I needed to disable self sign-ups because I’ve been getting too many spam-type accounts. Thanks.
Looking for clues
https://people.csail.mit.edu/seneff/sulfur_obesity_alzheimers_muscle_wasting.html
“In her recently published book, The Jungle Effect [Miller2009], Dr. Daphne Miller devotes a full chapter to Iceland (pp. 127-160). In this chapter, she struggles to answer the question of why Icelanders enjoy such remarkably low rates of depression, despite living at a northern latitude, where one would expect a high incidence of Seasonal Affective Disorder (SAD). She points out, furthermore, their excellent health record in other key areas: "When compared to North Americans, they have almost half the death rate from heart disease and diabetes, significantly less obesity, and a greater life expectancy. In fact, the average life span for Icelanders is amongst the longest in the world." (P. 133). While she proposes that their high fish consumption, with associated high intake of omega three fats, may plausibly be the main beneficial source, she puzzles over the fact that former Icelanders who moved to Canada and also eat lots of fish do not also enjoy the same decreased rate of depression and heart disease.”
Seneff adds:
“In my view, the key to Icelanders' good health lies in the string of volcanoes that make up the backbone of the island, which sits atop the mid-Atlantic ridge crest. Dr. Miller pointed out (p. 136) that the mass exodus to Canada was due to extensive volcanic eruptions in the late 1800's that blanketed the highly cultivated southeast region of the country. This means, of course, that the soils are highly enriched in sulfur. The cabbage, beets, and potatoes that are staples of the Icelandic diet are likely providing far more sulfur to Icelanders than their counterparts in the American diet provide.”
So, apparently the Icelanders are eating a fairly high-A diet but are also getting a boat-load of sulfur. There’s got to be something worthwhile about that detail. What happens when sulfur/sulfates are increased on a low-A diet?
Stephanie Seneff has quite a number of power point presentations on her MIT site that are very intriguing. She doesn’t agree on our A-team view, (yet), but her work on Cholesterol Sulfate and other things seems to intersect the problems we’re looking at, as the italicized above seem to indicate. I like the simplicity of the geographical analysis here. It was “hook” for me when first reading Grant’s books. I’m experimenting with whitefish eggs which are fairly high in cholesterol and not too big of a “hit” on low-A.
Pursuing the sulfate part of her researches, I came upon the idea of grinding Epsom Salts with MCT oil in a mortar. They don’t dissolve to any great extent but the liquid portion turns a tad gray and after applying it there’s no salty residue and feels real silky smooth, so I figure it’s transporting some MgSO4 past the skin. There are over 2,000 abstracts on PubMed for the search “Bile and Sulfate”, going all the way back to 1923. I’m going to plow through them looking for further insights. If sulfate (and cholesterol) are healthy for our livers, then it’s right up our alley on the healing journey. Best to y’all.
I find Icelandic longevity a bit confusing too. I made a post a while back on an Icelandic centenarian who avoids cod liver oil and any "health foods". She didn't eat fruit or vegetables apart from potatoes and occasionally some cauliflower and banana. She had dairy and fish in her diet which were her only VA sources I believe, not a very high VA diet.
Seafood is very health promoting (iodine, selenium, magnesium, DHA/EPA) and this could help explain their longevity.
Iceland is a wealthy country for how many citizens it has, I believe they have an easier life than in many other Western countries on average.
She's an icelandic on an icelandic diet, and so it works for her!
Perhaps where people go wrong it when they adopt the foods that aren't ancestral to them.
I've been scanning a lot of papers and thought I'd just post some relevant bits on cholesterol sulfate and other sulfur-related subjects. Stephanie Seneff has done some serious "heavy lifting" on this subject for years and one paper of hers that I'd recommend is https://people.csail.mit.edu/seneff/Entropy/entropy-15-00372.pdf
Also, this review paper is very informative.
https://www.ncbi.nlm.nih.gov/pubmed/?term=22254206 Role of taurine in the vasculature: an overview of experimental and human studies.
The following are from a variety of papers on PubMed.
"Taurine also acts as an anti-proliferative and antioxidant agent in VSMCs. In endothelial cells, taurine variably inhibits apoptosis, inflammation, oxidative stress and cell death, while increasing NO generation. Oral taurine supplementation alleviates the symptoms of hypertension in hypertensive human patients and reverses arterial stiffness and brachial artery reactivity in type 1 diabetic patients."
"All cells in the body are decorated around their exterior membrane with an abundant supply of glycosaminoglycans (GAGs), complex molecules consisting of sugars (polysaccharides) and proteins, which are typically highly sulfated."
"Characteristics of celiac disease point to impairment in many cytochrome P450 enzymes, which are involved with detoxifying environmental toxins, activating vitamin D3, catabolizing vitamin A, and maintaining bile acid production and sulfate supplies to the gut. Glyphosate is known to inhibit cytochrome P450 enzymes."
"Cholesterol sulfate translocation rates were however up to 8 times greater than those observed for cholesterol when equivalent concentrations of the two substrates were added to the mitochondria. We conclude that cholesterol sulfate is a better substrate than cholesterol for side-chain cleavage by isolated mitochondria and that both reactions are catalysed by the same cytochrome P-450scc enzyme."
"Taurine is a sulfur-containing amino acid that is present in mammalian tissues in millimolar concentrations. Taurine is involved in a diverse array of biological and physiological functions, including bile salt conjugation, osmoregulation, membrane stabilization, calcium modulation, anti-oxidation, and immunomodulation."
"Oxygenated cholesterol derivative oxysterols are known to be endogenous ligands of the liver X receptor (LXR), a nuclear receptor with anti-cholestasis activity, whereas the sulfated oxysterols antagonize LXR signaling."
"Although cholestasis was developed during the infusion of non-sulfated bile acids, no cholestatic effect was observed for sulfated bile acids. With the exception of cholic acid, sulfation significantly increased the bile acid secretory rate maximum.
"89% of urinary BAs [bile acids]existed in the sulfate form, indicating the role of sulfation in enhancing the urinary excretion of BAs."
"It is possible by the combined use of adequate amounts of magnesium sulfate and of heparin intravenously to prevent all stages of thrombus formation for from 1 to 3 hours."
"These findings suggest that the metabolic pathway leading to the formation of 25-hydroxyvitamin D3 3-O-sulfate may be mediated by the sulfation of 25-hydroxyvitamin D3 or by the conversion of 7-dehydrocholesterol-3-O-sulfate in the skin."
"Epidemiological and laboratory studies provide insight into the anticarcinogenic potential of garlic and its constituent compounds. Both water- and lipid-soluble allyl sulfur compounds are effective in blocking a myriad of chemically induced tumors. Part of the protection from these compounds probably relates to a block in nitrosamine formation and metabolism. However, blockage in the initiation and promotion phases of the carcinogenicity of various compounds, including polycyclic hydrocarbons, provide evidence that garlic and its constituents can alter several phase I and II enzymes. Their ability to block experimentally induced tumors in a variety of sites including skin, mammary and colon, suggests a general mechanism of action"
"Plasma vitamin A levels were significantly high in lead-methionine group compared to lead group (p<0.01). In conclusion, the data suggests that oxidative stress induced by lead is reduced by sulphur-containing compounds."
"The syntheses of sulfur and selenium isosteric substitution analogues of retinol, namely, retinyl phenyl thioether (2b), retinyl phenyl selenoether (2c), and retinyl thioacetate (2e) are described. These retinoid derivatives were examined for activity in terms of "chemoprevention" of cancer by measuring the reverse keratinization of epithelial cells in vitro. Retinoid analogues 2b, 2c, and 2e were found to be active in 20, 80, and 33.3% of the cultures, respectively, as compared to 72.7% activity for trans-retinol."
To be continued:
Neat stuff. Someone on another thread was talking about baking soda in the bath, but I suppose this research says that we should also put epsom salts in there?
I suppose this tells us why people "like" to live on the sides of volcanoes. I posted this story a while back:
https://www.rd.com/health/conditions/island-people-forget-to-die/
Love to hang out with those folks some day, what a civilized life-style!
Here's more snips from research papers.
“Since higher steroid sulfation capacity was associated with successful weight intervention in children disruption of sulfation may be associated with difficulties to lose weight. Future studies are necessary to prove this hypothesis.”
“Mass spectrometric quantification revealed that CS was most abundantly produced in the Harderian gland, which provides the lipids that form the oily layer of the tear film. Sulfation of cholesterol is mediated by the sulfotransferases SULT2B1b and, to a lesser extent, SULT2B1a, which are produced from the same gene through alternative splicing. By genetically inactivating Sult2b1, we showed that the lack of CS in mice augmented ultraviolet- and antigen-induced ocular surface inflammation, which was suppressed by administration of eye drops containing CS. Thus, CS is a naturally occurring DOCK2 inhibitor and contributes to the generation of the immunosuppressive microenvironment in the eye.”
“Targeted analyses confirmed that sebaceous FFA [free fatty acids] and epidermal FFA were increased and decreased, respectively, in areas at high SG [sebaceous gland] density. CHS [cholesterol sulfate] and squalene, which are biomarkers of epidermal and sebaceous lipid matrices, respectively, were both significantly higher in areas at elevated SG density. Overall, results indicated that the SG secretion intervenes in shaping the lipid composition of the epidermal permeability barrier.”
“Historically sulfonated steroids were primarily considered as inactive metabolites destined for elimination. However, more recently they have been increasingly recognized as precursors for the production of bioactive steroids in target tissues and as functional molecules without preceding hydrolysis.”
“CS-deficient mice showed heightened sensitivity to a self-antigen, whereas increasing CS content by intrathymic injection inhibited thymic selection, indicating that this molecule is an intrinsic regulator of thymocyte development. These results reveal a regulatory role for CS in TCR signaling and thymic selection, highlighting the importance of the membrane microenvironment in modulating cell surface receptor activation.”
“Here, we show that cholesterol sulfate, a molecule present in relatively high concentrations in the epithelial layer of barrier tissues, is selectively recognized by Mincle (Clec4e), a C-type lectin receptor of the innate immune system that is strongly up-regulated in response to skin damage.”
“The sodium-dependent organic anion transporter SOAT (gene name SLC10A6 in man and Slc10a6 in mice) is a plasma membrane transporter for sulfated steroids, which is highly expressed in germ cells of the testis. SOAT can transport biologically inactive sulfated steroids into specific target cells, where they can be reactivated by the steroid sulfatase (STS) to biologically active, unconjugated steroids known to regulate spermatogenesis”
“By thin layer chromatography (TLC) of extracts from these organotypic cultures, we could show the absence of cholesterol sulfate, the metabolite of SULT2B1, and an increased level of cholesterol, indicating a disturbed cholesterol metabolism of the skin upon loss-of-function mutation in SULT2B1. In conclusion, our study reveals an essential role for SULT2B1 in the proper development of healthy human skin. Mutation in SULT2B1 leads to an ARCI phenotype via increased proliferation of human keratinocytes, thickening of epithelial layers, and altered epidermal cholesterol metabolism.”
“Cholesterol-protein interactions are essential for the architectural organization of cell membranes and for lipid metabolism. While cholesterol-sensing motifs in transmembrane proteins have been identified, little is known about cholesterol recognition by soluble proteins. We reviewed the structural characteristics of binding sites for cholesterol and cholesterol sulfate from crystallographic structures available in the Protein Data Bank.”
“The Stratum corneum (SC) prevents water loss from the body and absorption of chemicals. SC intercellular spaces contain ceramides (Cer), free fatty acids (FFA), cholesterol (Chol) and cholesteryl sulfate (CholS). Cer with "very long" acyl chains (for example, N-lignoceroyl-sphingosine, CerNS24) are important for skin barrier function, whereas increased levels of "long" acyl Cer (for example, N-palmitoyl-sphingosine, CerNS16) occur in patients suffering from atopic eczema or psoriasis.”
“Permeation was measured after 30min, and retinyl acetate was found up to 20μm deep inside the stratum corneum. The delivery of retinyl acetate inside a skin membrane model was studied by molecular dynamics. The membrane model that was used represented normal young skin containing a lipid bilayer with 25% ceramide, 36% fatty acid, 30% cholesterol, and 6% cholesterol sulfate.”
“Macrophages are able to polarize to pro-inflammatory M1 or anti-inflammatory M2 states with distinct phenotypes and physiological functions. RORα is a member of the nuclear receptor super family and plays important roles in lipid, glucose metabolism, as well as the inflammatory response. In this study, we examined the potential function of RORα in the regulation of macrophage polarization. Treatment of RAW264.7 macrophages with RORα agonist cholesterol sulfate (CH-S) and overexpression of RORα increased M2 macrophage markers expressions (Arg1, Ym1 and Fizz1) both on mRNA and protein levels.”
“These additional ligand-protein interactions result in an increased affinity of cholesterol sulfate when compared with cholesterol, as shown by mass spectrometry analysis done under native conditions and differential scanning calorimetry. Moreover, mutational studies show that the higher binding affinity of cholesterol sulfate translates into an increased transcriptional activity of RORalpha. Our findings suggest that cholesterol sulfate could play a crucial role in the regulation of RORalpha in vivo.”
“NPC2 is a small lysosomal glycoprotein that binds cholesterol with submicromolar affinity. Deficiency in NPC2 is the cause of Niemann-Pick type C2 disease, a fatal neurovisceral disorder characterized by accumulation of cholesterol in lysosomes. As predicted from a previously determined structure of apoNPC2, the sterol binds in a deep hydrophobic pocket sandwiched between the two beta-sheets of NPC2, with only the sulfate substituent of the ligand exposed to solvent. In the two available structures of apoNPC2, the incipient ligand-binding pocket, which ranges from a loosely packed hydrophobic core to a small tunnel, is too small to accommodate cholesterol. In the presence of sterol, the pocket expands, facilitated by a slight separation of the beta-strands and substantial reorientation of some side chains, resulting in a perfect molding of the pocket around the hydrocarbon portion of cholesterol.”
“Profiling of steroid conjugates corrected by adiposity revealed decreased levels of steroid sulfates (P<0.01) in overweight and obese girls compared to normal girls.”
“Cellular membranes employ a variety of strategies for controlling the flow of small molecules into the cytoplasmic space, including incorporation of sterols for modulation of permeability and maintenance of lipid asymmetry to provide both sides of the membrane with differing biophysical properties. The specific case of cholesterol asymmetry, especially, is known to have profound effects in neurological cellular systems. The presence of S-Chol [sodium cholesterol sulfate] in DPhPC in symmetric DIB reduced the passive water permeability rate (P(f)) at all concentrations and increased the activation energy (E(a)) to 17-18 kcal/mol.”
“CS [cholesterol sulfate] and SULT2B1b inhibited gluconeogenesis by targeting the gluconeogenic factor hepatocyte nuclear factor 4α (HNF4α) in both cell cultures and transgenic mice. Treatment of mice with CS or transgenic overexpression of the CS-generating enzyme SULT2B1b in the liver inhibited hepatic gluconeogenesis and alleviated metabolic abnormalities both in mice with diet-induced obesity (DIO) and in leptin-deficient (ob/ob) mice. Mechanistically, CS and SULT2B1b inhibited gluconeogenesis by suppressing the expression of acetyl coenzyme A (acetyl-CoA) synthetase (Acss), leading to decreased acetylation and nuclear exclusion of HNF4α. Our results also suggested that leptin is a potential effector of SULT2B1b in improving metabolic function. We conclude that SULT2B1b and its enzymatic by-product CS are important metabolic regulators that control glucose metabolism, suggesting CS as a potential therapeutic agent and SULT2B1b as a potential therapeutic target for metabolic disorders.”
“Steroid sulfatase (STS) deficiency is the underlying cause of the skin condition known as recessive X-linked ichthyosis (RXLI). RXLI patients show scales on their skin caused by high concentrations of cholesterol sulfate (CS), as they are not capable of releasing the sulfate group from its structure to obtain free cholesterol. CS has been reported, so far, as the sole sulfated steroid with increased concentrations in the blood of RXLI patients.”
“In colorectal cancer cells, the putative ligand of RORα, cholesterol sulfate (CS), prevents cell cycle progression at the G1/S boundary and concurrently modulates the expression of cell cycle-regulatory genes in colorectal cancer cell. CS inhibits angiogenesis in chicken embryonic chorioallantoic membranes and concurrently decreases the mRNA expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α as well as the secretion of VEGF. In addition, lipogenic gene expression is higher in human colorectal tumor tissue compared with control colorectal tissue. CS inhibits the expression of lipogenic genes in colorectal cancer cells. These results suggest that RORα could represent a direct link between local lipid metabolism of colorectal tissue and colorectal cancer. Therefore, the reduction of the expression of RORα could represent a potential warning sign of colorectal cancer.”
“Top-down lipidomics analysis and manual examination of the data identified 352 lipid species, and automated comparative analysis demonstrated alterations in lipid profile in disease. The total lipid and cholesterol content were unchanged, but levels of triacylglycerides and N-acyltaurines were significantly increased, while phosphatidylcholines, plasmenyl ethanolamines, sulfatides, ceramides, and cholesterol sulfate were significantly decreased in chronic kidney disease (CKD) patients.”
“Recent research has shown significant health benefits deriving from high-dietary fiber or microbiome-accessible carbohydrate consumption. Compared with native starch (NS), dietary resistant starch (RS) is a high microbiome-accessible carbohydrate that significantly alters the gut microbiome. The aim of this study was to determine the systemic metabolic effects of high microbiome-accessible carbohydrate. Male C57BL/6 mice were divided into 2 groups and fed either NS or RS for 18 wk (n = 20/group). Metabolomic analyses revealed that plasma levels of numerous metabolites were significantly different between the RS-fed and NS-fed mice, many of which are microbiome-derived. Most strikingly, we observed a 22-fold increase in gut microbiome-derived tryptophan metabolite indole-3-propionate (IPA), which was positively correlated with several gut microbiota, including Allobaculum, Bifidobacterium, and Lachnospiraceae, with Allobaculum having the most consistently increased abundance of all the IPA-associated taxa across all RS-fed mice. In addition, major changes were observed for metabolites solely or primarily metabolized in the gut (e.g., trimethylamine-N-oxide), metabolites that have a significant entero-hepatic circulation (i.e., bile acids), lipid metabolites (e.g., cholesterol sulfate), metabolites indicating increased energy turnover (e.g., tricarboxylic acid cycle intermediates and ketone bodies), and increased antioxidants such as reduced glutathione. Our findings reveal potentially novel mediators of high microbiome-accessible carbohydrate-derived health benefits.”
“Here, we demonstrate that 7-oxygenated sterols function as high affinity ligands for both RORalpha and RORgamma by directly binding to their ligand-binding domains (K(i) approximately 20 nM), modulating coactivator binding, and suppressing the transcriptional activity of the receptors. One of the 7-oxygenated sterols, 7alpha-hydroxycholesterol (7alpha-OHC), serves as a key intermediate in bile acid metabolism, and we show that 7alpha-OHC modulates the expression of ROR target genes, including Glc-6-Pase and phosphoenolpyruvate carboxykinase, in a ROR-dependent manner. Furthermore, glucose output from hepatocytes is suppressed by 7alpha-OHC functioning as an RORalpha/gamma ligand.”
“The effect of complete sulfation of conjugated cholic, chenodeoxycholic and deoxycholic acids on bile formation was investigated in rats….. The sulfated bile acids increased bile flow with increasing the infusion doses, and the maximum bile flow was significantly higher than non-sulfated bile acids. Although cholestasis was developed during the infusion of non-sulfated bile acids, no cholestatic effect was observed for sulfated bile acids. With the exception of cholic acid, sulfation significantly increased the bile acid secretory rate maximum. The sulfates of chenodeoxycholic and deoxycholic acids were further hydroxylated. The choleretic activities for all the sulfated bile acids were significantly higher than the non-sulfated bile acids. All the sulfated bile acids significantly reduced the biliary lipid secretion, and a significant correlation was found between the choleretic activity and the phospholipid-dependent bile acid secretion. It is concluded that sulfated conjugated bile acids may have a role in protection during cholestasis either by stimulation of bile flow or by reduction of biliary lipid secretion, thus protecting cell membranes from the detergent properties of high concentrations of non-sulfated bile acids.”
“Heparanase is a heparan sulfate degrading enzyme that cleaves heparan sulfate (HS) chains present on HS proteoglycans (HSPGs), and has been well characterized for its roles in tumor metastasis and inflammation. However, heparanase is emerging as a contributing factor in the genesis and severity of a variety of neurodegenerative diseases and conditions. This is in part due to the wide variety of HSPGs on which the presence or absence of HS moieties dictates protein function. This includes growth factors, chemokines, cytokines, as well as components of the extracellular matrix (ECM) which in turn regulate leukocyte infiltration into the CNS. Roles for heparanase in stroke, Alzheimer's disease, and glioma growth have been described; roles for heparanase in other disease such as multiple sclerosis (MS) are less well established. However, given its known roles in inflammation and leukocyte infiltration, it is likely that heparanase also contributes to MS pathology. In this review, we will briefly summarize what is known about heparanase roles in the CNS, and speculate as to its potential role in regulating disease progression in MS and its animal model EAE (experimental autoimmune encephalitis), which may justify testing of heparanase inhibitors for MS treatment.”
“It is conceivable, although speculative, that the fever and seizures associated with encephalitis provide energy to allow the metabolism of taurine to sulfate. It has been observed anecdotally that fever often induces dramatic improvements in social interactions and speech in ASD children. If these ideas are valid, then the high fever and seizures associated with encephalitis may be vital for the regeneration of sulfate supplies. The fever produces an effect similar to that of the heat produced by infrared light, and seizures may induce an electromagnetic field to energize the water, for example inside the eNOS cavity, replacing the role of UV light. Such changes would support synthesis of sulfate, by both eNOS in endothelial cells, red blood cells, and platelets suspended in the blood stream, in addition to sulfate coming from the breakdown of taurine”
Quote from lil chick on July 11, 2019, 4:48 amNeat stuff. Someone on another thread was talking about baking soda in the bath, but I suppose this research says that we should also put epsom salts in there?
I suppose this tells us why people "like" to live on the sides of volcanoes. I posted this story a while back:
https://www.rd.com/health/conditions/island-people-forget-to-die/
In one of Stephanie Seneff's video interviews she recommended 1/4 cup of Epsom Salts in a bath.
Quote from lil chick on July 8, 2019, 4:10 pmShe's an icelandic on an icelandic diet, and so it works for her!
Perhaps where people go wrong it when they adopt the foods that aren't ancestral to them.
how about a person on a diet that is ancestral to them in a country that has a climate that is radically different to the one their ancestors are from? not this lady's case, but, say, the case of a northern european living in thailand...