I absolutely love all this information Dr. Topal and enjoyed hearing you speak at Warwick’s in La Jolla. I’m almost finished listening to your latest book on Audible. I would love nothing more than you know what AI model exists that has your entire book in the model where I could upload my complete electronic medical record and history to get recommendations. Is anything like this possible?
Thank you for this distillation of the latest information on how to reduce the incidence and impact of age-related diseases, and as you have stated, "While everything we know generally fits into this model, it is clearly reductionist, oversimplified. In thinking about how the human body works, it’s of course never this straightforward. However, we create models for their usefulness and I believe all of the data over recent years gets us to this synthesis for I/I."
It is sad and extremely frustrating that with the current regime's defunding of biomedical research we may be delayed or even prevented from exploring the full potential of these current findings. As a former healthcare provider it can be seen and proven repeatedly that PREVENTION is always the best way to minimize healthcare costs over the long run.
As you also said, "Ironically, primary prevention has enormous economic value and advantage compared to the cost of treatment of any of these age-related diseases."
This is still very useful to know, and greatly appreciated, and information like this is why I subscribe to your Substack. Thank you.
In food, the general public thinks that "anti-inflammatory" is good and "promotes immunity" is good. Since inflammation is a large part of immunity, that's an oxymoron. It is abnormal inflammation that is not good. Auto-immunity is bad. Similarly, mitochondria create oxygen free radicals to self-destruct malfunctioning cells. Eating "antioxidants" to prevent this (if it would work) is only likely to increase the load of senescent, malfunctioning cells in the body. Balance, Balance, Homeostasis. Let the body do it.
I am 71 and healthy. I walk daily, intermittent fast, and try to eat healthy. I am not overweight. I’m wondering if GLP-1 would benefit me and would like to take a low dose. I am positive for EBV (as so many are) and have never had COVID. I get vaccinated and have also had shingles vax.I have HPV-2 and for those reasons I’m thinking GLP-1 could be preventative. I have mild osteoporosis. My mother had dementia. I do not take any medication - only vitamin D, magnesium glycinate, Natto, collagen, and fatty15. What are your thoughts?
The immune system needs at least 50 ng/mL (125 nmol/L = 1 part in 20,000,00 by mass) circulating 25-hydroxyvitamin D to function properly. The only way most people can attain this is vitamin D3 supplementation in quantities, which while small, are 5 or more times the minimal quantities recommended by governments and many doctors, which are only sufficient to attain the 20 ng/mL circulating 25-hydroxyvitamin D levels the kidneys need to play their part in regulating calcium-phosphate-bone metabolism.
Rather than make a very long comment, here are links to and within a page in which the most pertinent research is cited and discussed: https://vitamindstopscovid.info/00-evi/ .
This begins with recommendations from New Jersey based Professor of Medicine, Sunil Wimalawansa on the average daily supplemental intake quantities of vitamin D3 which will attain least 50 ng/mL (125 nmol/L) circulating 25-hydroxyvitamin D, over several months, without the need for blood tests or medical monitoring:
70 to 90 IU / kg body weight for those not suffering from obesity (BMI < 30).
100 to 130 IU / kg body weight for obesity I & II (BMI 30 to 39).
140 to 180 IU / kg body weight for obesity III (BMI > 39).
For 70 kg (154 lb) body weight without obesity, this is about 0.125 milligrams (125 micrograms 5000 IU) a day. This takes several months to attain the desired > 50 ng/mL circulating 25-hydroxyvitamin D. This is 8 or more times what most governments recommend. "5000 IU" a day sounds like a lot, but it is a gram every 22 years - and pharma-grade vitamin D costs about USD$2.50 a gram ex-factory.
Many types of immune cell need a good supply of 25-hydroxyvitamin D calcifediol (made in the liver from vitamin D3 cholecalciferol) to run their 25-hydroxyvitamin D to calcitriol (1,25-dihydroxyvitamin D) intracrine and paracrine signaling systems. These are unrelated to hormonal (endocrine) signaling and are crucial to individual cells' ability to respond to their changing circumstances. Most medical professionals and immunologists have not heard of these. Intracrine signaling is within a single cell and paracrine is to nearby cells, including those of different types. Since there is no peer-reviewed explanation of these, I wrote a (non-peer-reviewed) tutorial in 2020: https://vitamindstopscovid.info/02-intracrine/.
Chauss et al. found permanently inflammatory Th1 regulatory lymphocytes in the lungs of hospitalised COVID-19 patients: "Autocrine vitamin D signaling switches off pro-inflammatory programs of Th1 cells" Nature Immunology 2021-11-11 https://www.nature.com/articles/ s41590-021-01080-3. (They are actually studying intracrine signalling - autocrine is with the receptors on the outside of the cell, but here they are in the cytosol. I made the same mistake at first). My summary of this dense cell biology article, or at least of its preprint, is at: https://aminotheory.com/cv19/icu/#2021-Chauss. These cells, unlike the Th1 cells from healthy controls, failed to transition from their pro-inflammatory startup program to their anti-inflammatory shutdown program, despite detecting the condition to do so (a high level of a complement protein). In the final article, researchers concluded that this failure was due largely or entirely to inadequate supplies of 25-hydroxyvitamin D. The circulating 25-hydroxyvitamin D levels of the patients was not available, but it is well known that people with even lower 25-hydroxyvitamin D levels than the poor levels in the general population (compared to 50 ng/mL) are most likely to develop severe COVID-19 symptoms.
The primary easily avoidable risk factor for Parkinson's disease and most or all other forms of dementia is low 25-hydroxyvitamin D: https:// vitamindstopscovid.info/00-evi/#3.3.
Low 25-hydroxyvitamin D levels "may reduce telomere shortening through anti-inflammatory and anti-cell proliferation mechanisms. Significant Low levels of telomerase activity create short telomeres, which in turn signal exit from the cell cycle resulting in cell senescence and apoptosis." https://www.sciencedirect.com/science/article/pii/S226013412400224X .
In 2020, Joseph and Carol Williams reported on this from the South of England: "Responsibility for vitamin D supplementation of elderly care home residents in England: falling through the gap between medicine and food" https://nutrition.bmj.com/content/3/2/256. The title and first sentence: "Daily vitamin D supplements are recommended for elderly care home residents; however, they are rarely given and vitamin D deficiency in care homes is widespread." tell us that the situation is bleak for most residents of aged care homes.
Inflammatory immune responses tend to involve indiscriminate cell destruction. These responses evolved largely or entirely to cope with multicellular parasites. Today, according to individual genetic variation, a significant proportion of the population suffer from auto-immune inflammatory disorders. These are worsened by the fact that most of these people don't have enough circulating 25-hydroxyvitamin D to run their immune systems, for instance to enable their Th1 lymphocytes to transition to their anti-inflammatory shutdown program. However, with 50 ng/mL circulating 25-hydroxyvitamin D, these problems typically persist.
The explanation, which is not widely enough known, is that tens of millions of years ago helminths (intestinal worms) evolved to exude multiple compounds which down-modulated the inflammatory, cytotoxic, immune responses which targeted them. Since one or more helminth infections were apparently ubiquitous in our ancestors, until around a century ago in advanced nations, the human (and before that, our pre-human mammalian ancestors) evolved stronger inflammatory responses than are healthy or would be required in the absence of this life-long down-modulation. Now we (in developed nations) are all de-wormed, our inflammatory responses, with considerable individual genetic variation, are overly strong, triggered by conditions other than multicellular parasites and prone to destroying our own cells.
I absolutely love all this information Dr. Topal and enjoyed hearing you speak at Warwick’s in La Jolla. I’m almost finished listening to your latest book on Audible. I would love nothing more than you know what AI model exists that has your entire book in the model where I could upload my complete electronic medical record and history to get recommendations. Is anything like this possible?
Not yet but there are several groups working on it....maybe in less than a year we'll see one that has been validated
Thank you for this distillation of the latest information on how to reduce the incidence and impact of age-related diseases, and as you have stated, "While everything we know generally fits into this model, it is clearly reductionist, oversimplified. In thinking about how the human body works, it’s of course never this straightforward. However, we create models for their usefulness and I believe all of the data over recent years gets us to this synthesis for I/I."
It is sad and extremely frustrating that with the current regime's defunding of biomedical research we may be delayed or even prevented from exploring the full potential of these current findings. As a former healthcare provider it can be seen and proven repeatedly that PREVENTION is always the best way to minimize healthcare costs over the long run.
As you also said, "Ironically, primary prevention has enormous economic value and advantage compared to the cost of treatment of any of these age-related diseases."
This is still very useful to know, and greatly appreciated, and information like this is why I subscribe to your Substack. Thank you.
Much appreciated.
In food, the general public thinks that "anti-inflammatory" is good and "promotes immunity" is good. Since inflammation is a large part of immunity, that's an oxymoron. It is abnormal inflammation that is not good. Auto-immunity is bad. Similarly, mitochondria create oxygen free radicals to self-destruct malfunctioning cells. Eating "antioxidants" to prevent this (if it would work) is only likely to increase the load of senescent, malfunctioning cells in the body. Balance, Balance, Homeostasis. Let the body do it.
I am 71 and healthy. I walk daily, intermittent fast, and try to eat healthy. I am not overweight. I’m wondering if GLP-1 would benefit me and would like to take a low dose. I am positive for EBV (as so many are) and have never had COVID. I get vaccinated and have also had shingles vax.I have HPV-2 and for those reasons I’m thinking GLP-1 could be preventative. I have mild osteoporosis. My mother had dementia. I do not take any medication - only vitamin D, magnesium glycinate, Natto, collagen, and fatty15. What are your thoughts?
The immune system needs at least 50 ng/mL (125 nmol/L = 1 part in 20,000,00 by mass) circulating 25-hydroxyvitamin D to function properly. The only way most people can attain this is vitamin D3 supplementation in quantities, which while small, are 5 or more times the minimal quantities recommended by governments and many doctors, which are only sufficient to attain the 20 ng/mL circulating 25-hydroxyvitamin D levels the kidneys need to play their part in regulating calcium-phosphate-bone metabolism.
Rather than make a very long comment, here are links to and within a page in which the most pertinent research is cited and discussed: https://vitamindstopscovid.info/00-evi/ .
This begins with recommendations from New Jersey based Professor of Medicine, Sunil Wimalawansa on the average daily supplemental intake quantities of vitamin D3 which will attain least 50 ng/mL (125 nmol/L) circulating 25-hydroxyvitamin D, over several months, without the need for blood tests or medical monitoring:
70 to 90 IU / kg body weight for those not suffering from obesity (BMI < 30).
100 to 130 IU / kg body weight for obesity I & II (BMI 30 to 39).
140 to 180 IU / kg body weight for obesity III (BMI > 39).
For 70 kg (154 lb) body weight without obesity, this is about 0.125 milligrams (125 micrograms 5000 IU) a day. This takes several months to attain the desired > 50 ng/mL circulating 25-hydroxyvitamin D. This is 8 or more times what most governments recommend. "5000 IU" a day sounds like a lot, but it is a gram every 22 years - and pharma-grade vitamin D costs about USD$2.50 a gram ex-factory.
Many types of immune cell need a good supply of 25-hydroxyvitamin D calcifediol (made in the liver from vitamin D3 cholecalciferol) to run their 25-hydroxyvitamin D to calcitriol (1,25-dihydroxyvitamin D) intracrine and paracrine signaling systems. These are unrelated to hormonal (endocrine) signaling and are crucial to individual cells' ability to respond to their changing circumstances. Most medical professionals and immunologists have not heard of these. Intracrine signaling is within a single cell and paracrine is to nearby cells, including those of different types. Since there is no peer-reviewed explanation of these, I wrote a (non-peer-reviewed) tutorial in 2020: https://vitamindstopscovid.info/02-intracrine/.
Chauss et al. found permanently inflammatory Th1 regulatory lymphocytes in the lungs of hospitalised COVID-19 patients: "Autocrine vitamin D signaling switches off pro-inflammatory programs of Th1 cells" Nature Immunology 2021-11-11 https://www.nature.com/articles/ s41590-021-01080-3. (They are actually studying intracrine signalling - autocrine is with the receptors on the outside of the cell, but here they are in the cytosol. I made the same mistake at first). My summary of this dense cell biology article, or at least of its preprint, is at: https://aminotheory.com/cv19/icu/#2021-Chauss. These cells, unlike the Th1 cells from healthy controls, failed to transition from their pro-inflammatory startup program to their anti-inflammatory shutdown program, despite detecting the condition to do so (a high level of a complement protein). In the final article, researchers concluded that this failure was due largely or entirely to inadequate supplies of 25-hydroxyvitamin D. The circulating 25-hydroxyvitamin D levels of the patients was not available, but it is well known that people with even lower 25-hydroxyvitamin D levels than the poor levels in the general population (compared to 50 ng/mL) are most likely to develop severe COVID-19 symptoms.
The primary easily avoidable risk factor for Parkinson's disease and most or all other forms of dementia is low 25-hydroxyvitamin D: https:// vitamindstopscovid.info/00-evi/#3.3.
Low 25-hydroxyvitamin D levels "may reduce telomere shortening through anti-inflammatory and anti-cell proliferation mechanisms. Significant Low levels of telomerase activity create short telomeres, which in turn signal exit from the cell cycle resulting in cell senescence and apoptosis." https://www.sciencedirect.com/science/article/pii/S226013412400224X .
In 2020, Joseph and Carol Williams reported on this from the South of England: "Responsibility for vitamin D supplementation of elderly care home residents in England: falling through the gap between medicine and food" https://nutrition.bmj.com/content/3/2/256. The title and first sentence: "Daily vitamin D supplements are recommended for elderly care home residents; however, they are rarely given and vitamin D deficiency in care homes is widespread." tell us that the situation is bleak for most residents of aged care homes.
Inflammatory immune responses tend to involve indiscriminate cell destruction. These responses evolved largely or entirely to cope with multicellular parasites. Today, according to individual genetic variation, a significant proportion of the population suffer from auto-immune inflammatory disorders. These are worsened by the fact that most of these people don't have enough circulating 25-hydroxyvitamin D to run their immune systems, for instance to enable their Th1 lymphocytes to transition to their anti-inflammatory shutdown program. However, with 50 ng/mL circulating 25-hydroxyvitamin D, these problems typically persist.
The explanation, which is not widely enough known, is that tens of millions of years ago helminths (intestinal worms) evolved to exude multiple compounds which down-modulated the inflammatory, cytotoxic, immune responses which targeted them. Since one or more helminth infections were apparently ubiquitous in our ancestors, until around a century ago in advanced nations, the human (and before that, our pre-human mammalian ancestors) evolved stronger inflammatory responses than are healthy or would be required in the absence of this life-long down-modulation. Now we (in developed nations) are all de-wormed, our inflammatory responses, with considerable individual genetic variation, are overly strong, triggered by conditions other than multicellular parasites and prone to destroying our own cells.
See the research cited and discussed at: https://vitamindstopscovid.info/06-adv/. I have not yet updated it to include my hypothesis for why much higher than normal - 100, 200 and beyond - 25-hydroxyvitamin D levels, such as according to the Coimbra Protocol, suppress much the same set of autoimmune inflammatory disorders as helminthic therapy (https://helminthictherapywiki.org) which involves introducing relatively benign helminth infections. See my comment at: https://hiddencomplexity.substack.com/p/epstein-barr-link-to-multisystem/comments.