10HDA is a longevity producing HDAC inhibitor

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Treon Verdery

Oct 4, 2022, 3:40:48 AM10/4/22
Testing numerous different lipid versions of 10HDA from royal jelly as longevity drugs, and finding human equivalents: When people eat fats like omega 3 lipids (DHA, others) the body makes a variety of things like triglyceride forms, ethyl esters, and phospholipid forms out of it it, at humans, but perhaps not mice or queen bees, pancreatic lipase likely emulsifies the 10HDA as well as 10H2DA at royal jelly; all of these suggest that feeding people various of perhaps 10 different lipid forms of 10HDA and then measuring the humans as to things like cognitive ability, and various physiological measures could find things that are more highly beneficial as 10HDA and royal jelly forms; as a longevity drug: noting the published longevity effects at mice, they could feed mice 10HDA preprepared form variants like phospholipid versions, triglyceride versions, ethyl esters, as well as things like methyl esters, and propyl esters, and emulsified creams, then see if there were any longevity differences between the lipid forms; they could also measure the kind and amount of the circulating form of 10HDA lipid at mouse blood, and then the human version of 10HDA and royal jelly could be engineered around producing the same kind of 10HDA lipid, at the human bloodstream, at the same ug/ml as the longest lived 10HDA (or royal jelly) supplemented mice have at their bloodstream; so, if its phospholipid 10HDA that is measured as causing the greatest measured mouse longevity then its also the phospholipid 10HDA amount at human blood, as well as a 10HDA phospholipid longevity supplement or drug for the humans; Similarly if the most longevizing version of 10HDA is 10DHA as triglycerides at some measured amount at the bloodstream of longevized mice then it is the triglyceride form of 10HDA at the same amount at the human bloodstream; Notably, this could also give humans using 10HDA or also 10H2DA, or 90DA, or other longevity decanoic acids, the ability to have the same ug/ml of the same kind of decanoic acid lipid at their bloodstream as the longevized mice; Notably, at DHA/EPA lipid supplements, humans taking an emulsified supplement had 3-5 times higher amounts of omega-3 lipids at their circulation after 8-24 hours than if they took a fish oil pill; feeding mice a 10HDA emulsion, and also humans, could be beneficial at finding a functional dosage;

A paper on greater longevity from HDACinhibition mentions HDAC yeast genes that when removed cause greater longevity, as well as RNAi effects on HDACs, reducing the HDAC effect cause greater longevity, https://www.embopress.org/doi/full/10.15252/emmm.201809854 Trichostatin A, an antifungal, causes greater longevity at drosophila from HDACi Trichostatin A is 50- $100/Kg at alibaba so is likely a longevity drug at less than 10c/24 hours Trichostatin A is soluble in ethanol, but not water, “Trichostatin A is soluble in DMSO, DMF, acetonitrile, and ethanol. It is not soluble in water. This product is tested at 2 mg/ml in methanol, yielding a clear, colorless solution. It is also soluble in lower alcohols” also, “Trichostatin A inhibits histone deacetylase at nanomolar concentrations. The resulting histone hyperacetylation leads to chromatin relaxation and modulation of gene expression.”

https://www.sigmaaldrich.com/content/dam/sigma-aldrich/docs/Sigma/Datasheet/8/t8552dat.pdf , is trichostatin soluble in melted sugar alcohols like sorbitol or xylitol that dissolve it when warm, and then turn to a dry, but trichostatin A dissolved powder to be placed at an enteric capsule? Or, noting liposomes can be made with a bunch of etoh, could a high etoh or DMSO liposome transport dissolved trichostatin A to the lymphatic compartment to be an effective dose?

Noting that omega-3 fats are is up to 9 times more absorbed as food than as pills, and that emulsions have 3-5 times more increase in measured omega-3 amount at the bloodstream after 8-24 hours than pills, eating royal jelly as an emulsion, with food, and a piperine capsule, could be beneficial; Also, a two form dose of royal jelly could be beneficial, a 10DHA calculated longevity dose amount, and then the same amount as the 10DHA calculated longevity dose again while being taken as an enteric pill, with food, with the benefit of the the possibly longevizing royalactin proteins passing the stomach, and the 10HDA likely being emulsified at the GI tract; So if 6 grams of royal jelly is a longevizing 10HDA dose, then 12 grams, half as enteric pill form, the other half as royal jelly (lecithin) emulsion with food, such as 12g or more of an oily food could cause 6G or more of functional 10HDA absorption; different lipid forms have different absorbabilities, but, “Absorption of both EPA and DHA from fish oil ethyl esters was increased three-fold[with the 44 gram fatty meal]”

a person eating 10HDA at royal jelly likely absorbs 90-95% of it; “direct measures of digestion calculate “digestibility coefficients,” or the digestion percentage (efficiency) of various nutrients based on the amount of nutrient consumed relative to that collected in total fecal excretion (i.e., undigested) over a period of a few days. For instance, human studies measuring the digestibility of dietary omega-6 polyunsaturated fatty acids, as linoleic acid, show digestibility efficiencies approaching 90–95%.”, note though that, “a diet higher in fat, rather than a low-fat meal, supports better omega-3 bioavailability.1 Earlier literature indicates absorption efficiencies for EPA in the triglyceride or ethyl ester form of 90% and 60%”

that a triglyceride is 90% absorbable at a human, but an ethyl ester lipid is just 60% absorbable suggests that a 10HDA version that is a triglyceride would be more efficient and effective, possibly better at longevizing, notably though it is possible that a 10HDA ethyl ester actually travels to different tissues than a triglyceride;

Note though that putting a royal jelly emulsion in an enteric capsule could be higher effectiveness, “that DHA, being protected by the encapsulation structure from oxidation and degradation under the acidic conditions of one’s stomach, is successfully released in the upper two parts of the small intestine”

taking the royal jelly 10HDA with a large, lipid-rich meal is the way to heighten absorption of the the 10HDA, “The absorption of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish oil triacylglycerols and fish oil ethyl esters consumed in a high-fat meal (44 g total fat) by male volunteers was measured and compared to values previously reported for consumption in a low-fat meal (8 g total fat). Absorption of EPA, but not of DHA, from fish oil triacylglycerols was significantly improved from 69% to 90% by co-ingestion with the high-fat meal. Absorption of both EPA and DHA from fish oil ethyl esters was increased three-fold, to about 60%, by co-ingestion with the high-fat meal, indicating that absorption of fatty acid ethyl esters is highly dependent on the amount of co-ingested fat.

It is likely the double dose, as an emulsion, with an enteric capsule, with food and piperine works better than: combining DMSO with royal jelly powder to make a paste, then putting it an enteric capsules, with a side enteric capsule of piperine could be a way to make the 10HDA 2(dmso) times 4 (piperine) 8 times more physiologically available; notably though, liposomes (4 times from skipping first pass metabolism) with DMSO (2 times) with piperine (4 times) could make the 10HDA as much as 32 times more physiologically available, noting the 6-60g dose of royal jelly, that suggests that a 4g dose, as DMSO liposomes with piperine could be like 128 gram dose.

During 48 hours, emulsified fish oil is about twice (.67 compared with .34) as physiologically available as encapsulated fish oil, “Over a 48 hour period there was enhanced absorption of total n–3 and EPA (0.67 ± 0.16, 0.45 ± 0.06, p<.01;

0.34 % ± 0.05, 0.23 % ± 0.04, p= .05;

EFO and CFO respectively was observed for the EFO treatment., “The emulsified and water soluble state increases exposure to lipase and diminishes the gastric clearance time. Therefore, we have examined the rate and extent of absorption of total n-3 and LCn-3 into the phospholipid fatty acid (PLFA) pool after an emulsified fish oil (EFO) supplement compared to capsules of the fish oil used in its production (capsular fish oil, CFO). We hypothesized that the EFO would have an increased rate and extent of absorption compared to the CFO. “ also, “Participants consumed a 4-g portion of fish oil provided as either 5g (∼ 1 teaspoon) of EFO (80 % lipid, providing 4 g of fish oil) or four 1-g capsules of CFO”, also, “The EFO was Coromega ™ (Carlsbad, CA) an emulsified, flavored lipid supplement produced from marine sources that is of pudding consistency”

Also, “The observed increases are likely due to improved digestion and absorption due to the enhancement of the action of pancreatic lipase on long chain fatty acids (23). Lipid emulsification in the stomach is a fundamental step in fat digestion through the generation of a lipid-water interface essential for the interaction between water-soluble lipases and insoluble lipids (24, 25). The ultimate bioavailability of dietary fat is dependant on this lipid water interface. Emulsification of fish oil bypasses this normal physiologic step and enhances its absorbability (24). Garaiova and colleagues (21) reported the increased absorption of long chain, highly unsaturated fatty acids and incorporation into plasma fatty acids with the administration of pre-emulsified fish oil. Our work demonstrates that in the short term the emulsification of fish oil allows for a similar enhanced absorption with improved rate and extent of incorporation into PLFA

Note: one graph of DHA at the paper shows the capsule oil being at about 7% and the emulsion being at 20%. so emulsified oils are 3 times more detectable at the circulatory system after 24 hours. 48 hours later the emulsified fish oil was still double the capsule concentration, another graph shows the emulsified oil being 4-5 times higher concentration after 8 hours;

Also, taking royal jelly with a meal could cause more 10HDA to be absorbed, “In one study comparing the effects of fish and fish oil, researchers found that levels of DHA after 6 weeks of salmon consumption were nine times higher than after fish oil administration.”

Also, “Another study confirmed this by demonstrating that fish oil is absorbed much better in the presence of a high-fat meal. They found that the content of n-3 fatty acids in the body tissues rose dramatically when the fish oil was taken along with 12g of olive oil.”
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