Month: December 2023

Take acetyl-L-carnitine if you are healthy

gettingwell4 4-5 stars Advanced knowledge, Acetylcholine, Cerebrum, Cortisol, Dopamine, Epigenetics, Glutamate, Hippocampus, Immune system, Limbic system, Memory, Neurochemicals, Serotonin, Stress , , , ,

Eight 2023 acetyl-L-carnitine / L-carnitine papers, starting with three healthy human studies:

“Thirty healthy volunteers aged between 19 and 52 years were divided randomly into two equal groups, one of which received 1000 mg of L-carnitine (LC) per day over a 12-week period. Total cholesterol and HDL-C increased significantly after supplementation. LC could be useful in impeding development of heart diseases in subjects with low HDL-C.”

https://journaljammr.com/index.php/JAMMR/article/view/5166 “L-Carnitine Increases High Density Lipoprotein-Cholesterol in Healthy Individuals: A Randomized Trial”

Rationale for dose selection wasn’t provided, and the possibility of limited results due to poor study design wasn’t mentioned.

“This study examined effects of 12 weeks of LC supplementation on bone mineral density (BMD) and selected blood markers involved in bone metabolism of postmenopausal women participating in a resistance training (RT) program. Participants’ diets were supplemented with either 1 g of LC-L-tartrate and 3 g of leucine per day (LC group) or 4 g of leucine per day as a placebo (PLA group), in a double-blind fashion.

Because the study protocol consisted of both exercise and supplementation, some favorable changes in the BMD could be expected. However, it was not possible to detect them in the short study period. No significant modification in BMDs of the spine, hip, and total skeleton and no differences between groups in one-repetition maximum could be due to the relatively short duration of the RT intervention.”

https://nutritionandmetabolism.biomedcentral.com/articles/10.1186/s12986-023-00752-1 “Effect of a 3-month L-carnitine supplementation and resistance training program on circulating markers and bone mineral density in postmenopausal women: a randomized controlled trial”

Same comments as the first study regarding no rationale for dose selection, and no mention that limited results were possibly due to an inadequate dose.

In a letter to the editor, a researcher took issue with a study’s methodology:

“Based on finding that intravenous provision with carnitine alone does not increase muscle carnitine accretion, and on the above-reevaluated data, it appears that the basis for carnitine with caffeine being able to increase muscle carnitine levels, and thereby manipulation of muscle metabolism and exercise performance, is uncertain.

Carnitine bioavailability in any group would have been 9.5%. This assessment would be in line with previously recorded values of 5%–18% carnitine bioavailability. It is firmly believed that low carnitine bioavailability is attributable to the inability of kidneys to reabsorb carnitine when the threshold concentration for tubular reabsorption (about 40–60 μmol/L) has passed this value.

The authors’ proposed long-term use of carnitine supplementation as an aid to improve fat oxidation in type II diabetes also seems to lack provision.”

https://physoc.onlinelibrary.wiley.com/doi/10.14814/phy2.15736 “LTE: Does caffeine truly raise muscle carnitine in humans?”

Two genetic studies:

“Our findings suggest that humans have lost a gene involved in carnitine biosynthesis. Hydroxytrimethyllysine aldolase (the second enzyme of carnitine biosynthesis) activity of serine hydroxymethyl transferase partially compensates for its function.”

https://www.researchsquare.com/article/rs-3295520/v1 “One substrate-many enzymes virtual screening uncovers missing genes of carnitine biosynthesis in human and mouse”

“Reported prevalence of primary carnitine deficiency (PCD) in the Faroe Islands of 1:300 is the highest in the world. The Faroese PCD patient cohort has been closely monitored and we now report results from a 10-year follow-up study of 139 PCD patients.

PCD is an autosomal recessive disorder that affects the function of organic cation transporter 2 (OCTN2) high-affinity carnitine transporters, that localizes to the cell membrane and transport carnitine actively inside the cell. Without proper functioning OCTN2 carnitine transporters, renal reabsorption of carnitine is impaired, and as a consequence, patients suffering from PCD have low plasma levels of carnitine. This can disturb cellular energy production and cause fatigue, but also in extreme cases lead to cellular dysfunction and severe symptoms of coma and sudden death.

PCD patients seem to adhere well to L-carnitine treatment, even though they have to ingest L-carnitine tablets at least three times a day. Overall mean L-carnitine dosage was 66.3 mg/kg/day.”

https://onlinelibrary.wiley.com/doi/10.1002/jmd2.12383 “Patients with primary carnitine deficiency treated with L-carnitine are alive and doing well—A 10-year follow-up in the Faroe Islands”

The average daily dose is (66.3 mg x 70 kg) = 4,641 mg. A third of this dose would be about 1.5 g.

The first study of Acetyl-L-carnitine dosing also suggested dosing L-carnitine three times a day because of 10-20% bioavailability.

A study with unhealthy humans:

“This retrospective study analyzed medical records of adult patients between March 2007 and April 2019, with presenting complaints of fatigue and lethargy. Acetyl-L-carnitine has physiological functions similar to L-carnitine but has higher bioavailability and antioxidant properties. This study confirmed that a triple combination therapy with γ-linolenic acid, V. vinifera extract, and acetyl-L-carnitine can improve arterial stiffness in patients.

Our study had some limitations:

  1. The study population may not be representative of the entire Korean adult population.
  2. The study did not have a medication-free control group. Instead, the comparison group comprised patients with medication compliance <80%.
  3. Drop-out rate of the triple-combination therapy (46.2%, 147/318) was relatively high, indicating the possibility of bias due to loss to follow-up.
  4. The study did not consider lifestyle factors such as smoking, diet, and physical activity level, which may affect arterial stiffness.
  5. The study did not examine interactions among drugs comprising the combination therapy, although all drugs are known to positively impact blood vessels.”

https://onlinelibrary.wiley.com/doi/10.1111/jch.14708 “Efficacy of γ-linolenic acid, Vitis vinifera extract, and acetyl-L-carnitine combination therapy for improving arterial stiffness in Korean adults: Real-world evidence”

This study’s acetyl-L-carnitine dose was 500 mg three times a day.

Wrapping up with two rodent studies:

“Acetyl L-carnitine (ALCAR) has proved useful in treatment of different types of chronic pain with excellent tolerability. The present work aimed at evaluating the anti-hyperalgesic efficacy of ALCAR in a model of persistent visceral pain associated with colitis.

The acetyl group in the ALCAR molecule can enhance cholinergic signalling by promoting synthesis of neurotransmitter acetylcholine, which plays an important role in both the enteric and central nervous systems. Acetylcholine signalling has significant antinociceptive effects in development of visceral pain, so it has been proposed as a therapeutic target.

ijms-24-14841-g001

ALCAR significantly reduced establishment of visceral hyperalgesia in DNBS-treated animals, though the interventive protocol showed a greater efficacy than the preventive one.

  • The interventive protocol partially reduced colon damage in rats, counteracting enteric glia and spinal astrocyte activation resulting from colitis.
  • The preventive protocol effectively protected enteric neurons from inflammatory insult.

These findings suggest the putative usefulness of ALCAR as a food supplement for patients suffering from inflammatory bowel diseases.”

https://www.mdpi.com/1422-0067/24/19/14841 “Anti-Hyperalgesic Efficacy of Acetyl L-Carnitine (ALCAR) Against Visceral Pain Induced by Colitis: Involvement of Glia in the Enteric and Central Nervous System

This study cited multiple animal studies that found acetyl-L-carnitine was effective for different types of pain. I’ve taken it every day for nineteen years, and haven’t noticed that effect.

“Repetitive mild traumatic brain injuries (rmTBI) may contribute to development of neurodegenerative diseases through secondary injury pathways. Acetyl-L-carnitine (ALC) shows neuroprotection through anti-inflammatory effects, and via regulation of neuronal synaptic plasticity by counteracting post-trauma excitotoxicity. This study aimed to investigate mechanisms implicated in etiology of neurodegeneration in rmTBI mice treated with ALC.

ALC is an endogenously produced carnitine metabolite present in tissue and plasma, and readily crosses the blood brain barrier, unlike its unacetylated form. ALC is also a commonly available nutritional supplement, with a known safety profile, and had been well-studied for its role in aiding β-oxidation of long chain fatty acids in the mitochondria.

While some studies have shown promise for improving clinical and psychometric outcomes in individuals with probable Alzheimer’s disease (AD) and mild cognitive impairment, other studies that included participants with moderate AD progression were less conclusive. It may be that this lack of improvement is related to a therapeutic window of opportunity. Once neurodegenerative mechanisms have commenced, a reversal of these processes is not attainable.

There is currently a lack of evidence for safe therapeutics that can be administered long-term to reduce the risk of individuals developing cognitive and neuropsychological deficits after rmTBIs. Prophylactic ALC treatment in a paradigm of neurotrauma may be a way to maximize its therapeutic potential.

While brain structures display differential vulnerability to insult as evidenced by location specific postimpact disruption of key genes, this study shows correlative mRNA neurodegeneration and functional impairment that was ameliorated by ALC treatment in several key genes. ALC may mitigate damage inflicted in various secondary neurodegenerative cascades – confirmed by improvements in behavioral and cognitive function – and contribute to functional protection following rmTBI.”

https://www.frontiersin.org/articles/10.3389/fphar.2023.1254382/full “Repetitive mild traumatic brain injury-induced neurodegeneration and inflammation is attenuated by acetyl-L-carnitine in a preclinical model”

I read many traumatic brain injury papers earlier this year, but only curated two in Brain endothelial cells. I came away thinking that there’s no permanent recovery from TBIs, as just symptoms are effectively treated.

Most TBIs happen to old people who have diminished brain reserves. I didn’t see studies that factored in evidence of what happened earlier in injured people’s lives that created TBI susceptibility but wasn’t remembered.

Unlike other years, I haven’t watched any football this season. It’s unsettling that transient entertainment value continues to take precedence over permanent effects on players’ lives.

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Oat sprout stressors

gettingwell4 2-3 stars Required further work, Epigenetics, Stress , ,

Two 2023 Avena sativa oat sprout studies, starting with one that found different effects during germination from varying temperature and relative humidity:

“This study evaluated effects of temperature (20, 25, and 30°C) and relative humidity (RH, 55, 60, and 65%) as abiotic stressors during oat germination. We identified eighty polyphenols, nine avenanthramides, twelve lignans, and five phytosterols.

  • 100% germination was achieved at 25°C/60% RH from day 3, yielding the longest radicle size.
  • The highest content of most phenolic acids, avenanthramides, and lignans occurred at 30°C/65% RH, where 100% germination was attained by day 5, but with a shorter radicle size.
  • The best flavonoid and phytosterol profile was obtained at 20°C/55% RH, achieving only a 67% germination rate by day 5.

sprouted oat temp rh

By considering germination conditions, end-users can harness the versatility of oat sprouting to meet their specific needs and maximize potential benefits of this promising cereal crop. For instance, manufacturers of functional foods and beverages could consider using sprouts from conditions that yield high polyphenol content for products targeting antioxidant benefits, whereas nutraceutical manufacturers could focus on sprouting conditions that result in elevated levels of avenanthramides, well-known for their health-promoting properties.”

https://www.sciencedirect.com/science/article/abs/pii/S0308814623027917 “Impact of temperature and humidity conditions as abiotic stressors on the phytochemical fingerprint of oat (Avena sativa L.) sprouts” (not freely available) Thanks to Dr. Iza F. Pérez-Ramírez for providing a copy.

Another study compared and contrasted eight sprouted grains to their ungerminated grains and to each other. I’ll highlight oat sprout results:

“The method used was germination for up to 72 h at temperatures ranging from 19–23°C. Oat germination rate was 80%.

Linoleic acid (omega-6) was the predominant fatty acid in oat grain powder, followed by similar amounts of oleic and palmitic acids and smaller amounts of stearic and linolenic (omega-3) acids. Since omega-6 content remained unchanged and omega-3 quantity increased slightly in sprouted oats, the omega-6/omega-3 ratio decreased.”

https://www.mdpi.com/2304-8158/12/17/3306 “Effect of Germination on Fatty Acid Composition in Cereal Grains”

My kitchen cupboard’s oat sprouting conditions are closer to this second study’s temperature, where relative humidity wasn’t specified. I doubt that kitchen winter-time relative humidity ever rises to the 55% lower threshold of the first study for more than a few minutes.

At this time of year in Sprouting hulled oats, I got a 97% germination rate over three days with an estimated 21°C (70°F) and a relative humidity closer to 30% than 55%. Couldn’t tell you why the first study’s germination rate with 20°C/55% RH was only 67% at day 5, or why the second study’s germination rate was only 80% at day 3 with 19–23°C.

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Suboccipital release

gettingwell4 2-3 stars Required further work

Here’s a 2023 paper on the subject, but let’s first see what it is, from Michigan State University:

https://hal.bim.msu.edu/CMEonLine/Autonomic/Sympathetic/Treatment/SuboccipitalRelease/start.html

and University of Wisconsin:

https://www.fammed.wisc.edu/suboccipital-release-technique/

An instruction paper for osteopaths:

“This technique treats migraines, headaches, and neck pain. It can also be used as an adjunct for treating conditions with autonomic dysfunction.

Before performing a suboccipital release, the patient should have a neurologic and musculoskeletal exam of the neck and upper extremities. Ensure that the patient does not have contraindications such as: Acute cervical fractures; concern for neurovascular compromise; focal neurologic deficit.”

https://www.ncbi.nlm.nih.gov/books/NBK582126/ “Osteopathic Manipulative Treatment: Suboccipital Release”

I read a half-dozen other 2023 papers comparing this technique with other suboccipital techniques. I’m not posting links because these papers didn’t completely specify their technique, what was its history, and what was its safety. It’s extremely easy to traumatize this area of our bodies.

I similarly won’t post links to other 2023 papers that claimed this technique improved other body problems, such as ankle range of motion, hamstring tightness, and lumbar pain. Mechanistic explanations are required, not just “they are connected by one neural system,” hand-waving, and woo.

This search for recent research was disappointing. I’ve performed suboccipital release on myself at least twice a day for years the same way I saw physical therapists do it to their patients while I was in physical therapy 13 years ago. Maybe there’s a video about self-suboccipital release that didn’t involve gadgets, but I couldn’t find it.

The point of this technique is to evoke a relaxation response. It usually relaxes areas from the neck to my feet. Sometimes it works quickly, other times it takes a while.

In any event – you and I are different, and I’m definitely not recommending suboccipital release for you. It isn’t a cure-all for neck pain, sitting most of the day, bad posture, poor ergonomic setup, being stuck in traffic, being glued to your phone, etc.

Guardians at your gates

gettingwell4 Immune system, Just me

This post emphasizes human agency in training our innate immune system. Otherwise, we are like agentless jellyfish I see almost every day on the beach, moved by tides and blown by winds, to their stranded graves.

I don’t cite studies here because none have been published regarding recent developments in human innate immune responses. Researchers keep their jobs by going along with the current narrative, no matter the evidence. I’ve presented evidence for taking personal responsibility for your own one precious life many times this decade.

There’s a JN.1 variant now that has emerged due to being evolutionarily driven to escape people’s adaptive immune systems who had one or more of the 2+ billion experimental gene therapy injections worldwide. People who are focused on this variant “tree” and missing the “forest” are allowing themselves to be herded for at least the tenth time this decade.

What can people who didn’t initially trust their innate immune systems, and subsequently slammed its functionality, do now in late 2023?

One avenue for redemption may be that taking off-patent anti-virals proven decades ago will work prophylactically. Even if people wait until they experience symptoms, luckily, the same proven anti-virals when administered early will also work therapeutically. Maybe people’s innate immune systems will recover, maybe they won’t, in which case they’ll hopefully keep taking anti-virals instead of unproven gene therapies.

Those who didn’t allow themselves to be propagandized this decade, and who initially trusted their innate immune systems’ functioning to maintain their health, will be fine. If they haven’t subsequently trained their innate immune systems, though, they may take longer to recover from another outbreak caused by people who acquiesced to experimental gene therapies.

I’ve trained my innate immune system every day for the past 19 years with yeast cell wall β-glucan because every disease is connected to the immune system. I’ve also exercised my endogenous antioxidant responses with weak pro-inflammatory isothiocyanates in broccoli sprouts every day for 3.5+ years.

Daily drills with weak threats will keep our body’s evolved systems tuned up and ready for real emergencies. Being sick takes away our ability to act independently, while simultaneously making us dependent on the broken medical care system.

So what is your preference? Be energized at sunrise?

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Or washed up on the beach?

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What you expect may not be what you find

gettingwell4 2-3 stars Required further work, Acetylcholine, Epigenetics, Glutamate, Hippocampus, Immune system, Limbic system, Memory, Neurochemicals, Stress , , , , ,

I’m halfway through a 90-day trial of plasmalogens coincident with improving peroxisomal function via resistance exercise and time-restricted eating. I haven’t curated related 2023 papers I’ve read concerning plasmalogens, peroxisomes, sphingolipids, ceramides, and mitochondrial interactions with these, mainly because I haven’t seen human-pertinent aspects similar to Dr. Goodenowe’s efforts.

The 2023 papers I’ve read have more to do with researcher incentives rather than actual human benefits. I’d guess that researchers care about these related subjects to the extent that they want to be the first to publish arcane details about them, like peroxisomes in the parotid salivary gland.

One area I expected to see a difference at the regimen’s beginning was in my peripheral nervous system Schwann cells. Instead, I had taste and smell improvements in my primary olfactory nervous system olfactory ensheathing cells, which are highly similar to Schwann cells. I was also happy to experience an immediate halt to my ulnar nerve elbow pain after what I interpret as ProdromeNeuro effects and perhaps coincident ProdromeGlia effects on items upstream of Schwann cells.

Here are three papers on Schwann cells that I haven’t yet seen as applicable to my current regimen, starting with a 2022 review:

“We summarise contributions of neurotransmitter receptors in regulation of morphogenetic events of glial cells, with particular attention paid to the role of acetylcholine receptors in Schwann cell physiology. This redundant and complex integrated regulation system could be explained as a mechanism of preserving glial cell physiology. In case of a single receptor signalling dysfunction, other neurotransmitters can overcome the deficit, preserving functions of glia and health of the nervous system.

Increased knowledge in medicinal chemistry and in bioinformatics accompanied by drug delivery studies might open a fascinating therapeutic perspective for cholinergic mimetics for treatment of several nervous system pathologies, and in reducing neuroinflammation both in the central and peripheral nervous systems.”

https://www.mdpi.com/2227-9059/11/1/41 “Emerging Roles of Cholinergic Receptors in Schwann Cell Development and Plasticity”

A 2023 study investigated the vagus nerve’s Schwann cells’ impact with gut function:

“The vagus nerve is the longest extrinsic cranial nerve in the body. It regulates gut physiology through the intrinsic nervous system (myenteric and submucosal plexus) and enteric glial cells interactions, which participate in controlling intestinal absorption, secretion, immune homeostasis, and motility.

Normal intestinal motility is critical for nutrition assimilation and several biological functions. The loss of normal gut function aggravates inflammation, oxidative stress, and other cellular stressors.”

https://bmcbiotechnol.biomedcentral.com/articles/10.1186/s12896-023-00781-x “A critical role for erythropoietin on vagus nerve Schwann cells in intestinal motility”

I haven’t curated a Buck Institute for Research on Aging sponsored study for a while, since their 2015 A study of how “age” itself wasn’t a causal factor for wound-healing differences detracted from science and their 2020 Linear thinking about biological age clocks wasted resources.

This 2023 rodent study couldn’t investigate anything outside of Buck’s limited paradigm’s echo chamber. This sponsor would rather break their arms patting themselves on their backs pretending they’re advancing science than fund relevant human research successes that do advance science:

“Following peripheral nerve injury, successful axonal growth and functional recovery require Schwann cell (SC) reprogramming into a reparative phenotype. This work provides the first characterization of senescent SCs and their influence on axonal regeneration in aging and chronic denervation.”

https://www.embopress.org/doi/full/10.15252/emmm.202317907 “Senescent Schwann cells induced by aging and chronic denervation impair axonal regeneration following peripheral nerve injury”

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Building your plasmalogen savings account

gettingwell4 4-5 stars Advanced knowledge, Acetylcholine, Brain development, Cerebrum, Dopamine, Epigenetics, Immune system, Limbic system, Lower brain, Memory, Neurochemicals, Stress , , , , , ,

A webinar from earlier this week with Dr. Goodenowe, a clinical trial facilitator, and a physician:

From the Q&A segment:

“Is there a particular age where it’s recommended to test for plasmalogen levels? And what levels would be considered normal?

That’s a good question. That actually raises this whole concept of optimal health and this concept of aging.

The best way to think about it – we talked about this paycheck-to-paycheck situation, where as long as our bills are paid every day, technically we think we’re normal. But we still feel this sense of health anxiety – if you will – like we just don’t know if my car breaks down, or my water heater breaks down, do I have enough money to pay these events in my life?

That’s what health feels like to a lot of people, because they’re just kind of getting by. From a health perspective, they’re considered normal, but they have no reserve capacity, and they have no vitality in terms of health.

Plasmalogens are a type of molecule that you build a savings account of, over years, over decades. Your heart builds them up, your brain builds them up, and you slowly accumulate them. Then when you get an oxidative stress like what’s happening now in today’s world with all the covid and myocarditis and brain fog – a lot of these things are being caused because that reserve of plasmalogens has been depleted.

We want plasmalogens for a longevity perspective. There are other situations that can have low plasmalogens, other things can really knock your plasmalogens down.

So you want to start early, you want to build a savings account, and you want to maintain it. Maintain health and function, and create a sustained surplus for optimal health, for optimal neuromuscular performance.”

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Another reason to chew broccoli sprouts

gettingwell4 4-5 stars Advanced knowledge, Immune system, Stress

This 2023 review explored a naturally produced antimicrobial:

“This review focuses on the role of abundant hypothiocyanous acid (HOSCN), a potent oxidant that kills bacteria but is non-toxic to human cells. Produced from thiocyanate (SCN−) and hydrogen peroxide (H2O2) in a variety of body sites by peroxidase enzymes, HOSCN has been explored as an agent of food preservation, pathogen killing, and even improved toothpaste.

Lactoperoxidase (LPO) is considered the main producer of HOSCN, and is secreted in saliva, tears, breastmilk, and lacrima of mammals. LPO regulates the oral microbiome and keeps breastmilk free of pathogens during the first few weeks after delivery. LPO has long been understood to play a role in prevention of dental caries.

Thiocyanate is mostly acquired from diet. Many food plants contain glucosinolates – precursors to isothiocyanates – found in vegetables of order Brassicales (broccoli, cabbages, turnips, mustard, horseradish, etc.).

HOSCN is likely to exist at substantial concentrations in the oral cavity and the respiratory tract, and is probably present under any inflammatory circumstances. Oxidative damage caused by HOSCN is largely reversible, since HOSCN cannot oxidize thiols to sulfinic or sulfonic acid.

mmi15025-fig-0002-m

The study of bacterial HOSCN stress response is in its infancy. Results summarized above suggest overlaps with both ROS and RCS responses, particularly in the areas of redox homeostasis (e.g., glutathione metabolism), cysteine metabolism, and prevention of protein aggregation, but considerable work needs to be done to more fully characterize this response.”

https://onlinelibrary.wiley.com/doi/10.1111/mmi.15025 “Hypothiocyanite and host–microbe interactions”

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What is the health utility of white blood cell type count ratios?

gettingwell4 4-5 stars Advanced knowledge, Epigenetics, Immune system, Memory, Stress , ,

This post explores CBC ratios of neutrophils-to-lymphocytes (NLR) and lymphocytes-to-monocytes (LMR) as healthy biomarkers.

Uses of the neutrophils-to-lymphocytes ratio asserted:

A normal range of NLR is between 1–2, and values higher than 3.0 and below 0.7 in adults are pathological.

I saw only one study out of 151 references, reference 61 from 2017, that demonstrated a “below 0.7” range. All of its sampled subjects had sepsis or septic shock, though. Not exactly people from which to derive healthy parameters for the general population.

I looked through all 2023 papers of the 223 papers that cited this review. I didn’t see any that questioned a healthy status of a low neutrophils-to-lymphocytes ratio in humans. Almost all 2023 papers focused on diseases, not health, as if that’s what we want from researchers and medical professionals.

So if a review gets enough citations, its assertions become a fait accompli, elevated to an indisputable fact. Nevermind that unlike study researchers, reviewers aren’t bound to demonstrate evidence from tested hypotheses. Citing paper writers also aren’t obligated to actually read and understand what they cite.

I looked at papers that cited any of the four papers in Uses of the lymphocytes-to-monocytes ratio. There were hundreds of citations over the years, but I didn’t see any 2023 papers that related the LMR to health rather than disease.

The reciprocal monocytes-to-lymphocytes ratio may have prognostic value or “association with” other disease conditions. But do patients care about abstract values such as area under the curve?

Are hormone ratios useful in explaining health? Behavior? Neurobiology? Anything? had a similar situation:

“Analysis of individual variables offers more information and a more accurate picture of underlying relationships.”

This paper suggested by analogy that researching treatments to increase lymphocyte and/or decrease monocyte absolute counts rather than change ratios should be emphasized for health.

Labcorp blood tests from earlier this week came back yesterday. I’ll repeat a paragraph from another blog post that illustrates my viewpoint on them:

“Every explanation of those reference ranges, and optimal ranges built from all-cause mortality statistics, requires a suffix “of people who didn’t positively change their healthspan and lifespan.”

  • What value is there in optimizing (pick a measurement) against those outcomes?
  • Why compare my efforts, or results, or any other aspect of my life, to people who didn’t actionably care about their one precious life?”

Relevant white blood cell type counts and ratios from the current and three previous blood tests are:

nlr lmr

I’ve trained my innate immune system every day for the past 19 years with yeast cell wall β-glucan because every disease is connected to the immune system. I also haven’t been sick even one day this decade.

Let’s start with high-specificity C-reactive protein (hsCRP). Bookend values show very low inflammation over the past 2.5 years. Missing and regular CRP <1 values were due to medical professionals ignoring my written instructions.

Next are innate immune system monocytes, counts of which haven’t changed over the past 2.5 years. There have been no viruses, bacteria, fungi, or parasites that survived initial defenses. So monocyte-derived dendritic cell and macrophage activity hasn’t changed.

Next are adaptive immune system lymphocyte (T cells, natural killer cells, and B cells) counts that had a steady 31% increase from 1.6 to 2.1. It would be interesting to see which lymphocyte subtypes responded to the various therapeutic regimes I’ve implemented over these past 2.5 years. But I won’t become a lab rat to find out.

Last are innate immune system neutrophil counts, which our bone marrow makes copious amounts every day to fight infections. Mine have undergone a 43% decrease over the past 2.5 years. My bone marrow apparently doesn’t have metabolic imperatives to produce more short-lived neutrophils, probably because there isn’t a health emergency to immediately defend against.

To summarize, focusing on white blood cell type counts rather than their ratios better serves health purposes. The CBC test has coarse measures, though, so more refinement could be achieved.

Here’s an epigenetic clock summary of this week’s metabolomic results:

2023 epigenetic age

This summary from 2.5 years ago used the same calculations:

2021 epigenetic age

Maybe the additional 5.6 year difference in this first measurement instead of an opposite 2.5 year change along with chronological age is a signal that I’m getting more healthy. Maybe it’s noise. Recent memories argue against phenotypic age having anywhere near the impact of chronological age.

Comparing my two results against people who didn’t positively change their healthspan and lifespan has limited value, although this could reduce their denominator’s influence. We each have our life at stake, and bad things will happen on their own. If we want good things to happen, we have to make them happen.

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