4029 replies to this topic

[Razor444]

PDE5 inhibitors are part of Lost's stack. Here's an excerpt from a paper with regards to PDE5's life extension potential:

 

Phosphodiesterase 5 (PDE5) degrades cGMP. PDE5 inhibitors, including sildenafil (Viagra), tadalafil (Cialis), vardenafil (Levitra), and avanafil (Stendra), are widely known for treatment of erectile dysfunction (ED). While sexual stimulation causes cGMP synthesis, PDE5 inhibitors cause its accumulation, relaxing corpus cavernosum and penile arteries. In addition, cGMP relaxes the tone of prostate muscle cells and decreases prostate inflammation. Tadalafil is effective and well-tolerated therapy for benign prostate hyperplasia (BPH) [209]. PDE5 inhibitors, such as long-acting tadalafil, can be added to anti-aging drug mixture because ED and BPH are most prevalent age-related conditions in aging men. Also, there is a fundamental reason to consider PDE5 inhibitors as anti-aging medicines (in both men and women). The key word is “relax”. Senescent cells are tense and stressed. Cellular senescence is manifested by hyper-function. On the organism levels hyper-function is translated in hypertension, hyperplasia, hyperlipidemia and so on. By ‘relaxing the tension’, PDE5 inhibitors may slow senescent-associated pathology. PFE5 inhibitors cause anti-vasoconstriction, anti-proliferative and anti-inflammatory effects. Not co-incidentally, PDE5 inhibitors are already approved or investigated for therapy of diverse age-related diseases and conditions. Sildenafil and tadalafil are approved for pulmonary arterial hypertension [210]. PDE5 inhibitors are under investigation for heart hypertrophy, myocardial infarction, cancer, neurodegenerative diseases, cystic fibrosis, diabetes, obesity and metabolic syndrome [210-213]. Inhibition of PDE5 increases levels of cGMP and hydrogen sulfate. These signaling molecules increase life span in C elegans [214, 215].

PDE5 inhibitors are remarkably safe for everyday use for a long term. In most studies, 5 mg tadalafil once a day had minimal side effect and improved BPH and ED [216]. Furthermore, even 40 mg of tadalafil is used in the treatment of pulmonary arterial hypertension without serious side effects [217]. PDE5 inhibition improves beta-cell function in metabolic syndrome [218, 219]. This may mitigate potential side effect of rapamycin on beta-cells.

 

 

[MBF]

Hey LostFalco, and all you guys!  I was planning on starting INI this week.. just came across this article., shouldn't we take this as a matter of concern?

 

LostFalco, I'd be great if you could take a look at the article and give us your take 

 

Thanks!

 

http://www.lifeexten...abetics/page-01

 

http://www.lifeexten...insulin/Page-01

 

http://www.lifeexten...p07unherio.html

 

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Risk Of Using Inhaled Insulin

The problem with inhaled forms of insulin is that it is effective only when the administered dose is more than three to 10 times the amount given by subcutaneous injection. That’s because little more than 10% of the inhaled insulin reaches the alveoli in the lungs where it is absorbed into the bloodstream.6,26

Another area of potential concern regarding inhaled insulin is the possible effect on the tissues that it comes in contact with on its way to the alveoli, including the linings of the mouth, throat, tongue, cheeks, gums, tonsils, trachea, bronchial tree, vocal cords, larynx, nasal air sinuses, and olfactory mucosa (which has a direct connection to the brain).27 Even the modified dry form of insulin is of concern. The powdered insulin will stick to the above-mentioned breathing passages on the way to the lungs. It is a known fact that insulin induces cell division wherever it is deposited.28

Furthermore, since insulin is a growth factor, there is also the potential concern that inhaled insulin could support aberrant cell growth, and potentially even change precancerous lesions into cancer. Cancer cells and precancerous cells have numerous insulin receptors that bind to the inhaled insulin. The fundamental problem with the insulin-inhalation delivery method is that the powder particulates stick to the naso-oro-pharyngeal-laryngeal-tracheobronchial tree. By sticking to these structures before it reaches the alveoli, inhaled insulin can facilitate the malignant transformation of cells.29

Researchers have noted that those with elevated blood sugar due to type II diabetes and other conditions are more prone to develop certain types of cancers than the healthy population.30Numerous cancers have more than the normal amount of insulin receptors to facilitate the entry of large amounts of glucose into the tumor cells, thus promoting their growth, multiplication, and spread.31,32

Inhaled insulin may potentially increase the risk of lung cancer. Studies of human epithelial cells suggest that insulin-receptor activation is in itself insufficient for malignant transformation. However, once malignant transformation has been induced by other agents, the insulin receptor pathway to promote malignant progression of these cells can be activated.32 Since inhaled insulin comes in contact with so many tissues, it is crucial that future research examines its impact on normal, precancerous, and cancerous cells of the upper respiratory and digestive systems.

POTENTIAL HEALTH RISKS OF INHALED INSULIN THERAPY

The following are documented and possible health risks of insulin inhalation therapy:

• Increased risk of respiratory tract irritation,33 which causes coughing, shortness of breath, sore throat, and dry mouth.34,35
• Development of hypoglycemia, with adverse outcomes in those who exercise immediately after inhalation and those who smoke. These effects may occur due to the rapid absorption of inhaled insulin from the alveoli.36,37
• Exacerbation of existing conditions in asthmatics that would require more inhaled insulin to control blood sugar.7,38 Furthermore, inhaled insulin could lead to smooth muscle contraction of the airway, which could precipitate or exacerbate chronic obstructive pulmonary disease (COPD) or episodes of asthma.39
• Adverse effects in people with pre-existing respiratory diseases such as chronic bronchitis, tuberculosis, tumors, and other chronic lung afflictions.8
• Increased insulin antibodies. In one study, inhaled insulin increased the level of insulin antibodies in the body from baseline levels of 6 to 35%.40 This could delay and retard the action of soluble insulin in the blood, since the removal of an insulin immune complex could make less insulin available to lower blood sugar.
• Unwanted tissue growth in normal and precancerous cells, which may lead to genetic defects and ultimately cause cancer. Long-term effects of supraphysiologic doses of insulin in the human lung or on neoplastic lung tissue have begun to unfold.13 Many of the insulin particles are deposited on the oro-pharyngeal-laryngeal-tracheobronchial tree, and nose lining. This might increase the incidence of tumors of the oral cavity, tongue, larynx, pharynx, trachea, bronchial tree, lungs, tonsils, nasal mucosa, nasal air sinuses, nasal polyps, vocal cords, esophagus, and any other structure where the insulin particulates are deposited during inhalation and nasal spray delivery methods.
• A potential increased tumor incidence in the tissues of the respiratory tract, although no evidence of this has been presented to date due to the withdrawal of inhalation insulin by Pfizer. With large-scale use of inhalation insulin, this may become apparent with increased tumors of the nasal sinuses, nasopharyngeal cavity, laryngeal, and respiratory tracheobronchial passages as well as the esophagus. The true health risks could take a long time to reveal themselves, as occurred with other drugs such as Vioxx® (an anti-inflammatory), Avandia® (an oral antidiabetic drug), and the diet drug combination, fenfluramine/phentermine (fen-phen).41-43

If you visit www.pubmed.gov and search for “insulin and cancer,” you will find almost 30,000 citings; if you search for “insulin causes cancer,” you will find nearly 17,000 citings. This is one indication of the intense research underway on the relationship of insulin to cancer. Many cancer and precancerous cells have two to four times more insulin receptors (IR) and more insulin-like growth factor 1 (IGF-1) receptors,32,44,45 which thrive on the high blood sugar and high insulin with which they come in direct contact.

Should You Use Inhaled Insulin?

The FDA’s recently approved inhaled insulin is a different formulation than Pfizer’s Exubera®, which was removed from the market,7,46,47 but that does not make it the method of choice for insulin delivery in type I and some type II diabetics. That’s because the powder still has to pass through the same air passages that Exubera® did, and almost 80 to 90% of it is going to be lost when it sticks to the respiratory passages before it ever reaches the lungs and is then delivered to all cells in the body.

I recommend that inhaled insulin should not be used by diabetics who smoke or patients with underlying lung diseases such as asthma or chronic obstructive pulmonary disease (COPD), chronic bronchitis, lung infections (including tuberculosis), and patients suspected of lung carcinomas and sarcomas. Until the drug’s full health risks versus benefits are known, I further discourage its use in patients with precancerous lesions (such as polyps, dysplasia, and leukoplakia), those with changes caused by tobacco use, those with chronic exposure to dust and other hydrocarbons, and patients with chronic infections.

It may take years before we know the benefits versus risks of inhaled insulin. The safety of using this type of product in pregnant women, adolescents, and children has not been established. I hope that the FDA and drug companies involved in licensing and developing an inhaled method of insulin delivery will fully investigate these health risks and concerns on a post-approval surveillance basis.

The Future Of Insulin Delivery

  

The future of insulin delivery with the fewest side effects and a less painful delivery method may come from:

• The development of slow-release injectable insulin that lasts days or weeks with a single shot,
• The implantation of insulin-producing stem cells,
• An insulin pump or painless microneedles that deliver insulin under the skin,
• A method to activate and induce primordial stem cells in the pancreas’ insulin-producing islet cells, or
• A transmucosal delivery patch as described in US patent publication 2009/0304776 Al.48

The market for new antidiabetic therapeutic agents is a multibillion-dollar market. I am sure the drug companies and research scientists are in a race to develop a method to control the blood sugar to treat diabetes, which has become an endemic disease in the current century.49

Summary

As the diabetes epidemic continues to grow, drug manufacturers are eager to develop new methods of insulin delivery. The FDA recently approved an inhaled insulin drug, despite the fact that Pfizer withdrew its inhaled insulin product due to its potential to cause cancer. Inhaled insulin affects all tissue it comes in contact with upon delivery, and since insulin induces cell division, this can lead to aberrant cell growth. Hypoglycemia, exacerbation of asthma symptoms, and adverse effects in those with pre-existing respiratory diseases are also areas of concern regarding inhaled insulin.

If you have any questions on the scientific content of this article, please call a Life Extension®Wellness Specialist at 1-866-864-3027.

Dr. T.R. Shantha has relentlessly battled and suffered at the hands of the entrenched medical establishment. He is currently pursuing novel approaches to better treat today’s diabetes epidemic. His exposés of the risks of the first FDA-approved inhaled insulin drug possibly saved countless lives. 

For more information, call, write, or email Dr. Shanta. 1946 Carrington Court Stone Mountain, GA 30087. Phone/Fax: 678-580-5446, Cell: 678-640-7705 Email: shantha35@aol.com;www.wedgetherapeutics.com

References

 

 

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Unknown Health Risks of Inhaled Insulin   September 2007

By T.R. Shantha, MD, PhD, FACA

 

"....

Development of Inhaled Insulin to Treat Diabetes

Based on today’s epidemic of diabetes, there is a large and growing demand for insulin drugs. However, the pain, inconvenience, and disruption of lifestyle associated with multiple daily insulin injections leads many patients to abandon their doctor-recommended treatment plans. As a result, many patients fail to achieve effective management of their condition. To eliminate pain and improve patient compliance—and thus treatment outcomes—increasing research has focused on alternatives to subcutaneous (SC) insulin injections. Some of the areas of investigation include: aerosolized insulin for inhalation, oral insulin, insulin-producing stem cell implantation, and insulin delivery pumps.

The first inhalation insulin has now been approved for use in US and Europe, and numerous similar products are on the horizon. This novel device delivers a powdered form of insulin to the alveoli of the lungs, where, since the lung is a large microvascular organ, insulin is absorbed into the bloodstream.1

Distribution of Inhaled Insulin, Insulin Receptors, and Cancer

The inhaled form of insulin is effective only when the administered dose is three to ten times the amount given by subcutaneous injection, because little more than 10% of the inhaled insulin reaches the alveoli.2,3 The interval between the administration of insulin and the onset of glucose-lowering activity is about 10 to 20 minutes. Given its rapid onset of activity, inhaled insulin is suitable for preprandial (before meal) but not for long-term basal (baseline) use.

Tight glucose control, however, may come at a price. One area of potential concern regarding inhaled insulin is the possible effects on the tissues that it comes in contact with on its way to the alveoli, such as the linings of the mouth, throat, tongue, cheeks, gums, tonsils, trachea, bronchial tree, vocal cords, larynx, nose and nasal air sinuses, and olfactory mucosa (which has a direct connection to the brain). Furthermore, since insulin is a weak growth factor, there is also the potential concern that inhaled insulin could support aberrant cell growth, and potentially even trigger or support cancer.

Scientists have noted that those with elevated blood sugar due to type 2 diabetes and other conditions are more prone to develop certain types of cancers than the healthy population.4Numerous cancers, and even non-cancerous fibrous tumors, have more than the normal amount of insulin receptors to facilitate the entry of large amounts of glucose into the tumor cells, thus promoting their growth, multiplication, and spread.5-10

Another important uncertainty about treatment with inhaled insulin is therefore the potentially increased risk of lung cancer. Studies of human bronchial epithelial cells suggest that insulin-receptor activation is in itself insufficient for malignant transformation. However, once malignant transformation has been induced by other agents, the insulin receptor pathway is thought to promote malignant progression of these cells.11

Since inhaled insulin comes in contact with so many tissues, it is crucial that future research examines its impact on normal, pre-cancerous, and cancerous cells of the upper respiratory and digestive systems.

INHALED INSULIN: WHAT YOU NEED TO KNOW

• • Insulin allows glucose to enter cells, and is thus essential for cell growth and energy production. Since people with diabetes either do not produce enough insulin, or their cells are not sensitive to its effects, insulin is an essential cornerstone of diabetes treatment.

  • Until recently, the only way to administer insulin was via injection. A recent breakthrough came with the introduction of an insulin preparation that can be inhaled.

  • While many people are embracing this new form of FDA-approved insulin, its long-term safety has not yet been established. Since insulin acts like a mild growth factor, it is possible that inhaled insulin could stimulate unwanted tissue growth in the respiratory tract.

  • Inhaled insulin is not approved for use in pregnant women, children, or adolescents. Smokers and patients with underlying lung diseases should avoid using inhaled insulin.

  • Unknown Health Risks of Inhaled Insulin   September 2007

    By T.R. Shantha, MD, PhD, FACA

    Potential Health Risks of Inhaled Insulin Therapy

    Other questions still remain unresolved about the potential health risks of inhaled insulin. Among the documented and possible health risks of insulin inhalation therapy are:

    1. Increased risk of respiratory tract irritation, causing cough, shortness of breath, sore throat, and dry mouth.12

    2. Development of hypoglycemia, with adverse outcomes in those who exercise immediately after inhalation and those who smoke. These effects may occur due to the rapid absorption of inhaled insulin from the alveoli.13-15

    3. Exacerbation of existing conditions in asthmatics who require more inhaled insulin to control their blood sugar.16 Furthermore, inhaled insulin could lead to airway smooth muscle contraction, which could precipitate or exacerbate chronic obstructive pulmonary disease or episodes of asthma.17

    4. Alveolar thickening, poor gas exchange, pulmonary hypertension, or pulmonary fibrosis. Additionally, inhaled insulin could cause adverse effects in people with pre-existing respiratory diseases such as chronic bronchitis, tuberculosis, tumors, and other chronic lung afflictions.18

    5. Increase in insulin anti-bodies. In one study, inhaled insulin increased the level of insulin anti-bodies in the body from baseline levels of 6% to 35%.19 This could have the adverse effect of retarding the action of soluble insulin in the blood, since the removal of an insulin immune complex could make less insulin available to lower blood sugar.

    6. Unknown long-term effects of supraphysiologic doses of insulin in the human lung or on neoplastic lung tissue. It is possible that insulin could stimulate unwanted tissue growth in normal and precancerous cells, which could lead to genetic defects and ultimately to cancer.

    7. Potentially increased tumor incidence in the tissues of the respiratory tract, although no evidence of this has been presented to date.

    The true health risks could take a long time to come to light, as occurred with other drugs such as Vioxx® (an anti-inflammatory) and Avandia® (an oral anti-diabetic drug). In addition to the eye-opening health risks of inhaled insulin, it is more expensive than other insulin preparations.

    Should You Use Inhaled Insulin?

    I recommend that inhaled insulin should not be used in smokers or in patients with underlying lung diseases such as asthma or chronic obstructive pulmonary disease. Until the drug’s full health risks are known, I further discourage its use in those with precancerous lesions (such as polyps, dysplasia, or the leukoplakia that can accompany tobacco use). Inhaled insulin is not approved for use in pregnant women, children, or adolescents. I hope that the FDA and drug companies involved in licensing and developing an inhaled method of insulin delivery will fully investigate these health risks and concerns on a post-approval surveillance basis. The future of insulin delivery with the fewest side effects may come from development of slow-release injectable insulin lasting days to weeks with a single shot, or from implantation of insulin-producing stem cells.

    References

    1. Heinemann L, Traut T, Heise T. Time-action profile of inhaled insulin. Diabet Med. 1997 Jan;14(1):63-72.

    2. Agu RU, Ugwoke MI, Armand M, Kinget R, Verbeke N. The lung as a route for systemic delivery of therapeutic proteins and peptides. Respir Res. 2001;2(4):198-209.

    3. Available at: http://formularyjour...=282691Accessed July 7, 2007.

    4. Stattin P, Bjor O, Ferrari P, et al. Prospective study of hyperglycemia and cancer risk. Diabetes Care. 2007 Mar;30(3):561-7.

    5. Li Y, Chang Q, Rubin BP, et al. Insulin receptor activation in solitary fibrous tumours. J Pathol. 2007 Apr;211(5):550-4.

    6. Ryan CJ, Haqq CM, Simko J, et al. Expression of insulin-like growth factor-1 receptor in local and metastatic prostate cancer. Urol Oncol. 2007 Mar;25(2):134-40.

    7. Mallikarjuna K, Pushparaj V, Biswas J, Krishnakumar S. Expression of insulin-like growth factor receptor (IGF-1R), c-Fos, and c-Jun in uveal melanoma: an immunohistochemical study. Curr Eye Res. 2006 Oct;31(10):875-83.

    8. Dearth RK, Cui X, Kim HJ, et al. Mammary tumorigenesis and metastasis caused by overexpression of insulin receptor substrate 1 (IRS-1) or IRS-2. Mol Cell Biol. 2006 Dec;26(24):9302-14.

    9. Shen MR, Hsu YM, Hsu KF, et al. Insulin-like growth factor 1 is a potent stimulator of cervical cancer cell invasiveness and proliferation that is modulated by alphavbeta3 integrin signaling. Carcinogenesis. 2006 May;27(5):962-71.

    10. Belfiore A. The role of insulin receptor isoforms and hybrid insulin/IGF-I receptors in human cancer. Curr Pharm Des. 2007;13(7):671-86.

    11. Zhao YL, Piao CQ, Wu LJ, Suzuki M, Hei TK. Differentially expressed genes in asbestos-induced tumorigenic human bronchial epithelial cells: implication for mechanism. Carcinogenesis. 2000 Nov;21(11):2005-10.

    12. Available at: http://www.pdrhealth...s/exu1734.shtml. Accessed July 7, 2007.

    13. Kohler D. Aerosols for systemic treatment. Lung. 1990;168 Suppl:677-84.

    14. Himmelmann A, Jendle J, Mellen A, et al. The impact of smoking on inhaled insulin. Diabetes Care. 2003 Mar;26(3):677-82.

    15. Rave K, Bott S, Heinemann L, et al. Time-action profile of inhaled insulin in comparison with subcutaneously injected insulin lispro and regular human insulin. Diabetes Care. 2005 May;28(5):1077-82.

    16. Henry RR, Mudaliar SR, Howland WC, III, et al. Inhaled insulin using the AERx Insulin Diabetes Management System in healthy and asthmatic subjects. Diabetes Care. 2003 Mar;26(3):764-9.

    17. Schaafsma D, Gosens R, Ris JM, et al. Insulin induces airway smooth muscle contraction. Br J Pharmacol. 2007 Jan;150(2):136-42.

    18. Aye M, Sheedy W, Harrison R, et al. Pulmonary vasodilation in the rat by insulin in vitro could indicate potential hazard for inhaled insulin. Diabetologia. 2003 Sep;46(9):1199-202.

    19. Hermansen K, Ronnemaa T, Petersen AH, Bellaire S, Adamson U. Intensive therapy with inhaled insulin via the AERx insulin diabetes management system: a 12-week proof-of-concept trial in patients with type 2 diabetes. Diabetes Care. 2004 Jan;27(1):162-7.

 

Edited by MBF, 15 June 2017 - 10:44 PM.

[mettmett]

Bro, "intranasal" is not the same as "inhaled."

[MBF]

Bro, "intranasal" is not the same as "inhaled."

Bro, thanks for your input!. I see the difference between the powder or liquid versions. But, it is still the same substance,  insulin, right? Not considering the effects on lungs, but  the areas in direct contact with the insulin ( lining of the nose, throat, tongue, gums,..)

 

"Another area of potential concern regarding inhaled insulin is the possible effect on the tissues that it comes in contact with on its way to the alveoli, including the linings of the mouth, throat, tongue, cheeks, gums, tonsils, trachea, bronchial tree, vocal cords, larynx, nasal air sinuses, and olfactory mucosa (which has a direct connection to the brain).27 Even the modified dry form of insulin is of concern. "

"It is a known fact that insulin induces cell division wherever it is deposited.28

Furthermore, since insulin is a growth factor, there is also the potential concern that inhaled insulin could support aberrant cell growth, and potentially even change precancerous lesions into cancer."

 

Btw, please don't take my post as negative or a criticism. I had plans to start INI .But, came across this article and thought we should discuss, evaluate risks and concerns. (And, it would be nice to hear from Falco, he is prob. aware of this, and have looked further..)

 

Thanks guys.

Edited by MBF, 16 June 2017 - 01:43 PM.

[Hyperflux]

I have noticed increased asthma and rhinitis from intranasal insulin (possibly insulin coming down my throat sometimes?)

Edited by Hyperflux, 17 June 2017 - 12:29 AM.

[Edgar]

Keep in mind the objective of INI is to absorb the insulin into your sinuses.  If you're exposing any other tissues to the insulin, you need to adjust how you're applying the medication.

 

INI done properly will have virtually no impact to blood insulin levels.  Do not confuse this with Inhaled Insulin, which is a therapy designed to have a large impact on blood insulin levels.

 

Also, consider the dose required to be effective.  The effective dose for INI is a couple orders of magnitude smaller than what's required for inhalation insulin therapy.  As it's commonly said, the dose makes the poison.

[Reformed-Redan]

I was wondering if anyone was interested in procuring insulin aspart powder from Alibaba. It's only my second trial with intranasal insulin and I'm a believer. 

 

Alibaba has insulin aspart, just don't know the price for 1g+

 

Insulin aspart is superior to insulin in one paper detailed on lostfalco's website. 

 

What are your thoughts on intranasal long acting insulin? I'm wondering if the detemir variant is superior due to its long half life. 

 

I won't handle any financial aspect of a group buy for insulin aspart but, I would like to participate in a group buy for a decent amount that could last me a long time preserved in my freezer. 

 

 

 

 

[Reformed-Redan]

Here's the paper referencing insulin aspart as superior to regular insulin:

 

• https://file.io/V2VMUu

[Hyperflux]

Keep in mind the objective of INI is to absorb the insulin into your sinuses.  If you're exposing any other tissues to the insulin, you need to adjust how you're applying the medication.

 

INI done properly will have virtually no impact to blood insulin levels.  Do not confuse this with Inhaled Insulin, which is a therapy designed to have a large impact on blood insulin levels.

 

Also, consider the dose required to be effective.  The effective dose for INI is a couple orders of magnitude smaller than what's required for inhalation insulin therapy.  As it's commonly said, the dose makes the poison.

 

What if it drips down your throat occasionally? 

[Razor444]

I've tried a PDE5 inhibitor. Viagra. It seems to have *some* cognitive effect. Nothing profound.

 

[lostfalco]

The data on IGF2 is getting more and more interesting. This article talks about a rodent study that connects circadian rhythms (clock genes) and bright light therapy to enhanced IGF2 expression and improved memory function. Definitely worth a quick read...ya know, since circadian rhythms, bright light therapy, and IGF2 are three of my favorite topics. 

 

Enjoy! =)

 

https://www.ncbi.nlm...les/PMC5478617/

 

"Based on our collective results, we propose that light-induced changes in hippocampal clock function leads to the de-repression of IGF2, which primes the hippocampus to enhance the acquisition and consolidation of long-term recognition memory. These results reveal new ways in which light regulates hippocampus-dependent memory formation and novel molecular mechanisms that may link the circadian clock to neuronal plasticity."

 

"The effects of light on memory in the current study are likely due to the alteration of hippocampal clock function that changes the daily regulation of IGF2. Because IGF2 signaling has been linked to MAPK signaling48, 49, this highlights new areas for future research investigating the molecular links between circadian and cognitive function."

 

Note: I put this bright light device on my bathroom counter and shine it in my eyes while I'm shaving, brushing my teeth, etc. before work every morning. Very energizing. http://amzn.to/2u4X8cO

Edited by lostfalco, 09 July 2017 - 01:13 AM.

[Razor444]

Lost,

 

I tried some canned oxygen yesterday, whilst fasting. I was flagging big time at about 20 hours in. Nut deep in fatigue. The oxygen was like a breath of fresh air!  Took 4 large gulps in all. I felt anew. Reinvigorated by the breath of god. 99% O2 coursing through my veins. Able to rip through the last few browser tabs which had previously been taunting me with their stasis.

 

I'm going to try again on my next fast.

[lostfalco]

Lost,

 

I tried some canned oxygen yesterday, whilst fasting. I was flagging big time at about 20 hours in. Nut deep in fatigue. The oxygen was like a breath of fresh air!  Took 4 large gulps in all. I felt anew. Reinvigorated by the breath of god. 99% O2 coursing through my veins. Able to rip through the last few browser tabs which had previously been taunting me with their stasis.

 

I'm going to try again on my next fast.

Hey, what's up Razor? That's awesome, man. As you know, I'm a huge concentrated oxygen fan. Definitely one of my favorite noots. I've never actually tried the canned O2...which one did you test out?

[Razor444]

This one, Lost:

 

1 X 7.2 Litre O2 Oxygen Can Inc 1 x Mask and 1.8 Metre Tubing

 

I'm going to look at different options if the O2 continues to work like a charm.

 

As an aside; oxygen therapy (well, HBO) is starting to be tested in cancer patients. Dominic D'Agostino (of keto diet fame) shares resources about it in on Twitter.

 

 

[mike888]

This is the best thread in the history of longcity. I'm just wondering is lostfalco.to smart is he promoting his own company selling lasers?
Any way this is what I like to add and hopefully discuss:

Peptide Bioregulators, gene switches that could replace stem cells!
This former Russian military secret is now available to the public!

Today Professor Vladimir Khavinson is the President of the European Academy of Gerontology and Geriatrics, but in the 1980’s he was a Colonel in the Soviet Union military medical corps. At the time, he and his team were approached by Kremlin officials, they wanted them to find a way to protect their troops from a myriad of problems; issues such as radiation for submariners in nuclear submarines to troops that may be blinded from known, (but thankfully unused) new weapons such as battlefield lasers.
What their secret research uncovered- that was used for two decades on many thousands of men and women- was a remarkable link between short chain peptides and DNA.
Now their published research is in the open and it identifies that each organ/ gland/ tissue uses a highly specific short chain peptide to act as a ‘short cut’ to initiate protein synthesis. These peptides can be found in food and unlike proteins they can enter the blood through the stomach. Through a comprehensive list of patents and even copyrighted PowerPoint slides, the Russian research group are showing that each of the concentrated peptide bioregulators so far examined interact with particular strands of DNA- effectively and very specifically activating repair and regenerative processes.
This is a remarkable story since what we are describing here are individualised gene switches and since they have been tested for many years on thousands of individuals, without report of any serious side effects or contraindications to date, they could be set to ‘out do’ stem cells. Why? Because this peptide therapy is relatively cheap, highly specific, can be taken orally and doesn’t require any suppression of the immune system to operate fully.
Professor Khavinson and his award winning team at the St Petersburg Institute of Biogerontology have discovered that each organ/ gland has a biological reserve and despite the origin of the tissue they have studied, incredibly each one is always set at 42%
Even dosing doesn’t need to be daily, these peptide bioregulators have been shown to act even after a simple course of 2 capsules daily for 10-days. Healthy individuals only being encouraged to repeat the course 6-months later, although of course depending on the need this course can be repeated every 3-months, 2-months or 1-month if necessary. But compared to a hormone replacement therapy this is interesting, since hormones would require almost daily application. But these peptide bioregulators aren’t hormones, they are acting on the gland concerned to ‘encourage’ it to become active and effectively ‘younger’ by triggering/ activating the DNA responsible.
Here at Biogenesis, we are excited about this emerging technology and have been following it since 2010 and will be reporting much more, though articles, interviews and videos etc., so please stay tuned. There’s more to learn including the synergistic interaction of the peptide bioregulators themselves and if individuals are using hormones concurrently, then there may well be a need to monitor their blood levels more closely with a view to lowering those doses and applications etc.
Note: Of the 20 or so peptide bioregulators available Biogenesis has chosen the following, (and will be adding more into the range in due course). All the sources of these Peptide Bioregulators are from carefully chosen Danish bovine tissues and processed through pharmaceutical processes and filters.
Currently all of these peptide regulator capsules enjoy registration on the Russian market as food supplements:
•Glandokort® - this is the peptide bioregulator from the adrenal glands and can help support and improve conditions related with weak adrenal glands, particularly for those suffering from adrenal fatigue.
•Libidon®- this is the peptide bioregulator from the prostate gland and can help support and improve conditions related to prostate enlargement.
•Testoluten®- this is the peptide bioregulator from the testes and can help support and improve conditions related to weak testosterone production.
•Visoluten®- this is the peptide bioregulator from the eye retina and can help support and improve conditions related to retinal dysfunction.

 

A question: why is it that the Russians publish secret war technology? Maybe, these peptides are not the real substances...

Greetings

Mike

[lostfalco]

Just a quick update on my recent experiments...As many of you know, I just graduated and got a job working in IT for a Fortune 500 company so my time is a bit limited when it comes to posting. Thankfully, my budget is not as limited as it used to be so I have a ton of experiments in the works. Right now, I am testing every element of Dr. Bredesen's protocol simultaneously (with a few of my own additions).

 

I'm still tweaking various dosages but I'll keep you guys updated on how it goes. After countless experiments over the years I've definitely come to the conclusion that a systems approach has the greatest probability of causing dramatic change. Here's Dr. Bredesen's protocol for those of you interested in taking a look. https://www.ncbi.nlm...les/PMC4221920/

 

He has a book coming out in just about a week which I am really looking forward to poring through. http://amzn.to/2wG9JkI

 

I know I've posted this before, but his talk at the Silicon Valley Health Institute is totally worth a look imo. 

 

 

 

Edited by lostfalco, 14 August 2017 - 05:54 PM.

[lostfalco]

Wth!?! Bone is an endocrine organ! Science never ceases to amaze me. 

 

https://www.ncbi.nlm...pubmed/28273060

 

Nature. 2017 Mar 16;543(7645):385-390. doi: 10.1038/nature21697. Epub 2017 Mar 8.

MC4R-dependent suppression of appetite by bone-derived lipocalin 2.

Mosialou I1, Shikhel S1, Liu JM1, Maurizi A1, Luo N1, He Z2,3, Huang Y2,3, Zong H4, Friedman RA5, Barasch J6, Lanzano P7, Deng L7, Leibel RL7, Rubin M8, Nicholas T9, Chung W7, Zeltser LM10, Williams KW3, Pessin JE4, Kousteni S1.

Author information

Abstract

Bone has recently emerged as a pleiotropic endocrine organ that secretes at least two hormones, FGF23 and osteocalcin, which regulate kidney function and glucose homeostasis, respectively. These findings have raised the question of whether other bone-derived hormones exist and what their potential functions are. Here we identify, through molecular and genetic analyses in mice, lipocalin 2 (LCN2) as an osteoblast-enriched, secreted protein. Loss- and gain-of-function experiments in mice demonstrate that osteoblast-derived LCN2 maintains glucose homeostasis by inducing insulin secretion and improves glucose tolerance and insulin sensitivity. In addition, osteoblast-derived LCN2 inhibits food intake. LCN2 crosses the blood-brain barrier, binds to the melanocortin 4 receptor (MC4R) in the paraventricular and ventromedial neurons of the hypothalamus and activates an MC4R-dependent anorexigenic (appetite-suppressing) pathway. These results identify LCN2 as a bone-derived hormone with metabolic regulatory effects, which suppresses appetite in a MC4R-dependent manner, and show that the control of appetite is an endocrine function of bone.

 

https://www.ncbi.nlm...pubmed/28778968

Cold Spring Harb Perspect Med. 2017 Aug 4. pii: a031666. doi: 10.1101/cshperspect.a031666. [Epub ahead of print]

Regulation of Energy Metabolism by Bone-Derived Hormones.

Mera P1, Ferron M2, Mosialou I1.

Author information

Abstract

Like many other organs, bone can act as an endocrine organ through the secretion of bone-specific hormones or "osteokines." At least two osteokines are implicated in the control of glucose and energy metabolism: osteocalcin (OCN) and lipocalin-2 (LCN2). OCN stimulates the production and secretion of insulin by the pancreatic β-cells, but also favors adaptation to exercise by stimulating glucose and fatty acid (FA) utilization by the muscle. Both of these OCN functions are mediated by the G-protein-coupled receptor GPRC6A. In contrast, LCN2 influences energy metabolism by activating appetite-suppressing signaling in the brain. This action of LCN2 occurs through its binding to the melanocortin 4 receptor (MC4R) in the paraventricular nucleus of the hypothalamus (PVN) and ventromedial neurons of the hypothalamus.

 

Edited by lostfalco, 15 August 2017 - 02:52 AM.

[lostfalco]

Fantastic new interview with Dr. Bredesen (see below). He pretty much focuses on everything we've talked about in this thread over the past four years: 1) increase mitochondrial function, 2) lower inflammation, 3) increase trophic signaling (BDNF, NGF, etc.), 4) avoid toxins. 

 

This is seriously life changing stuff! I hope everyone is checking out his book (I'm working on a blog post to summarize the main ideas...'dependence receptors' are crazy fascinating!). http://amzn.to/2wG9JkI

 

In the meantime, enjoy his recent interview with Dr. Gundry. 

 

Edited by lostfalco, 02 September 2017 - 02:22 PM.

[Amorphous]

Thanks for sharing. I especially like the part in fasting. Phase 1 is all I can do for now. Hopefully, I will be able to advance to phase 2. Looking forward to your blog.

[Nuke]

Just watched this interesting podcast, there are even more to psychedelics we thought. Maybe 2C-I or Psilocin microdoses can be added to the anti-neuroinflammation stack. It may also lead to increased expressions of BDNF and GDNF.* 

 

 

*https://www.ncbi.nlm...cles/PMC4910400

 

[Elkaer]

Hi everyone!

 

Ive read about ibudilast at your blog lost, and it is very difficult for me to source. (Eu)

I found a source but it is powder, would there be any problems with taking it in powder form?

Gastronomic issues, or anything else?

 

Thanks!

[Nuke]

Measuring it out your dose is probably the hardest part, 10mg is a small amount.. Even if you dissolve it and use liquid measure, you will still need a proper scale when making the solution.

 

Btw, see I typed 2C-I above. Meant DOI.

 

Interestingly, It seems that Selegiline also up regulates Nrf2 (atleast in some cells). Currently spending a lot of time studying it, its MOA and its metabolites. A low daily dose may be handy for many reasons...

[lostfalco]

Some recent studies on intranasal insulin. =)

 

https://www.ncbi.nlm...pubmed/28929339

 

Neurotox Res. 2017 Sep 19. doi: 10.1007/s12640-017-9809-7. [Epub ahead of print]

Intranasal Insulin Ameliorates Cerebral Hypometabolism, Neuronal Loss, and Astrogliosis in Streptozotocin-Induced Alzheimer's Rat Model.

Chen Y1, Guo Z1, Mao YF2, Zheng T1, Zhang B3.

Author information

Abstract

Intracerebroventricular injection of streptozotocin (ICV-STZ) in rodents leads to cognitive impairments and several pathological changes like Alzheimer's disease (AD). However, there is hardly any research about the effect of ICV-STZ on regional cerebral glucose metabolism in rodents. Previous studies have demonstrated that intranasal insulin improves cognition in AD patients. However, the underlying mechanism remains elusive. Here, we treated the ICV-STZ rats with daily intranasal delivery of insulin (2 U/day) for 6 consecutive weeks, then monitored 18F-fluorodeoxyglucose (18F-FDG) uptake using a high-resolution small-animal positron emission tomography (microPET) and studied the expression of neuronal nuclei (NeuN) and glial fibrillary acidic protein (GFAP) using immunohistochemical staining. We observed that 18F-FDG uptake decreased significantly at the prefrontal cortex, cingulate cortex, striatum, hippocampus, and entorhinal cortex in ICV-STZ rats as compared with the control rats. Intranasal insulin restores the cerebral glucose metabolism in prefrontal and cingulate cortex and attenuates astroglia activation and neuronal loss in the hippocampus of ICV-STZ rats. These findings provide the mechanistic basis for treating AD patients with intranasal insulin.

 

https://www.ncbi.nlm...pubmed/28917981

Neurosci Lett. 2017 Sep 13. pii: S0304-3940(17)30768-1. doi: 10.1016/j.neulet.2017.09.026. [Epub ahead of print]

Intranasal insulin treatment alleviates methamphetamine induced anxiety-like behavior and neuroinflammation.

Beirami E1, Oryan S1, Seyedhoseini Tamijani SM2, Ahmadiani A2, Dargahi L3.

Author information

Abstract

Insulin, as a peptide hormone, has recently gained attention for its pro-cognitive, anti-inflammatory and neuroprotective effects in the central nervous system (CNS). Most studies have indicated anxiogenic and neuroinflammatory effects of methamphetamine (MA) and other psychostimulants, even after periods of abstinence. The present study aimed to examine whether intranasal (IN) insulin treatment with high CNS bioavailability and minimal systemic side effects, can reverse the anxiety-like behavior and neuroinflammation induced by repeated MA administration. In male wistar rats, escalating doses of MA (1-10mg/kg, i.p.) were administrated twice a day for 10 consecutive days. IN insulin treatment (0.5 IU/day, for 7days after MA discontinuation) attenuated MA-induced anxiety-like behavior in the elevated plus maze task, and significantly decreased the levels of glial cell markers (GFAP and Iba1), pro-inflammatory cytokines (TNF-α and IL-6) as well as COX2 and NF-κB players of neuroinflammation, in the hippocampus of MA-treated animals. These findings introduce insulin as a potential therapeutic approach for the treatment of MA aversive symptoms.

 

https://www.ncbi.nlm...pubmed/28884876

 

J Cell Biochem. 2017 Sep 8. doi: 10.1002/jcb.26398. [Epub ahead of print]

  Intranasal insulin treatment restores cognitive deficits and insulin signaling impairment induced by repeated methamphetamine exposure.

Beirami E1, Oryan S1, Seyedhoseini Tamijani SM2, Ahmadiani A2, Dargahi L3.

Author information

Abstract

Long-term use of methamphetamine (MA) causes a broad range of cognitive deficits. Recently, it has been reported insulin signaling and mitochondrial biogenesis are involved in cognitive processes. This study aimed to examine whether MA induces cognitive deficits concomitant with insulin signaling impairment and mitochondrial dysfunctions and also intranasal (IN) insulin treatment can reverse cognitive deficits caused by MA. Rats were repeatedly treated with increasing doses of MA (1-10 mg/kg) twice a day for 10 days, and their cognitive functions were assessed using Y-maze, novel object recognition and passive avoidance tasks. The expression of components involved in insulin signaling (IR/IRS2/PI3K/Akt/GSK3β) and mitochondrial biogenesis (PGC-1α, NRF1 and TFAM) was measured in the hippocampus. Therapeutic effects of IN insulin delivery (0.5IU/day, for 7 days after MA discontinuation) were also investigated in MA-treated animals. Our results showed that repeated MA exposure induced cognitive deficits, and led to insulin signaling impairment and mitochondrial dysfunction. Interestingly, IN insulin treatment reduced MA-induced cognitive impairments possibly through activating insulin signaling, particularly PI3K/Akt/GSK3β pathway, and mitochondrial biogenesis. Thus, insulin and insulin signaling pathway can be considered as useful targets for the treatment of abnormalities associated with MA abuse. This article is protected by copyright. All rights reserved.

 

 

 

Edited by lostfalco, 23 September 2017 - 04:38 PM.

[lostfalco]

Hi everyone!

 

Ive read about ibudilast at your blog lost, and it is very difficult for me to source. (Eu)

I found a source but it is powder, would there be any problems with taking it in powder form?

Gastronomic issues, or anything else?

 

Thanks!

Hey Elkaer, Mimaki still carries ibudilast. It's just bit expensive.  https://www.mimaki-f...item_branch=001

Edited by lostfalco, 23 September 2017 - 04:11 PM.

[BieraK]

I have not read this post in a long time.
I think that this needs to be taken with caution, I don't know what is the interaction between LLLT generated ROS and drugs and specially with flavonols.
This study indicates that LLLT with Metformin is better than LLLT alone:
 

 

The effect of combined photobiomodulation and metformin on open skin wound healing in a non-genetic model of type II diabetes
 

Abstract

This study intended to examine the combined influences of photobiomodulation (PBM) and metformin on the microbial flora and biomechanical parameters of wounds in a non-genetic model of type II diabetes mellitus (TII DM). We induced a non-genetic model of TII DM in 20 rats by feeding them a 10% fructose solution for 2weeks followed by an injection of streptozotocin (STZ, 40mg/kg). After 21days from the injection of STZ, we induced one full-thickness skin wound in each of the diabetic rats. We randomly divided the rats into four groups: i) placebo; ii) pulsed wave laser (890nm, 80Hz, 0.324J/cm(2)); iii) metformin; and iv) laser+metformin. Rats received daily intraperitoneal injections of metformin (50mg/kg). On days 7and 15 we inspected the microbial flora of each wound. On day 15 we obtained a standard sample from each healing wound for biomechanical analyses. PBM significantly decreased colony-forming units (CFUs) 7days after wound infliction compared to the placebo group (LSD test, p=0.012). Metformin significantly enhanced the biomechanical property (stress high load) of the wounds compared to the placebo group (LSD test, p=0.028). We observed the same significant result for PBM compared to the placebo group (LSD test, p=0.047). PBM significantly accelerated the wound healing process and significantly reduced CFUs of bacteria in a non-genetic rat model of TII DM.

The effect of combined photobiomodulation and metformin on open skin wound healing in a non-genetic model of type II diabetes. Available from: https://www.research...ype_II_diabetes [accessed Nov 02 2017].

 
 

 

I don't understand why an AMPK activator like Metformin, as an mTOR inhibitor is better for wound healing, since mTOR is crucial for anabolic process and so for cell proliferation.

Edited by BieraK, 02 November 2017 - 04:32 AM.

[BieraK]

I have the following Question for LLLT users, Do you use it whit your regular consumption of supplements like flavonols. herbal extracts (Quercetin, curcumin, resveratrol, ginseng, gingko and similar )and drugs? or do you try to prevent that interaction?

[lostfalco]

Hamblin is still going strong. =)

 

"There is evidence that PBM can help the brain repair itself by stimulating neurogenesis, upregulating BDNF synthesis, and encouraging synaptogenesis."

 

"In healthy human volunteers (including students and healthy elderly women), PBM has been shown to increase regional cerebral blood flow, tissue oxygenation, and improve memory, mood, and cognitive function."

 

J Neurosci Res. 2017 Nov 13. doi: 10.1002/jnr.24190. [Epub ahead of print]

Photobiomodulation for Traumatic Brain Injury and Stroke.

Hamblin MR1,2,3.

Author information

 

Abstract

There is a notable lack of therapeutic alternatives for what is fast becoming a global epidemic of traumatic brain injury (TBI). Photobiomodulation (PBM) employs red or near-infrared (NIR) light (600-1100nm) to stimulate healing, protect tissue from dying, increase mitochondrial function, improve blood flow, and tissue oxygenation. PBM can also act to reduce swelling, increase antioxidants, decrease inflammation, protect against apoptosis, and modulate microglial activation state. All these mechanisms of action strongly suggest that PBM delivered to the head should be beneficial in cases of both acute and chronic TBI. Most reports have used NIR light either from lasers or from light-emitting diodes (LEDs). Many studies in small animal models of acute TBI have found positive effects on neurological function, learning and memory, and reduced inflammation and cell death in the brain. There is evidence that PBM can help the brain repair itself by stimulating neurogenesis, upregulating BDNF synthesis, and encouraging synaptogenesis. In healthy human volunteers (including students and healthy elderly women), PBM has been shown to increase regional cerebral blood flow, tissue oxygenation, and improve memory, mood, and cognitive function. Clinical studies have been conducted in patients suffering from the chronic effects of TBI. There have been reports showing improvement in executive function, working memory, and sleep. Functional magnetic resonance imaging has shown modulation of activation in intrinsic brain networks likely to be damaged in TBI (default mode network and salience network).

 

Edited by lostfalco, 19 November 2017 - 02:56 PM.

[lostfalco]

I have the following Question for LLLT users, Do you use it whit your regular consumption of supplements like flavonols. herbal extracts (Quercetin, curcumin, resveratrol, ginseng, gingko and similar )and drugs? or do you try to prevent that interaction?

I usually take flavanols in the morning and laser at night. 

[airplanepeanuts]

Hi lf,

sorry if this has been discussed before- are you sure that the products on amazon you recommend for lllt are safe to  apply on your brain? What's your evidence?

 

Thanks.

[lostfalco]

Hi lf,

sorry if this has been discussed before- are you sure that the products on amazon you recommend for lllt are safe to  apply on your brain? What's your evidence?

 

Thanks.

Hey airplanepeanuts, good question. I matched up the devices and the dosing recommendations as closely as possible with the scientific studies performed on human subjects. None of the transcranial studies on humans have had any side effects at all so I think we're in pretty safe territory.