Low carb and lipids

[donheff]

Some other very interesting things have been discovered recently as well. There is a theory that people who undergo fasting live longer. It turns out that this is partially true but the fasting is best achieved by going at least 14 hours once a day without food and not by starving for days at a time. So, if you have your last meal at 1800 then wait until 0800 in the morning for breakfast you can enjoy the benefits of fasting without the pain and suffering of actual starvation. We have done this for years without actually knowing it was beneficial. It is just how we live. Generally we have breakfast around 1030 and don't eat any lunch.

NIH is running studies to see if the benefits of fasting result from increases in cellular nicotinamide adenine dinucleotide (NAD+ which decreases with age). So far they have done a small scale study that indicates that a supplement with Nicotinamide Riboside (NR) significantly increased NAD+ levels in humans without apparent negative effects. A larger term study is underway to see if there is evidence of beneficial health results. Exciting life extension results were shown in mice but they were genetically engineered NAD+ deficient mice so that may not mean a whole lot for normals mice or normal humans. It will be interesting to see what comes out of this study.

 

[RAE]

Isn’t ammonia a byproduct of protein metabolism? The body readily eliminates that. In all the study and discussions of ketosis (not ketoacidosis), by many medical doctors and scientists from many disciplines, I have never run across ammonia mentioned as a dangerous byproduct of ketosis.

Yes, it is. But the body can usually handle the amount of ammonia produced from a typical keto diet without any issues. You would only run into problems if you consumed a huge amount of protein daily, and not much fat. Here is one explanation:

"One byproduct of protein metabolism is ammonia, which is toxic. Usually, your liver converts ammonia to urea, which comes out harmlessly in your urine. But if you eat more than about 230 grams of protein a day, your liver gets overwhelmed. At that point, you’ll turn extra protein into glucose, to avoid ammonia poisoning. Here’s the thing, though: 230 grams of protein is the equivalent of about ten burgers a day. And there are very few compelling reasons to eat ten burgers a day."

And here is another one, showing how consuming fat along with protein is also protective:

The body can only supply roughly 1000 calories per day through a protein-only diet because the liver is only capable of producing 250 grams of glucose from protein, no matter how much protein you eat. So, you will still feel hungry, and you'll eat more. Unfortunately, your liver will start struggling and failing to convert the ammonia into urea (not enough ATP) so the ammonia will reenter your blood stream. This starts messing with your nervous system.

According to the Back Across the Line blog,

"Excess intake of nitrogen leads in a short space of time to hyperammonemia, which is a build up of ammonia in the bloodstream. This is toxic to the brain. Many human cultures survive on a purely animal product diet, but only if it is high in fat.

"A lean meat diet, on the other hand cannot be tolerated; it leads to nausea in as little as three days, symptoms of starvation and ketosis in a week to ten days, severe debilitation in twelve days and possibly death in just a few weeks. A high-fat diet, however, is completely healthy for a lifetime.

 

[RAE]

There is a great deal of skepticism about the assumed link of elevated cholesterol and heart disease. We have believed this dogma for a very long time and statins became the answer. However, death rates from myocardial infarctions haven't changed at all despite massive and over-prescribed statins. On the other hand it is a great success story for the pharmaceutical companies. This would lead one to believe there is much more to the picture than cholesterol and that perhaps cholesterol becomes elevated as a natural process of aging. It is very difficult to study cause and effect in complex models. Animal models are fine up to a point but never perfectly model human disease. This was my area and modeling is just that, and not the actual process. Humans are very difficult to study as they lead complex lives with multiple risk factors. Stress and diet appear to be associative but the actual cause of myocardial disease has not yet been discovered. It very likely may turn out that myocardial disease is actually an infection or could be related directly to the microbiome.

We are a species that has evolved faster than our bodies can keep up with. We developed as hunter-gatherers and traveled from one food source to another with fairly long breaks between. Excess nutrients are converted into fat for storage for those times when we need it like when there is no food sources. Women specifically deposit fats more than men so as to provide nutrition to babies through breast feeding. However, we now have plenty of food (most people from western nations) and the excess is deposited as fat. The problem is excess consumption and reduced demand. The balance is to eat only enough to sustain and to consume the excess through exercise. Balancing the diet should all be done through moderation and forcing ketosis is probably dangerous (the end result molecule of acetone metabolism is ammonia which is toxic. Acetone itself is a carcinogen). Other extreme diets will also have deleterious effects. One can argue all of this ad nauseum but to me it is that simple. Eat in moderation a well balanced diet, exercise at least 1 hour a day and all should be fine. I am not concerned about high cholesterol and believe that the imbalances are caused by an altered gut microbiome. I developed my own yogurt using strains that are known to be beneficial (through double blinded studies) and use that to adjust the gut microbiome. I have normal cholesterol levels and reduced stress and inflammation. I have no proof whatsoever that my yogurt is beneficial but apparently it is working for moth of us which is enough proof for me. There is a great deal of work going on regarding the microbiome and it is becoming clear that many ailments are caused by having the wrong bacterial mix..

Interesting post, thanks. I would generally agree with most of your points. Eating in moderation can be good, but some people unfortunately take that advice as a license to eat whatever they want in moderation (including things that are clearly not healthy, in any amounts.......industrial seed oils, cookies, doughnuts, chips, etc). If you are eating mostly nutrient-dense foods, on the other hand, moderation and variety is a good thing.

You say that the cause of myocardial disease has not yet been discovered. That may be true, but over the last 20 years or so, quite a bit of evidence points toward insulin resistance as a driving factor. I've included links to two papers below that discuss this connection.

https://cardiab.biomedcentral.com/articles/10.1186/s12933-018-0762-4

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC380256/

With your background in microbiology, I would be interested to hear your thoughts about insulin resistance as it relates to cardiovascular disease.

 

[Old Microbiologist]

donheff, Unlike you, I read the literature and keep well informed. Please take the time to study at least the attached review article and stop assuming pharmaceutical companies are working to benefit mankind. It is big business and typical for American business practices anything is possible. Perhaps you received payment from drug reps for prescribing their pharmaceuticals which is a common practice in America. All of my work was at the behest of the US government and I only received my annual salary as any normal military officer. All of my patents were sold for $1 to pharmaceutical companies so I never received any personal benefit from them. All work done by government labs is the property of the US government. Some government researchers have made money from their inventions (usually 5%) but none of mine were lucrative. So, I have no personal profit bias in my research which is how it should be.

I am a scientist, albeit retired, and am a immunologist specializing in macrophage/lymphocyte interactions. My main role was aerosol infections of high consequence pathogens and as such I developed numerous animal models (mostly non-human primates) of infections for known and newly emerging pathogens. I was the go-to guy who was tasked with determining the pathogenesis for unknown pathogens (either natural or designed). I am also a pathologist as well and did most of my own necropsies in non-human primates, cut out, stained, and read my own samples. I also developed several novel molecular biology techniques for diagnostics and was instrumental in developing novel therapeutics and vaccines for orphan (non-profitable) pathogens. I also developed and conducted parallel human models on patients in endemic areas (third world or worse) to develop in vitro correlates of protection to marry up the animal and human models. So, I think I might just actually know what I am talking about.

The early literature on statins was found to be heavily biased. Oh, I also have a PhD in non-parametric statistics and was director of clinical research for quite some time at a major military medical center and sat on review boards for many research projects. I can tell you the bias in many of these studies is abhorrent. Changes made to publication requirements now require researchers state in publications who they receive support from making this bias more transparent. Clinical trial requirements now track who is rejected from a study, when and why and it was revealed in the early studies that patients not fitting into the desired outcomes were eliminated. Once you correct for that there is no statistical improvement in mortality from the use of statins. One interesting finding is that LDL have a positive correlation which is the opposite of dogma, in half the studies.

In my own case it was extremely interesting. Because I was working in a classified laboratory using high consequence pathogens (most completely antibiotic resistant and 99% fatal), I was in the biosurety program and monitored frequently. I had had an eye examination at my required annual and very complete physical and no evidence of cataracts was observed. I was having problems using my microscope 3 months later and none of my co-workers using the same instruments were seeing the same garbage in the lenses I was seeing. I self-reported to the biosurety officer, had a repeat eye examination and had developed severe cataracts in both eyes when re-examined. The garbage in the lenses of the microscope I was seeing was actually my own cataracts. The only thing that had changed was I had been put on high dose lipitor (100mg a day) as my HDL was zero although my total cholesterol was only 120. They did a carotid artery ultrasound and determined I had 50% occlusion hence the high dose lipitor. The latter diagnostic technique is now out of favor having been debunked a few years later. It turns out this is a fairly well known side effect of lipitor and other newer statins. I got the lens replacements and everything was hunky dory after that although now I had to wear half glasses while wearing my pressure suit making that work, especially surgeries (I implanted radiotelemetric monitors in the NHP prior to each challenge study) somewhat more difficult. Necropsies within a biosafety cabinet inside a containment room while wearing a pressure suit is not particularly easy and you can't sit anywhere comfortably as the filters and fan unit are on your lower back and the batteries on your hips. I am not complaining but I am describing my conditions of work on a daily basis.

Anyway, the simple test is if statins are so good why hasn't mortality from myocardial disease statistically changed? Statins are the single most prescribed drugs in the world yet don't seem to actually affect meaningful changes. But, they are highly profitable. They have been out for a long time now yet no effect is observed on a large scale which makes me think cholesterol is associative and not causative. I do believe it is involved in plaque deposition but no one knows whether if reducing cholesterol levels affect plaque deposition. It is inferred but not proven. Calcium probably is more important and there is a lot of work on iron metabolism which appears to have a stronger link to disease than cholesterol. Anyway, assuming statins are the answer or even that extreme diets to achieve lower cholesterol levels is based on dogma which is probably wrong given the statistics. Many physicians refuse to accept any other alternative as the dogma is so deeply engrained in their thinking which is unfortunate.

 

[Old Microbiologist]

RAE, I do agree that insulin resistance is a serious problem and I think it is associative to CAD. Personally, I believe there is something larger going on and suspect altered microbiome to be the actual cause. There is plenty of work going on to try and sort this out. The human body is a complex system and everything is connected. Each individual is different and has different life styles making analysis in humans very difficult. Animal models help to sort out system differences and lead us to look for similar things in humans and only through large scale studies can we figure out what is happening. The big question is a chicken verses egg problem. Is the altered microbiome a consequence or a cause? Here are a few articles discussing insulin resistance and the gut microbiome:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3705322/
https://www.sciencedirect.com/science/article/abs/pii/S1931312819303488
https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007727

As I said earlier I designed my own yogurt to try and overcome the microbiome. You can't get enough in capsules to be worthwhile. My home made yogurt has roughly 1x10^12 viable organisms per ml and I eat 250 ml a day. It dramatically affects your bowel process and my poop generally smells like baby poop when being breast fed as one of the 6 main organisms is Bifodobacterium infantis isolated from human breast milk. More strains are being identified so I will likely adjust my mix once these are studied more. One other thing we do is eat home made naturally fermented sauer kraut as it contains bacteria that can't be grown at home without using a fermenter. Between the yogurt and sauer kraut we are adding the essential bacteria which might not be present otherwise. So far I am still alive

 

[Old Microbiologist]

RAE, I caught this in my inbox this morning which you might find interesting with regards to insulin insensitivity:"Whole Body Vibration-Induced Omental Macrophage Polarization and Fecal Microbiome Modification in a Murine Model" https://www.mdpi.com/1422-0067/20/13/3125

 

[audreyh1]

+1. At my next physical/blood test, I am going to request that a fasting insulin test be done. I already have an HbAIC test done each year, but I want the fasting insulin test to see where I stand. It's absurd that this test is not routinely included in a standard blood test package, but it's not. If my doc declines to order the test, I'll just go have it tested on my own, at one of the labs. I think the cost is about $30, so not expensive at all.

This comes down to standard of care. Doctors are generally conservative about routine screening tests - they follow what is recommended.

Unless fasting insulin becomes one of the routine screening tests, few doctors will order it, even though it can detect problems years before fasting blood glucose indicates a problem/diabetes risk.

So it definitely seems like it should be. But who is going to push for that change? There is no drug to reduce insulin or reverse insulin resistance (well, metformin can help but it’s an older inexpensive drug).

 

[donheff]

donheff, Unlike you, I read the literature and keep well informed. Please take the time to study at least the attached review article and stop assuming pharmaceutical companies are working to benefit mankind...

The early literature on statins was found to be heavily biased...
.
Anyway, the simple test is if statins are so good why hasn't mortality from myocardial disease statistically changed?

Interesting stuff but I am not sure why you singled me out as an uninformed troglodyte since my quote of you was supportive and intended to tease out your opinion on a matter unrelated to statins. I have read (and agreed with you on, albeit not understanding it as well as you) much of the statin lterature you mention. I dropped statins years ago after reading about them and I didn't mention anything in this thread in support of big pharma. I did mention studies of supplements purported to improve cell health underway at NIH that are not being conducted by big pharna - probably because the supplements don't offer the opportunity of lucrative patents. I quoted you because you mentioned the potential benefits of extreme calorie restriction which led to the hypothesis that increased NAD+ might be a factor and ultimately to the NIH studies.

 

[Golden sunsets]

Ya Donheff, I was trying to figure out what you had said to this guy to tick him off, but I couldn't find anything to warrant his sarcasm. It seems like we are all drinking the same cool aid at this point and he's largely preaching to the choir.

 

[audreyh1]

Ya Donheff, I was trying to figure out what you had said to this guy to tick him off, but I couldn't find anything to warrant his sarcasm. It seems like we are all drinking the same cool aid at this point and he's largely preaching to the choir.

Don replied to a post by AllDone that scolded us that “The idea that elevated blood cholesterol levels are not associated with increased risk of cardiovascular disease is simply wrong.”

Perhaps that was the mixup?

 

[donheff]

Don replied to a post by AllDone that scolded us that “The idea that elevated blood cholesterol levels are not associated with increased risk of cardiovascular disease is simply wrong.”

Perhaps that was the mixup?

Yes, I was rather short in my response to AllDone and would have quietly accepted a rejoinder from him (probably).

 

[RAE]

Interesting stuff but I am not sure why you singled me out as an uninformed troglodyte since my quote of you was supportive and intended to tease out your opinion on a matter unrelated to statins. I have read (and agreed with you on, albeit not understanding it as well as you) much of the statin lterature you mention. I dropped statins years ago after reading about them and I didn't mention anything in this thread in support of big pharma. I did mention studies of supplements purported to improve cell health underway at NIH that are not being conducted by big pharna - probably because the supplements don't offer the opportunity of lucrative patents. I quoted you because you mentioned the potential benefits of extreme calorie restriction which led to the hypothesis that increased NAD+ might be a factor and ultimately to the NIH studies.

+1. Microbiologist, I agree with Golden Sunsets that you were way too hard on Donheff - perhaps you misconstrued what he was trying to say? From his prior posts, I know that Donheff reads the literature, and as he says, his feelings about statins are probably similar to yours. He was simply mentioning some studies underway on NAD+ (which I have read about also), and the fact that NAD+ may mimic the effects of fasting in some ways.

 

[audreyh1]

+1. Microbiologist, I agree with Golden Sunsets that you were way too hard on Donheff - perhaps you misconstrued what he was trying to say? From his prior posts, I know that Donheff reads the literature, and as he says, his feelings about statins are probably similar to yours. He was simply mentioning some studies underway on NAD+ (which I have read about also), and the fact that NAD+ may mimic the effects of fasting in some ways.

Maybe it was AllDone’s post that Old Microbiologist was actually responding to.

 

[RAE]

As I said earlier I designed my own yogurt to try and overcome the microbiome. You can't get enough in capsules to be worthwhile. My home made yogurt has roughly 1x10^12 viable organisms per ml and I eat 250 ml a day. It dramatically affects your bowel process and my poop generally smells like baby poop when being breast fed as one of the 6 main organisms is Bifodobacterium infantis isolated from human breast milk. More strains are being identified so I will likely adjust my mix once these are studied more. One other thing we do is eat home made naturally fermented sauer kraut as it contains bacteria that can't be grown at home without using a fermenter. Between the yogurt and sauer kraut we are adding the essential bacteria which might not be present otherwise. So far I am still alive

I don't doubt that the composition of the gut microbiome is very important for good health. You are probably familiar with Dr. William Davis ("Wheat Belly" author). He makes a yogurt similar to what you describe, using Lactobacillus reuteri. Here is more information on what he does, if anyone is interested:
https://www.luvele.com/blogs/recipe-blog/how-to-make-l-reuteri-yogurt

My wife and I eat quite a few fermented foods that we make at home, mostly from our garden produce......kimchi, sauerkraut, and lots more.

 

[RAE]

Calcium probably is more important and there is a lot of work on iron metabolism which appears to have a stronger link to disease than cholesterol.

With regard to iron, I was having some issues with my heart a few years ago now (premature ventricular contractions), and none of the doctors I saw had any clue what the cause was. I eventually figured out the cause on my own, after having my ferritin and serum iron checked as part of a blood test. Both were way too high, especially ferritin. After donating blood a few times, my symptoms started to fade away. After a few more donations, they were gone. I had my ferritin checked again after that, and it is now down to about 60 ng/mL, which is where it should be. I learned a whole lot about the dangers of excess iron while I was trying to figure out what was going on with my symptoms. I highly recommend that everyone beyond middle age or so get their serum ferritin checked as part of a routine blood test package. The human body has no effective way to get rid of excess iron, so it gradually accumulates over time in a lot of people. Free iron in the blood is highly oxidative and can damage all body organ systems, including the heart. The serum ferritin test is a $50 test, but most doctors will not order it for you unless you insist (similar to fasting insulin).

 

[Old Microbiologist]

My apologies if I offended anyone. I know I am more or less out of the box on these things and have been so for a long time. I recall being chastised over supporting Stanley Prusiner over his concept of prions which later was proved correct. I also was at the bleeding edge in suggesting that HIV was going to be a retrovirus and was ostracized over that for several years. Of course, that turned out to be correct as well. I personally believe that the insult which causes infarctions is due to localized mycoplasma infection which has been suggested by autopsy data but not yet proven. It is yet another associate finding. I believe it is a very complicated problem and probably related to a person's susceptibility which is in turn caused by our individual inherited Major Histocompatibility Complex (MHC) milieu and probably to some extent our infant infections of our parent's bacterial flora prior to immune tolerance being established. We have not yet figured out how to break tolerance although nature does it to us all the time (Lyme disease is a good example). Once someone figures that out then we might be able to permanently replace our bad flora for good ones assuming we also figure out which one's are good.

 

[audreyh1]

With regard to iron, I was having some issues with my heart a few years ago now (premature ventricular contractions), and none of the doctors I saw had any clue what the cause was. I eventually figured out the cause on my own, after having my ferritin and serum iron checked as part of a blood test. Both were way too high, especially ferritin. After donating blood a few times, my symptoms started to fade away. After a few more donations, they were gone. I had my ferritin checked again after that, and it is now down to about 60 ng/mL, which is where it should be. I learned a whole lot about the dangers of excess iron while I was trying to figure out what was going on with my symptoms. I highly recommend that everyone beyond middle age or so get their serum ferritin checked as part of a routine blood test package. The human body has no effective way to get rid of excess iron, so it gradually accumulates over time in a lot of people. Free iron in the blood is highly oxidative and can damage all body organ systems, including the heart. The serum ferritin test is a $50 test, but most doctors will not order it for you unless you insist (similar to fasting insulin).

Do you have a good reference on appropriate ferritin levels? Ferritin is included in my annual panels, and now that I'm post-menopause they are definitely higher. Mine is currently 112 ng/mL and the reference range given is 16-232 ng/mL. It was around half of that pre-menopause and I'm pretty sure I was also taking iron back then aiming for 90-110, then but stopped taking iron after periods stopped completely.

 

[Dalmore]

With regard to iron, I was having some issues with my heart a few years ago now

Have you been tested for hereditary hemochromatosis? It is a genetic condition where the body "hides" iron. It affects primarily white, northern Europeans whose ancestors survived the plague. Without regular blood letting it can cause organ failure starting in your late 40s for men. Women are less prone to early symptoms due to menses. I discovered I am a carrier for the gene after taking the 23&Me DNA test. My sister (65) got tested and was found to have both genes. She has been having blood taken every other week for a couple of months to get her iron numbers down to normal. She only recently started into a maintenance cycle. We think our mom may have had both genes also. Both had gallbladder issues in their late 50s, which can be one of the many symptoms.

 

[RAE]

Have you been tested for hereditary hemochromatosis? It is a genetic condition where the body "hides" iron. It affects primarily white, northern Europeans whose ancestors survived the plague. Without regular blood letting it can cause organ failure starting in your late 40s for men. Women are less prone to early symptoms due to menses. I discovered I am a carrier for the gene after taking the 23&Me DNA test. My sister (65) got tested and was found to have both genes. She has been having blood taken every other week for a couple of months to get her iron numbers down to normal. She only recently started into a maintenance cycle. We think our mom may have had both genes also. Both had gallbladder issues in their late 50s, which can be one of the many symptoms.

Yes, I've been tested and I don't have hemochromatosis. It's still possible (and not that uncommon, I found out) to have "iron overload" and not have hemochromatosis, which is my situation. That's why I suggest that everyone past about middle age start having their serum ferritin checked when they get their routine blood testing done. Oh, and don't believe the "reference ranges" most labs put on serum ferritin, either. My ferritin came back originally at over 400ng/mL, and since the reference range was something like 25 - 500 ng/mL, the doctors all said my number was within the reference range, so "nothing to worry about". Wrong!! I later found out that most of Europe, Japan and other places in the world uses a reference range for ferritin that tops out at 200 ng/mL, which is about the way it should be. And ideally, you want your ferritin below 100. I've done a lot of reading on iron overload and the serious health issues that can be caused by free iron in your system (heart disease, cancer, liver disease, and more), and I'm now convinced that a whole lot of people could benefit from having their ferritin checked at least once in a while. And if it's too high, it's easy to lower it by donating blood. One more fact of interest........people that donate blood at least once or twice yearly live several years longer, on average, than people who do not donate blood. This could very well be due getting their iron levels down to a safe level and keeping them that way, due to regular blood donation. I know that I will be donating blood at least twice yearly for the rest of my life now, for certain.

 

[RAE]

Do you have a good reference on appropriate ferritin levels? Ferritin is included in my annual panels, and now that I'm post-menopause they are definitely higher. Mine is currently 112 ng/mL and the reference range given is 16-232 ng/mL. It was around half of that pre-menopause and I'm pretty sure I was also taking iron back then aiming for 90-110, then but stopped taking iron after periods stopped completely.

Audrey, you are probably in decent shape with a ferritin level of 112, but based on what I've read, it wouldn't hurt you at all, and might be beneficial, to get it down a bit further. Here is a link to one paper that presents some pretty good evidence that it's best for both men and women to keep their ferritin near the low end of the reference range, for optimum health and disease prevention.

https://www.isom.ca/wp-content/uploads/The-Risk-of-Too-Much-Iron-Normal-Serum-Ferritin-Levels-May-Represent-Significant-Health-Issues-28.4.pdf

It's worth reading the whole paper, but here is a quite from the Conclusions section:

"This review suggest the hypothesis that optimum adult serum ferritin levels in the context of health issues may be in the range of 20-40 for women and 50-70 for men."

There are many more papers and articles online about iron overload, and you may want to review some of them also. I know that after reading many, many papers over a few months time (when I was having my issue with premature ventricular contractions, and other problems), I came to the conclusion that I wanted to get my ferritin down to about 60-70 or so, and keep it there, for the rest of my life. Every time you donate blood, your ferritin number drops by roughly 30 ng/mL. I get my ferritin tested now annually, to see how many times I need to donate blood in the coming year to keep it around that level.

P.D. Mangan, who is a microbiologist by training, has done a lot of research on iron overload, and written may articles (and a book) about it. Here is one article he wrote in 2016 that provides some good information about it:

https://medium.com/better-humans/why-iron-is-the-most-underrated-factor-in-health-a36e2db37258

As he says in the article, one reason no one hears much about the dangers of iron overload is that there is no money to be made from treating it. Donating blood fixes the issue, and of course that is free, so you will never see Big Pharma or anyone else talking about the dangers of excess iron.