#1

I’m looking at vitamin B5 that seems interesting, see for instance:

Pantothenic acid is vitamin B5. B5 is required for the synthesis of coenzyme A—a critical molecule in energy metabolism and fatty acid synthesis. Pantethine is a derivative of B5. It is a dimeric form of pantetheine, which can be converted into pantothenic acid in the body. “Although pantethine is considered the more biologically active form of vitamin B5, it is less stable than pantothenic acid and tends to degrade over time if it is not kept refrigerated”

Pantethine lowers LDL and triglycerides while B5 does not. Beyond that, is there a preference in using one or the other?

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#2

Pantethine can reduce clotting so you can end up with more bruising. It also helps with converting acetaldehyde into acetate.

Within the body B5 is metabolised in a rate limited manner into Pantethine which then creates CoEnxymeA. Hence Pantethine can create CoA in a more rapid manner.

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#3

My only concern is this paper: Association between plasma Vitamin B5 levels and all-cause mortality: A nested case-control study 2022

But I don’t know how relevant it is. Other association studies (see: Parkinson's disease - #657 by adssx ) found that higher was better for serum B5 (not causal ofc).

#4

It could be that the body is not using up b5 because of a shortage of the other substrate particularly citrate

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#5

Interesting ongoing trial in Toronto: A Study to Test the Benefit of Vitamin B5 in Patients With Melanoma (NCT06377111)

  • “This single-center, single-cohort study aims to investigate the effectiveness of oral calcium pantothenate (C-PAN) in raising plasma pantothenic acid levels in melanoma patients.”
  • “Patients will initially receive a run-in period of C-PAN at a dose of 2000 mg daily for 3 to 7 days, alongside approved SOC drugs. Subsequently, patients will continue with the maintenance dose of 2000 mg daily, starting on the same day as the first cycle of combined ICI. This maintenance dose will be continued until the occurrence of unacceptable toxicity, disease progression by iRECIST criteria, or for a maximum duration of 1 year, whichever comes first, unless there are specific criteria indicating the discontinuation of C-PAN.”
  • “C-PAN is an essential nutrient as it is required for the synthesis of CoA, a key cofactor in the tricarboxylic acid cycle and fatty acid metabolism, as well as for the synthesis of acyl carrier protein. Pantothenate appears to be safe in humans with studies describing the administration of doses up to 10 grams per day over prolonged periods of time; hence, no upper limit for tolerability has been established. In this study, oral supplement consisting of 2000 mg daily of C-PAN will be administered to a single cohort of patients.”

One paper looked at it for heart failure: Impaired coenzyme A homeostasis in cardiac dysfunction and benefits of boosting coenzyme A production with vitamin B5 and its derivatives in the management of heart failure 2024

Both observations were with pantethine supplementation only, and not pantothenate. Together, these results demonstrate that pantethine has unique properties in comparison to pantothenate and that like pantothenate, (4′-phospho)panteth(e)ine can also be taken up by Drosophila cells.
If restoring energy balance in HF by boosting CoA levels ameliorates clinical outcomes, and enhances patients’ quality of life and potentially duration of life, Pan, pantethine, or PPanSH could complement conventional treatments with angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, β-blockers, and mineralocorticoid-receptor antagonists targeting mainly dysregulation in the neurohormonal system or reducing cardiac workload.

Pan = Pantothenic acid
PPanSH = 4′-phosphopantetheine aka

Coenzyme A (CoA) is a crucial molecule involved in acetylation reactions relevant to metabolic processes, such as the citric acid cycle, fatty acid oxidation, amino acidic metabolism, ketogenesis, synthesis of neurotransmitters, and detoxification. CoA is synthesized de novo starting from vitamin B5, also referred to as pantothenic acid (Pan), through a five-step enzymatic process (Figure 1) highly conserved from prokaryotes to higher eukaryotes.1 In the first step, Pan is phosphorylated to phosphopantothenate (PPan) by pantothenate kinase enzymes (PANK1, *606160; PANK2, *606157; PANK3, *606161). This step involves the addition of a phosphate group to the pantothenate molecule. The following enzyme in the pathway, phosphopantothenoylcysteine synthetase (PPCS, *609853), catalyzes the condensation of cysteine and the phosphorylated pantothenate, forming phosphopantothenoylcysteine (PPan-Cys). Subsequently, phosphopantothenoylcysteine decarboxylase (PPCDC, *609854) catalyzes the decarboxylation of PPan-Cys, resulting in 4′-phosphopantetheine (PPanSH). In the final step, the bi-functional enzyme CoA synthase (COASY, *609855), possessing phosphopantetheine adenylyl-transferase (PPAT) and dephospho-CoA kinase (DPCK) domains, catalyzes a reaction of adenylation of PPanSH to form dephospho-CoA (dPCoA), which is finally phosphorylated to CoA.

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#6

Its worth me saying this: “I think you can have too much acetyl-CoA.”

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#7

I asked ChatGPT about the rate limit. The answer looks right, but I have not checked

Great question! Here’s a clear breakdown of how pantethine avoids the natural rate-limiting step in Coenzyme A (CoA) synthesis:

1. Normal CoA Synthesis Pathway

Coenzyme A is synthesized in the body from vitamin B5 (pantothenic acid) through a multi-step pathway:

  1. Pantothenic acid → 4’-phosphopantothenate (by pantothenate kinase, the rate-limiting enzyme).
  2. Series of steps → Coenzyme A.

:key: Pantothenate kinase is rate-limiting, meaning it controls the speed of CoA production. If the body has enough CoA, this enzyme is feedback-inhibited, preventing excess CoA production.

2. What is Pantethine?

Pantethine is a dimer (two linked molecules) of pantetheine, an intermediate downstream of pantothenic acid in the CoA synthesis pathway.

3. How Pantethine Bypasses the Rate Limit:

  • When pantethine is supplemented, it can be directly converted to pantetheine.
  • Pantetheine enters the CoA pathway after the rate-limiting pantothenate kinase step.
  • This bypasses the bottleneck created by pantothenate kinase, avoiding feedback inhibition and enabling faster CoA synthesis.

:white_check_mark: Summary of Key Points:

  • Pantethine → Pantetheine → CoA (bypassing pantothenate kinase).
  • It avoids the natural rate-limiting step, allowing increased CoA production.
  • Useful when you want to boost CoA levels efficiently (e.g., for metabolic or lipid-regulating benefits).
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#8

What’s the conversion rate of pantentine to pantothenic acid (vitamin B5)? I think it’s likely they are apples vs. oranges iirc, totally different (based on e.g effects on LDL cholesterol) and:

Although it appears to be well tolerated and potentially beneficial in improving cholesterol metabolism, pantethine is not a vitamin, and the decision to use pharmacological doses of pantethine to treat elevated blood cholesterol or triglycerides should only be made in collaboration with a qualified healthcare provider who provides appropriate follow up.

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#9

…which leads to what problem(s)? Offset by exercise or melatonin or mitophagy?

#10

It leads to the wrong proteins being produced and is perhaps unpredictable. I think it would be hard to acheive.

Depending upon how you get there it can be reduced by changing the dosing.

I think my last Rapamycin dose made a sufficient change to my metabolism to warrant making other changes.

#11

3 oz of beef liver will save you taking pills

#12

But give you lots of Vitamin A

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#13

Apparently pantothenic acid but not pantethine crosses the BBB:

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