George Ferman

If you want to read 100+ detailed articles (some are 70 pages long) with real scientific resources on topic such as gut health, hormonal health, brain health, supplements, peptides, fatigue, skin health, hair health, autoimmune conditions etc Go here: healthlibrary.substack.com/archive

A great way to get rid of a lot of useless fear, anger, sadness and so on is to actually read about what happens in your body under these states. It's way worse than you probably think, so it's a good idea not to poison your body for no solid reason.

"I feel so great on vacation and don't know why starter pack": -Eats actual food instead of ultra-processed sludge + pesticide residue -Grounding -Got out of a mold-infested house (unaware of it) -Low stress -High step count -Sunlight -Brain finally stops receiving the same inputs, in the same spot and does the same thing (most still can't comprehend that this is not normal for the human brain)

You are probably downplaying how many chronic health problems are partly the outcome of the fact that most people no longer get 12-17K steps a day outdoors and stop seriously lifting after like 35 because this doesn't apply to you. We are literally designed to move outside and we can't emphasize the dangers of a sedentary lifestyle enough.

@biohacker 🫡

@Helios_Movement Great thread George!

Pro-opiomelanocortin (POMC) is often the missing link for recovering from issues such as mold illness, obesity, depression, ED and more. Here's what you need to know about the archetypal polypeptide precursor hormone. Thread🧵

Who would have thought?

Chronic diseases are skyrocketing: -76.4% of American adults -30% of children -Nearly 60% of young adults are currently living with at least one chronic condition. This is insane and shouldn't become normalized. Even the number of individuals aged 20-24 years living with cardiovascular disease increased by 37%, almost 1 in 3 Americans will soon have NAFLD and 60–70 million Americans are affected by digestive diseases. So here's a brief summary of why we ended up sick within a few decades. Thread 🧵

This is partly one of the reasons why boosting NAD+ can suppress follicle atrophy and stimulate hair elongation in animal studies (there's a small human one as well in women). But most likely a B3 pill that costs cents can do more for you than a $400 NAD+ drip. Here's why🧵

Finasteride can come with a higher cost than most men are willing to pay, whether that's your d*ck literally not working for years (or even forever) no matter what you try or severe depression. Now you can do whatever you want, this post is just an attempt to help you make an informed decision. Use finasteride, don't use it. It makes no difference in my life. But handing over something THIS potent to EVERYONE as the go-to treatment is very problematic. For example: 1. Finasteride reduces the conversion of testosterone to dihydrotestosterone (DHT) and these effects on androgen signaling influence AR function and related pathways. In case it’s unclear: DHT has a higher affinity for ARs than testosterone (2–10 times stronger binding) and thus by inhibiting 5α-reductase it reduces AR activation. 2. Since ARs regulate gene expression through binding to androgen response elements (AREs) finasteride result in decreased transcription of DHT-dependent genes. 3. Reduced DHT levels can disrupt the hypothalamic-pituitary-gonadal (HPG) axis. So it giga fries your androgen receptors. Why does our body even need androgen receptors? Because the places where hormones are produced and the places that are utilized are not the same. So these receptors bridge the gap between hormone production (in the testes for example) and their action in distant tissues (the muscles for example). I hope that this was pretty simple. Now these intracellular proteins function as ligand-activated transcription factors and mediate the effects of androgens as you might be able to tell. They are expressed in a wide range of tissues such as the prostate, testes, seminal vesicles, epididymis, skeletal muscle, bones, hair follicles, sebaceous glands, hypothalamus, pituitary, liver, adipose tissue and cardiovascular system. So when we pair the effects of androgens with the tissues which ARs are expressed, we can better understand why their activation leads to sexual development, enhanced protein synthesis in muscles and osteoblast activity in bones, the regulation of lipid metabolism, insulin sensitivity, energy homeostasis but also how they modulate mood, cognition and sexual behavior (and plenty of other neurological effects (ARs in the hippocampus and amygdala for example greatly modulate stress-related behaviors)). ARs exists in an inactive state in the cytoplasm, bound to heat shock proteins (HSPs) and other chaperones, which stabilize it until ligand binding occurs. When it comes to the domains of ARs: -The N-terminal domain (NTD) contains activation function 1 (AF1), which is involved in transcriptional activation. It interacts with co-regulatory proteins to modulate gene expression. -The DNA-binding domain (DBD) contains zinc finger motifs that allow the receptor to bind to specific DNA sequences called androgen response elements (AREs) in the promoter regions of target genes. -The hinge region connects the DBD to the ligand-binding domain and contains a nuclear localization signal (NLS) to direct the receptor to the cell nucleus upon activation. -The ligand-binding domain (LBD) is located at the C-terminus, this domain forms a pocket that binds androgens with high specificity and affinity. It also contains activation function 2 (AF2), which is critical for recruiting co-activator proteins after ligand binding. Now chromosomes are structures in the nucleus of cells that carry genetic information in the form of DNA. Each chromosome contains many genes, and we typically have 46 chromosomes (23 pairs), including 22 pairs of autosomes (non-sex chromosomes) and one pair of sex chromosomes (XX for females and XY for males). Males (XY) inherit their single X chromosome (and X-linked genes) from their mother and the Y chromosome from their father. Females (XX): Inherit one X chromosome from each parent. Mitochondrial genes are also inherited solely from the mother, as mitochondria (and their DNA) come from the egg. Why do these matter? Because the AR gene, is located on the X chromosome (Xq11-12). Males, inherit their single AR gene from their mother’s X chromosome. The father contributes the Y chromosome, which lacks AR. Thus, for males, the androgen receptor is exclusively inherited from the mother’s side. Females, inherit one AR allele from the mother and one from the father (via his X chromosome). If these were too complicated here’s a brief summary of how androgen receptors work. A molecule of an androgen hormone slips through the cell’s outer membrane since it’s fat-soluble, it finds the androgen receptor and goes to the ligand-binding domain (LBD) in the cytoplasm. This causes the receptor to change shape and kick off the heat shock proteins (HSPs) in order to expose parts of the receptor that were hidden. Once activated, it travels to the cell’s nucleus with the help of nuclear localization signal (NLS) in order to influence the cell’s instructions (DNA is stored in the nucleus). Once in the nucleus, two activated receptors “team up” (just an analogy for dimerization) to form a “homodimer” which then binds to specific spots on the DNA called androgen response elements (AREs). In order to modulate gene expression, the receptor needs help from other proteins called co-activators or co-repressors that “open up” the DNA (by adding chemical tags to histones, which are like spools that DNA is wrapped around) or “close it off” to control whether genes are turned on or off. They also connect the receptor to the cell’s machinery that reads DNA. Then all these instruct the cell to make specific proteins by turning on or off certain genes, which then carry out the androgen’s effects. In order to understand how we can have healthy ARs and improve their function, we must remember that the activity of ARs is regulated by: -Ligand availability (controlled by enzymes like 5α-reductase and aromatase). -Co-activators such as SRC-1 and CBP/p300. -Co-repressors such as NCoR and SMRT. -Phosphorylation, acetylation and ubiquitination -Feedback mechanisms: Androgen signaling regulates the hypothalamic-pituitary-gonadal axis, controlling testosterone production. "So how do i know if i will get PFS or not". You don't know. But if your testosterone levels are already low for example, if you have insulin resistance or if you are in any medication such as SSRI, your chances of getting it skyrocket. "So how can i solve my PFS?" No one really knows with 100% certainty that's what makes PFS so scary. But i will save you the expensive coaching and creams by summarizing what everyone agrees upon. Ground zero: Wok on testosterone and overall androgen levels and manage estrogen.ncbi.nlm.nih.gov/pubmed/14556282 Even DHEA for example can increase ARs. Number 1: Fix your sleep and circadian rhythm. Poor sleep impairs testosterone production and AR expression through multiple mechanisms. It reduces testosterone production in Leydig cells for example, downregulates AR expression and lowers luteinizing hormone (LH) pulses. Number 2: Relax/manage cortisol. Chronic stress elevates cortisol, which can suppress AR sensitivity by competing with androgen signaling pathways, as cortisol binds to glucocorticoid receptors (GR) that interact with ARs. Adaptogens such as rhodiola or holy basil might also help to reduce cortisol in some people. Number 3: Get sunlight and go measure your vitamin D levels. Vitamin D not only enhances testosterone production but also boosts AR function. Number 4: Avoid digital overstimulation. Chronic overstimulation which is very easily accomplished these days through digital means, may deplete dopamine levels and desensitize dopamine receptors (D1/D2) in reward-related brain regions like the nucleus accumbens. Basically, by causing these unnatural dopamine spikes frequently, we are downregulating dopamine receptors and the problem is that dopamine signaling is linked to AR function. Try a combat sport instead of scrolling.pmc.ncbi.nlm.nih.gov/articles/PMC42… Number 5: Avoid endocrine-disrupting chemicals Things such as bisphenol A (BPA), phthalates and pesticides not only bind to AR as antagonists, preventing androgen binding, disrupting testosterone synthesis by inhibiting steroidogenic enzymes in Leydig cells but they also alter AR expression. Number 6: Regulate proinflammatory cytokines. Pro-inflammatory cytokines such as TNF-α and IL-6, suppress AR function by downregulating AR expression, increasing cortisol production and disrupting testosterone synthesis. Number 7: Avoid heavy metal exposure. Heavy metals bind to ARs and act as antagonists and inhibit testosterone synthesis through toxicity to Leydig cells (cadmium for example mimics estrogen). Number 8: Get a wide range of micronutrients. Deficiencies in key nutrients like zinc, magnesium, B vitamins, selenium and potassium impair AR function. But just like everything, an excess has the exact opposite effect so prioritize whole food sources over supplements when it comes to covering your baseline needs. Number 9: Avoid excessive alcohol consumption. Chronic or excessive alcohol intake disrupts AR function by suppressing testosterone production through inhibition of LH and steroidogenic enzymes, increasing oxidative stress, which impairs AR signaling, and promoting aromatization of testosterone to estrogen, reducing androgen availability. Number 10: Heal your gut An imbalanced gut microbiome (dysbiosis) can impair AR function by increasing systemic inflammation via leaky gut, which elevates cytokines that suppress AR, reducing short-chain fatty acid (SCFA) production which supports testosterone synthesis, and altering bile acid metabolism, which influences steroid hormone regulation. Gut bacteria also modulate estrogen metabolism, and dysbiosis may increase estrogen levels, reducing androgen availability. Number 11: Support your thyroid. ncbi.nlm.nih.gov/pubmed/8568470 Number 12: Fix your mitochondria. Mitochondria are critical for cellular energy production (ATP via oxidative phosphorylation, OXPHOS) and steroidogenesis (testosterone synthesis in Leydig cells). Number 13: Go train. Training is taken for granted a lot of the time, but it’s one of the fundamental aspects of hormonal health that should never be neglected. pubmed.ncbi.nlm.nih.gov/19429451/ ncbi.nlm.nih.gov/pubmed/15354030 Number 15: Eat post workout and do not eat right before going to bed. ncbi.nlm.nih.gov/pubmed/16826026 Number 16: Do not use NSAIDs (aspirin can be excluded from this) for no real reason. pubmed.ncbi.nlm.nih.gov/12917209/ Number 17: Consider ALCAR or niacinamide if your methylation status is fine. There are other supplements that can help such as forskolin, tribulus and maybe even lithium orotate for example. But if you are just starting out stick with ALCAR since it’s a better bang for your buck and forskolin needs regular blood work, tribulus will make more people hypomanic compared to ALCAR and lithium orotate interacts with a lot of medications and will blunt emotions for some people. I am not saying that these are useless, but i am saying that ALCAR is a better starting point. That's all. For more: fitandball.gumroad.com/l/dfgdfgdfgfg/…

When it comes to zinc and hair loss, in AGA the results are quite mixed and getting more zinc shouldn't be your number 1 priority. But if you have alopecia areata or TE, maybe it should. Overall, here are the top signs that your body is starving for zinc 🧵

An extremely neglected aspect of hair growth/slowing down hair loss is monitoring inflammation. Here's what you need to know. Thread🧵

Insulin resistance can severely exacerbate hair loss and even trigger it in susceptible individuals. There's up to a 68% increased risk of severe central scalp hair loss with type 2 diabetes. But it's no wonder why: -Chronically elevated blood sugar causes damage to the microvasculature (small blood vessels) of the scalp. -Diabetic hyperglycemia frequently induces mitochondrial dysfunction and an overproduction of reactive oxygen species (ROS), which can trigger premature cell death in hair follicle stem cells. Despite these facts, if you have T2D, there are some things you can keep in mind to help restore balance. Thread🧵

Vitamin D is probably a minor reason why lard reversed hair loss in this single case as well. *No, lard won't regrow your hair. MUFAs probably played a bigger role. **Can muslims use this btw? (i am not joking)

Oxidative stress is now recognised as a major underlying catalyst for hair loss and premature hair graying. Here are a few things worth knowing. Thread🧵

"In all, our three-dimensional co-culturing revealed mitochondrial dysfunction in balding DPC, suggesting a metabolic component in the aetiology of AGA".

Revealing the root causes of hair loss (with actual proof). An entire guide on understanding the common myths, realities, the real root causes and what to do about them. Thread🧵

Recent research strongly links hair loss to mitochondrial dysfunction. This obviously makes sense since hair follicles, being some of the fastest-dividing cells in the body, require massive amounts of ATP. So when mitochondrial dysfunction is present, the energy supply plummets, triggering cellular stress and hair follicle degeneration. Here are a few things that might help. Thread🧵

Plenty of times, your depression doesn't start in your head, it starts in your mitochondria. A lot of mental illnesses can be viewed as a "brain energy crisis". To demonstrate this point, here's for example an ancient enzyme system that not only controls your mood but is also key when it comes to resolving some side effects of psychiatric medications. Thread 🧵