Posts made by CrumblingCookie

@happyhanneke said in DMSO - is it as maligned as aspirin because of potential benefits?:

I know this topic is older.

But doesnt DMSO induce DNA methylation?

I read from Georgi Dinkov that DNA methylation is tied to cancer.

Both DMSO and MMS don't impact DNA methylation. Surprisingly. The studies seem very clear about that.

@gentlepotato
That seems like a pretty stable dietary schedule. Glad to read it's working out so well for you. I agree with that statement and remember that Dr. David Stephens also stressed the importance to maintain a proper, wholesome diet. It should be self-explanatory.

My sense is it's been very important to eat enough food overall, and enough nutrient dense foods, when taking large quantities of glucose.

How often and for how long do you go outside per week when you say you are 95-99.9% housebound?

@CrumblingCookie said:

All I know is that in the past, for years I used to have 95-99mg/dL in the mornings whereas a few months ago it was 82mg/dL one hour after 70grs of dextrose.

I can now add that my latest morning BG was 100mg/dL. I.e. there's neither improvement nor worsening of morning BG and it suggests my glycogen stores are still as insufficiently low as before. Which fits all the reactions I described previously.

@albion said in B-complex and or Multi recommendation?:

@CrumblingCookie Would you recommend someone trying to diagnose if they need more Cysteine to take NAC? If yes, just as a diagnostic tool or ok as a regular/intermittent supplement?

IMO both is possible. NAC is much much less excitatory than free cysteine and really good as long as there's no diarrhea from taking it. In the latter case it's better to work up with sulfate. It's difficult to forecast the full circle of interdependencies which depends on individual overall health.
For regular or continuous intermittent use I'd blend the NAC 1:1 with glycine and add a basis of 100mcg molybdenum per day. Lots of vegan protein powders are especially poor in cysteine (and total sulfur amino acids) so adding NAC to them can make them feel much more wholesome and nutritious imo.

@gloryus I didn't have it on my radar that biotin is strongly needed for B6 activity. When I had read those high doses of biotin I though these guys are going to get crazy carb cravings.
However
indeed I've noticed that biotin+P5P leads to decreased hunger for me. Whereas biotin alone drives it up a lot. I appreciate to have been made aware of this connection.

It's super wrong, though, to regard pyridoxin merely as an inactive form of B6 instead of a dirty antagonistic precursor.
And I reckon the huge amounts of biotin are not needed per se but may be serving as a crutch for sulfur to feed the molybdenum-dependent sulfite oxidase.
Then there's another question: If an increase of uric acid through molybdenum-dependent xanthine oxidase is indeed important for renal copper excretion are all the people doing this going go get intense feeding frenzies for meats or mushrooms so that they can replete and maintain their nucleotides?
However I haven't seen anything on uric acid binding to copper, but only on uric acid being protective against cuproptosis i.e. copper-induced cell apoptosis together with NO. So does the uric acid only protect against the damage from (temporarily) increased free copper? And should arginine be taken along with it?

My suggestion for a vitamin B complex is the Source Naturals "Coenzymate" B Complex plus extra a-GPC plus extra sulfate.

It's really hard to find a reasonable OTC B-complex with the proper ingredients and without ludicrous doses. IMO it's really important to provide those vitamins B steadily as in at least 2 times daily.

Not sure why no-one ever has yet pointed out that Energin contains the good P5P but in aqueous solution and hence that P5P is going to degrade very quickly within hours and days into toxic metabolites which actually inhibit P5P-dependent enzymes (https://doi.org/10.1111/jphp.12701, https://doi.org/10.1016/0304-4165(72)90148-1).

@LucH said:

Do you mean that when lowering homocysteine high enough with a high dose TMG, there is not enough cystine and cysteine remaining to ensure metabolic functions?

Yes. By doing this you deprave the CBS pathway. With use of TMG, betaine, creatinine, choline you also get less endogenous taurine at the end of that which is however the least important in this context.
IMO it's important to up sulfur intakes and get enough P5P for CBS if taking any of those.
It's also why supplementing methionine is mostly unwise whereas extra cysteine is effective as high methionine is never a full subsitute for low cysteine or sulfates in a diet and doesn't mitigate stunted metabolism.

If you're aware of the profound metabolic role of vitamin E you need to also be of sulfate because without either there's disturbed sulfate fixation onto cellular lipoproteins and overall failure in sulfomucopolysaccharide metabolism. Then there's also failure to form intramolecular crosslinkages and proper maturation of collagen fibers.

@albion
The thing about excessive methyl-groups especially through TMG / betaine but also through the better choice of choline is that they decrease the pressure on demethylation of methionine into cysteine and other downstream sulfur metabolites.
Hence they create a relative lack of cystine, cysteine and sulfate. A lack of cysteine messes with your glutathione synthesis and a lack of sulfate messes with your hormones.
That's also how to get avitaminosis E (in spite of sufficient vitamin E) because essential functions of vitamin E are about sulfation i.e. depending on sulfate as substrate.

@S-Holmes

The immunological shift from those 120.000 IUs will last for several months. It's kind of like parts of your building are on fire and you turn off the annoying sprinklers and alarm bell so you can move back in and redecorate the unaffected offices and corridors. Which you can keep up with such high doses but woe upon you when you stop. Or anyway over the course of time.

By showing strong immidiate short-term benefits you have essentially confirmed the magnitude of chronic inflammation from persistent infections acting out within your tissues.

@jjk_learning Thanks. It's rough.

This looks good for higher molybdenum, higher zinc, higher cobalamin, sufficient selenium and lower copper levels:

Associations of essential trace elements with epigenetic aging indicators and the potential mediating role of inflammation

Results: Plasma Se levels [and Mo levels] were significantly negatively associated with DunedinPACE*, whereas Cu levels were significantly positively associated with it.

*: DunedinPACE is a novel blood test that measures the pace of biological aging based on DNA methylation. It shows high reliability, predicts morbidity and mortality, and can be used to evaluate geroprotective interventions.

And this Chinese study finds the lowest metabolic syndrome at molybdenum plasma levels between 2-3 mcg/L, much above the typical lab reference range with an UL at only 1.3 or 1.4mcg/L. The latter is achievable with about 70mcg Mo daily. In the study with the 1490mcg Mo/day volunteer the plasma level was 5-6mcg/L.
Inverse Association of Plasma Molybdenum with Metabolic Syndrome in a Chinese Adult Population: A Case-Control Study

And this mice study finds serious thymus gland atrophy and disordered development of T cell subsets (viral infections, excess autoimmune response anyone?) in low molybdenum diets:
iTRAQ-based quantitative proteomic analysis of low molybdenum inducing thymus atrophy and participating in immune deficiency-related diseases

I have found this old gem in the 2016 - 2019 (2023) Molybdenum, Hard To Pronounce, Harder Still To Obtain thread on the RPF:

"A male health practitioner in his late thirties (the patient), apparently in full health, wanted to be even the healthier. His colleague suggested that he should try a molybdenum supplement (Molybdenum Chelated, 100 μg molybdenum per tbl., Nutriwest Co., Douglas, WY) to cure his »allergy« to perfume of his patients. That far he had had a remarkably empty medical record and was outstanding in his educational curriculum. According to his wife’s testimony, he was »easy going, doesn’t get angry often, and it takes a lot to rattle him«. The patient consumed a HCl supplement for »indigestion«, and other non-noxious nutriceuticals (Table 1) before he started to take molybdenum on 1 July 1997. The manufacturer’s recommendation read: »One tablet per day, or as directed«. Instead, the patient followed the recommendation from his physician »Take as needed« and consumed an average of 7 to 8 tablets of molybdenum per day (700–800 μg). He did not start with 700 μg; he started with about 300μg a day, and then gradually increased the intake over a period of 18 days. On day 7 he showed the first signs of anxiety and agitation. On day 14 he became mildly psychotic and experienced visual and auditory hallucinations. He also exhibited excessive craving for salt; so much so that he woke his spouse up at 2:00 a.m. to get him salt from a grocery store. On day 18 he could »smell the molybdenum all around him« and he abandoned molybdenum supplements. The smell was like the one of salt water, distinctive but mild. By the time the patient stopped taking molybdenum, he had already consumed a total cumulative dose of 13.5 mg of molybdenum. On day 19 he had severe psychosis with strong audio and visual hallucinations, insomnia, intense craving for salt, diarrhoea, and painful and cold extremities. On day 22 his hallucinations were accompanied by petit mal seizures and on day 24 he tried to take his life with a knife and, »chased by the devil«, he ran through a plate glass window and jumped headlong off a six-metre wall. The flight ended up with multiple body contusions and difficulties in movement. He struggled with an officer when the police picked him up, as he thought that they were trying to hurt him."

@Amazoniac 's comment on that back then:

Nice. This is what a true detox phase should look like.​

Thanks for this, Amazoniac. It made me laugh.

I'm not too worried about it, he was taking a lot of other stuff that could've created a favorable environment for trace mineral toxicity. As always, most of these reports involve people taking more than necessary, insisting despite bad reactions for too long, and including a cocktail of other questionable compounds.

I agree with that. That guy had also taken various glandular extracts, betaine (which spares methionine demethylation to gain cysteine and further downstream sulfur metabolites incl. crucial sulfate), lots of bone meals (heavy metals? copper overload?). Whereas he had taken no B6, no extra sulfur, no extra zinc.

@gentlepotato said:

May I ask how much you're eating, and your macros?

My diet is poor. Definitely too little protein. Are you having any specific thoughts?
In the first two months I was eating beef&lamb carnivore with then increasingly more rice for simple yet delayed carbohydrates. But I grew to dislike the fatty bits ever more and the metals as well.
It was either the high amounts of iron etc. from those months of carnivore or the glucose itself: My face skin has aged much since last year.
Unsurprisingly with the regular dextrose loading my utilization of fats is strongly inhibited:
Whenever I eat a chunk of cheese (due to protein+calcium cravings, I surmise) I don't even ever feel satiated by it and it all goes straight to weight gain in fat deposits.

Probably the best way to eat with the dextrose would be like a bodybuilder's diet: Rice as complementary carbs, rich greens for the fibres, the vitamins, the calcium and lean poultry for protein. Along with a lowly dosed (100-200% RDI) B+C complex. Along with potassium chloride or potassium sulfate or a mix thereof in amounts according to taste.

@S-Holmes said:

The next thing I'm going to try is higher dose vitamin D

Don't. It's a trap.

In this human study 300mg EGCG bound about 3-5mg (27%) of orally given iron but only 3% of intravenously given iron.
With only 150mg EGCG, curiously, there was 15% decreased retention of intravenously given iron. I.e. EGCG bound circulating iron but only when 150mg and not when 300mg EGCG were given at a time.
It's all a bit odd.
In this rat study the authors concluded "that green tea extract (GTE) ameliorates iron overload induced hepatotoxicity, apoptosis and oxidative stress in rat liver via inhibition of hepatic iron accumulation".

I'm now somewhat curious about this topic because of liver issues and taking any zinc causing extra nausea and headaches and insomnia.
By this currently trending RPF thread this should imply I had both too much iron and copper. Or mainly too much iron in case molybdenum doesn't improve such effects by zinc.
Which when I think about it becomes more interesting in the context of high ferroptosis observed in the causative chain of neurodegenerative diseases.

@cs3000 said:

not aware of the narratives

In brief the current narratives of that RPF thread are that EGCG chelates iron from iron-copper complexes, which raises copper, which needs molybdenum to antagonize, chelate and excrete through increased uric acid through Mo-dependent xanthine oxidase, all of which needs vast amounts of vitamin B6 to replenish circulating copper with tissue copper, which needs vast amounts of biotin, which needs balancing with large amounts of vitamin B5 because of their shared transporter and lots of vitamin C, depending individually, to activate B vitamins and to keep iron and copper mobilized in circulation. All that so age-dependent iron and copper stores decrease and their alleged inhibitions are replaced with supplemented zinc ions to restore functions.

I've now had a brief look into ECGC + iron and it does appear to form (Ngal-)EGCG-iron complexes and alleviate iron-dependent injuries and ferroptosis. In this study, e.g. they beneficially used "only" 10mg/kg EGCG "EGCG activates Keap1/P62/Nrf2 pathway, inhibits iron deposition and apoptosis in rats with cerebral hemorrhage".
The cited mice study in which 750mg/kg EGCG was used is probably highly problematic. Probably the binding affinities and or the priorities regarding iron and copper shift and are different from much much lower high doses of EGCG as in 10mg/kg in rats.

@jjk_learning
Trying to capture most of the benefits and limitations of taking dextrose, in my case:

Glucose hasn't made me a happier per se. However, when confronted with adverse events I now mostly feel and think more indifferently disappointed "meh"s instead of any "argh!".

I had been having symmetrical jerks moving down my spine reaching into my shoulders and arms and at bad times as far down as into my legs every few seconds throughout the days. Against which rasagiline proved insufficiently effective. Which I could only keep at bay by injecting thiamin-HCl every 10-14 days.

With dextrose I don't have these jerks at all. But they gradually return as soon as my dextrose servings are overdue or used up much more quickly by stressful events, environments or activities. The latter would include mere common daily errands. I.e. this is in the context of my thresholds having become abysmally low.

E.g. if I leave house in the morning without having loaded-up with glucose, those jerks return and my hand and arm starts twitching painfully etc. in an increasing manner.

With dextrose my heart rate is significantly lower and calmer and I can sleep and not tense up. As my glucose fades throughout the night, after 5-6 hours at the latest, I still wake up from a sudden violently high heart rate >150/min. I can calm that down with another serving and maybe doze off again c. 40 minutes thereupon.

I don't want to rely on glucose oxidation throughout the whole night. Of all times this is when accumulated extra fats are meant to be burned off in a continuous, orderly fashion.

I have less nausea with sufficient, regular dextrose than without dextrose previously but that is not completely absent either. Put simply I haven't had to spontaneously throw up anymore since on the dextrose. Also, I've experienced the dextrose hugely and quickly helps in alleviating the narcotics burden post-surgery. Which is a benefit I'm not too keen to have to appreciate many more times.

Blood sugar wasn't tracked by me. All I know is that in the past, for years I used to have 95-99mg/dL in the mornings whereas a few months ago it was 82mg/dL one hour after 70grs of dextrose. So I probably have lower BG when consistently taking dextrose.

That's more or less what I mean with the dextrose keeping me afloat yet not being curative. It'll probably remain an essential nutrient to go along with whatever actual remedy eludes me.

@cs3000
How would this study "Dietary Copper Reduces the Hepatotoxicity of (-)-Epigallocatechin-3-Gallate in Mice"
https://pubmed.ncbi.nlm.nih.gov/29295524/

"Following EGCG treatment, the survival rates were 12.5%, 50% and 100% in the Cu-deficient, -sufficient and Cu-super nutrition groups of mice, respectively."

"suggest that Cu can relieve EGCG hepatotoxicity, possibly by up-regulating ceruloplasmin activity, which can be used to promote EGCG applications."

fit in with any of the EGCG narratives of the latter binding iron and hence freeing up copper from iron-copper binding as currently discussed on the RPF?

It kind of says the opposite, i.e. EGCG application requiring additional copper for survival.

On the other hand the used dosage (EGCG, 750 mg/kg BW) seems gigantic and maybe there's another compensatory effect at play there fore bare survival.
Or the iron/copper binding molecules in mice could have slightly different structures than their human equivalents?

Many months ago I had elaborated on organic dextrose powder in this thread.
That was mainly with regard to the possibility of glyphosate residues in non-organic cereal-derived dextrose.
I settled with that it's probably well filtered out and that I wouldn't expect significantly different levels of glyphosate in organic vs. nonorganic dextrose.

Now here's a follow-up thought to that. Albeit speculative, as I am not certain on whether similar mechanisms apply in plants as they do in mammals*:
Because of the much higher glyphosate burden in non-organic cereals and its effects on various basic biological processes and the consequently relatively very high accumulation of 2H especially in sugars versus fats*,
I would expect dextrose from organic sources to contain considerably less deuterium in its molecular composition.
If that's true, organic dextrose would have much better efficacy and efficiency as an energy substrate and be subtly yet distinctly better for overall metabolism.
As would be sugar, starches and all the original cereal foods from organic (or Mexican) agriculture.

*(animal fats, but also coconut fat are reported to be lowest in deuterium content.)

Or expressed in the opposite way: Non-organic sugars could significantly meddle with ATP through their high deuterium content despite being such a direct energy substrate. Sort of like three steps forwards, one step backwards in overall energy benefits.

In other news:
I'm still doing the dextrose after 6 months. At >250grs daily over 4-7 servings.
It's keeping me afloat. But it's not leading me to recovery.

@wester130 said in Diclofenac gel to regrow hair on bald head and beard:

@Mossy tretinoin isn't a systematic drug so should be okay

Wrong. Tretinoin does cause systemic adverse effects. Which can be even long-lasting.
They are simply not publicly acknowledged.
I can't provide the specifics anymore as I once must have written them on paper or tried to remember them in my head. It's not a good ingredient to use IMO.

@DavidPS
Good find. How useful and practical would it be to take inhibitors every day to reduce hyaluronidase if HA reportedly only has a half-life of 1-3 days and wouldn't it be better to raise HA synthesis rather than block its degradation?
Is there decreased HA synthesis or increased HA degradation with age? And why so?
I see genistein as a related flavone inhibits the enzyme HA synthetase 2 through protein kinase - making it important to check if any of the other substances listed in the table above do the same. Similiar to how aromatase inhibitors often act as xenoestrogens themselves and therefore result in no overall benefit.

Dinitrophenole perhaps?