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4. What happens when this stress lasts too long?

Lets continue talking about cellular stress and depletions of things in a cell. We got on that topic because of the macronutrient squabble from AHS. But after following some twitter feeds (@DigiSurg if you want to follow me) about supplement regimes I thought I might try to tie some cellular mineral depletions together with how it causes the cell stress and causes it to affect its cellular terroir and our resultant hormone status. I think this story will help you understand just how important following the trial of biochemistry is.

Any type of cellular stress lowers our stores of ATP and of Magnesium (Mg) because they are coupled together by our ATPase enzyme as we saw in this post. This is classically seen in diabetes development as we mentioned there. Another interesting thing also occurs to the cell, that we clinicians can follow on our patients regular labs like a Chem 7. Their carbon dioxide (CO2) levels also fall because mitochondria are actively transfer tons of electrons to O2 to make more ATP to replace the deficit from the stress. This causes a simultaneous drop in CO2. The normal cellular response to ANY cellular stress however is rather telling to review for most lay people and MD’s because they may have forgot how that biochemistry works. The simultaneous fall in ATP and Mg stimulates the cell to make LDL cholesterol! Yes, you read that correctly folks, the supposedly bad LDL stuff, LOL! It is obviously not bad if the cell is making it for some reason. Let us look why the cell does this. You may want to reread this blog on cholesterol.




The other affect of hypothyroidism is that it causes decreased steroid synthesis due to pregnenolone steal syndrome. Remember steroids secretion are how the brain maintains control over the twenty trillion cells in our bodies. If you cant make the chemicals the brain needs to maintain this control all hell can break loose from a control stand point. It also stands to follow that the lowered levels of these hormones are predictive of this process to the inquiring physician by lab testing. What I look for in cases like this is decreased hormone levels early in the steroid cascade from cholesterol to the steroids. After cholesterol comes pregnenolone , DHEA, and progesterone. Those three are very proximal to the cholesterol conversion. If they are lowered then we know we really have got a problem brewing. So this is why I use those hormone assays as clues to what is going on in the cell during stress. For example, in ICU patients who are sick and cant sleep well they suffer from very low levels of DHEA. Low DHEA levels correlate with very high IL-6 levels and poor sleep. If this is allowed to go on long enough patients may get an acute ICU psychosis called delirium. In brain trauma patients we see very low levels of progesterone and this correlates with poor neurologic outcome because progesterone is a co factor in brain derived growth factor to make new neurons.


Now that we have covered an acute cellular stress response lets talk about a chronic one we all will become familiar with…..aging. In aging, our metabolic rates drop. This means that we will have a lower T3 level as we age. This is in fact what we see in aging. We just reviewed above what a low T3 can do in acute cellular stress. What do you think happens with aging? Your catching on now. Its does the same thing but the onset is more insidious. And as this happens slowly over time what occurs? Our hormone levels all decline slowly. For some this decline happens to certain hormones quicker than others. But with testing we can predict what this means means to the aging person’s cellular stress.




  1. Cameron House says:


    I just read this and reread the VAP post and was curious if Paleo diet will reverse atherosclerosis or just prevent it's worsening? If so how?

    Also thanks again for a GREAT BLOG!

    • It can reverse it if it contains all the correct micro nutrients and avoids dietary overproduction of sdLDL which it often does.

  2. This is putting so much together for me! Even though there are many things in your blogs I don't quite understand since I was not schooled in biochemistry of the body, as you explain it all I'm amazed at how "simple" it all really is and how the medical community that spent so many years studying science could NOT KNOW this stuff!!??!!?? Too much time studying MEDICINE (big pharma) and not so much time on the science of the body, I guess.

    One of my last doctor visits where my labs were presented to me, I was telling her I needed to fix my hypothyroidism and she was telling me, "No, maybe we need to increase your Prozac because the TSH was 'normal' (4 on scale of 1-4)." Also on those labs was a lowered LDL, for which I was praised, but also lowering HDL. It wasn't totally in a danger zone yet, but the doc was "concerned" … DUH? I WAS HYPOTHYROID!!! I see now, those two are connected and I'm just astonished my doc poo-pooed my insistence that my thyroid needed help!!! Makes me really angry when doctors don't pay enough attention to patients and now I can see more of the details that supported my claim … more than the low basal body temp, the sluggishness, fatigue, etc, etc, ad nauseum. It was signalled in those labs! (TSH range SHOULD BE more like 1-3) I'm really NOT wanting to EVER go back … but I might, with this article and the rest of the blogs in hand once I'm recovered. (I am also on Armour Thyroid now, and working on balancing the thyroid along with the Leptin reset. So it should be an interesting visit with that doctor in about another six months or so.)

    Thanks so much for all you're doing, Dr Kruse!

    • @Kaleein This is why I lean heavy on biochemistry. It may make your head hurt for many of my blogs but sooner or later you will see why I do it. It allows us to see clearly why an evolutionary approach is best for optimization. I will continue to integrate this info instead of trying to deconstruct theories and opinions. To me that is how we got in trouble in medicine. When someone argues with me now I just open a biochemistry book or an endocrine book and show them what it says. My patients really like the way I go about things because they know why they have the problem they do and I seek to fix it not only in surgery but in the grocery store and in their kitchens. Thanks for the kind words.

  3. @Cameron House: Proper diet, including paleo diets, both prevent and can reverse atherosclerosis over time.

    Check this video from the Ancestral Health Symposium, "Paleo Diet and Atheroma: A Cardiovascular Surgeon's Perspective" by Dr. Guy-Andre Pelouze http://goo.gl/0ORd3

    Among other things he explains that: native (reduced) LDL cholesterols in paleo diet meats are NOT atherogenic, only oxidized LDL causes atheroma, and without oxidized LDL it is very difficult to have plaque formation.

    Oxidized LDL cholesterols are comprised of straight molecules that pack together tightly like a bundle of straws and form dense plaque deposits that because of their molecular properties become polymer like and are difficult to emulsify with blood & plasma fluids. The reduced cholesterols in organic meats on the other hand have a different structure and do not & cannot pack together to form plaque deposits.

    From Wikipedia, Unsaturated fat: "Trans unsaturated fats are particularly risky because the double bond stereochemistry allows the fat molecules to assume a linear conformation, which leads to efficient packing (i.e., plaque formation).

    (Contrary to Trans fats,)The geometry of the CIS double bond introduces a bend in the molecule, thereby precluding (preventing) stable formations (see specific fatty acid links above for drawings that illustrate this). Natural sources of fatty acids (see above) are rich in the cis isomer." http://goo.gl/PhNnn

    From Wikipedia, Trans fat: "Trans fat is the common name for unsaturated fat with trans-isomer (E-isomer) fatty acid(s). Because the term refers to the configuration of a double carbon-carbon bond, trans fats may be monounsaturated or polyunsaturated **but never saturated**." This is why natural saturated fats and cholesterols made from them are superior to artificial fats. http://goo.gl/JrCI6

    Also, high spectrum chromatography studies of arterial plaques found over 10 different compounds but NO saturated fats. Again, this is due to the different molecular forms between oxidized fats & cholesterols as opposed to good natural saturated fats and cholesterols. http://goo.gl/wzegi

  4. Resurgent says:

    Once again a great post, Jack.. Thanx.!

    What is evolving is that, a normal person, regardless of his lifestyle and eating habits, regardless of his age and medical history, should regularly test for some bio-markers to know the real state of his cell health. What we need from you is a clear self help procedure, what should one test for and how often. This information, I think, should also become a very important part of the Insurance regime you proposed earlier.

    • @ Resurg Many people want this…..but it is useless unless you have someone who can decipher it. Just look at Patrik right now over at PH asking about his 23andme data? He bought it and has no clue how to make an actionable sense of it. So you must ask yourself was it any good or worthwhile?

  5. "Any type of cellular stress lowers our stores of ATP and of Magnesium (Mg) … This causes a simultaneous drop in CO2."

    That's interesting to know because then CO2 would be a pretty accurate indicator for current magnesium status, wherever a RBC magnesium test isn't available. Unless there would be too many other possible causes for low CO2. What do you think?

    • Not true Pam all the time. Context of the testing and the person has to be done clinically. This is what makes medicine an art and a science. A low CO2 does not always mean a low Magnesium. You can get a real low CO2 from an acute head injury in a normal person who has good intracellular Mg for example. Remember context!! This one of the largest errors I see in many blogs that argue about macronutrients and diet. They never put things in context because few scientific papers do this as well. That is why their conclusions are usually faulty and it requires really dissecting the paper.

  6. "This means that all the steroids formed from cholesterol will also be lower if this chronically goes one. That means the sex steroid hormones also fall, and so does Vitamin D levels."

    Does supplementing with Vit D help correct this or merely shift the problem?

  7. @Tim. Just correcting Vitamin D alone helps this area but it does nothing for the hormones that are made earlier in the chain. HAving an optimal Vitamin D and a real low DHEA level may mean that with a persistent poor diet you may not get autoimmune disease of cancer but you may wind up with terrible sleep from your cratering DHEA levels and you will also notice libido, ED, osteoporosis, and energy changes from the simultaneously decrease in sex steroids. It also may be why you cant get pregnant. It may also be by your cognistion is lower now and you cant learn as well because your progesterone is too low. These are all things I see daily……all caused by a bad diet and often go undiagnosed because no testing is done to uncover these biochemical secrets of optimal health.

  8. @Cameron House and everybody: For a REALLY sobering view of what TRANS fats do to your arteries take a look at the Wiki page about atherosclerosis, and the chart & pictures. http://goo.gl/QKIEA

    Might also want to look at the Wiki on atheroma, another pic and more good info there. http://goo.gl/1X5m3

    At the risk of sounding repetitive I cannot stress enough that the time to stop intake of ALL TRANS fats in processed "foods" & liquid vegetable oils is NOW, and ideally 10 or 20 years ago. But since most of us are just learning about these things we'll just have to be extra diligent with our diets from now on.


    Thought so already. For example had my lowest LDL after a ferocious infection. But guess the real problem would much more subtler determinators than acute injuries or infections..

    • If your LDL was low with infection that tells me something is not right biochemically…….so you need to monitor that. With acute infection your LDL should rise normally.

  10. Thanks for the comments. Think it might be related to testing 2 weeks later only. The infection itself occurred on vacation in India in Jan. 2010, the coldest winter there for a long time.

    However, that I had the most carbohydrates during that month for a long time (except for the week with infection, when I just fasted): chapatis made of wheat, sugar in Chai, and rice – leading to such a low LDL was for me the most wired of it all.

    From 180 mg/dl in Oct. 2009 down to 91 in Feb. and up to 142 again in April 2010. Guess the strong infection just depleted all my cholesterol stores.

  11. Don't know if it means much, but liver enzymes were actually at their best at that time: GOT 22, GPT 23 and 32 GGT. Though still low, but HDL was actually on an upward trend not interrupted by the infection. And Triglycerides made a similar move as LDL, just not as pronounced.

    However, HbA1c, EST and non-sensitive CRP have been the highest I've seen since I test regularly for almost 3 years, but still not that bad at 5.1%, 47 and 0.6.

  12. hi Dr. K,

    your answer to Resurgent sounds like something my doctor would say and that makes me sad. its like saying only people who can read should have access to books. why isn't it useful to have a medical history documented by specific tests even if you won't know what numbers mean? couldn't the results be used for comparison in the future as our understanding improves??

  13. Hi Jack,

    What do you think of this? This seems huge and dove tales nicely with your Quilt layering does it not?


  14. This link explains more about the proteins involved.


  15. The authors wrote that "All types of ALS are, indeed, tributaries, pouring into a common river of cellular incompetence."

    "Cellular incompetence", sounds like you wrote it for this post on depleted cells…

  16. http://www.ncbi.nlm.nih.gov/pubmed/20736141

    the reason I dont like serum Mg testing

  17. So how can I raise my cholesterol? I have been following a vlc paleo diet since May of this year. I have T2 diabetes almost under control and also am being treated for low thyroid with a natural thyroid by a naturpath. My cholesterol on SAD is around 150. It is now 114. My HDL is 32 (up from 29). My trigs are 58 and my LDL is 70 and VLDL is 12.


  1. […] This should help you guys understand it all a bit more………. CELLULAR DEPLETIONS….WHY SHOULD YOU CARE? | Jack Kruse Reply With Quote   + Reply to […]

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