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Old 04-08-2022, 03:27 AM
 
133 posts, read 95,739 times
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I was surprised to read that Medical Lab Guy has so many reservations about laboratory test results and their interpretation. Please don’t think that I’m questioning what he said; I’m just surprised that someone who has worked in that field has so many reservations. I can support his concerns to some extent.

In my last "paid" job as a mentor to post-grads, a part of their training was to do their own laboratory assays of whole blood, plasma and serum electrolytes, as well as all possible hematological tests. We used to be able to purchase standard reference sera that had been analysed by a number of different commercially-available testing methods. The one in particular that showed the greatest variability between tests was serum magnesium. There was up to a 30% difference in analyses depending on the tests used. If a postgrad was analyzing magnesium concentrations between two populations, then they had to use the same test for all cases to make a comparison. And the end result could be regarded as a valid comparison. There is a limitation on interpretation of such tests as well, if a calculation called a Coefficient of Variation of the test being used has a wider variation than the difference between populations. So, you can’t just send a blood sample off to a lab and expect that a single test on a single day will give you an accurate picture of your blood status of any particular component.

You can just regard it as a rough guide. If you consistently use the same lab over years, you can regard the trends as somewhat reliable.

Most of you have probably gleaned from my alias number that I am currently 90. I do not attend a geriatrician; my general practitioner suffices. I hadn’t bothered with a vitamin D test until recently, because I wear shorts and singlet most of the Spring, Summer and Autumn. The test I did request 6 months ago gave a reading in the 70s.

I personally think the evidence suggests that a satisfactory vitamin D concentration is important for satisfactory health. A couple of references suggest so:
The finding that there are vitamin D receptors in most cells of the body has now led to the acceptance of vitamin D more as a hormone than a vitamin with a much wider range of cellular functions. (Bikle 2009; https://academic.oup.com/jcem/article/94/1/26/2597530).

Hossein-nezhad (2013; https://vitamindwiki.com/291+genes+i...RCT+March+2013) compared the gene expression of white cells in subjects with serum 25-hydroxy vitamin D concentrations less than 25 nanograms per mL at baseline with those of subjects with greater than 25 ng/mL and found a significant difference in the expression of 66 genes. After supplementation with up to 2000 International Units of vitamin D3 daily for two months there was no difference in gene expression of the two groups. This suggests that vitamin D is essential for gene expression within cells. The deficient subjects were used as their own controls.

There is at least one double blind random controlled trial showing that 1000 IU a day significantly increased the microbial resistance of airway surface liquid in human subjects compared with placebos (Buongiglio et al 2017; https://bmjopenrespres.bmj.com/conte...00211.abstract) in Effect of vitamin D 3 on the antimicrobial activity of human airway surface liquid: preliminary results of a randomised placebo-controlled double-blind trial.

And of course, the most important role of vitamin D is its role in the cellular manufacture of not only immunoglobulins (anti-microbial peptides -- White (2022; https://www.mdpi.com/2072-6643/14/2/284/htm), but also its role in the manufacture of most of the raw proteins that are activated by vitamins K1 and K2 and which are involved in bone, brain and blood vessel health.
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Old 04-08-2022, 09:56 AM
 
Location: San Diego, California
1,147 posts, read 863,305 times
Reputation: 3503
Quote:
Originally Posted by Doogles31731 View Post
I was surprised to read that Medical Lab Guy has so many reservations about laboratory test results and their interpretation. Please don’t think that I’m questioning what he said; I’m just surprised that someone who has worked in that field has so many reservations. I can support his concerns to some extent.

In my last "paid" job as a mentor to post-grads, a part of their training was to do their own laboratory assays of whole blood, plasma and serum electrolytes, as well as all possible hematological tests. We used to be able to purchase standard reference sera that had been analysed by a number of different commercially-available testing methods. The one in particular that showed the greatest variability between tests was serum magnesium. There was up to a 30% difference in analyses depending on the tests used. If a postgrad was analyzing magnesium concentrations between two populations, then they had to use the same test for all cases to make a comparison. And the end result could be regarded as a valid comparison. There is a limitation on interpretation of such tests as well, if a calculation called a Coefficient of Variation of the test being used has a wider variation than the difference between populations. So, you can’t just send a blood sample off to a lab and expect that a single test on a single day will give you an accurate picture of your blood status of any particular component.

You can just regard it as a rough guide. If you consistently use the same lab over years, you can regard the trends as somewhat reliable.

Most of you have probably gleaned from my alias number that I am currently 90. I do not attend a geriatrician; my general practitioner suffices. I hadn’t bothered with a vitamin D test until recently, because I wear shorts and singlet most of the Spring, Summer and Autumn. The test I did request 6 months ago gave a reading in the 70s.

I personally think the evidence suggests that a satisfactory vitamin D concentration is important for satisfactory health. A couple of references suggest so:
The finding that there are vitamin D receptors in most cells of the body has now led to the acceptance of vitamin D more as a hormone than a vitamin with a much wider range of cellular functions. (Bikle 2009; https://academic.oup.com/jcem/article/94/1/26/2597530).

Hossein-nezhad (2013; https://vitamindwiki.com/291+genes+i...RCT+March+2013) compared the gene expression of white cells in subjects with serum 25-hydroxy vitamin D concentrations less than 25 nanograms per mL at baseline with those of subjects with greater than 25 ng/mL and found a significant difference in the expression of 66 genes. After supplementation with up to 2000 International Units of vitamin D3 daily for two months there was no difference in gene expression of the two groups. This suggests that vitamin D is essential for gene expression within cells. The deficient subjects were used as their own controls.

There is at least one double blind random controlled trial showing that 1000 IU a day significantly increased the microbial resistance of airway surface liquid in human subjects compared with placebos (Buongiglio et al 2017; https://bmjopenrespres.bmj.com/conte...00211.abstract) in Effect of vitamin D 3 on the antimicrobial activity of human airway surface liquid: preliminary results of a randomised placebo-controlled double-blind trial.

And of course, the most important role of vitamin D is its role in the cellular manufacture of not only immunoglobulins (anti-microbial peptides -- White (2022; https://www.mdpi.com/2072-6643/14/2/284/htm), but also its role in the manufacture of most of the raw proteins that are activated by vitamins K1 and K2 and which are involved in bone, brain, and blood vessel health.
it was more typical than not that people in my field would test themselves sometimes for mild nonspecific symptoms and would test for everything under the sun. Undoubtedly because they did so many tests that one would fall outside the normal range. By definition, the normal range is comprised of 95% of the normal population. It isn't 100% because there is nome overlap between the disease state and the normal state and in order to increase the sensitivity of detecting the disease state only 95% of the normal population is used. Statistically, if you test for many things you will get an abnormal test based on the odds alone. They would then ask me what is wrong with them and want to know what it means.

My work history allowed me to gain a perspective that I saw personally and upfront. I started off working for a for-profit private national laboratory chain and saw the president and CEO do prison time for using kickbacks. The private for-profit branch is there to make a profit and is less guarded with ethics. Test for everything and make money. The non-profit sector is more guarded but still involves a profit to survive.

The medical model was and still is a symptoms-based model. The reason for that is because of the first do no harm prime directive. It is also cost saving. Spending much more money in order to evaluate an outlier laboratory test that turns out to be 5% of the normal population that fell outside the reference range.

Laboratory tests have a more reliable and accurate positive predictor or negative predictor value for disease when you are more selective on who you test. If one is non-selective on who you test and on what you test for then false positives go way up.

After saying all of the above on proper testing strategies one can then see a problem below.

"In an interview, Dr. Holick acknowledged he has worked as a consultant to Quest Diagnostics, which performs vitamin D tests, since 1979. Dr. Holick, 72, said that industry funding “doesn’t influence me in terms of talking about the health benefits of vitamin D.”

Dr. Holick’s crucial role in shaping that debate occurred in 2011. Late the previous year, the prestigious National Academy of Medicine (then known as the Institute of Medicine), a group of independent scientific experts, issued a comprehensive, 1,132-page report on vitamin D deficiency. It concluded that the vast majority of Americans get plenty of the hormone naturally, and advised doctors to test only patients at high risk of certain disorders, such as osteoporosis.

A few months later, in June 2011, Dr. Holick oversaw the publication of a report that took a starkly different view. The paper, in the peer-reviewed Journal of Clinical Endocrinology & Metabolism, was on behalf of the Endocrine Society, the field’s foremost professional group, whose guidelines are widely used by hospitals, physicians and commercial labs nationwide, including Quest. The society adopted Dr. Holick’s position that “vitamin D deficiency is very common in all age groups” and advocated a huge expansion of vitamin D testing, targeting more than half the United States population, including those who are black, Hispanic or obese — groups that tend to have lower vitamin D levels than others.

The recommendations were a financial windfall for the vitamin D industry. By advocating such widespread testing, the Endocrine Society directed more business to Quest and other commercial labs. Vitamin D tests are now the fifth-most-common lab test covered by Medicare."

https://www.nytimes.com/2018/08/18/b...el-holick.html

We haven't even mentioned what the test numbers mean with regards to supplement industry and it's connection to the Vitmain D council created back then. A lot of people would simply bypass testing all together and simply supplement.

One needs to balance the position with facts and studies. Unfotunately most are retrospective epidemiological studies and have not panned out with interventional studies.
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Old 04-08-2022, 10:26 AM
 
761 posts, read 447,379 times
Reputation: 785
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Originally Posted by Medical Lab Guy View Post
My contextual reply concerning geriatric implications is as follows.

There have been overreaching implications with the use of vitamins and minerals in the general population. There are representations that vitamin D, folate, and B vitamin deficiency state in the elderly exist.

Some people often want to know what vitamins and minerals they are deficient in and want to go to the doctor and have them do testing in order to find out their status. That just isn't smart nor possible in any real practical sense. Off the top of my head, the only real common tests are for vitamin B12 and folate as far as vitamins. For minerals, there are slightly more but still just a handful such as iron, sodium, potassium, calcium, and magnesium.

The science is very limited to those I have mentioned and practically nonexistent in others not mentioned. There are disputes about what constitutes deficiency states with misrepresentations being made out there. If someone says that 80% of the population is magnesium deficient then you have to ask questions. If 80% are deficient then why don't we see 80% of the population have symptoms? If that many don't have symptoms then that means it probably isn't a deficiency state at whatever level you are using.

As far as TSH goes, some have argued for the use of an age-adjusted scale for the reference interval with TSH elevating with age. Historically a TSH over 10 was considered the cutoff for treating hypothyroidism. The value of 10 or greater reflected an inverse relationship between the TSH and free T4. A value over 10 would reflect a free T4 under the reference interval into the hypothyroidism range.

"In case of fit older (65–75 years) patients, LT4 replacement should be commenced when TSH levels are above 10 mUI/L (48, 49) while, fit oldest old (>75–80 years) should be treated when clear signs and symptoms of thyroid disease are present, after careful evaluation of cardiovascular and cognitive comorbidities;"

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438852/

There was a positive correlation between TSH value and longevity.

I understand what you are saying about your preferences for a geriatric practitioner but there is a caveat to that. No doctor is 100% competent in everything. If one has exceptional chronic health problems then it would behoove the person who has a competent doctor able to treat those health conditions. A possible negative effect is a practitioner who plays hero ball and doesn't defer or refer specialists and handles all the diagnosis and treatment themselves. Sometimes less is better but other times less is not enough.
Thanks, I read most of the long (NIH) article you provided and was disappointed that they combined young and old in the same article. It was too long. I think there should have been at least two separate articles.

Another big disappointment was the fact that they didn't give consideration to the influence that different diets may have on thyroid function. They didn't look at it so it's "out-of-sight, out-of-mind."

I have noticed over the years that many super-centenarians practice calorie restriction. And calorie restriction has been studied for several decades since it was first discovered to extend life. This is the way it is said to work: When a person eats a healthy, calorie-restricted diet, their metabolism is slowed, causing slower aging. And this also causes thyroid function to slow.

BTW, I practice calorie restriction and it's not dangerous as many people might fear. I lift weights and do aerobic exercising. Of course if you don't do it properly it could be dangerous.

Note: Calorie restriction doesn't mean being hungry all the time. I eat fairly big meals but they consist of healthy low calorie foods.

Last edited by LongevitySeeker; 04-08-2022 at 10:40 AM..
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