References: Wikipedia, Science Direct, Critical Care, Front Immunol, Future Microbiol., Science, Cell Phys, Jr Biomed Sci, Dermatoendocrinology,
Did you know you make an antibiotic called Cathelicidin? Yup! It’s a peptide otherwise known as LL-37. It makes a circular pore that basically binds to the cell wall of bacteria and then makes all their guts leak out. You don’t make it until your Vitamin D level is 32. Now, in Wisconsin, our D levels get to around 20 in the winter if you are Caucasian and less if you have any pigment in your skin. In summer, Wisconsin Caucasians get to 45 and make Vitamin D in response to sunlight. More skin pigment, less Vitamin D production (but better folate protection). Consequence: we get more flu and colds in winter because of less Vitamin D, resulting in lower cathelicidin. We used to treat tuberculosis by sending folks off to the mountains where they got fresh mountain air and sat in the sun. (So, they were actually getting more UVB radiation at high altitude, making more Vitamin D – raising their cathelicidin levels: LL-37)
Ok, so you tell me what you think would happen with patients in an ICU with sepsis, systemic infection in their blood when you study Vitamin D and cathelicidin levels. You got it. In 121 ICU patients, those with the top third of Vitamin D levels had 4.5 times LESS mortality than those in the bottom third, which also correlated with their LL-37 levels. Know any antibiotic that works that well? Hmmm. How about looking at over 10,000 patients starting dialysis and examining mortality from infection over the next year. Again, the lowest third of Vitamin D and LL-37 have double the mortality from infection.
Let’s expand our view of our immune system and look at cancer. What role does LL-37 play here? Once again, we find that Vitamin D turns on cathelicidin/LL-37 and that kills cancer cells. The mechanism in cancer doesn’t appear to be quite as simple as in bacteria where LL-37 just punctures a hole in the wall. In cancer, LL-37 binds to the surface of the cancer cell and mucks up its reproduction. But it works, on almost every kind of cancer.
Any human studies with LL-37 given in sepsis? Not that I can find. Lot’s of mice and rat studies, where it shows it helps. But we are getting a little far off the reservation when we jump to humans.
The theory is good. The toxicity is low. The activity is there. Would you do it?
WWW: What will work for me. This is the dilemma we are in. We can now purchase these powerful chemicals on the gray market. Not super cheap but not unattainable. The ability to manufacture them allows a new frontier of medical exploration. Am I ready for using it? Not really sure until you get into the right circumstance. If all else is failing, would you add this to your armamentarium? What I would do is make dead certain my Vitamin D level is sufficient. We are now nearing fall when the angle of the sun becomes such that we don’t make enough Vitamin D. 100,000 a month, 20,000 a week, 5,000 a day are doses that work. Do one of them.
- LL-37 is what? Answer: a peptide we mammals make that kills bacteria and viruses.
- How does it do it? Answer: It burrows into the cell wall of the bacteria and all their contents leak out.
- What Vitamin induces you to make your own LL-37? Answer: Vitamin D
- What blood level do you need to have to make your own LL-37/cathelicidin? Answer: 32
- Do we get more cancer in winter than in summer? (Just like more flu). Answer: Yup!
That’s it. It’s all in the title. If you want to sleep better at night, take a warm bath 1-2 hours before bed.
Ok, how does it work? This is a bit counterintuitive. Your natural 24-hour circadian cycle has a lower temperature at night at part of that rhythm. In some folks, it can be as much as a couple of degrees. You sleep better in a cool room because it helps cool you down. And in these lazy dog days of summer, you may have a bit of trouble sleeping well when it stays too warm at night.
How does a warm bath cool you off? That’s the interesting puzzle. When you warm up your skin with a shower, you dilate all your blood vessels over the surface of your body. Then, as you dry off you radiate off all your inner heat. The net effect, you are cooler an hour or so later. The fives minutes of warming is made up for by the hour of cooling.
How big an impact does it have? Well, if you take zolpidem every night to sleep, it allows you to fall asleep 16 minutes faster. And then you are addicted and can’t get off of it. Take a warm bath and you fall asleep 7 minutes faster than controls. Cheaper, less addicting.
Or, you could just try taking some glycine at bedtime too. Glycine, simplest amino acid. Turns out it also helps cool you down at bedtime by its effect on NDMA receptors.
So, there you have it. Two nice strategies to help you get to sleep.
WWW: What will work for me. I’ve just changed my bath time. I going to try bedtime showering instead of morning. Check-in after a month and I’ll let you know if it worked for me. And I ordered some glycine. And, I turned the AC down an extra degree last night.
- How much sooner do I fall asleep if I take a warm bath in the evening? Answer: About 9 minutes earlier than controls.
- How does that work? Answer: Paradoxically by dilating your surface blood vessels which is your natural radiator. You then dump all the heat stored up in your body that you naturally rid yourself of. If you are insulated with a layer of “insulation”, it may take you longer to dump the heat.
- I thought I had the same temperature all day long? What gives? When is my temperature the highest and the lowest? Answer: It follows your circadian rhythm. You peak cortisol in the morning which generates the access to energy and then you peak your temperature in the afternoon, a couple of hours later. Lowest temps are then in the middle of the night.
- What other strategies help me sleep? Answer: Cooler bedroom. Good and dark. Glycine, 500 mg at bedtime. No noise, no nightlight. Precise same time every night. Dim the lights an hour or two earlier. Don’t introduce fear into your heart with violent TV just before bed.
- Does counting sheep help? Answer: Not to be glib, but yes. You can call it mindfulness, or meditation, or counting……whatever. But there is pretty good evidence that taming your “monkey chatter” by disciplining your brain so a boring, calming, mundane train of thought allows it to then slip into sleep. In the one mile loop in our neighborhood, there are 54 houses on both sides of the road. If I recite them in my head, one by one, I mostly don’t make it around the whole loop. You are falling asleep just reading out it…..
References: Wikipedia,Mol Biol, Nature, Molecular Cell, J Am Chem Soc, Science, Hematologist,Proceedings Natl Acad Sci., Ann Clin Lab Sci., Cancer Research, Cancer Therapy,
Ready for a deep dive into how to kill cancer with peptides? This is real and it’s coming on the scene soon. Very exciting.
First, we have to start with how cancer cells become cancer cells. A normal cell develops, does its function, then gets out of the way with an organized, sensible collapse of the mitochondria. That leads to the term apoptosis, or cell death of the whole cell. When it’s done properly, it makes no inflammation and the cell gets “processed”. It is then replaced with a new baby stem cell of the same tissue. The gene that mediates that is the p53 gene. The p53 gene is essentially your watchdog for DNA damage that gets activated when the cell DNA gets too far broken and sets in motion a process of making the mitochondria get leaky. In swoops p53, the cell dies in an orderly fashion and the whole organism survives. You get a new liver cell, heart cell, skin cells, white blood cell….. and life goes on.
In cancer, something else happens. Cancers aren’t a problem because they are multiplying too fast. (Well, they do in some circumstances but bear with me.) The real problem with cancer is that the cancer cells live too long. Way too long. And just about every cancer depends on an “altered” p53 gene as part of its tool kit to live forever. We actually know down to the molecule how that happens in the majority of cancer cells. You read language like: “sequestration of the p53 in the cytoplasmic body correlates with the ability of the E18 55-kDa to repress p53-dependent apoptosis.”
Did you get that? Cancers all have a broken p53 system. What would happen if we repair it? What would happen if we put a proper p53 back into place? There’s a peptide for that! It’s actually probably all about protein folding and shape that gets us what we want. Cellular origami, if you will. You gotta know when to “hold em, and when to fold em“.
I don’t want to kill you off trying to explain it but it comes down to a tumor gene called Mdm2 that suppresses our friend p53. There is a binding site on Mdm2 that attaches and inactivates p53. It happens to have a peptide that fits right into it. Disrupt Mdm2 binding to p53. p53 refolds itself properly. It goes to work. It discovers all the broken DNA in the cancer cell and gets to work killing it. Cancer cell dies. Viola!
Ok. Get to the point. How do I get the peptide into the cancer cell? PNC-27. It’s actually a fragment of the Mdm2 protein. That’s what peptides are; fragments and pieces of bigger proteins that fit into the molecular lock and activate it.
There is a peptide called penetratin with a peptide sequence, KKWKMRRNQF- WVKVQRG. (Pronounce that for me.) Add that to the Mdm2 fragment so you can transport it into the cell, and lookout cancer! All with no toxicity to normal cells. p53 is your friend. Activating it is no big deal if your cells are normal.
There must be a fly in the ointment somewhere. There is. It takes 72 hours of continuous exposure to kill the ALL the cancer cells. How to do that? Tricky. Inject it into the tumor? Nope. The cancer is in too many places. Get it past your gut with a very slow-release form? That may be possible. Sound exciting? Hold on. The FDA has issued a warning about the premature enthusiasm. But there are clinics in Mexico administering it. There is experimental evidence it kills breast cancer in 30 minutes. Pancreatic cancer may need longer. The problem is not with the peptide. It’s the wild cat labs making the polluted or adulterated stuff that has it contaminated and has given some folks sepsis. What would you do?
WWW: What will work for me. I’m all over this with interest. If it causes no toxicity, and you are in a tough spot, would you try it? Do you have the right to do it? This is all sufficient material for a graduate course in medical ethics. Is there hope for the future? You bet. Would I try it on myself if I were in that spot? Anyone not caught up with the awful disease cancer can’t tell folks who are what they should do. My opinion. Some of the best research out there is with pancreatic cancer, one of the worst.
- What is the name of your own natural cancer cell killer protein? Answer. P53. Your friend.
- What happens in most human cancers that make p53 unavailable? Answer: It gets “sequestered” and refolded or attached to another cancer-associated protein called MdM2. In any case, it isn’t there to do the job of killing off a cell with too many DNA mutations.
- What is PNC-27? Answer: It is a fragment of Mdm2 that is the binding part to p-53. That appears to release P53 from its clutches so it can do its job of initiating cell death.
- What is the key peptide discovery to get PNC-27 to where it needs to do its job? Answer: Scientists had to find a way to get the blocking fragment into the cell through the cancer cell wall. They did that with a transporting peptide called KKWKMRRNQF- WVKVQRG. (Save that spelling for your next Scrabble)
- How quickly does PNC-27 work in lab samples? Answer. Between 30 minutes with some breast cancer lines. 72 hours for other cancers.
- Would you sign up for a 3 day IV of a drug that has zero toxicity to human cells if you had a wicked, aggressive cancer? Answer: You talk here.
- The FDA has issued warnings about PNC-27 because? Answer: there are so many desperate folks that crooks are taking advantage and selling awful, adulterated stuff and some folks have gotten sepsis.
References: Wikipedia, Jr of Atheroscl Res, Vet Research, Arch Fac Plast Surg, J Peri Nerve Sys., Genome Med,
If you have been to a beauty salon in the last 30 years and been asked if you “Would like the peptide skin treatment” you have been exposed to GHK-Cu already. It stands for a simple three amino acid sequence: Glycine, Histidine, Lysine. It strongly binds copper and is in you right now at about 200 ppm if you are 20, and at 80 ppm if you are 60. This is aging in a nutshell.
How can you demonstrate it’s importance? A scientist by the name of Loren Pickart in 1973 reported that liver cells from older folks (60-80) started functioning like they were from younger folks when they were exposed to their serum, eventually isolating the peptide.
By the 1980s, GHK-Cu was being found to be involved in wound repair with upregulation of collagen synthesis and impact on the metalloproteinases that dissolve and break down tissue. By 2003, rat research with full thickness woundsshowed wounds would heal by 67% compared to 28% with GHK-Cu. A study in humans with diabetic wounds showedsimilar dramatic improvements.
But let’s talk about the important stuff: women’s wrinkles and men’s hair. One study showed that applied twice a day to faces with wrinkles, the “copper peptide” dramatically reduced wrinkles. Men’s hair transplants survived and thrived better with it too. You can’t find many facial treatment creams today that don’t have a bit of it in it – at least if you are paying top dollar.
But cosmetics is only the tip of a very large iceberg. Turns out GHK-Cu turns on and off hundreds of genes. The implications of this might be huge. For example, radiation causes all sorts of damage to the DNA of healthy cells. GHK-Cu helps those cells recover. If you have a head and neck cancer, and are getting radiation. Make sure you are on it. How about any radiation? It helps with damaged nerves with peripheral nerve damage. In folks with severe COPD, it upregulates hundreds of good genes and downregulates hundreds of destructive ones.
Or is it all about the copper? Copper is an incredibly important metal that is a two-edged sword. Too much of it is way toxic on the brain. Too little, and you can’t repair. We have copper pipes in most of our homes and are being exposed to lots of metallic copper. Could our lower level of this important peptide by a natural response to too much copper in our environment. All conjecture. But the conversation is now starting around using this healing peptide for cancer care, for COPD, for diabetic wounds. Stay tuned. This is an interesting time.
WWW: What will work for me. I’m reading and learning about the use of peptides as fast as I can go. This is just another in the series of miracles our body pulls out and shows us. The hundreds of genes that are affected by GHK-Cu at the genomic level leads to believing that the next revolution in health will be about expertly managing your peptides, after reading your genomic signature. One step at a time. I’m working on getting the peptides under my belt.
- GHK-Cu binds what metal? Answer: If you don’t get this one, …
- Most American homes have what type of water pipes? Answer: Copper
- As we age, what happens to our GHK-Cu levels? Answer: Drops 60%
- In COPD, how many destructive genes are downregulated with GHK-Cu? Answer: Go read the link, it’s over 100 so far that we know of.
- f you had a diabetic wound on your leg, or a diabetic nerve damage, or radiation to your face, or breast, or prostate, would you want to take some? Answer: Too early to tell, but no known toxicity to date and lots of interesting, tantalizing data.
References: Wikipedia, Medline Encyclopedia, Neuroimag., Proceeding National Acad Sci,Neuropsychobiol,
As we get older, we spend less and less time in delta wave or deep, restorative sleep. That’s not just annoying, it’s dangerous as we now know that sleep is your brain on flush. Your glymphatic system opens up in your brain when you are in deep sleep, the flow of waste fluids increases several fold, your brain shrinks as it is wrung out and your brain tissue is cleansed of all its accumulated gunk. This is so important to the brain that every creature with a brain has to sleep. And if we don’t get a good night’s sleep,we suffer with accumulated detritus and eventually call that damage Alzheimer’s. No kidding!.
That’s the conundrum. You need a good night’s sleep to clean out your brain, and you gradually lose the ability to get that sleep. There you have it. And it is so self-evident, you don’t need to argue the point. You know it in your heart. A good night’s sleep feels good.
Want a shot at something better? Not happy with the drugs on the market that make you feel groggy, get you habituated, stop working and make your doctor antsy about your repeated requests? Here you are….maybe.
DSIP is not a perfect cure but it does appear to work. Delta sleep is the sleep in which you really are in the deepest, most restorative state. It’s what fades with aging. DSIP is a tiny peptide that is only 9 amino acids long. It’s gene hasn’t been found yet but it has been detected in all sorts of places from mothers’ milk to the gut, the hypothalamus, the limbic system. It appears to show up in lots of places and appears to have its effects modulated by ACTH, TSH and many other hormones. When modulated and stabilized so that it has a longer halflife, it appears to have powerful antioxidant effects, anti-cancer effects, geroprotective effects, goodness. Way beyond the scope of what we are trying to introduce but in line with many peptides that appear to have all sorts of effects beyond their initially discovered effect.
So back to sleep. It doesn’t put you to sleep. Its effect appears to be to lengthen the time in deep, delta wave sleep. It’s as though it is increasing the length of the wash cycle on your laundry machine. But that effect may be huge and anything in that category may be a worthy experiment for anyone with concerns for cognitive decline. (All of us.)
Are there detractors? Yes, one study says it doesn’t work very well. It could be countered with the comment that the authors didn’t try very hard either. Only one dose and one timing schedule. How about a bit more effort guys?
How do you take it? It appears that you should start with 0.1 mg just an hour before sleep three times a week. The folks who are teaching how to use it suggest that if you don’t feel a restorative sense from it, walk the timing back to earlier in the day. Take it at supper time for a week, then back to 2 pm. I’ve heard of some folks being dosed at 9 am, with good effect. Proven research on it? Precious little, but all sorts of interesting effects on growth hormone, chronic pain, ACTH. Side effects? Nope. Worth a try?
WWW: What will work for me. This gets back to the issue of the risk-benefit ratio. We don’t know much about these peptides but there are people reporting beneficial effects. With no evident side effects. Deep sleep is very valuable. I’m going to buy an Oura ring that tracks sleep and wear that while I explore my own effect. The Oura ring is a new device out of Finland that details on your smartphone your sleep patterns. Might be quite interesting.
- DSIP stands for? Answer: DELTA sleep-inducing peptide but you can sure put it DEEP for Delta
- What is the beneficial effect of sleep? Answer: it is your brain on flush, and it happens best in deep sleep. Accumulating gunk like beta-amyloid is a leading consideration in the cause of cognitive decline. As is lousy sleep.
- How do you take it? Answer: A sub Q shot of 0.1 ml at 1000 mcg a milliter three times a week, an hour before bed. If no effect, drop back to earlier in the day.
- How can you measure your benefit? Answer: Buy an Oura Ring. Another clever idea out of Finland.
- Where can you obtain pure DSIP? Answer: Best we know right now, are compounding pharmacies that sell you USP product. A physician is permitted to legally prescribe USP grade product in many states if not available through traditional pharmacies. Informed consent and all that.
- Side effects? Answer: Yes, mostly good ones, as best we can tell. You get pain relief, more growth hormone, better sleep, better cortisol, better thyroid….well, better? Augmented and changed. Time will tell if better. Clinical research is the ultimate answer. We need young PhD students to get on it.
References: Wikipedia, Jr Neurosurg, Drugs Today, J Amer Geriat Soc,
Cerebrolysin isn’t just one peptide. It is at least four. It is derived from pig brains, sort of the way insulin was initially derived from pig pancreases. (Insulin is a 51 amino acid peptide – the first and most famous of peptides.). It is a mixture of growth factors. BDNF (Brain-Derived Neurotropic Factor) is the most important but there are others. GDNF (Glial cell-line Derived Neurotophic Factor), NGF (Nerve Growth Factor) and CNTF (Ciliary Neurotrophic Factor).
All of these peptides are critical players in keeping your brain healthy. And many of them are absent or markedly reduced as we age.
BDNF is critical to long term memory. Most of our brain neurons are formed prenatally but memory requires new ones. BDNF is central to that.
GDNF is critical to the survival of motor and dopamine-secreting neurons.
NGF was found back in the 60s (earning a Nobel prize) and is critical to the growth of new neurons, but also to beta cells in the pancreas.
CNTF (Ciliary Neurotrophic Factor) is just as intriguing. It helps make your neurotransmitters and connect the neurons to each other.
We could spend all day in the details of each of these and I would encourage any reader to do so. Just Google away, starting with Wikipedia and off you go. It is fascinating physiology, central to how a healthy brain works. What happens if your brain isn’t so healthy? What would you want for your brain if you had a concussion? A stroke? Parkinson’s? Alzheimer’s?
For example: concussion. The shock wave of bonking your head disconnects millions of neurons. Folks report feeling brain fog for years after a concussion. This articlereferences the safety and beneficial effect of cerebrolysin on concussions in 55 people – published in 2005 – 15 years ago! Last year a rat study done in a randomized way showed statistical improvement. The CAPTAIN study in Asia has been started but doesn’t have results yet in humans.
How about cognitive decline and Alzheimer’s? There is early research that indicates it’s helpful. A pretty well-done study from Korea in 2000 showed benefit.
Parkinson’s Disease? Ditto! Rat studies and temptation’s in humans but still waiting long term trials.
Cerebrolysin is being widely used all over Asia. It’s actually pretty cheap. Therein lies the explanation. Why hasn’t it been used in America? It doesn’t have the promise of being a blockbuster drug that reverses these horrible illnesses. And because it’s in the public forum, it can’t be patented.
Does it cause harm? NOOOOOOO!!!! No adverse side effects. These exact same neuropeptides are in you. And I’ve heard of anecdotal cases with dramatic effects.
WWW: What will work for me, or you? Wow, if I have a severe concussion, I want to be able to crawl to my office and give myself big IV doses of cerebrolysin. I’m adding it to my offering to anyone with concerns of cognitive decline. I think everyone deserves a trial run of it. It can be given IV or by insulin shot needles in your tummy. It has no toxicity that we have detected. The other half of the Hippocratic Oath is “If there is something that helps more than what there is out there now, and what we have now is worthless, don’t withhold it!”
- Cerebrolysin is derived from? What? Answer: Pig Brains
- It is a mix of how many neuropeptides? Answer: At least 4 that we know of.
- What does BDNF stand for? Answer: Brain-derived neurotophic factor, the most most important brain factor.
- We have great research that shows it causes dramatic effects? Answer: Whoa Nellie. We have great anecdotes in acute concussion of dramatic effect and statistically valid rat studies but human studies are mostly overseas, where it is the best act in town, but still not curing.
- If you were fuzzy and couldn’t drive anymore because you weren’t sure you would find your way home, what would you do? Answer: Your call.
References: Wikipedia, Eur Jr Appl Phys, Cell Metabolism, Nature, FEBS Press,
Bear with me because this is the crux of aging. Bit by bit, your cells get tired, and senescent. They are still there in your tissue, but they don’t respond to signals and they don’t do their job, whatever tissue they are in. The mitochondria don’t talk to the nucleus and vice versa. Slowly they drift into cell death. You are done. That process shows up with the mitochondria losing their ability to make energy and gradually making more “oxidants”. We have frantically been taking anti-oxidants for decades, hoping that will help. Anti-oxidants soften the blow but don’t wake up the conversation between mitochondria and nucleus in each and every cell. Without that conversation between mitochondria and nucleus the inevitable slide into senescence continues.
That’s the key to reversing aging: waking up that conversation in aging cells (you) between your mitochondria and your nuclei. Now, if you exercise like crazy and induce a shortage of energy in each cell (pushing your muscles and cells to the point of exhaustion – that last pushup, curl, pump, lift) your mitochondria startle, send out help messages to the nucleus, and you start the conversation. That’s why exercise helps. Its effect lasts a few days. You can accelerate that with blood flow restriction training because you hasten the exhaustion of energy supplies. Ditto with Fast Mimicking Dieting: you turn on the conversation between nucleus and mitochondria because you exhaust energy supply and call the internal cellular 911 system. Fast mimicking’s effects last a few weeks to months.
Or, you can use CJC-1295/GHRP2 (Growth hormone inducing peptides). Growth hormone inducing peptides in your body do the same thing as exercise and fasting when it comes to waking up the conversation between your mitochondria and nuclei. What not to like? CJC-1295 is a growth hormone releasing hormone analog. It is a slight alteration of the original hypothalamic hormone but effectively results in the very prolonged release of growth hormone from your anterior pituitary. Your normal process of releasing growth hormone happens when your hypothalamus puts out GHRH (growth hormone releasing hormone) which then stimulates your pituitary to make it. Its use is not without controversy. CJC-1295 was being developed as a drug but one of the subjects taking it had a heart attack and diet. It was “ruled” to have been a random, non-related event, but it killed the clinical trial. Wikipedia refers to the “gray” market for bodybuilding but two minutes on Google will show you a lot more. (The deep dive can get into more detail, but the complexity would put you to sleep…..)
This topic of bringing understanding to the aging process is starting to burrow down into that space: how do we wake up those senescent cells in every tissue in your body? That’s the frontier. Getting a handle on the mitochondria-nucleus conversation has become the key topic. I even found it mentioned in this week’s AARP Magazine titled “Can A Single Pill Keep You Healthy Till 100?”.
WWW: What will work for me? I’m trying to learn this just as fast as I can go. I have now done 5 days of fasting for 14 months in a row and have lost about 15 pounds doing it. I can feel my brain perking up when I do my 5 day fast mimicking thing. And I’m trying to exercise using the 2 mile a day formula with daily pushups and situps. I want to learn the 4 minute high intensity workout, maybe with blood flow restriction. I think I’ll do a column on that (BFR) when I’m off my peptide kick. Am I ready to advise that people use CJC-1295? I want to educate you and me. You are an adult reader and can make your own decision.
- How does your body release growth hormone? Answer: Simple, from your pituitary gland after stimulation by GHRH secreted by your hypothalamus.
- What happens to growth hormone as we age? Answer: We make a lot less. We have the capacity to make more, indeed, but it gets blocked by somatostatin which rises as we age. (I warned you that this dive can go very deep.)
- One of the main problems with loss of growth hormone is what in older cells? Answer: They can’t wake up to do their job, whatever it may be. They slide from quiet waiting (good) to senescence (warning light) to dying (bad, bad, bad).
- You can wake up cells by what central process? Answer: putting stress on the energy supply in the cell: exercise to exhaustion, or fast until glucose is used up and inducing ketones: aka fasting. (You can accelerate this with various tricks: taking oral ketones, restricting blood flow in exercise….or various peptide treatments)
- CJC-1295 was about to be released as a drug and was held up because? Answer: One of the subjects had sudden death from a heart attack.
References: Women’s Health, NY Acad Sci, Wikipedia, You-Tube,
For 5,000 years humans have been touting various aphrodisiacs, to various effect. Most of them don’t work. Rhino horn and tiger’s penis don’t do much for the client, and just kill off precious rhinos. PT-141 works. Really. Read more….
Your hypothalamus/pituitary system make most of their hormones from one precursor protein called pro-opiomelanocortin. There are 11 peptide hormones made off POMC, depending on how you slice and dice it. The melanocortin part of that peptide ends up coding for something called melanotan. That’s what was being researched when they noticed that rats and monkeys that got melanotan all appeared to exhibit more “Sexual behavior”. We can go down the rabbit hole of melanotan another day, but for now, let’s just leave at that being the peptide being studied that started folks researching how they could alter it to increase potency. Melanotan II was meant to be developed for helping folks tan, and thereby reduce skin cancer from too much sun. Nice try. Some folks have been so enthusiastic about a possible tanning agent, that they have used more and more of it, making for too much tanning. Google “too much melanotan” and appreciate the pictures of people who get too tan. And they got turned on. PT-141 is a very simple 7 amino acid chain fragment off melanotan that was made into a circle. That alteration makes it have very high affinity for one of your brain receptors that set off sexual desire. There you have it.
Where does PT-141 fit today? It’s actually been pursued as a drug to give women a boost in their libido. The simplest conclusion would be to say that it doubles the likelihood of women having a “satisfying” occasion. Initial research using it as a nasal spray worked but caused blood pressure to pop up, leading to the FDA putting the kabash on it. In its injectable form, however, we haven’t seen near as much of that blood pressure elevation, and a lot more of the simple arousal effect in men and women. Instead of working on blood flow, it appears to have most of its effect in the brain.
No kidding, it works. Better than Viagra. Better, than Cialis. Better than Tri-Mix. Better than Tiger Penis or Rhino Horn (which have no effect). It works. It can take up to 6 hours before you feel much effect but then may last up to 72 hours. Some folks feel the effect in 15 minutes but not everyone and not reliably. Some folks feel a little hot or flushed, maybe a trace of nausea for the first half hour. The only bad part is that it’s a peptide and gets digested in your stomach. The only really effective way to take it is by injection with an insulin syringe. How much? Probably 1 mg is a pretty good starting dose. Some places say try 1 mg, wait 30 minutes and try a second milligram. I’ve had one report back of 1 mg making one unhappy male unable to sleep on his stomach for a whole night. Had to lay on his back. Too bad, huh!
WWW.What will work for me. I’ve tried every peptide I write about on myself. But here is where I invoke TMI. Boundaries, boundaries. But so far I have over a dozen folks try it and every report back so far has been a “thumbs up”, if I may use a gentle analogy. Better than Viagra, Better than Cialis and “it worked on both of us” to paraphrase one happy client. My conclusion? Someone, please tell the Chinese about this amazing peptide quick while there are still a few tigers. Once you use this, you won’t ever go back. Save a rhino.
- PT-141 does what to women? Answer: Doubles the likelihood of women having a “satisfying sexual encounter”. One of the only effective drugs for women.
- What is it? Answer: It is a 7 amino acid circle peptide that is a fragment of a natural human hormone. It’s not quite natural.
- It works where? Answer: In receptors in your brain, not on blood flow in your tender parts.
- How long does it last. Answer: Some 72 hours.
- Does it have side effects? Answer: A bit of flushing and nausea. The high blood pressure associated with a nasal spray has not been as reliably seen in injections. I could find no reports of having to make an ER visit for too long an effect.
References: CBS News, TransformYou, Self, 4-minute workout,
Want to know the most effective peptide for weight loss? Sure. Don’t we all! AOD-9064 (AOD: Advanced Obesity Drug) is the last 15 amino acids of growth hormone chopped off with a single amino acid added for stability. That’s it. It’s not a natural peptide in and of itself but it is derived from growth hormone. Growth hormone is 191 amino acids long and much more complicated to make. (It also is therefore technically not a “peptide” as the definition of a peptide is under 50 amino acids long.) Growth hormone does have some weight loss effects on its own, along with many other effects. The weight loss component appears to be that tail end.
What are the beneficial effects of AOD-9064? First of all, it has no growth hormone effect, and no effect on blood sugar. That part is good. Fat cells need to be “instructed” to become more responsive to energy demands and give up their fat. Nudging them to do that requires a whole host of activities. You want blood vessels to grow into the fat. You want the fat cell to turn into brown fat that actually get more mitochondria and generate heat. (Babies are born with 50% brown fat to help protect them in those first few hours when their tiny bodies are adjusting to a cold outside world.) But mostly you want tired old cells to start telling their mitochondria to wake and multiply. That’s not an easy task as many older cells are easily nudged into senescence and spiral on down to cell death. For a mitochondria to multiply, it has to get half of its genes from the cell nucleus, but also half from its own DNA. It does that best when there is some “demand” or “stress” put on it. Just like with exercise, you have “no gain without pain”. In exercise, you push your muscles to the point of failure. That last curl, pushup, step is the most important one as at the point of failure is where you gain strength. It’s at that point of failure that the cell internally flips on the switches for mitochondria to wake up and send off their signals to the nucleus and turn on growth. They get the idea that there is no sugar around, so let’s look around for ketones which come from fat. And that turns on getting fat out of your fat cell. That whole symphony kicks off together in one smooth transition.
How can you enhance all that? Actually this is where your “symphony” kicks in. Fasting with fast mimicking diet preps you magnificently. The fasting part is stressing your mitochondria to wake up. Your stem cells multiply, as do your mitochondria. What else rings that wake up alarm? Exercise! And you can do it in 4 minutes with high intensity exercise, or just plain 40 minutes of walking will do it too. Hormone replacement! If you are over 50, men and women need hormones. Just do it, balanced, with human hormones.
Then, start with a GHRP peptide and layer in AOD-9064. 250 mcg twice a day and watch the weight peel off. You don’t feel hungry. Your fat cells open up. And you convert that mushy, lazy white fat to brown fat that burns energy around the clock.
Any one of those by themselves will help lose a little, but so slowly you get discouraged. To succeed, you want to get the whole engine that is your body working at its optimal stage. And then your brain works better too. And that’s the real bonus.
WWW: What will work for me. I’m new at this but the professors I’ve listened to and watched are pretty enthusiastic about AOD-9064. I have one alpha adaptor who has gotten the AOD-9064 but hasn’t reported back yet. I want to understand the key ideas of the physiology first. I’m trying the GHRP right now on myself. I’m doing the Fast Mimicking and pretty close to the exercise target. The 4 minute workout looks pretty awful but I want to give it a whirl. See if I can do that.
- AOD-9064 is a natural peptide? T or F. Answer: Some nuance here. It is naturally a piece off the end of growth hormone but is not naturally in the human body by itself. It’s easier to manufacture when it only has to be 15 peptides long.
- To lose weight, you have to do what? Answer: Far more complex that just eat less and exercise more. We now know that we have to understand the pathways of fat burning and how they get turned on and stay on. As we age, we have to turn on the systems that stopped working years ago. Peptides help do that.
- You can buy AOD-9064 off the internet? Answer: True. However, you get what you pay for. One report from Switzerland (where the Olympic folks want to study and know just what athletes are up to when they push boundaries of legal drugs.) showed that about 80% of internet peptides were below sensible thresholds of purity, or even close to advertised content.
- How do you take it? Answer: Problem here. You have to take it by an insulin needle type shot. Twice a day. Peptides get digested pretty easily in the stomach.
- What is the good source for peptides? Answer: There are compounding pharmacies that will make 99% pure FDA threshold drugs. And it is legal to get them. All that costs more. The AOD-9064 on the market actually exists also. It takes a shot and costs $ 1000 a month.
References: Self-Hacked, Wikipedia, Neuro Endocrin Letters, Bull Exp Med Biol.,
Ready for real shocker! Want to lengthen your telomeres? Do you know what telomeres are? Here we go. (Do you trust Russian research?)
Epithalamin is a peptide found in the pineal gland of calves. It was discovered at the St. Petersburg Institute of Bioregulation and Gerontology by Vladimir Khavinson. It breaks down ever so easily so was altered to the new peptide called Epitalon which is only 4 amino acids long: Ala-Glu-Asp-Gly. This gets digested ever so easily in your stomach so has to be given IV or IM. But note, this is not a natural peptide but a slight modification of the original. That is not to take away from its effects, but this one isn’t natural. It’s just very simple.
What are telomeres? They are the tail ends of your chromosomes that are gradually used up as stem cells duplicate. The protein that duplicates DNA has a certain number of base pairs left inside it when it finishes copying DNA that then gets chopped off the end when it is done. The net effect is that cells can only duplicate so many times. That is called the Hayflick limit. It predicts that humans can only live to be about 120. Extending the Hayflick limit is the Holy Grail of anti-aging. Things like exercise, fasting, good sleep, stress control, less sugar all help extend the Hayflick limit. But not as much as we would like.
This is where Epitalon comes in. This was Khavinson’s first work. He showed that Epitalon extended human fibroblast telomere proliferation from expected termination at the 34th generation up to the 44th generation, making the treated cells have telomeres as long as original cells. Khavinson compared epitalon to epithalamin and found them to be equivalent in effect. And he conducted a prospective human cohort study in humans with 266 folks given epithalamin. Over the next 6 years, there was a 1.6-1.8 reduction in mortality with just one treatment. If combined with another peptide, thymulin, and treated annually, over the subsequent 6 years he reported a 4.1 fold reduction in mortality.
In another study of 79 coronary artery disease patients given 3 years of biannual epitalon treatment they had a 50% reduction in cardiovascular mortality and 28% reduction in overall mortality. These numbers are huge but are based on a tiny cohort. Just one or two deaths would make gigantic changes in the numbers.
Is there a feasible mechanism that explains these potentially huge results? Yes, possibly. It appears that epitalon has the effect of increasing the production of melatonin. Melatonin is a potentially awesome cancer fighter. It also helps you sleep and get better rest. We make much less of it as we age. In one study involving 14 elderly humans, Epitalon improved melatonin back to youthful levels. There is likely also a corroborative effect on the production of T cells, which are cancer fighters. There are now multiple rat studies showing dramatic reductions in cancer spread and size with epitalon. Human studies? Not so much.
Whoa, Nellie! These are over the top, too good to be true studies. And all from Russia. Do we trust the Russians? Is medicine a different forum than election politics? Does the FDA approve? What would you do?
WWW: What will work for me? I have tried every peptide on myself before writing about them. At least so far. I have heard from one of my faculty that he gives epitalon twice a year to all his serious anti-aging clients. (For the last year.). As in, just one year – so no long term experience. What’s a serious, ethical, honest scientist to do? I think every one of us has the right to make our own choices. Doctors have the obligation to first do no harm. To be sure of that, we should be following research-based evidence. Let’s see what research emerges. I’m staying tuned.
- Epitalon is a natural peptide. T or F. Answer: False. It is a modification of epithalamin which is a natural pineal peptide from calves. It has been reported to be equivalent to epthalamin.
- What is epitalon purported to do? Answer: Increase the length of telomeres and increase the production of melatonin. Those two may be linked.
- What has been shown to be the effect of epitalon in Russian elderly folks when combined with thymulin and given twice a year? Answer: An 80% reduction in mortality.
- How much longer do mice and rats live, given epitalon? Answer: Not fair. Not in the note above but if you read all the references: roughly 30% longer lifespans.
- Epitalon is FDA approved? Answer: No.