the pathogenesis of NS in CoQ deficiency, while defects of mitochondrial respiratory chain enzymes activities are not detrimental."

"We recently showed that CoQ deficiency in vitro and in vivo causes H2S oxidation abnormalities with consequent H2S accumulation [18,55]. H2S is a gasotransmitter with several physiological functions, but when accumulated, is toxic. Therefore, H2S levels are tightly regulated by its synthesis and catabolism pathways [56,57]. Kidney might be particularly vulnerable because it produces H2S not only through the transulfuration pathway (using L-cysteine), but also through the DAO/3-MST pathway, in which 3-MP is generated from D-cysteine by D-amino acid oxidase (DAO) [58,59]. DAO is richly expressed in the kidney and may generate more H2S than the L-cysteine pathway [60]. Interestingly, DAO is also highly expressed also in cerebellum [61,62], which is another organ frequently affected in human CoQ10 deficiency, primary and secondary [63,64]."

"Although the link between oxidative stress and H2S in kidney physiology and pathology is rather controversial due to conflicting data in this field, ROS production has been implicated as mechanism of H2S toxicity [20,21]. Since we excluded COX deficiency [16,18], we propose that low levels of GSH contribute to oxidative stress since we observed decreased GSH in kidney of 1 and 6 month-old Pdss2[kd/kd] mice, and GSH levels increased after CoQ10 supplementation. Low levels of GSH may be a direct consequence of the down-regulation of the H2S catabolic pathway and its intermediates. Alternatively, GSH deficiency might be due to limited availability of its precursor cysteine, because H2S accumulation in kidney of Pdss2[kd/kd] mice might trigger negative feedback on the H2S synthesis pathway, which uses cysteine as substrate. Finally, since we previously observed that CoQ10 deficiency in vitro causes increasing of S-sulfhydration of proteins involved in redox status of the cells [18], it is possible that this post-translational modification adversely affects their functions and contributes to oxidative stress in CoQ deficiency. In fact, protein S-sulfhydration has emerged as fundamental mechanism of H2S signaling [68,69]."

"Kidney, together with brain and muscle, has been described as one of the organs with poorest uptake of CoQ10 [38], a data confirmed by two previous studies of short-term CoQ10 supplementation in Pdss2[kd/kd] mice [17,45]. However, studies of long-term CoQ supplementation in wild-type animals showed accumulation of CoQ in kidney [74]. Our results not only confirm that long-term supplementation is necessary for CoQ10 to reach target organs, but they also demonstrate that even when CoQ10 reaches the target organ, not all of its biological functions are restored. It is noteworthy that SQOR and CoQ-dependent respiratory enzymes are both localized in the inner mitochondrial membrane and therefore should be equally reached by exogenous CoQ10."

"The lipidomic analysis also indicated that CoQ10 deficiency alters cholesterol homeostasis. Specifically, mutant mice showed significant increases in cholesterol esters (CEs) containing long-unsaturated acyl chain, which might result from up-regulation in the uptake of cholesterol, or reduction in its efflux. Interestingly, and in contrast to liver, CoQ10 supplementation rescued CEs levels in kidney, with a concomitant increase in the level of non-esterified cholesterol. In agreement with previous reports [78], this result suggests that CoQ10 supplementation activates cholesterol metabolism, in a tissue-specific manner." @lampofred