@haidut Metformin lowers iron, copper (could be good) ,influences zinc, magnesium, B9, B12, B1, chromium but restores Randle cycle to burn glucose zinc could lower demand on metformin metals and gallstones https://www.sciencedirect.com/science/article/pii/S1015958424011527 The roles of metal ions in gallstones formation Author links open overlay panelKuinan Tong 1, Chao Jing 1, Tingting Wang, Kun Liu, Wei Guo, Zhongtao Zhang https://doi.org/10.1016/j.asjsur.2024.05.243 https://ars.els-cdn.com/content/image/1-s2.0-S1015958424011527-gr1.jpg https://ars.els-cdn.com/content/image/1-s2.0-S1015958424011527-gr2.jpg AI Metformin disrupts the Randle cycle (glucose-fatty acid cycle) by inhibiting fatty acid oxidation and reducing free fatty acid (FFA) levels, thereby promoting glucose utilization over fats. By inhibiting this cycle, metformin reduces insulin resistance, decreases hepatic glucose production, and restores the body’s ability to utilize glucose efficiently. Key Aspects of Metformin and the Randle Cycle:Randle Cycle Overview: The Randle cycle is the competition between glucose and fatty acids for energy oxidation, where high fat levels inhibit glucose uptake and oxidation, promoting insulin resistance. Mechanism of Action: Metformin reduces the oxidation of long-chain fatty acids, specifically in red muscle, which restores glucose oxidation and reduces the reliance on fat as a primary fuel source. Impact on Diabetes: By inhibiting this cycle, metformin helps lower elevated blood glucose levels and reduces hypertriglyceridemia, which are common in type 2 diabetes. Insulin Sensitivity: Metformin-induced inhibition of the Randle cycle improves overall metabolic flexibility and improves insulin sensitivity, enhancing muscle and peripheral uptake of glucose. Energy Balance: The drug helps reverse the overactive Randle cycle that occurs in obese or diabetic patients, improving the balance between glucose and fat utilization. Both metformin and zinc appear to have protective effects against gallstones, often through improving metabolic health and reducing gallbladder inflammation. While they are frequently used together for diabetes management, their individual roles in gallbladder health are distinct. Metformin and Gallstones **Reduced Risk: Long-term use of metformin is associated with a significantly lower risk of developing gallstones in diabetic patients. Mechanism: Metformin helps by improving insulin sensitivity and gallbladder motility, which prevents the "stasis" of bile that leads to stone formation.** Animal Research Warning: In some mouse studies, while metformin prevented stones, it was also linked to porcelain gallbladder (mucosal calcification), though it is unclear if this occurs in humans. Zinc and Gallstones Zinc Deficiency Connection: Patients with gallstone disease often have significantly lower serum zinc levels. Protective Properties: Zinc may help prevent gallstones by reducing free radical formation and protecting against oxidative stress in the liver and gallbladder. Bile Flow: Supplementation has been shown in animal models to suppress liver fibrosis and improve the composition of bile, potentially aiding in stone prevention. Taking Zinc and Metformin TogetherSynergy: For diabetic patients, combining zinc and metformin can be more effective than metformin alone for overall metabolic health. Safety: There are no known direct drug interactions between zinc supplements and metformin. Metabolic Benefit: Both substances help lower HbA1c levels and improve lipid profiles (cholesterol/triglycerides), both of which are key risk factors for gallstone formation. Zinc deficiency causes significant muscle loss (muscle atrophy), reduced muscle strength, and impaired muscle repair, as zinc is essential for protein synthesis, cell growth, and tissue regeneration. Severe deficiency increases muscle protein breakdown (catabolism), reduces muscle mass, and is an independent factor for sarcopenia. Zinc Deficiency and Muscle Loss Mechanisms:Reduced Protein Synthesis & Regeneration: Low zinc levels restrict muscle regeneration by slowing down myogenesis (muscle cell formation) and impairing muscle cell activation. Increased Breakdown: Deficiency disrupts skeletal muscle proteostasis, activating the ubiquitin-proteasome system, which breaks down muscle proteins. Mitochondrial Dysfunction: Zinc is crucial for mitochondrial health; its lack can lead to impaired mitochondrial function, reducing energy supply (ATP) for muscle cells. Hormonal Imbalance: Zinc deficiency can lead to lower levels of testosterone and growth hormone, which are essential for maintaining muscle mass .Chronic Diseases & Aging: In patients with chronic liver disease, zinc deficiency is an independent predictor of sarcopenia (age-dependent loss of muscle). Zinc acts as a modulator of AMPK (AMP-activated protein kinase), a key cellular energy sensor, influencing its activity in ways that can be beneficial or harmful depending on the context. It helps maintain metabolic homeostasis and is crucial for muscle protein synthesis, with zinc deficiency often increasing susceptibility to muscle atrophy via AMPK. Key Aspects of Zinc-AMPK Interaction:Muscle Metabolism: AICAR (an AMPK activator) increases intracellular zinc levels, and zinc-depleted conditions lead to greater muscle atrophy under stress. Neural Protection: Zinc can regulate glucose metabolism in spinal cord neurons via the AMPK signaling pathway. It has been shown to induce autophagy and protect against neuronal apoptosis following injury. Neurotoxicity Mechanism: Excessive free zinc (zinc excitotoxicity) can trigger neuronal death by overactivating the LKB1-AMPK-Bim cascade, leading to ATP depletion. Metabolic Regulation: Zinc affects the AMPK pathway by modifying the Thr172 phosphorylation of AMPK, which in turn regulates downstream targets like ACC (acetyl-CoA carboxylase).Cellular Energy: Studies suggest zinc exposure can influence energy metabolism by activating the AMPK pathway. In summary, zinc helps regulate AMPK activity, with appropriate levels aiding in energy management and tissue health, while excessive free zinc can trigger toxic, AMPK-dependent cell death. Signs of Zinc-Related Muscle Issues: Difficulty gaining or maintaining muscle mass.Reduced endurance and increased muscle fatigue.Slow recovery after exercise.Slow wound healing. Important Context:Athletes: Athletes are susceptible to zinc loss through excessive sweating and elevated metabolic demand, necessitating adequate intake to avoid muscle performance decline. Cancer Cachexia: Interestingly, excess zinc accumulation in muscles—driven by a protein called ZIP14 during severe illnesses like cancer—can also lead to severe muscle wasting, not just deficiency. Ensuring adequate zinc intake through diet (meat, shellfish, legumes, nuts) is key to preventing this type of muscle loss. Insulin-degrading enzyme (IDE), or insulinase, is a zinc-dependent metalloproteinase (~110 kDa) that breaks down insulin, amylin, and other small polypeptides. It plays a crucial role in regulating insulin levels and is a key target in diabetes research. It is often found in the cytoplasm of human cells and acts with a unique (HXXEH) zinc-binding motif. Key Details About Zinc Insulinase (IDE):Function: Degrades insulin, amylin, glucagon, and amyloid (\beta ) (A(\beta )). Structure: It belongs to the M16 metalloprotease family and requires zinc as a cofactor for activity. Location: Found in mammalian cytosol, peroxisomes, and endosomes. Alternative Names: Insulysin, insulin protease, or bacterial protease III (in E. coli). Medical Relevance: Because it degrades insulin, IDE is studied for its impact on insulin resistance and type 2 diabetes. Key Characteristics:Active Site: Unlike many zinc proteases, it uses an "inverted" (HXXEH) motif to bind zinc. pH Stability: The enzyme has an optimal pH around (7.0).Inhibitors: Its activity can be inhibited by endogenous factors or specific compounds.

@sunsunsun well, avocados are a different thing. With pufas you have the mechanistic biochemistry for why they're bad and that doesn't seem to be wrong.

Trenbolone or nicotine or caffeine or magnesium sulfate (10g) or the combo has reduced my appetite a lot.

@Cicero salicylic acid is also an ultra cheap commodity (you can get pounds for mere dollars from Bezos Mart) so good call there

@alfredoolivas fuck AI

Beautiful (minus the x-ray's in principal).

@Korven random question and it's not that important but just wondering, with your tortillas did you eat raw onions or not? or any other antimicrobial food with these foods and additives that have negative effects in studies due to microbial fermentation (choline, gums, proteins) I think eating antimicrobial foods with it probably lessens or ameliorates the negative effect

Yes, actually. At the beginning of the year, I had a scaly growth on my scalp. I went to a skin cancer clinic to get it checked out, and it was confirmed as a seborrheic keratosis. It was suggested to me by the doctor that it was best to leave it alone, or alternatively I could get electrocautery with the risk of a permanent bald spot. I was unsatisfied with those options so I did some Googling. The solution I found was diclofenac gel. It's an NSAID sold as a topical solution for muscle pains, arthritis, etc. The product I used is sold as "Voltaren Pain Relief Gel 12 Hourly" in Australia, which is 23.2mg/g diclofenac gel (or 2.32%). It's generally suggested to use a strength between 1% and 3% for seborrheic keratosis. I applied it every morning for about 6 weeks and it started to flake off after a few weeks, leaving brand new skin underneath. Completely gone. I'm pretty thrilled because I was told to live with it for the rest of my life. It cost me literally $12 to get rid of it. I hope it helps you too. -- Here's some literature to support it: Diclofenac gel may be a new treatment option for seborrheic keratosis: https://pmc.ncbi.nlm.nih.gov/articles/PMC4886602/ Comparative evaluation of topical diclofenac sodium versus topical ibuprofen in the treatment of seborrheic keratosis https://pubmed.ncbi.nlm.nih.gov/33022801/ Novel Research Regarding Topical Use of Diclofenac in Dermatology—Non-Clinical and Clinical Data https://www.mdpi.com/2218-0532/93/3/34 Comparative study between Diclofenac 3% Cream and 17% Salicylic acid + 2.5% 5 fluorouracil cream in the treatment of Seborrheic Keratosis https://ijced.org/archive/volume/12/issue/1/article/26344/pdf

No evidence for prolactin’s involvement in the post-ejaculatory refractory period Prolactin is released during sexual behavior in male mice. "Baseline levels of circulating PRL in male mice were low for both strains (**BL6 0.86 ± 0.46; PWK: 2.31 ± 1.37 ng/ml; please see ref. 46 for BL6), but are significantly increased during sexual interaction (Bl6: F3,7 = 21.26, P < 0.0001; PWK: F3,8 = 17.18, P < 0.0001; RM one-way ANOVA) (Fig. 1a)." [image: 1778097373887-b12138a6-0a0b-4432-8de4-f8b9628819e8-image.jpeg] Acute prolactin release does not induce a refractory period-like state. "However, the involvement of PRL in the establishment and duration of the PERP is controversial and has not been formally tested" "The fact that PRL levels are already elevated during sexual interaction in BL6 and PWK males further suggests that PRL cannot promote by itself reduced sexual activity, at least in male mice" Mice have different prolactin responses to ejaculation then humans, but it was interesting experiment that does demonstrate how little is known about independent prolactin.

@engineer you dont know ish about the lantic table syrup then, nibba it is actually goyim-coded to think that a 100% maple syrup is better than the above just because the latter is only 5% maple syrup. I have many examples of this. explain to me how rolls Royce is still charging $600k+ for a phantom when they replaced the artful analog and analog/digital combo instrument cluster with basically a rectangular iPad. just because it is luxury doesn't mean it isnt goyim-coded

use the stirrer. who knows if the alcohol solvent leaches the plastic coated stirrer rod tho lol fwiw transdermal t dissolved in straight olive oil with some vitamin e seems to work

Update I did 4 drops (0.25mg) last night and another 4 drops this morning. So far, it's not even CLOSE to what this person and a few others have reported: https://www.reddit.com/r/masturbation/comments/1my2drs/ropinirole_is_a_hell_of_a_drug_nonstop/ So, I've been taking this drug [ropinirole] that stimulates the release of dopamine. Other people have had major trouble with it, but I've been okay with it because suddenly loving masturbating again after a long time has been really cool. I get naked every day, get out the lube, cue up some female friendly, lesbian or bi porn (Shout out to Malena Morgan! You're a fucking girl on girl sexpert and I've cummed to you so many times.) and then I smear myself from ass to tits with lube or petrolatum and rub and prod for at least 8 hours per 24 hour period. This has been going on for at least three weeks. I woke up this morning at 4 and started rubbing and fingering myself. I did have sex last weekend. I was at a party, and some 23 year old kid, a friend of one of my good friend's son, was kind of drunk and REALLY horny. He started hitting on me hard, which I thought was weird and suspicious, but he let me feel his dick, and it was rock hard. He was cute and young with a decent sized dick, so I wasn't going to pass this up. I took him back to my place, and we went at it for 2 to 3 hours. I sucked his dick, and he stuck it in my pussy and my ass. I let him do whatever he wanted as long as it wasn't violent or painful. When he had to come, I told him to come in me, and I held his ass and pulled him deeper as he blew his load. Then he wanted to kiss for about 10 minutes, which was nice. The next morning, he was hard again, and I let him fuck me, of course. It was really good, and I told him he can come back anytime. Now I'm going to lube up and try to get to that point where the orgasms hit like a skipping stone hitting water.

A thought popped into my head; saying dead hanging makes you grow taller is like saying letting your penis hang freely makes it longer. You need more stress than just gravity (which is being countered by your trunk muscles).

Hi Guys, ordered caffeine just now and will make conditioner with caffeine/taurine/aspirin/b3. I use essential oil of rosemary daily before bed and microniddling weekly with 1mm deep. Saw some regrowth, black baby hairs, so it works, but unresolved hypothyroidism and itchiness as a result made me lose them, yep. planning to dilute them in water higher concentrations and use whenever taking a shower to massage in my head. Any idea what else could be in water base conditioner like this?

@alfredoolivas Sure, although my appetite is already naturally pretty low, so the effects might not be that noticeable for me.

@mag-me said: why would high dose aspirin have a negative effect on the liver please explain HD aspirin impact the detox pathway Cyp450 (slow down + remain longer) What does CYP450 do in the liver? The cytochrome P450 (CYP450) system describes a group of enzymes found predominantly in the liver that are responsible for the metabolism of most drugs in clinical use. CYP450 enzymes are typically involved in phase I oxidation, reduction, and hydrolysis reactions within the liver.

@Cicero I'm almost ready to make my own SolBan too and have everything except distilled water. Are you using a magnetic stir plate? It seems like it's the way to get the salicylic acid to dissolve completely but I haven't tried it yet.

this post makes me mad

@Luke lol tbh it is, in a sense, Peaty. It's a party game to play with your friends, and it relies on dice rolls (synchronicity) to win.

@BearWithMe said in Mysterious gallbladder disease - can't digest fat for no apparent reason: I was surprised my PTH is so low because my symptoms and clinical findings (hypercalcemia, hypophosphatemia) exactly match those of hyperparathyroidism, minus the low PTH of course. I agree that this doesn't match up. Not elegant. What would retesting PTH change about it? How much calcium do you take per day? I have not many new ideas since the past ones. I'd rather do a full electrolyte panel (Na, Cl, K, Ca, Mg), kidney function, total protein, urea, uric acid, complete blood count, liver enzymes, cobalamin and H. pylori IgG & IgA immunoblotting, all in serum. And consider artichoke leaf extract and pinning Bpc 157.