An interesting metabolic valve, mfge8

In human studies involving an overnight fast (24 hours) followed by refeeding, researchers used SOMAScan technology to analyze serum protein changes. MFGE8 was among the proteins that increased upon refeeding and was elevated compared to the fasting state PubMed.

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Summary Table

Metabolic State	MFGE8 Levels
Fasting (5–16 h)	Decreased
Refeeding (After Fast)	Increased

Reducing insulin sensitivity after refeeding seems paradoxical at first, but it makes sense when you consider the physiological priorities of a mammal that just transitioned from fasting to feeding:

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1. Preventing hypoglycemia after a large nutrient influx

• After refeeding, blood glucose spikes. If insulin sensitivity were maximized everywhere (muscle, adipose, liver), glucose would be cleared from the blood too quickly.

• That could risk a sudden dip (reactive hypoglycemia), leaving the brain under-fueled.

• By slightly dampening insulin sensitivity, peripheral tissues don’t “over-suck” glucose out of circulation, keeping a steady supply for the brain and red blood cells.

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2. Prioritizing safe storage over rapid uptake

• Insulin resistance is not a binary state — it can be tissue-specific and context-dependent.

• After refeeding, reducing insulin sensitivity in muscle may favor directing glucose toward liver glycogen storage and lipid synthesis in adipose tissue rather than immediate burning in muscle.

• This helps rebuild energy reserves for the next fasting period.

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3. Supporting immune cell function

• Postprandial periods are often when the gut immune system is most active (monitoring incoming antigens, microbes).

• Immune cells rely heavily on glucose. A slight reduction in muscle/adipose glucose uptake ensures immune cells have access to fuel.

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4. Evolutionary “thrifty” strategy

• Wild mammals did not eat 3–5 regular meals per day; feeding was intermittent and unpredictable.

• A mechanism that slows down glucose disposal after feeding would help stretch nutrient availability between meals and stabilize energy supply.

• From this angle, MFGE8’s rise upon refeeding could be part of an energy allocation program: allow some storage, avoid overshoot, and keep circulation glucose levels safe for the brain/immune system.

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✅ In short:
Reducing insulin sensitivity after refeeding helps avoid dangerous glucose crashes, ensures brain and immune access to glucose, and promotes balanced storage rather than immediate overconsumption by muscle/fat.

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Hypoglycemia, despite the appearance of being good for you, sets you up for heart attack and stroke.  How?  The following is how:

Effect of Hypoglycemia on Inflammatory Responses and the Response to Low-Dose Endotoxemia in Humans 

It causes a storm to erupt in the blood stream, that which is very conducive to plaque rupture, plaque destabilization, and thrombosis.

 

Another amazing facet of human essential amino acid, L-Lysine: Reducing adiposity and hyperlipidemia

 Anti-obesity effects of amino acid in high-fat diet induced obese mice

Salk Institute discovers that Serine improves diabetic neuropathy

 Supplementation with amino acid serine eases neuropathy in diabetic mice

 

"Foods naturally rich in serine include soybeans, nuts, eggs, chickpeas, lentils, meat, and fish, and serine supplements are inexpensive and available over the counter."

Lysine and (+) Catechin disable melanoma cells from establishing metastases

 (+)-Catechin in a 1:2 Complex with Lysine Inhibits Cancer Cell Migration and Metastatic Take in Mice

 

10uM preincubation for 6 hours before inoculation into the mice.  This is different from establishing a xenograft and administering catechin:lysine orally.  They openly state that the anti-metastatic activity is independent of a lack of cytotoxic effect, attributed to EGCG, but not catechin. 

 

 

Then one would ask, is 5-10uM Catechin achievable in the blood?   Yes.  Is 5-10uM lysine achievable in blood?  Yes.

One could imagine a solid tumor, when constantly bathed in this complex in a live mammal, would encounter this effect described.  

 

The next step would be to administer this complex by IV catheter and in an oral formulation in mice with established solid malignancy and check for met burden in non-hormone driven malignancy.  I guess that hormone driven malignancies will not respond, but non-hormone driven maligancies will be contained.

Is there any evidence whatsoever that dietary L-Lysine is helpful against atherosclerosis? Yes, but

It was not until 2014, until a group in Japan studied a kidney disease related calcification disorder of the arteries.  It wouldn't be scientific to conflate this discovery to any other etiologies or use this for a cross claim where there was no evidence, although it recommends that L-Lysine be studied in atherosclerosis arrived through various pathologies.  A novel MOA, not considered before is the suppression of iPTH.  Very profound.  Importantly, they do not claim it reverts pre-existing calcification, and that this is an open question.  

The General Electric Lysine-Sepharose column for Lipoprotein(a) purification relies on the lysine binding sites (LBS) of apo(a) to capture it before eluting it with stronger affinity lysine analogs.  The study was never done in rodents to see if lysine could dislodge Lp(a) deposits in atherosclerotic plaque.  There certainly was ample time and resources available to do so and it remains an open question.

Dietary l-Lysine Prevents Arterial Calcification in Adenine-Induced Uremic Rats

 

 

Vitamin C and Cancer - The Research Isn't Finished.

New evidence shows very different mechanisms of action than that expounded about, such as pro-oxidant and antioxidant effects, pro-drug effects, immune side effects, tumor side effects, stromal effects, epithelial to mesenchyme transition effects, and useful fibrosis.  The last mechanism, reliant on dense collagen meshes from the "schirrous response" or foreign body response is the same an oyster does to a grain of sand, except instead of pearl, the human body uses collagen.  Sometimes, the tumor turns into a fibrous, benign cyst.  Other times, the stroma prevents TIL from approaching it.  Certainly, when a tumor is free to break away from the primary, it makes for more metastases, which is what makes cancer so lethal.  No doubt the capsule buys more time, even with a very vascularized tumor.  Pauling noted a new compound made, between ascorbic acid and the cements between cells that inhibits hyaluronidase, which dissolves the cement and allows tumor cells to spread.  This enzymatic inhibitor was called a physiological hyaluronidase inhibitor, PHI.

"It now seems clear that the active component of PHI is a tetrasaccharide with a terminal glucuronic acid unit replaced by an ascorbate residue, resistant to exoglycosidase activity, and therefore capable of blocking the whole process of glycosaminoglycan depolymerization." Cameron, et. al 1979

There was no compelling body of work since then to prove or disprove the in situ generation of such a PHI around tumors that required vitamin C to be made.  As in zero papers since then.

In 2023, epigenetic reprogramming, a reset mechanism, was discovered.  This isn't ammunition for the loony bin and death bed burglars of Linus Pauling to scream in vindication.  Hardly so, for this discovery isn't theirs and they claimed all sorts of outlandish buffoon thoughts.

 Vitamin C boosts DNA demethylation in TET2 germline mutation carriers

Copper Deficiency Can Cause Heart Failure

Here is some good science out of the British Medical Journal that will spare a lot of good people from a lot of bad grief, mysteriously caused by a simple lack of dietary copper.

Copper deficiency may be a leading cause of ischaemic heart disease