Posts made by Amazoniac

@S-Holmes said in BIOHACKING by Nathan Hatch, "F*** Portion Control":

https://www.fuckportioncontrol.com/casestudies

Come on, Holmes. I suggested a few simple trials in his presence, for us to verify with little method some of the promises, and you send me a link with 5 unrelated cases, susceptible to selection and filled with additional dubious claims? I'm looking for quality, not volume. It's funny, we can sniff the aroma of uncredited Seneff and Gominak in passages just by the wording.

It's also funny that I got more interrogation so far than the individual who is pushing the absurds.

One important discovery in a field is enough for a researcher to be considered exceptional. This guy has declared to have the cure for cancer, metabolic syndrome, diabetes, thyroid disease, kidney disease, autism, baldness, acne, erectile dysfunction, depression, learned hopelessness, PTSD, anxiety, insomnia, addiction, gut dysbiosis, microbial overgrowth, varicose veins, oral disease, viral infections, weight issues, migraine, chronic pain, hyperphosphatemia, and so on.

What's the problem in putting the silver bullets to test in front of us? Anything that works in his moderated bubble should work outside of it too. Is demonstration with a group too much to ask from someone who has the cure for all major conditions?

People are lured to pay to unlock the access to the majority of them. From the recent example:

"Yes—I have figured out why hair loss happens and how it can be restored! But you'll have to buy the book for this one."

If he's confident about what he writes, why he doesn't offer refunds for his $36.. ebook?

"THERE ARE NO REFUNDS GIVEN ON EBOOKS."

Emphasis not mine. And it was underlined as well.

"There are no refunds on eBooks or opened/used books."

In other words, you also can't open the printed book to inspect; it has to remain sealed as your mitochondria under silicic acid. Wouldn't it be the norm for readers to overlook any vulgarity to keep a vitality masterpiece that saves everyone around? It's flamboyant authorship without ownership.

Last week or so I received a promotional email from a proficient author whose book I recommended before. Compare the message:

"If you’re unhappy with your purchase please contact me within 30 days and I’ll refund you in full."

A long time ago I shared a link to some other public book as a comment below one of his articles, something friendly like: 'For readers who want further information on the topic, check out the following material'. He approved comments containing links, but this one was barred. Your savior seems to prefer for his readers to not be directed to detailed information than to divide the spotlight. It only served to reinforce what I already knew about the guy.

A peek at his coaching page is enough to raise suspicion of priorities. The guy keeps a picture of him shirtless, lying down, trying to put a provocative face and sensualize—right beside the description of his advising program and the following words:

"Just like my book the focus of my insight and advice is not on physical appearance"

It's a strange way to show the physique. For $100, is he offering health coaching or prostitution services?

Every couple of months we have a new sensationalism released and an enthusiast to pick it up. You're not the first and won't be the last. Both of us are part of the publicity and this helps him to maintain his relevance. Just like the Garrettes, some people don't mind being treated as fools and will hop on board regardless. But if he respected and didn't underestimate the audience, he would moderate the discourse in each assumption and would at least bother reading the summary of the sole source to feature in his publication.

I should add to the previous post that if the excess lactate is a consequence of cancer, it would bring more complicating factors to consider in supplementing sodium acetate. You can find therapeutic uses of acetate in this condition, but it can be tricky.

• The metabolic fate of acetate in cancer

Unlike pyruvate-derived acetyl-CoA—that's formed in the mitochondria (ACSS1), added to form citrate and exported to the cytosol for lipid synthesis—dietary acetate can skip this process and form acetyl-CoA without involving the mitochondria (ACSS2), which would be useful for tumors.

"Intracellular acetate is quickly converted into acetyl-CoA by acetyl-CoA synthetase 2 (ACSS2; nucleocytosolic) or ACSS1 (mitochondrial)."

Intestinal absorption of magnesium from food and supplements

A suggestion when dealing with gut microbial imbalances:

This is considering it a microbial growth factor that's worth restricting or exceeding in each extreme.

The food content will add some more magnesium per meal and the total must not be too off from the efficient absorption range.

Antifungal Activity of Stabilized Ortho Silicic Acid (OSA) against Foliar Plant Pathogens

You can find more related material, and it may be relevant for humans.

Probiotic characteristics and in vitro compatibility of a combination of Bifidobacterium breve M-16 V, Bifidobacterium longum subsp. infantis M-63 and Bifidobacterium longum subsp. longum BB536

"Obviously, bacteria used in probiotic products should not inhibit the growth of other probiotic strains. However, one of the most dangerous traits of bifidobacteria and LAB is the potential transfer of antibiotic resistance genes to pathogenic bacteria within the gastrointestinal flora (Teuber et al. 1999). A European Food Safety Authority (EFSA) document recommends that commercial strains used in the production of food supplements should not harbour transferable antibiotic resistance; for this reason, EFSA guidelines strongly recommended that minimum inhibitory concentrations (MICs) of the most important antimicrobial agents used in human care be evaluated (EFSA 2008). Many routes of antibiotic resistance transfer exist: integrons, transposons, insertional elements, bacteriophages and conjugative plasmids are all implicated in such mechanisms (EFSA 2008). The intense use of antimicrobial agents for medical use and also in animal husbandry has led to the selection of antibiotic-resistant strains within the gut microbiota of humans and livestock; consequently, in the last decades, there has been a massive spread of antibiotic-resistant bacteria worldwide (Devirgiliis et al. 2011)."

Antibiotic resistance propagation through probiotics

"With the discovery of the transfer of gene content containing antimicrobial resistance (AMR) genes to other microorganisms (primarily through mobile genetic elements or plasmids), there has been speculation that this complication may also occur as a side effect of probiotics, especially in the longtime use [10]."

"Alarmingly, in-vitro and in-vivo studies proved that carrying resistance genes by probiotics and, as a gene reservoir, are capable of transferring AMR genes to other present microorganisms such as the normal microbiota or pathogenic bacteria in the intestine, oral, and vaginal cavities [15,16,17]."

"Probiotics are associated with various types of adverse events, and according to the safety regards, performing some tests such as toxin production, hemolytic potential, antibiotic resistance, and analyzing metabolic activities are recommended [48]. Bacteremia, fungemia, GI ischemia, diarrhea or constipation, bloating and flatulence, skin rashes or skin acne, metabolic problems such as D-lactic acidosis, extreme immune stimulation, endocarditis, AMR, etc. are correlated with the consumption of different species of probiotics in human [8]. The exact mechanism of probiotics' adverse effects is still unknown that increases the current concern of scientists. However, it is reported that if the endogenous microbial community cannot occupy all functional niches in the target site (e.g., intestine), the available niches can be occupied by the pathogens and may lead to infection [1]."

"[..]due to the involvement of antibodies in the etiology of IBD, the immune-stimulatory property of probiotics can worsen the situation and the immunocompromised patients are at higher risk of infections caused directly or indirectly by probiotic bacteria [87]."

"Moreover, during antibiotic treatment, which establishes an imbalance in the microbiota, colonization of pathogenic bacteria is escalated. It provides an environment to transfer genetic content among available microorganisms such as pathogenic bacteria, probiotics, and the normal microbiota. HGT [Horizontal Gene Transfer] among existing microorganisms (donors or recipients) leads to resistance toward a wide range of antibiotics."

"Molecular studies reported sequence similarities between resistance genes in different bacteria and identical sequences in gram-positive and gram-negative bacteria, which shed light on the transfer of mutant genetic content across the mentioned microorganisms. Although different strains of probiotics carry specific resistance genes, they are capable of transferring to other microorganisms. Taken all together, this review supports the double-edged impact of probiotic consumption, and taking adequate precaution for the prevention of probiotics’ wide-spreading side effects is recommended."

Involvement of Probiotics and Postbiotics in the Immune System Modulation

"For the beneficial effects of probiotic microorganisms to be seen, it is recommended that the number of viable cells reaching the intestine should be at least 10^6–10^7 colony-forming units (cfu)/g [125]. However, in most commercial probiotic products, many beneficial microorganisms, especially near the end of their shelf life, lose their “viability” [126]. Therefore, probiotic products are produced to contain more microorganisms (on average 2.5 times) than the number of live probiotic microorganisms written on the label."

"Interestingly, studies found that when probiotics were administered in humans following antibiotic therapy, the increase in probiotic strain-induced colonization in the colon microbiota was associated with persistent or prolonged dysbiosis [131,137]."

"The latest Cochrane report states that probiotics are successfully used to prevent infectious diarrhea in both children and adults [138]. However, there are also studies reporting cases of bacteremia, sepsis, fungemia, endocarditis, meningitis, endometritis, peritonitis, and pneumonia as a negative consequence of probiotic administration [139]. This pathological phenomenon may develop due to an impaired gut barrier, immunosuppression, or leaky gut conditions [140]. It has been suggested that factors facilitating translocation by probiotics may be linked to the intestinal mucosal adhesion capacity or mucolytic activity [141,142]."

"Evidence suggests that microbial vitality is not required to achieve health benefits as with probiotic supplements and postbiotics produced from probiotics provide similar health benefits to probiotics [149]. Despite various health benefits, postbiotic ingredients derived from probiotics are thought to be promising alternative supplements to eradicate the above-mentioned risky conditions of probiotics [150]."

"Some postbiotics are cell-free supernatants, vitamins, organic acids, SCFA, secreted proteins/peptides, bacteriocins, neurotransmitters, secreted biosurfactants, amino acids, flavonoids derived from postbiotics (desaminotyrosine, equol daidzein, daidzein, and norathyriol), postbiotics derived from postbiotics (genipin, paeoniflorin, paeoni lactone glycosides, paeonimetabolin I, II, and III), metabolites of probiotic microorganisms such as phenolic-derived postbiotics (equol, urolithins, valerolactones, enterolactone, enterodiolen, and 8-prenylnarenin) and teichoic acids, peptidoglycan-derived muropeptides, molecules protruding from the surface (pili, fimbriae, and flagella), exopolysaccharides (EPS), cell surface related proteins, and inactivated/dead/non-viable microbial cell components of probiotics, such as cell wall-bound bio-surfactants [154,155]."

"In addition to eliminating the disadvantages of probiotics for microbiota and the immune system, postbiotics can also reduce the use of food additives because they act as emulsifiers and preservatives in ensuring the stability of the products they are used. There is also some evidence about immunomodulatory and the therapeutic effects regarding products containing commercial postbiotics. Although the use of them in the food and pharmaceutical industry is promising, more studies are required to avoid the side effects and disadvantages that may occur with the use of products containing probiotics, especially in people with a weak immune system."

@vocedilegno said in BIOHACKING by Nathan Hatch, "F*** Portion Control":

Amazoniac, you have much more knowledge of chemistry than I do. I would be interested in knowing whether you might have an opinion regarding the use of sodium acetate as a means of lowering lactic acid as recommended by Hatch in the book?

What I do: consult anesthesiology book , find all there and parrot))

Sodium acetate can be an effective substitute for baking soda, but it's chosen over the latter for secondary reasons: availability, stability, price and ease of production. Otherwise, baking soda would be preferred.

• Sodium Acetate as a Replacement for Sodium Bicarbonate in Medical Toxicology: a Review

The primary purpose of such salts in conditions that tend to 'lactate acidosis' would be to counteract acidity rather than lactate. The metabolism of sodium acetate is complex relative to that of baking soda, that reaches the stomach, reacts with acid instantaneously, and from then onwards it behaves as dietary sodium chloride.

An incomplete comparison:

I don't have clear how carbon dioxide produced after these salts would affect lactate. The principle seems to be based on the dissociation of oxygen from hemoglobin to tissues to promote oxidative metabolism, but we would have opposing factors:

• Additional carbon dioxide (↑CO2) increases oxygen dissociation (as if tissues could handle more of it)
• Alkalinization (↑pH) decreases oxygen dissociation

When baking soda is injected, extra hydrocarbonate ions would react with protons to produce carbon dioxide. This happens in the stomach, but part of the carbon dioxide is lost. So, with ingested baking soda, we might not be able to count on substantial amounts of extra carbon dioxide.

Alkalinization tends to increase the rate of glycolysis (glucose → pyruvate) and it may have an effect on cells that are already overproducing lactate from pyruvate. Acetate would have an edge in this regard for yielding CO2 locally. On the other hand, an elevation in the ratio of acetyl-CoA to CoA can further inhibit pyruvate oxidation, as suggested in this extreme version.

With the liver cells becoming acidic, they appear to shift from influx to efflux of lactate.

The Effect of Simulated Metabolic Acidosis on Intracellular pH and Lactate Metabolism in the Isolated Perfused Rat Liver

This could be an issue considering that the liver is a major site of lactate clearance. It would be a point in favor of ingested baking soda (alkalinization with less carbonic acid or carbon dioxide recovered). However, since acidification can slow down the rate of glycolysis and control lactate synthesis, sodium acetate would be advantageous because of the proton consumption and carbon dioxide production.

I don't remember how much L-lactate can be urinated intact, yet the additional sodium from either salt would help in this regard. But the body must try to conserve lactate to resynthesize glucose.

Sodium acetate has other applications. For example, prior to its popularization in weight loss circles, salts of organic have been extensively used by the livestock industry to shape the gut of animals.

Overall, when it comes to the burden of 'lactate acidosis', sodium acetate would add layers of potential complications to consider. Lowering the doses should also lower the concerns, yet doesn't eliminate them. The main target is acidity and I would favor baking soda to counteract it, while focusing on the more immediate measures that are known to help to deal with excess lactate (people's beloved thiamin, for example).

As a side note, different forms of lactate dehydrogenase occur in tissues:

From these.

It may seem counterintuitive for such forms to prevail in liver (as an important organ for lactate clearance), but it's also under the influence of the state of cells:

Role of mitochondrial lactate dehydrogenase and lactate oxidation in the intracellular lactate shuttle

"Three conclusions with regard to electrophoretic separation of LDH isozymes in mitochondria and cytosol appear appropriate. First, differences in LDH patterns between mitochondria and surrounding cytosol suggest that LDH within mitochondrial preparations did not result from cytosolic contamination. Second, the greater abundance of LDH-1 (H4) in heart than liver is expected on the basis of the high oxidative capacity of cardiac tissue. However, like heart, liver is also a net lactate consumer. Thus, differences in mitochondrial LDH pattern in liver compared with heart may be more related to the gluconeogenic, as opposed to oxidative nature of liver. Third, the ability of mitochondria to convert lactate to pyruvate is governed by mitochondrial redox rather than LDH isoenzyme pattern. This latter conclusion is reached because of similar abilities of liver and cardiac mitochondria to oxidize exogenous lactate despite very different LDH isozyme patterns."

@S-Holmes said in BIOHACKING by Nathan Hatch, "F*** Portion Control":

@Amazoniac This is beginning to sound personal. What harm is there in trying Nathan's hacks? Are they dangerous? He uses food and a few low dose supplements. Pretty scary!

Re balding, he still has full, thick hair (unlike everyone's favorite low A "detective.") So he must be doing something right. How else would you expect him to prove his claim?

Perhaps you're one of those fortunate enough to have never suffered from metabolic syndrome. I, like Nathan have had it my entire life. I have been able to control it using various "unproven" methods (homeopathy is one) for 20 plus years.... until Covid. Like Nathan, I have suffered from many maladies, including Epstein Barr, chronic sinusitis, cancer, Meniere's...my body is not kind to me. Like Nathan, RP helped me survive, but sadly, we did not thrive. It appears Nathan is now thriving. If he has gone off the reservation...doesn't have "research" to support his claims... why should anyone care? If he makes said claims based on his own experiences, I'm happy to help test his theories.

Why must you constantly challenge my posts in this thread? Is it your intention to direct others away (who, like me and Nathan, have tried literally everything to little or no avail)? What if he can help them with his simple, cheap and self tested solutions? As a homeopath for more than 30 years (it has kept me alive and symptom free for MOST of my life...trust me, no small feat) I trust empirical evidence over 95% of the lab research available. Two of my sisters took their own lives, one in 2017 and the other in 2019, one overdosed and the other with a gun. They both had metabolic syndrome and just finally lost hope. What if Nathan's work can save others who have lost hope?

So in conclusion, I do not believe your heart is in the right place. Also...don't you have ANYTHING better to do?

If you go back to my first post in this thread, it was already clear that I find his experimentations valid, but the explanations and how they are communicated in ruling tone are an insult.

You post something and it's meant to be read. The challenge is to illustrate why it's worth to be wary of the concepts put forward by this author. I also wrote that helping others through shared experiences doesn't give the person a free pass to confuse them out of carelessness.

In addition, his articles aren't based on self-experimentation alone, it's an author who declared to also go by "scientific research" and to be well-read. He's making use of researchers' works, twisting them and not informing the origins, which would encourage verification.

Can't you tell the difference between these?

• What worked for me in reversing hair loss
• "THE CURE FOR BALDNESS"

How do I expect him to prove his claim? I would like to witness the savior to gather a group of 10-20 volunteers and deliver the promise.

The position of my heart doesn't invalidate criticisms, but I can tell you that it's in the right place for thoughtful authors.

The horseradish peroxidase used in the only backup material linked was for assisting in the detection and measurement—Polymyxin B (derived from gram-positive bacteria) is the actual endotoxin binder and inactivator of these experiments. The researchers even wrote that "horseradish peroxidase alone [..] did not bind to lipid A" and made explicit its function as a "reporter enzyme." He's misattributing the effects of Polymyxin B to horseradish (peroxidase).

I insist: be watchful with the interpretations of this author.

On the practical aspect, lots of promises and not enough demonstration. Is there any health problem that he hasn't found the cure yet? As an example, he has "THE CURE FOR BALDNESS".

"Yes—I have figured out why hair loss happens and how it can be restored!"

Then, why not show us in practice here? Imagine how many guys around the world would be willing to discontinue finasteride for what he has to offer and document the restoration for others.

Methionine Dependence of Cancer

"[..]even though flux through polyamine synthesis needs to be high, especially in dividing cells, neither the methionine cycle nor polyamine synthesis consumes methionine. However, methionine is removed by protein synthesis and indirectly through the transsulfuration pathway leading to cysteine synthesis and feeding antioxidant production (Figure 2A)."

"Most cancer cells cannot proliferate in medium where methionine is replaced by homocysteine, even though they readily synthesize methionine from homocysteine (Figure 1)."

"Several cancer cell lines and tumors depend on exogenous serine. This is surprising because serine can usually be synthesized from glucose in sufficient amounts via the glycolysis intermediate 3-phosphoglycerate [40,41]. However, the increased demand of cancer cells on glycolysis for energy production may divert the flux of 3-phosphoglycerate from serine synthesis to glycolysis. Serine requirement for cancer cell proliferation may thus link the Warburg and Hoffman effects by connecting glycolytic flux with SAM synthesis."

"Preclinical models have shown promise with dietary methionine restriction significantly suppressing tumor growth in multiple models, which include both solid tumors and blood cancers [59,65,66,67,68,69]."

Serine synthesis | Eigenbrodt and Mazurek

Serine hydroxymethyltransferase | Proteopedia

I had thought of depleting methionine by overwhelming sulfotransferases, increasing its internal consumption to derive sulfate for conjugation of other molecules, but it seems that it's not viable and the body switches to glucuronidation when needed.

Human Sulfotransferases and Their Role in Chemical Metabolism

"Many of the substrates metabolized by sulfotransferases are also substrates for UDP-glururonosyltransferases, and in this context, the former system has generally been considered a high-affinity, low-capacity pathway, whereas the latter system is considered a low-affinity, high-capacity pathway (Burchell and Coughtrie, 1997). This suggests that SULTs may be more important than UDP-glucuronosyltransferases in the metabolism of chemicals via low-level exposure from the environment or through food consumption."

"[..]the expression of SULTs in humans has been shown to exhibit a pronounced extra hepatic pattern, whereas in rodents it appears to be predominantly hepatic (Eisenhofer et al., 1999, Hempel et al., 2005)."

Molecular Cloning, Expression, and Characterization of Novel Human SULT1C Sulfotransferases That Catalyze the Sulfonation of N-Hydroxy-2-acetylaminofluorene

It must be best for the methionine restriction to affect its concentration in circulation (or else cells keep acquiring it) and to moderate the one-carbon donors that promote its regeneration.

• One-Carbon Metabolism in Health and Disease

I remember a discussion on the following publication that Bulgaria brought up on the 'amino acid supplementation' thread of the Garrey Smeat Forum, and it shows that it's possible to be extreme about it:

Nutrient Intake and Nutritional Indexes in Adults With Metastatic Cancer on a Phase I Clinical Trial of Dietary Methionine Restriction

"A recent study designed to quantify dietary methionine requirements in normal subjects sheds light on this issue (22). In that study, stable isotope methods were used to measure obligatory methionine oxidation in normal subjects on a diet completely devoid of sulfur amino acids (methionine and cysteine) for 5 days. Although somewhat controversial (23), obligatory oxidation rates are considered by many to represent the minimum requirement for amino acids, that is, the amount that is oxidized despite maximal body conservation. The obligatory oxidative loss of methionine was 13 mg/kg/ day in that study (22). Patients in our trial, who were restricted to 2 mg methionine/kg/day, therefore, consumed 11 mg/kg/day less than the minimum requirement. However, they consumed adequate amounts of cysteine, which is present in Hominex-2. They therefore may have had obligatory methionine oxidation rates <13 mg/kg/day. The fact that all patients reversibly lost weight, despite what would normally be considered adequate energy and protein intake, may actually be encouraging, since it confirms that patients adhered to the diet. The basic premise of this strategy is that dietary methionine restriction will have a greater deleterious effect on tumors than on normal host tissues."

The effect was achieved with dietary restriction, without involving methioninase.

One claim in this guy's article that has basis:

"I discovered how B12 promotes healthy gastrointestinal microbial activity[.]"

I think that it originated from here, where authors suggest..

"Based on recent studies of the role of corrinoids in the human gut, we propose that targeted manipulations of the gut microbiota could be achieved by altering the levels of specific corrinoids. This hypothesis is based on the following observations.

• First, over 80% of sequenced human gut bacteria are predicted to use corrinoids, but less than 25% have the genetic capacity to synthesize these molecules (Degnan et al., 2014);
• Second, human fecal samples have been found to contain up to eight distinct corrinoids (Allen and Stabler, 2008).
• Third, only a fraction of the corrinoids available in a microbial community can be used by a given organism because corrinoid-dependent enzymes have native specificity for their preferred cofactors (Keller et al., 2013; Mok and Taga, 2013; Yi et al., 2012).
• Fourth, corrinoids other than cobalamin are poorly recognized by human intrinsic factor, the key protein required for transport of cobalamin from the lumen of the small intestine.
• Finally, corrinoids are synthesized exclusively by bacteria and archaea, unlike many other vitamins that are also prevalent in plant-based dietary components (Roth et al., 1996).

Thus, because different bacteria require distinct groups of corrinoids, we hypothesize that microbial communities can be manipulated by altering the levels of particular corrinoids."

You can find it on the Garrey Smeat Forum.

The authors above adopted a more conservative tone, similar to that of the group who did a comprehensive review on the topic:

Vitamin B-12 and the Gastrointestinal Microbiome: A Systematic Review

"Findings from in vitro, animal, and human studies suggest that vitamin B-12 may be associated with changes in bacterial abundance. While evidence from in vitro studies indicates that vitamin B-12 may increase alpha-diversity and shift gut microbiome composition (beta-diversity), results from animal studies and observational human studies were heterogeneous."

They added:

"Potential mechanisms Modulation of the gut microbiome by vitamin B-12 or other nutrients in one-carbon metabolism may occur via several potential mechanisms. The impact of vitamin B-12 on the gut microbiome may be explained by vitamin B-12–dependent enzymes and riboswitches (14, 18); however, the mechanisms that link vitamin B-12 and the human gut microbiome have not been fully established. One-carbon metabolism. The role of other nutrients in one-carbon metabolism may provide further insights into the links between vitamin B-12 and the gut microbiome. For example, SAM production (i.e., a methyl donor and product of one-carbon metabolism) can be used for DNA methylation in bacteria to alter gene expression (100) or in mucosal cells, which could impact the intestinal environment (99, 101, 102). SAM is also a substrate for production of metabolites used in communication between bacteria (i.e., quorum sensing) (103, 104). Through B-vitamin sharing among bacteria in the gut microbiome (20), bacteria may benefit from an abundance or stability of B-vitamin availability in the gut environment (105). Additionally, products of B-vitamin metabolism may be used by other bacteria in the gut (20, 105, 106), which may offer competitive advantage to some bacteria without B-vitamin–dependent enzymes. Other mechanisms. Choline can be metabolized by bacteria in the gut microbiome to produce trimethylamine (82), which may decrease choline availability for the host (107) and limit production of SAM. Additionally, niacin may have a role in decreasing bacterial endotoxin production and improving intestinal barrier function (108, 109), and Steinert and colleagues (92, 110) hypothesized that riboflavin may reduce oxidative stress via NADH-redox reactions in bacteria."

"Findings from in vitro and animal studies suggest that specific cobalamin forms may differentially impact alpha-diversity and beta-diversity and bacterial abundance. Although in humans, all cobalamin forms are interconverted and transported within the cell (64), different forms of cobalamin may have distinct roles in bacteria metabolism. Differences in cellular transport among forms is unlikely, as the predominant transporter, an ATP-binding cassette (ABC)-type BtuFCD transport system, recognizes the lower ligand of cobalamin that is shared among all forms (18). In contrast, cobalamin forms may differ in enzyme affinity (i.e., adenosylcobalamin-dependent enzymes) or ability to control gene expression through riboswitches—regulatory elements of mRNA."

"Most cobalamin riboswitches are thought to be adenosylcobalamin-dependent, as demonstrated in some model bacterial species (65–67), but some Escherichia coli riboswitches have over 500 times higher affinity for methylcobalamin and aquocobalamin, compared with adenosylcobalamin (68). Zhu et al. (26) found that cyanocobalamin improved growth and increased Shiga toxin production of E. coli compared with methylcobalamin, whereas Lactobacillus reuti had similar growth with both cobalamin forms. Cyanocobalamin and methylcobalamin also had different effects on enzyme activity, and cyanocobalamin had greater inhibition of riboswitch expression. In contrast, in the Propionibacterium strain UF1, cyanocobalamin, methylcobalamin, hydroxycobalamin, and adenosylcobalamin had similar regulation of genes involved in vitamin B-12 biosynthesis (69). As genomic studies elucidate mechanisms of gene regulation in bacteria, in vivo studies are needed to determine how different cobalamin forms impact the bacterial community."

The positive outcomes are uncertain and, just as with various other nutrients, it's possible for B12 to be a virulence factor.

• To B12 or not to B12: Five questions on the role of cobalamin in host-microbial interactions

When only good effects are anticipated, people are tempted to exaggerate.

Over supplementation with vitamin B12 alters microbe-host interactions in the gut leading to accelerated Citrobacter rodentium colonization and pathogenesis in mice

"Daily oral cobalamin supplements can contain doses that far exceed (as high as 10,000 μg/tablet) the recommended daily amount of 2.4 μg/day in humans. High exposures are required when normal absorption is impeded and are generally considered safe. The practice of over-supplementing cobalamin to ensure adequate absorption is supported by the fact that no upper limit has been set for B12 supplementation. A study in C57BL/6J mice using a dose comparable to a 5000 μg tablet (30.46 μg/day) for humans found a depletion in Bacteroides but no change in cecal short-chain fatty acids (SCFAs) or markers of dextran sulfate sodium (DSS)-induced colitis with B12 treatment, including colon length and fluorescein isothiocyanate-dextran permeability test [15]. Since competition exists between enteric pathogens and commensal microbes for B12 sequestering and sharing, we hypothesized that excessive cobalamin supplementation alters the gut microbiota’s functional activity, creating a favorable environment for pathogen colonization and pathogenesis. Due to the fact that no upper limit has been determined for B12, we supplemented a megadose of B12 to mice in drinking water and challenged with Citrobacter rodentium, a natural mouse-specific pathogen that mirrors the attaching and effacing pathology seen in human EHEC infections [16]. We evaluated the direct and indirect impact of oral B12 supplementation on the gut microbiota and ability of the host to resist enteric pathogen colonization and pathogenesis."

"According to water intake, B12 supplemented in drinking water at 10 μg/ml and 40 μg/ml were estimated to reach a total dose of 30 μg and 120 μg per mouse a day, respectively. The human equivalent dose for the cyano- and methyl-cobalamin drinking water used in these studies is ~5000 μg/day (CNCbl10 & MeCbl10) and ~25,000 μg/day (CNCbl40 & MeCbl40), which was calculated using the standard human equivalent dose parameters [18]. A megadose was used in the present study to push the phenotype and ensure high B12 levels were maintained in the gut to disrupt competition, cross-feeding and microbe-host interactions related to B12 utilization by the gut microbiota. These levels were considered feasible within the human population, where 10,000 μg B12 capsules are available and would be taken as a single bolus. Comparing B12 supplementation between humans and mice using a multiplicity factor of their respective recommended dietary allowance (RDA) shows that a dose of 5000–10,000 μg tablet per day in an adult human is equal to 2083–4167 × their RDA of 2.4 μg/day, whereas mice receiving a 120 μg/day in the present study is equal to 2400 × their RDA. The RDA of B12 for mice is approximately 0.05 μg/day and is based on a diet containing 10 μg of B12 per kilogram that was deemed adequate for mice [19]."

"In the present study, we showed that excessive B12 concentrations in the gut can induce a dysbiosis that promotes C. rodentium colonization and pathogenesis in mice. The B12-induced dysbiosis can be characterized by the decrease in members belonging to Clostridia vadinBB60 and Lachnospiraceae NK4A136 groups, along with an increased abundance of Parasutterella in the cecum and colon. The changes to the gut microbiota from B12 supplementation stimulated the production of the IL-12/23p40 subunit and IL-17A cytokines in the colon and opened the gut niche for C. rodentium colonization without any obvious tissue damage prior to pathogen challenge. In general, oral B12 supplementation can contribute to a dysbiosis that promotes low-grade inflammation and a virulent C. rodentium population regardless of cobalamin type. Through changes to the microbiota, a B12-saturated gut environment shifts the metabolism of C. rodentium from avirulent to virulent as determined by the decrease in glucose enzyme activity and increase in virulent gene expression."

As for seafood broth containing free B12 and the broth being superior to supplemental form in correcting a deficiency, it's tricky.

Broth from Canned Clams Is Suitable for Use as an Excellent Source of Free Vitamin B12

Not all B12 that's extracted is free (or perhaps in the desired form). They point out that it may be 70% of the cobalamin present in the broth, lowering its content to no more than 10 mcg free B12 per can.

We have other sources reporting higher amounts:

Characterization of vitamin B12 compounds from marine foods

"Vitamin B12 is synthesized by only certain bacteria and archaea but not by animals or plants. In marine environments, bacterial vitamin B12 is transferred and concentrated into fish and shellfish bodies by plankton in the marine food chain. Moreover, marine macrophytic red algae, Porphyra spp. specifically contain substantial amounts of vitamin B12, due to microbial interaction. Although some meats or viscera of edible fish and shellfish are excellent sources of biologically active vitamin B12, an inactive corrinoid, pseudovitamin B12, was found in some edible shellfish using liquid chromatography/electrospray ionization–tandem mass spectrometry. To prevent elderly people from developing vitamin B12 deficiency due to food protein-bound vitamin B12 malabsorption, we present a survey of marine foods containing free vitamin B12. The results of our study suggest that bonito and clam extracts (or soup stocks), which contain considerable amounts of free vitamin B12 are useful not only as seasonings and flavorings but also as excellent sources of free vitamin B12."

"Various types of fish soup stocks and extracts are manufactured for use as seasonings or flavoring. A certain extract made from raw muscle of bonito contains the highest free B12 (approximately 41 μg/100 g wet weight) among various fish extracts tested (Nishioka et al. 2008). Moreover, short-necked clam extract contains substantial amounts of free B12 (approximately 132 μg/100 g wet weight) (Ueta et al. 2010). The broth of canned clams also contains free B12 (approximately 14.1 μg/100 g wet weight) (Ueta et al. 2011b ⇈). Salted and fermented salmon kidneys (called "Mefun"), which have a delicate flavor and are popular only in Japan, contain substantial amounts of B12 (approximately 328 μg/100 g wet weight) (Adachi et al. 2005), most of which are derived from free B12. These results suggest that these fish and shellfish products are excellent sources of free B12 for preventing B12 deficiency among elderly persons with food-bound B12 malabsorption."

Based on the previous material, they picked the highest content of all options and treated it entirely as free B12. Maybe they did the same with other values, but I haven't checked.

If the person can't digest food properly, the poor liberation of B12 would only be one of the consequences of a greater concern, that possibly involves a more generalized state of malnutrition.

In addition, free B12 doesn't guarantee sufficient absorption, the problem can be compounded by not being able to synthesize the protein needed to bind it (to maximize absorption) or an inability to absorb the complex after it forms in the gut. These are the majority of cases that are prone to progress to a serious deficiency, increasing the reliance on the passive process, that doesn't depend on protein complexation in the gut.

How I treat cobalamin (vitamin B12) deficiency

"In more limited absorptive disorders, such as malabsorption confined to food-bound cobalamin (FBCM),[27] impaired cobalamin release from food limits but does not incapacitate the IF system, which also presumably continues reabsorbing biliary cobalamin. Some forms of FBCM remit after antibiotics.[28,29] The rate of cobalamin depletion is unknown but is probably many years slower than in IF-related disorders (Table 2). If the underlying disorder is nonmalabsorptive, such as dietary insufficiency, clinical consequences are delayed even longer[30,31] because absorption and reabsorption are intact and because intake fluctuates. Only in rare disorders of cellular utilization do consequences appear rapidly (Table 2)."

"Not surprisingly, most adults who come to medical attention with clinically expressed cobalamin deficiency are those with IF-related malabsorption. Savage et al[32] reported that 94% of patients with clinically expressed deficiency had IF-related malabsorption, such as PA or sprue; only 1% were vegetarians or had (presumptive) FBCM."

So, if we're communicating with people who are deficient, they might have these compounding factors present.

Supposing that the person finds seafood appetizing for frequent consumption and doesn't discard the arguably off-putting broth when products are canned, a generous content of 100 mcg free B12/100 g of broth would fall within a questionable therapeutic range. It's rare to find guidelines for B12 repletion with doses around 100 mcg, for being too high for the easily-saturable and (possibly) dysfunctional active process, and too low to compensate for the inefficiency of the passive absorption.

The graphed values:

The content of about 10 mcg free B12 in broth per can would barely tickle someone with malabsorption (the majority who are prone to deficiency). But when the only issue is releasing it from food and smaller amounts of free B12 are enough to avoid the problem, some hours are needed to renew the dose when counting primarily on the active process.

Dietary Reference Intakes for Vitamin B12 | Institute of Medicine

"The second of two doses of B12 given 4 to 6 hours apart is absorbed as well as the first (Heyssel et al., 1966)."

Making it impractical to depend on a food for this dose renewal.

Altogether, if you're deficient in B12, rather than relying on clam soup to get you covered, it's preferable to skip to the superior option: supplements. These allow the selection of form, amount, and timing depending on needs. Some people don't respond unless they take 500 mcg or more.

@ilovethesea said in New "Mission" of RPF:

@Amazoniac said in New "Mission" of RPF:

Did you, BioEclectic and other members have the chance to open the initial version of the forum, at the time when Ray agreed with its creation? The appearance was almost a variation of his website, with a picture of him and some of his favorite foods.

I vaguely remember that yes. Just checked archive.today and it’s not great - https://archive.is/raypeatforum.com Random selection of pages and the oldest I found was 2016.

I wonder what are the thresholds for protesting for those who remain indifferent. They need a footage of the lion incinerating members with ethanol retinol to act?

Maybe some of the indifferent ones are struggling with serious health problems and don’t want to provoke the lion in case they get banned and lose the ability to ask questions there.

As for the few supportive militants, they're intriguing. They identify themselves as the open-minded camp while watching unfazed the tyranny in front of them. If these people were liberals as claimed, they would repudiate the administration and wouldn't be willing to be part of it.

Other than Mosaic and Christ lady, does anyone recognize the current pro-vitamin A posters at RPF? Could they be infiltrators or “sleeper” accounts that were already in position for this purpose?

So the same entity as Thor Torrens and company - put in place to slowly ramp up the slander of Ray and create the illusion of a consensus for low vitamin A BS. Perfect example is this Sebastian B guy referring to “the high-toxin Ray Peat cancer diet." They’re definitely escalating their lies.

Yes, but my attention is on the people who are not in critical situations, and they represent a considerable part of the indifferent.

Unlike before, that members of the community were limited in alternatives and had to put up with maladministration to stay in touch with persons into Ray's work, we now have multiple platforms embracing the community as the forum disintegrates. So, people can more and more rely on the Garrey Pith Forum as an archive and interact elsewhere.

For the few militants over there who think that they belong to the open-minded camp, start to question your leader for fair reasons and let's see how long you last in this broad-minded, philanthropic group that you support.

While it's true that administrators in general want their platform to be busy, and we're also utilitarian in a sense, I haven't spotted such kind of corrupted behavior in the alternatives.

Tip: if you decide to be a questioner on the Garrey Pith Forum, you may write 'Cheese!' on your message to look good on the screenshot of your final post. #toxicpawnapocalypse

Photodegradation of cobalamins in aqueous solutions and in human blood

"Human plasma contains a variety of cobalamins (Fig. 1) including methylcobalamin (MeCbl, 64%), adenosylcobalamin (AdCbl, 15%), hydroxocobalamin (OHCbl, 12%) and cyanocobalamin (CNCbl (sometimes called vitamin B12), 9%) [3]."

"It is known that intracellular cobalamins react rapidly with nitric oxide and superoxide [21,30-32], which can be generated in skin or blood during exposure to UVA [33,34]. Additionally, skin and blood contain many endogenous photosensitizers (porphyrins, flavins) absorbing in the UVA region, and exposure to UVA leads to the generation of reactive oxygen species [35,36]. Singlet oxygen, superoxide anions, hydrogen peroxide and triplet-state riboflavin radicals are generated under exposure of riboflavin (RF) to UVA [37]. Reactive oxygen species are quenched by antioxidants in human skin which may, due to this, indirectly be degraded. Cobalamins may also quench singlet oxygen and hydrogen peroxide, and it may photodegrade indirectly. However, the indirect photodegradation of cobalamins due to their antioxidant properties have not been studied."

"In the present study we have investigated the photodegradation of four major forms of vitamin B12 (MeCbl, AdCbl, OHCbl and CNCbl) under UVA exposure in aqueous solutions at physiological pH by absorption spectroscopy. The degradation of OHCbl exposed to UVA in the absence and presence of the endogenous photosensitizer RF was investigated. Serum vitamin B12 concentrations before and after summer were measured in four patients with psoriasis."

"All studied cobalamins degrade under UVA exposure in aqueous solutions at physiological pH (Fig. 4-5). OHCbl was found to be the most stable cobalamin under our experimental conditions (Fig. 4A and 5A)."

"However, OHCbl is an antioxidant, and may degrade indirectly in the presence of reactive oxygen and nitrogen species generated under UVA exposure. The presence of endogenous photosensitizer RF during UVA exposure increased the degradation of OHCbl (Fig. 7, 8A). RF and nicotinamide enhance the degradation of CNCbl in aqueous solution [24]. CNCbl is phototransformed to OHCbl [20,23]. It is possible that after entering a cell, OHCbl is transformed back to AdCbl and MeCbl, and thus may retain the biological activity of the vitamin, even in the case that the active forms will first be degraded in vivo. Nevertheless, high doses of solar radiation (or artificial UV radiation, e.g. sunbeds) may, at least theoretically, diminish the effectiveness of vitamin B12 and impair its organic functions. However, it is not simple to measure the changes of MeCbl, AdCbl or OHCbl concentrations in blood."

"AdCbl and MeCbl were extremely unstable and photodegrade in seconds (Fig. 4C-D and 5C-D). They were photoconverted to OHCbl (Fig. 6), which is in agreement with the earlier observations by others [18,21]. MeCbl was around 3-fold more sensitive to UVA radiation than AdCbl (Fig. 5CD)."

"The degradation rate of OHCbl in the presence of RF was around 3 times faster than alone (Fig. 8A), while the degradation rate of RF was not influenced by the presence of OHCbl (Fig. 8B)."

"The vitamin B12 status is most often assessed by measuring serum or plasma total cobalamins. Due to the fact that OHCbl is quite photostable, it is not surprising that seasonal variations of serum vitamin B12 were not observed in healthy people [47,48]. Our preliminary results on the influence of solar radiation on vitamin B12 levels in psoriasis patients demonstrate that sun exposure during a summer in Norway was not able to destroy the vitamin, while the same exposures increased the levels of 25-hydroxyvitamin D in serum by 66% (Table 1). This means that significant doses of UV radiation reached tissues below the stratum corneum. We also found that serum homocysteine levels were not significantly increased (indirect measurement of vitamin B12 and folate changes). However, longer exposure times in sunlight at lower latitudes or in sunbeds (which have several times higher UVA fluence rates than found in solar radiation [49,50]) may lead to increased plasma homocysteine concentrations due to the photodegradation of vitamin B12 but not to any photodegradation of folate, as was observed in patients with psoriasis by Osmancevic et al. [16]."

"Cobalamins circulate in blood bound to two transport proteins, haptocorrin and transcobalamin [51-53]. The major part of cobalamins are bound to haptocorrin (80-96%) [53], which has an unknown function, but it has been proposed that haptocorrin serves to protect cobalamins [22,51]. It was demonstrated that haptocorrin protects MeCbl from 442 nm photodegradation [22]. Calculations show that this mechanism may be of significance at light doses penetrating the skin, and act to protect cobalamins [22,51]."

"It is interesting to note that vitamin B12 deficiency may cause cutaneous hyperpigmentation [56-61]. The dominant mechanism of hyperpigmentation is an increase in melanin synthesis [62]. This clearly demonstrates that vitamin B12 is involved in melanin synthesis, and that vitamin B12 might have had a more important evolutionary role than folate (which absorbs only in the UVB region) in the development of different skin colours. American and British black-skinned persons have significantly higher serum vitamin B12 concentrations than white persons have [63-66]. The ethnic differences in vitamin B12 levels probably arise from combinations of hereditary and acquired properties unrelated to cobalamin intake, storage, or deficiency [67]."

@ilovethesea said in New "Mission" of RPF:

@Amazoniac He’s taken the entire site off the wayback machine. Stolen all our content, banned us from accessing it, and now we can’t even look up prior versions. Unbelievable!

Did you, BioEclectic and other members have the chance to open the initial version of the forum, at the time when Ray agreed with its creation? The appearance was almost a variation of his website, with a picture of him and some of his favorite foods.

It's thanks to the limited access that I had to resort to the Internet Archive and could compare the initial to a recent version of the front page, which was a wall of warnings, pushy subscriptions, misinformation campaigns, and senseless slandering.

"CO2 , The Gas of Life" | William Happer

"If I see a madman driving a car into a group of innocent bystanders, then I can’t simply wait for the catastrophe and then comfort the wounded and bury the dead. I must try to wrestle the steering wheel out of the hands of the driver."

Contrary to Ray, the lion isn't a 'killer', but the apathy of some participants in being spectators of power abuses by him is perplexing.

The forum has become the antithesis of the person that it represents.

I wonder what are the thresholds for protesting for those who remain indifferent. They need a footage of the lion incinerating members with ethanol retinol to act?

At this stage, I'm more wary of people who haven't positioned than those who are enraged.

As for the few supportive militants, they're intriguing. They identify themselves as the open-minded camp while watching unfazed the tyranny in front of them. If these people were liberals as claimed, they would repudiate the administration and wouldn't be willing to be part of it.

The recent access restrictions were based on the forum being under attack, but what about everything that was already archived? These were a threat to defend against too?

Even CloudFlare takes a more balanced approach than radical blocking:

• The Trouble with Tor | CloudFlare

"We didn’t want to make blocklisting easier because, again, we believe there’s value in the anonymous web surfing that Tor offers."

• The Trouble with CloudFlare | The Tor Project

@T-3

Another topic that appeared in conversations with my pastors is how work that starts to get complex can bring hesitation in modifying it in further, for fear of losing parts by accident or messing up. Despite being possible to undo changes or resort to file history offered by some programs, it's more guaranteed to advance the work through duplicate files, relying on a copy of the latest version.

• If the modification goes well, the duplicate file is adopted and the original is kept as record.
• If the modification goes bad, the experimental copy is abandoned and you're left at where you were, with an intact material.

This makes experimentations riskless and must contribute to creativity.
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Learning in double time: The effect of lecture video speed on immediate and delayed comprehension

"We presented participants with lecture videos at different speeds and tested immediate and delayed (1 week) comprehension. Results revealed minimal costs incurred by increasing video speed from 1x to 1.5x, or 2x speed, but performance declined beyond 2x speed. We also compared learning outcomes after watching videos once at 1x or twice at 2x speed. There was not an advantage to watching twice at 2x speed but if participants watched the video again at 2x speed immediately before the test, compared with watching once at 1x a week before the test, comprehension improved. Thus, increasing the speed of videos (up to 2x) may be an efficient strategy, especially if students use the time saved for additional studying or rewatching the videos, but learners should do this additional studying shortly before an exam. However, these trends may differ for videos with different speech rates, complexity or difficulty, and audiovisual overlap."

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Examining Increasing Playback Speed in Recorded Lectures on Memory, Attention, and Experience

"Recorded lectures represent a popular means of delivering educational content. These lectures afford increasing the playback speed which could be used to reduce time demands and increase the likelihood that a lecture is consumed. In two experiments (N = 320), we examined the impact of increasing the playback speed of lectures across a range of speeds on memory for the lecture material, mind wandering, and the learner’s experience of the lecture. For speeds up until 2x, findings revealed no significant differences in memory for the material, mind wandering, and learner’s subjective experience of the lecture, with the exception that “enjoyment of speed” decreased as speed increased. Beyond a speed of 2x, however, significant impairments in memory for the lecture material and decreases in liking toward both the video lecture and the speed were observed. Moreover, the increase in mind wandering with time on task often observed in recorded lectures was not modulated by lecture playback speed. These results reinforce extant results in the literature on the effects of increasing playback speed on memory for lecture material and add new insights in terms of this strategy’s influence on mind wandering and learner’s subjective experience of the lecture."

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I'm not shure why lavalier microphones aren't favored over radio station ones. They work well, are cheap, give the person some mobility, don't clutter the view with an alien arm and nor make the video obsolete by the time that it's published.

Perhaps it helps to feel less vulnerable when there's an object between the speaker and the camera? If this is the case, increasing comfort may be a valid reason to keep it. Otherwise, the clean option seems better.

Member jwayne will help us in the comparison between lavalier and vintage mics:

I think that it's advantageous for the forum to keep material containing unproven miraculous cures and baseless rules in the Junkyard, so that visitors aren't caught off-guard. But it's my opinion, and it's simple to disconsider.

Tissue-specific effect of colitis on protein synthesis in mice: impact of the dietary protein content

"As previously reported, acute inflammation severely affects colon metabolism by stimulating protein anabolism [4, 9, 18]. Because colon protein content was not modified along the colitis course and resolution despite a higher protein synthesis rate, this increase in biosynthesis might reflect colon repair after epithelium erosion, with possibly a higher epithelial cell loss in the lumen. The locally induced inflammation is known to provoke an increased amino acid need for protein synthesis in the colon, not only when inflammation is maximal (day 7–10) [19], but also likely during the healing process. This increase, notably at a time when dietary daily intake was reduced, could have been compensated by amino acids supplied by other tissues, such as muscle. A reduced protein synthesis in muscle would also spare amino acids for increased protein synthesis in the colon, liver and spleen. Indeed, muscle is a major contributor to restore protein and energy losses in situations where protein catabolism is manifest such as starvation [20], acute injury [21] or chronic inflammation [9]."

"The present study shows that the protein metabolism modifications are modulated by the dietary protein content. The moderately high-protein diet (P30%), which has been recently shown to improve epithelial repair after an acute colitis episode [14], was associated with a lower protein synthesis rate, restoring initial level in colon compared to the two other diets [14% and 55% protein]. It is noteworthy that several colitis induced alterations were restored earlier with P30 diet consumption compared to the two other diets, such as body weight, caecal protein content, spleen and muscle protein synthesis rates. These changes coincided with the recovery of P30-fed mice that showed less inflammation and bacterial translocation (as evidenced by measuring the circulating LPS-BP concentration [14]) and faster colon repair in accordance with an earlier restoration of initial protein synthesis colon as shown in the present study."

"Our finding that the P30 diet restores rapidly and sustainably the initial (before colitis induction) colon protein synthesis can be related to our previous study in which we showed that P30 diet improved (when compared to the P14 diet) the colonic mucosal healing process by accelerating inflammation resolution, increasing epithelial repair, reducing permeability, and inducing epithelial hyperproliferation [14]. This suggests that the P30 diet, by furnishing an increased amount of amino acids, helps in the restoration of the colon epithelium, thus explaining the less active protein synthesis at this site. However, the relative amount of amino acids that is devoted to the restoration of the colonic epithelium remains to be determined when compared to other amino acid-consuming processes involved in inflammation. We previously showed that a specific mixture of amino acids given to rats after colitis induction was able to improve the colon regeneration/re-epithelialization, and this amelioration was found to coincide with a reduction of the stimulated protein synthesis rate in the colon when compared to control animals not receiving the amino acid mixture [23]. In sharp contrast, by further increasing the protein content in the diet (P53), we did not observe in this study any effect on the colon protein synthesis rate when compared to the P14 diet. This result can be ascribed to the deleterious effects of the P53 diet on the disease activity index, both in intensity and duration after a DSS challenge [14]. The reasons that would explain how a very high-protein diet consumption, although furnishing more amino acids is counterproductive after colitis induction, are not clear. One possibility is that by increasing the protein content in the diet, a larger amount of the dietary and endogenous protein escapes digestion in the small intestine, and thus reaches the large intestine. As a consequence, the microbiota produces an increased amount of amino acid-derived metabolites, some of which (hydrogen sulphide, ammonium, p-cresol) being known to be deleterious for the colonic epithelial cells, notably in terms of energy metabolism [24]."

"In conclusion, our study highlights the severe impact of acute colonic inflammation not only on the metabolism of proteins in the splanchnic area, but also in the peripheral tissues. The ability of the P30 diet to restore a normal protein synthesis in the colon may correspond to its documented beneficial effect on mucosal healing. In addition, the recovery of the initial protein synthesis rate in the various tissues in the period of time following colitis induction appears to be modulated by the amount of protein in the diet, with the P30 diet being more effective than the P53 diet."

Programmers may use code editors for general purposes and some people are fond of the basic notepad with the default font.

If your writing involves reflecting on what you just wrote, monospaced fonts can be an issue. However, the split screen with the goofy font for editing and a live preview with a readable font perhaps addresses this.

Learnability in Information Design

"Text can be presented in a monospaced font or a proportional font; extensive research has demonstrated that a proportional font is more readable than a monospaced font [4]."

User Interface Design For Programmers

"You may have noticed that almost every edit box on the Macintosh uses a fat, wide, bold font called Chicago which looks kind of ugly and distresses graphic designers to no end. Graphic designers (unlike UI designers) have been taught that thin, variable spaced fonts are more gracious, look better, and are easier to read. All this is true. But graphic designers learned their skills on paper, not on the screen. When you need to edit text, monospace has a major advantage over variable spaced fonts: it’s easier to see and select narrow letters like “l” and “i”. I learned this lesson after watching a sixty year old man in a usability test painfully trying to edit the name of his street, which was something like Fillmore Street. We were using 8 point Arial, so the edit box looked like this:"

"Notice that the I and the Ls are literally one pixel wide. The difference between a lower case I and a lower case L is literally one pixel. (Similarly, it is almost impossible to see the difference between “RN” and “M” in lower case, so this edit box might actually say Fillrnore.)"

"There are very few people who would notice if they mistyped Flilmore or Fiilmore or Fillrnore, and even if they did, they would have a heck of a time trying to use the mouse to select the offending letter and correct it. In fact, they would even have a hard time using the blinking cursor, which is two pixels wide, to select a single letter. Look how much easier it would have been if we had used a fat font (shown here with Courier Bold)"

"Fine, OK, so it takes up more space and doesn’t look as cool to your graphic designers. Deal with it! It’s much easier to use; it even feels better to use because as the user types, they get sharp, clear text, and it’s so much easier to edit."

From Monospace to Duospace: In Search of the ideal writing font

"In contrast to proportional fonts that communicate “this is almost done” monospace fonts suggest “this text is work in progress.” It is the more honest typographic choice for a text that is not ready to publish."

"The typographic rawness of a monospace font tells the writer: “This is not about how it looks, but what it says. Say what you mean and worry about the style later.” Proportional fonts suggest “This is as good as done” and stand in an intimidating contrast to a raw draft."

"Proportional fonts are optimized for high reading speed. That makes them the perfect choice for reading. Good writing, on the other hand, is measured, reflected, slow. It takes one step at a time. In a monospace font every letter, every number, every punctuation mark and every space takes the same visual space, which slows us down. And, for writing that’s a good thing."

"Proportional fonts save space. They suggest that you “hurry up and fill the page.” Monospaced fonts, on the other hand, feel more productive. Every typed letter translates into a homogenous visual progress in writing. It is both more relaxing to write at a slower pace and more satisfying as the progress is more tangible."

"Programmers use monospaced fonts for their indentation and because it allows them to spot typos. In a perfectly regular horizontal and vertical raster, letters and words become easily discernible: A typical proportional font comes with word spaces as wide as an i. Monospace fonts come with rather large word spaces. This makes it easier to discern each word and letter."

"Designers have pointed out that, with all the structural benefits that may or may not come from using a monospace font when writing, there are typographical compromises in typewriter fonts that are mere mechanical constraints that can and should be overcome. Due to the way mechanical typewriters worked, using the same horizontal space for each letter was inevitable at the time."

Making Code Beautiful With Type

Gain the Upper Hand with Good Typography

"Times New Roman was invented in the early 20th century for the Times of London and quickly gained traction among newspaper publishers. The Times commissioned it as an intentionally narrow font to fit more text per line and to enable quick reading.[6] Even from the beginning, it was criticized as unappealing to the eye."

"For all its ubiquity in self-published documents, when was the last time you saw Times New Roman in a book? Maybe never. Fonts used in professionally published books are comparably easier to read. This visual appeal, in turn, fosters comprehension and retention.[7]"

Are you able to access the archived forum pages on the Internet Archive?

"This URL has been excluded from the Wayback Machine."

"No URL has been captured for this URL prefix [raypeatforum.com/*]."

Have you ever seen one of those videos where a dog barks at something and the companion brushes it off, as if it was an overreaction to nothing? These authors are good storytellers and have a luring speech, making them prone to influence. Once you realize how they operate, the pattern becomes obvious and it's natural to be compelled to alert others, pointing out why it's worth being watchful with them. It's somewhat revolting to spot the same people, employing similar methods, fooling over and over again.

Either way, if you would like to help, consider placing junk in the Junkyard next time. It warns readers while reminding them that they can eventually find valuable stuff.

Otherwise, you can lead by example and ignore my posts. I've been making this easier in no longer tagging or quoting you, as it can be the case that the message won't resonate while you continue to admit that false information is not much of a concern.

@Jakeandpace said in Conditional problems with vitamin A: a place for sane discussions:

So do you think there are any cases where restriction could be helpful?

I’ve read your article on daily excretion rates and it seems you said hepatic stores of 30ug/g is what the body wants as after that point it tends to dramatically increase the disposal of retinol.

Do you think restriction for a short while could be useful followed by introduction of retinol back into the diet with other things that may prop up the metabolism to help utilise it. It seems a lot of these low A people can’t go too long on it and end up resorting to eggs. I personally tried Low A for about a month now and each time I restrict to much I feel what I can only describe as though I am becoming dumber, I lose inspiration for life and just drift. Then as soon as I eat some cheese and or eggs I feel my gusto coming back again…

Is restoring thyroid function the best way to deal with this and some sort of mild restriction?

However going low A brought some relief in terms of anxiety and other problems like that but if I go to long I feel mentally impaired.

Just to clarify, the expert here is Kvothe. It's why I tried to get him to embark on a project for mentorship.

Yes, moderating any "nutrient" makes sense if it's doing more harm than good, but calls for alternative means to increase the tolerance to normal instead of finding comfort in labeling it as a toxin, as the poison A crowd do.

I don't know what you consider a short period, but to get to the therapeutic range, people need to be extreme and consistent. A month of restriction won't get you any lasting result and it's preferable to skip it.

If the issue is immunological, focusing on adequate metabolic rate (and the nourishment needed to sustain it) probably won't be enough. Compromised barrier integrity and disturbed gut composition can be the underlying problems.

Shared on the Garrey Pith Forum, but worth reposting here:

Kinetic Analysis Shows that Vitamin A Disposal Rate in Humans Is Positively Correlated with Vitamin A Stores

"Previous studies have demonstrated that serum retinol is the main determinant of VA disposal rate in rats with low to moderate VA intake (16), whereas VA status affected disposal rate in rats with higher liver stores (15). Our results appear to support those observed in rats with high liver VA stores (15) by showing that the model-predicted VA disposal rate was strongly correlated to VA total traced mass in Chinese (Fig. 3 A), U.S. (Fig. 3 B), and all subjects (Fig. 4 A). Moreover, when we compared VA disposal rate to serum retinol concentrations in all subjects, we observed that retinol concentrations were correlated with VA disposal rate (Fig. 4 B, C), indicating that serum retinol also contributes to whole-body VA disposal as previously reported (16)."

"[..]differences in VA nutriture will lead to changes in VA kinetics that will alter VA disposal rate to either conserve VA (VA deficiency) or prevent excessive accumulation of VA (VA sufficiency) even when VA levels are adequate."