Can Lymphocytes And RDW Be Optimized Towards Youth? (51-Test Analysis)

[@monnoo8221]

yep, as Goethe let his mephistoles saying "blood is a very particular juice"... we should not forget 2 things: both the immune cells and the RBC derive fom the same stem cells, and WBC are related to the amount of functioning thymus, which unfortunately starts to disappear after the age of 35. So, given that your diet is highly constant, outside of the experiments, i would guess that lower calorie intake leads to a relative shortage of some key micro nutrients, probably B1, B12 and selenium. So, I would like to refer to two very exciting sources: First is Greg Fahy, (YT: "you Are Only As Young As Your Immune System with Dr. Greg Fahy"). In essence, the simultaneous optimization of HGH, DHEA-S and AMPK via Berberine revives the thymus. HGH increases by a manifold via fasting, and fasted exercise, DHEA-s is on a good way in your case, and Berberine may be a supplement to consider. The other one is the research about sea buckthorn, which improves stem cell health and their mobility. This could be a true food addon for you to introduce. ...and thanks for sharing and always providing food fo thought!!!

[@conqueragingordietrying123]

Based on the RDA, B1, B12, and selenium are far from deficient...

[@chickenlittle829]

@@conqueragingordietrying123 Since you have quantified so much of your intakes and blood results over a long period of time, and since you also sleuth out so much research on all cause mortality and aging, you are in a unique position to comment on the adequacy and suitability of various RDAs for optimizing your various health markers. I would love to hear your observations. From my own limited testing, it seems that at least these few RDAs are not suitable at all for getting my blood levels of various things where I want them. Homocysteine and B-12 is a key case in point. I get plenty of B-12 from diet, and my blood levels were in the 400s (SI) without supplementation. My homocysteine was 7.8 when first tested a few years ago. After supplementing B12, B6, and folate, my homocysteine fell to 5.5, my B12 went up to 560, and unexpectedly my thyroid numbers also improved. I have 4 or 5 other examples where the RDA is demonstrably not enough for me to be at my best…Vitamin D, Omega-3, zinc, protein…I would only be guessing Vitamin C, iodine, glycine, are in the same category.

[@Ivana.0405]

Mike, when you have a healthy, largely plant-based diet, inflammation is lower than on a standard American diet. As a result, the White Blood Cell count is also lower resulting in lower Lymphocytes. For example, what profile do you think is best: Profile 1: White Blood Cell count 6.0, Lymphocytes @ 40% = 2,400 Profile 2: White Blood Cell count 3.5, Lymphocytes @ 40% = 1,400 With low inflammation and a healthy WBC count of 3.5, it is practically impossible to reach a level of 2,000 Lymphocytes, but I would never increase inflammation in order to increase Lymphocytes. Do the studies that you used to determine that Lymphocytes at 2000 are optimal for lifespan consider a healthy population from the perspective of having very low inflammation. My inflammation is quite low, HSRC < 0.3, and so is your inflammation, how can you target low inflammation and Lymphocytes > = to 2000. The math does not work because low inflammation leads to lower White Blood Cell count. Thoughts?

[@kleffbois]

Valter Longo has often made the point that although calorie restriction has many benefits, it tends to weaken the immune system against infection and other illnesses. Your lymphocyte data might be a an example of this trade off

[@conqueragingordietrying123]

Yep, definitely

[@babybalrog]

but is that long term or temporary?

[@michaelayalaathotmai]

​@@conqueragingordietrying123 Have you stratified macronutrient content to see if protein, fat, or carbs disproportionately affect the distribution relative to calorie intake and biomarker levels? Does keto or carnivore make a noticeable difference?

[@conqueragingordietrying123]

@@michaelayalaathotmai I haven't tried carnivore, but the diet is ~45% fat, albeit not high enough for keto. Protein intake has ranged from ~70 - 150g/d since 2015 I look at correlations for all aspects of diet (micronutrients, too) with biomarkers...

[@michaelayalaathotmai]

@@conqueragingordietrying123 Have you been able to shift the needle on any of the biomarkers by altering, say upping fat or going zero carb? I know some intractable disease states disappear with longer fasting, 5-days plus. Ketosis in nearly impossible to avoid after three days. The older one is the more careful one must be to maintain lean body mass. I think a lot of people do not understand fasting and fear missing meals. The goal is achieving solid sustained autophagy at least some time. Proper amino acid intake is critical to promote muscle protein synthesis at any age. I think it helps to improve muscle protein turnover that tends to decline with age. I'm sure there is a sweet spot between the occasional multi-day fast and avoiding frailty and keeping the immune system in top shape. It would be interesting to see if carnivore improves the biomarkers while allowing lower caloric intake. I also suspect higher calories from animal fat have less of a negative impact on the metrics than from plant sources or excessive super lean protein. Not all calories are the same.

[@cravarc]

Thanks!

[@conqueragingordietrying123]

Thanks for your support @cravarc!

[@jamesgilmore8192]

To assess function at counts 1800-2000, you could test: immunoglobulins, flow cytometry for lymphocyte subtypes, blood smear to vsualise the immune cells, complement and more advanced tests. Targeted tests like CMV IgM, RF, ANA might be relevant. And don't discount the obvious symptoms like number of auto immune diseases, how often sick, etc.

[@conqueragingordietrying123]

Yep, definitely, I'm thinking about adding each of those measures, thanks James

[@aljosarojac8575]

Another fanstastic research / analysis. Thank you Mike.

[@conqueragingordietrying123]

Thanks @aljosarojac8575!

[@andrewtaylor9799]

Good video, thanks.

[@jamesgilmore8192]

Seems like there might be a breakdown in the correlation assumptions at low calories for lymphocytes. Namely, below 2100 calories, there is a cliff and lymphocyte numbers fall off.

[@conqueragingordietrying123]

Could definitely be true...

[@larsnystrom6698]

To me it seemed like 2400 - 2500 kCal was best for him, while it was worse at both ends. But I have never belived CR being the right thing for humans. So I quite like that middle ground!

[@DavidMartz-e2d]

A factor to consider is the reduction of digestive enzymes with age. Since the immune system reacts when food is ingested and digested, as the years go by what constitutes a fasted, baseline state for the immune system takes longer to achieve. What is achieved in youth in ten hours may require a 14-hour or longer fast to achieve later in life. A series of tests as the fasted time goes from 10 to 18 hours could reveal the point/value where your baseline is achieved.

[@Viertelfranzose]

That's a good point and use since years some extra Supplements for better fooddigestion and to improve the Gutmicrobiom..eating Garlic and red Onions every day is Standard since years.

[@KoiRun50]

I really would like to see you list biomarkers in order perceived priority. It would be interesting how it would change over time. It seems impossible to keep all biomarker in ideal range. So pick and choose.

[@conqueragingordietrying123]

Hi @KoiRun50, I rank them all equally. When calculating correlations with diet and supplements, I calculate the net correlative score for each food, macro and micronutrient, then course-correct based on the data. If the score is positive, I aim for increased intake, and vice versa.

[@monnoo8221]

@@conqueragingordietrying123 that's then basically a valid surrogate for a fuzzy lgics approach, feasible in a zero knowledge situation. Long term, however, if more data will be available, a latent state trait variable approach, or a sensitivity analysis can be very valuable, when crossing with sructural biophysiological knowledge

[@OneDougUnderPar]

Are you able to further break down calories intake into fat/carbs/protein, and even even subdivide those? I know you've mentioned before that fructose is strongly negative for you, and I have trouble believing that all calories are equal when it comes to biomarkers.

[@conqueragingordietrying123]

Hi @OneDougUnderPar, I can definitely do that, digging deeper into which dietary components aspects may be related to higher lymphocytes...

[@newdata]

I would take biomarkets to check that cr is working not the other way round to adjust cr to suit the biomarkets

[@ladagspa2008]

Wbc goes low due to omega3 as well as calorie deficit. Fish oil is a well known immunosuppressant.

[@ayasugihada]

The problem I have with mice studies isn't so much mechanism-related (ie mice are too different than people to draw conclusions), but environment-related (mice living in near-sterile environment of a lab are not model for highly polluted and highly infectious environments of human cities). Which is why I take the robustness of my immune response to pathogens over all other metrics.

[@conqueragingordietrying123]

Human data matches the mouse data in the video

[@ayasugihada]

@@conqueragingordietrying123 yep. Just saying I am putting more emphasis on immune system, compared to other markers. Not because I don't believe in mouse data from mechanistic perspective but because of vast differences in environment.

[@monnoo8221]

what are you doing for the robustness of your immune system, given the fac that the thymus starts to lose its funcional tissue at the age of 35'

[@ayasugihada]

@@monnoo8221 aiming for a high-antioxidant diet, supplementing additional anti-oxidants and potential "immune strengthening" substances. Exercising but trying to avoid long-term overexertion. And relevant to the current video - not calorie-restricting myself. I'm also not 35...yet.

[@matttee1319]

Seems like extra calories is an opportunity to add interesting nutrients

[@hvglaser]

I think it’s worth considering quality of life in the last part of your life, too. Some mice may live as long as others, but have an extended period of bioage-related complications? So total lifespan is similar, but youthful lifespan is shorter?

[@conqueragingordietrying123]

Throughout the duration of their lifespan, the 40% CR mice in the linked study also ran more on running wheels (relative to the other groups, which declined), so it's hard to believe that their lifespan wasn't more youthful, too

[@Testoflove-z7n]

I don’t understand caloric restriction. What does 40% CR mean ? If you’re eating a calorie deficit, aren’t you losing weight and it’s unsustainable? At some point you need to be at equilibrium right ?

[@conqueragingordietrying123]

40% CR is 40% less food relative to the AL group. For example, my AL intake is ~2800, but current intake is 2150/day, which is 23% CR (2150/2800).

[@joeextraknow2854]

I would agree on this. CR may not really mean to Calorie Deficit in long term.

[@Testoflove-z7n]

@@conqueragingordietrying123 but is that sustainable long term ?

[@andreacolombo2918]

Hi, So if is probably not possible top have optimal level of lymphocytes with calorie restriction ( the correlation is very similar in my case also) if we follow the mice study that the more you calories restriction the more you live, that mean that is possible to have a life extension also with a relative low lymphocytes level? (and so the restriction in calorie is more important for extend lifespan) thanks

[@conqueragingordietrying123]

Hi @andreacolombo2918, I wouldn't say that it's not possible to have optimal lymphocyte levels on CR, instead, what level of CR is too much, thereby resulting in suboptimal levels? In other words, finding the lowest CR amount that optimizes as many biomarkers as possible, including lymphocytes. In my case, ~20-25% CR is best-so far, going below that may not be good for the net effect on many biomarkers.

[@davidford8539]

@@conqueragingordietrying123 Are you still losing weight with this CR? How low in weight do you want to go?

[@zdeneksipek7237]

Are there any other correlations for optimising RDW besides calorie restriction and higher Omega-3 intake? My RDW went up from 12.7 to 13.2 during the last test (but it can be only fluctuation). All other results were improved though (mostly to optimal range) with 14 years younger phenoage in total. I didn´t increase calorie intake but made changes towards higher protein intake (1.8g/kg/day) and focused on strength training, build some muscle (around 0.5kg) and lost 1kg of fat. I´m 46, 185cm, 74 kg, 13.9% body fat.

[@conqueragingordietrying123]

Yep, which are posted here: www.patreon.com/posts/biomarker-with-7-115306129 Beyond that, I'd recommend tracking diet, supplements, etc in conjunction with blood testing to see what may be impacting your RDW...

[@monnoo8221]

except that i am older my body composition is quite similar. My RDW went from 12.5 to 12.0 ercently after i introduced methylation capacity in the form of methyl B12 and methyl folate, which reduced my homocystein from 15.3 to 8.2. My antioxidant status always was quite good, as well as protection by HDL. So, homocystein could be a factor for you too, as it is first often neglected, and its damaging capacity would make your RBC aging faster, increasing their size. Other reasons could be folate + B12 deficiency, impacting the rate of production and turnover. Note that the RDA for B12 is highly misleading (absorption, utilization issues). Everyone should titrate B12 with respect to HCys and RDW

[@zdeneksipek7237]

@@monnoo8221 Thank you. My homocysteine was 8.8 in April but I eat only a limited amount of meat (mostly fish and some dairy) so B12 can be an issue. How much B12 did you supplement to get your RDW to 12.0?

[@bobbobson4030]

Any longitudinal analysis of change in lymphocytes on the population level? Because in the linked study, age only explained 0.7% of variance in lymphocyte levels. Perhaps each individual has a different curve that is vertically shifted but the same decline over time?

[@conqueragingordietrying123]

Population averages for the age-related lymphocyte decline starts at 4:55

[@monnoo8221]

they would need to standardize individual longitudinal data, which they did not. I found 1 study developing a concept of immuno aging: "A clinically meaningful metric of immune age derived from high-dimensional longitudinal monitoring". it runs over 9 y. Yet a lot of research is rather deficient not only regarding data analysis, but also regarding the width of data in studies. Millions are spent to track hundreds of people over 20y for CVD, but no measurements for immune status gets taken...

[@rm6857]

With calorie restriction isnt there more sleep/rest needed? which basically means we live longer, but just sleeping and resting?

[@conqueragingordietrying123]

On CR, my sleep need hasn't increased-I'm not sure what the published data shows, though.

[@Earwaxfire909]

How do seasons affect biomarkers? Winter has less sunlight and can be much colder, so might it show a decrease in positive biomarkers? Is there a way to correlate any markers with the weather?

[@conqueragingordietrying123]

That's a good point, @Earwaxfire909. In support of that, seasonal allergies usually hit me hard in July-mid August, but otherwise I don't experience seasonality for the biomarkers...

[@Earwaxfire909]

@@conqueragingordietrying123 Thanks! Would be great to see a seasonal plot of these data.

[@stellarblur]

Warped red blood cells from leaking digestive enzymes? Lowered white blood cells?

[@conqueragingordietrying123]

Maybe indirectly for RBCs, I haven't seen any published data I'd expect higher WBCs with an increased leak of digestive enzymes into the blood, i.e. immune activation...

[@Ivana.0405]

Related to my prior comment, good clips from Dr Greger on WBC count: kzbin.info/www/bejne/mn2zYZptZZKFr8Usi=xm5b-gD8tOKKSQwN kzbin.info/www/bejne/mn2zYZptZZKFr8Usi=TgFE4P7RudpNRtpI

[@conqueragingordietrying123]

I've covered WBCs, too, with the perspective of age-related changes and all-cause mortality risk: kzbin.info/www/bejne/fJSclamNi813ntE

[@Ivana.0405]

@@conqueragingordietrying123 . Thank you, Mike, I had seen that clip which states that optimal WBC based on those studies are 3.5-6, and optimal Lymphocytes are ~2000+. I just wonder if those ranges apply also to people with extremely high-quality diets and very low inflammation. The studies that those ranges are based on might include a population of people with average inflammation, not very low inflammation. For a population of HsCRP

[@conqueragingordietrying123]

Thanks@@Ivana.0405. The population of people with high-quality diet is very small, which is why very large population based studies is the best way to try to capture data from those people. 108k people in the lymphocyte study in the video... The population of people with hsCRP < 0.3mg/L is also very small...

[@eruiluvatar236]

RDW is a marker of red blood cell turn over. As such I believe it won't be causative but a proxy mesaurement for conditions that would kill cells before their time. I'd like to know where does blood loss sit in that picture as blood loss does increase RDW but may or may not cause other cells to die. I have a RDW of 22.5 due to GI blood loss and I'd love to know if beyond the direct concerns of blood loss if it is also signifying longern term damage.

[@monnoo8221]

that's very bad... yep with blood loss one would expect a lower RDW, because blood cells do not age in this case. They get large when they age. Or your blood loss is in exacerbated bouts such that the body compensates for anemia, leading o a mx f older and a lor of very young RBC. But RBC is not a primary cause, it is an integrating indicator. You smiply need to heal your GI tract.

[@viracocha2021]

Sorry, how blood loss would decrease RDW? Also, where did you find RBC grow bigger when they age? Reticulocytes have a higher MCV than normal.

[@eruiluvatar236]

@@monnoo8221 I am not that sure of the mechanism for the increase in RDW with blood loss but it is a well known thing. If I was to speculate I'd imagine that some red blood cells are large and old while many are small and young while if there isn't blood loss the population of small and young cells will be much smaller . I know that I need to heal my GI or rather to get my immune system to stop wreking havok on it.

[@chickenlittle829]

I might suggest RDW is a marker of red cell consistency, rather than just turnover.

[@rolfpoelman3486]

Do an only raw sweet tropical fruits diet experiment.

[@conqueragingordietrying123]

Fructose intake (which is abundant in fruit) is significantly correlated with more biomarkers going in the wrong direction vs right, and accordingly, I've reduced fruit intake by about half over the past 9 years of tracking. Strawberries are still my #1 food in terms of intake (~500g/d), though.

[@monnoo8221]

simply: never.